Tag: 上海楼凤419论坛

Microglia play vital role in regulating neuroinflammation research shows

first_imgReviewed by James Ives, M.Psych. (Editor)Apr 23 2019A research team at Massachusetts Eye and Ear has shown that microglia, the primary immune cells of the central nervous system–including the retina of the eye–serve as “gatekeepers,” or biosensors and facilitators, of neuroinflammation in a preclinical model of autoimmune uveitis. Uveitis is one of the leading causes of blindness, accounting for approximately 10% of significant visual impairment worldwide.In a report published online today in Proceedings of the National Academy of Sciences (PNAS), the researchers describe, for the first time, a role for microglia in directing the initiation of autoimmune uveitis by orchestrating the inflammatory response within the retina. In reaction to disease induction, microglia closely associate with the retinal vasculature and facilitate inflammatory immune cell entry past the blood-brain, or ocular, barrier into the retina. When the researchers depleted microglia in this model, they observed that the disease was completely blocked.”Normally, the blood-brain barrier serves as an impediment and prevents the immune response from going into tissues of the central nervous system, including the retina. However, our results provide clear evidence, that in the context of uveitis, microglia can facilitate entry of inflammatory immune cells into the retina, and enable the host immune responses to attack cells that are not normally recognized by the immune system,” said senior author Kip M. Connor, PhD, vision researcher at Mass. Eye and Ear and Associate Professor of Ophthalmology at Harvard Medical School. “Until now, the role of microglia in retinal disease has not been fully understood, but our research shows–for the first time–that these cells serve as gatekeepers from the immune system to the central nervous system. This gateway not only has implications for treating uveitis, but may provide future avenues for drug delivery across the blood-brain barrier for other diseases of the central nervous system.”Despite significant advances in research and therapeutics, the prevalence of uveitis has not been reduced in the past 30 years. Uveitis is characterized as inflammation of the retina as well as the uveal tissues, optic nerve and vitreous, wherein a large influx of immune cells into the eye coincides with elevated inflammatory destruction. Uveitis caused by an autoimmune disease occurs in a variety of diseases including Bechet’s disease, sarcoidosis, and Vogt-Koyanagi-Harada disease. Patients with uveitis often suffer serious visual loss after persistent inflammation due to immune-mediated damage to the neuronal cells of the retina.Related StoriesPatientSource’s e-prescribing technology reduces prescription errors at RHNWhat happens when you eliminate sugar and adopt the keto diet?Botulinum toxin may offer relief from chronic pelvic pain in women with endometriosisSince microglia have multiple phenotypes and/or different stages of activation that can be associated with either harmful or beneficial effects in disease pathogenesis, their role and function in disease progression is not well defined. Researchers across all fields of medicine have recently begun to elucidate the function of microglial cells in various conditions. For example, in Alzheimer’s, Parkinson’s and other neurodegenerative diseases of the brain, microglia are thought to be harmful. In ophthalmology, it is known that microglial cells are activated in response to a number of developmental and disease indications and their roles in disease are thought to be context-dependent, where they can be either beneficial or harmful.”These findings provide the first insights into how microglia respond and function during a systemic autoimmune disease targeting the eye,” said lead author Yoko Okunuki, MD, PhD, an investigator in Dr. Connor’s laboratory and Instructor of Ophthalmology at Harvard Medical School.”This novel work by Dr. Connor and colleagues identifies that microglia regulate entry through the blood-retinal barrier, and it is our hope that these finding can be harnessed for future targeted therapies for uveitis,” says Joan W. Miller, MD, the David Glendenning Cogan Professor and Chair of Ophthalmology at Harvard Medical School, Chief of Ophthalmology at Mass. Eye and Ear and Massachusetts General Hospital, and Ophthalmologist-in-Chief at Brigham and Women’s Hospital. “It is becoming increasingly clear that microglia are involved in a number of retinal disorders as well as neuroinflammatory disorders of the central nervous system.Source: https://www.masseyeandear.org/news/press-releases/2019/04/microglia-shown-to-regulate-neuroinflammationlast_img read more

