Zebrafish scl functions independently in hematopoietic and endothelial development

AbstractThe SCL transcription factor is critically important for vertebrate hematopoiesis and angiogenesis, and has been postulated to induce hemangioblasts, bipotential precursors for blood and endothelial cells. To investigate the function of scl during zebrafish hematopoietic and endothelial development, we utilized site-directed, anti-sense morpholinos to inhibit scl mRNA. Knockdown of scl resulted in a loss of primitive and definitive hematopoietic cell lineages. However, the expression of early hematopoietic genes, gata2 and lmo2, was unaffected, suggesting that hematopoietic cells were present but unable to further differentiate. Using gene expression analysis and visualization of vessel formation in live animals harboring an lmo2 promoter-green fluorescent protein reporter transgene (Tg(lmo2:EGFP)), we show that angioblasts were specified normally in the absence of scl, but later defects in angiogenesis were evident. While scl was not required for angioblast specification, forced expression of exogenous scl caused an expansion of both hematopoietic and endothelial gene expression, and a loss of somitic tissue. In cloche and spadetail mutants, forced expression of scl resulted in an expansion of hematopoietic but not endothelial tissue. Surprisingly, in cloche, lmo2 was not induced in response to scl over-expression. Taken together, these findings support distinct roles for scl in hematopoietic and endothelial development, downstream of hemangioblast development

Burnout, Depression, Anxiety, and Stress Among Resident Physicians 18 Months into the COVID-19 Pandemic: A Cross-Sectional Study

INTRODUCTION. Burnout among resident physicians has been an area of concern that predates the COVID-19 pandemic. With the significant turmoil during the pandemic, this study examined resident physicians’ burnout, depression, anxiety, and stress as well as the benefits of engaging in activities related to  wellness, mindfulness, or mental wellbeing. METHODS. The authors conducted a cross-sectional survey of 298 residents from 13 residency programs sponsored by the University of Kansas School of Medicine-Wichita, in October and November 2021. Authors used a 31-item questionnaire to measure levels of burnout, depression, anxiety, and stress. A mixed method approach was used to collect, analyze, and interpret the data. Descriptive statistics, One-way ANOVA/Kruskal-Wallis tests, adjusted odds ratios (aOR), and immersion-crystallization methods were used to analyze the data. RESULTS. There was a 52% response rate, with 65.8% (n=102) of the respondents reporting manifestations of burnout. Those who reported at least one manifestation of burnout experienced a higher level of emotional exhaustion (aOR=6.73; 95% CI, 2.66-16.99; P<.01), depression (aOR=1.21; 95% CI, 1.04-1.41; P=.01), anxiety (aOR=1.14; 95% CI, 1.00-1.30; P=.04), and stress (aOR=1.36; 95% CI, 1.13-1.64; P<.01). Some wellness activities respondents engaged in included regular physical activities, meditation and yoga, support from family and friends, religious activities, time away from work, and counseling sessions. CONCLUSIONS. The findings suggest the COVID-19 pandemic continues to pose a significant and worsening prevalence of burnout and other negative mental health effects on residents. Appropriate wellness and mental health support initiatives are needed to help resident physicians thrive in the health care environment

Enantiomer-Specific Binding of Ruthenium(II) Molecular Wires by the Amine Oxidase of Arthrobacter globiformis

The copper amine oxidase from Arthrobacter globiformis (AGAO) is reversibly inhibited by molecular wires comprising a Ru(II) complex head group and an aromatic tail group joined by an alkane linker. The crystal structures of a series of Ru(II)-wire−AGAO complexes differing with respect to the length of the alkane linker have been determined. All wires lie in the AGAO active-site channel, with their aromatic tail group in contact with the trihydroxyphenylalanine quinone (TPQ) cofactor of the enzyme. The TPQ cofactor is consistently in its active (“off-Cu”) conformation, and the side chain of the so-called “gate” residue Tyr296 is consistently in the “gate-open” conformation. Among the wires tested, the most stable complex is produced when the wire has a −(CH_2)_4− linker. In this complex, the Ru(II)(phen)(bpy)_2 head group is level with the protein molecular surface. Crystal structures of AGAO in complex with optically pure forms of the C4 wire show that the linker and head group in the two enantiomers occupy slightly different positions in the active-site channel. Both the Λ and Δ isomers are effective competitive inhibitors of amine oxidation. Remarkably, inhibition by the C4 wire shows a high degree of selectivity for AGAO in comparison with other copper-containing amine oxidases

The Frequency of Malaria Is Similar among Women Receiving either Lopinavir/Ritonavir or Nevirapine-based Antiretroviral Treatment

HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; ClinicalTrials.gov: NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population

Properties that influence business process management maturity and its effect on organizational performance

Abstract BPM maturity is a measure to evaluate how professionally an organization manages its business processes. Previous research provides evidence that higher BPM maturity leads to better performance of processes and of the organization as a whole. It also claims that different organizations should strive for different levels of maturity, depending on their properties. This paper presents an empirical investigation of these claims, based on a sample of 120 organizations and looking at a selection of organizational properties. Our results reveal that higher BPM maturity contributes to better performance, but only up to a point. Interestingly, it contradicts the popular belief that higher innovativeness is associated with lower BPM maturity, rather showing that higher innovativeness is associated with higher BPM maturity. In addition, the paper shows that companies in different regions have a different level of BPM maturity. These findings can be used as a benchmark and a motivation for organizations to increase their BPM maturity

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Welcome and Orientation

Dr. Elizabeth Dooley, Vice Provost of Teaching and Learning, Dean of College of Undergraduate Studies, and Dr. Kimberly Schneider, Director, Office of Undergraduate Research, welcome and orient attendees to the Symposium

Co-producing climate policy and negative emissions: trade-offs for sustainable land-use

Under the Paris Agreement, nations have committed to preventing dangerous global warming. Scenarios for achieving net-zero emissions in the second half of this century depend on land (forests and bioenergy) to remove carbon from the atmosphere. Modelled levels of land-based mitigation could reduce the availability of productive agricultural land, and encroach on natural land, with potentially significant social and environmental consequences. However, these issues are poorly recognized in the policy-uptake of modelled outputs. Understanding how science and policy interact to produce expectations about mitigation pathways allows us to consider the trade-offs inherent in relying on land for mitigation