Environmental exposure to common pesticide induces synaptic deficit and social memory impairment driven by neurodevelopmental vulnerability of hippocampal parvalbumin interneurons.

Environmental exposure to pesticides at levels deemed safe by regulatory agencies has been linked to increased risk for neurodevelopmental disorders. Yet, the mechanisms linking exposure to these disorders remain unclear. Here, we show that maternal exposure to the pesticide deltamethrin (DM) at the no observed adverse effect level (NOAEL) disrupts long-term potentiation (LTP) in the hippocampus of adult male offspring three months after exposure, a phenotype absent in female offspring.

Microbial determinants of dementia risk in subjects of Mexican descent with type 2 diabetes living in South Texas.

Type 2 diabetes (T2D) is a common forerunner of neurodegeneration and dementia, including Alzheimer's Disease (AD), yet the underlying mechanisms remain unresolved. Individuals of Mexican descent living in South Texas have increased prevalence of comorbid T2D and early onset AD, despite low incidence of the predisposing APOE-e4 variant and an absence of the phenotype among relatives residing in Mexico - suggesting a role for environmental factors in coincident T2D and AD susceptibility. Here, in a small clinical trial, we show dysbiosis of the human gut microbiome could contribute to neuroinflammation and risk for AD in this population.

Monospecies probiotic preparation and administration with downstream analysis of sex-specific effects on gut microbiome composition in mice.

Dysbiosis of the gut microbiome is implicated in the growing burden of non-communicable chronic diseases, including neurodevelopmental disorders, and both preclinical and clinical studies highlight the potential for precision probiotic therapies in their prevention and treatment. Here, we present an optimized protocol for the preparation and administration of Limosilactobacillus reuteri MM4-1A (ATCC-PTA-6475) to adolescent mice. We also describe steps for performing downstream analysis of metataxonomic sequencing data with careful assessment of sex-specific effects on microbiome composition and structure.

Diet-induced dysbiosis of the maternal gut microbiome in early life programming of neurodevelopmental disorders.

The maternal gut microbiome plays a critical role in fetal and early postnatal development, shaping fundamental processes including immune maturation and brain development, among others. Consequently, it also contributes to fetal programming of health and disease. Over the last decade, epidemiological studies and work in preclinical animal models have begun to uncover a link between dysbiosis of the maternal gut microbiome and neurodevelopmental disorders in offspring.

A study of innate immune kinetics reveals a role for a chloride transporter in a virulent Francisella tularensis type B strain.

Tularemia is a zoonotic disease of global proportions. Francisella tularensis subspecies tularensis (type A) and holarctica (type B) cause disease in healthy humans, with type A infections resulting in higher mortality. Repeated passage of a type B strain in the mid-20th century generated the Live Vaccine Strain (LVS).

Polynucleotide phosphorylase promotes the stability and function of Hfq-binding sRNAs by degrading target mRNA-derived fragments.

In many Gram-negative and some Gram-positive bacteria, small regulatory RNAs (sRNAs) that bind the RNA chaperone Hfq have a pivotal role in modulating virulence, stress responses, metabolism and biofilm formation. These sRNAs recognize transcripts through base-pairing, and sRNA-mRNA annealing consequently alters the translation and/or stability of transcripts leading to changes in gene expression. We have previously found that the highly conserved 3'-to-5' exoribonuclease polynucleotide phosphorylase (PNPase) has an indispensable role in paradoxically stabilizing Hfq-bound sRNAs and promoting their function in gene regulation in Escherichia coli.

Polynucleotide phosphorylase: Not merely an RNase but a pivotal post-transcriptional regulator.

Almost 60 years ago, Severo Ochoa was awarded the Nobel Prize in Physiology or Medicine for his discovery of the enzymatic synthesis of RNA by polynucleotide phosphorylase (PNPase). Although this discovery provided an important tool for deciphering the genetic code, subsequent work revealed that the predominant function of PNPase in bacteria and eukaryotes is catalyzing the reverse reaction, i.e.

Poly(A) polymerase is required for RyhB sRNA stability and function in .

Small regulatory RNAs (sRNAs) are an important class of bacterial post-transcriptional regulators that control numerous physiological processes, including stress responses. In Gram-negative bacteria including , the RNA chaperone Hfq binds many sRNAs and facilitates pairing to target transcripts, resulting in changes in mRNA transcription, translation, or stability. Here, we report that poly(A) polymerase (PAP I), which promotes RNA degradation by exoribonucleases through the addition of poly(A) tails, has a crucial role in the regulation of gene expression by Hfq-dependent sRNAs.

Alcohol Consumption and Incident Stroke Among Older Adults.

Objectives: This study examines the relationship between alcohol consumption and incident stroke among older adults and tests whether alcohol consumption contributes to observed race and sex differences in stroke.

Method: Data are from a U.S.