Variation in Coral Thermotolerance Across a Pollution Gradient Erodes as Coral Symbionts Shift to More Heat-Tolerant Genera

Phenotypic plasticity is one mechanism whereby species may cope with stressful environmental changes associated with climate change. Reef building corals present a good model for studying phenotypic plasticity because they have experienced rapid climate-driven declines in recent decades (within a single generation of many corals), often with differential survival among individuals during heat stress. Underlying differences in thermotolerance may be driven by differences in baseline levels of environmental stress, including pollution stress. To examine this possibility, acute heat stress experiments were conducted on Acropora hyacinthus from 10 sites around Tutuila, American Samoa with differing nutrient pollution impact. A threshold-based heat stress assay was conducted in 2014 and a ramp-hold based assay was conducted in 2019. Bleaching responses were measured by assessing color paling. Endosymbiont community composition was assessed at each site using quantitative PCR. RNA sequencing was used to compare differences in coral gene expression patterns prior to and during heat stress in 2019. In 2014, thermotolerance varied among sites, with polluted sites holding more thermotolerant corals. These differences in thermotolerance correlated with differences in symbiont communities, with higher proportions of heat-tolerant Durusdinium found in more polluted sites. By 2019, thermotolerance varied less among sites, with no clear trend by pollution level. This coincided with a shift toward Durusdinium across all sites, reducing symbiont community differences seen in 2014. While pollution and symbiont community no longer could explain variation in thermotolerance by 2019, gene expression patterns at baseline levels could be used to predict thermotolerance thresholds. These patterns suggest that the mechanisms underlying thermotolerance shifted between 2014 and 2019, though it is possible trends may have also been affected by methodological differences between heat stress assays. This study documents a shift in symbiont community over time and captures potential implications of that shift, including how it affects variation in thermotolerance among neighboring reefs. This work also highlights how gene expression patterns could help identify heat-tolerant corals in a future where most corals are dominated by Durusdinium and symbiont-driven thermotolerance has reached an upper limit

Mapping Concentrations of Posttraumatic Stress and Depression Trajectories Following Hurricane Ike

We investigated geographic concentration in elevated risk for a range of postdisaster trajectories of chronic posttraumatic stress symptom (PTSS) and depression symptoms in a longitudinal study (N = 561) of a Hurricane Ike affected population in Galveston and Chambers counties, TX. Using an unadjusted spatial scan statistic, we detected clusters of elevated risk of PTSS trajectories, but not depression trajectories, on Galveston Island. We then tested for predictors of membership in each trajectory of PTSS and depression (e.g., demographic variables, trauma exposure, social support), not taking the geographic nature of the data into account. After adjusting for significant predictors in the spatial scan statistic, we noted that spatial clusters of PTSS persisted and additional clusters of depression trajectories emerged. This is the first study to show that longitudinal trajectories of postdisaster mental health problems may vary depending on the geographic location and the individual- and community-level factors present at these locations. Such knowledge is crucial to identifying vulnerable regions and populations within them, to provide guidance for early responders, and to mitigate mental health consequences through early detection of mental health needs in the population. As human-made disasters increase, our approach may be useful also in other regions in comparable settings worldwide

ChIP-less analysis of chromatin states

BACKGROUND: Histone post-translational modifications (PTMs) are key epigenetic regulators in chromatin-based processes. Increasing evidence suggests that vast combinations of PTMs exist within chromatin histones. These complex patterns, rather than individual PTMs, are thought to define functional chromatin states. However, the ability to interrogate combinatorial histone PTM patterns at the nucleosome level has been limited by the lack of direct molecular tools. RESULTS: Here we demonstrate an efficient, quantitative, antibody-free, chromatin immunoprecipitation-less (ChIP-less) method for interrogating diverse epigenetic states. At the heart of the workflow are recombinant chromatin reader domains, which target distinct chromatin states with combinatorial PTM patterns. Utilizing a newly designed combinatorial histone peptide microarray, we showed that three reader domains (ATRX-ADD, ING2-PHD and AIRE-PHD) displayed greater specificity towards combinatorial PTM patterns than corresponding commercial histone antibodies. Such specific recognitions were employed to develop a chromatin reader-based affinity enrichment platform (matrix-assisted reader chromatin capture, or MARCC). We successfully applied the reader-based platform to capture unique chromatin states, which were quantitatively profiled by mass spectrometry to reveal interconnections between nucleosomal histone PTMs. Specifically, a highly enriched signature that harbored H3K4me0, H3K9me2/3, H3K79me0 and H4K20me2/3 within the same nucleosome was identified from chromatin enriched by ATRX-ADD. This newly reported PTM combination was enriched in heterochromatin, as revealed by the associated DNA. CONCLUSIONS: Our results suggest the broad utility of recombinant reader domains as an enrichment tool specific to combinatorial PTM patterns, which are difficult to probe directly by antibody-based approaches. The reader affinity platform is compatible with several downstream analyses to investigate the physical coexistence of nucleosomal PTM states associated with specific genomic loci. Collectively, the reader-based workflow will greatly facilitate our understanding of how distinct chromatin states and reader domains function in gene regulatory mechanisms

