Title: Rates of Premature Adult Death Declining Worldwide
Category: Health News
Created: 4/30/2010 8:10:00 AM
Last Editorial Review: 4/30/2010 12:00:00 AM

Title: Low Testosterone Raises Heart Death Rates in Impotent Men
Category: Health News
Created: 4/29/2010 2:10:00 PM
Last Editorial Review: 4/30/2010 12:00:00 AM

Title: Microneedle Patch Might Boost Global Measles Vaccination Rates
Category: Health News
Created: 4/28/2015 12:00:00 AM
Last Editorial Review: 4/29/2015 12:00:00 AM

Title: C-Section Rates Drop Slightly With Hospital Review Program
Category: Health News
Created: 4/29/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM

Title: Rates of Severe Obesity Among U.S. Kids Still Rising: Study
Category: Health News
Created: 4/26/2016 12:00:00 AM
Last Editorial Review: 4/26/2016 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: High Measles Rates Mean Kids, Adults Need Proper Vaccination: CDC
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

ABSTRACT

Iron is a vital mineral for almost all living organisms and has a pivotal role in central metabolism. Despite its great abundance on earth, the accessibility for microorganisms is often limited, because poorly soluble ferric iron (Fe³⁺) is the predominant oxidation state in an aerobic environment. Hence, the reduction of Fe³⁺ is of essential importance to meet the cellular demand of ferrous iron (Fe²⁺) but might become detrimental as excessive amounts of intracellular Fe²⁺ tend to undergo the cytotoxic Fenton reaction in the presence of hydrogen peroxide. We demonstrate that the complex formation rate of Fe³⁺ and phenolic compounds like protocatechuic acid was increased by 46% in the presence of HCO₃^– and thus accelerated the subsequent redox reaction, yielding reduced Fe²⁺. Consequently, elevated CO₂/HCO₃^– levels increased the intracellular Fe²⁺ availability, which resulted in at least 50% higher biomass-specific fluorescence of a DtxR-based Corynebacterium glutamicum reporter strain, and stimulated growth. Since the increased Fe²⁺ availability was attributed to the interaction of HCO₃^– and chemical iron reduction, the abiotic effect postulated in this study is of general relevance in geochemical and biological environments.

IMPORTANCE In an oxygenic environment, poorly soluble Fe³⁺ must be reduced to meet the cellular Fe²⁺ demand. This study demonstrates that elevated CO₂/HCO₃^– levels accelerate chemical Fe³⁺ reduction through phenolic compounds, thus increasing intracellular Fe²⁺ availability. A number of biological environments are characterized by the presence of phenolic compounds and elevated HCO₃^– levels and include soil habitats and the human body. Fe²⁺ availability is of particular interest in the latter, as it controls the infectiousness of pathogens. Since the effect postulated here is abiotic, it generally affects the Fe²⁺ distribution in nature.

ABSTRACT

The initiation of Escherichia coli chromosomal DNA replication starts with the oligomerization of the DnaA protein at repeat sequences within the origin (ori) region. The amount of ori DNA per cell directly correlates with the growth rate. During fast growth, the cell generation time is shorter than the time required for complete DNA replication; therefore, overlapping rounds of chromosome replication are required. Under these circumstances, the ori region DNA abundance exceeds the DNA abundance in the termination (ter) region. Here, high ori/ter ratios are found to persist in (p)ppGpp-deficient [(p)ppGpp⁰] cells over a wide range of balanced exponential growth rates determined by medium composition. Evidently, (p)ppGpp is necessary to maintain the usual correlation of slow DNA replication initiation with a low growth rate. Conversely, ori/ter ratios are lowered when cell growth is slowed by incrementally increasing even low constitutive basal levels of (p)ppGpp without stress, as if (p)ppGpp alone is sufficient for this response. There are several previous reports of (p)ppGpp inhibition of chromosomal DNA synthesis initiation that occurs with very high levels of (p)ppGpp that stop growth, as during the stringent starvation response or during serine hydroxamate treatment. This work suggests that low physiological levels of (p)ppGpp have significant functions in growing cells without stress through a mechanism involving negative supercoiling, which is likely mediated by (p)ppGpp regulation of DNA gyrase.

