A Research Operations, Management, and Strategy Fellowship for Life Sciences PhD Graduates.

Problem: With less than 25% of PhD-trained scientists in the United States securing a tenure-track faculty position following training, nonacademic careers have become common. As the academic research enterprise has increased, business-oriented careers have emerged. The Research Operations, Management, and Strategy (ROMS) Fellowship was developed to increase awareness of and prepare life sciences PhD graduates for business-focused careers.

Bridging the gap: increasing collaboration between research mentors and career development educators for PhD and postdoctoral training success.

National reports and funding mandates have called for trainee-centered PhD and postdoctoral training and the need to support diverse career outcomes. As a result, career and professional development (CPD) resources have expanded at several institutions. Despite the growth of innovative and impactful CPD resources, access to and awareness of resources have been inconsistent and inequitable for graduate and postdoctoral trainees.

A structured professional development curriculum for postdoctoral fellows leads to recognized knowledge growth.

Postdoctoral training enables research independence and professional readiness. National reports have emphasized professional development as a critical component of this training period. In response, many institutions are establishing transferable skills training workshops for postdocs; however, the lack of structured programs and an absence of methods to assess outcomes beyond participant satisfaction surveys are critical gaps in postdoctoral training.

Remote Learning Barriers and Opportunities for Graduate Student and Postdoctoral Learners in Career and Professional Skill Development: A Case Study.

Career and professional development competencies are critical for biomedical PhD and postdoctoral training. In the current educational landscape, programs that meet these competencies are offered and attended in an ad hoc manner. During the COVID-19 pandemic and the accompanying switch to virtual learning, our team observed a surge in interest for our weekly nonsequential programs.

Inherent variability in airway characteristics of simulation manikins: is it time we standardised assessments of crisis management skills?

Introduction: Learning of simulation-based crisis management skills involves technologically advanced manikins and use of automated scenarios. Progressions in preprogrammed scenarios require finite task completion such as successful airway intubations for achieving optimal learning outcomes aligned to curricular goals. The study was set to explore the existing variability among various simulation manikins in use at our institute for undergraduate medical education.

One year of sitagliptin treatment protects against islet amyloid-associated β-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice.

The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve β-cell mass. However, sitagliptin also increases β-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated β-cell toxicity.

Matrix metalloproteinase-9 reduces islet amyloid formation by degrading islet amyloid polypeptide.

Deposition of islet amyloid polypeptide (IAPP) as amyloid is a pathological hallmark of the islet in type 2 diabetes, which is toxic to β-cells. We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby reduces β-cell apoptosis, by inhibiting fibril formation. Two other enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, are extracellular gelatinases capable of degrading another amyloidogenic peptide, Aβ, the constituent of amyloid deposits in Alzheimer disease.

cis- and trans-acting localization determinants of pH response regulator Rim13 in Saccharomyces cerevisiae.

The Rim101/PacC pathway governs adaptation to alkaline pH in many fungi. Output of the pathway is mediated by transcription factors of the Rim101/PacC family, which are activated by proteolytic cleavage. The proteolytic complex includes scaffold protein Rim20 and endosome-associated subunits of the endosomal sorting complex required for transport (ESCRT).

β-cell loss and β-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition.

Amyloid deposition and reduced β-cell mass are pathological hallmarks of the pancreatic islet in type 2 diabetes; however, whether the extent of amyloid deposition is associated with decreased β-cell mass is debated. We investigated the possible relationship and, for the first time, determined whether increased islet amyloid and/or decreased β-cell area quantified on histological sections is correlated with increased β-cell apoptosis. Formalin-fixed, paraffin-embedded human pancreas sections from subjects with (n = 29) and without (n = 39) diabetes were obtained at autopsy (64 ± 2 and 70 ± 4 islets/subject, respectively).

Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes.

Interleukin 1β (IL-1β) is an important inflammatory mediator of type 2 diabetes. Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1β. One therapy for type 2 diabetes, glyburide, suppressed IAPP-mediated IL-1β production in vitro.

Neprilysin impedes islet amyloid formation by inhibition of fibril formation rather than peptide degradation.

Deposition of islet amyloid polypeptide (IAPP) as islet amyloid in type 2 diabetes contributes to loss of beta-cell function and mass, yet the mechanism for its occurrence is unclear. Neprilysin is a metallopeptidase known to degrade amyloid in Alzheimer disease. We previously demonstrated neprilysin to be present in pancreatic islets and now sought to determine whether it plays a role in degrading islet amyloid.

Intervention of Bro1 in pH-responsive Rim20 localization in Saccharomyces cerevisiae.

Yeast cells contain two Bro1 domain proteins: Bro1, which is required for endosomal trafficking, and Rim20, which is required for the response to the external pH via the Rim101 pathway. Rim20 associates with endosomal structures under alkaline growth conditions, when it promotes activation of Rim101 through proteolytic cleavage. We report here that the pH-dependent localization of Rim20 is contingent on the amount of Bro1 in the cell.

Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3.

The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches.

Second primary malignancy risk in thyroid cancer survivors: a systematic review and meta-analysis.

Objective: To determine the risk of second primary malignancies (SPMs) in thyroid cancer survivors.

Design: We performed a systematic review and meta-analysis examining the standardized incidence ratios (SIRs) of SPMs in thyroid cancer survivors (compared to individuals without thyroid cancer). Two independent reviewers screened citations and reviewed all full-text papers deemed potentially relevant.

Falcipain cysteine proteases require bipartite motifs for trafficking to the Plasmodium falciparum food vacuole.

The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 hydrolyze hemoglobin in an acidic food vacuole to provide amino acids for erythrocytic malaria parasites. Trafficking to the food vacuole has not been well characterized. To study trafficking of falcipains, which include large membrane-spanning prodomains, we utilized chimeras with portions of the proteases fused to green fluorescent protein.

Pbn1p: an essential endoplasmic reticulum membrane protein required for protein processing in the endoplasmic reticulum of budding yeast.

PBN1 was identified as a gene required for production of protease B (PrB) activity in Saccharomyces cerevisiae. PBN1 encodes an endoplasmic reticulum (ER)-localized, type I membrane glycoprotein and is essential for cell viability. To study the essential function(s) of Pbn1p, we constructed a strain with PBN1 under control of the GAL promoter.

The Sec1/Munc18 protein, Vps33p, functions at the endosome and the vacuole of Saccharomyces cerevisiae.

The Sec1/Munc18 (SM) family of proteins is thought to impart compartmental specificity to vesicle fusion reactions. Here we report characterization of Vps33p, an SM family member previously thought to act exclusively at the vacuolar membrane with the vacuolar syntaxin Vam3p. Vacuolar morphology of vps33Delta cells resembles that of cells lacking both Vam3p and the endosomal syntaxin Pep12p, suggesting that Vps33p may function with these syntaxins at the vacuole and the endosome.