In vivo binding of active heat shock transcription factor 1 to human chromosome 9 heterochromatin during stress

Activation of the mammalian heat shock transcription factor (HSF)1 by stress is a multistep process resulting in the transcription of heat shock genes. Coincident with these events is the rapid and reversible redistribution of HSF1 to discrete nuclear structures termed HSF1 granules, whose function is still unknown. Key features are that the number of granules correlates with cell ploidy, suggesting the existence of a chromosomal target. Here we show that in humans, HSF1 granules localize to the 9q11-q12 heterochromatic region. Within this locus, HSF1 binds through direct DNA–protein interaction with a nucleosome-containing subclass of satellite III repeats. HSF1 granule formation only requires the DNA binding competence and the trimerization of the factor. This is the first example of a transcriptional activator that accumulates transiently and reversibly on a chromosome-specific heterochromatic locus

Gradual Recovery of Building Plumbing-Associated Microbial Communities after Extended Periods of Altered Water Demand during the COVID-19 Pandemic

COVID-19 pandemic-related building restrictions heightened drinking water microbiological safety concerns post-reopening due to the unprecedented nature of commercial building closures. Starting with phased reopening (i.e., June 2020), we sampled drinking water for 6 months from three commercial buildings with reduced water usage and four occupied residential households. Samples were analyzed using flow cytometry and full-length 16S rRNA gene sequencing along with comprehensive water chemistry characterization. Prolonged building closures resulted in 10-fold higher microbial cell counts in the commercial buildings [(2.95 ± 3.67) × 105 cells mL-1] than in residential households [(1.11 ± 0.58) × 104 cells mL-1] with majority intact cells. While flushing reduced cell counts and increased disinfection residuals, microbial communities in commercial buildings remained distinct from those in residential households on the basis of flow cytometric fingerprinting [Bray-Curtis dissimilarity (dBC) = 0.33 ± 0.07] and 16S rRNA gene sequencing (dBC = 0.72 ± 0.20). An increase in water demand post-reopening resulted in gradual convergence in microbial communities in water samples collected from commercial buildings and residential households. Overall, we find that the gradual recovery of water demand played a key role in the recovery of building plumbing-associated microbial communities as compared to short-term flushing after extended periods of reduced water demand

High-Resolution Spectral Sleep Analysis Reveals a Novel Association Between Slow Oscillations and Memory Retention in Elderly Adults

Objective: In recognition of the mixed associations between traditionally scored slow wave sleep and memory, we sought to explore the relationships between slow wave sleep, electroencephalographic (EEG) power spectra during sleep and overnight verbal memory retention in older adults. Design, Setting, Participants, and Measurements: Participants were 101 adults without dementia (52% female, mean age 70.3 years). Delayed verbal memory was first tested in the evening prior to overnight polysomnography (PSG). The following morning, subjects were asked to recall as many items as possible from the same List (overnight memory retention; OMR). Partial correlation analyses examined the associations of delayed verbal memory and OMR with slow wave sleep (SWS) and two physiologic EEG slow wave activity (SWA) power spectral bands (0.5–1 Hz slow oscillations vs. 1–4 Hz delta activity). Results: In subjects displaying SWS, SWS was associated with enhanced delayed verbal memory, but not with OMR. Interestingly, among participants that did not show SWS, OMR was significantly associated with a higher slow oscillation relative power, during NREM sleep in the first ultradian cycle, with medium effect size. Conclusions: These findings suggest a complex relationship between SWS and memory and illustrate that even in the absence of scorable SWS, older adults demonstrate substantial slow wave activity. Further, these slow oscillations (0.5–1 Hz), in the first ultradian cycle, are positively associated with OMR, but only in those without SWS. Our findings raise the possibility that precise features of slow wave activity play key roles in maintaining memory function in healthy aging. Further, our results underscore that conventional methods of sleep evaluation may not be sufficiently sensitive to detect associations between SWA and memory in older adults

ORegAnno 3.0: A community-driven resource for curated regulatory annotation

The Open Regulatory Annotation database (ORegAnno) is a resource for curated regulatory annotation. It contains information about regulatory regions, transcription factor binding sites, RNA binding sites, regulatory variants, haplotypes, and other regulatory elements. ORegAnno differentiates itself from other regulatory resources by facilitating crowd-sourced interpretation and annotation of regulatory observations from the literature and highly curated resources. It contains a comprehensive annotation scheme that aims to describe both the elements and outcomes of regulatory events. Moreover, ORegAnno assembles these disparate data sources and annotations into a single, high quality catalogue of curated regulatory information. The current release is an update of the database previously featured in the NAR Database Issue, and now contains 1 948 307 records, across 18 species, with a combined coverage of 334 215 080 bp. Complete records, annotation, and other associated data are available for browsing and download at http://www.oreganno.org/

Photodegradation of ciprofloxacin and levofloxacin by Au@ZnONPs-MoS2-Rgo nanocomposites

