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HIV/AIDS in Asia: We Need to Keep the Focus on Key Population Groups

By Tim Brown and Wiwat Peerapatanapokin HONOLULU (September 17, 2019)—In 2018, roughly 6 million people were living with HIV in Asia and the Pacific, and 310,000 were newly infected, according to UNAIDS estimates. Despite these troubling numbers, financial support for the fight against AIDS is stagnant, and international resources for HIV programs in the region are declining. Given the continued HIV infection levels and limited funds for halting the epidemic, it is more important than ever for prevention efforts to achieve maximum impact with the resources available. This means that programs need to target the key populations most at risk of contracting HIV. In Asia, these key populations are female sex workers and their clients, people who inject drugs, and men who have sex with men....

This is a summary only. Click the title for the full article, or visit www.EastWestCenter.org/Research-Wire for more.




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Can Technology Offset the Effects of Population Aging on Economic Growth? New Report from the Asian Development Bank

By East-West Center HONOLULU (March 27, 2020)—Population aging is affecting countries all across Asia. This ongoing demographic transition will leave many of the region’s economies increasingly dependent on an aging, and eventually a shrinking, workforce. Economists disagree, however, on whether population aging will necessarily lead to a slowdown in economic growth.

This is a summary only. Click the title for the full article, or visit www.EastWestCenter.org/Research-Wire for more.




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An Aging Population in Asia Creates Economic Challenges

By Andrew Mason, Sang-Hyop Lee, and Donghyun Park HONOLULU (8 May 2020)—Elderly populations in Asia are expanding more quickly than other age groups. Low fertility rates result in fewer children and eventually fewer working-age adults, while elderly populations are living longer.

This is a summary only. Click the title for the full article, or visit www.EastWestCenter.org/Research-Wire for more.





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Coronavirus: Indian manager of popular Chennai biotech firm consumes drug he invented to cure COVID-19, dies

Dubai: A 47-year-old pharmacist in the Indian state of Tamil Nadu, died on Thursday after consuming a “new cure” he had made for COVID-19. Indian tweeps shared reports of how the man, K. Sivanesan, made and drank the chemical concoction along with the owner of a popular Chennai-based herbal pharmaceutical company where he worked. According to a report by Indian newspaper, The Indian Express, the owner of Sujatha Bio Tech, along with his employee, tried to create a coronavirus cure, but consumed a...




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Coronavirus: Milan mayor hits out at crowds descending on popular streets as lockdown lifts

Milan's mayor has condemned "shameful" crowds heading to a popular area of the city during Italy’s relaxed lockdown. Images...




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Most popular Turkish pilot on social media changes job

Ebru Ünsal, who has been described as the most popular Turkish pilot on social media, has switched jobs. Click through for the story in photos...




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Thousands have already booked their seats for popular Eastern Express

With the winter approaching, the demand for seats on the Eastern Express, a train service that links the capital Ankara with the eastern province of Kars, has surged again, as the number of tickets sold so far for the winter months reached 10,000. Click through for the story in photos...




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Why Maltese-licensed casinos are so popular overseas

In many markets, the MGA license is most respected by players and many new regulatory frameworks are modelled after it




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The Illegitimacy of the Pope

As the head of the Roman Catholic Church, the pope is often called the “Holy Father” and the “Vicar of Christ”—names and roles that apply only to God. He claims the ability to speak ex cathedra, exercising godlike infallibility to add to and augment Scripture (Revelation 22:18). He wields unbiblical, unholy authority over his followers, usurping the headship of Christ and perverting the work of the Holy Spirit.

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British population in Czech Republic growing faster since Brexit referendum

Prague Daily Monitor

According to data released by the Ministry of Interior, the number of British citizens living in the Czech Republic has increased about 35% since the Brexit referendum, and Brits with their permanent residence in the Czech Republic have risen almost 55% since 2016.

read more




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ANO continues to be the most popular party, two January polls show

Prague Daily Monitor

Whether PM Andrej Babis (ANO) was attacked by the Million Moments demonstrations, accused by the European Commission of a conflict of interest in wrongfully taking European subsidies after an audit was completed, or the December investigation reopening concerning a construction project, his party continues to lead by a huge margin in polls.

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Hong Kong Canto-pop star Aaron Kwok’s online charity concert draws about 2 million viewers, raising more than HK$1 million

Hong Kong’s Canto-pop “dancing king” Aaron Kwok Fu-shing’s online charity concert on Saturday afternoon to help the city’s struggling dancers attracted about 2 million viewers and raised more than HK$1 million, amid local signs of an easing coronavirus threat.Kwok’s onstage moves are known to be inspired by Michael Jackson. The one-hour performance by the singer-dancer-actor, 54, flanked by about 100 dancers, was live-streamed on multiple channels on social media from 5pm to 6pm.He performed on…




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Global Impact of New Corona Virus and Population Issues

The new coronavirus (COVID-19) continues to wreak havoc across the world, as the number of infections and deaths rapidly rise. It has the potential to infect anybody regardless of age or gender. There are grave concerns that the economic fallout from COVID-19 may be comparable to that of the Great Depression. According to Johns Hopkins […]

The post Global Impact of New Corona Virus and Population Issues appeared first on Inter Press Service.