Community views on active case finding for tuberculosis in low‐ and middle‐income countries: a qualitative evidence synthesis

Background Active case finding (ACF) refers to the systematic identification of people with tuberculosis in communities and amongst populations who do not present to health facilities, through approaches such as door‐to‐door screening or contact tracing. ACF may improve access to tuberculosis diagnosis and treatment for the poor and for people remote from diagnostic and treatment facilities. As a result, ACF may also reduce onward transmission. However, there is a need to understand how these programmes are experienced by communities in order to design appropriate services. Objectives To synthesize community views on tuberculosis active case finding (ACF) programmes in low‐ and middle‐income countries. Search methods We searched MEDLINE, Embase, and eight other databases up to 22 June 2023, together with reference checking, citation searching, and contact with study authors to identify additional studies. We did not include grey literature. Selection criteria This review synthesized qualitative research and mixed‐methods studies with separate qualitative data. Eligible studies explored community experiences, perceptions, or attitudes towards ACF programmes for tuberculosis in any endemic low‐ or middle‐income country, with no time restrictions. Data collection and analysis Due to the large volume of studies identified, we chose to sample studies that had 'thick' description and that investigated key subgroups of children and refugees. We followed standard Cochrane methods for study description and appraisal of methodological limitations. We conducted thematic synthesis and developed codes inductively using ATLAS.ti software. We examined codes for underlying ideas, connections, and interpretations and, from this, generated analytical themes. We assessed the confidence in the findings using the GRADE‐CERQual approach, and produced a conceptual model to display how the different findings interact. Main results We included 45 studies in this synthesis, and sampled 20. The studies covered a broad range of World Health Organization (WHO) regions (Africa, South‐East Asia, Eastern Mediterranean, and the Americas) and explored the views and experiences of community members, community health workers, and clinical staff in low‐ and middle‐income countries endemic for tuberculosis. The following five themes emerged. • ACF improves access to diagnosis for many, but does little to help communities on the edge. Tuberculosis ACF and contact tracing improve access to health services for people with worse health and fewer resources (High confidence). ACF helps to find this population, exposed to deprived living conditions, but is not sensitive to additional dimensions of their plight (High confidence) and out‐of‐pocket costs necessary to continue care (High confidence). Finally, migration and difficult geography further reduce communities' access to ACF (High confidence). • People are afraid of diagnosis and its impact. Some community members find screening frightening. It exposes them to discrimination along distinct pathways (isolation from their families and wider community, lost employment and housing). HIV stigma compounds tuberculosis stigma and heightens vulnerability to discrimination along these same pathways (High confidence). Consequently, community members may refuse to participate in screening, contact tracing, and treatment (High confidence). In addition, people with tuberculosis reported their emotional turmoil upon diagnosis, as they anticipated intense treatment regimens and the prospect of living with a serious illness (High confidence). • Screening is undermined by weak health infrastructure. In many settings, a lack of resources results in weak services in competition with other disease control programmes (Moderate confidence). In this context of low investment, people face repeated tests and clinic visits, wasted time, and fraught social interaction with health providers (Moderate confidence). ACF can create expectations for follow‐up health care that it cannot deliver (High confidence). Finally, community education improves awareness of tuberculosis in some settings, but lack of full information impacts community members, parents, and health workers, and sometimes leads to harm for children (High confidence). • Health workers are an undervalued but important part of ACF. ACF can feel difficult for health workers in the context of a poorly resourced health system and with people who may not wish to be identified. In addition, the evidence suggests health workers are poorly protected against tuberculosis and fear they or their families might become infected (Moderate confidence). However, they appear to be central to programme success, as the humanity they offer often acts as a driving force for retaining people with tuberculosis in care (Moderate confidence). • Local leadership is necessary but not sufficient for ensuring appropriate programmes. Local leadership creates an intrinsic motivation for communities to value health services (High confidence). However, local leadership cannot guarantee the success of ACF and contact tracing programmes. It is important to balance professional authority with local knowledge and rapport (High confidence). Authors' conclusions Tuberculosis active case finding (ACF) and contact tracing bring a diagnostic service to people who may otherwise not receive it, such as those who are well or without symptoms and those who are sick but who have fewer resources and live further from health facilities. However, capturing these 'missing cases' may in itself be insufficient without appropriate health system strengthening to retain people in care. People who receive a tuberculosis diagnosis must contend with a complex and unsustainable cascade of care, and this affects their perception of ACF and their decision to engage with it