IMPORTANCE Bacterial cells regulate their own chromosomal DNA synthesis and cell division depending on the growth conditions, producing more DNA when growing in nutritionally rich media than in poor media (i.e., human gut versus water reservoir). The accumulation of the nucleotide analog (p)ppGpp is usually viewed as serving to warn cells of impending peril due to otherwise lethal sources of stress, which stops growth and inhibits DNA, RNA, and protein synthesis. This work importantly finds that small physiological changes in (p)ppGpp basal levels associated with slow balanced exponential growth incrementally inhibit the intricate process of initiation of chromosomal DNA synthesis. Without (p)ppGpp, initiations mimic the high rates present during fast growth. Here, we report that the effect of (p)ppGpp may be due to the regulation of the expression of gyrase, an important enzyme for the replication of DNA that is a current target of several antibiotics.

ABSTRACT

Human noroviruses (HuNoVs) are the leading cause of nonbacterial gastroenteritis worldwide. Histo-blood group antigen (HBGA) expression is an important susceptibility factor for HuNoV infection based on controlled human infection models and epidemiologic studies that show an association of secretor status with infection caused by several genotypes. The fucosyltransferase 2 gene (FUT2) affects HBGA expression in intestinal epithelial cells; secretors express a functional FUT2 enzyme, while nonsecretors lack this enzyme and are highly resistant to infection and gastroenteritis caused by many HuNoV strains. These epidemiologic associations are confirmed by infections in stem cell-derived human intestinal enteroid (HIE) cultures. GII.4 HuNoV does not replicate in HIE cultures derived from nonsecretor individuals, while HIEs from secretors are permissive to infection. However, whether FUT2 expression alone is critical for infection remains unproven, since routinely used secretor-positive transformed cell lines are resistant to HuNoV replication. To evaluate the role of FUT2 in HuNoV replication, we used CRISPR or overexpression to genetically manipulate FUT2 gene function to produce isogenic HIE lines with or without FUT2 expression. We show that FUT2 expression alone affects both HuNoV binding to the HIE cell surface and susceptibility to HuNoV infection. These findings indicate that initial binding to a molecule(s) glycosylated by FUT2 is critical for HuNoV infection and that the HuNoV receptor is present in nonsecretor HIEs. In addition to HuNoV studies, these isogenic HIE lines will be useful tools to study other enteric microbes where infection and/or disease outcome is associated with secretor status.

IMPORTANCE Several studies have demonstrated that secretor status is associated with susceptibility to human norovirus (HuNoV) infection; however, previous reports found that FUT2 expression is not sufficient to allow infection with HuNoV in a variety of continuous laboratory cell lines. Which cellular factor(s) regulates susceptibility to HuNoV infection remains unknown. We used genetic manipulation of HIE cultures to show that secretor status determined by FUT2 gene expression is necessary and sufficient to support HuNoV replication based on analyses of isogenic lines that lack or express FUT2. Fucosylation of HBGAs is critical for initial binding and for modification of another putative receptor(s) in HIEs needed for virus uptake or uncoating and necessary for successful infection by GI.1 and several GII HuNoV strains.

