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She is preceded in death by her beloved son
14 grandchildren and 12 great grandchildren to honor and cherish her memory.
A Visitation will be held from 5:00 pm - 9:00 pm on Thursday
2025 with a Rosary at 7:00 pm at Sunset Funeral Home- Americas
A Funeral Mass will be held at 11:00 am on Friday
A Graveside will follow at 12:30 pm at Mount Carmel Cemetery
Services are entrusted to Sunset Funeral Home- Americas
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shown in a 2018 photograph by the California Department of Corrections and Rehabilitation
(California Department of Corrections and Rehabilitation/TNS)
hasn’t walked the streets of his hometown on the eastern edge of Los Angeles County since the 1980s
when he was convicted of murder and sentenced to life in prison
he controls an “empire” of gang members and drug dealers who pay him a cut of their illicit profits
Pomona was once a haven for millionaires called “Queen of the Citrus Belt.” Today
Cherryville and 12th Street have carved up its streets
killing each other over territory and old grudges
whose power “transcends rivalries,” Kyle Kahan
said in his closing argument at Lerma’s recent trial in downtown Los Angeles
where he was convicted along with three other Pomona gang members of murder and racketeering
In Pomona and the prisons where he has spent the last 43 years of his life
Lerma has “the power to decide life or death or just plain old pain,” Kahan said
Prosecutors alleged that Lerma — a squat man with a bald head, walrus mustache and deep bags under his eyes — is part of the Mexican Mafia, a criminal syndicate based in California’s prison system
From lockups near the Oregon border and later in downtown Los Angeles
said prosecutors were perpetuating whispers in Pomona of a faraway prisoner who “owns and runs” the city
“They’ve had since 2012 to get evidence of this evil genius Michael Lerma — and there’s nothing,” she said
Lerma seized control of the drug trade within a federal jail
A witness testified Lerma called the shots for Latino inmates in the Metropolitan Detention Center
cleaning regimens — even which prisoners were allowed to hold jobs
“Anything that happened went through him,” the witness said
When an inmate ran up a heroin debt that he couldn’t pay
Lerma ordered three Pomona gang members to murder him
“If Michael Lerma wills it,” Kahan told the jury
RELATED | 15 prison tattoos and their meanings
Pomona grew rich from the citrus groves that flourished in the Southern California sun
Among its early residents was Louis Phillips
described by The Times as the richest man in Los Angeles County in 1892
Kellogg once raised Arabian horses on a 377-acre ranch that today is a campus of California State Polytechnic University
Citrus groves were replaced by cheap homes that drew families from Los Angeles
but the city was no longer a refuge for millionaires
Lerma said he and his six siblings were raised by his mother and grandmother after his father — a heroin dealer — abandoned the family
He wasn’t yet a teenager when he joined the 12th Street gang
Lerma was arrested on suspicion of attempted murder
Released after three days in jail without being charged
“That year in the Marine Corps was probably the best year of my life,” Lerma told the board
He learned about discipline and “chain of command,” he said
Lerma returned to Pomona and went cruising with his younger brother
and killed a 21-year-old man with a shotgun
Both brothers pleaded guilty to second-degree murder
Michael Lerma and his wife moved to Sacramento
He had two children to support and couldn’t find a good job
robbed him at gunpoint of heroin and a power tool
Keastner was sitting in his car outside a 7-Eleven in Sacramento when gunmen in a Chevrolet Monte Carlo pulled up and shot him to death
Prosecutors charged the Lerma brothers with the murder
Michael Lerma told the parole board he struck a plea deal that sent him to prison for life but let his younger brother walk free
Lerma got a troubling letter from his goddaughter
Two men — “Danny Boy” and “Franky B” — were “threatening our family,” she wrote
authorities suspected she was talking about Frank Buelna
a Mexican Mafia member who was shaking down drug dealers in Pomona with his right-hand man
Lerma assured his goddaughter: “As for those a—holes
Things have a way of working out in time.”
authorities had tapped the phones of leaders of 12th Street
when they overheard talk of killing Buelna
They arrested four suspects before the plot was carried out
Three were convicted of conspiring to murder Buelna
a reputed Mexican Mafia member from Ontario — posted $1-million bail and vanished
Buelna went to his usual Pomona watering hole
Lerma spent 26 years in solitary confinement at Pelican Bay
a maximum-security prison near the Oregon border
an FBI agent testified that the task of collecting “taxes” from Pomona’s gangs fell to a woman named Cheryl Perez
Lerma told the parole board he’d known Perez
Authorities said Perez acted as Lerma’s mouthpiece and handled his money
although she didn’t seem to be kicking up much
Financial records showed Perez and her daughter deposited $570 over a three-year period into an account Lerma used to buy commissary items in prison
“There’s zero evidence of the hundreds of thousands of dollars that Michael Lerma should have allegedly been getting from drug dealers and extortions,” his lawyer said
One of Perez’s associates was Seferino “Spooky” Gonzalez
who called her often in 2013 using the recorded jail phones at the North County Correctional Facility in Castaic
According to recorded calls played in court
he told his girlfriend he was desperate to make bail so he could make enough money to repay a debt he owed Perez
“If I’m not bailed out,” he said in one call
“then I’m going to end up dead in this b—.”
FBI agent Joseph Talamantez testified that Gonzalez tried to extort money from dealers selling at a place called “The Compound.” A vacant lot filled with junked cars
its operators charged people $25 a day to sell drugs
“They’re selling a hell of a lot of s— there,” Gonzalez told his brother
Seferino Gonzalez also offered Perez a Mercedes Benz sport utility vehicle that he said a fellow inmate had “donated” to him
“And I’m still going to give you what I owe.”
But when Perez showed up with Gonzalez’s brother to collect the SUV
Perez passed the phone to Gonzalez’s brother
Talamantez testified the victim survived being shot in the leg
Perez and Gonzalez pleaded guilty to racketeering and firearms charges and were sentenced to 12 and 13 years in prison
said his client’s crime was a “personal” one and not “committed for the Mexican Mafia or Michael Lerma.”
But Gonzalez was heard on a recorded call describing to Perez their work for the Pomona godfather: “We’re his eyes
Lerma was brought to the Metropolitan Detention Center to face racketeering charges
He and his co-defendants were held in a wing of the jail called Six North that looked more like a college dormitory than a cell block
Inmates decorated their walls with posters of scantily clad women
Among the other detainees was Jose Martinez
who testified he collected “taxes” from Pomona drug dealers before being indicted with Lerma
drug trafficking and gun crimes and is serving a 13-year term
said Lerma set the tone for Latino inmates at Six North
work out and “keep the house clean,” he testified
Inmates who didn’t follow “the program” were beaten or stabbed
Lerma and his associates secured coveted orderly jobs that allowed them to roam the jail to clean and deliver food while others were locked down
let out of their cells for just 15 minutes a day
heroin and synthetic cannabis called “spice” within Six North
The markups were substantial: A gram of meth that cost $20 on the street cost up to $250 inside the jail
Inmates who couldn’t cover their debts were stabbed
Martinez said he was $300 in debt when two inmates grabbed him and brought him to a cell where Lerma and Valencia Gonzalez were waiting
The two prisoners held his arms as Valencia Gonzalez stabbed him 12 times
Lerma didn’t allow inmates to get medical treatment after being stabbed because it would draw attention from the guards
He smeared coffee grounds into his wounds and stayed for two days in the cell that he shared with Steve Bencom
a member of the King Kobras gang called “Risky.”
