In an attempt to stem the spread of coronavirus, China has shut its wildlife markets for good. It is a welcome move, says Adam Vaughan

Shards of pottery probably used for transporting food suggest a mountain site in the Czech Republic may have been a nature retreat for Iron Age religious hermits

N. K. Jemisin's latest book sees New York itself come alive to fight off aliens in the first part of a new trilogy with ethnicity at its heart

A London bus stop has been transformed into a children's art gallery by a local resident who wanted to brighten the drudgery of lockdown life, creating a colourful community hub amid the anxiety and isolation of the COVID-19 pandemic.

Antwerp is regaining its glitz as Belgium eases a two-month nationwide coronavirus lockdown that virtually halted business in the world's largest diamond trade centre.

Analysts are forecasting that 250 million connected cars will be on the road as early as 2020. At the same time, the magnitude of data transfers between these cars and their environment will only continue to grow. The automotive industry is at a tipping...

STAMFORD, CT –  January 16, 2020 –  HARMAN, a wholly-owned subsidiary of Samsung Electronics Co., Ltd., focused on connected technologies and solutions for automotive, consumer and enterprise markets, today announced HARMAN RCP, a remote patient...

It has been a prized commodity for millennia – but a cocktail of conflict, poverty and burgeoning demand is putting frankincense under pressure

Notorious for making us sick, viruses are weird, undead organisms – but new insights are revealing they may have created life's glorious complexity in the first place

By closely tracking how cancer cells evolve in our bodies, we can identify their hidden weaknesses and find powerful new ways to treat tumours

The "wave function collapse" transforms vague clouds of quantum possibilities into the physical reality we know – but no one knows how. New experiments are finally revealing reality in the making

For years, the oldest turtle fossils we could find had fully formed shells. Now, more primitive fossils are revealing the strange tale of how turtle shells evolved

Expensive, risky and involving scores of people, live theater may be the last form of entertainment to come back - and will likely look very different when the curtain raises.

The low-cost carrier’s shares have a choppy morning as it reports a solid jump in annual profits and a 35% hike in its dividend.

A well-preserved fossilised tail from Spinosaurus suggests this massive dinosaur may have been able to propel itself and hunt for prey in the water

For years, the oldest turtle fossils we could find had fully formed shells. Now, more primitive fossils are revealing the strange tale of how turtle shells evolved

Wealth Enhancement Group's Nicole Webb says small cap stocks make good bets emerging from a recession but not amid the current market volatility.

Millions more Americans sought unemployment benefits last week, suggesting layoffs broadened from consumer-facing industries to other segments of the economy and could remain elevated even as many parts of the country start to reopen. This report produced by Yahaira Jacquez.

Millions more Americans sought unemployment benefits last week, suggesting layoffs broadened from consumer-facing industries to other segments of the economy and could remain elevated even as many parts of the country start to reopen. This report produced by Yahaira Jacquez.

Title: Cleaner Air Quickly Brings Big Health Benefits, Study Finds
Category: Health News
Created: 12/6/2019 12:00:00 AM
Last Editorial Review: 12/6/2019 12:00:00 AM

Title: Napping Habits Tied to Sleep Disorders
Category: Health News
Created: 5/2/2008 2:00:00 AM
Last Editorial Review: 5/2/2008 12:00:00 AM

Title: Tai Chi Benefits Heart Patients
Category: Health News
Created: 4/26/2011 1:54:00 PM
Last Editorial Review: 4/27/2011 12:00:00 AM

Title: Group Doctor Visits May Help Parkinson's Patients
Category: Health News
Created: 4/28/2011 11:01:00 AM
Last Editorial Review: 4/28/2011 12:00:00 AM

Title: ER Visits Tied to Ambien on the Rise
Category: Health News
Created: 5/1/2013 10:35:00 AM
Last Editorial Review: 5/1/2013 12:00:00 AM

Title: Home Visits May Help Heart Bypass Patients Fare Better
Category: Health News
Created: 5/1/2014 9:35:00 AM
Last Editorial Review: 5/1/2014 12:00:00 AM

Title: Trampolines Linked to More Than 1 Million ER Visits Over a Decade
Category: Health News
Created: 5/2/2014 12:35:00 PM
Last Editorial Review: 5/2/2014 12:00:00 AM