ABSTRACT

The archaeal cytoplasmic membrane provides an anchor for many surface proteins. Recently, a novel membrane anchoring mechanism involving a peptidase, archaeosortase A (ArtA), and C-terminal lipid attachment of surface proteins was identified in the model archaeon Haloferax volcanii. ArtA is required for optimal cell growth and morphogenesis, and the S-layer glycoprotein (SLG), the sole component of the H. volcanii cell wall, is one of the targets for this anchoring mechanism. However, how exactly ArtA function and regulation control cell growth and morphogenesis is still elusive. Here, we report that archaeal homologs to the bacterial phosphatidylserine synthase (PssA) and phosphatidylserine decarboxylase (PssD) are involved in ArtA-dependent protein maturation. Haloferax volcanii strains lacking either HvPssA or HvPssD exhibited motility, growth, and morphological phenotypes similar to those of an artA mutant. Moreover, we showed a loss of covalent lipid attachment to SLG in the hvpssA mutant and that proteolytic cleavage of the ArtA substrate HVO_0405 was blocked in the hvpssA and hvpssD mutant strains. Strikingly, ArtA, HvPssA, and HvPssD green fluorescent protein (GFP) fusions colocalized to the midcell position of H. volcanii cells, strongly supporting that they are involved in the same pathway. Finally, we have shown that the SLG is also recruited to the midcell before being secreted and lipid anchored at the cell outer surface. Collectively, our data suggest that haloarchaea use the midcell as the main surface processing hot spot for cell elongation, division, and shape determination.

IMPORTANCE The subcellular organization of biochemical processes in space and time is still one of the most mysterious topics in archaeal cell biology. Despite the fact that haloarchaea largely rely on covalent lipid anchoring to coat the cell envelope, little is known about how cells coordinate de novo synthesis and about the insertion of this proteinaceous layer throughout the cell cycle. Here, we report the identification of two novel contributors to ArtA-dependent lipid-mediated protein anchoring to the cell surface, HvPssA and HvPssD. ArtA, HvPssA, and HvPssD, as well as SLG, showed midcell localization during growth and cytokinesis, indicating that haloarchaeal cells confine phospholipid processing in order to promote midcell elongation. Our findings have important implications for the biogenesis of the cell surface.

ABSTRACT

Microbial pathogens exploit host nutrients to proliferate and cause disease. Intracellular pathogens, particularly those exclusively living in the phagosome such as Histoplasma capsulatum, must adapt and acquire nutrients within the nutrient-limited phagosomal environment. In this study, we investigated which host nutrients could be utilized by Histoplasma as carbon sources to proliferate within macrophages. Histoplasma yeasts can grow on hexoses and amino acids but not fatty acids as the carbon source in vitro. Transcriptional analysis and metabolism profiling showed that Histoplasma yeasts downregulate glycolysis and fatty acid utilization but upregulate gluconeogenesis within macrophages. Depletion of glycolysis or fatty acid utilization pathways does not prevent Histoplasma growth within macrophages or impair virulence in vivo. However, loss of function in Pck1, the enzyme catalyzing the first committed step of gluconeogenesis, impairs Histoplasma growth within macrophages and severely attenuates virulence in vivo, indicating that Histoplasma yeasts rely on catabolism of gluconeogenic substrates (e.g., amino acids) to proliferate within macrophages.

IMPORTANCE Histoplasma is a primary human fungal pathogen that survives and proliferates within host immune cells, particularly within the macrophage phagosome compartment. The phagosome compartment is a nutrient-limited environment, requiring Histoplasma yeasts to be able to assimilate available carbon sources within the phagosome to meet their nutritional needs. In this study, we showed that Histoplasma yeasts do not utilize fatty acids or hexoses for growth within macrophages. Instead, Histoplasma yeasts consume gluconeogenic substrates to proliferate in macrophages. These findings reveal the phagosome composition from a nutrient standpoint and highlight essential metabolic pathways that are required for a phagosomal pathogen to proliferate in this intracellular environment.

OBJECTIVES:

Children born very preterm (VPT) are at an increased risk of developing mental health (MH) disorders. Our aim for this study was to assess rates of MH disorders in children born VPT and term at 13 years of age and stability of MH disorders between ages 7 and 13 years by using a diagnostic measure.

BACKGROUND:

Although autodialer centralized reminder and recall (C-R/R) from state immunization information systems (IISs) has been shown to raise childhood vaccination rates, its impact on human papillomavirus (HPV) vaccination rates is unclear.

