A developmental approach to diversifying neuroscience through effective mentorship practices: perspectives on cross-identity mentorship and a critical call to action.

Many early-career neuroscientists with diverse identities may not have mentors who are more advanced in the neuroscience pipeline and have a congruent identity due to historic biases, laws, and policies impacting access to education. Cross-identity mentoring relationships pose challenges and power imbalances that impact the retention of diverse early career neuroscientists, but also hold the potential for a mutually enriching and collaborative relationship that fosters the mentee\u27s success. Additionally, the barriers faced by diverse mentees and their mentorship needs may evolve with career progression and require developmental considerations. This article provides perspectives on factors that impact cross-identity mentorship from individuals participating in Diversifying the Community of Neuroscience (CNS)-a longitudinal, National Institute of Neurological Disorders and Stroke (NINDS) R25 neuroscience mentorship program developed to increase diversity in the neurosciences. Participants in Diversifying CNS were comprised of 14 graduate students, postdoctoral fellows, and early career faculty who completed an online qualitative survey on cross-identity mentorship practices that impact their experience in neuroscience fields. Qualitative survey data were analyzed using inductive thematic analysis and resulted in four themes across career levels: (1) approach to mentorship and interpersonal dynamics, (2) allyship and management of power imbalance, (3) academic sponsorship, and (4) institutional barriers impacting navigation of academia. These themes, along with identified mentorship needs by developmental stage, provide insights mentors can use to better support the success of their mentees with diverse intersectional identities. As highlighted in our discussion, a mentor\u27s awareness of systemic barriers along with active allyship are foundational for their role

Low- and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy: a prospective study

Background. Selective urinary biomarkers have been considered superior to total proteinuria in predicting response to treatment and outcome in patients with membranous nephropathy (MN). Methods. We prospectively tested whether urinary (U) excretion of retinol-binding protein (RBP), α1-microglobulin (α1M), albumin, immunoglobulinIgG and IgM and/or anti-phospholipase 2 receptor (PLA2R) levels could predict response to rituximab (RTX) therapy better than standard measures in MN. We also correlated changes in antibodies to PLA2R with these urinary biomarkers. Results. Twenty patients with MN and proteinuria (P) >5 g/24 h received RTX (375 mg/m2 × 4) and at 12 months, 1 patient was in complete remission (CR), 9 were in partial remission (PR), 5 had a limited response (LR) and 4 were non-responders (NR). At 24 months, CR occurred in 4, PR in 12, LR in 1, NR in 2 and 1 patient relapsed. By simple linear regression analysis, UIgG at baseline (mg/24 h) was a significant predictor of change in proteinuria at 12 months (Δ urinary protein) (P = 0.04). In addition, fractional excretion (FE) of IgG, urinary alpha 1 microglobulin (Uα1M) (mg/24 h) and URBP (μg/24 h) were also predictors of response (P = 0.05, 0.04, and 0.03, respectively). On the other hand, UIgM, FEIgM, albumin and FE albumin did not predict response (P = 0.10, 0.27, 0.22 and 0.20, respectively). However, when results were analyzed in relation to proteinuria at 24 months, none of the U markers that predicted response at 12 m could predict response at 24 m (P = 0.55, 0.42, 0.29 and 0.20). Decline in anti-PLA2R levels was associated with and often preceded urinary biomarker response but positivity at baseline was not a predictor of proteinuria response. Conclusions. The results suggest that in patients with MN, quantification of low-, medium- and high-molecular-weight urinary proteins may be associated with rate of response to RTX, but do not correlate with longer term outcomes

The Kalanchoe genome provides insights into convergent evolution and building blocks of crassulacean acid metabolism