The 3rd Fermi GBM Gamma-Ray Burst Catalog: The First Six Years

Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has triggered and located on average approximately two gamma-ray bursts (GRB) every three days. Here we present the third of a series of catalogs of GRBs detected by GBM, extending the second catalog by two more years, through the middle of July 2014. The resulting list includes 1405 triggers identified as GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM detected GRBs. For each GRB the location and main characteristics of the prompt emission, the duration, peak flux and fluence are derived. The latter two quantities are calculated for the 50-300~keV energy band, where the maximum energy release of GRBs in the instrument reference system is observed, and also for a broader energy band from 10-1000 keV, exploiting the full energy range of GBM's low-energy NaI(Tl) detectors. Using statistical methods to assess clustering, we find that the hardness and duration of GRBs are better fitted by a two-component model with short-hard and long-soft bursts, than by a model with three components. Furthermore, information is provided on the settings and modifications of the triggering criteria and exceptional operational conditions during years five and six in the mission. This third catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center (HEASARC).Comment: 225 pages, 13 figures and 8 tables. Accepted for publication in Astrophysical Journal Supplement 201

Error mitigation, optimization, and extrapolation on a trapped ion testbed

Current noisy intermediate-scale quantum (NISQ) trapped-ion devices are subject to errors around 1% per gate for two-qubit gates. These errors significantly impact the accuracy of calculations if left unchecked. A form of error mitigation called Richardson extrapolation can reduce these errors without incurring a qubit overhead. We demonstrate and optimize this method on the Quantum Scientific Computing Open User Testbed (QSCOUT) trapped-ion device to solve an electronic structure problem. We explore different methods for integrating this error mitigation technique into the Variational Quantum Eigensolver (VQE) optimization algorithm for calculating the ground state of the HeH+ molecule at 0.8 Angstrom. We test two methods of scaling noise for extrapolation: time-stretching the two-qubit gates and inserting two-qubit gate identity operations into the ansatz circuit. We find the former fails to scale the noise on our particular hardware. Scaling our noise with global gate identity insertions and extrapolating only after a variational optimization routine, we achieve an absolute relative error of 0.363% +- 1.06 compared to the true ground state energy of HeH+. This corresponds to an absolute error of 0.01 +- 0.02 Hartree; outside chemical accuracy, but greatly improved over our non error mitigated estimate. We ultimately find that the efficacy of this error mitigation technique depends on choosing the right implementation for a given device architecture and sampling budget.Comment: 16 pages, 11 figure

Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors

Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by the ENCODE Consortium. We identified highly enriched sequence motifs in most data sets, revealing new motifs and validating known ones. The motif sites (TF binding sites) are highly conserved evolutionarily and show distinct footprints upon DNase I digestion. We frequently detected secondary motifs in addition to the canonical motifs of the TFs, indicating tethered binding and cobinding between multiple TFs. We observed significant position and orientation preferences between many cobinding TFs. Genes specifically expressed in a cell line are often associated with a greater occurrence of nearby TF binding in that cell line. We observed cell-line-specific secondary motifs that mediate the binding of the histone deacetylase HDAC2 and the enhancer-binding protein EP300. TF binding sites are located in GC-rich, nucleosome-depleted, and DNase I sensitive regions, flanked by well-positioned nucleosomes, and many of these features show cell type specificity. The GC-richness may be beneficial for regulating TF binding because, when unoccupied by a TF, these regions are occupied by nucleosomes in vivo. We present the results of our analysis in a TF-centric web repository Factorbook (http://factorbook.org) and will continually update this repository as more ENCODE data are generated

Increased AID results in mutations at the CRLF2 locus implicated in Latin American ALL health disparities

Activation-induced cytidine deaminase (AID) is a B cell-specific mutator required for antibody diversification. However, it is also implicated in the etiology of several B cell malignancies. Evaluating the AID-induced mutation load in patients at-risk for certain blood cancers is critical in assessing disease severity and treatment options. We have developed a digital PCR (dPCR) assay that allows us to quantify mutations resulting from AID modification or DNA double-strand break (DSB) formation and repair at sites known to be prone to DSBs. Implementation of this assay shows that increased AID levels in immature B cells increase genome instability at loci linked to chromosomal translocation formation. This includes the CRLF2 locus that is often involved in translocations associated with a subtype of acute lymphoblastic leukemia (ALL) that disproportionately affects Hispanics, particularly those with Latin American ancestry. Using dPCR, we characterize the CRLF2 locus in B cell-derived genomic DNA from both Hispanic ALL patients and healthy Hispanic donors and found increased mutations in both, suggesting that vulnerability to DNA damage at CRLF2 may be driving this health disparity. Our ability to detect and quantify these mutations will potentiate future risk identification, early detection of cancers, and reduction of associated cancer health disparities