spa

Bye bye space-time: is it time to free physics from Einstein’s legacy?

Einstein’s framework for the universe, space-time, is at odds with quantum theory. Overcoming this clash and others is vital to unravelling the true nature of the cosmos




spa

The end of the open plan office? Workspaces get post-pandemic makeovers

One-way corridors, buffer zones around desks, and clear plastic screens to guard against colleagues' coughs and sneezes may become office standards after coronavirus stay-at-home orders are lifted,...




spa

Test flight shows balloon space tourism no flight of fancy

Arizona-based company World View Enterprises says it has taken a major step towards launching commercial balloon flights to the edge of space, with a successful unmanned test flight that reached an altitude of about 23 miles. The company hopes to begin taking tourists to near space in 2016 with advanced technology it says will open up a new view of the Earth. Sharon Reich reports.




spa

Dazzling damselflies and a SpaceX plume commended by photo awards

An aerial view of crabeater seals in Antarctica, mating damselflies and a twilight rocket launch were among the most lauded entries to the inaugural Nature TTL Photographer of the Year award




spa

NASA’s deep-space mission to a $10 quintillion all-metal world

The unique metal asteroid Psyche may be a space miner's fantasy – but there are better reasons to want to visit it, says mission leader Lindy Elkins-Tanton




spa

Don’t miss: Earth from space, asteroid workouts and nature’s giants

Watch a new series charting our planet from above, read all about the biggest living things, fend off space rocks for fun, plus more picks for your diary




spa

Dazzling damselflies and a SpaceX plume commended by photo awards

An aerial view of crabeater seals in Antarctica, mating damselflies and a twilight rocket launch were among the most lauded entries to the inaugural Nature TTL Photographer of the Year award




spa

Color Out of Space: Another Nicolas Cage film that's so bad it's good

Nicolas Cage grapples with a weird luminous alien presence in the movie Color Out of Space. It's a story that has roots in a late-19th-century obsession with new forms of radiation, says Simon Ings




spa

Spain's Economy Minister, Nadia Calviño, speaks to Reuters

Minister of Economy, Nadia Calviño, only the second woman to hold the position in Spanish history, speaks to Breakingviews Global Editor Rob Cox as Spain prepares to hold parliamentary elections on Nov. 10 for the second time in a year.




spa

SpaceX, Blue Origin get contracts to build NASA's astronaut moon lander

NASA on Thursday selected space firms SpaceX, Blue Origin and Dynetics to build lunar landing systems that can carry astronauts to the moon by 2024, the White House's accelerated deadline under the space agency's moon-to-Mars campaign. Jillian Kitchener has more.




spa

Destination Space: Cleaning up space junk

It might be hard to imagine but space is getting crowded. ‘Space junk’ is becoming a dangerous hazard for orbiting satellites, and now some countries are joining forces to tackle it.




spa

The sparkling history of tonic, from medical miracle to G&T essential

The story of how gin and tonic came together fizzes with adventure, discovery, imperial ambition, biopiracy and a generous splash of fake news




spa

How red is a black hole? The strange reality of what space looks like

Our images of deep space are spectacular, but don’t reflect what our eyes would see. Here's what their stunning true colours reveal about the cosmos




spa

Weird radio signals spotted in our galaxy could solve a space mystery

Weird blasts of radio waves from space called fast radio bursts have been baffling astronomers since they were discovered, but after finding one in our galaxy we may finally know what creates them




spa

SpaceX mission control to do social distancing for first crewed flight

SpaceX’s first crewed launch is planned for 27 May and will be run from a mission control with desks set six feet apart to comply with social distancing protocols




spa

I'm a space archaeologist studying junk strewn across the solar system

From vintage satellites to lunar rovers, space archaeologist Alice Gorman is teasing out a unique history of humanity from the objects we've dispatched from Earth




spa

China just tested a spacecraft that could fly to the moon and beyond

China just tested its biggest rocket yet, along with a new capsule designed to carry humans to its planned space station, the moon and beyond




spa

Spam and phishing in 2019

In the search for new ways to bypass spam filters, attackers are developing new methods of delivering their messages. This year, they made active use of various Google services, as well as popular social networks and video hosting sites.