Title: HPV Vaccine Produces Early Benefits for Teen Girls: Study
Category: Health News
Created: 4/27/2015 12:00:00 AM
Last Editorial Review: 4/27/2015 12:00:00 AM

Title: Health Visits May Offer Chance to Prevent Suicide
Category: Health News
Created: 4/24/2015 12:00:00 AM
Last Editorial Review: 4/27/2015 12:00:00 AM

Title: Start Healthy Eating Habits Early to Head Off Obesity in Kids
Category: Health News
Created: 4/28/2015 12:00:00 AM
Last Editorial Review: 4/29/2015 12:00:00 AM

Title: The Family That Eats Together, Benefits
Category: Health News
Created: 5/3/2017 12:00:00 AM
Last Editorial Review: 5/3/2017 12:00:00 AM

Title: No One-Size-Fits-All for Hydrating During Sports
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM

Title: Home Gym: The Benefits of a Cross-Country Ski Machine
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM

Title: Make Your Amusement Park Visits Safe
Category: Health News
Created: 5/4/2018 12:00:00 AM
Last Editorial Review: 5/4/2018 12:00:00 AM

Title: The Surprising Benefits of Weekend Workouts
Category: Health News
Created: 5/3/2019 12:00:00 AM
Last Editorial Review: 5/3/2019 12:00:00 AM

Title: There Aren't Enough Coronavirus Test Kits to Safely Reopen America, Experts Warn
Category: Health News
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: Eating Fish in Moderation During Pregnancy Benefits Fetus: Study
Category: Health News
Created: 3/20/2020 12:00:00 AM
Last Editorial Review: 3/23/2020 12:00:00 AM

It's official—PMC has just become home to two million articles! The record-breaking article, which came from the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, became publicly available in the PMC archive on June 23. This new PMC milestone has occurred almost three years to the day since PMC reached its last one: the one-million article mark in June 2007. See also: PubMed Central Hits One Million Article Mark.

Since March 2016, the NIH Manuscript Submission (NIHMS) system has added support for researchers from the following federal agencies to deposit in PMC any manuscripts that fall under the agency’s public access policy:

• Assistant Secretary for Preparedness and Response (ASPR/HHS; intramural only at this time)
• Environmental Protection Agency (EPA; intramural only at this time)
• National Aeronautics and Space Administration (NASA; intramural/civil servants and grantees)

Manuscript deposit support for all Administration for Community Living (ACL/HHS) researchers will be available in NIHMS by October 2017 and for Department of Homeland Security researchers in early 2018.

Additionally, the Bill & Melinda Gates Foundation Open Access Policy now requires their grantees to make their published research results available in PMC immediately upon publication under a Creative Commons Attribution (CC-BY) license. Manuscript deposit support is not provided in NIHMS for Gates-funded researchers; rather the final published version of any Gates-funded article is to be deposited directly to PMC by the publisher or a funder-supported data provider without author involvement. More information on this open access policy is available on the Gates Foundation website.

PMC will continue to update the list of participating funding agencies at Public Access and PMC as support is implemented.

Title: Seniors, Getting Off the Sofa Brings Big Health Benefits
Category: Health News
Created: 3/5/2020 12:00:00 AM
Last Editorial Review: 3/6/2020 12:00:00 AM

Title: Flu Season That's Sickened 26 Million May Be at Its Peak
Category: Health News
Created: 2/21/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM

Title: Is the 'Gratitude Movement' Overrated? Study Finds It Has Limits
Category: Health News
Created: 3/16/2020 12:00:00 AM
Last Editorial Review: 3/17/2020 12:00:00 AM

Title: Erratic Sleep Habits May Boost Risk of Heart Problems: Study
Category: Health News
Created: 3/4/2020 12:00:00 AM
Last Editorial Review: 3/5/2020 12:00:00 AM

Title: First Good Evidence That Brain Hits 'Replay' While You Sleep
Category: Health News
Created: 5/5/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM

There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor–targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1–targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC₅₀ and striking regressions of Ewing sarcoma xenografts. To determine whether these compounds may also be liver protective, we performed a qPCR screen of all known liver toxicity genes in HepG2 cells to identify mithramycin-driven transcriptional changes that contribute to the liver toxicity. Mithramycin induces expression of the BTG2 gene in HepG2 but not Ewing sarcoma cells, which leads to a liver-specific accumulation of reactive oxygen species (ROS). siRNA silencing of BTG2 rescues the induction of ROS and the cytotoxicity of mithramycin in these cells. Furthermore, CDK9 inhibition blocked the induction of BTG2 to limit cytotoxicity in HepG2, but not Ewing sarcoma cells. These studies provide the basis for a synergistic and less toxic EWS-FLI1–targeted combination therapy for Ewing sarcoma.

ABSTRACT

The opportunistic bacterium Pseudomonas aeruginosa produces the fucose-specific lectin LecB, which has been identified as a virulence factor. LecB has a tetrameric structure with four opposing binding sites and has been shown to act as a cross-linker. Here, we demonstrate that LecB strongly binds to the glycosylated moieties of β1-integrins on the basolateral plasma membrane of epithelial cells and causes rapid integrin endocytosis. Whereas internalized integrins were degraded via a lysosomal pathway, washout of LecB restored integrin cell surface localization, thus indicating a specific and direct action of LecB on integrins to bring about their endocytosis. Interestingly, LecB was able to trigger uptake of active and inactive β1-integrins and also of complete α3β1-integrin–laminin complexes. We provide a mechanistic explanation for this unique endocytic process by showing that LecB has the additional ability to recognize fucose-bearing glycosphingolipids and causes the formation of membrane invaginations on giant unilamellar vesicles. In cells, LecB recruited integrins to these invaginations by cross-linking integrins and glycosphingolipids. In epithelial wound healing assays, LecB specifically cleared integrins from the surface of cells located at the wound edge and blocked cell migration and wound healing in a dose-dependent manner. Moreover, the wild-type P. aeruginosa strain PAO1 was able to loosen cell-substrate adhesion in order to crawl underneath exposed cells, whereas knockout of LecB significantly reduced crawling events. Based on these results, we suggest that LecB has a role in disseminating bacteria along the cell-basement membrane interface.

IMPORTANCE Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the leading causes of nosocomial infections. P. aeruginosa is able to switch between planktonic, intracellular, and biofilm-based lifestyles, which allows it to evade the immune system as well as antibiotic treatment. Hence, alternatives to antibiotic treatment are urgently required to combat P. aeruginosa infections. Lectins, like the fucose-specific LecB, are promising targets, because removal of LecB resulted in decreased virulence in mouse models. Currently, several research groups are developing LecB inhibitors. However, the role of LecB in host-pathogen interactions is not well understood. The significance of our research is in identifying cellular mechanisms of how LecB facilitates P. aeruginosa infection. We introduce LecB as a new member of the list of bacterial molecules that bind integrins and show that P. aeruginosa can move forward underneath attached epithelial cells by loosening cell-basement membrane attachment in a LecB-dependent manner.

ABSTRACT

A bioinformatics approach was employed to identify transcriptome alterations in the peripheral blood mononuclear cells of well-characterized human subjects who were diagnosed with early disseminated Lyme disease (LD) based on stringent microbiological and clinical criteria. Transcriptomes were assessed at the time of presentation and also at approximately 1 month (early convalescence) and 6 months (late convalescence) after initiation of an appropriate antibiotic regimen. Comparative transcriptomics identified 335 transcripts, representing 233 unique genes, with significant alterations of at least 2-fold expression in acute- or convalescent-phase blood samples from LD subjects relative to healthy donors. Acute-phase blood samples from LD subjects had the largest number of differentially expressed transcripts (187 induced, 54 repressed). This transcriptional profile, which was dominated by interferon-regulated genes, was sustained during early convalescence. 6 months after antibiotic treatment the transcriptome of LD subjects was indistinguishable from that of healthy controls based on two separate methods of analysis. Return of the LD expression profile to levels found in control subjects was concordant with disease outcome; 82% of subjects with LD experienced at least one symptom at the baseline visit compared to 43% at the early convalescence time point and only a single patient (9%) at the 6-month convalescence time point. Using the random forest machine learning algorithm, we developed an efficient computational framework to identify sets of 20 classifier genes that discriminated LD from other bacterial and viral infections. These novel LD biomarkers not only differentiated subjects with acute disseminated LD from healthy controls with 96% accuracy but also distinguished between subjects with acute and resolved (late convalescent) disease with 97% accuracy.