Bencom used his 15 minutes out of the cell to work the phone
trying to reach someone who could pay his debt
Martinez testified he saw Bencom hang up the phone and get pushed into their cell by Juan “Squeaks” Sanchez
who told him: “Your celly’s a little bit tired
Martinez said he found Bencom unresponsive on the bottom bunk in their cell
The Los Angeles County Department of Medical Examiner determined Bencom was strangled and stabbed in the heart and eye
Martinez testified Valencia Gonzalez came to his door and told him: “Keep your mouth shut.”
guards did not require him — or Bencom — to stand for two routine counts that evening
He was forced to remain in the cell overnight until Bencom’s body began to bloat
“I had to sleep the whole night with a dead body
It’s not normal to sleep with a dead body.”
When correctional officers let out Martinez the next morning to take a shower
he told them his cellmate was “man down.” A guard walked in the cell
“He came out screaming,” Martinez recalled
Defense attorneys argued it was Martinez who killed Bencom in a drug-induced rage
manipulative junkie,” Carlos Gonzalez’s attorney
There was no DNA or fingerprint evidence tying the defendants to Bencom’s homicide
And defense lawyers pointed to the records of correctional officers who attested
that Bencom was alive on the day that Martinez said he was killed
said this was because the guards at the Metropolitan Detention Center kept poor records and didn’t follow their own protocols
The trial has “blown the lid off the worst-kept secret” in the Metropolitan Detention Center
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Colossal
When Jose Lerma encountered “Reception of the Grand Condé by Louis XIV” by Jean-Léon Gérôme at the Musée d’Orsay in Paris
he found himself drawn to the figures tucked far behind the crowd
Gérôme rendered these small characters with minimal brushstrokes
a decision that has influenced Lerma’s work for more than a decade
Exaggerating the sparse quality of the figures, Lerma (previously) paints portraits in wide swaths of acrylic applied with brooms and industrial tools
The new works retain the contrasts of earlier pieces as well-defined strokes sweep across the burlap to form heavy
At Nino Mier Gallery in Brussels
Lerma’s new solo exhibition Bayamonesque presents the culmination of his current style
The title references his upbringing in Bayamón
Painting both real subjects and manufactured characters
the portraits reference those who might otherwise be relegated to the background
stripping down their likeness to only what’s necessary
Vacillating between figurative and abstract
the compositions are what Lerma refers to as “the summary of a portrait…The abstract painter in me is
drawn to certain people for specific features that can be broken down to their bare minimum as paintable elements: an expressive cowl
Bayamonesque is on view from March 14 to April 17 in Brussels. Find more from Lerma on Instagram
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ascended to eternal peace on Christmas Day at the age of 45
and inspiration that will continue to uplift and empower those who were blessed to know her
A visitation will be held from 1:00 to 3:00 PM
at Marshall & Marshall Funeral Directors in Hillsboro
Mandy's love and spirit will live on through her two brothers
Her memory will be a blessing to her three nephews
We will all deeply cherish her passion for singing and her gift of sharing love and joy with her family
The Lerma River originates in the state of Mexico
flows into Lake Chapala and emerges in Jalisco as the Santiago River
The two rivers are among the most polluted in the country
contaminated by so much human and industrial waste that treatment plants are overwhelmed
exposing locals to a toxic environment and a nauseating stench
Numerous projects have been launched to clean up the Lerma-Santiago river system
prompting people living alongside the rivers to seek their own solutions
Two of these grassroots approaches have stood the test of time
Both are schemes to filter the noxious river water
one employing eggshells and the other volcanic tezontle stones also known as clinkers or scoria
The eggshell movement got its start around 2019 when Lerma resident Elvia Evangelina Árias discovered that her neighbor
a water researcher named Verónica Martínez Miranda
Both Árias and Martínez got their water from wells partially contaminated by the Lerma River
but Martínez had protected her well with a homemade filter made of eggshells
Martínez I learned that eggshells — which are made of calcium carbonate — contain countless tiny pores that trap heavy metals and contaminants like nitrogen and phosphorus.”
a plan was formed: to create filters around wells near the Lerma River
The filters would be ditches filled with eggshells
and the aim would be to transform contaminated wells into sources of clean
With this in mind, Árias and Martínez formed a civil society organization called H2O Lerma con Encanto which put out a call for eggshells
The response was widespread and surprising
People all over began to save their eggshells and to take them to collection centers
“We made 10 protective barriers around 10 wells,” Árias told me
“Our barriers filter out the contaminants from the river
Each well is different and each requires a study
if needed— it all depends on the contaminants present
The upshot is that all 10 wells are now producing clean
potable water and they will continue to produce it for five to 40 years
depending on how close the well is to the river.”
After demonstrating the effectiveness of their filters near Mexico City and Toluca
plans were made to protect a well near the town of El Salto on the bank of the Santiago River in Jalisco
Hundreds of people contributed eggshells from all over the state
citing legal requirements that had not been met
the project had to be abandoned in Jalisco
the donation of eggshells continued unabated and today has reached the point where around five tons are collected every month
has started using Martínez’s system for a new purpose: to help wastewater treatment plants do their job better
“We are creating eggshell biofilters for these plants,” says Árias
we are helping a treatment plant in the town of Jocotitlán meet its standards
It used to have to pay a fine for not meeting them
the plant’s consumption of electricity has been reduced
While the use of eggshell filters has been put on hold in Jalisco
a different approach to cleaning contaminated water — using volcanic rock — is presently undergoing testing on the banks of the Santiago at one of its most polluted points
“All along the trajectory from Lake Chapala to Guadalajara,” says water researcher Joshua Greene
“there are 2,000 families that have concessions to use the river for irrigation purposes
They are trying to eke out a living by farming
they have no choice but to irrigate their crops with the malodorous
“They’re using it to grow wheat and oats and hopefully not so much for vegetables
they don’t consume the stuff that grows on their own land because they know what they’re putting on it
So they sell it and buy their wheat and oats from somewhere else.”
In 2016 Greene helped local people get funding to build the prototype of a simple filtration system that might allow farmers to take the filthy water from the river and transform it into grey water suitable for irrigation purposes
readily available volcanic rock called tezontle in Mexican Spanish and scoria or volcanic clinkers in English
This lightweight rock is full of holes which are home to bacteria that break down human waste
Reeds and certain flowers are then planted in the bed of wet tezontle to absorb chemicals and heavy metals
“We set up our system for educational purposes,” says Greene
but you could make something simpler: just a channel the width of a backhoe would do the trick
It’s on the property of a farmer whose family now happily uses the water that comes from it to grow things like moringa and tobacco and to water a small orchard.”
The pros and cons of using eggshell and tezontle filters to clean dirty water are presently being looked into by the government of President Claudia Sheinbaum
Worried Mexicans living alongside the Lerma
the Santiago and many other polluted rivers are hopeful that the great clean-up of filthy rivers will finally become a reality
John Pint has lived near Guadalajara, Jalisco, for more than 30 years and is the author of “A Guide to West Mexico’s Guachimontones and Surrounding Area” and co-author of “Outdoors in Western Mexico.” More of his writing can be found on his website
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Albino Christopher "Pempi" Lerma
He is survived by his loving wife; Celia Lerma
He will be greatly missed by all who knew him
A Visitation will be from 4:00 to 8:00 PM with a Vigil/Rosary at 6:00 PM
2024 at Our Lady of the Light Catholic Church
A Graveside Service will follow at 1:30 PM at Evergreen East Cemetery.
A manual recount intended to determine the ultimate winner of Corpus Christi City Council’s District 1 race is expected to get underway Monday and Tuesday
wrote City Secretary Rebecca Huerta in an email to the Caller-Times last week
only “persons expressly permitted to attend by law may be in the room where the recount is taking place or in a hallway within 30 feet of the entrance to the room,” she wrote
Those include the recount chair and committee
“any state or federal inspectors,” and Nueces County Clerk Kara Sands
An electronic recount was automatically triggered after District 1 candidates Everett Roy and Billy Lerma were found in a canvass of the Dec
Lerma “filed a petition requesting a manual recount,” Huerta wrote in the email
including mail-in and in-person (election day and early voting) ballots.”
