Evolution of a self-renewing, participant-centered workshop series in BMB assessment.

We present as a case study the evolution of a series of participant-centered workshops designed to meet a need in the life sciences education community-the incorporation of best practices in the assessment of student learning. Initially, the ICABL (Inclusive Community for the Assessment of Biochemistry and Molecular Biology/BMB Learning) project arose from a grass-roots effort to develop material for a national exam in biochemistry and molecular biology. ICABL has since evolved into a community of practice in which participants themselves-through extensive peer review and reflection-become integral stakeholders in the workshops.

Development of a Certification Exam to Assess Undergraduate Students' Proficiency in Biochemistry and Molecular Biology Core Concepts.

With support from the American Society for Biochemistry and Molecular Biology (ASBMB), a community of biochemistry and molecular biology (BMB) scientist-educators has developed and administered an assessment instrument designed to evaluate student competence across four core concept and skill areas fundamental to BMB. The four areas encompass energy and metabolism; information storage and transfer; macromolecular structure, function, and assembly; and skills including analytical and quantitative reasoning. First offered in 2014, the exam has now been administered to nearly 4000 students in ASBMB-accredited programs at more than 70 colleges and universities.

Breathing new life into the rational design of Alzheimer's therapeutics.

γ-secretase is a promising therapeutic target for Alzheimer's disease, but all inhibitors and modulators have failed due to toxicity or low efficacy. In this issue of Cell, Yang et al. provide cryo-EM structures of γ-secretase bound to three inhibitors and a modulator, giving new promise to targeting γ-secretase therapeutically.

Meeting report: BioMolViz workshops for developing assessments of biomolecular visual literacy.

While molecular visualization has been recognized as a threshold concept in biology education, the explicit assessment of students' visual literacy skills is rare. To facilitate the evaluation of this fundamental ability, a series of NSF-IUSE-sponsored workshops brought together a community of faculty engaged in creating instruments to assess students' biomolecular visualization skills. These efforts expanded our earlier work in which we created a rubric describing overarching themes, learning goals, and learning objectives that address student progress toward biomolecular visual literacy.

APOE gene and neuropsychiatric disorders and endophenotypes: A comprehensive review.

The Apolipoprotein E (APOE) gene is one of the main candidates in neuropsychiatric genetics, with hundreds of studies carried out in order to explore the possible role of polymorphisms in the APOE gene in a large number of neurological diseases, psychiatric disorders, and related endophenotypes. In the current article, we provide a comprehensive review of the structural and functional aspects of the APOE gene and its relationship with brain disorders. Evidence from genome-wide association studies and meta-analyses shows that the APOE gene has been significantly associated with several neurodegenerative disorders.

An expanded framework for biomolecular visualization in the classroom: Learning goals and competencies.

A thorough understanding of the molecular biosciences requires the ability to visualize and manipulate molecules in order to interpret results or to generate hypotheses. While many instructors in biochemistry and molecular biology use visual representations, few indicate that they explicitly teach visual literacy. One reason is the need for a list of core content and competencies to guide a more deliberate instruction in visual literacy.

Loss of Nicastrin from Oligodendrocytes Results in Hypomyelination and Schizophrenia with Compulsive Behavior.

The biological underpinnings and the pathological lesions of psychiatric disorders are centuries-old questions that have yet to be understood. Recent studies suggest that schizophrenia and related disorders likely have their origins in perturbed neurodevelopment and can result from a large number of common genetic variants or multiple, individually rare genetic alterations. It is thus conceivable that key neurodevelopmental pathways underline the various genetic changes and the still unknown pathological lesions in schizophrenia.

Gamma-secretase-regulated proteolysis of the Notch receptor by mitochondrial intermediate peptidase.

Notch is a transmembrane receptor that controls a diverse array of cellular processes including cell proliferation, differentiation, survival, and migration. The cellular outcome of Notch signaling is dependent on extracellular and intracellular signals, but the complexities of its regulation are not well understood. Canonical Notch signaling involves ligand association that triggers sequential and regulated proteolysis of Notch at several sites.

Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia.

Progranulin (GRN) haploinsufficiency is a frequent cause of familial frontotemporal dementia, a currently untreatable progressive neurodegenerative disease. By chemical library screening, we identified suberoylanilide hydroxamic acid (SAHA), a Food and Drug Administration-approved histone deacetylase inhibitor, as an enhancer of GRN expression. SAHA dose-dependently increased GRN mRNA and protein levels in cultured cells and restored near-normal GRN expression in haploinsufficient cells from human subjects.

TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor.

TDP-43, or TAR DNA-binding protein 43, is a pathological marker of a spectrum of neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. TDP-43 is an RNA/DNA-binding protein implicated in transcriptional and posttranscriptional regulation. Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress.

Expression, localization, and biochemical characterization of nicotinamide mononucleotide adenylyltransferase 2.

Nicotinamide mononucleotide (NMN) adenylyltransferase 2 (Nmnat2) catalyzes the synthesis of NAD from NMN and ATP. The Nmnat2 transcript is expressed predominately in the brain; we report here that Nmnat2 is a low abundance protein expressed in neurons. Previous studies indicate that Nmnat2 localizes to Golgi.

Glu-333 of nicastrin directly participates in gamma-secretase activity.

gamma-Secretase is a proteolytic membrane complex that processes a variety of substrates including the amyloid precursor protein and the Notch receptor. Earlier we showed that one of the components of this complex, nicastrin (NCT), functions as a receptor for gamma-secretase substrates. A recent report challenged this, arguing instead that the Glu-333 residue of NCT predicted to participate in substrate recognition only participates in gamma-secretase complex maturation and not in activity per se.

Assembly, maturation, and trafficking of the gamma-secretase complex in Alzheimer's disease.

In this review, we discuss the biology of gamma-secretase, an enigmatic enzyme complex that is responsible for the generation of the amyloid-beta peptide that constitutes the amyloid plaques of Alzheimer's disease. We begin with a brief review on the processing of the amyloid precursor protein and a brief discussion on the family of enzymes involved in regulated intramembrane proteolysis, of which gamma-secretase is a member. We then identify the four major components of the gamma-secretase complex - presenilin, nicastrin, Aph-1, and Pen-2 - with a focus on the identification of each and the role that each plays in the maturation and activity of the complex.

Kinetic analysis of the interaction of the C1 domain of protein kinase C with lipid membranes by stopped-flow spectroscopy.

The diacylglycerol (DG)/phorbol ester-dependent translocation of conventional protein kinase C (PKC) isozymes is mediated by the C1 domain, a membrane-targeting module that also selectively binds phosphatidylserine (PS). Using stopped-flow spectroscopy, we dissect the contribution of DG/phorbol esters (C1 ligand) and PS in driving the association and dissociation of the C1 domain from membranes. Specifically, we examine the binding to membranes of the C1B domain of PKCbeta with a substituted Trp (Y123W) whose fluorescence is quenched upon binding to membranes.

A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production.

The C1 domain mediates the diacylglycerol (DAG)-dependent translocation of conventional and novel protein kinase C (PKC) isoforms. In novel PKC isoforms (nPKCs), this domain binds membranes with sufficiently high affinity to recruit nPKCs to membranes in the absence of any other targeting mechanism. In conventional PKC (cPKC) isoforms, however, the affinity of the C1 domain for DAG is two orders of magnitude lower, necessitating the coordinated binding of the C1 domain and a Ca2+-regulated C2 domain for translocation and activation.