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Jobs first: Bolsonaro fires popular health expert

Few global leaders have done more than Bolsonaro to play down the pandemic, which has killed nearly 2000 Brazilians.




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Five myths about population, aging and environmental sustainability -- by Jane O'Sullivan, Francesco Ricciardi, Susann Roth

For sustainable development, universal wellbeing should be the goal, rather than endless growth. Minimizing further growth in human populations is only part of the solution, but an essential part. 




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Charting Sri Lanka's aging population -- by Utsav Kumar

These charts illustrate how Sri Lanka’s elderly population is increasing while the number of working-age people to help support them is declining. Forward-thinking policies are needed to address the challenges arising from this imbalance.




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How to protect Asia’s rapidly aging population from COVID-19 -- by Meredith Wyse

The COVID-19 pandemic highlights the need to strengthen programs and policies affecting older persons both in times of crisis and afterward.




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We've figured out why bubbles make a 'pop' sound when they burst

A number of difference forces are involved in producing sound when a bubble pops, and the exact noise depends on the chemical properties of the soap film




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Releasing rescued orangutans into the wild doesn’t boost populations

Orangutan orphanages nurse animals back to health and release them into the wild, but that doesn’t seem to increase the population of these endangered apes




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Trypophobia: Why a fear of holes is real – and may be on the rise

Some people have a visceral fear-like reaction to the holes in sponges, Swiss cheese or seed pods. Known as trypophobia, this response is increasingly common but isn’t what it seems




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Leisurely Strolls More Popular, Yet Walk Times Shorter: CDC

Title: Leisurely Strolls More Popular, Yet Walk Times Shorter: CDC
Category: Health News
Created: 4/27/2012 2:06:00 PM
Last Editorial Review: 4/30/2012 12:00:00 AM




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Health Tip: Popeye Wasn't Wrong About Spinach

Title: Health Tip: Popeye Wasn't Wrong About Spinach
Category: Health News
Created: 5/1/2013 8:35:00 AM
Last Editorial Review: 5/1/2013 12:00:00 AM




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'Breast Milk Banks' Gain in Popularity

Title: 'Breast Milk Banks' Gain in Popularity
Category: Health News
Created: 4/29/2014 9:35:00 AM
Last Editorial Review: 4/29/2014 12:00:00 AM




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Do Your Knees Crackle and Pop?

Title: Do Your Knees Crackle and Pop?
Category: Health News
Created: 5/5/2017 12:00:00 AM
Last Editorial Review: 5/5/2017 12:00:00 AM




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GPIHBP1, a partner protein for lipoprotein lipase, is expressed only in capillary endothelial cells [Images In Lipid Research]




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Erratum for Dubrovsky et al., "Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts"




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Deletion of the Zinc Transporter Lipoprotein AdcAII Causes Hyperencapsulation of Streptococcus pneumoniae Associated with Distinct Alleles of the Type I Restriction-Modification System

ABSTRACT

The capsule is the dominant Streptococcus pneumoniae virulence factor, yet how variation in capsule thickness is regulated is poorly understood. Here, we describe an unexpected relationship between mutation of adcAII, which encodes a zinc uptake lipoprotein, and capsule thickness. Partial deletion of adcAII in three of five capsular serotypes frequently resulted in a mucoid phenotype that biochemical analysis and electron microscopy of the D39 adcAII mutants confirmed was caused by markedly increased capsule thickness. Compared to D39, the hyperencapsulated adcAII mutant strain was more resistant to complement-mediated neutrophil killing and was hypervirulent in mouse models of invasive infection. Transcriptome analysis of D39 and the adcAII mutant identified major differences in transcription of the Sp_0505-0508 locus, which encodes an SpnD39III (ST5556II) type I restriction-modification system and allelic variation of which correlates with capsule thickness. A PCR assay demonstrated close linkage of the SpnD39IIIC and F alleles with the hyperencapsulated adcAII strains. However, transformation of adcAII with fixed SpnD39III alleles associated with normal capsule thickness did not revert the hyperencapsulated phenotype. Half of hyperencapsulated adcAII strains contained the same single nucleotide polymorphism in the capsule locus gene cps2E, which is required for the initiation of capsule synthesis. These results provide further evidence for the importance of the SpnD39III (ST5556II) type I restriction-modification system for modulating capsule thickness and identified an unexpected linkage between capsule thickness and mutation of adcAII. Further investigation will be needed to characterize how mutation of adcAII affects SpnD39III (ST5556II) allele dominance and results in the hyperencapsulated phenotype.