Scientists discover biological barrier that keeps cancer at bay

first_imgReviewed by Alina Shrourou, B.Sc. (Editor)May 6 2019Activins are proteins involved in a number of important biological functions, including the regulation of the menstrual cycle, cell proliferation, differentiation, apoptosis, metabolism, homeostasis, immune response, wound repair, and endocrine function.Activin B is one of the activin proteins. It binds and activates a receptor called ALK7 – a member of the tumor growth factor beta (TGFβ) receptors superfamily. When activated, ALK7 triggers a domino effect of molecular and biochemical reactions (a “signaling pathway”) that result in various changes across the cell.Now, a team of researchers spearheaded by the lab of Douglas Hanahan at EPFL have found that activin B and ALK7 expressed by cancer cells can form a “barrier” that not only prevents them from forming new tumors, but also from metastasizing. The project was led by Iacovos P. Michael, a former postdoc in Hanahan’s lab.Related StoriesStudy reveals link between inflammatory diet and colorectal cancer riskBacteria in the birth canal linked to lower risk of ovarian cancerNew study to ease plight of patients with advanced cancerThe researchers studied the ALK7 signaling pathway in mice with either pancreatic neuroendocrine tumors or breast cancer. They found that when the receptor is activated by activin B, cancer cells died via a process called apoptosis. On the contrary, blocking ALK7 activation allowed cancer cells to evade death and successfully metastasize to various organs, such as the liver, lungs and brain. And the way by which cancer cells evaded the activin B/ALK7 “barrier” was by either downregulating activin B and/or downregulating ALK7.”This study enforces the notion that apoptosis is an important barrier of tumorigenesis, and that its evasion by cancer cells is a key hallmark capability of cancer cells during malignancy and metastasis,” says Hanahan.Furthermore, this study also revealed that the presence of ALK7 correlated with prolonged relapse-free survival (longer time for reappearance) of patients with various cancers, including breast cancer. Notably, comparatively higher levels of ALK7 expression were also associated with a longer period before metastasis became apparent in breast-cancer patients.This study introduces a heretofore unappreciated role of a protective activin B/ALK7 “barrier”, which triggers apoptosis in ALK7-expressing cells that are therefore not ”authorized” to proliferate in a particular tissue microenvironment bathed in its ligand.”Elucidating how cancer cells manage to overcome nature’s various ‘safety checkpoints’ to prevent malignancy is an important step towards understanding tumor biology and disease pathogenesis,” says Iacovos Michael. Source:https://actu.epfl.ch/news/a-barrier-that-keeps-cancer-at-bay/last_img read more

