Application of C-Terminal Clostridium Perfringens Enterotoxin in Treatment of Brain Metastasis from Breast Cancer.

Claudin-4 is part of the Claudin family of transmembrane tight junction (TJ) proteins found in almost all tissues and, together with adherens junctions and desmosomes, forms epithelial and endothelial junctional complexes. Although the distribution of Claudin-4 occurs in many cell types, the level of expression is cell-specific. Claudin proteins regulate cell proliferation and differentiation by binding cell-signaling ligands, and its expression is upregulated in several cancers. As a result, alterations in Claudin expression patterns or distribution are vital in the pathology of cancer. Profiling the genetic expression of Claudin-4 showed that Claudin-4 is also a receptor for the clostridium perfringens enterotoxin (CPE) and that Claudin-4 has a high sequence similarity with CPE's high-affinity receptor. CPE is cytolytic due to its ability to form pores in cellular membranes, and CPE treatment in breast cancer cells have shown promising results due to the high expression of Claudin-4. The C-terminal fragment of CPE (c-CPE) provides a less toxic alternative for drug delivery into breast cancer cells, particularly metastatic tumors in the brain, especially as Claudin-4 expression in the central nervous system (CNS) is low. Therefore, c-CPE provides a unique avenue for the treatment of breast-brain metastatic tumors.

COVID-19 Incidence and Mortality in Long-Term Care Facilities in Tennessee.

Background: Coronavirus Disease 2019, COVID-19, a viral infection, responsible for the latest pandemic has been shown to particularly affect the older population. Older adults, those aged 65 years and older, and individuals with serious underlying medical conditions are at a higher risk for severe illness from COVID-19 with a greater likelihood for hospitalization, admittance to the intensive care unit (ICU), and mortality. In this article, we describe the incidence and mortality rate found in Long Term Care facilities (LTCFs) and delineate any variations observed across varying types of LTCFs in the state of Tennessee (TN). Methods: Using aggregated data from the Tennessee (TN) Department of Health on COVID-19 Cases and Deaths from June 2020 to November 2021, we compare and contrast the incidence and fatality of COVID-19 among Long Term Care Facilities (LTCFs) in TN and describe the trends observed in these settings. Results: Our study indicates that there were major variations in COVID-19 prevalence rates in Nursing Homes (NHs) - 49% versus Assisted Care Living Facilities (ACLFs) in TN -16%. Although COVID-19 prevalence rates differed for NH and ACLFs, 12% of infected residents died in NHs while 13% of infected residents died in ACLFs. (Odds Ratio [OR]: 1.08 95% Confidence Interval [CI]: 0.93 -1.3, z-score: 1.37, p value: 0.085). Cases were more prevalent in five counties namely Davidson, Shelby, Hamilton, Knox, and Rutherford, majority of which were Metropolitan. Conclusion: As new variants continue to appear, counties with higher prevalence of COVID-19 should take continued effort to protect both resident and staff members especially in NHs settings and Metropolitan cities, where prevalence rate of the illness is higher.

Glial Expression of the Caenorhabditis elegans Gene swip-10 Supports Glutamate Dependent Control of Extrasynaptic Dopamine Signaling.

Glial cells play a critical role in shaping neuronal development, structure, and function. In a screen for Caenorhabditis elegans mutants that display dopamine (DA)-dependent, Swimming-Induced Paralysis (Swip), we identified a novel gene, swip-10, the expression of which in glia is required to support normal swimming behavior. swip-10 mutants display reduced locomotion rates on plates, consistent with our findings of elevated rates of presynaptic DA vesicle fusion using fluorescence recovery after photobleaching. In addition, swip-10 mutants exhibit elevated DA neuron excitability upon contact with food, as detected by in vivo Ca(2+) monitoring, that can be rescued by glial expression of swip-10. Mammalian glia exert powerful control of neuronal excitability via transporter-dependent buffering of extracellular glutamate (Glu). Consistent with this idea, swip-10 paralysis was blunted in mutants deficient in either vesicular Glu release or Glu receptor expression and could be phenocopied by mutations that disrupt the function of plasma membrane Glu transporters, most noticeably glt-1, the ortholog of mammalian astrocytic GLT1 (EAAT2). swip-10 encodes a protein containing a highly conserved metallo-ß-lactamase domain, within which our swip-10 mutations are located and where engineered mutations disrupt Swip rescue. Sequence alignments identify the CNS-expressed gene MBLAC1 as a putative mammalian ortholog. Together, our studies provide evidence of a novel pathway in glial cells regulated by swip-10 that limits DA neuron excitability, DA secretion, and DA-dependent behaviors through modulation of Glu signaling.