IMPORTANCE The Streptococcus pneumoniae capsule affects multiple interactions with the host including contributing to colonization and immune evasion. During infection, the capsule thickness varies, but the mechanisms regulating this are poorly understood. We have identified an unsuspected relationship between mutation of adcAII, a gene that encodes a zinc uptake lipoprotein, and capsule thickness. Mutation of adcAII resulted in a striking hyperencapsulated phenotype, increased resistance to complement-mediated neutrophil killing, and increased S. pneumoniae virulence in mouse models of infection. Transcriptome and PCR analysis linked the hyperencapsulated phenotype of the adcAII strain to specific alleles of the SpnD39III (ST5556II) type I restriction-modification system, a system which has previously been shown to affect capsule thickness. Our data provide further evidence for the importance of the SpnD39III (ST5556II) type I restriction-modification system for modulating capsule thickness and identify an unexpected link between capsule thickness and adcAII, further investigation of which could further characterize mechanisms of capsule regulation.




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YejM Modulates Activity of the YciM/FtsH Protease Complex To Prevent Lethal Accumulation of Lipopolysaccharide

ABSTRACT

Lipopolysaccharide (LPS) is an essential glycolipid present in the outer membrane (OM) of many Gram-negative bacteria. Balanced biosynthesis of LPS is critical for cell viability; too little LPS weakens the OM, while too much LPS is lethal. In Escherichia coli, this balance is maintained by the YciM/FtsH protease complex, which adjusts LPS levels by degrading the LPS biosynthesis enzyme LpxC. Here, we provide evidence that activity of the YciM/FtsH protease complex is inhibited by the essential protein YejM. Using strains in which LpxC activity is reduced, we show that yciM is epistatic to yejM, demonstrating that YejM acts upstream of YciM to prevent toxic overproduction of LPS. Previous studies have shown that this toxicity can be suppressed by deleting lpp, which codes for a highly abundant OM lipoprotein. It was assumed that deletion of lpp restores lipid balance by increasing the number of acyl chains available for glycerophospholipid biosynthesis. We show that this is not the case. Rather, our data suggest that preventing attachment of lpp to the peptidoglycan sacculus allows excess LPS to be shed in vesicles. We propose that this loss of OM material allows continued transport of LPS to the OM, thus preventing lethal accumulation of LPS within the inner membrane. Overall, our data justify the commitment of three essential inner membrane proteins to avoid toxic over- or underproduction of LPS.

IMPORTANCE Gram-negative bacteria are encapsulated by an outer membrane (OM) that is impermeable to large and hydrophobic molecules. As such, these bacteria are intrinsically resistant to several clinically relevant antibiotics. To better understand how the OM is established or maintained, we sought to clarify the function of the essential protein YejM in Escherichia coli. Here, we show that YejM inhibits activity of the YciM/FtsH protease complex, which regulates synthesis of the essential OM glycolipid lipopolysaccharide (LPS). Our data suggest that disrupting proper communication between LPS synthesis and transport to the OM leads to accumulation of LPS within the inner membrane (IM). The lethality associated with this event can be suppressed by increasing OM vesiculation. Our research has identified a completely novel signaling pathway that we propose coordinates LPS synthesis and transport.




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Tracing the Evolutionary History and Global Expansion of Candida auris Using Population Genomic Analyses

ABSTRACT

Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris.

IMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.




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Killer Archaea: Virus-Mediated Antagonism to CRISPR-Immune Populations Results in Emergent Virus-Host Mutualism

ABSTRACT

Theory, simulation, and experimental evolution demonstrate that diversified CRISPR-Cas immunity to lytic viruses can lead to stochastic virus extinction due to a limited number of susceptible hosts available to each potential new protospacer escape mutation. Under such conditions, theory predicts that to evade extinction, viruses evolve toward decreased virulence and promote vertical transmission and persistence in infected hosts. To better understand the evolution of host-virus interactions in microbial populations with active CRISPR-Cas immunity, we studied the interaction between CRISPR-immune Sulfolobus islandicus cells and immune-deficient strains that are infected by the chronic virus SSV9. We demonstrate that Sulfolobus islandicus cells infected with SSV9, and with other related SSVs, kill uninfected, immune strains through an antagonistic mechanism that is a protein and is independent of infectious virus. Cells that are infected with SSV9 are protected from killing and persist in the population. We hypothesize that this infection acts as a form of mutualism between the host and the virus by removing competitors in the population and ensuring continued vertical transmission of the virus within populations with diversified CRISPR-Cas immunity.