Governments around the world must rapidly mobilize and make difficult policy decisions to mitigate the coronavirus disease 2019 (COVID-19) pandemic. Because deaths have been concentrated at older ages, we highlight the important role of demography, particularly, how the age structure of a population may help explain differences in fatality rates...

A growing literature at the intersection of personality psychology and behavioral economics investigates the interplay between personality and decision making in social dilemmas (1, 2). Engelmann et al. (3) extend prior research in this area by investigating the role of antisocial personality in the context of a trust game with...

Background and Objectives:

The goal of this study was to decrease admission and readmission rate for the 2296 Medicaid patients in our clinic. Our focus was to eliminate patient identified barriers to care that led to decreased quality of care. The identified barriers for our clinic included distance to care, poor same-day access, communication, and fragmented care. A team-based, collaborative approach using members from all aspects of patient care.

Upper Lutetian–Bartonian sedimentary mélanges, corresponding to ancient mud-rich submarine mass transport deposits, are widely distributed over an area c. 300 km long and tens of kilometres wide along the exhumed outer part of the External Ligurian accretionary wedge in the Northern Apennines. The occurrence of methane-derived carbonate concretions (septarians) in a specific tectonostratigraphic position below these sedimentary mélanges allows us to document the relationships among a significant period of regional-scale slope failure, climate change (the Early and Mid-Eocene Optimum stages), the dissociation of gas hydrates and accretionary tectonics during the Ligurian Tectonic Phase (early–mid-Lutetian). The distribution of septarians at the core of thrust-related anticlines suggests that the dissociation of gas hydrates was triggered by accretionary tectonics rather than climate change. The different ages of slope failure emplacement and the formation of the septarians support the view that the dissociation of gas hydrates was not the most important trigger for slope failure. The latter occurred during a tectonic quiescence stage associated with a regressive depositional trend, and probably minor residual tectonic pulses, which followed the Ligurian Tectonic Phase, favouring the dynamic re-equilibrium of the External Ligurian accretionary wedge. Our findings provide useful information for a better understanding of the factors controlling giant slope failure events in modern accretionary settings, where they may cause tsunamis.

The decline or drying up of groundwater sources near a tunnel route is damaging to groundwater users. Therefore, forecasting the impact of a tunnel on nearby groundwater sources is a challenging task in tunnel design. In this study, numerical and analytical approaches were applied to the Qomroud water conveyance tunnel (located in Lorestan province, Iran) to assess the impact of tunnelling on the nearby extraction water wells. Using simulation of groundwater-level fluctuation owing to tunnelling, the drawdown at the well locations was determined. From the drawdowns and using Dupuit's equation, the depletion of well flow rates after tunnelling was estimated. To evaluate the results, observed well flow rates before and after tunnelling were compared with the predicted flow rates. The observed and estimated water well flows (before and after tunnelling) showed a regression factor of 0.64, pointing to satisfactory results

Cinnamaldehyde (Cin), a bioactive cinnamon essential oil from traditional Chinese medicine herb Cinnamomum cassia, has been reported to have multipharmacological activities including anti-inflammation. However, its role and molecular mechanism of anti-inflammatory activity in musculoskeletal tissues remains unclear. Here, we first investigated the effects and molecular mechanisms of Cin in human synoviocyte cells. Then in vivo therapeutic effect of Cin on collagen-induced arthritis (CIA) also studied. Cell Counting Kit ‎CCK-8 assay was performed to evaluate the cell cytotoxicity. Proinflammatory cytokine expression was evaluated using quantitative polymerase chain reaction and ELISA. Protein expression was measured by western blotting. The in vivo effect of Cin (75 mg/kg per day) was evaluated in rats with CIA by gavage administration. Disease progression was assessed by clinical scoring, radiographic, and histologic examinations. Cin significantly inhibited interleukin (IL)-1β–induced IL-6, IL-8, and tumor necrosis factor-α release from human synoviocyte cells. The molecular analysis revealed that Cin impaired IL-6–induced activation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 1 (STAT1), and STAT3 signaling pathway by inhibiting the phosphorylation of JAK2, STAT1, and STAT3, without affecting NF-B pathway. Cin reduced collagen-induced swollen paw volume of arthritic rats. The anti-inflammation effects of Cin were associated with decreased severity of arthritis, joint swelling, and reduced bone erosion and destruction. Furthermore, serum IL-6 level was decreased when Cin administered therapeutically to CIA rats. Cin suppresses IL-1β–induced inflammation in synoviocytes through the JAK/STAT pathway and alleviated collagen-induced arthritis in rats. These data indicated that Cin might be a potential traditional Chinese medicine–derived, disease-modifying, antirheumatic herbal drug.

