Cells undergoing cell death protect their neighbors to maintain tissue integrity.
To enable tissue renewal, human tissues constantly eliminate millions of cells, without jeopardizing tissue integrity, form, and connectivity. The mechanisms involved in maintaining this integrity remain unknown. Scientists from the Institut Pasteur and the CNRS recently revealed a new process that allows eliminated cells to temporarily protect their neighbors from cell death, thereby maintaining tissue integrity. This protective mechanism is vital, and if disrupted can lead to a temporary loss of connectivity. The scientists observed that when the mechanism is deactivated, the simultaneous elimination of several neighboring cells compromises tissue integrity. This lack of integrity could be responsible for chronic inflammation. The results of the research were published in the journal Developmental Cell on June 2, 2021.
Human epithelia are tissues found in several parts of the body (such as the epidermis and internal mucosa). They are composed of layers of contiguous cells that serve as a physical and chemical barrier. This role is constantly being put to the test by both the outside environment and their own renewal. Tissue renewal involves the formation of new cells by cell division and the elimination of dead cells. The mechanisms that regulate the ability of epithelia to maintain their integrity in contexts involving large numbers of eliminated cells remain poorly understood, despite the fact that this situation occurs regularly during embryogenesis or the maintenance of adult tissues. For example, more than ten billion cells can be eliminated every day in an adult intestine. How are these eliminations orchestrated to maintain tissue integrity and connectivity?
Scientists from the Institut Pasteur and the CNRS set out to identify the mechanisms involved in epithelial integrity and the conditions that can affect epithelial connectivity by using Drosophila (or vinegar flies), an organism studied in the laboratory with a similar epithelial architecture to humans.
Using protein-sensitive fluorescent markers, the research team revealed that when a cell dies, the EGFR-ERK pathway – a cell activation signaling pathway known for its involvement in the regulation of cell survival – is temporarily activated in the neighboring cells. The scientists observed that the activation of the EGFR-ERK pathway protected neighboring cells from cell death for approximately one hour, thereby preventing the simultaneous elimination of a group of cells. “We already knew that this pathway plays a key role in regulating cell survival in epithelial tissue, but we were surprised to observe such protective dynamics between cells,” comments Romain Levayer, Head of the Cell Death and Epithelial Homeostasis Unit at the Institut Pasteur and last author of the study.
The scientists’ research also shows that inhibiting this protective mechanism has a drastic effect on epithelial tissue: cell elimination becomes random and neighboring cells can be eliminated simultaneously, leading to repeated losses of connectivity. The elimination of groups of neighboring cells is never observed in epithelial tissue in normal conditions, when the EGFR-ERK pathway is not deliberately inhibited, even if a large number of cells are eliminated.
By using a new optogenetic tool that can control cell death in time and space and bypass the protective mechanism, the scientists confirmed that epithelial integrity was compromised when neighboring cells were eliminated simultaneously. “Surprisingly, epithelial tissue is highly sensitive to the spatial distribution of eliminated cells. Although it can withstand the elimination of a large number of cells, epithelial integrity is affected if just three neighboring cells are eliminated simultaneously,” explains Léo Valon, a scientist in the Cell Death and Epithelial Homeostasis Unit at the Institut Pasteur and first author of the study.
The scientists’ observations confirm that tissues need to develop mechanisms preventing the elimination of neighboring groups of cells. “These observations are important as they illustrate the incredible self-organizing ability of biological tissues, a property that enables them to withstand stressful conditions. So there is no need for a conductor to orchestrate where and when the cells should die; everything is based on highly local communications between neighboring cells,” adds Romain Levayer.
This process seems to have been conserved during evolution. The same protective mechanism based on local EGFR-ERK activation was discovered independently in human cell lines by the research group led by Olivier Pertz at the University of Bern in Switzerland (the results are published in the same journal2). The results of the other study suggest that the protective mechanism is conserved between species separated by hundreds of millions of years, indicating that it is a relatively universal mechanism.
