Kolkata is all set to turn into a blue-and-white city during the Mamata government. The Kolkata Municipal Corporation (KMC) announced Monday that if you paint your house’ exterior blue-and-white, you will be fully exempted from paying property tax to the government. The Trinamool Congress-run KMC has come up with a proposal to waive the property tax for 2014-15 if a residential building or house is painted in the party’s favorite color combination — white and sky blue. “We will allow full waiver of property tax for 2014-15 if anybody wishes to paint his/her house or even apartment buildings, of course residential, in white and sky blue – the theme color […]

STAMFORD, CT – May 5, 2016 – Today, HARMAN International Industries, Incorporated (NYSE:HAR), the premier connected technologies company for automotive, consumer and enterprise markets, announced it will showcase the industry’s first  developer-ready ...

Google engineers have spoken out about their claims of quantum supremacy, questioning IBM’s challenges and revealing some of their big plans for coming years

Welsh mezzo-soprano Katherine Jenkins will stream a concert from an empty Royal Albert Hall on Friday evening, as locked-down Britain marks the 75th anniversary of "Victory in Europe" Day.

Investors in SkyBridge Capital asked for hundreds of millions of dollars back after the fund suffered a 23% loss in March when investments made by its debt-focused hedge fund managers soured, Anthony...

Hundreds of protesters gathered in front of a Georgia courthouse on Friday to decry the killing of an unarmed black man in February and the delay in charging two white men in a shooting captured on video that was released earlier this week.

New Scientist combines mixology with science fiction to produce recipes for the finest drinks in this – or any other – universe, from Bantha Milk to Ambrosia

The White House shelved a step-by-step guide prepared by U.S. health officials to help states safely reopen mass transit and businesses closed by the coronavirus pandemic, an administration official said on Thursday. This report produced by Chris Dignam.

Whitney Houston is headed back to the big screen in a feature film about the singer's life that took her to the heights of fame but ended in drug addiction and tragedy.

The White House shelved a step-by-step guide prepared by U.S. health officials to help states safely reopen mass transit and businesses closed by the coronavirus pandemic, an administration official said on Thursday. This report produced by Chris Dignam.

Tara Reade, the woman who alleges Joe Biden sexually assaulted her in 1993, said in a video interview on Thursday that he should withdraw from the White House race. Gloria Tso reports.

The White House shelved a step-by-step guide prepared by U.S. health officials to help states safely reopen mass transit and businesses closed by the coronavirus pandemic, an administration official said on Thursday. This report produced by Chris Dignam.

Title: White House to Challenge Ruling on Unlimited Access to 'Morning-After' Pill
Category: Health News
Created: 5/2/2013 10:35:00 AM
Last Editorial Review: 5/2/2013 12:00:00 AM

Title: Heroin Use Surges Among Whites Who Abuse Prescription Painkillers
Category: Health News
Created: 4/30/2015 12:00:00 AM
Last Editorial Review: 5/1/2015 12:00:00 AM

Title: U.S. Youth Suicide Rates Hit 19-Year High After '13 Reasons Why'
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Most Americans Hit Hard by Medical Bills
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Title: CDC Draft Guidelines For Reopening U.S. Being Reviewed by White House
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

Title: White House Says Coronavirus Vaccine Could Be Ready By January
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM

The new coronavirus is disproportionately striking minority populations—particularly urban blacks and Navajo Indians living on their reservation. Experts say social and economic factors that predate the COVID-19 crisis may help explain why.

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.

