Early Exposure of Medical Students to a Formal Research Program Promotes Successful Scholarship in a Multi-Campus Medical School.

Objectives: Many physicians today struggle to learn the complexities of the biological basis for evidence-based medicine. To bridge this gap, the Medical Scholar Research Pathway Program (MSRPP) founded in 2019 prepares medical students for analytical reasoning and critical thinking while engaging in faculty-mentored research projects in a community-based public medical school.

Methods: MSRPP is an application-based extracurricular research program, designed for novice and experienced medical students.

Correction to: Early Exposure of Medical Students to a Formal Research Program Promotes Successful Scholarship in a Multi-Campus Medical School.

[This corrects the article DOI: 10.1007/s40670-024-02098-6.].

Guiding Preclinical Medical Students in Finding, Synthesizing, and Communicating Translational Basic Research Literature: Roles for Basic Science Research Mentors.

Problem: Understanding and communicating medical advances driven by basic research, and acquiring foundational skills in critically appraising and communicating translational basic research literature that affects patient care, are challenging for medical students to develop.

Approach: The authors developed a mandatory course from 2012 to 2018 at Texas A&M University College of Medicine to address this problem. Medical Student Grand Rounds (MSGR) trains first-year students to find, critically assess, and present primary research literature about self-selected medically relevant topics.

Development of single-cell-level microfluidic technology for long-term growth visualization of living cultures of .

Analysis of growth and death kinetics at single-cell resolution is a key step in understanding the complexity of the nonreplicating growth phenotype of the bacterial pathogen . Here, we developed a single-cell-resolution microfluidic mycobacterial culture device that allows time-lapse microscopy-based long-term phenotypic visualization of the live replication dynamics of mycobacteria. This technology was successfully applied to monitor the real-time growth dynamics of the fast-growing model strain () while subjected to drug treatment regimens during continuous culture for 48 h inside the microfluidic device.

Desmoplakin interacts with the coil 1 of different types of intermediate filament proteins and displays high affinity for assembled intermediate filaments.

The interaction of intermediate filaments (IFs) with the cell-cell adhesion complexes desmosomes is crucial for cytoskeletal organization and cell resilience in the epidermis and heart. The intracellular desmosomal protein desmoplakin anchors IFs to the cell adhesion complexes predominantly via its four last carboxy-terminal domains (C-terminus). However, it remains unclear why the C-terminus of desmoplakin interacts with different IF types or if there are different binding affinities for each type of IFs that may influence the stability of cell-specific adhesion complexes.

Allostery revealed within lipid binding events to membrane proteins.

Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein-lipid assemblies. Despite this inherent complexity, the identification of specific protein-lipid interactions and the crucial role of lipids in the folding, structure, and function of membrane proteins is emerging from an increasing number of reports. Fundamental questions remain, however, regarding the ability of specific lipid binding events to membrane proteins to alter remote binding sites for lipids of a different type, a property referred to as allostery [Monod J, Wyman J, Changeux JP (1965) 12:88-118].

αB-crystallin is a sensor for assembly intermediates and for the subunit topology of desmin intermediate filaments.

Mutations in the small heat shock protein chaperone CRYAB (αB-crystallin/HSPB5) and the intermediate filament protein desmin, phenocopy each other causing cardiomyopathies. Whilst the binding sites for desmin on CRYAB have been determined, desmin epitopes responsible for CRYAB binding and also the parameters that determine CRYAB binding to desmin filaments are unknown. Using a combination of co-sedimentation centrifugation, viscometric assays and electron microscopy of negatively stained filaments to analyse the in vitro assembly of desmin filaments, we show that the binding of CRYAB to desmin is subject to its assembly status, to the subunit organization within filaments formed and to the integrity of the C-terminal tail domain of desmin.

Nebulette is a powerful cytolinker organizing desmin and actin in mouse hearts.

In the hearts of patients bearing nebulette mutations, a severe general disorganization in cardiomyocytes of the extrasarcomeric desmin intermediate filament system is frequently observed. However, the molecular and functional relationship between the desmin cytoskeleton and nebulette-containing sarcomeres is still unclear. Here we report a high-affinity in vitro interaction between nebulette and desmin filaments.

Nebulin binding impedes mutant desmin filament assembly.

Desmin intermediate filaments (DIFs) form an intricate meshwork that organizes myofibers within striated muscle cells. The mechanisms that regulate the association of desmin to sarcomeres and their role in desminopathy are incompletely understood. Here we compare the effect nebulin binding has on the assembly kinetics of desmin and three desminopathy-causing mutant desmin variants carrying mutations in the head, rod, or tail domains of desmin (S46F, E245D, and T453I).

The desmin coil 1B mutation K190A impairs nebulin Z-disc assembly and destabilizes actin thin filaments.

Desmin intermediate filaments intimately surround myofibrils in vertebrate muscle forming a mesh-like filament network. Desmin attaches to sarcomeres through its high-affinity association with nebulin, a giant F-actin binding protein that co-extends along the length of actin thin filaments. Here, we further investigated the functional significance of the association of desmin and nebulin in cultured primary myocytes to address the hypothesis that this association is key in integrating myofibrils to the intermediate filament network.

A myopathy-linked desmin mutation perturbs striated muscle actin filament architecture.

Desmin interacts with nebulin establishing a direct link between the intermediate filament network and sarcomeres at the Z-discs. Here, we examined a desmin mutation, E245D, that is located within the coil IB (nebulin-binding) region of desmin and that has been reported to cause human cardiomyopathy and skeletal muscle atrophy. We show that the coil IB region of desmin binds to C-terminal nebulin (modules 160-164) with high affinity, whereas binding of this desmin region containing the E245D mutation appears to enhance its interaction with nebulin in solid-phase binding assays.

Legionella pneumophila EnhC is required for efficient replication in tumour necrosis factor alpha-stimulated macrophages.

Legionella pneumophila enhC(-) mutants were originally identified as being defective for uptake into host cells. In this work, we found that the absence of EnhC resulted in defective intracellular growth when dissemination of intracellular bacteria to neighbouring cells was expected to occur. No such defect was observed during growth within the amoeba Dictyostelium discoideum.

Phosphatidylcholine synthesis is required for optimal function of Legionella pneumophila virulence determinants.

The function of phosphatidylcholine (PC) in the bacterial cell envelope remains cryptic. We show here that productive interaction of the respiratory pathogen Legionella pneumophila with host cells requires bacterial PC. Synthesis of the lipid in L.

The DotL protein, a member of the TraG-coupling protein family, is essential for Viability of Legionella pneumophila strain Lp02.

Legionella pneumophila is able to survive inside phagocytic cells by an internalization route that bypasses fusion of the nascent phagosome with the endocytic pathway to allow formation of a replicative phagosome. The dot/icm genes, a major virulence system of L. pneumophila, encode a type IVB secretion system that is required for intracellular growth.

The Legionella pneumophila LidA protein: a translocated substrate of the Dot/Icm system associated with maintenance of bacterial integrity.

Legionella pneumophila establishes a replication vacuole within phagocytes that requires the bacterial Dot/Icm apparatus for its formation. This apparatus is predicted to translocate effectors into host cells. We hypothesized that some translocated proteins also function to maintain the integrity of the Dot/Icm translocator.