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This dissertation argues that Black lesbian literature, as well as film and other new media, is a direct response to the marginalization and exclusion of Black lesbians and their cultural texts in literary, scholarly, and public discourses. I argue that Black lesbian literature and other cultural products mirror Black lesbians’ social, political, and cultural statuses, in that they are marginalized and often excluded from both Black and lesbian, gay, bisexual, and transgender (LGBT) communities. I contend that Black lesbian cultural texts have two main goals: 1) to lay bare the experiences of Black lesbians in a raced, gendered, classed, and homophobic society; and 2) to challenge the notion that the claiming of a Black lesbian identity is “marginal and forbidden.” In reading these black lesbian cultural texts, I purposefully take a Black lesbian feminist approach to reading their work, as I believe that queer theory has relegated into theoretical abstractions significant material realities that impact the cultural productions of same-sex desiring Black women in the United States.

Founded by Alfred C. Kinsey in 1947, the Kinsey Institute has been a leading organization in developing an understanding of human sexuality. In this new book with over 65 images of Kinsey and the Institute's collections, Judith A. Allen and the coauthors look at the work Kinsey started over 70 years ago and how the Institute has continued to make an impact on understanding on our culture. Covering the early years of the Institute through the \"Sexual Revolution,\" into the AIDS pandemic of the Reagan era, and on into the \"internet hook-up\" culture of today, the book illuminates the Institute's work and its importance to society.

The future response of marine ecosystem diversity to continued anthropogenic forcing is poorly constrained. Phytoplankton are a diverse set of organisms that form the base of the marine ecosystem. Currently, ocean biogeochemistry and ecosystem models used for climate change projections typically include only 2−3 phytoplankton types and are, therefore, too simple to adequately assess the potential for changes in plankton community structure. Here, we analyse a complex ecosystem model with 35 phytoplankton types to evaluate the changes in phytoplankton community composition, turnover and size structure over the 21st century. We find that the rate of turnover in the phytoplankton community becomes faster during this century, that is, the community structure becomes increasingly unstable in response to climate change. Combined with alterations to phytoplankton diversity, our results imply a loss of ecological resilience with likely knock-on effects on the productivity and functioning of the marine environment. Phytoplankton form the base of the marine ecosystem but current ocean models used for climate change projections are too simple to assess potential changes in plankton community structure. This study analyses a complex ecosystem model with 35 phytoplankton types to evaluate the changes in phytoplankton community composition, turnover and size structure over the 21st century.

This handbook explains, in detail, each section of the Certified Supplier Quality Professional Body of Knowledge (updated 2023). It is a handy reference for those already working in the field and is an essential text for those working toward a CSQP certification.

Non-invasive prenatal diagnosis (NIPD) makes use of cell-free fetal DNA (cffDNA) in the mother's bloodstream as an alternative to invasive sampling methods such as amniocentesis or CVS, which carry a 0.5-1% risk of fetal loss. We describe a droplet digital PCR (ddPCR) assay designed to inform the testing options for couples whose offspring are at risk of suffering from cystic fibrosis via compound heterozygosity. By detecting the presence or absence of the paternal mutation in the cffDNA, it is possible to predict whether the fetus will be an unaffected carrier (absence) or whether further invasive testing is indicated (presence). We selected a family in which the parents were known to carry different mutated CFTR alleles as our test system. NIPD was performed for three of their pregnancies during the first trimester (at around 11-12 weeks of gestation). Taqman probes were designed against an amplicon in exon 11 of the CFTR gene, to quantify the proportion of mutant (ΔF508-MUT; FAM) and normal (ΔF508-NOR; VIC) alleles at position c.1521_1523 of the CFTR gene. The assay correctly and unambiguously recognized the ΔF508-MUT CFTR allele in the cffDNA of all three proband fetuses and none of the six unaffected control fetuses. In conclusion, the Bio-Rad QX100 was found to be a cost-effective and technically undemanding platform for designing bespoke NIPD assays.