Peripheral somatosensory input is modulated in the dorsal spinal cord by a network of excitatory and inhibitory interneurons. PTF1A is a transcription factor essential in dorsal neural tube progenitors for specification of these inhibitory neurons. Thus, mechanisms regulating Ptf1a expression are key for generating neuronal circuits underlying somatosensory behaviors. Mutations targeted to distinct cis-regulatory elements for Ptf1a in mice, tested the in vivo contribution of each element individually and in combination. Mutations in an autoregulatory enhancer resulted in reduced levels of PTF1A, and reduced numbers of specific dorsal spinal cord inhibitory neurons, particularly those expressing Pdyn and Gal. Although these mutants survive postnatally, at ~3–5 wk they elicit a severe scratching phenotype. Behaviorally, the mutants have increased sensitivity to itch, but acute sensitivity to other sensory stimuli such as mechanical or thermal pain is unaffected. We demonstrate a requirement for positive transcriptional autoregulatory feedback to attain the level of the neuronal specification factor PTF1A necessary for generating correctly balanced neuronal circuits.

Vitamin D deficiency has been associated with increased incidence of diabetes, both in humans and in animal models. In addition, an association between vitamin D receptor (VDR) gene polymorphisms and diabetes has also been described. However, the involvement of VDR in the development of diabetes, specifically in pancreatic β-cells, has not been elucidated yet. Here, we aimed to study the role of VDR in β-cells in the pathophysiology of diabetes. Our results indicate that Vdr expression was modulated by glucose in healthy islets and decreased in islets from both type 1 diabetes and type 2 diabetes mouse models. In addition, transgenic mice overexpressing VDR in β-cells were protected against streptozotocin-induced diabetes and presented a preserved β-cell mass and a reduction in islet inflammation. Altogether, these results suggest that sustained VDR levels in β-cells may preserve β-cell mass and β-cell function and protect against diabetes.

Metabolic reprogramming is critical for the polarization and function of tumor-associated macrophages (TAM) and hepatocarcinogenesis, but how this reprogramming occurs is unknown. Here, we showed that receptor-interacting protein kinase 3 (RIPK3), a central factor in necroptosis, is downregulated in hepatocellular carcinoma (HCC)–associated macrophages, which correlated with tumorigenesis and enhanced the accumulation and polarization of M2 TAMs. Mechanistically, RIPK3 deficiency in TAMs reduced reactive oxygen species and significantly inhibited caspase1-mediated cleavage of PPAR. These effects enabled PPAR activation and facilitated fatty acid metabolism, including fatty acid oxidation (FAO), and induced M2 polarization in the tumor microenvironment. RIPK3 upregulation or FAO blockade reversed the immunosuppressive activity of TAMs and dampened HCC tumorigenesis. Our findings provide molecular basis for the regulation of RIPK3-mediated, lipid metabolic reprogramming of TAMs, thus highlighting a potential strategy for targeting the immunometabolism of HCC.

Plazomicin was active against 97.0% of 8,783 Enterobacterales isolates collected in the United States (2016 and 2017), and only 6 isolates carried 16S rRNA methyltransferases conferring resistance to virtually all aminoglycosides. Plazomicin (89.2% to 95.9% susceptible) displayed greater activity than amikacin (72.5% to 78.6%), gentamicin (30.4% to 45.9%), and tobramycin (7.8% to 22.4%) against carbapenem-resistant and extensively drug-resistant isolates. The discrepancies among the susceptibility rates for these agents was greater when applying breakpoints generated using the same stringent contemporary methods applied to determine plazomicin breakpoints.