14 runoff election after the general election found none of the original six candidates who had vied for the seat securing the 50.1% or more of the vote required to win outright
Roy and Lerma had been the two highest vote-getters among the six contenders
with Roy garnering 3,916 votes and Lerma bringing in 3,393
City officials expect to have the recount results by Friday
Huerta wrote in her email to the Caller-Times
Should a recount show Roy and Lerma still tied in votes
a decision is expected to be made with a “casting of lots” — which essentially finds the successful candidate between two who are tied in votes via a chance means
In other cities and states where election ties have occurred
that has been carried out through a variety of methods
from a coin toss and drawing names from a hat to literally rolling a dice
City records show a special council meeting scheduled for Jan
but with a range of possibilities: a “one-reading Ordinance to review Recount results for purposes of electing District One Council Member; canvassing if necessary; casting lots to resolve a tie pursuant to Texas Election Code Sec
2.028 if necessary; and declaring the person elected to be the Council Member for District One.”
should the recount not find one candidate earning more votes than the other
How the lots would be cast — if the recount doesn’t resolve a winner — hasn’t yet been determined
Lerma was not immediately available late last week for an interview
said officials need to “just go through the process.”
“The reality is every vote counted,” he said
Roy and Lerma competed for the seat in 2022
Roy bested Lerma in a runoff election that year
Guajardo wins reelection as Corpus Christi mayor, unofficial returns show
What can I recycle in Corpus Christi? Here are some answers to your questions.
The community organization Esperanza Peace and Justice Center and community members have rehabilitated the building to be used by the public once again and continue the building’s legacy as a community hub and cultural center
Lerma's bay is utilized by the Conjunto Heritage Taller and offers free accordion and bajo sexto classes for future Conjunto musicians to learn
The two northernmost bays will be a part of the Bexar County BiblioTech starting in December 2024
https://texashistory.unt.edu; crediting Rose Marine Theatre
conjunto (pronounced con-HOON-toh) is folk music that tells the story of every day working class people
specifically of Tejanos (descendants of people who settled in Texas before it was the United States
It is also used to describe Texans of Mexican Descent) from the late 1800s to today
Conjunto music originated along the Texas-Mexico border
It's deeply tied to Mexican folk music like Norteño and Tejano
conjunto often features a smaller ensemble with button accordion and bajo sexto
In addition to the bajo sexto and accordion
it also involves instruments like bass and drums
This genre is rooted not only in German sounds but also reflects the contributions of other cultures that settled in the region and utalized the button accordion
Conjunto emerged as a form of working-class expression born in the fields of German
Weekend dances on these farms and ranches served as pivotal gatherings
allowing the Tejano community to foster connections and plan for the future after a hard week’s worth of labor
The lyrics typically illustrate stories of love
reflecting the experiences of Tejanos throughout different time periods in US history
Conjunto’s sounds and popularity evolved through distinct eras
from its early roots in the late 1800s to the post WWII commercialization boom
to its rebirth and popularization in the early 2000s
Conjunto celebrations or dances were held frequently as a way to get together after long days of work
Gatherings were typically promoted through word of mouth
unlike other venues that promoted their music through flyers and newspapers
The sounds of the button accordion had a limited reach until the advent of radio programming
and the emergence of a new generation of musicians in the 1920s and 1930s
These elements collectively contributed to the post-WWII boom of conjunto music along the Texas-Mexico border
the music is celebrated both in tradition and through institutions and events such as the annual Tejano Conjunto Festival in San Antonio
Tejano R.O.O.T.S Hall of Fame Museum in Alice
TX and the Texas Conjunto Music Hall of Fame and Museum in San Benito
and many more included in the Conjunto Hall of Fame have helped conjunto music thrive
Modern conjunto today continues to innovate while honoring its traditional foundations
Lerma’s is a good example of late Art Moderne design
The octagonal windows and rounded corners are a distinctive architectural feature of Art Deco style buildings
Art Deco is a decorative art style that originated in Paris
France that is defined by bold geometric shapes and strong colors
The floor level windows and the upper windows are different in both size and shape
Black and white tile detailing along the bottom half of the building was painted over for many years but has recently been uncovered
The cinder block building consists of five separate sections
All these features are demonstrations of Art Deco and Art Moderne design
Courtesy of Esperanza Peace and Justice Center
The Wu Family: A Chinese American family who are the original owners of the building that housed Lerma’s
Theodore Hong Wu was a prominent businessman in the area
Wu leased out each of the five sections of the building to different members of the community
Lerma: In 1951 the lease for the music venue was taken over by Pablo H
a local business owner who had previously owned a bar a few streets down
Upon taking over the lease Lerma changed the name of the club from El Sombrero to Lerma’s Nite Club and began featuring exclusively conjunto music
Armando Lerma: Pablo’s son Armando took over the lease after Pablo retired
Armando ran the business until 1981 when after falling ill he decided to retire
He decided to offer the lease to some family friends on the condition they keep using the name Lerma’s Nite Club
Mary and Gilbert Garcia: Mary and Gilbert Garcia were avid fans of conjunto music
so they agreed to taking over the lease when Armando retired
The Garcias eventually became the owners of the building that houses Lerma’s
which they kept open until 2010 when the building was closed by the city of San Antonio for code violations
Lerma’s Nite Club is one of the longest continually running conjunto dance halls in the US
Lerma’s stage was active for sixty years until it was forced to close down after a threat of demolition in 2010
Lerma’s was most active during the post WWII peak of conjunto and acted as a space where working class people and their families could gather to form community and express their cultural traditions
Tardeadas or afternoon dances were broadcast live on the radio
The black and white tiled floor of Lerma’s was a literal foundation for the many musical adaptations that revolutionized conjunto and was a frequent stage for artists who read like the line up for the Conjunto Hall of Fame
Despite its popularity within the conjunto community
the larger San Antonio community often disregarded Lerma’s cultural heritage due to harmful stereotypes of the West Side
“Unfortunately though many San Antonians will probably never know the charms of the 20-year-old establishment because it sees to fit the “West Side bar” stereotype” (San Antonio Express News
Lerma’s achievement in preserving both tangible and intangible heritage held significant symbolic value for the West Side community
including disinvestment in public infrastructure
and insufficient representation in preservation efforts
numerous buildings with significant West Side history have been demolished
a beloved music venue that was torn down in 2002
prompting a profound sense of mourning and loss of cultural heritage within the community
In response to the threats posed by demolition
community members and activists have tirelessly worked to protect landmarks like Lerma’s from similar fates
Thanks to the power of preservation, the Esperanza Peace and Justice Center and community members from Save Lerma’s coalition saved Lerma’s from demolition. That same year, San Antonio’s city council approved a historic landmark designation
the building was added to the National Register of Historic Places
Preservation Texas included Lerma’s on its list of Texas’s Most Endangered Places in 2014
the community hopes to open its doors again as a cultural center where people can once again come together and enjoy conjunto
Preserving a site can be difficult if you don’t know where to start
nominating a site for the National Register of Historic Places involves thorough research into its historical
You can start by gathering supporting documentation like historical records and photographs
Consider consulting with experts in relevant fields
Contact your State Historic Preservation Office (SHPO) or Tribal Historic Preservation Office (THPO) for guidance and obtain the official nomination form
Complete the form with detailed information about the site's history and physical characteristics (this is where the research and consultation come in handy.) Submit the nomination according to the SHPO’s instructions
The nomination typically is evaluated by a State Review Board and the National Park Service
the site will be listed on the National Register
helping to preserve its heritage now and for future generations
Read more on the National Register of Historic Places site where you can find step by step information on listing a site
The National Park Service’s Underrepresented Communities Grant Program (URC) works towards diversifying the nominations submitted to the National Register of Historic Places
URC grants are funded by the Historic Preservation Fund (HPF) and are administered by the NPS
Projects include surveys and inventories of historic properties associated with communities underrepresented in the National Register
as well as the development of nominations to the National Register for specific sites
Read more on the Historic Preservation Fund site where you can find step by step information on applying for a grant
Alejandro Wolbert Pérez, “Lerma's Nite Club,” Handbook of Texas Online, accessed May 15, 2024, https://www.tshaonline.org/handbook/entries/lermas-nite-club
"San Antonio's Redlining and Segregation," Methods of Historical Research (Spring 2020)
Anglos and Mexicans in the Making of Texas
and the Esperanza Peace and Justice Center
The Texas-Mexican Conjunto History of a Working-class Music
Bridging cultures: reflections on the heritage identity of the Texas-Mexico borderlands
San Antonio Light, May 26, 1985. Gregory Smith and Susana Segura, “Lerma’s Nite Club, San Antonio, Bexar County, Texas,” National Register of Historic Places Registration Form, United States Department of the Interior, National Park Service, 2011 (https://atlas.thc.state.tx.us/NR/pdfs/11000135/11000135.pdf)
Download the NPS app to navigate the parks on the go
Tension filled the room at City Hall during a special council meeting Tuesday as the District 1 candidates cast lots to name a winner after a runoff election showed a tie — a first for Corpus Christi
After drawing a pebble numbered “3,” incumbent City Councilman Everett Roy bested former council member Billy Lerma for the win
Mayor Paulette Guajardo explained that Roy and Lerma would roll a die to determine who would go first in drawing from a box full of numbered pebbles
Whoever had the highest number on his pebble would be deemed the winner
After Guajardo announced Roy as the winner
Lerma shook hands with Roy and quickly exited the chambers
Attempts to reach Lerma via phone for comment were unsuccessful Tuesday
he will be able to continue his work for District 1 and the city
"I think we have to continue to work on job creation and economic stability," Roy said
I'm seeing people struggling and I want to help the people in Corpus Christi be successful."
