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In this quasi-experimental field study, bar drinkers (0.00-0.23% blood alcohol content) viewed a photographic sequence in which a male took a laptop from a helpdesk assistant, either on loan or at gunpoint. Following a brief retention period, participants answered 20 multiple-choice questions about the male, his actions, and details of the scene, then attempted to identify him from a simultaneous target-present or target-absent line-up. Alcohol was associated with a reduction in correct identifications and an increase in false identifications. Surprisingly, the presence of a weapon in the scene enhanced identification accuracy, though wider scene memory was not influenced by alcohol or the weapon. Findings offer some support for the view that alcohol restricts face encoding, perhaps through the narrowing of attention to salient external features (e.g., hair). We also suggest that curiosity about mock-crime perpetrators may produce weapon focus reversals, although the factors that might elicit such curiosity remain unclear.

Introduction: Metabolic adaptability, including glucose metabolism, enables cells to survive multiple stressful environments. Glycogen may serve as a critical storage depot to provide a source of glucose during times of metabolic demand during the metastatic cascade; therefore, understanding glycogen metabolism is critical. Our goal was to determine mechanisms driving glycogen accumulation and its role in metastatic (MCF10CA1a) compared to nonmetastatic (MCF10A-ras) human breast cancer cells. Methodology:13C6-glucose flux analysis in combination with inhibitors of the gluconeogenic pathway via phosphoenolpyruvate carboxykinase (PCK), the anaplerotic enzyme pyruvate carboxylase (PC), and the rate-limiting enzyme of the pentose phosphate pathway (PPP) glucose 6-phosphate dehydrogenase (G6PD). To determine the requirement of glycogenolysis for migration or survival in extracellular matrix (ECM) detached conditions, siRNA inhibition of glycogenolysis (liver glycogen phosphorylase, PYGL) or glycophagy (lysosomal enzyme α-acid glucosidase, GAA) enzymes was utilized. Results: Metastatic MCF10CA1a cells had 20-fold greater glycogen levels compared to non-metastatic MCF10A-ras cells. Most glucose incorporated into glycogen of the MCF10CA1a cells was in the five13C-containing glucose (M+5) instead of the expected M+6 glycogen-derived glucose moiety, which occurs through direct glucose conversion to glycogen. Furthermore,13C6-glucose in glycogen was quickly reduced (~50%) following removal of13C-glucose. Incorporation of 13C6-glucose into the M+5 glucose in the glycogen stores was reduced by inhibition of PCK, with additional contributions from flux through the PPP. Further, inhibition of PC reduced total glycogen content. However, PCK inhibition increased total unlabeled glucose accumulation into glycogen, suggesting an alternative pathway to glycogen accumulation. Inhibition of the rate-limiting steps in glycogenolysis (PYGL) or glycophagy (GAA) demonstrated that both enzymes are necessary to support MCF10CA1a, but not MCF10A-ras, cell migration. GAA inhibition, but not PYGL, reduced viability of MCF10CA1a cells, but not MCF10A-ras, in ECM detached conditions. Conclusion: Our results indicate that increased glycogen accumulation is primarily mediated through the gluconeogenesis pathway and that glycogen utilization is required for both migration and ECM detached survival of metastatic MCF10CA1a cells. These results suggest that glycogen metabolism may play an important role in the progression of breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Objective: This study sought to understand the roles of partners in pregnancy, childbirth, and childrearing in Indigenous communities. It explores supportive and unsupportive attitudes in the relationships mothers experienced, and how these relationships affected their lives. Background: Settler colonialism has negatively impacted Indigenous communities. However, little research has explored how it has influenced partner and social support during the perinatal time period. Methods: Through 31 semistructured interviews with women from a tribe in the southeastern United States, participants described their experiences with supportive and unsupportive partners and how that shaped their experiences during pregnancy, childbirth, and childrearing. Results: Participants described themes of (a) supportive and unsupportive partner relationships, (b) importance of partner support in childbirth, and (c) mothers as primary caregivers. Conclusion: Results suggest that women experienced a wide range of partner relationships, and they relied more on their female family members to provide support during this time, rather than counting on their male counterparts. Implications: Health care providers may want to take these findings into consideration when approaching their patient's care. These findings indicate that the impacts of settler colonialism continue to impact family relationships for the participants in this study. [ABSTRACT FROM AUTHOR]

The cultural activities, including the performance of music and spoken word are documented. The cultural activities in the San Diego-Tijuana region that is described is emerged from rhizomatic, transnational points of contact.

