Evans syndrome caused by a deleterious mutation affecting the adaptor protein SASH3.

Increasing evidence suggests multilineage cytopenias (also known as Evans syndrome) may be caused by inborn errors of immunity (IEI) with immune dysregulation. We studied a patient with autoimmune haemolytic anaemia and immune thrombocytopenia and identified a germline mutation in SASH3 (c.862C>T;p.

Investigating evolutionary relationships through cluster analysis: A teaching science with big data workshop session.

Biochemistry is a data-heavy discipline, yet teaching students to work with large datasets is absent from many undergraduate Biochemistry programs. Ensuring that future generations of students arevbv confident in tackling problems using big data first requires that educators become comfortable teaching big data skills. The activity described herein introduces educators to working with big data and a framework for generating sequence similarity networks using JupyterLab and Python.

Case Report: Refractory Cytopenia With a Switch From a Transient Monosomy 7 to a Disease-Ameliorating del(20q) in a -Deficient Long-term Survivor.

We report the case of a male Pakistani patient with a pathogenic homozygous loss of function variant in the non-homologous end-joining factor 1 () gene. The growth retarded and microcephalic boy with clinodactyly of both hands and hyperpigmentation of the skin suffered from recurrent respiratory infections. He was five and a half years old when he came to our attention with refractory cytopenia and monosomy 7.

Modeling an Enzyme Active Site using Molecular Visualization Freeware.

Biomolecular visualization skills are paramount to understanding key concepts in the biological sciences, such as structure-function relationships and molecular interactions. Various programs allow a learner to manipulate 3D structures, and biomolecular modeling promotes active learning, builds computational skills, and bridges the gap between two dimensional textbook images and the three dimensions of life. A critical skill in this area is to model a protein active site, displaying parts of the macromolecule that can interact with a small molecule, or ligand, in a way that shows binding interactions.

Lung Ultrasound: The Essentials.

Although US of the lungs is increasingly used clinically, diagnostic radiologists are not routinely trained in its use and interpretation. Lung US is a highly sensitive and specific modality that aids in the evaluation of the lungs for many different abnormalities, including pneumonia, pleural effusion, pulmonary edema, and pneumothorax. This review provides an overview of lung US to equip the diagnostic radiologist with knowledge needed to interpret this increasingly used modality.

Integration of Point-of-Care Ultrasound Education Into the Internal Medicine Core Clerkship Experience.

Point-of-care ultrasound (POCUS) is becoming an essential skill for internists. To date, there are no professional guidelines for how POCUS skills should be taught to medical students. A panel of POCUS experts from seven academic medical centers in the United States was convened to describe the components of independently developed IM clerkship POCUS training programs, identify areas of similarity and difference, and propose recommendations for alignment.

Occurrence of autoimmune pancreatitis after chronic immune thrombocytopenia in a Caucasian adolescent.

Autoimmune pancreatitis is a rare, distinct and increasingly recognized form of chronic inflammatory pancreatic disease secondary to an underlying autoimmune mechanism. We report on a 14-year-old boy who developed autoimmune pancreatitis, while he was under treatment with eltrombopag for chronic immune thrombocytopenia. Therapy with corticosteroids resulted in complete remission of both.

SARS-CoV-2 virtual biochemistry labs on bioinformatics and drug design.

Colleges and universities are learning to provide relevant virtual lab experiences for students due to the COVID-19 pandemic. Even schools attempting in-person instruction often need to utilize virtual experiences for students absent due to quarantine or illness. Much of biochemistry is amenable to molecular visualization and/or computational study; however, many faculty face learning how to utilize new computational and molecular visualization software.

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.

De novo design of bioactive protein switches.

Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'.

The Procedure Coordinator: A Resident-Driven Initiative to Increase Opportunity for Inpatient Procedures.

Background: Training residents to become competent in common bedside procedures can be challenging. Some hospitals have attending physician-led procedure teams with oversight of all procedures to improve procedural training, but these teams require significant resources to establish and maintain.