spa

Health Tip: Create a Space for Sleep

Title: Health Tip: Create a Space for Sleep
Category: Health News
Created: 4/30/2008 2:00:00 AM
Last Editorial Review: 4/30/2008 12:00:00 AM




spa

Breast Cancer Risks Not Same for Hispanic Women

Title: Breast Cancer Risks Not Same for Hispanic Women
Category: Health News
Created: 4/26/2010 8:10:00 AM
Last Editorial Review: 4/26/2010 12:00:00 AM




spa

What a Bad Lifestyle Does to Your Life Span

Title: What a Bad Lifestyle Does to Your Life Span
Category: Health News
Created: 4/27/2010 10:28:00 AM
Last Editorial Review: 4/27/2010 10:28:05 AM




spa

Health Care Disparities Might Affect Black Kids' Cancer Survival

Title: Health Care Disparities Might Affect Black Kids' Cancer Survival
Category: Health News
Created: 5/1/2012 10:05:00 AM
Last Editorial Review: 5/1/2012 12:00:00 AM




spa

Testicular Cancer on Rise in U.S., Especially Among Hispanic Men

Title: Testicular Cancer on Rise in U.S., Especially Among Hispanic Men
Category: Health News
Created: 5/3/2013 12:35:00 PM
Last Editorial Review: 5/3/2013 12:00:00 AM




spa

Spanking May Be More Common Than Parents Admit

Title: Spanking May Be More Common Than Parents Admit
Category: Health News
Created: 4/29/2014 7:36:00 PM
Last Editorial Review: 4/30/2014 12:00:00 AM




spa

Dispatcher-Assisted CPR Boosts Cardiac Arrest Survival in Kids: Study

Title: Dispatcher-Assisted CPR Boosts Cardiac Arrest Survival in Kids: Study
Category: Health News
Created: 4/30/2014 4:36:00 PM
Last Editorial Review: 5/1/2014 12:00:00 AM




spa

Hispanic Women's Upbeat Outlook May Boost Heart Health

Title: Hispanic Women's Upbeat Outlook May Boost Heart Health
Category: Health News
Created: 4/29/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM




spa

Certain Cancers Seem Less Likely for Kids of Hispanic Moms Born Outside U.S.

Title: Certain Cancers Seem Less Likely for Kids of Hispanic Moms Born Outside U.S.
Category: Health News
Created: 4/25/2016 12:00:00 AM
Last Editorial Review: 4/26/2016 12:00:00 AM




spa

U.S. Health Report Card Finds Racial, Ethnic Disparities Persist

Title: U.S. Health Report Card Finds Racial, Ethnic Disparities Persist
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/27/2016 12:00:00 AM




spa

Spanking: More Harm Than Good?

Title: Spanking: More Harm Than Good?
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM




spa

Vampire Facials at New Mexico Spa Linked to HIV Infections

Title: Vampire Facials at New Mexico Spa Linked to HIV Infections
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/1/2019 12:00:00 AM




spa

COVID-19 Pandemic May Lead to 75,000 'Deaths of Despair'

Title: COVID-19 Pandemic May Lead to 75,000 'Deaths of Despair'
Category: Health News
Created: 5/8/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM




spa

Religion Helps Protect Against 'Deaths of Despair': Study

Title: Religion Helps Protect Against 'Deaths of Despair': Study
Category: Health News
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM




spa

Long Periods in Space Alter Astronauts' Brains

Title: Long Periods in Space Alter Astronauts' Brains
Category: Health News
Created: 4/14/2020 12:00:00 AM
Last Editorial Review: 4/15/2020 12:00:00 AM




spa

Novel Divisome-Associated Protein Spatially Coupling the Z-Ring with the Chromosomal Replication Terminus in Caulobacter crescentus