An electronic recount and a manual recount showed the candidates tied with 1,916 votes
The casting of lots was used as a tiebreaker in accordance with the Texas Election Code
More: It's cold out there. Here's where you can get warm at no cost in Corpus Christi
More: Will Selena's killer be released? Yolanda Saldívar's parole eligibility date approaches
John Oliva covers entertainment and community news in South Texas. Contact him at john.oliva@caller.com or Bluesky @johnpoliva.bsky.social
Consider supporting local journalism with a subscription to the Caller-Times
2025 at 12:50 PM UTC·1 min readThe FA Cup has been going for almost 125 years
The old competition has seen some truly remarkable moments and landmark goals but we were almost treated to one of its very best this afternoon
This Jefferson Lerma effort almost broke the deadlock between Fulham and Crystal Palace
with just the outside of the post stopping one of the best goals we've ever seen
Metrics details
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system
Inflammation is gradually compartmentalized and restricted to specific tissue niches such as the lesion rim
the precise cell type composition of such niches
their interactions and changes between chronic active and inactive stages are incompletely understood
We used single-nucleus and spatial transcriptomics from subcortical MS and corresponding control tissues to map cell types and associated pathways to lesion and nonlesion areas
We identified niches such as perivascular spaces
the inflamed lesion rim or the lesion core that are associated with the glial scar and a cilia-forming astrocyte subtype
Focusing on the inflamed rim of chronic active lesions
we uncovered cell–cell communication events between myeloid
Our results provide insight into the cellular composition
multicellular programs and intercellular communication in tissue niches along the conversion from a homeostatic to a dysfunctional state underlying lesion progression in MS
understanding the cellular composition and molecular dynamics of the lesion microenvironment would have a critical impact on future biomarker and interventional studies in people diagnosed with MS
due to a lack of spatially resolved molecular tools
it has not been possible to discern spatially restricted areas of cell-type-specific pathology and map back those changes to defined lesion and nonlesion areas
we paired single-nucleus RNA sequencing (snRNA-seq) with spatial transcriptomics (ST) to create a large atlas of subcortical MS lesion pathology
We characterized how cell types organize in MS lesions and found a previously unreported ciliated astrocyte subtype in the demyelinated core of MS lesions
We reported the molecular differences between control
we identified spatially restricted cell–cell interactions involving glial
endothelial and immune cells specific to the rims of chronic active lesions
Our findings can be further used to target potential key events in MS pathology
Lesion characterization design (left) and histological assessment (right) of MS lesions with IHC for CD163 and CD68 (myeloid cells) and stains for iron and LFB (myelin)
Study design showing different data modalities and associated metadata
Links between samples indicate that they come from the same tissue block
Barplot with number of cell subtypes per main cell type (left)
UMAP of integrated snRNA-seq data (n = 103,794
center) and dot plot of averaged z-transformed gene expression of marker genes for each cell type (right)
Spatial panel displaying H&E staining (left)
feature plots of cell type deconvolution results (center) and inferred pathway activities (right) in CTRL and MS lesion types
Pipeline design using MOFA+ to generate a spatial clustering from the integration of gene expression and deconvoluted cell type proportions (left) and comparison of histopathological areas with the computationally annotated niches between lesion types (right)
Dot plot of averaged z-transformed gene expression of marker genes for each niche
Heatmap of z-transformed cell type proportions for each niche
asterisks indicate significance (adjusted P < 0.05)
interferon gamma signaling (R-HSA-877300) was predicted to be active in the demyelinated core and at inflamed lesion rims
Pathways related to tissue remodeling by assembly of collagen fibrils (R-HSA-2022090) mapped strongly to demyelinated lesion areas
these results show that spatial cell type mapping using deconvolution prediction models
can accurately predict the presence of cell types and associated pathways in lesion and nonlesion tissue areas
niche annotations revealed a precise cell type organization in subcortical MS and CTRL tissues
These results indicate that unsupervised niche characterization recapitulates tissue organization in subcortical MS lesions
integration of snRNA-seq with ST enabled us to generate a comprehensive paired dataset of subcortical WM in MS pathology
enabling investigation of gene expression profiles and spatial cell-type relationships
Dot plot of averaged z-transformed gene expression of marker genes for each AS subtype
Violin plots of Cilia AS marker genes compared with other AS subtypes (n = 283 for Cilia AS
n = 12,704 for rest) (two-tailed t-test; BH-adjusted P < 0.05)
Predicted number of Cilia AS per niche (empirical P < 0.05)
Spatial feature plots showing the niches (left) and spots predicted to contain Cilia AS (right)
Quantification of Cilia AS as percentage of total AS population in MS-CA
Cilia AS were quantified at lesion border (PPWM and LR) and in LC (n = 25 for border
n = 11 for LC) (two-sided Wilcoxon rank-sum test; P < 0.05)
IF staining of cilia (SPAG17) in EP cells adjacent to the lateral ventricle
IF staining of damaged axons (SMI32) and cilia (SPAG17) in the LC of MS-CA lesions
Two IF examples showcasing the length of AS cilia in the LC of MS-CA lesions; note presence of elongated SPAG17+ cilia in AS versus EP cells
Color indicates overrepresentation significance by Fisher exact test
and size indicates odds ratio between Cilia AS marker genes and each geneset
Violin plots of predicted transcription factor activity from snRNA-seq (n = 283 for Cilia AS
with the ends of the black box indicating Q1 and Q3; the whiskers extend to the furthest datapoint within 1.5 times the interquartile range (IQR)
Transcription factor FOXJ1 (square) and its target genes (circles)
Spatial feature plots showing FOXJ1 predicted activity (blue/red) and gene expression of some of its target genes (purple/green)
these results confirm an AS subtype generating large cilia structures associated with glial scar in demyelinated cores of subcortical MS lesions
MDS plot based on the aggregation of molecular and compositional differences across paired samples
Color indicates MS lesion type and control
Cumulative number of DEGs per cell type across conditions
Venn diagram visualizing overlap of aggregated DEGs between CTRL and MS lesion types
OL DEGs (left) and subtype composition (rigplot of enriched pathways for DEGst) associated with DEGs
AS DEGs (left) and subtype composition (right) associated with DEGs
MC DEGs (left) and subtype composition (right) associated with DEGs (n = 6 for CTRL
Cumulative number of DEGs per niche between MS lesion types
Color indicates association to a MS lesion type as in a
Heatmap of pathway enrichment activities between niches
AS and MC compositional changes per individual niches between MS lesion types (n = 8 for MS-CA
Violin plots illustrate the median (white dot)
25th percentile (Q1) and 75th percentile (Q3)
with the ends of the black box indicating Q1 and Q3; the whiskers extend to the furthest datapoint within 1.5× the IQR
while CTRL tissue had a unique signature having minimal overlap with MS-CA and MS-CI
MS-enriched genes derived from CA and Dis subtypes
MS-CA genes were related to MC activation (TRAF3
complement activation and heparin binding (C1QB
MS-CI MC genes were linked to tissue remodeling and regulatory functions (ANXA2
together with genes encoding proteins related to pattern recognition
cell motility and cell–cell signaling (CLEC7A
pathways enriched in MS-CI were related to tissue integrity
mitochondrial damage and cellular starvation
Although niche abundances did not change between MS lesion types
reflecting AS-mediated build-up of the glial scar in the chronic LC
suggesting sustained inflammation at the rim
these results help better characterize different lesion types by offering high-resolution spatial insights into cell types and gene expression changes across different niches
Pipeline design for the inference and filtering of CCC events
DGE analysis results obtained from snRNA-seq were used to obtain significant cell type pair ligand–receptor interactions (BH-adjusted P < 0.15)
Color scale indicates association with condition
spatially weighted interaction local scores are computed for the selected interactions and tested for significance across lesion types (BH-adjusted P < 0.15)
Violet to yellow scale indicates spatial weight; blue to red scales indicate magnitude of interaction scores
interactions are only kept if their ligand or receptor was a marker gene for a MS lesion type and specific cell subtype