Objective: We sought to improve resident procedural training by implementing a resident-run procedure team without routine attending involvement.

Proteolysis of truncated hemolysin A yields a stable dimerization interface.

Wild-type and variant forms of HpmA265 (truncated hemolysin A) from Proteus mirabilis reveal a right-handed, parallel β-helix capped and flanked by segments of antiparallel β-strands. The low-salt crystal structures form a dimeric structure via the implementation of on-edge main-chain hydrogen bonds donated by residues 243-263 of adjacent monomers. Surprisingly, in the high-salt structures of two variants, Y134A and Q125A-Y134A, a new dimeric interface is formed via main-chain hydrogen bonds donated by residues 203-215 of adjacent monomers, and a previously unobserved tetramer is formed.

Enhancing student retention of prerequisite knowledge through pre-class activities and in-class reinforcement.

To foster the connection between biochemistry and the supporting prerequisite concepts, a collection of activities that explicitly link general and organic chemistry concepts to biochemistry ideas was written and either assigned as pre-class work or as recitation activities. We assessed student learning gains after using these activities alone, or in combination with regularly-integrated clicker and discussion questions. Learning gains were determined from student performance on pre- and post-tests covering key prerequisite concepts, biochemistry course exams, and student self-evaluation.

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.

Plasma Decontamination: A Case Study on Kill Efficacy of Geobacillus stearothermophilus Spores on Different Carrier Materials.

Unlabelled: A new technology to the pharmaceutical field is presented: surface decontamination by plasmas The technology is comparable to established barrier systems like e-beam, volatile hydrogen peroxide, or radiation inactivation of microbiological contaminations. This plasma technology is part of a fully automated and validated syringe filling line at a major pharmaceutical company and is in production operation. Incoming pre-sterilized syringe containers ("tubs") are processed by plasma, solely on the outside, and passed into the aseptic filling isolator upon successful decontamination.

Sequential unfolding of the hemolysin two-partner secretion domain from Proteus mirabilis.

Protein secretion is a major contributor to Gram-negative bacterial virulence. Type Vb or two-partner secretion (TPS) pathways utilize a membrane bound β-barrel B component (TpsB) to translocate large and predominantly virulent exoproteins (TpsA) through a nucleotide independent mechanism. We focused our studies on a truncated TpsA member termed hemolysin A (HpmA265), a structurally and functionally characterized TPS domain from Proteus mirabilis.

Prediction of distal residue participation in enzyme catalysis.

A scoring method for the prediction of catalytically important residues in enzyme structures is presented and used to examine the participation of distal residues in enzyme catalysis. Scores are based on the Partial Order Optimum Likelihood (POOL) machine learning method, using computed electrostatic properties, surface geometric features, and information obtained from the phylogenetic tree as input features. Predictions of distal residue participation in catalysis are compared with experimental kinetics data from the literature on variants of the featured enzymes; some additional kinetics measurements are reported for variants of Pseudomonas putida nitrile hydratase (ppNH) and for Escherichia coli alkaline phosphatase (AP).

Cloning, expression, purification and characterization of an iron-dependent regulator protein from Thermobifida fusca.

Iron-dependent regulators (IdeRs) control the transcription of a variety of genes associated with iron homeostasis in Gram-positive bacteria. In this study we report the cloning of a putative IdeR gene from the moderate thermophile Thermobifida fusca into the pET-21a(+) expression vector. The expressed protein, Tf-IdeR, was purified using immobilized metal affinity and size-exclusion chromatography, and yielded approximately 12-16 mg of protein per liter of culture.

A bulky hydrophobic residue is not required to maintain the V-conformation of enzyme-bound thiamin diphosphate.

It is widely accepted that, in thiamin diphosphate (ThDP)-dependent enzymes, much of the rate acceleration is provided by the cofactor. Inter alia, the reactive conformation of ThDP, known as the V-conformation, has been attributed to the presence of a bulky hydrophobic residue located directly below the cofactor. Here we report the use of site-saturation mutagenesis to generate variants of this residue (Leu403) in benzoylformate decarboxylase.