Future research will reveal whether disruption to this cell death coordination mechanism and repeated loss of connectivity in epithelial tissue could be one of the roots of chronic inflammation, a phenomenon responsible for various diseases that are currently among the leading causes of death worldwide.
Distribution of cell deaths in a Drosophila epithelium:
“Robustness of epithelial sealing is an emerging property of local ERK feedback driven by cell elimination” by Léo Valon, Anđela Davidović, Florence Levillayer, Alexis Villars, Mathilde Chouly, Fabiana Cerqueira-Campos and Romain Levayer, 2 June 2021, Developmental Cell. DOI: 10.1016/j.devcel.2021.05.006
“Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival” by Paolo Armando Gagliardi, Maciej Dobrzyński, Marc-Antoine Jacques, Coralie Dessauges, Pascal Ender, Yannick Blum, Robert M. Hughes, Andrew R. Cohen and Olivier Pertz, 2 June 2021, Developmental Cell. DOI: 10.1016/j.devcel.2021.05.007
This research project was supported by the European Research Council (ERC), a Marie Skłodowska-Curie post-doctoral fellowship, the Fondation pour la Recherche Médicale (FRM) et the Cercle Fondation Schlumberger pour l’Education et la Recherche (FSER), R.Levayer 2019 laureate.
AUSTIN (Nexstar) — A bill that could lead to new restrictions on early voting passed the Texas Senate on Thursday morning.
Senate Bill 7 passed with support from all 18 Republican state senators and opposition from all 13 Democrats. The bill limits extended early voting hours, bans drive-thru voting and forbids local election officials from encouraging voters to submit vote-by-mail applications.
If signed into law, the bill would likely impact Texas’ largest cities where voters have often faced long lines during recent elections. Some of the state’s largest counties expanded early voting hours and created drive-thru polling locations to allow more people to vote in the 2020 elections.
State Senator Bryan Hughes (R-Mineola) authored SB 7. He said the bill would require large counties with 1 million or more residents to distribute polling locations based on eligible voters, not voter turnout.
“Some of our larger counties, in recent election cycles have used their partisan power to put more polling places where their party’s voters are, and fewer polling places where the opposition party has their voters,” Hughes said.
Jim Henson, director of the Texas Politics Project, expressed concerns about the effect SB 7 may have on voter turnout.
“Texas has, typically, one of the lowest turnout rates in the country to the extent that there are people that think that that’s a problem and think that there should be more participation.” Henson said. “This legislation works in the opposite direction of solving that problem.”
Many Texas Republicans believe the bigger problem is voter fraud. Supporters believe the bill will stop people from cheating in elections. Senator Hughes said SB 7 will make voting easier and cheating more difficult.
Hughes said SB 7 also provides tracking for mail-in ballots and gives poll watchers more access to the voting process.
Similar bills have been circulating in other states, like Georgia and Pennsylvania. Hughes emphasizes this bill is only about Texas, not national politics.
“It just seems to divide us,” Hughes said. “But Senate Bill 7, on Texas elections, is about making the process safer, more effective, and more reliable for everyone across the board.”
Hours after the Senate passed SB 7, a Texas House committee held a hearing on another Republican-led effort to tighten voting rules. House Bill 6 would block election judges from removing poll watchers, tighten restrictions on those helping disabled voters, and prohibit government officials from sending mail-in ballot applications unsolicited.
The hearing was originally scheduled a week earlier, but a mistake by committee chair Rep. Briscoe Cain (R-Deer Park) unexpectedly ended the hearing early, forcing people who traveled to testify to wait for the rescheduled date.
More than 200 people turned out Thursday to speak on the bill. The testimony lasted overnight, wrapping up just before 6:00 AM Friday. With no decision made, the bill was left pending in committee. State Representative John Bucy (D-Austin), who serves on the House Elections Committee, said the public had a lot to say about HB 6.
“There’s a lot of deep concern from all over Texas about this bill, it’s gonna make it harder for people to vote, especially individuals with a disability, individuals who their English is not their first language, and our friends and in black and brown community,” Bucy said.