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

ABSTRACT

The malaria parasite Plasmodium falciparum traffics the virulence protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of infected red blood cells (RBCs) via membranous organelles, known as the Maurer’s clefts. We developed a method for efficient enrichment of Maurer’s clefts and profiled the protein composition of this trafficking organelle. We identified 13 previously uncharacterized or poorly characterized Maurer’s cleft proteins. We generated transfectants expressing green fluorescent protein (GFP) fusions of 7 proteins and confirmed their Maurer’s cleft location. Using co-immunoprecipitation and mass spectrometry, we generated an interaction map of proteins at the Maurer’s clefts. We identified two key clusters that may function in the loading and unloading of PfEMP1 into and out of the Maurer’s clefts. We focus on a putative PfEMP1 loading complex that includes the protein GEXP07/CX3CL1-binding protein 2 (CBP2). Disruption of GEXP07 causes Maurer’s cleft fragmentation, aberrant knobs, ablation of PfEMP1 surface expression, and loss of the PfEMP1-mediated adhesion. GEXP07 parasites have a growth advantage compared to wild-type parasites, and the infected RBCs are more deformable and more osmotically fragile.

IMPORTANCE The trafficking of the virulence antigen PfEMP1 and its presentation at the knob structures at the surface of parasite-infected RBCs are central to severe adhesion-related pathologies such as cerebral and placental malaria. This work adds to our understanding of how PfEMP1 is trafficked to the RBC membrane by defining the protein-protein interaction networks that function at the Maurer’s clefts controlling PfEMP1 loading and unloading. We characterize a protein needed for virulence protein trafficking and provide new insights into the mechanisms for host cell remodeling, parasite survival within the host, and virulence.

ABSTRACT

The appressoria that are generated by the rice blast fungus Magnaporthe oryzae in response to surface cues are important for successful colonization. Previous work showed that regulators of G-protein signaling (RGS) and RGS-like proteins play critical roles in appressorium formation. However, the mechanisms by which these proteins orchestrate surface recognition for appressorium induction remain unclear. Here, we performed comparative transcriptomic studies of Morgs mutant and wild-type strains and found that M. oryzae Aa91 (MoAa91), a homolog of the auxiliary activity family 9 protein (Aa9), was required for surface recognition of M. oryzae. We found that MoAA91 was regulated by the MoMsn2 transcription factor and that its disruption resulted in defects in both appressorium formation on the artificial inductive surface and full virulence of the pathogen. We further showed that MoAa91 was secreted into the apoplast space and was capable of competing with the immune receptor chitin elicitor-binding protein precursor (CEBiP) for chitin binding, thereby suppressing chitin-induced plant immune responses. In summary, we have found that MoAa91 is a novel signaling molecule regulated by RGS and RGS-like proteins and that MoAa91 not only governs appressorium development and virulence but also functions as an effector to suppress host immunity.

IMPORTANCE The rice blast fungus Magnaporthe oryzae generates infection structure appressoria in response to surface cues largely due to functions of signaling molecules, including G-proteins, regulators of G-protein signaling (RGS), mitogen-activated protein (MAP) kinase pathways, cAMP signaling, and TOR signaling pathways. M. oryzae encodes eight RGS and RGS-like proteins (MoRgs1 to MoRgs8), and MoRgs1, MoRgs3, MoRgs4, and MoRgs7 were found to be particularly important in appressorium development. To explore the mechanisms by which these proteins regulate appressorium development, we have performed a comparative in planta transcriptomic study and identified an auxiliary activity family 9 protein (Aa9) homolog that we named MoAa91. We showed that MoAa91 was secreted from appressoria and that the recombinant MoAa91 could compete with a chitin elicitor-binding protein precursor (CEBiP) for chitin binding, thereby suppressing chitin-induced plant immunity. By identifying MoAa91 as a novel signaling molecule functioning in appressorium development and an effector in suppressing host immunity, our studies revealed a novel mechanism by which RGS and RGS-like proteins regulate pathogen-host interactions.