conflicting interactions were dropped to ensure robustness
Cumulative number of differential interactions grouped by cell type across conditions
Venn diagram of overlapping interactions between MS lesion types and CTRL
Edge size indicates number of interactions
Green indicates healthy (CTRL) and purple disease (MS-CA and MS-CI) specificity
Top 30 significant interactions grouped by gene across conditions
Top 30 significant interactions per MS lesion types and CTRL across niches
Text color indicates sender (left) and receiver (right) cell types
Box plots of AS-encoded ligand HMGB1 and MC-encoded receptors CD163 (g) or TLR2 (h) between conditions (top left and center)
Note box plot showing cell–cell interaction scores between ligand and receptor together with predicted ST mapping (top right)
Box plots of MC-encoded ligand CD14 and both the EC-encoded (i) or AS-encoded (j) receptor ITGB1 (top left and center)
Note box plot showing interaction scores between MC and EC/AS cells with predicted ST mapping
Two-tailed Wald test for gene expression; BH-adjusted P < 0.05; n = 6 for CTRL
n = 4 for MS-CI; two-tailed Wilcoxon rank-sum test for interaction scores; BH-adjusted P < 0.10; n = 6 for CTRL
Box plots illustrate the median (white dot)
unsupervised analysis and validation of CCC events in spatially restricted MS niches can help identify disease-relevant targets
Combining unsupervised single-cell computational tools with multiplex imaging techniques would offer a holistic approach to deep tissue profiling in MS pathology
we generated a paired snRNA-seq and ST dataset
This combined approach permitted us to generate a high-resolution transcriptomic atlas of subcortical WM in CTRL and MS lesions
we focused on the composition of the main cell types and their subtypes
highlighting tissue changes between inflamed CA and noninflamed CI lesions
our analysis highlights perivascular spaces and their cellular components as a key tissue niche in MS
These results demonstrate that unsupervised computational approaches can reveal biologically relevant targets previously identified in MS and related neuroinflammatory models
this glial–immune–vascular interaction might have specific roles in blood vessel remodeling and immune cell trafficking at inflamed MS LRs
illustrate how computational methods can be used to identify disease-specific interactions and link them to specific cell subtypes and tissue niches in MS
we generated and analyzed paired snRNA-seq and ST data to reveal the complex tissue microenvironment underlying MS lesion progression
focusing on the rim area and identifying cell-type-specific and spatially restricted drivers of pathology
While future research should examine different lesion types in individual patients
our results enhance understanding of the molecular cytoarchitecture of the subcortical WM across MS lesion types
As our approach is highly driven by computational prediction models in combination with in situ validation on RNA and protein level
future work will be necessary to functionally validate the findings obtained
Data collection and analysis were not performed blind to the conditions of the experiments
The following antibodies were used: mouse anti-CD68 (cat
For chromogenic CD163 IHC and histochemistry
tissue sections were fixed on slides by thawing and drying
followed by immersion in acetone for 10 min at 4 °C
slides were allowed to dry at room temperature
CD163 was stained with an Autostainer Link 48 by Dako
Endogenous peroxidase was blocked using a ready-to-use peroxidase-blocking solution (cat
The primary antibody was diluted in antibody diluent (cat
Dako) and applied for 60 min at room temperature
slides were exposed to a mouse-specific biotinylated secondary antibody (cat
followed by incubation with streptavidin-linked horseradish peroxidase (cat
The staining was developed using a 1:50 dilution of 3,3′-diaminobenzidine (DAB) chromogen in DAB+ substrate buffer (cat
Sections were counterstained using hematoxylin and eosin (H&E) and coverslipped
Sections were stained for myelin with LFB by incubation with 0.1% LFB at 56 °C overnight
After washing with 96% ethanol and rehydration
the slides were immersed in 0.1% aqueous lithium-carbonate solution for 5 min
The staining was differentiated in 70% ethanol until the myelin sheaths obtained an intense blue color
tissue slides were washed with distilled water
counterstained with periodic acid-Schiff and
To localize ferrous and ferric iron, DAB-enhanced Turnbull Blue (TBB) was applied as described previously66
the slides were dried and exposed to 10% ammonium sulfide solution (cat
Merck) in double-distilled water for 90 min
slides were immersed in 10% potassium ferricyanide and 0.5% hydrogen chloride in an aqueous solution for 15 min
This step was followed by blocking the endogenous peroxidase with 0.01 M sodium azide and 0.3% hydrogen peroxide in methanol for 60 min
The slides were washed with 0.1 M Sorensen’s phosphate buffer and the staining was developed with a 1:50 solution of DAB chromogen (cat
Dako) and 0.005% hydrogen peroxide in Sorensen’s phosphate buffer for 20 min
Slides were counterstained with H&E and coverslipped
4% paraformaldehyde or acetone at room temperature for 10 min
Primary antibodies were diluted in PBS-T or Intercept-TBS (cat
LI-COR) and then incubated overnight at 4 °C
The slides were washed twice with PBS for 5 min and then incubated with secondary antibodies diluted in PBS-T for 2 h
Slides were then washed twice with PBS for 5 min and mounted using Fluoromount-G with 4,6-diamidino-2-phenylindole (DAPI) (cat
The following primary antibodies were used: rabbit anti-SPAG17 (cat
Separate slides were stained only with secondary antibody
The following human RNAscope assay probes were used: HMGB1 (C1)
probes were labeled with TSA Vivid Fluorophores (Fluorescein
Slides with positive ISH and human ACD bio-techne 3-plex negative probes
TBB (iron) and LFB were acquired using a Leica DM6 B microscope with Leica K3C camera at ×20 magnification
Pictures were imaged with the Leica Application Suite X (LAS X) software (v.3.8.1.26810) and exported as TIFF files and later processed using ImageJ (v.2-2.14.0) software
Images were also acquired using Hamamatsu NanoZoomer 2.0HT at ×40 magnification and exported as NPD files
Image processing of histological data was performed using GIMP-v.2.10 software
and subcellular spot detection was run for ADCY2 and SPAG17
Double positive cells were classified using a composite classifier on the estimated subcellular spots of ADCY2 and SPAG17
Staging of lesion types was performed by a trained neuropathologist specializing in MS pathology
Chronic active lesions showed a hypocellular
demyelinated lesion center but a distinct inflamed rim with presence of CD68- and CD163-positive cells
regularly containing LFB-positive myelin degradation products
Some of these lesions showed accumulation of iron-laden microglia and macrophages at the rim
Chronic inactive lesions were characterized by a fully demyelinated
a low frequency of CD68- and CD163-positive macrophages or microglia within lesions and a distinct rim without accumulation of CD68- or CD163-positive cells
The RNA integration number (RIN) was used as a sample selection criteria
and only samples with a value of ≥5.9 were included for both transcriptomic analysis
We cut 70-µm-thick sections of tissue on a Leica Microsystems CM3050S cryostat to obtain a final weight of 15 mg of tissue
QIAGEN) following the manufacturer’s recommendations
RNA integrity was measured on an Agilent 2100 Bioanalyzer using the High Sensitivity RNA ScreenTape (cat
Agilent) according to the manufacturer’s instructions
each nuclei raw expression was normalized by the median of total counts (target_sum = None) and log-transformed (log1p)
genes were filtered based on the following hyperparameters: min_count = 10
we filtered the profiles by the intersection of genes between the two atlases and log-normalized them with scanpy (target_sum = None)
the Pearson correlation between the different profiles was performed and the P value adjusted by Benjamini–Hochberg (BH) correction (BH-adjusted P < 0.05; r > 0.75)
Clusters with no clear molecular profiles were removed (denoted as NA)
The 10x Genomics Visium Spatial Gene Expression platform was used for the ST experiments
Tissue samples (RIN ≥ 5.9) were cut into 10 µm sections using a Leica CM3050 S cryostat and placed into a Spatial Gene Expression Slides (cat
region of interest (ROI) 6.5 × 6.5 mm) that was precooled inside the cryostat at −22 °C
The slides were stored in a container at −80 °C until further processing
The sections were then fixed and stained using protocol CG000160 Rev B
The sections were then imaged for a general morphological analysis and for future spatial alignment of the data using a ×10 lens equipped to a Leica DMi8 microscope and processed by LAS X
slides were permeabilized enzymatically for 18 min
This time was assessed using the 10x Visium Tissue Optimization kit (PN-1000191) and following the protocol CG000238 Rev D
The generation of the libraries was performed according to published protocols (10x Genomics): CG000239 Rev D