Bucy’s main concern is with the language in HB 6 tightening rules on people who assist a voter. The current process for vote-by-mail with the assistance of a translator or reader is to check a box saying you had assistance. HB 6 would add the requirement of filling out a form. Bucy is concerned people’s ballots will be ineligible if they are unaware of new processes.
“The result is that the ballot would be thrown out and those Texans who made that honest mistake would be disenfranchised from their right to vote,” Bucy said.
Some Texas-based corporations have spoken up against the new voting legislation, including Dell, AT&T and American Airlines.
“In a state that relies on big business, we need their voice, we need more big business to speak up if we don’t have the votes alone,” Bucy said. “As Democrats to stop this legislation, we rely on the people of Texas showing up and that includes our business partners that call Texas home.”
Bucy points to a different solution for ensuring election integrity: online voter registration.
“I think if we truly want safe and secure elections, the best way to do that is through modernization,” Bucy said. “Online voter registration is more accurate, it’s more safe and it’s more secure.”
Six bills, two women: life experiences shape perspectives on abortion legislation
The Texas Senate on Tuesday approved six bills that would further restrict access to abortions in the state. Each of the proposals still need approval from the Texas House in order for Gov. Greg Abbott to sign them into law.
Senate Bill 8, a so-called heartbeat bill, passed the Texas Senate by a vote of 19-12 on Tuesday afternoon. If approved by the House, it would ban abortions after the detection of a fetal heartbeat and establishes civil liability for abortion providers. The bill only provides an exception for a medical emergency.
“To not make any exceptions for rape or incest, for someone being a survivor, that would kill me,” said Maleeha Aziz, a community organizer for the Texas Equal Access Fund.
The bill’s author, Republican Sen. Bryan Hughes of Mineola, believes the Texas Heartbeat Act will stand up better to legal challenges than heartbeat bills in several other states, which have been blocked or held up by courts.
Senate Bill 9 serves as a “trigger” to ban nearly all abortions in the event the U.S. Supreme Court repeals the landmark abortion rights ruling of Roe v. Wade. The Texas Senate approved SB 9 by a vote of 19-12 on Tuesday.
For State Senator Angela Paxton (R-McKinney), abortion is a deeply personal topic.
“I’m an adopted child,” Sen. Angela Paxton shared Monday on the Senate floor. “My life began under circumstances that might very well have led to an abortion. I was very grateful that my mother chose life for me.”
ACLU Texas condemned Lt. Gov. Dan Patrick and the Texas Senate ahead of the votes.
“Lieutenant Governor Dan Patrick continues to push his extreme agenda by forcing seven anti-abortion bills through the Texas Senate,” Drucilla Tigner, policy and advocacy strategist for the ACLU of Texas, wrote in a statement. “Most Texans believe abortion should be legal, yet Lt. Governor Patrick has made banning abortion a top priority. The Senate should stop peddling Lt. Governor Patrick’s extreme agenda, and instead focus on the real crises facing Texans.”
State law already requires a physician to provide a woman seeking an abortion with “informed consent” materials. Senate Bill 802 would require a woman to also receive consultation from a third-party service provider under the Texas Health and Human Services Commission.
A physician would have to verify that a woman seeking an abortion received the “unique identifying number” provided by the service provider and recorded in a government database.
While federal guidelines say pill-induced abortion treatments are suitable up to 10 weeks of pregnancy, Senate Bill 394 would ban the option after seven weeks.
Aziz used the pill abortion treatment twice — once as a college student who, despite being on birth control, was faced with an unplanned pregnancy and recently after an unplanned pregnancy with her husband.
Aziz and her husband have a young daughter, but she faced a difficult pregnancy and worried about potential health complications.
“I feel like all abortions are valid, regardless of the circumstances, because only the person going through it knows their circumstances the best,” Aziz told KXAN. “It’s also nobody’s business.”
Senate Bill 1173 would ban abortions “on the basis of race, ethnicity, sex, probability or confirmed diagnosis of Down Syndrome or probability or diagnosis of a disability.”