ABSTRACT

Cell division requires proper spatial coordination with the chromosome, which undergoes dynamic changes during chromosome replication and segregation. FtsZ is a bacterial cytoskeletal protein that assembles into the Z-ring, providing a platform to build the cell division apparatus. In the model bacterium Caulobacter crescentus, the cellular localization of the Z-ring is controlled during the cell cycle in a chromosome replication-coupled manner. Although dynamic localization of the Z-ring at midcell is driven primarily by the replication origin-associated FtsZ inhibitor MipZ, the mechanism ensuring accurate positioning of the Z-ring remains unclear. In this study, we showed that the Z-ring colocalizes with the replication terminus region, located opposite the origin, throughout most of the C. crescentus cell cycle. Spatial organization of the two is mediated by ZapT, a previously uncharacterized protein that interacts with the terminus region and associates with ZapA and ZauP, both of which are part of the incipient division apparatus. While the Z-ring and the terminus region coincided with the presence of ZapT, colocalization of the two was perturbed in cells lacking zapT, which is accompanied by delayed midcellular positioning of the Z-ring. Moreover, cells overexpressing ZapT showed compromised positioning of the Z-ring and MipZ. These findings underscore the important role of ZapT in controlling cell division processes. We propose that ZapT acts as a molecular bridge that physically links the terminus region to the Z-ring, thereby ensuring accurate site selection for the Z-ring. Because ZapT is conserved in proteobacteria, these findings may define a general mechanism coordinating cell division with chromosome organization.

IMPORTANCE Growing bacteria require careful tuning of cell division processes with dynamic organization of replicating chromosomes. In enteric bacteria, ZapA associates with the cytoskeletal Z-ring and establishes a physical linkage to the chromosomal replication terminus through its interaction with ZapB-MatP-DNA complexes. However, because ZapB and MatP are found only in enteric bacteria, it remains unclear how the Z-ring and the terminus are coordinated in the vast majority of bacteria. Here, we provide evidence that a novel conserved protein, termed ZapT, mediates colocalization of the Z-ring with the terminus in Caulobacter crescentus, a model organism that is phylogenetically distant from enteric bacteria. Given that ZapT facilitates cell division processes in C. crescentus, this study highlights the universal importance of the physical linkage between the Z-ring and the terminus in maintaining cell integrity.




spa

Federal funding for gun violence prevention research sparks hopes: Priorities, direction being explored

After more than 20 years of minimal funding, the U.S. is opening its purse strings to research on gun violence prevention.




spa

Place Matters: From Health and Health Care Disparities to Equity and Liberation

Place—a confluence of the social, economic, political, physical, and built environments—is fundamental to our understanding of health and health inequities among marginalized racial groups in the United States. Moreover, racism, defined as a system of structuring opportunity and assigning value based on the social interpretation of how one looks (i.e., race), has shaped the places people live in North Carolina. This problem is deeply imbedded in all of our systems, from housing to health care, affecting the ability of every resident of the state to flourish and thrive.




spa

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.




spa

Spatial orientation based on multiple visual cues in non-migratory monarch butterflies [RESEARCH ARTICLE]

Myriam Franzke, Christian Kraus, David Dreyer, Keram Pfeiffer, M. Jerome Beetz, Anna L. Stöckl, James J. Foster, Eric J. Warrant, and Basil el Jundi

Monarch butterflies (Danaus plexippus) are prominent for their annual long-distance migration from North America to their overwintering area in Central Mexico. To find their way on this long journey, they use a sun compass as their main orientation reference but will also adjust their migratory direction with respect to mountain ranges. This indicates that the migratory butterflies also attend to the panorama to guide their travels. While the compass has been studied in detail in migrating butterflies, little is known about the orientation abilities of non-migrating butterflies. Here we studied if non-migrating butterflies - that stay in a more restricted area to feed and breed - also use a similar compass system to guide their flights. Performing behavioral experiments on tethered flying butterflies in an indoor LED flight simulator, we found that the monarchs fly along straight tracks with respect to a simulated sun. When a panoramic skyline was presented as the only orientation cue, the butterflies maintained their flight direction only during short sequences suggesting that they potentially use it for flight stabilization. We further found that when we presented the two cues together, the butterflies incorporate both cues in their compass. Taken together, we here show that non-migrating monarch butterflies can combine multiple visual cues for robust orientation, an ability that may also aid them during their migration.




spa

Membrane peroxidation index and maximum lifespan are negatively correlated in fish of genus Nothobranchius [SHORT COMMUNICATION]