IMPORTANCE Multiple studies, especially those focusing on the role of lytic viruses in key model systems, have shown the importance of viruses in shaping microbial populations. However, it has become increasingly clear that viruses with a long host-virus interaction, such as those with a chronic lifestyle, can be important drivers of evolution and have large impacts on host ecology. In this work, we describe one such interaction with the acidic crenarchaeon Sulfolobus islandicus and its chronic virus Sulfolobus spindle-shaped virus 9. Our work expands the view in which this symbiosis between host and virus evolved, describing a killing phenotype which we hypothesize has evolved in part due to the high prevalence and diversity of CRISPR-Cas immunity seen in natural populations. We explore the implications of this phenotype in population dynamics and host ecology, as well as the implications of mutualism between this virus-host pair.




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Polygenic risk scores of several subtypes of epilepsies in a founder population

Objective

Polygenic risk scores (PRSs) are used to quantify the cumulative effects of a number of genetic variants, which may individually have a very small effect on susceptibility to a disease; we used PRSs to better understand the genetic contribution to common epilepsy and its subtypes.

Methods

We first replicated previous single associations using 373 unrelated patients. We then calculated PRSs in the same French Canadian patients with epilepsy divided into 7 epilepsy subtypes and population-based controls. We fitted a logistic mixed model to calculate the variance explained by the PRS using pseudo-R2 statistics.

Results

We show that the PRS explains more of the variance in idiopathic generalized epilepsy than in patients with nonacquired focal epilepsy. We also demonstrate that the variance explained is different within each epilepsy subtype.

Conclusions

Globally, we support the notion that PRSs provide a reliable measure to rightfully estimate the contribution of genetic factors to the pathophysiologic mechanism of epilepsies, but further studies are needed on PRSs before they can be used clinically.




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The Occurrence of Sulfated Salicinoids in Poplar and Their Formation by Sulfotransferase1

Salicinoids form a specific class of phenolic glycosides characteristic of the Salicaceae. Although salicinoids accumulate in large amounts and have been shown to be involved in plant defense, their biosynthesis is unclear. We identified two sulfated salicinoids, salicin-7-sulfate and salirepin-7-sulfate, in black cottonwood (Populus trichocarpa). Both compounds accumulated in high amounts in above-ground tissues including leaves, petioles, and stems, but were also found at lower concentrations in roots. A survey of salicin-7-sulfate and salirepin-7-sulfate in a subset of poplar (Populus sp.) and willow (Salix sp.) species revealed a broader distribution within the Salicaceae. To elucidate the formation of these compounds, we studied the sulfotransferase (SOT) gene family in P. trichocarpa (PtSOT). One of the identified genes, PtSOT1, was shown to encode an enzyme able to convert salicin and salirepin into salicin-7-sulfate and salirepin-7-sulfate, respectively. The expression of PtSOT1 in different organs of P. trichocarpa matched the accumulation of sulfated salicinoids in planta. Moreover, RNA interference-mediated knockdown of SOT1 in gray poplar (Populus x canescens) resulted in decreased levels of sulfated salicinoids in comparison to wild-type plants, indicating that SOT1 is responsible for their formation in planta. The presence of a nonfunctional SOT1 allele in black poplar (Populus nigra) was shown to correlate with the absence of salicin-7-sulfate and salirepin-7-sulfate in this species. Food choice experiments with leaves from wild-type and SOT1 knockdown trees suggest that sulfated salicinoids do not affect the feeding preference of the generalist caterpillar Lymantria dispar. A potential role of the sulfated salicinoids in sulfur storage and homeostasis is discussed.




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Compensatory Guaiacyl Lignin Biosynthesis at the Expense of Syringyl Lignin in 4CL1-Knockout Poplar

The lignin biosynthetic pathway is highly conserved in angiosperms, yet pathway manipulations give rise to a variety of taxon-specific outcomes. Knockout of lignin-associated 4-coumarate:CoA ligases (4CLs) in herbaceous species mainly reduces guaiacyl (G) lignin and enhances cell wall saccharification. Here we show that CRISPR-knockout of 4CL1 in poplar (Populus tremula x alba) preferentially reduced syringyl (S) lignin, with negligible effects on biomass recalcitrance. Concordant with reduced S-lignin was downregulation of ferulate 5-hydroxylases (F5Hs). Lignification was largely sustained by 4CL5, a low-affinity paralog of 4CL1 typically with only minor xylem expression or activity. Levels of caffeate, the preferred substrate of 4CL5, increased in line with significant upregulation of caffeoyl shikimate esterase1. Upregulation of caffeoyl-CoA O-methyltransferase1 and downregulation of F5Hs are consistent with preferential funneling of 4CL5 products toward G-lignin biosynthesis at the expense of S-lignin. Thus, transcriptional and metabolic adaptations to 4CL1-knockout appear to have enabled 4CL5 catalysis at a level sufficient to sustain lignification. Finally, genes involved in sulfur assimilation, the glutathione-ascorbate cycle, and various antioxidant systems were upregulated in the mutants, suggesting cascading responses to perturbed thioesterification in lignin biosynthesis.