The bill would also ban abortions in the third trimester of pregnancy unless there is a medical emergency.
‘I wonder about their families’ – One night on patrol along the border
On a windswept ranchland full of rattlesnakes and prickly pear cactus and illuminated only by a rising moon, Luis Alberto Paredes emerged limping and struggling.
The 34-year-old Guatemalan had been lost in the brush for five days without food. His two friends left him when he couldn’t keep up, he told Border Report on Friday night in a remote section of South Texas where many migrants have died trying to get around a U.S. Border Patrol checkpoint.
Paredes was spotted on surveillance cameras walking in circles on a 20,000-acre cattle ranch wearing blue jeans and a hooded sweatshirt, carrying only a small bottle of water.
His knees could not bend. His eyes rolled back as he spoke. And he barely had the energy to talk before a Border Patrol agent took him away.
Paredes said he was grateful to God for the ranch’s private security guards, who spent four hours searching for him well into dark.
“It’s my first time coming. But I couldn’t keep going with my friends. My knees hurt and they left me, but thank God for the men who found me out there,” Paredes said in Spanish, clutching a tattered silver tent cloth that he said he used to sleep.
The security guards found him about 70 miles north of the U.S.-Mexico border. He was 16 miles northeast of the Border Patrol checkpoint that is located south of the small town of Falfurrias, Texas, in an area dense with brush that migrants must traverse if they are to have any hope of making it to the interior.
With Border Patrol agents, state troopers, and law enforcement personnel concentrating on an area along the Rio Grande about an hour’s drive south to help with the overwhelming influx in migrant families and unaccompanied migrant youth crossing from Mexico, desolate regions of Texas farther north, like rural Brooks County, often contend with a harsher reality: Recovering the bodies of migrants hopelessly lost in an unforgiving terrain.
South Texas for years has had the most migrant deaths of any Southwest border area, and with law enforcement now preoccupied to the south, officials fear many more will die here.
Human traffickers known as coyotes are taking advantage of the diversion in law enforcement forces to try to move more migrants north through this dangerous region. This includes mostly single adults, who under the Biden administration’s current policies and travel restrictions implemented due to coronavirus pandemic, are not allowed to enter the United States.
Another day without food or help and Paredes likely would have died, said Brooks County Sheriff’s Patrol Deputy Roberto Castañon, who gave Border Report an exclusive overnight ride-along during his 12-hour shift through this rural county.
“He’s lucky because much longer and he wouldn’t have been walking out,” Castañon said,
As the only Brooks County sheriff’s deputy on duty that night, Castañon was called to the ranch and fetched Paredes and drove him to the entrance where he was transferred to an awaiting Border Patrol agent who took him for medical care.
“They’re usually compliant. Especially when they’re giving up. All they want is just help and they’re trying to get caught. The ones who are not compliant they usually run away from you,” Castañon said.
Castañon said he has retrieved the remains of many migrants, mostly from Central America, who lost their way in the brush and died from dehydration, rattlesnake bites, or were attacked by wild boars or coyotes when they rested or slept or were propped beneath mesquite trees to nurse injuries.
He describes how swollen their faces get and the purple and dark marks that form on their skin. He can usually tell how long they have been dead; if they were “soft” they had recently passed. Castañon talks about zipping them into body bags, showing up for his next shift, and the possibility of doing it all over again the very next day.
As triple-digit temperatures arrive and the hot, punishing South Texas sun beats down, Castañon fears he will be called out to retrieve more remains as more and more undocumented migrants continue to cross in this area.
He blames it all on the coyotes, human traffickers affiliated with drug cartels who know this region well and who even hire children to drive the migrants north from the Rio Grande Valley and then drop them off as close to the eight-lane Border Patrol checkpoint as they can. The migrants are then forced to navigate — often at night and by foot — around immigration authorities to areas north of the checkpoint to meet up with other coyotes, who take them to the interior of Texas.