Jorge de Costa, Gustavo Barja, and Pedro F. Almaida-Pagan

Lipid composition of cell membranes is linked to metabolic rate and lifespan in mammals and birds but very little information is available for fishes. In this study, three fish species of the short-lived annual genus Nothobranchius with different maximum lifespan potentials (MLSP) and the longer-lived outgroup species Aphyosemion australe were studied to test whether they conform to the predictions of the longevity-homeoviscous adaptation (LHA) theory of aging. Lipid analyses were performed in whole fish samples and peroxidation indexes (PIn) for every PL class and for the whole membrane, were calculated. Total PL content was significantly lower in A. australe and N. korthausae, the two species with the highest MLSP, and a negative correlation between membrane total PIn and fish MLSP was found, this meaning that the longer-lived fish species have more saturated membranes and therefore, a lower susceptibility to oxidative damage, as the LHA theory posits.




spa

Quantification of the affinities of CRISPR-Cas9 nucleases for cognate protospacer ad&#x0237;acent motif (PAM) sequences [Molecular Biophysics]

The CRISPR/Cas9 nucleases have been widely applied for genome editing in various organisms. Cas9 nucleases complexed with a guide RNA (Cas9–gRNA) find their targets by scanning and interrogating the genomic DNA for sequences complementary to the gRNA. Recognition of the DNA target sequence requires a short protospacer adjacent motif (PAM) located outside this sequence. Given that the efficiency of target location may depend on the strength of interactions that promote target recognition, here we sought to compare affinities of different Cas9 nucleases for their cognate PAM sequences. To this end, we measured affinities of Cas9 nucleases from Streptococcus pyogenes, Staphylococcus aureus, and Francisella novicida complexed with guide RNAs (gRNAs) (SpCas9–gRNA, SaCas9–gRNA, and FnCas9–gRNA, respectively) and of three engineered SpCas9–gRNA variants with altered PAM specificities for short, PAM-containing DNA probes. We used a “beacon” assay that measures the relative affinities of DNA probes by determining their ability to competitively affect the rate of Cas9–gRNA binding to fluorescently labeled target DNA derivatives called “Cas9 beacons.” We observed significant differences in the affinities for cognate PAM sequences among the studied Cas9 enzymes. The relative affinities of SpCas9–gRNA and its engineered variants for canonical and suboptimal PAMs correlated with previous findings on the efficiency of these PAM sequences in genome editing. These findings suggest that high affinity of a Cas9 nuclease for its cognate PAM promotes higher genome-editing efficiency.




spa

High-Definition Mapping of Four Spatially Distinct Neutralizing Epitope Clusters on RiVax, a Candidate Ricin Toxin Subunit Vaccine [Vaccines]

RiVax is a promising recombinant ricin toxin A subunit (RTA) vaccine antigen that has been shown to be safe and immunogenic in humans and effective at protecting rhesus macaques against lethal-dose aerosolized toxin exposure. We previously used a panel of RTA-specific monoclonal antibodies (MAbs) to demonstrate, by competition enzyme-linked immunosorbent assay (ELISA), that RiVax elicits similar serum antibody profiles in humans and macaques. However, the MAb binding sites on RiVax have yet to be defined. In this study, we employed hydrogen exchange-mass spectrometry (HX-MS) to localize the epitopes on RiVax recognized by nine toxin-neutralizing MAbs and one nonneutralizing MAb. Based on strong protection from hydrogen exchange, the nine MAbs grouped into four spatially distinct epitope clusters (namely, clusters I to IV). Cluster I MAbs protected RiVax's α-helix B (residues 94 to 107), a protruding immunodominant secondary structure element known to be a target of potent toxin-neutralizing antibodies. Cluster II consisted of two subclusters located on the "back side" (relative to the active site pocket) of RiVax. One subcluster involved α-helix A (residues 14 to 24) and α-helices F-G (residues 184 to 207); the other encompassed β-strand d (residues 62 to 69) and parts of α-helices D-E (154 to 164) and the intervening loop. Cluster III involved α-helices C and G on the front side of RiVax, while cluster IV formed a sash from the front to back of RiVax, spanning strands b, c, and d (residues 35 to 59). Having a high-resolution B cell epitope map of RiVax will enable the development and optimization of competitive serum profiling assays to examine vaccine-induced antibody responses across species.




spa

Geospatial assessment methods for geotechnical asset management of legacy railway embankments

