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Glacier-archived records are powerful windows into past climates and ecosystems, but variation in co-preserved microbiota is rarely characterized over long time periods or connected to changing climates. In a 310-meter ice core from the Guliya ice cap, Tibetan Plateau, we linked microbial communities to concomitant climatic conditions across 33 depths, spanning at least the last 150,000 years. Communities differed significantly between cold and warm periods, and among the three major climate epochs Holocene, Last Glacial Stage (LGS), and Pre-LGS. Although source inputs varied during these periods, the microbial changes appeared independently impacted by climate as well. Co-occurrence network analyses suggested the importance of glacial surface-growing communities, and their phototrophs, to the preserved microbial record. The inferred microbial growth (by cell densities, diversity, and potential doubling times pre-compaction into solid ice) on Guliya’s surfaces was higher during cold periods than warm periods, likely associated with deeper snow and firn layers under colder conditions. Three Cyanobacteria “blooms” were captured in the record, and were significantly correlated to overall microbial concentration and diversity, as well as the abundance of two heterotrophic photosynthetic clades (the genus Geodermatophilus and the class Chloroflexia). Taxonomically, 6 genera were historically persistent and dominant throughout the record (Polaromonas, Flavobacterium, Massilia, Aquaspirillum, Pedobacter, and Cryobacterium), one of which (Cryobacterium) exhibited a shift in dominant strains from the Pre-LGS to the LGS, indicating a possible speciation event. Collectively, these findings advance our understanding of ancient glacier-archived microbial communities and the ecological forces they experienced, provide evidence for microbiological responses to the prevailing climate regime, and may shed new light on the microbial evolution across a long-term history over at least the last >150,000 years.

Although next-generation per- and polyfluorinated substances (PFAS) were designed and implemented as safer and environmentally degradable alternatives to "forever" legacy PFAS, there is little evidence to support the actual transformation of these compounds and less evidence of the safety of transformed products in the environment. Multiple congeners of one such PFAS alternative, the chloro-perfluoropolyether carboxylates (Cl-PFPECAs), have been found in New Jersey soils surrounding a manufacturing facility. These compounds are ideal candidates for investigating environmental transformation due to the existence of potential reaction centers including a chlorinated carbon and ether linkages. Transformation products of the chemical structures of this class of compounds were predicted based on analogous PFAS transformation pathways documented in peer-reviewed literature. Potential reaction products were used as the basis for high-resolution mass-spectrometric suspect screening of the soils. Suspected transformation products of multiple congeners, the Cl-PFPECAs, including H-PFPECAs, epox-PFPECAs, and diOH-PFPECAs, were tentatively observed in these screenings. Although ether linkages have been hypothesized as potential reaction centers under environmental conditions, to date, no documentation of ether scission has been identified. Despite exhaustive scrutiny of the high-resolution data for our Cl-PFPECA-laden soils, we found no evidence of ether scission.

Purpose:This study tested the hypothesis that a patient-derived orthotopic xenograft (PDOX) model would recapitulate the common clinical phenomenon of breast cancer–induced skeletal muscle (SkM) fatigue in the absence of muscle wasting. This study additionally sought to identify drivers of this condition to facilitate the development of therapeutic agents for patients with breast cancer experiencing muscle fatigue.Experimental Design:Eight female BC-PDOX–bearing mice were produced via transplantation of tumor tissue from 8 female patients with breast cancer. Individual hind limb muscles from BC-PDOX mice were isolated at euthanasia for RNA-sequencing, gene and protein analyses, and an ex vivo muscle contraction protocol to quantify tumor-induced aberrations in SkM function. Differentially expressed genes (DEG) in the BC-PDOX mice relative to control mice were identified using DESeq2, and multiple bioinformatics platforms were employed to contextualize the DEGs.Results:We found that SkM from BC-PDOX–bearing mice showed greater fatigability than control mice, despite no differences in absolute muscle mass. PPAR, mTOR, IL6, IL1, and several other signaling pathways were implicated in the transcriptional changes observed in the BC-PDOX SkM. Moreover, 3 independent in silico analyses identified PPAR signaling as highly dysregulated in the SkM of both BC-PDOX–bearing mice and human patients with early-stage nonmetastatic breast cancer.Conclusions:Collectively, these data demonstrate that the BC-PDOX model recapitulates the expected breast cancer–induced SkM fatigue and further identify aberrant PPAR signaling as an integral factor in the pathology of this condition.