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Sulfotransferase1 Is the Enzymatic Hub of Sulfated Salicinoids in Poplar




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Space is the Place: Effects of Continuous Spatial Structure on Analysis of Population Genetic Data [Population and Evolutionary Genetics]

Real geography is continuous, but standard models in population genetics are based on discrete, well-mixed populations. As a result, many methods of analyzing genetic data assume that samples are a random draw from a well-mixed population, but are applied to clustered samples from populations that are structured clinally over space. Here, we use simulations of populations living in continuous geography to study the impacts of dispersal and sampling strategy on population genetic summary statistics, demographic inference, and genome-wide association studies (GWAS). We find that most common summary statistics have distributions that differ substantially from those seen in well-mixed populations, especially when Wright’s neighborhood size is < 100 and sampling is spatially clustered. "Stepping-stone" models reproduce some of these effects, but discretizing the landscape introduces artifacts that in some cases are exacerbated at higher resolutions. The combination of low dispersal and clustered sampling causes demographic inference from the site frequency spectrum to infer more turbulent demographic histories, but averaged results across multiple simulations revealed surprisingly little systematic bias. We also show that the combination of spatially autocorrelated environments and limited dispersal causes GWAS to identify spurious signals of genetic association with purely environmentally determined phenotypes, and that this bias is only partially corrected by regressing out principal components of ancestry. Last, we discuss the relevance of our simulation results for inference from genetic variation in real organisms.




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Toward an Evolutionarily Appropriate Null Model: Jointly Inferring Demography and Purifying Selection [Population and Evolutionary Genetics]

The question of the relative evolutionary roles of adaptive and nonadaptive processes has been a central debate in population genetics for nearly a century. While advances have been made in the theoretical development of the underlying models, and statistical methods for estimating their parameters from large-scale genomic data, a framework for an appropriate null model remains elusive. A model incorporating evolutionary processes known to be in constant operation, genetic drift (as modulated by the demographic history of the population) and purifying selection, is lacking. Without such a null model, the role of adaptive processes in shaping within- and between-population variation may not be accurately assessed. Here, we investigate how population size changes and the strength of purifying selection affect patterns of variation at "neutral" sites near functional genomic components. We propose a novel statistical framework for jointly inferring the contribution of the relevant selective and demographic parameters. By means of extensive performance analyses, we quantify the utility of the approach, identify the most important statistics for parameter estimation, and compare the results with existing methods. Finally, we reanalyze genome-wide population-level data from a Zambian population of Drosophila melanogaster, and find that it has experienced a much slower rate of population growth than was inferred when the effects of purifying selection were neglected. Our approach represents an appropriate null model, against which the effects of positive selection can be assessed.




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Identifying and Classifying Shared Selective Sweeps from Multilocus Data [Population and Evolutionary Genetics]

Positive selection causes beneficial alleles to rise to high frequency, resulting in a selective sweep of the diversity surrounding the selected sites. Accordingly, the signature of a selective sweep in an ancestral population may still remain in its descendants. Identifying signatures of selection in the ancestor that are shared among its descendants is important to contextualize the timing of a sweep, but few methods exist for this purpose. We introduce the statistic SS-H12, which can identify genomic regions under shared positive selection across populations and is based on the theory of the expected haplotype homozygosity statistic H12, which detects recent hard and soft sweeps from the presence of high-frequency haplotypes. SS-H12 is distinct from comparable statistics because it requires a minimum of only two populations, and properly identifies and differentiates between independent convergent sweeps and true ancestral sweeps, with high power and robustness to a variety of demographic models. Furthermore, we can apply SS-H12 in conjunction with the ratio of statistics we term and to further classify identified shared sweeps as hard or soft. Finally, we identified both previously reported and novel shared sweep candidates from human whole-genome sequences. Previously reported candidates include the well-characterized ancestral sweeps at LCT and SLC24A5 in Indo-Europeans, as well as GPHN worldwide. Novel candidates include an ancestral sweep at RGS18 in sub-Saharan Africans involved in regulating the platelet response and implicated in sudden cardiac death, and a convergent sweep at C2CD5 between European and East Asian populations that may explain their different insulin responses.




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Phosphoflow Protocol for Signaling Studies in Human and Murine B Cell Subpopulations [NOVEL IMMUNOLOGICAL METHODS]

Key Points

  • Method for highly sensitive detection of phosphorylation in B cell subpopulations.