Most British railway embankments were constructed between 120 and 180 years ago without the benefit of modern design and construction methods. This can result in undesirable load-deformation characteristics and consequent disruption to present-day railway operations, for which there is unprecedented demand. Annual rail passenger kilometres have approximately doubled in the last 20 years and freight has increased by 60% over the same period. Whereas elements such as rails or bridges can be refurbished or replaced to meet increasing demand, the same is not usually feasible for embankments. Development of techniques to assess embankment performance risks posed by operational capacity enhancements is therefore of increasing significance to railway geotechnical asset management. The two case studies presented in this paper demonstrate how geospatial analysis and data management techniques may be applied to this challenge at both strategic (regional or national) and tactical (site-specific) scales for embankments incorporating plastic clay fill. The case studies also demonstrate, in a world of ever more abundant data, the growing need for engineering geologists and geotechnical engineers to augment their traditional knowledge with comprehensive data management and geospatial analysis skills, these being essential for modern infrastructure asset management.

Thematic collection: This article is part of the ‘Ground-related risk to transportation infrastructure’ collection available at: https://www.lyellcollection.org/cc/Ground-related-risk-to-transportation-infrastructure




spa

A large palaeo-landslide reactivated by high-speed railway construction works (northern Spain)

The presence of large palaeo-landslides can hinder the construction of railway lines if they cause an alteration of the natural balance of the slope, significantly increasing the cost of the project. During the construction works in a section of the Madrid–Asturias high-speed railway line (Spain), a large-scale hillside instability affected 460 m of the section. The ground movement began 10 months after the start of the excavations and remained active throughout the observation period (2008–2010). Data provided by fieldwork, boreholes and instrumental monitoring have allowed the investigation of the geological units involved, together with the geometry and the kinematics of the mass movement. This landslide involves a Paleozoic basement with an estimated volume of 4 400 000 m3. It shows low displacement rates (<45 mm a–1) and was accommodated on a single surface of rupture, which reaches more than 60 m depth. The kinematics is favoured by structural and lithological conditions, there being a strong rheological contrast in the lower part of the mobilized ground. This movement is linked to a large palaeo-landslide that was partially reactivated when excavations undermined the lower slopes of the hillside. Technical solutions for the stabilization have already caused an additional cost of 17% over the initial budget.




spa

Differentiation of Community-Associated and Livestock-Associated Methicillin-Resistant Staphylococcus aureus Isolates and Identification of spa Types by Use of PCR and High-Resolution Melt Curve Analysis [Clinical Veterinary Microbiology]

Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are present worldwide and represent a major public health concern. The capability of PCR followed by high-resolution melt (HRM) curve analysis for the detection of community-associated and livestock-associated MRSA strains and the identification of staphylococcal protein A (spa) locus was evaluated in 74 MRSA samples which were isolated from the environment, humans, and pigs on a single piggery. PCR-HRM curve analysis identified four spa types among MRSA samples and differentiated MRSA strains accordingly. A nonsubjective differentiation model was developed according to genetic confidence percentage values produced by tested samples, which did not require visual interpretation of HRM curve results. The test was carried out at different settings, and result data were reanalyzed and confirmed with DNA sequencing. PCR-HRM curve analysis proved to be a robust and reliable test for spa typing and can be used as a tool in epidemiological studies.




spa

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.




spa

Diabetes, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging Results (HCHS/SOL)

OBJECTIVE

Hispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos.

RESEARCH DESIGN AND METHODS

The Study of Latinos–Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years (n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes.

RESULTS

Prevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (βGC = –0.16 [95% CI –0.25; –0.07]; P < 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P < 0.001) compared with no diabetes in age- and sex-adjusted models.

CONCLUSIONS

Diabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos.




spa

The contact system proteases play disparate roles in streptococcal sepsis

Sepsis causes an activation of the human contact system, an inflammatory response mechanism against foreign surfaces, proteins and pathogens. The serine proteases of the contact system, factor XII and plasma kallikrein, are decreased in plasma of septic patients, which was previously associated with an unfavorable outcome. However, the precise mechanisms and roles of contact system factors in bacterial sepsis are poorly understood. We, therefore, studied the physiological relevance of factor XII and plasma kallikrein in a mouse model of experimental sepsis. We show that decreased plasma kallikrein concentration in septic mice is a result of reduced mRNA expression plasma prekallikrein gene, indicating that plasma kallikrein belong to negative acute phase proteins. Investigations regarding the pathophysiological function of contact system proteases during sepsis revealed different roles for factor XII and plasma kallikrein. In vitro, factor XII decelerated bacteria induced fibrinolysis, whereas plasma kallikrein supported it. Remarkably, depletion of plasma kallikrein (but not factor XII) by treatment with antisense-oligonucleotides, dampens bacterial dissemination and growth in multiple organs in the mouse sepsis model. These findings identify plasma kallikrein as a novel host pathogenicity factor in Streptococcus pyogenes sepsis.