using the Gene Expression Reagent kit (cat
PN-1000190) and the Dual Index Plate TT Set A (cat
To assess the correct amplification of obtained cDNA
For full length of cDNA and indexed libraries analysis
the TapeStation 4200 analyzer (Agilent) was used
The libraries were loaded at 300 pM and sequenced on a NovaSeq 6000 system (Illumina) with a sequencing depth of 250 million reads per sample
The data were subjected to demultiplexing using SpaceRanger software (10x
These files were then used by SpaceRanger count to perform alignment with the human reference genome GRCh38-2020-A
fiducial detection and barcode/unique molecular identifier counting generating a spatial gene count matrix per slide
spatial coordinates were annotated manually by a trained neuropathologist based on myelin (MOG
and GFAP) marker staining into different area types using the Loupe Browser v.6.3.0 software (10x Genomics)
spots were filtered by genes (<200 genes) and genes were kept if they were expressed across different spots (number of expressed spots >3) using scanpy
raw expression of each spot was normalized by the median of total counts (target_sum = none) and log-transformed
slides were concatenated into a single AnnData object and the scanpy’s function rank_genes_groups (method = t-test_overstim_var) was used
to identify characteristic cell types per niche
cell type proportions were averaged per slide and then tested for differences against the rest (Wilcoxon rank-sum test
To assess the level of overlap between the computationally annotated niches and the ones annotated by a pathologist
the Jaccard index and the ARI were computed for each slide
ignoring categories that were not shared between annotations
similarities between intra and interniche spots were computed using the Pearson correlation at the pseudobulked gene expression and mean clr-transformed cell type proportions
Neighborhood analysis of spatial niches was performed by computing local spatial proportions
a binary matrix (spots as rows and niches as features) was generated based on the obtained niche annotations
Niche binary values per spot were weighted spatially by averaging neighboring spots using an L1-norm Gaussian kernel (bandwidth = 150)
Values were then averaged per niche across slides
INFECTION or SARS were removed before computing the enrichment
Each pseudobulk profile was built by summing the gene counts of all cells belonging to a cell type and a sample
Pseudobulk profiles built from at least ten cells were kept in the analysis
genes expressed in at least 25% of the samples were kept for the analysis
A gene was considered to be expressed in a sample if at least 100 counts were identified
Samples within a cell type with a gene coverage of <90% were excluded
Cell types with fewer than ten samples or greater than 50 genes were not included in the analysis
we inferred three factors using multicellular factor analysis on the pseudobulk expression profiles of each niche and disease sample
Pseudobulk profiles were filtered as described above
except that niches with fewer than nine samples were excluded
Distances were then computed between samples for each different level by computing the following term: distance = 1 − corr(x
where corr is the Pearson correlation coefficient between the vector values of sample x with the vector values of sample y
generating a distance matrix between samples of the same level
Each distance matrix was used to generate a level-specific MDS
Distances were summed into a single matrix
keeping only samples with paired snRNA-seq and ST data since unpaired ones have missing values
This cumulative distance matrix was also used to perform joint MDS summarizing the differences across levels
silhouette coefficient as implemented in sklearn was computed from each distance matrix at the sample level to quantify the clustering of lesion types
low expressed genes were removed using the function filter_by_expr from decoupler (group = Lesion type
Genes were tested to be differentially expressed using PyDESeq2 (v.0.3.5)
The covariates lesion type and biological sex were used as design factors
and the contrast was performed between different pairwise lesion types: MS-CA versus CTRL
MS-CI versus CTRL and MS-CA versus MS-CI (cooks_filter = False
Contrasts were performed only if enough replicates were available for a particular cell type (min samples > 2)
MS-CA and MS-CI typed MS slides were pseudobulked per niche and slide
and genes were tested for differential expression per niche between the two lesion types using the same approach described above
SC and BC were removed to make compositions as comparable as possible since they were missing in most CTRL samples
NEU were also removed due to their presence caused by the nature of the tissue sampled rather than the lesion type
Cell subtype compositions in snRNA-seq data were computed per sample and cell type in the same fashion
Niche compositions in ST data were computed per sample by summing the number of spots per niche
divided by the total number of spots in the slide and log-ratio transforming the obtained proportions
GM and EP were removed due tissue sampling reasons as described above
Cell type compositions per niche and slide were computed by summing the deconvoluted cell type abundances per cell type across spots of each niche
divided by the total sum of abundances for the niche
The obtained proportions were log-ratio transformed
Cell type compositions per slide were computed by summing all deconvoluted cell type abundances per cell type
divided by the total sum of abundances across the whole slide and log-ratio transforming the obtained proportions
The Kruskal–Wallis test was used to test for differences in each compositional type (adjusted P < 0.05)
the Wilcoxon rank-sum test was used to test for pairwise differences between lesion types (adjusted P < 0.10)
LIANA+ was used to compute a differential interaction score between a ligand of cell type A and a receptor of cell type B as the mean value between their differential gene statistics
generating lesion type-specific cellA–cellB–ligand–receptor interaction tetramers
Interactions with conflicting signs between ligand–receptor or with both genes not being significant (BH-adjusted P < 0.15) were not considered
Due to the low number of replicates for BC
TC and SC for differential expression analysis
a separate strategy was employed to infer their communications events
snRNA-seq data was filtered for the lesion type being tested keeping only genes that were expressed in at least 5% of cells
and the method rank aggregate from LIANA+ was used to infer CCC scores
Interactions that belonged to any of the three cell types and were significant were kept (BH-adjusted P < 0.15)
For the remaining significant interactions
spatially informed local scores were inferred across slides using a custom multivariate version of the normalized product method from LIANA+
cell type proportions and gene expression were binarized for each slide (proportion > (1/No
of cell types); log-normalized expression >0)
Feature values per spot were then spatially weighted by averaging neighboring spots using an L1-norm Gaussian kernel (bandwidth = 150)
The local score for a given cellA–cellB–ligand–receptor interaction was computed for each spot by the following formula:
where CA and CB are the normalized spatially weighted cell type proportions of cell type A and B
and L and R are the normalized spatially weighted gene expression values of the ligand and receptor genes
Differences of interaction scores between lesion types were tested using the Wilcoxon rank-sum test
Significant interactions with no conflicting sign with the scores obtained in snRNA-seq were selected (BH-adjusted P < 0.15)
Candidate interactions were further filtered based on the results of cell subtype compositional changes and cell subtype marker gene described in the previous sections
Interactions were kept only if the ligand or the receptor was a marker gene for at least one cell subtype that significantly changes its abundance in the corresponding lesion type (BH-adjusted P < 0.15)
Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article
All other data supporting the findings of the present study are available from the corresponding authors upon request
The custom scripts used in this work are available via GitHub at https://github.com/saezlab/VisiumMS
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Download references
Gveric (Imperial College London) for help with selection of human brain samples from the UK MS Tissue Bank
funded by the MS Society of Great Britain and Northern Ireland and A
Heidelberg University) for technical assistance and help with spatial transcriptomic preparations
We gratefully acknowledge the data storage service SDS@hd supported by the Ministry of Science
Research and the Arts Baden-Württemberg (MWK) and the German Research Foundation (DFG) through grant INST 35/1314-1 FUGG and support by the state of Baden-Württemberg through bwHPC and the DFG through grant INST 35/1134-1 FUGG
This work was supported by intramural funding provided by the Medical Faculty Mannheim of Heidelberg University (to L.S.)