This study aimed to investigate the photocatalytic performance of diverse zinc oxide catalysts containing gold nanoparticles (AuNPs), molybdenum disulfide (MoS2), and reduced graphene oxide (rGO) toward the degradation of the antibiotics levofloxacin (LFX) and ciprofloxacin (CFX) in aqueous solutions. The obtained results demonstrate that LFX is more resistant to degradation when compared with CFX and that the principal route of degradation under visible light is the formation of hydroxyl radicals. Photoluminescence (PL) measurements were employed to verify the inhibitory effect of electron–hole recombination when AuNPs, MoS2, and rGO are integrated into a semiconductor. The catalyst that achieved the highest percentage of CFX degradation was 1%Au@ZnONPs-3%MoS2-1%rGO, exhibiting a degradation efficiency of 96%, while the catalyst that exhibited the highest percentage of LFX degradation was 5%Au@ZnONPs-3%MoS2-1%rGO, displaying a degradation efficiency of 99.8%. A gas chromatography–mass spectrometry (GC-MS) analysis enabled the identification of reaction intermediates, facilitating the determination of a potential degradation pathway for both antibiotics. Additionally, recyclability assessments showed that the synthesized catalysts maintained stable photocatalytic efficiencies after 15 cycles, indicating that the heterostructures have the potential for further usage and may be tested with other organic contaminants as wellThe financial support from the NSF Center for the Advancement of Wearable TechnologiesCAWT (grant 1849243), from the Consortium of Hybrid Resilient Energy Systems (DE-NA0003982), and from the Spanish Ministry of Economy and Competitiveness, under NanoCat-Com Project (PID2021-124667OB-I00), are gratefully acknowledgedThe financial support from the NSF Center for the Advancement of Wearable TechnologiesCAWT (grant 1849243), from the Consortium of Hybrid Resilient Energy Systems (DE-NA0003982), and from the Spanish Ministry of Economy and Competitiveness, under NanoCat-Com Project (PID2021-124667OB-I00), are gratefully acknowledge

Personalized ctDNA micro-panels can monitor and predict clinical outcomes for patients with triple-negative breast cancer

Circulating tumor DNA (ctDNA) in peripheral blood has been used to predict prognosis and therapeutic response for triple-negative breast cancer (TNBC) patients. However, previous approaches typically use large comprehensive panels of genes commonly mutated across all breast cancers. Given the reduction in sequencing costs and decreased turnaround times associated with panel generation, the objective of this study was to assess the use of custom micro-panels for tracking disease and predicting clinical outcomes for patients with TNBC. Paired tumor-normal samples from patients with TNBC were obtained at diagnosis (T0) and whole exome sequencing (WES) was performed to identify somatic variants associated with individual tumors. Custom micro-panels of 4-6 variants were created for each individual enrolled in the study. Peripheral blood was obtained at baseline, during Cycle 1 Day 3, at time of surgery, and in 3-6 month intervals after surgery to assess variant allele fraction (VAF) at different timepoints during disease course. The VAF was compared to clinical outcomes to evaluate the ability of custom micro-panels to predict pathological response, disease-free intervals, and patient relapse. A cohort of 50 individuals were evaluated for up to 48 months post-diagnosis of TNBC. In total, there were 33 patients who did not achieve pathological complete response (pCR) and seven patients developed clinical relapse. For all patients who developed clinical relapse and had peripheral blood obtained ≤ 6 months prior to relapse (n = 4), the custom ctDNA micro-panels identified molecular relapse at an average of 4.3 months prior to clinical relapse. The custom ctDNA panel results were moderately associated with pCR such that during disease monitoring, only 11% of patients with pCR had a molecular relapse, whereas 47% of patients without pCR had a molecular relapse (Chi-Square; p-value = 0.10). In this study, we show that a custom micro-panel of 4-6 markers can be effectively used to predict outcomes and monitor remission for patients with TNBC. These custom micro-panels show high sensitivity for detecting molecular relapse in advance of clinical relapse. The use of these panels could improve patient outcomes through early detection of relapse with preemptive intervention prior to symptom onset

Imprisonment and internment: Comparing penal facilities North and South

Recent references to the ‘warehouse prison’ in the United States and the prisión-depósito in Latin America seem to indicate that penal confinement in the western hemisphere has converged on a similar model. However, this article suggests otherwise. It contrasts penal facilities in North America and Latin America in terms of six interrelated aspects: regimentation; surveillance; isolation; supervision; accountability; and formalization. Quantitatively, control in North American penal facilities is assiduous (unceasing, persistent and intrusive), while in Latin America it is perfunctory (sporadic, indifferent and cursory). Qualitatively, North American penal facilities produce imprisonment (which enacts penal intervention through confinement), while in Latin America they produce internment (which enacts penal intervention through release). Closely entwined with this qualitative difference are distinct practices of judicial involvement in sentencing and penal supervision. Those practices, and the cultural and political factors that underpin them, represent an interesting starting point for the explanation of the contrasting nature of imprisonment and internment

Open-Sourced CIViC Annotation Pipeline to identify and annotate clinically relevant variants using single-molecule molecular inversion probes

PURPOSE: Clinical targeted sequencing panels are important for identifying actionable variants for patients with cancer; however, existing approaches do not provide transparent and rationally designed clinical panels to accommodate the rapidly growing knowledge within oncology. MATERIALS AND METHODS: We used the Clinical Interpretations of Variants in Cancer (CIViC) database to develop an Open-Sourced CIViC Annotation Pipeline (OpenCAP). OpenCAP provides methods to identify variants within the CIViC database, build probes for variant capture, use probes on prospective samples, and link somatic variants to CIViC clinical relevance statements. OpenCAP was tested using a single-molecule molecular inversion probe (smMIP) capture design on 27 cancer samples from 5 tumor types. In total, 2,027 smMIPs were designed to target 111 eligible CIViC variants (61.5 kb of genomic space). RESULTS: When compared with orthogonal sequencing, CIViC smMIP sequencing demonstrated a 95% sensitivity for variant detection (n = 61 of 64 variants). Variant allele frequencies for variants identified on both sequencing platforms were highly concordant (Pearson\u27s CONCLUSION: The OpenCAP design paradigm demonstrates the utility of an open-source and open-access database built on attendant community contributions with peer-reviewed interpretations. Use of a public repository for variant identification, probe development, and variant interpretation provides a transparent approach to build dynamic next-generation sequencing-based oncology panels