Signs of deceleration of the real estate market have appeared quite clearly in many segments since the beginning of this year, according to Tran Khanh Quang, General Director of Viet An Hoa Real Estate Company.

Robots that can control puppets could one day learn to manipulate complex physical objects like clothing and flexible sheets

A new study found that organic nitrates do not have clinically relevant effects on bone mineral density or bone turnover in postmenopausal women, and the medications caused significant side effects.

The infection is being eliminated as a public health threat by countries that introduce widespread testing and treatment for those at risk

Lendbreen, a pass high in the Norwegian mountains, was an important route from the Roman era until the late Middle Ages

Researchers analyzed patient data from 10 countries. The team found a correlation between low vitamin D levels and hyperactive immune systems. Vitamin D strengths innate immunity and prevents overactive immune responses. The finding could explain several mysteries, including why children are unlikely to die from COVID-19.

The fed funds futures market is pricing in negative U.S. interest rates next year, a scenario the Federal Reserve has said it wants to avoid as many doubt that it would be an effective tool to stimulate growth.

Follow our live coronavirus updates HERE Coronavirus: the symptoms

Follow our live Covid-19 updates HERE Coronavirus: The symptoms

Follow our live coronavirus updates HERE Coronavirus: The symptoms

Read our live coronavirus updates HERE

Piers Morgan today hit out at the Government's "spectacular failure" for doing fewer coronavirus tests than 12 days ago.

Coronavirus death rates could be between 50 and 80 per cent higher in rural communities, according to scientists.

BBC presenter Jeremy Vine has trialled a "have you had it?" antibody coronavirus test not yet approved by the Government.

Boris Johnson has hailed Captain Tom Moore a "point of light" in the lives of the nation as he led tributes to the war veteran on his 100th birthday.

A huge blaze broke out at a 48-storey skyscraper in the United Arab Emirates city of Sharjah.

Latest study on nitrogen dioxide reinforces earlier research linking air pollutants and Covid-19 deaths

"Today, 75 years later, we are forced to commemorate alone, but we are not alone!" Germany's President Frank-Walter Steinmeier says, celebrating international unity in the post-war era.

To mark our 175th anniversary year, we feature a different front page each week from past editions of the Ottawa Citizen.

Coronavirus is much more likely to claim the lives of black people than white. Socio-economic factors are a significant contributor

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A universal experience is highlighting the sharp divides in our society. Few are as stark and shocking as those revealed by Thursday’s news that black people in England and Wales are more than four times as likely to die from Covid-19 as white people. Bangladeshi and Pakistani people were about three and a half times more likely, and those of Indian origin two and a half times as likely, the Office for National Statistics reported.

The disproportionately high toll of BAME people was already evident, notably among medical staff: a review of just over a hundred NHS staff who died found that almost two-thirds were black or Asian, though those groups account for less than one in seven workers in the health service. It is all the more striking, given that age is one of the biggest risk factors and the over-65s comprise only one in 20 of the BAME population, compared with almost one in five of the white population.

Fans think The Simpsons predicted everything from Trump's presidency to coronavirus

The Smile singer has often talked candidly about her previous alcohol and drug use

The snap sees the star pose in a black minidress and heels

Take a look through the model turned First Lady's sartorial history

Every year on March 8th, people around the world celebrate International Women’s Day, and at Music Canada we’re showing our commitment to gender equality by celebrating this year’s theme of #EachForEqual. The theme draws from a notion of ‘Collective Individualism,’ and the way that our individual actions can collectively make change and help create a […]

The post Music Canada Celebrates International Women’s Day 2020 appeared first on Music Canada.

Spin-off subsidiary subsequently shan't subsidize sickly smartphone setup.