Why should early-career scientists publish in society journals.

In this editorial, written by early-career scientists, we advocate for the invaluable role of society journals in our scientific community. By choosing to support these journals as authors, peer reviewers, and as editors, we can reinforce our academic growth and benefit from their re-investment back into the scientific ecosystem. Considering the numerous clear merits of this system for future generations of microbiologists and more broadly, society, we argue that early-career researchers should publish our high-quality research in society journals to shape the future of science and scientific publishing landscape.

Re-Envisioning the Culture of Undergraduate Biology Education to Foster Black Student Success: A Clarion Call.

The purpose of this paper is to present an argument for why there is a need to re-envision the underlying culture of undergraduate biology education to ensure the success, retention, and matriculation of Black students. The basis of this argument is the continued noted challenges with retaining Black students in the biological sciences coupled with existing research that implicates science contexts (i.e., the cultural norms, values, and beliefs manifesting through policies and practices) as being the primary source of the challenges experienced by Black students that lead to their attrition. In presenting this argument, we introduce the Re-Envisioning Culture Network, a multigenerational, interdisciplinary network comprised of higher education administrators, faculty, staff, Black undergraduate students majoring in biology, Black cultural artists, community leaders, and STEM professionals to work together to curate and generate resources and tools that will facilitate change. In introducing the REC Network and disseminating its mission and ongoing endeavors, we generate a clarion call for educators, researchers, STEM professionals, students, and the broader community to join us in this endeavor in fostering transformative change.

Computational Modeling of Virally-encoded Ion Channel Structure.

Viroporins are ion channels encoded within a virus's genome, that facilitate a range of devastating infectious diseases such as COVID-19, HIV, and rotavirus. The non-structural protein 4 (NSP4) from rotavirus includes a viroporin domain that disrupts cellular Ca2+ homeostasis, initiating viral replication, and leading to life-threatening vomiting and diarrhea. Though the structure of soluble segments of NSP4 has been determined, membrane-associated regions, including the viroporin domain, remain elusive when utilizing well-established available experimental methods such as x-ray crystallography. However, two recently published protein folding algorithms, AlphaFold2 and trRosetta, demonstrated a high degree of accuracy, when determining the structure of membrane proteins from their primary amino acid sequences, though their training datasets are known to exclude proteins from viral systems. We tested the ability of these non-viral algorithms to predict functional molecular structures of the full-length NSP4 from SA11 rotavirus. We also compared the accuracy of these structures to predictions of other experimental structures of eukaryotic proteins from the Protein Data Banks (PDB), and show that the algorithms predict models more similar to corresponding experimental data than what we saw for the viroporin structure. Our data suggest that while AlphaFold2 and trRosetta each produced distinct NSP4 models, constructs based on either model showed viroporin activity when expressed in E. coli, consistent with that seen from other historical NSP4 sequences.

Rotavirus infection induces glycan availability to promote ileum-specific changes in the microbiome aiding rotavirus virulence.

Multiple studies have identified changes within the gut microbiome in response to diarrheal-inducing bacterial pathogens. However, examination of the microbiome in response to viral pathogens remains understudied. Compounding this, many studies use fecal samples to assess microbiome composition; which may not accurately mirror changes within the small intestine, the primary site for most enteric virus infections. As a result, the functional significance of small intestinal microbiome shifts during infection is not well defined. To address these gaps, rotavirus-infected neonatal mice were examined for changes in bacterial community dynamics, host gene expression, and tissue recovery during infection. Profiling bacterial communities using 16S rRNA sequencing suggested significant and distinct changes in ileal communities in response to rotavirus infection, with no significant changes for other gastrointestinal (GI) compartments. At 1-d post-infection, we observed a loss in Lactobacillus species from the ileum, but an increase in Bacteroides and Akkermansia, both of which exhibit mucin-digesting capabilities. Concomitant with the bacterial community shifts, we observed a loss of mucin-filled goblet cells in the small intestine at d 1, with recovery occurring by d 3. Rotavirus infection of mucin-producing cell lines and human intestinal enteroids (HIEs) stimulated release of stored mucin granules, similar to in vivo findings. In vitro, incubation of mucins with Bacteroides or Akkermansia members resulted in significant glycan degradation, which altered the binding capacity of rotavirus in silico and in vitro. Taken together, these data suggest that the response to and recovery from rotavirus-diarrhea is unique between sub-compartments of the GI tract and may be influenced by mucin-degrading microbes.

A role for Toll-like receptor 3 variants in host susceptibility to enteroviral myocarditis and dilated cardiomyopathy.

The innate antiviral response is mediated, at least in part, by Toll-like receptors (TLRs). TLR3 signaling is activated in response to viral infection, and the absence of TLR3 in mice significantly increases mortality after infection with enteroviruses that cause myocarditis and/or dilated cardiomyopathy. We screened TLR3 in patients diagnosed with enteroviral myocarditis/cardiomyopathy and identified a rare variant in one patient as well as a significantly increased occurrence of a common polymorphism compared with controls. Expression of either variant resulted in significantly reduced TLR3-mediated signaling after stimulation with synthetic double-stranded RNA. Furthermore, Coxsackievirus B3 infection of cell lines expressing mutated TLR3 abrogated activation of the type I interferon pathway, leading to increased viral replication. TLR3-mediated type I interferon signaling required cellular autophagy and was suppressed by 3-methyladenine and bafilomycin A1, by inhibitors of lysosomal proteolysis, and by reduced expression of Beclin 1, Atg5, or microtubule-associated protein 1 light chain 3beta (MAP1LC3beta). However, TLR3-mediated signaling was restored upon exogenous expression of Beclin 1 or a variant MAP1LC3beta fusion protein refractory to RNA interference. These data suggest that individuals harboring these variants may have a blunted innate immune response to enteroviral infection, leading to reduced viral clearance and an increased risk of cardiac pathology.