Immune checkpoint inhibitors induce durable tumor regressions in some, but not all, cancer patients. Understanding the mechanisms that determine tumor sensitivity to these drugs could potentially expand the number of patients who benefit (see the Perspective by Ghorani and Quezada). Pan et al. discovered that tumor cells in which a specific SWI/SNF chromatin remodeling complex had been experimentally inactivated were more sensitive to T cell–mediated killing. The cells were more responsive to interferon-γ, leading to increased secretion of cytokines that promote antitumor immunity. Miao et al. examined the genomic features of tumors from patients with metastatic renal cell carcinoma who had been treated with immune checkpoint inhibitors. Tumors harboring inactivating mutations in PBRM1 , which encodes a subunit of the same SWI/SNF complex, were more likely to respond to the drugs. Science , this issue p. 770 , p. 801 ; see also p. 745 Renal cell cancers with mutations in a specific chromatin regulator have a better clinical response to immunotherapy. Immune checkpoint inhibitors targeting the programmed cell death 1 receptor (PD-1) improve survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). To identify genomic alterations in ccRCC that correlate with response to anti–PD-1 monotherapy, we performed whole-exome sequencing of metastatic ccRCC from 35 patients. We found that clinical benefit was associated with loss-of-function mutations in the PBRM1 gene ( P = 0.012), which encodes a subunit of the PBAF switch-sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. We confirmed this finding in an independent validation cohort of 63 ccRCC patients treated with PD-1 or PD-L1 (PD-1 ligand) blockade therapy alone or in combination with anti–CTLA-4 (cytotoxic T lymphocyte-associated protein 4) therapies ( P = 0.0071). Gene-expression analysis of PBAF-deficient ccRCC cell lines and PBRM1 -deficient tumors revealed altered transcriptional output in JAK-STAT (Janus kinase–signal transducers and activators of transcription), hypoxia, and immune signaling pathways. PBRM1 loss in ccRCC may alter global tumor-cell expression profiles to influence responsiveness to immune checkpoint therapy.

The presence of per- and polyfluoroalkyl substances (PFAS) in U.S. drinking water has recently garnered significant attention from the media, federal government, and public health professionals. While concerns for PFAS exposure continue to mount, the general public’s awareness and knowledge of the contaminant has remained unknown. This exploratory study sought to fill this data gap by administering a nationwide survey in which the awareness of PFAS and community contamination, awareness of PFAS containing products and intentions to change product use, and awareness and concern about PFAS in drinking water were assessed. The results indicated that almost half the respondents had never heard of PFAS and do not know what it is (45.1%). Additionally, 31.6% responded that they had heard of PFAS but do not know what it is. A large portion of respondents (97.4%) also responded that they did not believe their drinking water had been impacted by PFAS. Demographic association did not influence knowledge of PFAS or levels of concern with PFAS in drinking water. The strongest predictor of PFAS awareness was awareness due to known community exposure. The respondents aware of community exposure were more likely to have knowledge of PFAS sources, change their use of items with potential PFAS contamination, and answer that their drinking water sources were also contaminated with PFAS. Based on the received responses, PFAS information and health risks need to be better communicated to the public to help increase awareness. These efforts should also be coordinated between government agencies, utilities, the research community, and other responsible entities to bolster their effectiveness.