Many complex human traits exhibit differences between sexes. While numerous factors likely contribute to this phenomenon, growing evidence from genome-wide studies suggest a partial explanation: that males and females from the same population possess differing genetic architectures. Despite this, mapping gene-by-sex (GxS) interactions remains a challenge likely because the magnitude of such an interaction is typically and exceedingly small; traditional genome-wide association techniques may be underpowered to detect such events, due partly to the burden of multiple test correction. Here, we developed a local Bayesian regression (LBR) method to estimate sex-specific SNP marker effects after fully accounting for local linkage-disequilibrium (LD) patterns. This enabled us to infer sex-specific effects and GxS interactions either at the single SNP level, or by aggregating the effects of multiple SNPs to make inferences at the level of small LD-based regions. Using simulations in which there was imperfect LD between SNPs and causal variants, we showed that aggregating sex-specific marker effects with LBR provides improved power and resolution to detect GxS interactions over traditional single-SNP-based tests. When using LBR to analyze traits from the UK Biobank, we detected a relatively large GxS interaction impacting bone mineral density within ABO, and replicated many previously detected large-magnitude GxS interactions impacting waist-to-hip ratio. We also discovered many new GxS interactions impacting such traits as height and body mass index (BMI) within regions of the genome where both male- and female-specific effects explain a small proportion of phenotypic variance (R² < 1 x 10^–4), but are enriched in known expression quantitative trait loci.

G-quadruplex, assembled from a square array of guanine (G) molecules, is an important structure with crucial biological roles in vivo but also a versatile template for ordered functional materials. Although the understanding of G-quadruplex structures is the focus of numerous studies, little is known regarding the control of G-quartet stacking...

Jack Nguyen and Meir M. Barak

Cortical bone remodeling is an ongoing process triggered by microdamage, where osteoclasts resorb existing bone and osteoblasts deposit new bone in the form of secondary osteons (Haversian systems). Previous studies revealed regional variance in Haversian systems structure and possibly material, between opposite cortices of the same bone. As bone mechanical properties depend on tissue structure and material, it is predicted that bone mechanical properties will vary in accordance with structural and material regional heterogeneity. To test this hypothesis, we analyzed the structure, mineral content and compressive stiffness of secondary bone from the cranial and caudal cortices of the white-tailed deer proximal humerus. We found significantly larger Haversian systems and canals in the cranial cortex but no significant difference in mineral content between the two cortices. Accordingly, we found no difference in compressive stiffness between the two cortices and thus our working hypothesis was rejected. Seeing that the deer humerus is curved and thus likely subjected to bending during habitual locomotion, we expect that similar to other curved long bones, the cranial cortex of the deer humerus is likely subjected primarily to tensile strains and the caudal cortex is likely subject primarily to compressive strains. Consequently, our results suggest that strain magnitude (larger in compression) and sign (compression vs. tension) affect differently the osteoclasts and osteoblasts in the BMU. Our results further suggest that osteoclasts are inhibited in regions of high compressive strains (creating smaller Haversian systems) while osteoblasts’ osteoid deposition and mineralization is not affected by strain magnitude and sign.

Background

Nephropathic cystinosis, a hereditary lysosomal storage disorder caused by dysfunction of the lysosomal cotransporter cystinosin, leads to cystine accumulation and cellular damage in various organs, particularly in the kidney. Close therapeutic monitoring of cysteamine, the only available disease-modifying treatment, is recommended. White blood cell cystine concentration is the current gold standard for therapeutic monitoring, but the assay is technically demanding and is available only on a limited basis. Because macrophage-mediated inflammation plays an important role in the pathogenesis of cystinosis, biomarkers of macrophage activation could have potential for the therapeutic monitoring of cystinosis.

Background

Previous studies showed that Cdc42, a member of the prototypical Rho family of small GTPases and a regulator of the actin cytoskeleton, is critical for the normal development and health of podocytes. However, upstream regulatory mechanisms for Cdc42 activity in podocytes are largely unknown.

The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1–17, domains 1–17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1–17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability.