Crassulacean acid metabolism (CAM) is a water-use efficient adaptation of photosynthesis that has evolved independently many times in diverse lineages of flowering plants. We hypothesize that convergent evolution of protein sequence and temporal gene expression underpins the independent emergences of CAM from C3 photosynthesis. To test this hypothesis, we generate a de novo genome assembly and genome-wide transcript expression data for Kalanchoë fedtschenkoi, an obligate CAM species within the core eudicots with a relatively small genome (~260 Mb). Our comparative analyses identify signatures of convergence in protein sequence and re-scheduling of diel transcript expression of genes involved in nocturnal CO2 fixation, stomatal movement, heat tolerance, circadian clock, and carbohydrate metabolism in K. fedtschenkoi and other CAM species in comparison with non-CAM species. These findings provide new insights into molecular convergence and building blocks of CAM and will facilitate CAM-into-C3 photosynthesis engineering to enhance water-use efficiency in crops

Dietary patterns and risk of inflammatory bowel disease in Europe: Results from the EPIC study

Background: Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are limited. We investigated the association between prediagnostic intake of these foods and dietary calcium and the subsequent development of Crohn’s disease (CD) and ulcerative colitis (UC). Methods: In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n=110) or UC (n=244) during followup were matched with four controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking. Results: Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI 0.32-1.19, p trend=0.19) and 0.63 (95% CI 0.28-1.42, p trend=0.23) for CD and 0.80 (95% CI 0.50-1.30, p trend=0.40) and 0.81 (95% CI 0.49-1.34, p trend=0.60) for UC. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI 0.49-1.47). Conclusions: Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect

Ligand activation of peroxisome proliferator-activated receptor-b/d (PPARb/d) and inhibition of cyclooxygenase 2 (COX2) attenuate colon carcinogenesis through independent signaling mechanisms

Cyclooxygenase (COX) 2-derived prostaglandin E 2 (PGE 2 ) promotes colorectal carcinoma growth and invasion, and inhibition of COX2 by non-steroidal anti-inflammatory drugs is known to inhibit these processes. There is controversy regarding the effect of ligand activation of peroxisome proliferator-activated receptor (PPAR)-b/d on colon carcinogenesis, although collective evidence from independent laboratories suggest that ligand activation of PPARb/d leads to the induction of terminal differentiation coupled with inhibition of cell growth in a variety of models. The present study examined the hypothesis that ligand activation of PPARb/d and inhibition of COX2 attenuate colon cancer through independent mechanisms and that combining these two mechanisms will enhance this inhibition. Colon cancer was induced by administering azoxymethane to wild-type and PPARb/d-null mice. Cohorts of mice were treated with GW0742 (a PPARb/d ligand), nimesulide (a COX2 inhibitor) or a combination of GW0742 and nimesulide. Inhibition of COX2 by nimesulide attenuated colon cancer and ligand activation of PPARb/d by GW0742 had inhibitory effects. However, the combined treatment of GW0742 and nimesulide did not cause an enhancement in the attenuation of colon cancer. Mechanistically, the effects of these compounds occurred through independent mechanisms as increased levels of differentiation markers as a result of ligand activation of PPARb/d were not found with COX2 inhibition, and a reduction in PGE 2 levels resulting from COX2 inhibition was not observed in response to ligand activation of PPARb/d. Results from these studies effectively dissociate COX2 inhibition and PPARb/d activity during colon carcinogenesis

Engineering crassulacean acid metabolism to improve water-use efficiency.

Climatic extremes threaten agricultural sustainability worldwide. One approach to increase plant water-use efficiency is to introduce crassulacean acid metabolism (CAM) into C3 crops. Such a task requires comprehensive systems-level understanding of the enzymatic and regulatory pathways underpinning this temporal CO2 pump. Here, we review the progress that has been made in achieving this goal. Given that CAM arose through multiple independent evolutionary origins, comparative transcriptomics and genomics of taxonomically diverse CAM species are being used to define the genetic ‘parts list’ required to operate the core CAM functional modules of nocturnal carboxylation, daytime decarboxylation, and inverse stomatal regulation. Engineered CAM offers the potential to sustain plant productivity for food, feed, fiber, and biofuel production in hotter and drier climates