Key Points Single-celled eukaryotes (protists) constitute a tremendously diverse group of microorganisms. These species exhibit a wide range of nutritional modes (many species possess multiple nutritional modes simultaneously) and are essential components at several trophic levels within food webs. Genetic analyses of protists have lagged behind those of other microbial taxa because protists have much larger genomes and more complicated gene expression patterns. Consequently, we have very limited knowledge about gene number, identity and function within many protistan lineages. Widespread application of targeted gene sequencing (most notably, of small-subunit rRNA genes) has greatly improved our knowledge of eukaryote phylogeny and provided a framework for an emerging taxonomy incorporating morphological and molecular information. A recently developed alternative approach to provide genetic information for ecologically important protistan taxa is transcriptome sequencing of cultured species. Transcriptomes are providing vital databases of genes for species that lack sequenced genomes. Transcriptomic studies of cultures and natural assemblages of phototrophic protists (phytoplankton) are revealing complex metabolic responses to environmental conditions (such as nutrient limitation and light regime), pathways that are involved in toxin production by some harmful algal species and changes in gene expression that are related to shifts in nutritional mode for mixotrophic species. The application of transcriptomic approaches to the study of protistan symbioses, predator–prey interactions and protist–bacterium interactions are beginning to reveal the molecular signalling that is involved in the recognition and response between microorganisms, providing insights into the origin of eukaryotic organelles and the structure of aquatic food webs. We now have an improved understanding of the physiological responses of ecologically relevant protistan species and trophic groups to environmental changes. This understanding, which has been garnered through omics studies, is being harnessed to improve the predictive capabilities of global biogeochemical models. Protists are an important part of the marine food web. In this Review, Caron et al . summarize recent insights from transcriptomic studies of cultured and free-living protists and discuss how these findings highlight the functions and interactions of these single-celled eukaryotes in the global oceans. Protists, which are single-celled eukaryotes, critically influence the ecology and chemistry of marine ecosystems, but genome-based studies of these organisms have lagged behind those of other microorganisms. However, recent transcriptomic studies of cultured species, complemented by meta-omics analyses of natural communities, have increased the amount of genetic information available for poorly represented branches on the tree of eukaryotic life. This information is providing insights into the adaptations and interactions between protists and other microorganisms and macroorganisms, but many of the genes sequenced show no similarity to sequences currently available in public databases. A better understanding of these newly discovered genes will lead to a deeper appreciation of the functional diversity and metabolic processes in the ocean. In this Review, we summarize recent developments in our understanding of the ecology, physiology and evolution of protists, derived from transcriptomic studies of cultured strains and natural communities, and discuss how these novel large-scale genetic datasets will be used in the future.

With the advent of massively parallel sequencing (MPS), DNA analysis can now be performed in a genomewide manner. Recent studies have demonstrated the high precision of MPS for quantifying fetal DNA in maternal plasma. In addition, paired-end sequencing can be used to determine the size of each sequenced DNA fragment. We applied MPS in a high-resolution investigation of the clearance profile of circulating fetal DNA. Using paired-end MPS, we analyzed serial samples of maternal plasma collected from 13 women after cesarean delivery. We also studied the transrenal excretion of circulating fetal DNA in 3 of these individuals by analyzing serial urine samples collected after delivery. The clearance of circulating fetal DNA occurred in 2 phases, with different kinetics. The initial rapid phase had a mean half-life of approximately 1 h, whereas the subsequent slow phase had a mean half-life of approximately 13 h. The final disappearance of circulating fetal DNA occurred at about 1 to 2 days postpartum. Although transrenal excretion was involved in the clearance of circulating fetal DNA, it was not the major route. Furthermore, we observed significant changes in the size profiles of circulating maternal DNA after delivery, but we did not observe such changes in circulating fetal DNA. MPS of maternal plasma and urinary DNA permits high-resolution study of the clearance profile of circulating fetal DNA.

Aging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging by preventing or reversing microglial hyperactivation. Butyrate, a short-chain fatty acid (SCFA) produced primarily by bacterial fermentation of fiber in the colon, has been extensively studied pharmacologically as a histone deacetylase inhibitor and serves as an attractive therapeutic candidate, as butyrate has also been shown to be anti-inflammatory and improve memory in animal models. In this study, we demonstrate that butyrate can attenuate pro-inflammatory cytokine expression in microglia in aged mice. It is still not fully understood, however, if an increase in butyrate-producing bacteria in the gut as a consequence of a diet high in soluble fiber could affect microglial activation during aging. Adult and aged mice were fed either a 1% cellulose (low fiber) or 5% inulin (high fiber) diet for 4 weeks. Findings indicate that mice fed inulin had an altered gut microbiome and increased butyrate, acetate, and total SCFA production. In addition, histological scoring of the distal colon demonstrated that aged animals on the low fiber diet had increased inflammatory infiltrate that was significantly reduced in animals consuming the high fiber diet. Furthermore, gene expression of inflammatory markers, epigenetic regulators, and the microglial sensory apparatus (i.e., the sensome) were altered by both diet and age, with aged animals exhibiting a more anti-inflammatory microglial profile on the high fiber diet. Taken together, high fiber supplementation in aging is a non-invasive strategy to increase butyrate levels, and these data suggest that an increase in butyrate through added soluble fiber such as inulin could counterbalance the age-related microbiota dysbiosis, potentially leading to neurological benefits.