  • B cell subpopulations show different phosphorylation levels upon BCR stimulation.




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    Apolipoprotein E Triggers Complement Activation in Joint Synovial Fluid of Rheumatoid Arthritis Patients by Binding C1q [INNATE IMMUNITY AND INFLAMMATION]

    Key Points

  • ApoE was found in complex with C4d in RA patient SF.

  • Deposited ApoE activates complement whereas ApoE in solution is inhibitory.

  • Posttranslational modifications alter ApoE's capacity to bind FH and C4BP.




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    Leishmania donovani Subverts Host Immune Response by Epigenetic Reprogramming of Macrophage M(Lipopolysaccharides + IFN-{gamma})/M(IL-10) Polarization [INFECTIOUS DISEASE AND HOST RESPONSE]

    Key Points

  • L. donovani induces histone lysine methyltransferases/demethylases in the host.

  • L. donovani–induced epigenetic enzymes induce host M(IL-10) polarization.

  • Knockdown of epigenetic enzymes inhibited parasite multiplication in infected host.




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    Complexes between C-Reactive Protein and Very Low Density Lipoprotein Delay Bacterial Clearance in Sepsis [INFECTIOUS DISEASE AND HOST RESPONSE]

    Key Points

  • Kupffer cells phagocytose both bacteria and CRP–VLDL complexes.

  • High levels of CRP–VLDL complexes delay bacterial clearance.

  • Pch disrupts CRP–VLDL complexes to improve bacterial clearance.




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    Novel Insights into the Roles of Bcl-2 Homolog Nr-13 (vNr-13) Encoded by Herpesvirus of Turkeys in the Virus Replication Cycle, Mitochondrial Networks, and Apoptosis Inhibition [Virus-Cell Interactions]

    The Bcl-2 (B cell lymphoma 2)-related protein Nr-13 plays a major role in the regulation of cell death in developing avian B cells. With over 65% sequence similarity to the chicken Nr-13, herpesvirus of turkeys (HVT) vNr-13, encoded by the HVT079 and HVT096 genes, is the first known alphaherpesvirus-encoded Bcl-2 homolog. HVT-infected cells were reported to be relatively more resistant to serum starvation, suggested that vNr-13 could be involved in protecting the cells. Here, we describe CRISPR/Cas9-based editing of exon 1 of the HVT079 and HVT096 genes from the HVT genome to generate the mutant HVT-vNr-13 to gain insights into its functional roles. Overall, wild-type HVT and HVT-vNr-13 showed similar growth kinetics; however, at early time points, HVT-vNr-13 showed 1.3- to 1.7-fold-lower growth of cell-associated virus and 3- to 6.2-fold-lower growth of cell-free virus. In transfected cells, HVT vNr-13 showed a mainly diffuse cytoplasmic distribution with faint nuclear staining. Further, vNr-13 localized to the mitochondria and endoplasmic reticulum (ER) and disrupted mitochondrial network morphology in the transfected cells. In the wild-type HVT-infected cells, vNr-13 expression appeared to be directly involved in the disruption of the mitochondrial network, as the mitochondrial network morphology was substantially restored in the HVT-vNr-13-infected cells. IncuCyte S3 real-time apoptosis monitoring demonstrated that vNr-13 is unequivocally involved in the apoptosis inhibition, and it is associated with an increase of PFU, especially under serum-free conditions in the later stages of the viral replication cycle. Furthermore, HVT blocks apoptosis in infected cells but activates apoptosis in noninfected bystander cells.

    IMPORTANCE B cell lymphoma 2 (Bcl-2) family proteins play important roles in regulating apoptosis during homeostasis, tissue development, and infectious diseases. Several viruses encode homologs of cellular Bcl-2-proteins (vBcl-2) to inhibit apoptosis, which enable them to replicate and persist in the infected cells and to evade/modulate the immune response of the host. Herpesvirus of turkeys (HVT) is a nonpathogenic alphaherpesvirus of turkeys and chickens that is widely used as a live vaccine against Marek’s disease and as recombinant vaccine viral vectors for protecting against multiple avian diseases. Identical copies of the HVT genes HVT079 and HVT096 encode the Bcl-2 homolog vNr-13. While previous studies have identified the potential ability of vNr-13 in inhibiting apoptosis induced by serum deprivation, there have been no detailed investigations on the functions of vNr-13. Using CRISPR/Cas9-based ablation of the vNr-13 gene, we demonstrated the roles of HVT vNr-13 in early stages of the viral replication cycle, mitochondrial morphology disruption, and apoptosis inhibition in later stages of viral replication.