Discovery of the Breagh gas field in the Southern North Sea (SNS) has demonstrated the potential that the Lower Carboniferous (Visean, 346.7–330.9 Ma) Farne Group reservoirs have to contribute to the UK's future energy mix. New biostratigraphic correlations provide a basis to compare Asbian and Brigantian sedimentary cores from the Breagh Field and age-equivalent sediments exposed on the Northumberland Coast, which has proved critical in gaining an understanding of exploration and development opportunities. Thirteen facies associations characterize the mixed carbonate–siliciclastic system, grouped into: marine, delta front, delta shoreface, lower delta plain and upper delta plain gross depositional environments. The facies associations are interpreted as depositing in a mixed carbonate and siliciclastic fluvio-deltaic environment, and are arranged into coarsening- and cleaning-upward cycles (parasequences) bounded by flooding surfaces. Most cycles are characterized by mouth bars, distributary channels, interdistributary bays and common braided rivers, interpreted as river-dominated deltaic deposits. Some cycles include rare shoreface and tidally-influenced deposits, interpreted as river-dominated and wave- or tide-influenced deltaic deposits. The depositional processes that formed each cycle have important implications for the reservoir net/gross ratio (where this ratio indicates the proportion of sandstone beds in a cycle), thickness and lateral extent. The deltaic deposits were controlled by a combination of tectonic and eustatic (allocyclic) events and delta avulsion (autocyclic) processes, and are likely to reflect a changing tectonic regime, from extension within elongate fault-bounded basins (synrift) to passive regional thermal subsidence (post-rift). Deep incision by the Base Permian Unconformity across the Breagh Field has removed the Westphalian, Namurian and upper Visean, to leave the more prospective thicker clastic reservoirs within closure.

Thematic collection: This article is part of the Under-explored plays and frontier basins of the UK continental shelf collection available at: https://www.lyellcollection.org/cc/under-explored-plays-and-frontier-basins-of-the-uk-continental-shelf

Genome-wide association studies have implicated thousands of noncoding variants across common human phenotypes. However, they cannot directly inform the cellular context in which disease-associated variants act. Here, we use open chromatin profiles from discrete mouse cell populations to address this challenge. We applied stratified linkage disequilibrium score regression and evaluated heritability enrichment in 64 genome-wide association studies, emphasizing schizophrenia. We provide evidence that mouse-derived human open chromatin profiles can serve as powerful proxies for difficult to obtain human cell populations, facilitating the illumination of common disease heritability enrichment across an array of human phenotypes. We demonstrate that signatures from discrete subpopulations of cortical excitatory and inhibitory neurons are significantly enriched for schizophrenia heritability with maximal enrichment in cortical layer V excitatory neurons. We also show that differences between schizophrenia and bipolar disorder are concentrated in excitatory neurons in cortical layers II-III, IV, and V, as well as the dentate gyrus. Finally, we leverage these data to fine-map variants in 177 schizophrenia loci nominating variants in 104/177. We integrate these data with transcription factor binding site, chromatin interaction, and validated enhancer data, placing variants in the cellular context where they may modulate risk.

Chitotriosidase (CHIT1) is a highly conserved and regulated chitinase secreted by activated macrophages; it is a member of the 18-glycosylase family (GH18). CHIT1 is the most prominent chitinase in humans, can cleave chitin and participates in the body's immune response and is associated with inflammation, infection, tissue damage and remodelling processes. Recently, CHIT1 has been reported to be involved in the molecular pathogenesis of pulmonary fibrosis, bronchial asthma, COPD and pulmonary infections, shedding new light on the role of these proteins in lung pathophysiology. The potential roles of CHIT1 in lung diseases are reviewed in this article.

An aging global population combined with sedentary lifestyles and unhealthy diets has contributed to an increasing incidence of obesity and type 2 diabetes. These metabolic disorders are associated with perturbations to nitric oxide (NO) signaling and impaired glucose metabolism. Dietary inorganic nitrate, found in high concentration in green leafy vegetables, can be converted to NO in vivo and demonstrates antidiabetic and antiobesity properties in rodents. Alongside tissues including skeletal muscle and liver, white adipose tissue is also an important physiological site of glucose disposal. However, the distinct molecular mechanisms governing the effect of nitrate on adipose tissue glucose metabolism and the contribution of this tissue to the glucose-tolerant phenotype remain to be determined. Using a metabolomic and stable-isotope labeling approach, combined with transcriptional analysis, we found that nitrate increases glucose uptake and oxidative catabolism in primary adipocytes and white adipose tissue of nitrate-treated rats. Mechanistically, we determined that nitrate induces these phenotypic changes in primary adipocytes through the xanthine oxidoreductase–catalyzed reduction of nitrate to NO and independently of peroxisome proliferator–activated receptor-α. The nitrate-mediated enhancement of glucose uptake and catabolism in white adipose tissue may be a key contributor to the antidiabetic effects of this anion.

