Biotic Interactions Shape the Ecological Distributions of Staphylococcus Species.

Many metagenomic sequencing studies have observed the presence of closely related bacterial species or genotypes in the same microbiome. Previous attempts to explain these patterns of microdiversity have focused on the abiotic environment, but few have considered how biotic interactions could drive patterns of microbiome diversity. We dissected the patterns, processes, and mechanisms shaping the ecological distributions of three closely related Staphylococcus species in cheese rind biofilms. Paradoxically, the most abundant species (S. equorum) is the slowest colonizer and weakest competitor based on growth and competition assays in the laboratory. Through in vitro community reconstructions, we determined that biotic interactions with neighboring fungi help resolve this paradox. Species-specific stimulation of the poor competitor by fungi of the genus Scopulariopsis allows S. equorum to dominate communities in vitro as it does in situ Results of comparative genomic and transcriptomic experiments indicate that iron utilization pathways, including a homolog of the S. aureus staphyloferrin B siderophore operon pathway, are potential molecular mechanisms underlying Staphylococcus-Scopulariopsis interactions. Our integrated approach demonstrates that fungi can structure the ecological distributions of closely related bacterial species, and the data highlight the importance of bacterium-fungus interactions in attempts to design and manipulate microbiomes.ImportanceDecades of culture-based studies and more recent metagenomic studies have demonstrated that bacterial species in agriculture, medicine, industry, and nature are unevenly distributed across time and space. The ecological processes and molecular mechanisms that shape these distributions are not well understood because it is challenging to connect in situ patterns of diversity with mechanistic in vitro studies in the laboratory. Using tractable cheese rind biofilms and a focus on coagulase-negative staphylococcus (CNS) species, we demonstrate that fungi can mediate the ecological distributions of closely related bacterial species. One of the Staphylococcus species studied, S. saprophyticus, is a common cause of urinary tract infections. By identifying processes that control the abundance of undesirable CNS species, cheese producers will have more precise control on the safety and quality of their products. More generally, Staphylococcus species frequently co-occur with fungi in mammalian microbiomes, and similar bacterium-fungus interactions may structure bacterial diversity in these systems

Transcriptional networks specifying homeostatic and inflammatory programs of gene expression in human aortic endothelial cells.

Endothelial cells (ECs) are critical determinants of vascular homeostasis and inflammation, but transcriptional mechanisms specifying their identities and functional states remain poorly understood. Here, we report a genome-wide assessment of regulatory landscapes of primary human aortic endothelial cells (HAECs) under basal and activated conditions, enabling inference of transcription factor networks that direct homeostatic and pro-inflammatory programs. We demonstrate that 43% of detected enhancers are EC-specific and contain SNPs associated to cardiovascular disease and hypertension. We provide evidence that AP1, ETS, and GATA transcription factors play key roles in HAEC transcription by co-binding enhancers associated with EC-specific genes. We further demonstrate that exposure of HAECs to oxidized phospholipids or pro-inflammatory cytokines results in signal-specific alterations in enhancer landscapes and associate with coordinated binding of CEBPD, IRF1, and NFκB. Collectively, these findings identify cis-regulatory elements and corresponding trans-acting factors that contribute to EC identity and their specific responses to pro-inflammatory stimuli

Electrical characterization of the soft breakdown failure mode in MgO layers

The soft breakdown (SBD) failure mode in 20 nm thick MgO dielectric layers grown on Si substrates was investigated. We show that during a constant voltage stress, charge trapping and progressive breakdown coexist, and that the degradation dynamics is captured by a power-law time dependence. We also show that the SBD current-voltage (I-V) characteristics follow the power-law model I = aVb typical of this conduction mechanism but in a wider voltage window than the one reported in the past for SiO2. The relationship between the magnitude of the current and the normalized differential conductance was analyzed

A massive, distant proto-cluster at z=2.47 caught in a phase of rapid formation?

Numerical simulations of cosmological structure formation show that the Universe's most massive clusters, and the galaxies living in those clusters, assemble rapidly at early times (2.5 < z < 4). While more than twenty proto-clusters have been observed at z > 2 based on associations of 5-40 galaxies around rare sources, the observational evidence for rapid cluster formation is weak. Here we report observations of an asymmetric, filamentary structure at z = 2.47 containing seven starbursting, submillimeter-luminous galaxies and five additional AGN within a comoving volume of 15000 Mpc$^{3}$. As the expected lifetime of both the luminous AGN and starburst phase of a galaxy is ~100 Myr, we conclude that these sources were likely triggered in rapid succession by environmental factors, or, alternatively, the duration of these cosmologically rare phenomena is much longer than prior direct measurements suggest. The stellar mass already built up in the structure is $\sim10^{12}M_{\odot}$ and we estimate that the cluster mass will exceed that of the Coma supercluster at $z \sim 0$. The filamentary structure is in line with hierarchical growth simulations which predict that the peak of cluster activity occurs rapidly at z > 2.Comment: 7 pages, 3 figures, 2 tables, accepted in ApJL (small revisions from previous version

Transdiagnostic treatment of bipolar disorder and comorbid anxiety using the Unified Protocol for Emotional Disorders: A pilot feasibility and acceptability trial