How Amazon delivers holiday gifts from the buy button to your door

first_imgElizabeth Moran of Farmers Branch wears gloves on her hands and Nikes on her feet. Her hair is pulled back and up in a ponytail, that’s a safety rule. No hair longer than shoulder length allowed.From behind, she could be in the front row of a workout step class, moving to one side, up one step, next time, two steps. Her arms move up and down as she picks and puts a toy, a frying pan, a package of party paper plates into bins. She scans each item and monitors a screen, then pushes yellow tubs out to ride along conveyor belts to the next station.Demanding work conditions at Amazon’s fulfillment centers and similar operations are no secret. Job review posts warn of the repetitiveness of the work and being on your feet for 10 hours a day.Asked if her job allows her to skip aerobics workouts, Moran simply smiled.This is an Amazon Robotics warehouse for small items. No big screen TVs and trampolines here. In another online fulfillment center, she would be walking up and down aisles putting small items into a cart. Here, robots deliver the goods to Moran, who has worked at Amazon for one year.In this Amazon fulfillment center, employees make $15 to $18.75 an hour depending on experience and up to up to $28.13 an hour for overtime. Amazon raised its minimum wage to $15 an hour effective Nov. 1 for all its facilities.Moran fills multiple tubs and orders at once, even as a crew from The Dallas Morning News observes her in action.She’s picking from tall, four-sided pods that arrive automatically at her station and wait in line to serve up the next item ordered by a customer. The pods are randomly filled with merchandise and made mobile by sitting on top of robots that resemble a large version of a Roomba vacuum.Pods scurry off and wait to the side to be summoned again, either to a picking station like Moran’s or to a “stowing” station operated by Sal Ribaul, who has worked at Amazon since the center opened in March.Rhyme and reasonThe yellow pods sense when they have space to be filled and line up for Ribaul. He likened his job “to playing Tetris,” a computer game that its creators say embraces a desire to make order out of chaos.He loads a lemon zester, a fondue pot, a Star Wars toy, containers of juice, a children’s book, kids’ walkie-talkies. It all seems random. But random stowing works here. If all the lemon zesters were in one pod, it might have to travel longer to get to a picking station.The pods slide along without crashing into one another because they’re guided by software and QR codes along the floor.Picked merchandise in tubs are assigned a unique barcode and ride conveyors to the next stop on the main floor to a station where the order is boxed up.Wearing an elf hat, Jeffrey Tucker scans the order. Software suggests the box size he should pull and the amount of protective packing it needs. Automatically, the proper length of tape to seal the box comes out of a dispenser. No time to talk to Tucker because it’s almost break time and there’s one more process to witness.A small QR code on the box prompts another robot with a printer and an arm called SLAM—which stands for scan, label, apply and manifest—to create the mailing label and adhere it to the box.Along the way, scanners are looking for mix-ups and mess-ups like an item that won’t fit in the suggested box or a label wrongly placed. Those items and boxes go to another chute where people solve the issues.Truck readyPackages ready to go are moved at hundreds of feet per minute along the center’s longest conveyor, past a scanner that reads ZIP codes. That triggers sliders to position themselves behind each box to push it just at the right moment when it’s speeding by its designated chute.Down it goes in a spiral shaped tube that slows the box to land safely at a loading dock. It’s in front of the correct truck.Employees inside the trucks pack boxes to maximize the space. The trucks are driven to sorting centers, Amazon facilities that are smaller than fulfillment centers and where more packages are sorted by ZIP codes onto pallets for pick up every morning by the U.S. Postal Service.This is repeated every minute, every hour, every day in 185 fulfillment and sorting centers across 30 states. There are 10 centers in Texas.Some cities also have Prime Now hubs. They’re located in densely populated areas where Amazon offers one-hour and two-hour delivery service. Those buildings are stocked with the most purchased items that people want fast, like diapers and phone chargers. Amazon is also filling fresh food orders from Whole Foods in 63 cities.When employees exit the Coppell fulfillment center, they’re sort of scanned, too, as they walk through a metal detector that resembles ones used at airports.Alfred said Amazon doesn’t want any proprietary information leaving with employees. “We have 2,000 operational processes and we’re protective of them,” she said.And as of Wednesday, no visitors are allowed in FTW6 until after the holidays. It’s crunch time. A couple of weeks before Christmas, the inside of an Amazon Robotics fulfillment center near Dallas-Fort Worth International Airport looks more industrial than anything having to do with holiday shopping. Citation: How Amazon delivers holiday gifts from the buy button to your door: Go inside a fulfillment center (2018, December 14) retrieved 17 July 2019 from https://phys.org/news/2018-12-amazon-holiday-gifts-button-door.html Explore further As Amazon customers hit the “buy” button over and over again, workers, scanners and robots are set in motion across the sprawling 1-million-square-foot facility in a real-time display of software engineering.It’s clear why the whole place takes two 15-minute breaks and a 30-minute lunch at the same time. Everything moves in synchrony.The newest of Amazon’s local fulfillment centers, located in Coppell on airport property on West Bethel Road, is one giant assembly line operated by 2,000 full-time employees. They work 10 or 12 hours a day, four days a week. Three different day shifts and two night shifts keep the center operating 24/7.In the weeks leading up to Christmas, the fulfillment center’s lobby is decorated with twinkle lights, red and white balloons, an inflatable snowman and a Christmas tree made with garlands and, of course, Amazon boxes. The traditional box men at the entrance of every fulfillment center are dressed up for the season like toy soldiers.Why is it so loud? Because every conveyor belt throughout the four-level building is moving and carrying yellow plastic tubs and packages, said Amazon spokeswoman Brenda Alfred. The more tubs, the more bumping and clanking, the louder it gets.Conveyor belts look like roller coaster tracks in a place that she said is big enough to fit 28 football fields and made up of enough steel to construct two Eiffel Towers.Each day, employees file through subway-like grated metal turnstiles at the entrance of FTW6, the center’s given name.A white board message congratulates the staff: “Thank you FTW6 associates for successful Black Friday and Cyber Monday at FTW6. We shipped 600K units to customers and 120K units to other Amazon buildings on both days.”Last year, Amazon represented about 40 percent of U.S. e-commerce sales and about 6 percent of total retail sales, and it’s growing faster than most retailers. This year, it’s expected to capture almost 50 percent of U.S. online sales.Robots and peopleEmployees stand at stations scattered across the shiny concrete factory floor. They handle arriving inventory, pick it, package it and are always scanning it. This place would never work without scanner technology. Spanish Amazon workers in ‘Black Friday’ strike ©2018 The Dallas Morning News Distributed by Tribune Content Agency, LLC. Credit: CC0 Public Domain This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.last_img read more