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    A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption [Microbiology]

    HIV-1 persists in cellular reservoirs that can reignite viremia if antiretroviral therapy (ART) is interrupted. Therefore, insight into the nature of those reservoirs may be revealed from the composition of recrudescing viremia following treatment cessation. A minor population of macrophage-tropic (M-tropic) viruses was identified in a library of recombinant viruses...




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    Octopamine mobilizes lipids from honey bee (Apis mellifera) hypopharyngeal glands [RESEARCH ARTICLE]

    Vanessa Corby-Harris, Megan E. Deeter, Lucy Snyder, Charlotte Meador, Ashley C. Welchert, Amelia Hoffman, and Bethany T. Obernesser

    Recent widespread honey bee (Apis mellifera) colony loss is attributed to a variety of stressors, including parasites, pathogens, pesticides and poor nutrition. In principle, we can reduce stress-induced declines in colony health by either removing the stressor or increasing the bees' tolerance to the stressor. This latter option requires a better understanding than we currently have of how honey bees respond to stress. Here, we investigated how octopamine, a stress-induced hormone that mediates invertebrate physiology and behavior, influences the health of young nurse-aged bees. Specifically, we asked whether octopamine induces abdominal lipid and hypopharyngeal gland (HG) degradation, two physiological traits of stressed nurse bees. Nurse-aged workers were treated topically with octopamine and their abdominal lipid content, HG size and HG autophagic gene expression were measured. Hemolymph lipid titer was measured to determine whether tissue degradation was associated with the release of nutrients from these tissues into the hemolymph. The HGs of octopamine-treated bees were smaller than control bees and had higher levels of HG autophagy gene expression. Octopamine-treated bees also had higher levels of hemolymph lipid compared with control bees. Abdominal lipids did not change in response to octopamine. Our findings support the hypothesis that the HGs are a rich source of stored energy that can be mobilized during periods of stress.




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    Responses of activity rhythms to temperature cues evolve in Drosophila populations selected for divergent timing of eclosion [RESEARCH ARTICLE]

    Lakshman Abhilash, Arshad Kalliyil, and Vasu Sheeba

    Even though the rhythm in adult emergence and rhythm in locomotor activity are two different rhythmic phenomena that occur at distinct life-stages of the fly life cycle, previous studies have hinted at similarities in certain aspects of the organisation of the circadian clock driving these two rhythms. For instance, the period gene plays an important regulatory role in both rhythms. In an earlier study, we have shown that selection on timing of adult emergence behaviour in populations of Drosophila melanogaster leads to the co-evolution of temperature sensitivity of circadian clocks driving eclosion. In this study, we were interested in asking if temperature sensitivity of the locomotor activity rhythm has evolved in our populations with divergent timing of adult emergence rhythm, with the goal of understanding the extent of similarity (or lack of it) in circadian organisation between the two rhythms. We found that in response to simulated jetlag with temperature cycles, late chronotypes (populations selected for predominant emergence during dusk) indeed re-entrain faster than early chronotypes (populations selected for predominant emergence during dawn) to 6-h phase-delays, thereby indicating enhanced sensitivity of the activity/rest clock to temperature cues in these stocks (entrainment is the synchronisation of internal rhythms to cyclic environmental time-cues). Additionally, we found that late chronotypes show higher plasticity of phases across regimes, day-to-day stability in phases and amplitude of entrainment, all indicative of enhanced temperature sensitive activity/rest rhythms. Our results highlight remarkably similar organisation principles between emergence and activity/rest rhythms.




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    Circular RNA hsa_circ_0014130 Inhibits Apoptosis in Non-Small Cell Lung Cancer by Sponging miR-136-5p and Upregulating BCL2

    Previous studies indicated that circular RNAs (circRNA) played vital roles in the development of non–small cell lung cancer (NSCLC). Although hsa_circ_0014130 might be a potential NSCLC biomarker, its function in NSCLC remains unknown. Thus, this study aimed to investigate the role of hsa_circ_0014130 in the progression of NSCLC. The levels of hsa_circ_0014130 in NSCLC tissues and adjacent normal tissues were determined by qRT-PCR. In addition, the expressions of Bcl-2 and cleaved caspase-3 in A549 cells were detected with Western blot analysis. Meanwhile, the dual luciferase reporter system assay was used to determine the interaction of hsa_circ_0014130 and miR-136-5p or Bcl-2 and miR-136-5p in NSCLC, respectively. The level of hsa_circ_0014130 was significantly upregulated in NSCLC tissues. Downregulation of hsa_circ_0014130 markedly inhibited the proliferation and invasion of A549 cells via inducing apoptosis. In addition, downregulation of hsa_circ_0014130 inhibited the tumorigenesis of subcutaneous A549 xenograft in mice in vivo. Meanwhile, mechanistic analysis indicated that downregulation of hsa_circ_0014130 decreased the expression of miR-136-5p–targeted gene Bcl-2 via acting as a competitive "sponge" of miR-136-5p. In this study, we found that hsa_circ_0014130 was upregulated in NSCLC tissues. In addition, hsa_circ_0014130 functions as a tumor promoter in NSCLC to promote tumor growth through upregulating Bcl-2 partially via "sponging" miR-136-5p.