BACKGROUND Comorbid anxiety in bipolar disorder (BD) is associated with greater illness severity, reduced treatment response, and greater impairment. Treating anxiety in the context of BD is crucial for improving illness course and outcomes. The current study examined the feasibility, acceptability and preliminary efficacy of the Unified Protocol (UP), a transdiagnostic cognitive behavioral therapy, as an adjunctive treatment to pharmacotherapy for BD and comorbid anxiety disorders. METHODS Twenty-nine patients with BD and at least one comorbid anxiety disorder were randomized to pharmacotherapy treatment-as-usual (TAU) or TAU with 18 sessions of the UP (UP+TAU). All patients completed assessments every four weeks to track symptoms, functioning, emotion regulation and temperament. Linear mixed-model regressions were conducted to track symptom changes over time and to examine the relationship between emotion-related variables and treatment response. RESULTS Satisfaction ratings were equivalent for both treatment groups. Patients in the UP+TAU group evidenced significantly greater reductions over time in anxiety and depression symptoms (Cohen's d's>0.80). Baseline levels of neuroticism, perceived affective control, and emotion regulation ability predicted magnitude of symptom change for the UP+TAU group only. Greater change in perceived control of emotions and emotion regulation skills predicted greater change in anxiety related symptoms. LIMITATIONS This was a pilot feasibility and acceptability trial; results should be interpreted with caution. CONCLUSIONS Treatment with the UP+TAU was rated high in patient satisfaction, and resulted in significantly greater improvement on indices of anxiety and depression relative to TAU. This suggests that the UP may be a feasible treatment approach for BD with comorbid anxiety.This work was supported by a Postdoctoral National Research Service Award from the National Institutes of Health [F32 MH098490] to K. Ellard. (F32 MH098490 - Postdoctoral National Research Service Award from the National Institutes of Health)Accepted manuscrip

Novel missense mutation in the bZIP transcription factor, MAF, associated with congenital cataract, developmental delay, seizures and hearing loss (Ayme-Gripp syndrome)

Published online: 08 May 2017Background: Cataract is a major cause of severe visual impairment in childhood. The purpose of this study was to determine the genetic cause of syndromic congenital cataract in an Australian mother and son. Method: Fifty-one genes associated with congenital cataract were sequenced in the proband using a custom Ampliseq library on the Ion Torrent Personal Genome Machine (PGM). Reads were aligned against the human genome (hg19) and variants were annotated. Variants were prioritised for validation by Sanger sequencing if they were novel, rare or previously reported to be associated with paediatric cataract and were predicted to be protein changing. Variants were assessed for segregation with the phenotype in the affected mother. Result: A novel likely pathogenic variant was identified in the transactivation domain of the MAF gene (c.176C > G, p.(Pro59Arg)) in the proband and his affected mother., but was absent in 326 unrelated controls and absent from public variant databases. Conclusion: The MAF variant is the likely cause of the congenital cataract, Asperger syndrome, seizures, hearing loss and facial characteristics in the proband, providinga diagnosis of Aymé-Gripp syndrome for the family.Shari Javadiyan, Jamie E. Craig, Shiwani Sharma, Karen M. Lower, Theresa Casey, Eric Haan, Emmanuelle Souzeau and Kathryn P. Burdo

Satellite-derived, melt-season surface temperature of the Greenland Ice Sheet (2000–2005) and its relationship to mass balance

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 33 (2006): L11501, doi:10.1029/2006GL026444.Mean, clear-sky surface temperature of the Greenland Ice Sheet was measured for each melt season from 2000 to 2005 using Moderate-Resolution Imaging Spectroradiometer (MODIS)–derived land-surface temperature (LST) data-product maps. During the period of most-active melt, the mean, clear-sky surface temperature of the ice sheet was highest in 2002 (−8.29 ± 5.29°C) and 2005 (−8.29 ± 5.43°C), compared to a 6-year mean of −9.04 ± 5.59°C, in agreement with recent work by other investigators showing unusually extensive melt in 2002 and 2005. Surface-temperature variability shows a correspondence with the dry-snow facies of the ice sheet; a reduction in area of the dry-snow facies would indicate a more-negative mass balance. Surface-temperature variability generally increased during the study period and is most pronounced in the 2005 melt season; this is consistent with surface instability caused by air-temperature fluctuations.Support for this work was provided by NASA’s Earth Observing System and Cryospheric Sciences Programs

Progress and gaps in reproductive health services in three humanitarian settings: mixed-methods case studies

Background Reproductive health (RH) care is an essential component of humanitarian response. Women and girls living in humanitarian settings often face high maternal mortality and are vulnerable to unwanted pregnancy, unsafe abortion, and sexual violence. This study explored the availability and quality of, and access barriers to RH services in three humanitarian settings in Burkina Faso, Democratic Republic of the Congo (DRC), and South Sudan. Methods Data collection was conducted between July and October 2013. In total, 63 purposively selected health facilities were assessed: 28 in Burkina Faso, 25 in DRC, and nine in South Sudan, and 42 providers completed a questionnaire to assess RH knowledge and attitudes. Thirty-four focus group discussions were conducted with 29 members of the host communities and 273 displaced married and unmarried women and men to understand access barriers. Results All facilities reported providing some RH services in the prior three months. Five health facilities in Burkina Faso, six in DRC, and none in South Sudan met the criteria as a family planning service delivery point. Two health facilities in Burkina Faso, one in DRC, and two in South Sudan met the criteria as an emergency obstetric and newborn care service delivery point. Across settings, three facilities in DRC adequately provided selected elements of clinical management of rape. Safe abortion was unavailable. Many providers lacked essential knowledge and skills. Focus groups revealed limited knowledge of available RH services and socio-cultural barriers to accessing them, although participants reported a remarkable increase in use of facility-based delivery services. Conclusion Although RH services are being provided, the availability of good quality RH services was inconsistent across settings. Commodity management and security must be prioritized to ensure consistent availability of essential supplies. It is critical to improve the attitudes, managerial and technical capacity of providers to ensure that RH services are delivered respectfully and efficiently. In addition to ensuring systematic implementation of good quality RH services, humanitarian health actors should meaningfully engage crisis-affected communities in RH programming to increase understanding and use of this life-saving care