research grants from the Hertie Foundation (medMS MyLab
the European Research Council (DecOmPress ERC StG
the National Multiple Sclerosis Society (RFA-2203-39300
the German Research Foundation (InCheck GRK 2727 to L.S.
research support through the Priority Program SPP 2395 to L.S
and a WU 1098/1-1 Walter-Benjamin fellowship to F.W.)
the German Federal Ministry of Education and Research (BMBF 01ZZ2004
and D.S.) the Silicon Valley Community Foundation (2017-171531(5022) to M.H.)
the National Institute Of Neurological Disorders And Stroke (R01NS114227 to S.H
the National Institute of Mental Health (RF1MH132662 to M.H.)
California Institute for Regenerative Medicine (DISC0-14514) and the National Human Genome Research Institute and NIH (U24HG002371 to M.H.)
This work was supported by the DFG Research Infrastructure NGS_CC (project 407495230) as part of the Next Generation Sequencing Competence Network (project 423957469)
NGS analyses were carried out at the Competence Center for Genomic Analysis (Kiel
These authors contributed equally: Celia Lerma-Martin
These authors jointly supervised this work: Julio Saez-Rodriguez
Heidelberg University and Heidelberg University Hospital
European Bioinformatics Institute (EMBL-EBI)
Division of Neuropathology and Neurochemistry
Comprehensive Center for Clinical Neurosciences and Mental Health
Mannheim Center for Translational Neuroscience
Translational Spatial Profiling Center (TSPC)
Interdisciplinary Center for Neurosciences
acquired images for histopathological assessment
assessed CTRL and MS tissue samples (supervised by L.S
annotated lesion and nonlesion areas of ST samples
carried out the snRNA-seq libraries and ST experiments
Trobisch acquired immunofluorescence images
performed ciliated AS quantification (supervised by S.H
designed the computational analysis (supervised by J.S.-R.)
analyzed and integrated the snRNA-seq and ST datasets (advised by C.L.-M.
generated the web browser for visualization of snRNA-seq and ST data
edited and approved submission of the manuscript
has received travel expenses from Bayer Health Care
a GSK company and received honorariums from Immunai
Pfizer and Sanofi and fees/honoraria from Travere Therapeutics
reports research support from Roche and Merck and filed a patent for the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis (WO2015166057A1)
The remaining authors declare no competing interests
reviewer(s) for their contribution to the peer review of this work
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
For each cell type: original UMAP colored by the given cell type and cell subtype name abbreviations (left); UMAP colored by cell subtypes (center left); dot plot of averaged z-transformed gene expression of marker genes for each cell subtype (center right); proportion of nuclei per condition and snRNA-seq sample grouped by cell subtype (right)
Distribution of number of genes per spot (left)
distribution of number of UMIs per spot (center) and total number of spots per ST sample (n per sample is represented at the right)
number of expressed genes per spot and annotated histopathological areas for each analyzed sample
IHC for LFB (left) to visualize demyelinated lesion areas in MS samples and IHC for CD163 (right) to highlight inflamed lesion areas of analyzed samples
Correlation plots between inferred ST cell type proportions and snRNA-seq data grouped by sample
Correlation plots comparing predicted ST cell type proportions and snRNA-seq data grouped by cell type
Proportions in a and b were log10-transformed to make them comparable
ST feature plots visualizing niches annotated in an unsupervised way per sample
Proportion of ST spots per sample grouped by niche
Proportion of ST spots per MS lesion type and CTRL grouped by niche
Jaccard index between manually annotated areas and computationally annotated niches per shared category (top) (n = 6 for WM
ST spots belonging to annotation-specific categories were ignored in the calculation
Adjusted Rand index between histopathologically annotated areas and niches annotated in an unsupervised way per ST sample (bottom) (n = 6 for CTRL
values above 0 indicate agreement between annotations
Intra-niche and inter-niche pairwise Pearson correlations of normalized pseudobulked gene expression (up) and mean centered log-ratio transformed cell type proportion (bottom) (n = 120 for EP
n = 387 for WM) (two-tailed Wilcoxon-rank sum test
IHC staining of blood vessels and perivascular spaces in MS-CA lesions with antibodies against CD3 (TC)
Mean spatially weighted proportions of neighboring niches for each niche
Heatmap of z-scaled expression of top 10 genes (positive and negative scores) per niche based on Spearman correlation corresponding to a spatial trajectory from MS lesion to CTRL white matter (VI-LC-LR-PPWM-WM)
Mean pathway activity across ST samples grouped by niche
Top enriched pathways for genes with a decreased expression along the spatial trajectory
Top enriched pathways for genes with an increased expression along the spatial trajectory
Quantification of Cilia AS as percentage of total AS population in MS-CI
Ciliated AS were quantified at lesion borders (combination of PPWM and LR) and in lesion core (LC) (n = 8 for Border
Quantification of Cilia AS density in MS-CA and MS-CI (n = 14 for Border in MS-CA
n = 4 for LC in MS-CI) (two-sided Wilcoxon rank-sum test
Cilium assembly pathway activity score for spots containing Cilia AS
Box and Violin plots illustrate the median (represented by the white dot)
Summary statistics of the multicellular factor analysis model (MOFAcellulaR) for snRNA-seq
the lower panel shows the hierarchical clustering of the factor scores for the samples in the study
Patient and sample metrics data and lesion type are indicated in each row
p-values) of testing for associations between the factor scores and if they were MS or CTRL (Dis)
The upper panel shows the percentage of explained variance of each cell type expression matrix recovered by the factor
Right box plots visualize distribution of Factor 1 and 4 scores between CTRL and MS lesion types (n = 6 for CTRL
Summary statistics of MOFAcellular for ST data of MS samples
and percentage of explained variance for each spatial niche
Right box plots visualize distribution of Factor 3 between MS lesion types (n = 8 for MS-CA
MDS computed on distances at the snRNA-seq cell type proportion level
MDS computed on distances at the ST deconvoluted cell type proportion level
MDS computed on distances at the snRNA-seq cell subtype proportion level
MDS computed on distances at the snRNA-seq MOFAcellulaR factor level
MDS computed on distances at the ST MOFAcellulaR factor level
MDS computed on distances at the aggregated distances across all levels
Distribution of silhouette coefficient for each sample grouped by level (n = 16 for snRNA-seq prop
Box plots illustrate the median (represented by the white dot)
Color indicates association to a condition
Dot plot of enriched pathways for DEGs of OL
Remaining cell type and subtype compositional changes across conditions
n = 4 for MS-CI) (two-tailed Wilcoxon rank-sum test
Volcano plot of DEGs for PPWM and LC niches
Color indicates association to an MS lesion type
Violin plots illustrate the median (represented by the white dot)
Number of cell-cell interactions obtained at each step of the pipeline
Heatmap showing multicellular ligand-receptor interactions
Numbers indicate the number of cell type pairs
Color indicates association to MS lesion type
smFISH of CTRL samples shwoing cell-cell interaction events between ADCY2 (AS)
Barplot of CD14 (ligand) and ITGB1 (receptor) in MC across the different conditions (left