The article focuses on the use of traditional healers and family members for health care in Indigenous communities. It explores the reasons behind this preference, including cultural desires, discrimination in Western health-care services, and limited availability of Western health-care options. It mentions that the use of traditional healers is seen as a holistic approach to healing that addresses various facets of health and is culturally important for many Indigenous people.

Family relationships are an important source of emotional and instrumental support. In American Indian (AI) communities, families often provide support for women during childbirth and childrearing. The present study sought to gain insight into the influence of family during the pregnancy, childbirth, and childrearing experiences of AI women from a Gulf Coast tribe. A qualitative descriptive research design was used, and 31 interviews were conducted with women from the tribe. The average age of participants was 51.17, and the majority of women had 2 to 3 children. Data was analyzed using a content analysis approach. Themes that emerged include: Influence of Childhood on Participant’s Families and Parenting Styles, Significance of Family Emotional Closeness, Significance of Family Physical Closeness, Importance of Taking Care of Family Members, Importance of Family in Childbirth, and Generational Shifts in Caregiving. Results of the study may influence health interventions for this community, and results should encourage health care providers to consider positive implications of including family and community supports in care. [ABSTRACT FROM AUTHOR]

Regions of hypoxia are common in solid tumors and drive changes in gene expression that increase risk of cancer metastasis. Tumor cells must respond to the stress of hypoxia by activating genes to modify cell metabolism and antioxidant response to improve survival. The goal of the current study was to determine the effect of hypoxia on cell metabolism and markers of oxidative stress in metastatic (metM-Wntlung) compared with nonmetastatic (M-Wnt) murine mammary cancer cell lines. We show that hypoxia induced a greater suppression of glutamine to glutamate conversion in metastatic cells (13% in metastatic cells compared to 7% in nonmetastatic cells). We also show that hypoxia increased expression of genes involved in antioxidant response in metastatic compared to nonmetastatic cells, including glutamate cysteine ligase catalytic and modifier subunits and malic enzyme 1. Interestingly, hypoxia increased the mRNA level of the transaminase glutamic pyruvic transaminase 2 (Gpt2, 7.7-fold) only in metM-Wntlung cells. The change in Gpt2 expression was accompanied by transcriptional (4.2-fold) and translational (6.5-fold) induction of the integrated stress response effector protein activating transcription factor 4 (ATF4). Genetic depletion ATF4 demonstrated importance of this molecule for survival of hypoxic metastatic cells in detached conditions. These findings indicate that more aggressive, metastatic cancer cells utilize hypoxia for metabolic reprogramming and induction of antioxidant defense, including activation of ATF4, for survival in detached conditions. [ABSTRACT FROM AUTHOR]

Rapid on-site measurements of arsenic (As) are essential for the timely remediation of As-contaminated groundwater for both municipal and emergency response applications. Current field tests suffer from either complicated end-user instructions or a lack of accuracy and specificity. The system presented here combines a whole-cell bacterial biosensor with an electrochemical measurement that provides enhanced accuracy and signal intensity compared to traditional bacterial-detection approaches. When integrated within a customized hardware system, this whole-cell sensor demonstrated excellent specificity and sensitivity. This fast, sensitive, and easy-to-use approach is a viable alternative for on-site arsenic testing. [ABSTRACT FROM AUTHOR]

