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The article is an introduction to the latest issue of Public Culture, which features a range of topics related to chronopolitics, or the forms and terrains of time. The issue includes conversations with artist Shahzia Sikander and historian Faisal Devji about Sikander's public installations, as well as articles on postcolonial architecture in Nigeria, Philip Morris' involvement with Auschwitz, settler colonialism in Canada, Turkey's influence in Guinea-Conakry, and the concept of "sacropolitics" in contemporary political life. The article also mentions the new editor in chief, Vyjayanthi Rao, and bids farewell to an assistant editor. [Extracted from the article]

An introduction is presented in which the editor discusses articles in the issue on topics including solidarity, labors of making public culture, the difficulties of remembrance.

Abstract Objective: To provide guidance and resources on how to practice culturally safe and humble neuropsychology with transgender and gender diverse (TGD) individuals and communities. Methods: We gathered a multidisciplinary team of clinicians with relevant professional and/or lived experience to review pertinent literature, discuss important concepts, and identify key resources. From this process, we outline practical steps to advance gender affirmative neuropsychological practice. Results: Professional awareness and knowledge regarding how to gather context-relevant, gender identity information is critical. TGD individuals form a heterogenous group; a one-size-fits-all approach is not adequate. It is incumbent upon neuropsychologists to engage in clinical and research practices in a manner that does not perpetuate gender minority stress and trauma. Creating an open, safe environment of care requires intentionality and careful thinking to determine what information is relevant for a particular referral question. We provide recommendations and resources for neuropsychologists. Conclusion: When neuropsychologists are proactive, responsible, and intentional, they can better provide individualized, person-centered, and trauma-informed care to TGD individuals. [ABSTRACT FROM AUTHOR]

The article reports that Public Culture to the world of immediacies beyond Euro-American horizons with critical reflections that privilege suppressed minorities to the arts of catastrophe, from public secrets to secret publics, from post-grid sovereignties to vitalized sexualities. Topics include meditations on incalculable costs to reckoning with unpayable debts; and the U.S. military withdrawal from its twenty-year occupation of Afghanistan.

The article focuses on the challenge which seemed to be the emergent global diaspora of the idea of the public sphere and multiple forms of modernity that global journey was beginning to produce. Topics include examines to use observations of emergent modernities to engage with Jürgen Habermas, Stuart Hall and Benedict Anderson, who shaped then-dominant views of such qualifiers as "mass" "public" and "popular" in definitions of culture.

An introduction is presented in which author discusses articles on topics including focuses on scholars work with the enlarged register of substances, sensations, ontologies, and practices such that mediation is a constitutive feature of social life.

An introduction is presented in which the editor discusses articles in the issue on topics including academic department; Communication; and transitions.

To reduce possible ecological impact from oil spill events, the chemical dispersant Corexit 9500A (C-9500A) is approved for widespread application. Interactions with changing environmental factors such as temperature are necessary to appropriately use dispersants in field applications, particularly in susceptible early life stages of certain marine organisms. The 24 h LC25, LC50, and LC75 values for C-9500A exposure for 3 (hours post fertilization) embryos of the teleost model Danio rerio (Hamilton, 1822) exposed to C-9500A at the standard husbandry temperature of 28.5 ˚ C were 71, 110, and 171 ppm, respectively (Probit analysis, n=5 trials of 10 individuals each). We also examined survival, early development, and hatch success of embryos and survival of larvae exposed to C-9500A while maintained at 24.7, 27.0, 29.5, and or 31.7˚ C representing both lower and higher normative thermal exposures. An interactive effect between C- 9500A and higher exposure temperature on embryo survival and hatch success was observed. Hatched larvae showed a highly reduced sensitivity to C-9500A exposure (24 h LC50 > 200 ppm), but higher variability in response than exposed embryos. We hypothesize that C-9500A application, particularly when temperatures are elevated, could negatively affect wild fish populations in nurseries and ultimately community structure. [ABSTRACT FROM AUTHOR]

The melanocortin peptides derived from pro-opiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte-stimulating hormone (α-MSH) on pigmentation and adrenocorticotrophic hormone on adrenocortical glucocorticoid production. However, the discovery of POMC mRNA and melanocortin peptides in the CNS generated activities directed at understanding the direct biological actions of melanocortins in the brain. Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the development of pharmacological tools and genetic models leading to the demonstration that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Indeed, mutations in MC4R are now known to be the most common cause of early onset syndromic obesity, accounting for 2-5% of all cases. This review discusses the history of these discoveries, as well as the latest work attempting to understand the molecular and cellular basis of regulation of feeding and energy homeostasis by the predominant melanocortin peptide in the CNS, α-MSH. [ABSTRACT FROM AUTHOR]

Abstract: The performance of a diagnostic method for detection and identification of Enterococcus spp. directly from positive blood culture was evaluated in a clinical study. The method, Enterococcus QuickFISH BC, is a second-generation peptide nucleic acid (PNA) fluorescence in situ hybridization (FISH) test, which uses a simplified, faster assay procedure. The test uses fluorescently labeled PNA probes targeting 16S rRNA to differentiate Enterococcus faecalis from other Enterococcus spp. by the color of the cellular fluorescence. Three hundred fifty-six routine blood culture samples were tested; only 2 discordant results were recorded. The sensitivities for detection of Enterococcus faecalis and non-faecalis Enterococcus were 100% (106/106) and 97.0% (65/67), respectively, and the combined specificity of the assay was 100%. The combined positive and negative predictive values of the assay were 100% (171/171) and 98.9% (185/187), respectively. [Copyright &y& Elsevier]

The article presents a report on a Candida auris outbreak in a coronavirus disease 2019 (COVID-19) specialty care unit in Florida from July to August 2020. Also cited are the measures implemented by the Florida Department of Health to limit the spread like contact tracing and screening upon detection and observation of health care personnel (HCP) use of personal protective equipment (PPE), and the support provided by the U.S. Centers for Disease Control and Prevention (CDC) in outbreak control.

The article features the Crystal Cathedral in California which is formerly known as the Garden Grove Community Church (GGCC). The GGCC was able to raise financial and organizational resources to erect a small stained-glass chapel within its first two years of operation. It was 1980 when the GGCC became the Crystal Cathedral, a megachurch and an emblem of mediated congregation. The Crystal Cathedral is reportedly in the process of being purchased by the Catholic Church.

Background: Recent studies have confirmed the presence of viable Chlamydia in the bronchoalveolar lavage (BAL) fluid of pediatric patients with airway hyperresponsiveness. While specific IgG and IgM responses to C. pneumoniae are well described, the response and potential contribution of Ag-specific IgE are not known. The current study sought to determine if infection with Chlamydia triggers the production of pathogen-specific IgE in children with chronic respiratory diseases which might contribute to inflammation and pathology.Methods: We obtained BAL fluid and serum from pediatric respiratory disease patients who were generally unresponsive to corticosteroid treatment as well as sera from age-matched control patients who saw their doctor for wellness checkups. Chlamydia-specific IgE was isolated from BAL and serum samples and their specificity determined by Western blot techniques. The presence of Chlamydia was confirmed by species-specific PCR and BAL culture assays.Results: Chlamydial DNA was detected in the BAL fluid of 134/197 (68%) patients. Total IgE increased with age until 15 years old and then decreased. Chlamydia-specific IgE was detected in the serum and/or BAL of 107/197 (54%) patients suffering from chronic respiratory disease, but in none of the 35 healthy control sera (p < 0.0001). Of the 74 BAL culture-positive patients, 68 (91.9%, p = 0.0001) tested positive for Chlamydia-specific IgE. Asthmatic patients had significantly higher IgE levels compared to non-asthmatics (p = 0.0001). Patients who were positive for Chlamydia DNA or culture had significantly higher levels of serum IgE compared to negative patients (p = 0.0071 and p = 0.0001 respectively). Only 6 chlamydial antigens induced Chlamydia-specific IgE and patients with C. pneumoniae-specific IgE had significantly greater levels of total IgE compared to C. pneumoniae-specific IgE negative ones (p = 0.0001).Conclusions: IgE antibodies play a central role in allergic inflammation; therefore production of Chlamydia-specific IgE may prove significant in the exacerbation of chronic, allergic airway diseases, thus highlighting a direct role for Chlamydia in asthma pathogenesis. [ABSTRACT FROM AUTHOR]

Sternal wound infection is a life-threatening complication after cardiac surgery associated with high morbidity and mortality. Past treatment options have included closed suction and continuous irrigation. Current paradigms in the management of sternal wound infection include surgical debridement, vacuum-assisted closure therapy, flap coverage, and sternal plating. We provide a general overview of sternal wound infection and treatment options for the plastic surgeon. [ABSTRACT FROM AUTHOR]

Bioinspired synthetic materials can be designed as reliable, cost‐effective, and fully controlled alternatives to natural biomaterials for treating damaged tissues and organs. However, several hurdles need to be overcome for clinical translation, particularly for biomaterials gelled in situ. These include the potential toxicity of chemical crosslinkers used in the materials' assembly or breakdown products they generate and the challenges of fine‐tuning the mechanical properties of the materials. Here, a minimalistic, adhesive soft material is developed by screening hundreds of potential formulations of self‐assembling, custom‐designed collagen‐like peptide sequences for the in situ formation of tissue‐bonding 3D hydrogels. Nine promising formulations for tissue repair are identified using a low‐volume and rapid combinatory screening approach. It is shown that simply varying the ratio of the two key components promotes adhesion and fine‐tunes the material's mechanical properties. The materials' skin and heart repair capabilities are assessed in vitro and clinically relevant animal models. The materials are also tested for corneal applications using ex vivo pig cornea models complemented by in vitro cell compatibility assays. [ABSTRACT FROM AUTHOR]

SCN2A -related disorders secondary to altered function in the voltage-gated sodium channel Nav1.2 are rare, with clinically heterogeneous expressions that include epilepsy, autism and multiple severe to profound impairments and other conditions. To advance understanding of the clinical phenotypes and their relationship to channel function, 81 patients (36 female, 44%, median age 5.4 years) with 69 unique SCN2A variants were systematically phenotyped and their Nav1.2 channel function systematically assessed. Participants were recruited through the FamileSCN2A Foundation. Primary phenotype (epilepsy of neonatal onset, n = 27; infant onset, n = 18; and later onset n = 24; and autism without seizures, n = 12) was strongly correlated with a non-seizure severity index (P = 0.002), which was based on presence of severe impairments in gross motor, fine motor, communication abilities, gastrostomy tube dependence and diagnosis of cortical visual impairment and scoliosis. Non-seizure severity was greatest in the neonatal-onset group and least in the autism group (P = 0.002). Children with the lowest severity indices were still severely impaired, as reflected by an average Vineland Adaptive Behavior composite score of 49.5 (>3 standard deviations below the norm-referenced mean of the test). Epileptic spasms were significantly more common in infant-onset (67%) than in neonatal (22%) or later-onset (29%) epilepsy (P = 0.007). Primary phenotype was also strongly correlated with variant function (P < 0.0001); gain-of-function and mixed function variants predominated in neonatal-onset epilepsy, shifting to moderate loss of function in infant-onset epilepsy and to severe and complete loss of function in later-onset epilepsy and autism groups. Exploratory cluster analysis identified five groups, representing: (i) primarily later-onset epilepsy with moderate loss-of-function variants and low severity indices; (ii) mostly infant-onset epilepsy with moderate loss-of-function variants but higher severity indices; and (iii) late-onset and autism only, with the lowest severity indices (mostly zero) and severe/complete loss-of-function variants. Two exclusively neonatal clusters were distinguished from each other largely on non-seizure severity scores and secondarily on variant function. The relationship between primary phenotype and variant function emphasizes the role of developmental factors in the differential clinical expression of SCN2A variants based on their effects on Nav1.2 channel function. The non-seizure severity of SCN2A disorders depends on a combination of the age at seizure onset (primary phenotype) and variant function. As precision therapies for SCN2A -related disorders advance towards clinical trials, knowledge of the relationship between variant function and clinical disease expression will be valuable for identifying appropriate patients for these trials and in selecting efficient clinical outcomes. [ABSTRACT FROM AUTHOR]

Presents a guide for conducting plant tissue culture experiments using tobacco rhizogenesis to introduce students to science process skills. Information on tobacco organogenesis; Ways to improve the process of rhizogenesis; Materials and methods for the experiments.

Energy stores in fat tissue are determined in part by the activity of hypothalamic neurones expressing the melanocortin‐4 receptor (MC4R). Even a partial reduction in MC4R expression levels in mice, rats or humans produces hyperphagia and morbid obesity. Thus, it is of great interest to understand the molecular basis of neuromodulation by the MC4R. The MC4R is a G protein‐coupled receptor that signals efficiently through GαS, and this signalling pathway is essential for normal MC4R function in vivo. However, previous data from hypothalamic slice preparations indicated that activation of the MC4R depolarised neurones via G protein‐independent regulation of the ion channel Kir7.1. In the present study, we show that deletion of Kcnj13 (ie, the gene encoding Kir7.1) specifically from MC4R neurones produced resistance to melanocortin peptide‐induced depolarisation of MC4R paraventricular nucleus neurones in brain slices, resistance to the sustained anorexic effect of exogenously administered melanocortin peptides, late onset obesity, increased linear growth and glucose intolerance. Some MC4R‐mediated phenotypes appeared intact, including Agouti‐related peptide‐induced stimulation of food intake and MC4R‐mediated induction of peptide YY release from intestinal L cells. Thus, a subset of the consequences of MC4R signalling in vivo appears to be dependent on expression of the Kir7.1 channel in MC4R cells. [ABSTRACT FROM AUTHOR]

Using Notable's ex vivo platform, researchers have identified new preclinical combination therapies in JMML. PURPOSE: Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric malignancy with myelodysplastic and myeloproliferative features. Curative treatment is restricted to hematopoietic stem-cell transplantation. Fludarabine combined with cytarabine (FLA) and 5-azacitidine (AZA) monotherapy are commonly used pre-transplant therapies. Here, we present a drug screening strategy using a flow cytometry–based precision medicine platform to identify potential additional therapeutic vulnerabilities. METHODS: We screened 120 dual- and 10 triple-drug combinations (DCs) on peripheral blood (n = 21) or bone marrow (n = 6) samples from 27 children with JMML to identify DCs more effectively reducing leukemic cells than the DCs' components on their own. If fewer leukemic cells survived a DC ex vivo treatment compared with that DC's most effective component alone, the drug effect was referred to as cooperative. The difference between the two resistant fractions is the effect size. RESULTS: We identified 26 dual- and one triple-DC more effective than their components. The differentiation agent tretinoin (TRET; all-trans retinoic acid) reduced the resistant fraction of FLA in 19/21 (90%) samples (decrease from 15% [2%-61%] to 11% [2%-50%] with a mean effect size of 3.8% [0.5%-11%]), and of AZA in 19/25 (76%) samples (decrease from 69% [34%-100+%] to 47% [17%-83%] with a mean effect size of 16% [0.3%-40%]). Among the resistant fractions, the mean proportion of CD38+ cells increased from 7% (0.03%-25%; FLA) to 17% (0.3%-38%; FLA + TRET) or from 10% (0.2%-31%; AZA) to 51% (0.8%-88%; AZA + TRET). CONCLUSION: TRET enhanced the effects of FLA and AZA in ex vivo assays with primary JMML samples. [ABSTRACT FROM AUTHOR]

Inhibition of the protein-protein interaction between B-cell lymphoma 6 (BCL6) and corepressors has been implicated as a therapeutic target in diffuse large B-cell lymphoma (DLBCL) cancers and profiling of potent and selective BCL6 inhibitors are critical to test this hypothesis. We identified a pyrazolo[1,5-a]pyrimidine series of BCL6 binders from a fragment screen in parallel with a virtual screen. Using structure-based drug design, binding affinity was increased 100000-fold. This involved displacing crystallographic water, forming new ligand-protein interactions and a macrocyclization to favor the bioactive conformation of the ligands. Optimization for slow off-rate constant kinetics was conducted as well as improving selectivity against an off-target kinase, CK2. Potency in a cellular BCL6 assay was further optimized to afford highly selective probe molecules. Only weak antiproliferative effects were observed across a number of DLBCL lines and a multiple myeloma cell line without a clear relationship to BCL6 potency. As a result, we conclude that the BCL6 hypothesis in DLBCL cancer remains unproven. [ABSTRACT FROM AUTHOR]

The life cycle of Bacillus anthracis includes both vegetative and endospore morphologies which alternate based on nutrient availability, and there is considerable evidence indicating that the ability of this organism to cause anthrax depends on its ability to progress through this life cycle in a regulated manner. Here we report the use of a custom B. anthracis GeneChip in defining the gene expression patterns that occur throughout the entire life cycle in vitro. Nearly 5,000 genes were expressed in five distinct waves of transcription as the bacteria progressed from germination through sporulation, and we identified a specific set of functions represented within each wave. We also used these data to define the temporal expression of the spore proteome, and in doing so we have demonstrated that much of the spore's protein content is not synthesized de novo during sporulation but rather is packaged from preexisting stocks. We explored several potential mechanisms by which the cell could control which proteins are packaged into the developing spore, and our analyses were most consistent with a model in which B. anthracis regulates the composition of the spore proteome based on protein stability. This study is by far the most comprehensive survey yet of the B. anthracis life cycle and serves as a useful resource in defining the growth-phase-dependent expression patterns of each gene. Additionally, the data and accompanying bioinformatics analyses suggest a model for sporulation that has broad implications for B. anthracis biology and offer new possibilities for microbial forensics and detection. [ABSTRACT FROM AUTHOR]

Simple Summary: Children with acute myeloid leukemia (AML) experience unacceptably poor survival outcomes and are at high risk of relapse. Current treatment options are limited, and standard strategies rely on intensive chemotherapy to achieve remission, frequently resulting in treatment-related morbidities and significant late adverse effects. The use of an ex vivo drug sensitivity platform has potential clinical utility to aid individualized patient risk assignment, and it could allow for personalized treatment regimens, including identifying novel therapies for patients who are identified to be at a very high risk of treatment failure. In this study, we show that ex vivo drug sensitivity correlates with clinical response measures in a cohort of children with AML who received conventional chemotherapy. We also demonstrate preferential sensitivity ex vivo between conventional chemotherapy and the combination of bortezomib and panobinostat in a subset of patient samples. Our results support the value of an ex vivo drug sensitivity platform to identify individualized precision therapy for children with AML. Acute myeloid leukemia (AML) is a heterogeneous disease that accounts for ~20% of all childhood leukemias, and more than 40% of children with AML relapse within three years of diagnosis. Although recent efforts have focused on developing a precise medicine-based approach towards treating AML in adults, there remains a critical gap in therapies designed specifically for children. Here, we present ex vivo drug sensitivity profiles for children with de novo AML using an automated flow cytometry platform. Fresh diagnostic blood or bone marrow aspirate samples were screened for sensitivity in response to 78 dose conditions by measuring the reduction in leukemic blasts relative to the control. In pediatric patients treated with conventional chemotherapy, comprising cytarabine, daunorubicin and etoposide (ADE), ex vivo drug sensitivity results correlated with minimal residual disease (r = 0.63) and one year relapse-free survival (r = 0.70; AUROC = 0.94). In the de novo ADE analysis cohort of 13 patients, AML cells showed greater sensitivity to bortezomib/panobinostat compared with ADE, and comparable sensitivity between venetoclax/azacitidine and ADE ex vivo. Two patients showed a differential response between ADE and bortezomib/panobinostat, thus supporting the incorporation of ex vivo drug sensitivity testing in clinical trials to further evaluate the predictive utility of this platform in children with AML. [ABSTRACT FROM AUTHOR]

The rapidly growing racially diverse ageing population in the United States presents unique challenges for the country's social, economic, and healthcare systems. Rising health care costs, increased patient cost-sharing, and limited financial resources make this generation of older Americans susceptible to large medical bills or debt, which disproportionally impacts older adults who are from racial/ethnic minority communities. Cost of care (CoC) conversations between patients and healthcare providers is one recommended approach for containing healthcare costs and alleviating patients' financial burden of care. The current study used focus group methods to qualitatively explore the contextual factors that influence CoC conversations in a diverse sample of older adults (N = 27). Three focus groups were held with non-Hispanic White (n = 10), Black/African American (n = 9), and Hispanic (n = 8) participants. Thematic analysis yielded four broad themes. The results suggest that CoC conversations do not occur with physicians. The facilitators of CoC conversations included positive provider affect, rapport/relationship building, and communication. Barriers included lack of physician training, wait time, lack of focus on the patient, language, provider preferences, fear of physicians, and religion. There were significant differences in the facilitators and barriers across racial/ethnic groups. It is critical for physicians to have the tools and training to successfully discuss CoC with older patients. Cultural competency training and provider awareness of patient preferences and expectations may be important when it comes to enhancing rapport and increase the likelihood of these important conversations within racial/ethnic minority communities. [ABSTRACT FROM AUTHOR]

Although social work educators generally agree upon the importance of teaching spirituality and religion, there is significant contention about the place of religion within social work education. This study explores social work educators' perceptions of social work programs that follow a particular religious tradition. Educators from Bachelor of Social Work (BSW) programs across the United States were surveyed to determine their perceptions of the potential benefits and concerns regarding faith-based programs. The findings identified perceived benefits in relation to ethical inspiration, cultural competence, and preparation for certain types of practice. Common concerns were related to potential conflicts between religious beliefs and social work ethics. The study also indicated significant differences of opinion between educators from faith-based programs and non-faith-based programs. By identifying specific differences, it is hoped that BSW educators can move the discussion from making broad statements about the ethics of faithbased programs to a constructive dialogue about particular benefits and ethical concerns. [ABSTRACT FROM AUTHOR]

Nutrient-dependent germination of Bacillus anthracis spores is stimulated when receptors located in the inner membrane detect combinations of amino acid and purine nucleoside germinants. B. anthracis produces five distinct germinant receptors, GerH, GerK, GerL, GerS and GerX. Otherwise isogenic mutant strains expressing only one of these receptors were created and tested for germination and virulence. The GerH receptor was necessary and sufficient for wild-type levels of germination with inosine-containing germinants in the absence of other receptors. GerK and GerL were sufficient for germination in 50 mM L-alanine. When mutants were inoculated intratracheally, any receptor, except for GerX, was sufficient to allow for a fully virulent infection. In contrast, when inoculated subcutaneously only the GerH receptor was able to facilitate a fully virulent infection. These results suggest that route of infection determines germinant receptor requirements. A mutant lacking all five germinant receptors was also attenuated and exhibited a severe germination defect in vitro. Together, these data give us a greater understanding of the earliest moments of germination, and provide a more detailed picture of the signals required to stimulate this process. [ABSTRACT FROM AUTHOR]

The bacterial spore cortex is critical for spore stability and dormancy and must be hydrolyzed by germination-specific lytic enzymes (GSLEs), which allows complete germination and vegetative cell outgrowth. We created in-frame deletions of three genes that encode GSLEs that have been shown to be active in Bacillus anthracis germination: sleB, cwlJ1, and cwlJ2. Phenotypic analysis of individual null mutations showed that the removal of any one of these genes was not sufficient to disrupt spore germination in nutrient-rich media. This finding indicates that these genes have partially redundant functions. Double and triple deletions of these genes resulted in more significant defects. Although a small subset of ΔsleB ΔcwlJ1 spores germinate with wild-type kinetics, for the overall population there is a 3-order-of-magnitude decrease in the colony-forming efficiency compared with wild-type spores. ΔsleB ΔcwlJ1 ΔcwlJ2 spores are unable to complete germination in nutrient-rich conditions in vitro. Both ΔsleB ΔcwlJ1 and ΔsleB ΔcwlJ1 ΔcwlJ2 spores are significantly attenuated, but are not completely devoid of virulence, in a mouse model of inhalation anthrax. Although unable to germinate in standard nutrient-rich media, spores lacking SleB, CwlJ1, and CwlJ2 are able to germinate in whole blood and serum in vitro, which may explain the persistent low levels of virulence observed in mouse infections. This work contributes to our understanding of GSLE activation and function during germination. This information may result in identification of useful therapeutic targets for the disease anthrax, as well as provide insights into ways to induce the breakdown of the protective cortex layer, facilitating easier decontamination of resistant spores. [ABSTRACT FROM AUTHOR]

Abstract: Organophosphorus (OP) esters are known to bind covalently to the active site serine of enzymes in the serine hydrolase family. It was a surprise to find that proteins with no active site serine are also covalently modified by OP. The binding site in albumin, transferrin, and tubulin was identified as tyrosine. The goal of the present work was to determine whether binding to tyrosine is a general phenomenon. Fourteen proteins were treated with a biotin-tagged organophosphorus agent called FP-biotin. The proteins were digested with trypsin and the labeled peptides enriched by binding to monomeric avidin. Peptides were purified by HPLC and fragmented by collision induced dissociation in a tandem ion trap mass spectrometer. Eight proteins were labeled and six were not. Tyrosine was labeled in human alpha-2-glycoprotein 1 zinc-binding protein (Tyr 138, Tyr 174 and Tyr 181), human kinesin 3C motor domain (Tyr 145), human keratin 1 (Tyr 230), bovine actin (Tyr 55 and Tyr 200), murine ATP synthase beta (Tyr 431), murine adenine nucleotide translocase 1 (Tyr 81), bovine chymotrypsinogen (Tyr 201) and porcine pepsin (Tyr 310). Only 1–3 tyrosines per protein were modified, suggesting that the reactive tyrosine was activated by nearby residues that facilitated ionization of the hydroxyl group of tyrosine. These results suggest that OP binding to tyrosine is a general phenomenon. It is concluded that organophosphorus-reactive proteins include not only enzymes in the serine hydrolase family, but also proteins that have no active site serine. The recognition of a new OP-binding motif to tyrosine suggests new directions to search for mechanisms of long-term effects of OP exposure. Another application is in the search for biomarkers of organophosphorus agent exposure. Previous searches have been limited to serine hydrolases. Now proteins such as albumin and keratin can be considered. [Copyright &y& Elsevier]

Abstract: North America is a center of biodiversity for freshwater crayfish, with >300 described species, mostly in the family Cambaridae. However, the phylogenetic and phylogeographic relationships among these taxa are poorly understood, despite their ubiquitous occurrence in North American freshwater habitats. Here, we target the geographically widespread Orconectes virilis and its sister taxa for genetic and morphological investigation. We used sequence data from two mitochondrial genes (16S rRNA and cytochrome oxidase I) and from one nuclear gene (glyceraldehyde-3-phosphate dehydrogenase), as well as morphological data from the male gonopod, to gain insights into phylogenetic relationships among individuals collected in the northeastern United States, where this taxon is considered to be invasive, and from Kansas. Our data reveal evidence for three cryptic species in our collections, in addition to O. virilis sensu stricto; all four clades are separated by both mitochondrial and nuclear sequence data. In addition, two of the newly discovered species, O. sp. nov. A and O. sp. nov. B, are distinguishable from O. virilis by significant differences in gonopod morphology (no data on gonopod morphology were available for O. sp. nov. C). O. sp. nov. A was collected at numerous sites in Massachusetts; additional sampling is required to determine if this species is native to New England. Two other taxa, O. sp. nov. B and O. sp. nov. C, were both collected from sites in eastern Kansas, and historically have probably been considered to be O. nais. In summary, this investigation indicates that this species complex may harbor a great deal of unknown biodiversity over the rest of its described range, and suggests that further attention to the phylogenetics and phylogeography of North American crayfishes may yield interesting insights into the evolution of biodiversity. [Copyright &y& Elsevier]

Targeting of postmitotic neurons selectively for gene delivery poses a challenge. One way to achieve such a selective targeting is to link the gene delivery vector with small ligand-binding polypeptides which have selective affinity to intact neurons. In order to identify such novel neuron selective polypeptides, we screened a phage-display library displaying random 12-mer polypeptides and subtractively bio-panned for clones having selectivity towards cultured mouse cerebellar granule neurons. The selected phage clones were amplified and sequenced. Affinities of these clones to neurons were determined by the visible presence or absence of fluorescence of phage particles as detected by immunocytochemistry using an antibody to M-13 phage. This affinity was further qualified by how much phage was bound, and where in or on the cell it tended to accumulate. The selectivity of binding to neurons was determined by the negative binding of these clones to several cultured non-neuronal cells, including, primary glial cells, NT2 cells, human embryonic kidney 293 cells, neuroblastoma cells, and mouse 3T3 cells. Among the 46 clones that we have sequenced and characterized, four clones appeared to have excellent selectivity in binding to neurons. Homology comparison of these polypeptides revealed that three of them contained a consensus D(E)–W(F)–I(N)–D–W motif. This motif was also present in the Bdm1 gene product which was predominantly expressed in postnatal brains. Further characterizations of these polypeptides are required to reveal the utilities of these peptides to function as an effective linker to facilitate gene transfer selectively to neurons. [Copyright &y& Elsevier]

In yeast the Sir proteins and Rap1p are key regulators of transcriptional silencing at telomeres and the silent mating-type loci. Rap1 and Sir4 also possess anchoring activity; the rotation of plasmids bound by Sir4 or Rap1 is constrained in vivo, and Rap1 or Sir4 binding can also correct the segregation bias of plasmids lacking centromeres. To investigate the mechanistic link between DNA anchoring and regulation of transcription, we examined the ability of a third defined anchor in yeast, the 2μ circle REP3 segregation element, to mediate transcriptional silencing. We find that placement of the REP3 sequence adjacent to the HML locus in a strain deleted for natural silencer sequences confers transcriptional repression on HML. This repression requires the Sir proteins and is decreased in strains lacking the REP3-binding factors Rep1 and Rep2. The yeast cohesin complex associates with REP3; we show that REP3 silencing is also decreased in strains bearing a mutated allele of the MCD1/SCC1 cohesin gene. Conventional silencing is increased in some strains lacking the 2μ circle and decreased in strains overexpressing the Rep1 and Rep2 proteins, suggesting that the Rep proteins antagonize conventional silencing. [ABSTRACT FROM AUTHOR]

The Care Transitions Intervention (CTI) is an evidence-based intervention aimed at supporting the transition from hospital back to the community for patients to ultimately reduce preventable re-hospitalization. In a pilot randomized controlled trial, we examined the preliminary effectiveness of an Enhanced Care Transitions Intervention (ECTI), CTI with the addition of peer support, for a racially/ethnically diverse sample of older adults (age 60+) with co-morbid major depression. We observed a significant decline in health-related quality of life (HRQOL) after being discharged from the hospital among those who received CTI. Additionally, those who received ECTI either maintained HRQOL scores, or, saw improvement in HRQOL scores. Findings suggest the Enhanced Care Transitions Intervention can maintain or improve HRQOL and reduce disparities for older participants from diverse racial/ethnic backgrounds with clinical depression. [ABSTRACT FROM AUTHOR]

The article presents the discussion on uterine transplantation and donation in transgender individuals. Topics include decreasing social stigmatization, improved insurance coverage, and expanding access to gender-affirmation surgery; and cisgender woman cannot carrying a pregnancy due to either lack of a uterus or a malfunctioning uterus.

Cultural factors influence the development of all children. Yet, current knowledge of explicit cultural socialization processes in childhood remains limited, mainly by failing to incorporate the experiences of young children. To address this critical gap, the authors introduce the OMERS-Peds task, an observational measurement designed to systematically identify and compare the content of cultural messages passed down from caregivers to offspring during early school age years. The OMERS-Peds was administered to mothers and children (n = 275) from three diverse racial/ethnic backgrounds (African American (n = 153), Hispanic (n = 61), and non-Hispanic White (n = 61)) within the longitudinal Multidimensional Assessment of Preschoolers (MAPS) Study. The OMERS-Peds coding system was used to rate how strongly families endorsed 5 key constructs: family culture, religion, identity, ethnicity, and race. A series of χ2 statistic tests were used to compare scores across racial/ethnic backgrounds, and within families (between children and their mothers). Analyses revealed that in the cultural socialization conversations occurring in early childhood, parents and children prioritize talking about their family's culture and religion. Independent of their racial/ethnic backgrounds, mothers and children seldom discussed race and ethnicity. Contrary to research with older children, differences were mainly identified within families, rather than across racial/ethnic groups. Findings support the need to include children's perspectives in the assessments of cultural socialization, as opposed to relying primarily on parent reports, and highlight the importance of having an observational methodology that allows researchers to examine parent-child bidirectional interactions during early school age years in a systematic manner. (PsycInfo Database Record (c) 2021 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

Irritability is a substrate of more than one dozen clinical syndromes. Thus, identifying when it is atypical and interfering with functioning is crucial to the prevention of mental disorder in the earliest phase of the clinical sequence. Advances in developmentally based measurement of irritability have enabled differentiation of normative irritable mood and tantrums from indicators of concern, beginning in infancy. However, developmentally sensitive assessments of irritability-related impairment are lacking. We introduce the Early Childhood Irritability-Related Impairment Interview (E-CRI), which assesses impairment associated with irritable mood and tantrums across contexts. Reliability and validity are established across two independent samples varied by developmental period: the Emotional Growth preschool sample (EmoGrow; N = 151, M = 4.82 years) and the When to Worry infant/toddler sample (W2W; N = 330, M = 14 months). We generated a well-fitting two-factor E-CRI model, with tantrum- and irritable mood-related impairment factors. The E-CRI exhibited good interrater, test-retest, and longitudinal reliability. Construct and clinical validity were also demonstrated. In both samples, E-CRI factors showed association to internalizing and externalizing problems, and to caregiver-reported concern in W2W. Tantrum-related impairment demonstrated stronger and more consistent explanatory value across outcomes, while mood-related impairment added explanatory utility for internalizing problems. The E-CRI also showed incremental utility beyond variance explained by the Family Life Impairment Scale (FLIS) survey indicator of developmental impairment. The E-CRI holds promise as an indicator of impairment to inform identification of typical versus atypical patterns reflecting early emerging irritability-related syndromes in the initial phase of the clinical sequence. [ABSTRACT FROM AUTHOR]

Background Contextual variation in child disruptive behavior is well documented but remains poorly understood. We first examine how variation in observed disruptive behavior across interactional contexts is associated with maternal reports of contextual variation in oppositional-defiant behavior and functional impairment. Second, we test whether child inhibitory control explains the magnitude of contextual variation in observed disruptive behavior. Methods Participants are 497 young children (mean age = 4 years, 11 months) from a subsample of the MAPS, a sociodemographically diverse pediatric sample, enriched for risk of disruptive behavior. Observed anger modulation and behavioral regulation problems were coded on the Disruptive Behavior Diagnostic Observation Schedule ( DB- DOS) during interactions with parent and examiner. Oppositional-defiant behavior, and impairment in relationships, with parents and nonparental adults, were measured with the Preschool Age Psychiatric Assessment ( PAPA) interview with the mother. Functional impairment in the home and out-and-about was assessed with the Family Life Impairment Scale ( FLIS), and expulsion from child care/school was measured with the baseline survey and FLIS. Results Observed disruptive behavior on the DB- DOS Parent Context was associated with oppositional-defiant behavior with parents, and with impairment at home and out-and-about. Observed disruptive behavior with the Examiner was associated with oppositional-defiant behavior with both parents and nonparental adults, impairment in relationships with nonparental adults, and child care/school expulsion. Differences in observed disruptive behavior in the Parent versus Examiner Contexts was related to the differences in maternal reports of oppositional-defiant behavior with parents versus nonparental adults. Children with larger decreases in disruptive behavior from Parent to Examiner Context had better inhibitory control and fewer attention-deficit/hyperactivity disorder symptoms. Conclusions The DB- DOS showed clinical utility in a community sample for identifying contextual variation that maps onto reported oppositional-defiant behavior and functioning across contexts. Elucidating the implications of contextual variation for early identification and targeted prevention is an important area for future research. [ABSTRACT FROM AUTHOR]

The authors reflect on the variability of the context of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms through the consideration of basic moderating factor. It regards variability in symptoms' number and contextual expression as key factor for diagnostic and treatment procedure improvement. They conclude that ADHD is not insensitive viewing it as a genetically determine disorder.

Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the gene coding for FIBRILLIN-1 (FBN1), an extracellular matrix protein. MFS is inherited as an autosomal dominant trait and displays major manifestations in the ocular, skeletal, and cardiovascular systems. Here we report molecular and phenotypic profiles of skeletogenesis in tissues differentiated from human embryonic stem cells and induced pluripotent stem cells that carry a heritable mutation in FBN1. We demonstrate that, as a biological consequence of the activation of TGF-β signaling, osteogenic differentiation of embryonic stem cells with a FBN1 mutation is inhibited; osteogenesis is rescued by inhibition of TGF-β signaling. In contrast. chondrogenesis is not perturbated and occurs in a TGF-β cell-autonomous fashion. Importantly, skeletal phenotypes observed in human embryonic stem cells carrying the monogenic FBN1 mutation (MFS cells) are faithfully phenocopied by cells differentiated from induced pluripotent-stem cells derived independently from MFS patient fibroblasts. Results indicate a unique phenotype uncovered by examination of mutant pluripotent stem cells and further demonstrate the faithful alignment of phenotypes in differentiated cells obtained from both human embryonic stem cells and induced pluripotent-stem cells, providing complementary and powerful tools to gain further insights into human molecular pathogenesis, especially of MFS. [ABSTRACT FROM AUTHOR]

Iron acquisition mechanisms play an important role in the pathogenesis of many infectious microbes. In Bacillus anthracis, the siderophore petrobactin is required for both growth in iron-depleted conditions and for full virulence of the bacterium. Here we demonstrate the roles of two putative petrobactin binding proteins FatB and FpuA (encoded by GBAA5330 and GBAA4766 respectively) in B. anthracis iron acquisition and pathogenesis. Markerless deletion mutants were created using allelic exchange. The Δ fatB strain was capable of wild-type levels of growth in iron-depleted conditions, indicating that FatB does not play an essential role in petrobactin uptake. In contrast, Δ fpuA bacteria exhibited a significant decrease in growth under low-iron conditions when compared with wild-type bacteria. This mutant could not be rescued by the addition of exogenous purified petrobactin. Further examination of this strain demonstrated increased levels of petrobactin accumulation in the culture supernatants, suggesting no defect in siderophore synthesis or export but, instead, an inability of Δ fpuA to import this siderophore. Δ fpuA spores were also significantly attenuated in a murine model of inhalational anthrax. These results provide the first genetic evidence demonstrating the role of FpuA in petrobactin uptake. [ABSTRACT FROM AUTHOR]

Lack of available iron is one of many environmental challenges that a bacterium encounters during infection and adaptation to iron starvation is important for the pathogen to efficiently replicate within the host. Here we define the transcriptional response of B. anthracis Sterne (34F2) to iron depleted conditions. Genome-wide transcript analysis showed that B. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known and candidate virulence factors. Two genes encoding putative internalin proteins were chosen for further study. Deletion of either gene (GBAA0552 or GBAA1340) resulted in attenuation in a murine model of infection. This attenuation was amplified in a double mutant strain. These data define the transcriptional changes induced during growth in low iron conditions and illustrate the potential of this dataset in the identification of putative virulence determinants for future study. [ABSTRACT FROM AUTHOR]

Petrobactin, a virulence-associated siderophore produced by Bacillus anthracis, chelates ferric iron through the rare 3,4-isomer of dihydroxybenzoic acid (3,4-DHBA). Most catechol siderophores, including bacillibactin and enterobactin, use 2,3-DHBA as a biosynthetic subunit. Significantly, siderocalin, a factor involved in human innate immunity, sequesters ferric siderophores bearing the more typical 2,3-DHBA moiety, thereby impeding uptake of iron by the pathogenic bacterial cell. In contrast, the unusual 3,4-DHBA component of petrobactin renders the siderocalin system incapable of obstructing bacterial iron uptake. Although recent genetic and biochemical studies have revealed selected early steps in petrobactin biosynthesis, the origin of 3,4-DHBA as well as the function of the protein encoded by the final gene in the B. anthracis siderophore biosynthetic (asb) operon, asbF (BA1 986), has remained unclear. In this study we demonstrate that 3,4-DHBA is produced through conversion of the common bacterial metabolite 3-dehydroshikimate (3-DHS) by AsbF-a 3-DHS dehydratase. Elucidation of the cocrystal structure of AsbF with 3,4-DHBA, in conjunction with a series of biochemical studies, supports a mechanism in which an enolate intermediate is formed through the action of this 3-DHS dehydratase metalloenzyme. Structural and functional parallels are evident between AsbF and other enzymes within the xylose isomerase TIM-barrel family. Overall, these data indicate that microbial species shown to possess homologs of AsbF may, like B. anthracis, also rely on production of the unique 3,4-DHBA metabolite to achieve full viability in the environment or virulence within the host. [ABSTRACT FROM AUTHOR]