Box xfplot showing cell-cell interactions scores between ligand-receptor together with predicted ST mapping of the interaction (right) (two-tailed Wald test for gene expression
n = 4 for MS-CI; two-tailed Wilcoxon rank-sum test for interaction scores
smFISH of CTRL samples showing cell-cell interaction events between VWF (EC)
Pearson correlations between interaction spatial local scores and spatial pathway activities per ST sample
compositional analysis (Wilcoxon rank-sum)
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Tx — The person who will represent Corpus Christi residents who live in District 1 will be determined by casting lots
Nueces County Clerk Kara Sands told KRIS 6 News that the recount of ballots cast during the Corpus Christi City Council
runoff is now complete and candidates remain tied
As KRIS 6 News reported
the results of the runoff election had candidates incumbent Everett Roy and Billy Lerma tied at 1,916 votes
Lerma filed a petition asking that the recount be a complete manual recount
including mail-in and in-person election day and early voting ballots," according to an email sent to the council by Corpus Christi City Secretary Rebecca Huerta
Supervision for the recount was designated to Huerta
but she asked that the task be delegated to her assistant
given she currently works for Roy and has worked for Lerma previously
The City Secretary is one of three city employees directly hired by and supervised by the City Council
given the candidates remain tied following this recount
Roy and Lerma must cast lots to determine who will represent the residents of District 1
We spoke with both candidates Thursday afternoon
shortly after the announcement was made that the recount ended in a tie
When we asked Roy if he was nervous that the future of his district would depend on a game of chance
"I've got a few people in my camp that are looking at the rules and making sure that we've following them
but it's what happens when people don't go out to vote," Roy added
Billy Lerma also said he wasn't surprised with the tie and he was at peace
That's the important thing that we've done everything and we've been very transparent with it," Lerma said
A Special City Council meeting is Tuesday at 10 a.m
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Mexico is celebrating a premier with its first ever North American league World Cup qualifier hosted at Rancho St
Show organizer Equo put its shoulders under this high-level dressage competition and set a milestone for Mexico and Latin America by hosting the first of its kind in the region
offering riders an important opportunity to qualify for the prestigious 2025 World Cup Final
The CDI-W will be held during Mexico’s traditional holiday
of which the theme features prominently in the decoration and color scheme
It adds a unique and vibrant cultural dimension to the event which over the years at the national shows has been highly appreciated by everyone in attendance
World Cup dressage in a festive atmosphere celebrating Mexico's Day of the Dead tradition"The Day of the Dead theme gives a festive atmosphere to the show
which celebrates both sport and local customs," said Mexican judge and show organizer Omar Zayrik
"We expect around 1500 people to attend this weekend and have made it into a "dressage and wine" social event with VIP seating and family friendly activities
This show will introduce dressage sport to a wider audience in Mexico as it promises to deliver top performances and a competitive spirit unmatched in the region."
An esteemed panel of international judges is officiating this weekend
For the World Cup qualifier Floridians Kevin Kohmann and Devon Kane have flown from the U.S.A.
joined by Canadians Evi and Tanya Strasser
Spanish Olympic team rider Borja Carrascosa has come all the way from Germany to compete in this North American league qualifier
The stage is set for the first ever CDI-W in Mexico (Photo © L
Kowalski)The weekend will be action packed as the International Dressage Officials Club (IDOC) is also hosting an FEI Judges and Steward Seminar during the weekend
Equo TV provides live streaming of the competition
making the event accessible to audiences worldwide
Claro Sports will also be broadcasting key moments of the competition
offering unprecedented coverage of this major event
Live scores can be found on Equestrian Hub
« Back
Adriana Lerma has always harbored a deep passion for Mediterranean cuisine
This inclination led her to create restaurants that reflected these culinary influences
the latter of which specializes in American-style sliders
To hone her skills in preparing Neapolitan pizza
Adriana embarked on a research trip to Naples
There she studied with master pizza makers such as Giuseppe Manuele Scalya and Joshua Serrano
winners of the Mexican Pizza Championship in 2016 and 2017
After more than six months of experimentation
he perfected the dough that characterizes the pizzas served at his Pizza Félix location
located in Mexico City's Roma Norte neighborhood
has quickly become a landmark for pizza lovers
The menu offers pizzas cooked in a wood-fired oven
and salads that combine Italian roots with American influences and Mexican ingredients
Among the most iconic creations is the “Carbo Pepe” pizza
a reinterpretation of classic cacio e pepe and carbonara pastas
Pizza Félix was ranked 45th in the world by “The Best Pizza Awards,” cementing the restaurant's international reputation
Do you want to discover the latest news and recipes of the most renowned chefs and restaurants in the world
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"We lost a lot of things that can't be replaced," said Robinson resident Michael Lerma
Lerma woke up to the smell of smoke filling his house on Saturday — he quickly rushed his family out before heading back inside to get his dogs
they found him passed out in the backyard from the smoke
Eva Lerma says she was at work when the fire started
'I know that's my home Lord' — I could tell by that smoke it's gone
but protect everyone else around it," said Robinson resident Eva Lerma
The family lost all of their belongings — including Eva’s wedding ring and two of the family dogs
we lost everything that we had,” Michael said
pictures of our kids when they were small growing up
little things that they did in school that we'd save,"
Angela Dodd heard about the fire through social media — she's one of the many who shared the family's donation needs
"We're going to be a donation site for them
so if you have something that you wanna bring by
you can bring it by and drop it off and we'll coordinate getting it to the family," said Launch Pad Espresso and Bakery owner Angela Dodd
"We're very grateful for everyone," Eva said
The Lerma family says they are overwhelmed by the support from our community
including plenty of clothes and toiletries
"Seeing everybody here in our community and the family
I have definitely been walking in that love that He wants us to show," Eva said
The Lerma family says they are thankful for the first responders and neighbors that showed up for them on Saturday
The Robinson Volunteer Fire Department says they still do not know the cause of the fire
If you'd like to help donate to the family
they are accepting drop offs at 708 Dogwood Drive in Robinson and are looking for: size extra small to small shirts and size seven shoes for their daughter; medium to large shirts and size nine shoes for their son; size large shirts
size 10 pants and size 7 shoes for the mother; and size extra large shirts
36/32 jeans and size 10.5 shoes for the father