Intraventricular 5,7-Dihydroxytryptamine Increases Thyrotropin-Releasing Hormone Content in Regions of Rat Brain

Rats received intraventricular (i.v.t.) injections of 5,7-dihydroxytryptamine (5,7-DHT) (100-600 micrograms). Some animals also received intraperitoneal injections of the 5-hydroxytryptamine uptake blocker fluoxetine (FX) (20 mg/kg) or the norepinephrine uptake blocker desmethylimipramine (DMI) (48 mg/kg) 30-90 min prior to i.v.t. 5,7-DHT. Rats were killed between 2 and 35 days following i.v.t. 5,7-DHT, brains were dissected, and regions were assayed for thyrotropin-releasing hormone (TRH) by radioimmunoassay. Dose-dependent increases in TRH content following i.v.t. 5,7-DHT were noted in the brainstem and hippocampus. DMI pretreatment blocked the increase in hippocampal TRH, but not in brainstem TRH. FX pretreatment was ineffective in blocking any increases in TRH content. These results suggest differential regulation of regional TRH content by interactions with specific neurotransmitter systems.     

Safety Evaluation of Lactobacillus delbrueckii subsp. lactis CIDCA 133: a Health-Promoting Bacteria

Probiotics and Antimicrobial Proteins - Lactobacillus delbrueckii subsp. lactis CIDCA is a new potential probiotic strain whose molecular basis attributed to the host’s benefit has been...     

Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease Model

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Agrobacterium tumefaciens divisome proteins regulate the transition from polar growth to cell division

The mechanisms that restrict peptidoglycan biosynthesis to the pole during elongation and re‐direct peptidoglycan biosynthesis to mid‐cell during cell division in polar‐growing Alphaproteobacteria are largely unknown. Here, we explore the role of early division proteins of Agrobacterium tumefaciens including three FtsZ homologs, FtsA and FtsW in the transition from polar growth to mid‐cell growth and ultimately cell division. Although two of the three FtsZ homologs localize to mid‐cell, exhibit GTPase activity and form co‐polymers, only one, FtsZ_AT, is required for cell division. We find that FtsZ_AT is required not only for constriction and cell separation, but also for initiation of peptidoglycan synthesis at mid‐cell and cessation of polar peptidoglycan biosynthesis. Depletion of FtsZ_AT in A. tumefaciens causes a striking phenotype: cells are extensively branched and accumulate growth active poles through tip splitting events. When cell division is blocked at a later stage by depletion of FtsA or FtsW, polar growth is terminated and ectopic growth poles emerge from mid‐cell. Overall, this work suggests that A. tumefaciens FtsZ makes distinct contributions to the regulation of polar growth and cell division.     

Design and development of a series of borocycles as selective,covalent kallikrein 5 inhibitors

The connection between Netherton syndrome and overactivation of epidermal/dermal proteases, particularly Kallikrein 5 (KLK5) has been well established and it is expected that a KLK5 inhibitor would improve the dermal barrier and also reduce the pain and itch that afflict Netherton syndrome patients. One of the challenges of covalent protease inhibitors has been achieving selectivity over closely related targets. In this paper we describe the use of structural insight to design and develop a selective and highly potent reversibly covalent KLK5 inhibitor from an initial weakly binding fragment.