spa

Genetic Influences of the Microbiota on the Life Span of Drosophila melanogaster [Invertebrate Microbiology]

To better understand how associated microorganisms ("microbiota") influence organismal aging, we focused on the model organism Drosophila melanogaster. We conducted a metagenome-wide association (MGWA) as a screen to identify bacterial genes associated with variation in the D. melanogaster life span. The results of the MGWA predicted that bacterial cysteine and methionine metabolism genes influence fruit fly longevity. A mutant analysis, in which flies were inoculated with Escherichia coli strains bearing mutations in various methionine cycle genes, confirmed a role for some methionine cycle genes in extending or shortening fruit fly life span. Initially, we predicted these genes might influence longevity by mimicking or opposing methionine restriction, an established mechanism for life span extension in fruit flies. However, follow-up transcriptome sequencing (RNA-seq) and metabolomic experiments were generally inconsistent with this conclusion and instead implicated glucose and vitamin B6 metabolism in these influences. We then tested if bacteria could influence life span through methionine restriction using a different set of bacterial strains. Flies reared with a bacterial strain that ectopically expressed bacterial transsulfuration genes and lowered the methionine content of the fly diet also extended female D. melanogaster life span. Taken together, the microbial influences shown here overlap with established host genetic mechanisms for aging and therefore suggest overlapping roles for host and microbial metabolism genes in organismal aging.

IMPORTANCE Associated microorganisms ("microbiota") are intimately connected to the behavior and physiology of their animal hosts, and defining the mechanisms of these interactions is an urgent imperative. This study focuses on how microorganisms influence the life span of a model host, the fruit fly Drosophila melanogaster. First, we performed a screen that suggested a strong influence of bacterial methionine metabolism on host life span. Follow-up analyses of gene expression and metabolite abundance identified stronger roles for vitamin B6 and glucose than methionine metabolism among the tested mutants, possibly suggesting a more limited role for bacterial methionine metabolism genes in host life span effects. In a parallel set of experiments, we created a distinct bacterial strain that expressed life span-extending methionine metabolism genes and showed that this strain can extend fly life span. Therefore, this work identifies specific bacterial genes that influence host life span, including in ways that are consistent with the expectations of methionine restriction.




spa

TRPV6 as a Putative Genomic Susceptibility Locus Influencing Racial Disparities in Cancer

It is well established that African Americans exhibit higher incidence, higher mortality, and more aggressive forms of some cancers, including those of breast, prostate, colon, stomach, and cervix. Here we examine the ancestral haplotype of the TRPV6 calcium channel as a putative genomic factor in this racial divide. The minor (ancestral) allele frequency is 60% in people of African ancestry, but between 1% and 11% in all other populations. Research on TRPV6 structure/function, its association with specific cancers, and the evolutionary-ecological conditions that impacted selection of its haplotypes are synthesized to provide evidence for TRPV6 as a germline susceptibility locus in cancer. Recently elucidated mechanisms of TRPV6 channel deactivation are discussed in relation to the location of the allele favored in selection, suggesting a reduced capacity to inactivate the channel in those who have the ancestral haplotype. This could result in an excessively high cellular Ca2+, which has been implicated in cancer, for those in settings where calcium intake is far higher than in their ancestral environment. A recent report associating increasing calcium intake with a pattern of increase in aggressive prostate cancer in African-American but not European-American men may be related. If TRPV6 is found to be associated with cancer, further research would be warranted to improve risk assessment and examine interventions with the aim of improving cancer outcomes for people of African ancestry.




spa

Reliability of CT Angiography in Cerebral Vasospasm: A Systematic Review of the Literature and an Inter- and Intraobserver Study [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm.

MATERIALS AND METHODS:

In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study.

RESULTS:

In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best ( ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial ( > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters’ judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial ( ≤ 0.6).

CONCLUSIONS:

The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH.