Reactivity of a Sterically Unencumbered α-Borylated Phosphorus Ylide towards Small Molecules

The influence of substituents on α‐borylated phosphorus ylides (α‐BCPs) has been investigated in a combined experimental and quantum chemical approach. The synthesis and characterization of Me$_{3}$PC(H)B(iBu)$_{2}$ (1), consisting of small Me substituents on phosphorous and iBu residues on boron, is reported. Compound 1 is accessible through a novel synthetic approach, which has been further elucidated through DFT studies. The reactivity of 1 towards various small molecules was probed and compared with that of a previously published derivative, Ph$_{3}$PC(Me)BEt$_{2}$ (2). Both α‐BCPs react with NH$_{3}$ to undergo heterolytic N−H bond cleavage. Different di‐ and trimeric ring structures were observed in the reaction products of 1 with CO and CO$_{2}$. With PhNCO and PHNCS, the expected insertion products [Me$_{3}$PC(H)(PhNCO)B(iBu)$_{2}$] and [Me$_{3}$PC(H)(PhNCS)B(iBu)$_{2}$], respectively, were isolated

Minderheitenstress und psychische Gesundheit von Lesben, Schwulen und Bisexuellen

Einleitung: Laut dem Minderheitenstressmodell (Meyer, 2003) sagt eine lesbische, schwule oder bisexuelle Orientierung, mediiert über Minderheitenstressoren, psychische Symptome vorher. Das Modell wird durch eine Vielzahl westlicher Studien gestützt. Die vornehmlichen Ziele des Kumulus sind es, in Deutschland erstmalig auf Prävalenzunterschiede zwischen Lesben, Schwulen und Bisexuellen (LSB) versus Heterosexuellen zu testen sowie Zusammenhänge zwischen Minderheitenstress und psychischen Symptomen zu überprüfen. Methode: Es wurden vier Manuskripte erstellt, die Daten aus vier Ad-hoc-Stichproben sexueller Minderheiten, einer heterosexuellen Ad-hoc-Stichprobe und einer repräsentativen, männlichen Stichprobe untersuchten. Die Datenanalysen wurden mit IBM SPSS Statistics 22 und 24 durchgeführt. Ergebnisse: LSB gaben mehr psychische Symptome als Heterosexuelle an. Eine minoritäre sexuelle Identität sagte Minderheitenstress bzw. sexuellen Identitätsstress vorher, während dieser wiederum psychische Symptome bedingte. Gruppenbezogenes Coping und soziale Unterstützung moderierten die Zusammenhänge nicht. Zudem berichtete ein kleiner Anteil Heterosexueller von erlebtem sexuellem Identitätsstress. Diskussion: Der Kumulus bestätigt mehrere Vorhersagen des Minderheitenstressmodells und widerlegt andere. Ein adaptiertes Minderheitenstressmodell wird vorgestellt, das durch zukünftige Studien überprüft werden sollte. Minderheitenstress sollte flächendeckend verringert werden, um die psychische Gesundheit von LSB zu erhöhen

Characterization of novel \u3ci\u3eBrown midrib 6\u3c/i\u3e mutations affecting lignin biosynthesis in sorghum

The presence of lignin reduces the quality of lignocellulosic biomass for forage materials and feedstock for biofuels. In C4 grasses, the brown midrib phenotype has been linked to mutations to genes in the monolignol biosynthesis pathway. For example, the Bmr6 gene in sorghum (Sorghum bicolor) has been previously shown to encode cinnamyl alcohol dehydrogenase (CAD), which catalyzes the final step of the monolignol biosynthesis pathway. Mutations in this gene have been shown to reduce the abundance of lignin, enhance digestibility, and improve saccharification efficiencies and ethanol yields. Nine sorghum lines harboring five different bmr6 alleles were identified in an EMS-mutagenized TILLING population. DNA sequencing of Bmr6 revealed that the majority of the mutations impacted evolutionarily conserved amino acids while three-dimensional structural modeling predicted that all of these alleles interfered with the enzyme’s ability to bind with its NADPH cofactor. All of the new alleles reduced in vitro CAD activity levels and enhanced glucose yields following saccharification. Further, many of these lines were associated with higher reductions in acid detergent lignin compared to lines harboring the previously characterized bmr6-ref allele. These bmr6 lines represent new breeding tools for manipulating biomass composition to enhance forage and feedstock quality

Mucosal associated invariant T cells are differentially impaired in tolerant and immunosuppressed liver transplant recipients

Mucosal associated invariant T (MAIT-) cells represent a semi-invariant T cell population responsive to microbial vitamin B metabolite and innate cytokine stimulation, executing border tissue protection and particularly contributing to human liver immunity. The impact of immunosuppressants on MAIT cell biology alone and in context with solid organ transplantation has not been thoroughly examined. Here, we demonstrate that in vitro cytokine activation of peripheral MAIT cells from healthy individuals was impaired by glucocorticoids, whereas antigen-specific stimulation was additionally sensitive to calcineurin inhibitors. In liver transplant (LTx) recipients, significant depletion of peripheral MAIT cells was observed that was largely independent of the type and dosage of immunosuppression, equally applied to tolerant patients, and was reproducible in kidney transplant recipients. However, MAIT cells from tolerant LTx patients exhibited a markedly diminished ex vivo activation signature, associated with individual regain of functional competence toward antigenic and cytokine stimulation. Still, MAIT cells from tolerant and treated liver recipients exhibited high levels of PD1, accompanied by functional impairment particularly toward bacterial stimulation that also affected polyfunctionality. Our data suggest interlinked effects of primary liver pathology and immunosuppressive treatment on overall MAIT cell fitness after transplantation and propose their monitoring in context with tolerance induction protocols

Identification of an orthologous clade of peroxidases that respond to feeding by greenbugs (\u3ci\u3eSchizaphis graminum\u3c/i\u3e) in C\u3csub\u3e4\u3c/sub\u3e grasses

Knowledge of specific peroxidases that respond to aphid herbivory is limited in C4 grasses, but could provide targets for improving defence against these pests. A sorghum (Sorghum bicolor (L.) Moench) peroxidase (SbPrx-1; Sobic.002G416700) has been previously linked to biotic stress responses, and was the starting point for this study. Genomic analyses indicated that SbPrx-1 was part of a clade of five closely related peroxidase genes occurring within a ~30 kb region on chromosome 2 of the sorghum genome. Comparison of this ~30-kb region to syntenic regions in switchgrass (Panicum virgatum L.) and foxtail millet (Setaria italica L.) identified similar related clusters of peroxidases. Infestation of a susceptible sorghum cultivar with greenbugs (Shizaphis graminum Rondani) induced three of the five peroxidases. Greenbug infestation of switchgrass and foxtail millet plants showed similar inductions of peroxidases. SbPrx-1 was also induced in response to aphid herbivory in a greenbug-resistant sorghum line, Cargill 607E. These data indicate that this genomic region of C4 grasses could be valuable as a marker to assess potential insect resistance in C4 grasses

Extended Criteria Donors in Living Kidney Transplantation Including Donor Age, Smoking, Hypertension and BMI

Purpose: An expansion of selection criteria for deceased organ transplantation already exists to manage the current donor shortage. Comparable evaluation of risk factors for living donors should be investigated to improve this issue. Patients and methods: Our retrospective single-centre study analysed 158 patients with living kidney transplants performed between February 2006 and June 2012. We investigated the influence of donor risk factors (RF) including body mass index over 30 kg/m2, age >60 years, active nicotine abuse and arterial hypertension on postoperative kidney function with focus on the recipients. This was measured for long-term survival and glomerular filtration rate (GFR) in a 5-year follow-up. Results: Overall, out of 158 living donors, 84 donors were identified to have no risk factors, whereas 74 donors had at least one risk factor. We noted a significant higher delayed graft function (p=0.042) in the first 7 days after transplantation, as well as lower GFR of recipients of allografts with risk factors in the first-year after transplantation. In our long-term results, there was no significant difference in the functional outcome (graft function, recipient and graft survival) between recipients receiving kidneys from donors with no and at least one risk factors. In the adjusted analysis of subgroups of different risk factors, recipients of donors with "age over 60 years" at time of transplantation had a decreased transplant survival (p=0.014). Conclusion: Thus, a careful expansion for selection criteria for living donors with critical evaluation could be possible, but especially the age of the donors could be a limited risk factor