Supplementary Figures S1-S4 from Molecularly Targeted Radiosensitization of Human Prostate Cancer by Modulating Inhibitor of Apoptosis

Purpose: The inhibitor of apoptosis proteins (IAP) are overexpressed in hormone-refractory prostate cancer, rendering the cancer cells resistant to radiation. This study aims to investigate the radiosensitizing effect of small-molecule IAP inhibitor both in vitro and in vivo in androgen-independent prostate cancer and the possible mechanism of radiosensitization.Experimental Design: Radiosensitization of SH-130 in human prostate cancer DU-145 cells was determined by clonogenic survival assay. Combination effect of SH-130 and ionizing radiation was evaluated by apoptosis assays. Pull-down and immunoprecipitation assays were employed to investigate the interaction between SH-130 and IAPs. DU-145 xenografts in nude mice were treated with SH-130, radiation, or combination, and tumor suppression effect was determined by caliper measurement or bioluminescence imaging. Nuclear factor-κB activation was detected by luciferase reporter assay and quantitative real-time PCR.Results: SH-130 potently enhanced radiation-induced caspase activation and apoptosis in DU-145 cells. Both X-linked IAP and cIAP-1 can be pulled down by SH-130 but not by inactive SH-123. Moreover, SH-130 interrupted interaction between X-linked IAP/cIAP-1 and Smac. In a nude mouse xenograft model, SH-130 potently sensitized the DU-145 tumors to X-ray radiation without increasing systemic toxicity. The combination therapy suppressed tumor growth more significantly than either treatment alone, with over 80% of complete tumor regression. Furthermore, SH-130 partially blocked tumor necrosis factor-α- and radiation-induced nuclear factor-κB activation in DU-145 cells.Conclusions: Our results show that small-molecule inhibitors of IAPs can overcome apoptosis resistance and radiosensitize human prostate cancer with high levels of IAPs. Molecular modulation of IAPs may improve the outcome of prostate cancer radiotherapy.

NADPH is a critical reductant needed in cancer cells to fuel the biosynthesis of deoxynucleotides and antioxidants and to sustain stress-survival responses after radiation-induced DNA damage. Thus, one rational strategy to attack cancer cells is to target their heavy reliance on NADPH. Here, we report that the isocitrate dehydrogenase IDH1 is the most strongly upregulated NADPH-producing enzyme in glioblastoma (GBM). IDH1 silencing in GBM cells reduced levels of NADPH, deoxynucleotides, and glutathione and increased their sensitivity to radiation-induced senescence. Rescuing these metabolic restrictions was sufficient to reverse IDH1-mediated radiosensitization. In a murine xenograft model of human GBM, we found that IDH1 silencing significantly improved therapeutic responses to fractionated radiotherapy, when compared with either treatment alone. In summary, our work offers a mechanistic rationale for IDH1 inhibition as a metabolic strategy to improve the response of GBM to radiotherapy. Cancer Res; 77(4); 960–70. ©2016 AACR.

Supplementary Table 1: Experimental Details of Mass Spectrometry Supplemental Figure 1: Effects of IDH1 KD on radiation-induced apoptosis and autophagy. Effect of low dose radiation on expression of NADPH-producing enzymes Supplemental Figure 2: Effect of IDH1 KD on radiation induced DNA double strand break repair and homologous recombination repair Supplemental Figure 3: Cell cycle effects of IDH1 knockdown. Supplemental Figure 4: Effects of doxycycline and radiation on control i-shNT xenografts.

Table S3 shows data for correlational analyses between muscle contractile parameters and STAT activation

Figure S1 shows additional data from Enrichr in silico analyses, and protein analyses of STAT 3 and STAT5.

Supplemental legend

Currently in review. Methods are described in the full text. Please consult the README.mdfile for information about the included data.&nbsp

This article, based on the author’s Engels Memorial Lecture on 26 November 2020, examines the significance of Friedrich Engels’s seminal work on the origin of the family, the oppression of women and the relationship of both to the development of private property. While accepting his overall analysis and rejecting alternatives, the article questions the application of Engels’s theory to an understanding of the working-class family. It suggests a way in which this lacuna can be remedied from a Marxist perspective.