In order to go around the checkpoint, the migrants — mostly adults — must cross through private properties and trek through the thick cactus and mesquite trees and soft, sandy soil. Some break into ranch trailers looking for food or shelter, Castañon said. Others die as they walk for days headed toward a “pinpoint” that coyotes have put on a cellphone they’ve been given. If they don’t reach the pickup zone in time, like Paredes, they are left behind.
Earlier this month, in an area south of the checkpoint, Castañon said he stopped a car driven by a 13-year-old boy transporting seven undocumented migrants. Castañon said it was the second time the boy from Mission, Texas, had been arrested, but charges weren’t brought against him because he is a minor, and he refused to talk with law enforcement.
Castañon said the cartels are crafty and hire people who know where to go and what not to say or do if arrested. Many will drive through ranchlands to evade arrest, he said, often endangering residents and livestock, damaging fences and property, and putting migrants at risk.
Sometimes, out of desperation, migrants will jump on the roof of resting 18-wheelers in hopes of making it north.
Castañon said a delivery truck driver parked to rest near a weigh station two weeks ago “and a migrant got on his roof. He called 911 after he found the migrant wedged in a compartment on his roof.” Castañon says they have found as many as three migrants crammed in spaces barely big enough for one adult.
They also have found hidden compartments carved into the hundreds of cars confiscated by the Brooks County Sheriff’s Department, which are on an impound lot waiting to be auctioned.
It is a game of numbers — how many they are, how few the Border Patrol and law enforcement agents are, and how vast the countryside here is. The coyotes are betting the numbers favor the migrants, and are willing to bet their lives.
With fewer than 7,000 residents, most of the residents in Brooks County own or work on cattle or hunting ranches. It’s a sparsely populated place in South Texas where the ranches span thousands of acres and where residents like their privacy and treasure peace and quiet.
But many of these ranches and fields are littered with water jugs, shoes, backpacks and remnants from where migrants have camped. Some areas smell of urine where security guards say massive groups of migrants camp nightly.
“Today more migrants die in South Texas than anywhere else in the country,” the report says.
Paredes, the migrant found Friday night, said he survived because of the water he found in the familiar blue “agua” containers. Some containers have 20-foot-tall blue flags so they can be more easily spotted by migrants.
The volunteers must negotiate with private ranchers for permission to place the water containers and not all are willing.
Many ranchers hire their own private security guards. Most do not allow Border Patrol onto their lands, said Castañon, who is allowed on as the county sheriff’s deputy and works hand in hand with the other law enforcement personnel.
The security guard who found Paredes on Friday night wished to remain anonymous. He said his boss is private and does not allow media onto the property.
On his cellphone, the private security guard scrolled through photos taken from cameras on the property showing dozens of migrants crossing, mostly walking in single-file through the waist-high brush and soft, sandy terrain. On Wednesday night, a rattlesnake bit a migrant, and another migrant carried him to them, he told Border Report.
Castañon said about 95% of all migrants he encounters say they were trying to get to Houston. “They’re not trying to get to San Antonio or Austin. It’s always Houston,” he said.
With so many places to hide, so much land and so few agents, the human traffickers are taking advantage of this current immigration swell on the border, said Castañon.
“If I don’t stop them then they’ll make it past the checkpoint,” he said as he waited at a familiar spot where he has apprehended several migrants south of the Border Patrol checkpoint.
Texas troopers used to line Highway 281 at one-mile intervals leading to the Border Patrol checkpoint, and border agents filled in the gaps and hunted migrants off-road in the fields, Castañon said. But Texas Gov. Greg Abbott earlier this month announced Operation Lone Star, which, so far, has resulted in 1,000 additional state troopers deploying further south in the Rio Grande Valley.
Aside from rescuing and tracking migrants, Castañon’s duties are vast and varied and include regularly having to assist ranchers to get cattle and goats back in their fences. The fences often are damaged by smugglers during pursuits, and aside from costing ranchers a lot in repairs, large livestock could severely damage vehicles or even kill motorists if they come upon them in the dead of the night.