Cushing syndrome results from chronic excessive exposure to glucocorticoids, impacting virtually every organ system with the most dominant effects on fat metabolism, immune function, and musculoskeletal systems. Endogenous Cushing syndrome is rare, most usually due to excess ACTH secretion from pituitary, and less frequently from ectopic tumors. Other cases result from ACTH-independent adrenal overproduction of cortisol.

This interesting case report from South Africa focuses on a difficult diagnostic challenge: apparent Cushing syndrome with inconsistent laboratory findings.

Cushing syndromeExogenousDexamethasoneSkinWhiteningCream

Summary:

Over the last two decades HER2 aberrations have been thoroughly investigated as potential therapeutic targets in advanced non–small cell lung cancer, with relatively modest results. Two articles published in this issue of Cancer Discovery further expand the knowledge on therapeutic exploitation of HER2 in lung cancer, addressing a large unmet medical need.

See related article by Li et al., p. 674.

See related article by Tsurutani et al., p. 688.

Unlike replicative senescence, oncogene-induced senescence caused heterochromatin-body formation.

BACKGROUND AND PURPOSE:

The increased severity of white matter disease is associated with worse outcomes and an increased rate of intracerebral hemorrhage in patients with ischemic stroke undergoing thrombolytic treatment. However, whether white matter disease is associated with outcomes in patients undergoing endovascular treatment remains unclear.

City of Windsor payouts on personal injury and property damage claims totaled $2.1 million in 2019, the lowest number in eight years. The total — for settlements as well as court decisions — was well below the $3 million budgeted for the hundreds of claims made each year against the city for everything from trip-and-falls, […]

As anticipated due to the COVID-19 pandemic, Windsor’s unemployment rate closed in on historic levels in April as it reached 12.9 per cent of the labour force, according to the latest numbers released Friday by Statistics Canada. There were 21,800 people in the Windsor area recorded as being unemployed in the latest StatsCan survey. But […]

White dwarf stars are common in the galaxy, but astronomers have found one that doesn't seem to obey the rules. They think it was born when two smaller white dwarfs merged together

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His cause of death is unknown.

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Researchers have used synchrotron light to study what happens to the nerves in diabetes. The technique shows the 3D-structure of nerve fibers in very high resolution.

Following a strikingly white and male list of Bafta nominees, this year’s Academy Awards shortlists are barely more diverse. It’s a chronic problem in an industry running out of excuses for its slow pace of change. Lanre Bakare examines why the Oscars are still so white. Plus: Joan E Greve on a hectic week of US politics

When the lists of nominees for the major film awards in 2020 were announced, there was, once again, a glaring anomaly. Not a single person of colour was nominated in the Bafta acting categories, while the Oscars managed only Cynthia Erivo for her part in Harriet.

It is an issue that the industry is well aware of: in 2015, the ceremony saw #OscarsSoWhite trending on Twitter, while actors such as Eddie Murphy were rebuking the academy from the stage back in the 1990s. So what explains the glacial pace of change? Guardian arts and culture correspondent Lanre Bakare tells Anushka Asthana that there have been plenty of false dawns over the years in the quest for greater diversity.

Have you ever noticed that in film and on TV, period dramas tend to have almost entirely white casts? It’s almost as if, at least in film and TV land, black people do not feature in British history at all. The Guardian’s Josh Toussaint-Strauss finds out how accurate costume dramas are in terms of racial diversity, and looks into the reasons why period dramas might get whitewashed

The White House is making "contingency plans" for a second wave of coronavirus after emails reportedly contradict their claims that Centers for Disease Control and Prevention guidelines to safely reopen the economy were set aside because medical experts did not approve of them.