Vascular leak is a key driver of organ injury in diseases, and strategies that reduce enhanced permeability and vascular inflammation are promising therapeutic targets. Activation of the angiopoietin‐1 (ANG1)‐Tie2 tyrosine kinase signaling pathway is an important regulator of vascular quiescence. Here we describe the design and construction of a new soluble ANG1 mimetic that is a potent activator of endothelial Tie2 in vitro and in vivo. Using a chimeric fusion strategy, we replaced the extracellular matrix (ECM) binding and oligomerization domain of ANG1 with a heptameric scaffold derived from the C‐terminus of serum complement protein C4‐binding protein α. We refer to this new fusion protein biologic as Hepta‐ANG1, which forms a stable heptamer and induces Tie2 phosphorylation in cultured cells, and in the lung following intravenous injection of mice. Injection of Hepta‐ANG1 ameliorates vascular endothelial growth factor‐ and lipopolysaccharide‐induced vascular leakage, in keeping with the known functions of Angpt1‐Tie2 in maintaining quiescent vascular stability. The new Hepta‐ANG1 fusion is easy to produce and displays remarkable stability with high multimericity that can potently activate Tie2. It could be a new candidate ANG1 mimetic therapy for treatments of inflammatory vascular leak, such as acute respiratory distress syndrome and sepsis. [ABSTRACT FROM AUTHOR]

The carnivorous plant family Sarraceniaceae comprises three genera of wetland-inhabiting pitcher plants: Darlingtonia in the northwestern United States, Sarracenia in eastern North America, and Heliamphora in northern South America. Hypotheses concerning the biogeographic history leading to this unusual disjunct distribution are controversial, in part because genus- and species-level phylogenies have not been clearly resolved. Here, we present a robust, species-rich phylogeny of Sarraceniaceae based on seven mitochondrial, nuclear, and plastid loci, which we use to illuminate this family's phylogenetic and biogeographic history. The family and genera are monophyletic: Darlingtonia is sister to a clade consisting of Heliamphora+Sarracenia. Within Sarracenia, two clades were strongly supported: one consisting of S. purpurea, its subspecies, and S. rosea; the other consisting of nine species endemic to the southeastern United States. Divergence time estimates revealed that stem group Sarraceniaceae likely originated in South America 44-53 million years ago (Mya) (highest posterior density [HPD] estimate = 47 Mya). By 25-44 (HPD = 35) Mya, crown-group Sarraceniaceae appears to have been widespread across North and South America, and Darlingtonia (western North America) had diverged from Heliamphora+Sarracenia (eastern North America+South America). This disjunction and apparent range contraction is consistent with late Eocene cooling and aridification, which may have severed the continuity of Sarraceniaceae across much of North America. Sarracenia and Heliamphora subsequently diverged in the late Oligocene, 14-32 (HPD = 23) Mya, perhaps when direct overland continuity between North and South America became reduced. Initial diversification of South American Heliamphora began at least 8 Mya, but diversification of Sarracenia was more recent (2-7, HPD = 4 Mya); the bulk of southeastern United States Sarracenia originated co-incident with Pleistocene glaciation, ,3 Mya. Overall, these results suggest climatic change at different temporal and spatial scales in part shaped the distribution and diversity of this carnivorous plant clade. [ABSTRACT FROM AUTHOR]