    Implications:

    In conclusion, hsa_circ_0014130 might function as a prognostic factor for patients with NSCLC and might be a therapeutic target for the treatment of NSCLC in future.




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    Impact of a Multidisciplinary, Endocrinologist-Led Shared Medical Appointment Model on Diabetes-Related Outcomes in an Underserved Population

    A multidisciplinary endocrinologist-led shared medical appointment (SMA) model showed statistically significant reductions in A1C from baseline over 3 years that were not significantly different from appointments with endocrinologists or primary care providers alone within a resource-poor population. Similarly, the SMA model achieved clinical outcomes on par with endocrinologist-only visits with the added benefit of improving endocrine provider productivity and specialty access for patients. Greater patient engagement with the SMA model was associated with significantly lower A1C.




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    Prevalence and incidence of, and risk factors for chronic cough in the adult population: the Rotterdam Study

    Chronic cough is a common complaint in the general population but there are no precise data on the incidence of, and prospectively examined risk factors for chronic cough in a population-based setting. Therefore, we investigated the period prevalence, incidence and risk factors for chronic cough in adult subjects.

    In a prospective population-based cohort study among subjects aged ≥45 years, data on chronic cough were collected on two separate occasions using a standardised questionnaire. Chronic cough was defined as daily coughing for at least 3 months duration during the preceding 2 years. Potential risk factors were gathered by interview, physical examination and several investigations.

    Of the 9824 participants in this study, 1073 (10.9%) subjects had chronic cough at baseline. The prevalence of chronic cough increased with age and peaked in the eighth decade. In subjects aged <70 years, chronic cough was more common in women. During an average follow-up of 6 years, 439 incident cases of chronic cough occurred with an overall incidence rate of 11.6 per 1000 person-years (95% CI 10.6–12.8). In current smokers, the incidence of chronic cough was higher in men. In the multivariable analysis, current smoking, gastro-oesophageal reflux disease (GORD), asthma and COPD were identified as risk factors for chronic cough.

    Chronic cough is common among adults and highly prevalent in the older population. Current smoking, GORD, asthma and COPD are independent risk factors for chronic cough. Individuals at risk of developing chronic cough may benefit from smoking cessation and control of the underlying disease.




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    Sex Disparities in Cardiovascular Outcome Trials of Populations With Diabetes: A Systematic Review and Meta-analysis

    BACKGROUND

    Sex differences have been described in diabetes cardiovascular outcome trials (CVOTs).

    PURPOSE

    We systematically reviewed for baseline sex differences in cardiovascular (CV) risk factors and CV protection therapy in diabetes CVOTs.

    DATA SOURCES

    Randomized placebo-controlled trials examining the effect of diabetes medications on major adverse cardiovascular events in people ≥18 years of age with type 2 diabetes.

    STUDY SELECTION

    Included trials reported baseline sex-specific CV risks and use of CV protection therapy.

    DATA EXTRACTION

    Two reviewers independently abstracted study data.

    DATA SYNTHESIS

    We included five CVOTs with 46,606 participants. We summarized sex-specific data using mean differences (MDs) and relative risks (RRs) and pooled estimates using random effects meta-analysis. There were fewer women than men in included trials (28.5–35.8% women). Women more often had stroke (RR 1.28; 95% CI 1.09, 1.50), heart failure (RR 1.30; 95% CI 1.21,1.40), and chronic kidney disease (RR 1.33; 95% CI 1.17; 1.51). They less often used statins (RR 0.90; 95% CI 0.86, 0.93), aspirin (RR 0.82; 95% CI 0.71, 0.95), and β-blockers (RR 0.93; 95% CI 0.88, 0.97) and had a higher systolic blood pressure (MD 1.66 mmHg; 95% CI 0.90, 2.41), LDL cholesterol (MD 0.34 mmol/L; 95% CI 0.29, 0.39), and hemoglobin A1c (MD 0.11%; 95% CI 0.09, 0.14 [1.2 mmol/mol; 1.0, 1.5]) than men.

    LIMITATIONS

    We could not carry out subgroup analyses due to the small number of studies. Our study is not generalizable to low CV risk groups nor to patients in routine care.

    CONCLUSIONS

    There were baseline sex disparities in diabetes CVOTs. We suggest efforts to recruit women into trials and promote CV management across the sexes.