Reversible Resistance Induced by FLT3 Inhibition: A Novel Resistance Mechanism in Mutant FLT3-Expressing Cells

Clinical responses achieved with FLT3 kinase inhibitors in acute myeloid leukemia (AML) are typically transient and partial. Thus, there is a need for identification of molecular mechanisms of clinical resistance to these drugs. In response, we characterized MOLM13 AML cell lines made resistant to two structurally-independent FLT3 inhibitors.MOLM13 cells were made drug resistant via prolonged exposure to midostaurin and HG-7-85-01, respectively. Cell proliferation was determined by Trypan blue exclusion. Protein expression was assessed by immunoblotting, immunoprecipitation, and flow cytometry. Cycloheximide was used to determine protein half-life. RT-PCR was performed to determine FLT3 mRNA levels, and FISH analysis was performed to determine FLT3 gene expression.We found that MOLM13 cells readily developed cross-resistance when exposed to either midostaurin or HG-7-85-01. Resistance in both lines was associated with dramatically elevated levels of cell surface FLT3 and elevated levels of phosphor-MAPK, but not phospho-STAT5. The increase in FLT3-ITD expression was at least in part due to reduced turnover of the receptor, with prolonged half-life. Importantly, the drug-resistant phenotype could be rapidly reversed upon withdrawal of either inhibitor. Consistent with this phenotype, no significant evidence of FLT3 gene amplification, kinase domain mutations, or elevated levels of mRNA was observed, suggesting that protein turnover may be part of an auto-regulatory pathway initiated by FLT3 kinase activity. Interestingly, FLT3 inhibitor resistance also correlated with resistance to cytosine arabinoside. Over-expression of FLT3 protein in response to kinase inhibitors may be part of a novel mechanism that could contribute to clinical resistance

AI assistance in aesthetic medicine–A consensus on objective medical standards

Background: Aesthetic medicine has traditionally relied on clinical scales for the objective assessment of baseline appearance and treatment outcomes. However, the scales focus on limited aesthetic areas mostly and subjective interpretation inherent in these scales can lead to variability, which undermines standardization efforts. Objective: The consensus meeting aimed to establish guidelines for AI application in aesthetic medicine. Materials and methods: In February 2024, the AI Consensus Group, comprising international experts in various specialties, convened to deliberate on AI in aesthetic medicine. The methodology included a pre-consensus survey and an iterative consensus process during the meeting. Results: AI's implementation in Aesthetic Medicine has achieved full consensus for enhancing patient assessment and consultation, ensuring standardized care. AI's role in preventing overcorrection is recognized, alongside the need for validated objective facial assessments. Emphasis is placed on comprehensive facial aesthetic evaluations using indices such as the Facial Aesthetic Index (FAI), Facial Youth Index (FYI), and Skin Quality Index (SQI). These evaluations are to be gender-specific and exclude makeup-covered skin at baseline. Age and gender, as well as patients' ancestral roots, are to be considered integral to the AI assessment process, underlining the move towards personalized, precise treatments. Conclusion: The consensus meeting established that AI will significantly improve aesthetic medicine by standardizing patient assessments and consultations, with a strong endorsement for preventing overcorrection and advocating for validated, objective facial assessments. Utilizing indices such as the FAI, FYI, and SQI allows for gender-specific, age adjusted evaluations and insists on a makeup-free baseline for accuracy.</p

Community-associated Methicillin-resistant Staphylococcus aureus in Pediatric Patients

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections increased from 2000 to 2003 in hospitalized pediatric patients in Houston. CA-MRSA was associated with greater illness than was infection with methicillin-susceptible strains. Children with CA-MRSA were younger and mostly African American. Of MRSA isolates, 4.5% had the inducible macrolide-lincosamide-streptogramin B phenotype