R2065 --> 705.5 --> In the past two years, the COVID‐19 pandemic has caused over 5 million deaths and 250 million infections worldwide. Despite successful vaccination efforts and emergency approval of small molecule therapies, diverse antivirals are still needed to combat the inevitable viral resistance that will arise. The main protease of SARS‐CoV‐2 (Mpro) is an attractive drug target due to the clinical success of protease inhibitors against other viruses, such as HIV and HCV. However, in order to combat resistance, diverse chemical scaffolds need to be identified that have the potential to be developed into potent inhibitors. To this end, we screened a high‐content protease inhibitor library against Mproin vitro, in order to identify structurally diverse compounds that may be further developed into antiviral leads. Our high‐content screening efforts retrieved 27 hits each with >50% inhibition in our Mpro FRET assay. Of these, three natural product compounds, anacardic acid, aloesin, and aloeresin D, were chosen for follow up IC50 screening due to their strong druglike properties (high bioavailability, low toxicity). Further analysis via dose response curves revealed IC50 values of 6.8 μM, 38.9 μM, and 125.3 μM respectively. Molecular docking studies demonstrated that the three inhibitors bound at the catalytic active site of Mpro with varying binding energies (‐7.8 to ‐5.6 kcal/mol). Furthermore, we determined that our kinetic data from the Mpro FRET assay fit better to a sigmoidal Hill model than the standard Michaelis‐Menten hyperbola, indicating substantial cooperativity between enzyme monomers, suggesting that the dimerization interface could be an attractive target for allosteric inhibitors. In conclusion, we identified two natural product compounds from the Aloe plant (aloesin and aloeresin D) as novel scaffolds for Mpro inhibitor design and confirmed the cooperative kinetics of Mpro. These results advance our knowledge of structure‐function relationships in Mpro and offer new molecular scaffolds for inhibitor design. [ABSTRACT FROM AUTHOR]

R2988 --> Nevirapine (NVP), a non‐nucleoside HIV reverse transcriptase (RT) inhibitor, is generally a well‐tolerated drug. However, certain toxicological issues have been reported, including idiosyncratic drug reactions (IDRs) such as skin rash and hepatotoxicity. Additionally, NVP is a known mechanism‐based inactivator (MBI) and inducer of CYP3A cytochrome P450 enzymes (CYPs), with the potential to cause drug‐drug interactions. It has been demonstrated previously that the 12‐hydroxynevirapine metabolite and a reactive quinone methide species, produced by CYP3A4 and CYP2B6, are responsible for the observed IDRs. The reactive quinone methide species also leads to mechanism‐based inactivation of CYP3A4, while NVP itself is an inducer of both CYP3A4 and CYP2B6. The goal of our study was to characterize a series of NVP analogs with respect to their safety and efficacy to treat HIV by examining target engagement efficiency and metabolic liability through in vitro characterization. Our hypothesis was that a NVP analog will be able to inhibit RT with similar efficacy, but with limited production of the toxic metabolites. Initial studies were conducted to determine the IC50 values of NVP and each analog in the RT inhibition assay, followed by determining the CYP induction/inhibition potential of NVP and its associated analogs in cryopreserved primary human hepatocytes. mRNA fold induction, CYP3A4 activity fold change, and % lactate dehydrogenase (LDH) release were all studied via qPCR, LC‐MS/MS, and LDH assays respectively. In total, NVP and eight analogs were tested. The RT assay IC50 of NVP was 0.5 uM and the three analogs with the lowest IC50 values were: nevirapine‐d3 (NVP‐d3, 0.8 uM), 2‐nitro nevirapine (2‐N‐NVP, 1.1 uM), and 3‐bromo nevirapine (3‐B‐NVP, 3.0 uM). The induction experiments demonstrated that CYP3A4 was induced ~2 fold at 25 uM NVP, and ~6 fold at 100 uM NVP. CYP2B6 showed higher induction, with ~5 fold at 25 uM NVP and ~13 fold at 100 uM NVP. For CYP3A4 activity, 25 uM NVP showed ~1.4 fold increase in activity, while 100 uM NVP resulted in no fold change. This is likely due to the combined induction/inhibition effect of NVP; i.e., at higher concentrations more NVP is present to inactivate CYP3A4 and thus inhibition wins out over induction, while at lower concentrations of NVP induction dominates. %LDH release along with observation of the monolayer revealed low levels of hepatocyte mortality. Overall, three analogs were identified as potential candidates to replace NVP, due to their low IC50 values in the RT inhibition assay and reduced potential for CYP induction. Further characterization of these analogs is ongoing with the goal to identify an efficacious and safer NVP analog that can be used to treat HIV in pregnant women and children in developing countries, where NVP is still often used. [ABSTRACT FROM AUTHOR]