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Found 34783 matches. Displaying 51-60
Bredbenner K
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One Ph. D., hold the pastries

SCIENCE 2019 JUL 5; 365(6448):94-94
Estrogens receptors (ER) are involved in several sociosexual behaviors and fear responses. In particular, the ER alpha is important for sexual behaviors, whereas ER beta modulates anxiolytic responses. Using shRNA directed either against the ER alpha or the ER beta RNAs (or containing luciferase control) encoded within an adeno-associated viral vector, we silenced these receptors in the ventromedial nucleus of the hypothalamus (VMN) and the central amygdala (CeA). We exposed ovariectomized female rats, sequentially treated with estradiol benzoate and progesterone, to five stimuli, previously reported to elicit positive and negative affect. The subjects were housed in groups of 4 females and 3 males in a seminatural environment for several days before hormone treatment. We analyzed the frequency of a large number of behavior patterns. In addition, we performed analyses of co-occurrence in order to detect changes in the structure of behavior after infusion of the vectors. Silencing the ER alpha in the VMN disrupted lordosis and showed some anxiolytic properties in aversive situations, whereas silencing of the ER beta in this structure had no effect. This was also the case after silencing the ER alpha in the CeA. Silencing of the ER beta in this structure increased risk assessment, an expression of anxiety, and increased olfactory exploration of the environment. We hypothesize that the ER beta in the CeA has an important role in the well-established anxiolytic effects of estrogens, and that it may modulate arousal level. Furthermore, it seems that the ER alpha in the VMN is anxiogenic in aversive or threatening situations, in agreement with other studies.
Wang WS, Ishibashi J, Trefely S, Shao ML, Cowan AJ, Sakers A, Lim HW, O'Connor S, Doan MT, Cohen P, Baur JA, King MT, Veech RL, Won KJ, Rabinowitz JD, Snyder NW, Gupta RK, Seale P
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A PRDM16-Driven Metabolic Signal from Adipocytes Regulates Precursor Cell Fate

CELL METABOLISM 2019 JUL 2; 30(1):174-189.e5
The precursor cells for metabolically beneficial beige adipocytes can alternatively become fibrogenic and contribute to adipose fibrosis. We found that cold exposure or beta 3-adrenergic agonist treatment of mice decreased the fibrogenic profile of precursor cells and stimulated beige adipocyte differentiation. This fibrogenic-to-adipogenic transition was impaired in aged animals, correlating with reduced adipocyte expression of the transcription factor PRDM16. Genetic loss of Prdm16 mimicked the effect of aging in promoting fibrosis, whereas increasing PRDM16 in aged mice decreased fibrosis and restored beige adipose development. PRDM16-expressing adipose cells secreted the metabolite beta-hydroxybutyrate (BHB), which blocked precursor fibrogenesis and facilitated beige adipogenesis. BHB catabolism in precursor cells, mediated by BDH1, was required for beige fat differentiation in vivo. Finally, dietary BHB supplementation in aged animals reduced adipose fibrosis and promoted beige fat formation. Together, our results demonstrate that adipocytes secrete a metabolite signal that controls beige fat remodeling.
Fava VM
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Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and

Type-1 reactions (T1R) are pathological inflammatory episodes and main
Poyhonen L, Bustamante J, Casanova JL, Jouanguy E, Zhang Q
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Life-Threatening Infections Due to Live-Attenuated Vaccines: Early Manifestations of Inborn Errors of Immunity (vol 39, pg 376, 2019)

Kobayashi M
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AGO CLIP Reveals an Activated Network for Acute Regulation of Brain

CELL REPORTS 2019 JUL 23; 28(4):979-991.e6
Post-transcriptional regulation by microRNAs (miRNAs) is essential for
Frew JW
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Lack of photographic documentation undermines assessment of hidradenitis suppurativa phenotypes: reply from the author

Linked Article: Albrecht et al. Br J Dermatol 2019; 180:749-55.
Perea-Gomez A
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Loss of Cubilin, the intrinsic factor-vitamin B12 receptor, impairs

SCIENTIFIC REPORTS 2019 JUL 15; 9(?):? Article 10168
The visceral endoderm is a polarized epithelial monolayer necessary for
Farfara D, Feierman E, Richards A, Revenko AS, MacLeod RA, Norris EH, Strickland S
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Knockdown of circulating C1 inhibitor induces neurovascular impairment, glial cell activation, neuroinflammation, and behavioral deficits

GLIA 2019 JUL; 67(7):1359-1373
The cross-talk between blood proteins, immune cells, and brain function involves complex mechanisms. Plasma protein C1 inhibitor (C1INH) is an inhibitor of vascular inflammation that is induced by activation of the kallikrein-kinin system (KKS) and the complement system. Knockout of C1INH was previously correlated with peripheral vascular permeability via the bradykinin pathway, yet there was no evidence of its correlation with blood-brain barrier (BBB) integrity and brain function. In order to understand the effect of plasma C1INH on brain pathology via the vascular system, we knocked down circulating C1INH in wild-type (WT) mice using an antisense oligonucleotide (ASO), without affecting C1INH expression in peripheral immune cells or the brain, and examined brain pathology. Long-term elimination of endogenous C1INH in the plasma induced the activation of the KKS and peritoneal macrophages but did not activate the complement system. Bradykinin pathway proteins were elevated in the periphery and the brain, resulting in hypotension. BBB permeability, extravasation of plasma proteins into the brain parenchyma, activation of glial cells, and elevation of pro-inflammatory response mediators were detected. Furthermore, infiltrating innate immune cells were observed entering the brain through the lateral ventricle walls and the neurovascular unit. Mice showed normal locomotion function, yet cognition was impaired and depressive-like behavior was evident. In conclusion, our results highlight the important role of regulated plasma C1INH as it acts as a gatekeeper to the brain via the neurovascular system. Thus, manipulation of C1INH in neurovascular disorders might be therapeutically beneficial.
Simunovic M, Metzger JJ, Etoc F, Yoney A, Ruzo A, Martyn L, Croft G, You DS, Brivanlou AH, Siggia ED
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A 3D model of a human epiblast reveals BMP4-driven symmetry breaking

NATURE CELL BIOLOGY 2019 JUL; 21(7):900-910
Breaking the anterior-posterior symmetry in mammals occurs at gastrulation. Much of the signalling network underlying this process has been elucidated in the mouse; however, there is no direct molecular evidence of events driving axis formation in humans. Here, we use human embryonic stem cells to generate an in vitro three-dimensional model of a human epiblast whose size, cell polarity and gene expression are similar to a day 10 human epiblast. A defined dose of BMP4 spontaneously breaks axial symmetry, and induces markers of the primitive streak and epithelial-to-mesenchymal transition. We show that WNT signalling and its inhibitor DKK1 play key roles in this process downstream of BMP4. Our work demonstrates that a model human epiblast can break axial symmetry despite the absence of asymmetry in the initial signal and of extra-embryonic tissues or maternal cues. Our three-dimensional model is an assay for the molecular events underlying human axial symmetry breaking.