IMPORTANCE Lyme disease (LD), caused by Borrelia burgdorferi, is the most common tick-borne infectious disease in the United States. We examined gene expression patterns in the blood of individuals with early disseminated LD at the time of diagnosis (acute) and also at approximately 1 month and 6 months following antibiotic treatment. A distinct acute LD profile was observed that was sustained during early convalescence (1 month) but returned to control levels 6 months after treatment. Using a computer learning algorithm, we identified sets of 20 classifier genes that discriminate LD from other bacterial and viral infections. In addition, these novel LD biomarkers are highly accurate in distinguishing patients with acute LD from healthy subjects and in discriminating between individuals with active and resolved infection. This computational approach offers the potential for more accurate diagnosis of early disseminated Lyme disease. It may also allow improved monitoring of treatment efficacy and disease resolution.

ABSTRACT

A microfluidic system coupled with fluorescence microscopy is a powerful approach for quantitative analysis of bacterial growth. Here, we measure parameters of growth and dynamic localization of the cell division initiation protein FtsZ in Bacillus subtilis. Consistent with previous reports, we found that after division, FtsZ rings remain at the cell poles, and polar FtsZ ring disassembly coincides with rapid Z-ring accumulation at the midcell. In cells mutated for minD, however, the polar FtsZ rings persist indefinitely, suggesting that the primary function of the Min system is in Z-ring disassembly. The inability to recycle FtsZ monomers in the minD mutant results in the simultaneous maintenance of multiple Z-rings that are restricted by competition for newly synthesized FtsZ. Although the parameters of FtsZ dynamics change in the minD mutant, the overall cell division time remains the same, albeit with elongated cells necessary to accumulate a critical threshold amount of FtsZ for promoting medial division. Finally, the minD mutant characteristically produces minicells composed of polar peptidoglycan shown to be inert for remodeling in the wild type. Polar peptidoglycan, however, loses its inert character in the minD mutant, suggesting that the Min system not only is important for recycling FtsZ but also may have a secondary role in the spatiotemporal regulation of peptidoglycan remodeling.

IMPORTANCE Many bacteria grow and divide by binary fission in which a mother cell divides into two identical daughter cells. To produce two equally sized daughters, the division machinery, guided by FtsZ, must dynamically localize to the midcell each cell cycle. Here, we quantitatively analyzed FtsZ dynamics during growth and found that the Min system of Bacillus subtilis is essential to disassemble FtsZ rings after division. Moreover, a failure to efficiently recycle FtsZ results in an increase in cell size. Finally, we show that the Min system has an additional role in inhibiting cell wall turnover and contributes to the "inert" property of cell walls at the poles.

ABSTRACT

Recent advances in the analysis of microbial communities colonizing the human body have identified a resident microbial community in the human urinary tract (UT). Compared to many other microbial niches, the human UT harbors a relatively low biomass. Studies have identified many genera and species that may constitute a core urinary microbiome. However, the contribution of the UT microbiome to urinary tract infection (UTI) and recurrent UTI (rUTI) pathobiology is not yet clearly understood. Evidence suggests that commensal species within the UT and urogenital tract (UGT) microbiomes, such as Lactobacillus crispatus, may act to protect against colonization with uropathogens. However, the mechanisms and fundamental biology of the urinary microbiome-host relationship are not understood. The ability to measure and characterize the urinary microbiome has been enabled through the development of next-generation sequencing and bioinformatic platforms that allow for the unbiased detection of resident microbial DNA. Translating technological advances into clinical insight will require further study of the microbial and genomic ecology of the urinary microbiome in both health and disease. Future diagnostic, prognostic, and therapeutic options for the management of UTI may soon incorporate efforts to measure, restore, and/or preserve the native, healthy ecology of the urinary microbiomes.

This season’s flu vaccine was 45% effective overall and 55% effective among children and teens, the Centers for Disease Control and Prevention reported in February.