Through an extensive review of the literature, our objective will be to clarify the current concept that exists about the pathogenesis of peri-implantitis, as well as the implications that bacteria may have on it. To date, different longitudinal and cross-sectional studies have identified some of the risk factors or risk indicators of peri-implantitis. Previous history of periodontal disease, diabetes, genetic load, poor oral hygiene, tobacco, alcohol consumption, absence of keratinized gingiva and the surface of the implants are some of the factors that have been analyzed in detail in the literature. The colonization of new surgically implanted surfaces represents a risk situation in partially edentulous patients, where periodontopathogenic bacteria from the residual bag play an important role.

The authors present a mixed-methods research study that has resulted in a framework to characterize public programs offered by US libraries. This categorization lays the foundation for long...

This paper presents a study of the specific disciplinary competencies required of library programming professionals and the training pathways where they develop those skills. Most existing competency frameworks focus on general library service or audience, rather than the specializations required for public programming. Reflecting the emerging importance of programming to libraries’ service model, this US research study demonstrates that excellence in programming requires a unique set of competencies not found in other areas of library practice. The evidence shows that most public-programming competencies are learned outside of MLIS training but could be introduced as an MLIS concentration or learned as professional development.

Limited studies are available on how decisions and perceptions on SARS-CoV-2 vaccination have changed since the start of vaccination availability. We performed a qualitative study to identify factors critical to SARS-CoV-2 vaccination decision making and how perspectives evolved among African American/Black, Native American, and Hispanic communities disproportionately affected by COVID-19 and social and economic disadvantage. We conducted 16 virtual meetings, with 232 participants in wave 1 meetings (December 2020) and with 206 returning participants in wave 2 meetings (January and February 2021). Wave 1 vaccine concerns in all communities included information needs, vaccine safety, and speed of vaccine development. Lack of trust in government and the pharmaceutical industry was influential, particularly among African American/Black and Native American participants. Participants showed more willingness to get vaccinated at wave 2 than at wave 1, indicating that many of their information needs had been addressed. Hesitancy remained greater among African American/Black and Native American participants than among Hispanic participants. Participants in all groups indicated that conversations tailored to their community and with those most trustworthy to them would be helpful. To overcome vaccine hesitancy, we propose a model of fully considered SARS-CoV-2 vaccine decision making, whereby public health departments supply information, align with community values and recognize lived experiences, offer support for decision making, and make vaccination easy and convenient.

Background: Residents of Webb County, Texas, along the U.S.-Mexico border suffer from health disparities which stem from extreme poverty, lower levels of educational attainment, and inadequate access to basic health care. The scarcity of primary care and behavioral health service providers is a key factor influencing higher-than-average disease prevalence and unfavorable disease management in the region. In 2015 Mercy Ministries of Laredo became one of eight subgrantees of a grant awarded by the Social Innovation Fund to Methodist Healthcare Ministries of San Antonio to enhance/expand integrated primary care and behavioral health care services in medically underserved areas of South Texas. Methods: Mercy’s project embodied a 3-dimensional model of health and healthcare, to include physical, behavioral and spiritual needs and interventions. With strong support from a research design and analysis group, this small clinic was able to demonstrate statistically significant improved health outcomes of several interventions. A non-randomized quasi experimental design (QED) was used and participants chose whether to participate in the intervention (207) or control (203) group. Common variables for all eight subgrantees included five overarching measures (HbA1C, blood pressure, BMI, PHQ-9 and quality of life score) and depression outcomes were used to statistically power all subgrantee studies. Results: Intervention group participants had significantly greater improvements in quality of life and anxiety symptoms when compared with comparison group participants. Intervention participants had a Duke General Health score 4.01 points higher and a GAD-7 score 0.79 points lower than those in the comparison group. There were also significant improvements for intervention participants over time for these two outcomes as well as depression symptoms. Conclusions: Grant funded resources enhanced health outcomes and prompted this small clinic to expand integrated primary and behavioral health services to serve the entire clinic population and promote integrated primary and behavioral health care for other underserved populations.

This chapter examines the operation of general strike and includes detailed regional and sectoral trade union responses to it, highlighting in particular the wholehearted involvement of the TGWU and Bevin’s initial enthusiastic supportive leadership. However, the chapter examines how after 9 days the TUC on the initiative of the NUR leader, J.H.Thomas, fell into a trap, and called off the strike on the false assumption indicated by the Samuel memorandum, of government involvement in securing a settlement. This was not forthcoming –TUC called off the strike without winning a single concession and the miners were defeated. Baldwin’s portrayed the strike as a constitutional challenge to State authority, encapsulated in the question: ‘Who rules Britain?’ TUC answered with a white flag.