Publications by authors named "Pablo A Alvarez"

Tens of thousands of severe COVID-19 cases are hospitalized weekly in the U.S., often driven by an imbalance between antiviral responses and inflammatory signaling, leading to uncontrolled cytokine secretion.

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Several alphaviruses bypass the blood-brain barrier (BBB), causing debilitating or fatal encephalitis. Sindbis virus (SINV) has been extensively studied to understand alphavirus neuropathogenesis; yet the molecular details of neuroinvasion at the BBB remain poorly understood. We investigated alphavirus-BBB interactions by pairing a physiologically relevant, human pluripotent stem cell derived model of brain microvascular endothelial cells (BMECs) with SINV strains of opposite neuroinvasiveness.

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Botulinum neurotoxins (BoNTs) are valuable tools to unveil molecular mechanisms of exocytosis in neuronal and non-neuronal cells due to their peptidase activity on exocytic isoforms of SNARE proteins. They are produced by Clostridia as single-chain polypeptides that are proteolytically cleaved into light, catalytic domains covalently linked via disulfide bonds to heavy, targeting domains. This format of two subunits linked by disulfide bonds is required for the full neurotoxicity of BoNTs.

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Article Synopsis
  • The selective transport of proteins to lysosomes in epididymal cells can occur through mannose-6-phosphate receptors or sortilin, with some lysosomal proteins being secreted into the lumen by unknown methods.
  • In a study using RCE-1 epididymal cell lines, researchers found that knocking down sortilin changed the expression and behavior of lysosomal proteins like cathepsin D and prosaposin.
  • The knock-down of sortilin led to increased CD-MPR levels as a compensatory response, suggesting that this pathway is important for understanding how lysosomal proteins are transported and their potential role in exocytosis within the epididymis.
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The type III secretion system (T3SS) is an appendage used by many bacterial pathogens, such as pathogenic Yersinia, to subvert host defenses. However, because the T3SS is energetically costly and immunogenic, it must be tightly regulated in response to environmental cues to enable survival in the host. Here we show that expression of the Yersinia Ysc T3SS master regulator, LcrF, is orchestrated by the opposing activities of the repressive H-NS/YmoA histone-like protein complex and induction by the iron and oxygen-regulated IscR transcription factor.

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Article Synopsis
  • Yersinia pseudotuberculosis and Yersinia pestis require a type III secretion system (T3SS) to evade immune defenses and cause disease, but its expression needs careful regulation due to its link to growth arrest and immune recognition.
  • The expression of T3SS in Y. pseudotuberculosis is low in anaerobic, iron-rich conditions typical of the intestines, but increases in aerobic or iron-poor conditions faced when they encounter immune cells.
  • The transcription factor IscR regulates T3SS expression by responding to oxygen and iron levels, and its binding to the lcrF promoter is crucial for virulence; this regulatory mechanism is conserved in both Y. pseudotuberculosis and Y. pest
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Exploration is one of most basic adaptive behavioural responses, giving the animal an important evolutionary advantage to survive in a changing environment. Inspection of novel environments might be come with motivated exploratory behaviour. In spite that this type of exploration in the rat is known for many years, little attention has been given to the intrinsic mechanisms or the brain structures that are involved in.

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