Castañon puts upwards of 300 miles on his vehicle every night, mostly driving up and down Highway 285, which runs east to west into Kleberg County, as well as caliche and dirt backroads, where he often comes upon wild dogs, coyotes, and wild boar.
During last month’s deep freeze, three migrants flagged him down on Highway 285.
“One had icicles in his hair,” Castañon said. It was 27-degrees out and windy. “They just gave up and jumped into my vehicle,” he said.
His flashlight is his go-to equipment in the darkness and he says usually the animals leave him alone.
As he patrols for miles, kicking up dust and rocks and scraping paint from his vehicle on mesquite tree branches, his radio crackles with a dispatcher announcing they have a “walker” on the radio. A group of migrants have been spotted far north in the county.
But as he races miles to get there, dispatch reports that the “walkers” have migrated into Jim Wells County, the next county north, and they have lost sight of them.
He turns his vehicle around and heads back to sit and wait at the spot south of the checkpoint. He will wait there past 3 a.m.
“We’re helping them. They need help as soon as they can,” he says as he shakes his head wondering if that group will make it safely by daybreak. “It gets to me because I have a 2-year-old,” he said. “I wonder about their families.”
Tracking health equity in Texas
When we spoke to Rep. Garnet Coleman, D-Houston, last November via Zoom, he was sitting in his COVID-19 safe haven at home preparing for the current legislative session.
He is now at the Texas capitol, and has followed through on his plan to fight to reinstate a state office that used to seek out and tackle health inequities among Texans.
The legislative bill Coleman filed March 12 would direct the office to help implement programs and strategies to address the social factors that cause health disparities related to race, ethnicity, culture, socioeconomic status, gender, age, language and region. The office would serve under the umbrella of the Texas Health and Human Services Commission but also work with other state agencies to achieve its goals.
The House Public Health Committee will hear testimony on the bill on April 7. A live feed will be available online here.
Coleman believes the employees’ first order of business should be to create a comprehensive report on the disproportionate impact the COVID-19 pandemic has had on different communities. He said the story hasn’t changed even with the vaccine rollout.
“I feel like people of color were still left behind and not treated equally,” said Coleman.
In February, CNN reported Black and brown communities were being vaccinated at far lower rates. The investigation pointed out in Harris County, where Coleman lives and serves, only a small percentage of the county’s vaccine providers were in majority-Hispanic ZIP Codes. Whiter, wealthier areas of the county had a higher concentration of provider locations.
Coleman said when he got his own vaccination, no one took down demographic information, even though it is mandated by the federal government and many people are being asked to fill out a form that asks about race and ethnicity.
“I think what happens is people go fast, and when they go fast, they skip steps,” said Coleman.
This week, his proposed legislation that also renames the Center for Elimination of Disproportionality and Disparities to something much easier to say: the Office for Health Equity, was referred to the House Public Health Committee, which Rep. Coleman serves on.
Coleman believes he will have a much easier time convincing fellow lawmakers to support the bill now that it doesn’t appear the money will have to come from the state’s general fund. Coleman said the funding needed to revive the office will likely come from the feds in the $ 1.9 trillion COVID relief bill signed by President Joe Biden in early March.
Biden also signed an executive order in January that outlined steps federal agencies need to take to address the disproportionate and severe impact of the coronavirus on communities of color and underserved populations. The federal order calls for the creation of a COVID-19 Health Equity Task Force. It’s a step that sounds very familiar to what Coleman was already working on 20 years ago when Texas lawmakers passed his bill in 2001 that created the Health Disparities Task Force.
If Coleman’s bill gets voted out of committee, it will move to the Calendars Committee and then go to the House floor for an up or down vote. Next, it will be sent to the Senate or the Senate version can come over to the House.
“This is the beginning, not the end,” said Coleman. “I believe that the COVID pandemic has exposed — just like many other general illnesses and disproportionate data and disproportionate circumstances — have exposed the fact that we don’t have an equitable health system, and we need to create an equitable health system no matter who it is.”