Deficiency of Capicua disrupts bile acid homeostasis

Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type 1 and cancer in mammals; however, the in vivo physiological functions of CIC remain largely unknown. Here we show that Cic hypomorphic (Cic-L-/-) mice have impaired bile acid (BA) homeostasis associated with induction of proinflammatory cytokines. We discovered that several drug metabolism and BA transporter genes were down-regulated in Cic-L-/- liver, and that BA was increased in the liver and serum whereas bile was decreased within the gallbladder of Cic-L-/- mice. We also found that levels of proinflammatory cytokine genes were up-regulated in Cic-L-/- liver. Consistent with this finding, levels of hepatic transcriptional regulators, such as hepatic nuclear factor 1 alpha (HNF1 alpha), CCAAT/enhancer-binding protein beta (C/EBP beta), forkhead box protein A2 (FOXA2), and retinoid X receptor alpha (RXR alpha), were markedly decreased in Cic-L-/- mice. Moreover, induction of tumor necrosis factor alpha (Tnf alpha) expression and decrease in the levels of FOXA2, C/EBP beta, and RXRa were found in Cic-L-/- liver before BA was accumulated, suggesting that inflammation might be the cause for the cholestasis in Cic-L-/- mice. Our findings indicate that CIC is a critical regulator of BA homeostasis, and that its dysfunction might be associated with chronic liver disease and metabolic disorders.open11810Ysciescopu

Selective complexation of divalent cations by a cyclic α,β-peptoid hexamer: a spectroscopic and computational study

We describe the qualitative and quantitative analysis of the complexation properties towards cations of a cyclic peptoid hexamer composed of alternating α- and β-peptoid monomers, which bear exclusively chiral (S)-phenylethyl side chains (spe) that have no noticeable chelating properties. The binding of a series of monovalent and divalent cations was assessed by 1H NMR, circular dichroism, fluorescence and molecular modelling. In contrast to previous studies on cations binding by 18-membered α-cyclopeptoid hexamers, the 21-membered cyclopeptoid cP1 did not complex monovalent cations (Na+, K+, Ag+) but showed selectivity for divalent cations (Ca2+, Ba2+, Sr2+ and Mg2+). Hexacoordinated C-3 symmetrical complexes were demonstrated for divalent cations with ionic radii around 1 Å (Ca2+ and Ba2+), while 5-coordination is preferred for divalent cations with larger (Ba2+) or smaller ionic radii (Mg2+)

Serum amyloid A inhibits RANKL-induced osteoclast formation

When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast-associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor 8). Moreover, SAA decreased c-fms expression on the cell surface via shedding of the c-fms extracellular domain. SAA also restrained the fusion of osteoclast precursors by blocking intracellular ATP release. This inhibitory response of SAA is not mediated by the well-known SAA receptors (formyl peptide receptor 2, Toll-like receptor 2 (TLR2) or TLR4). These findings provide insight into a novel inhibitory role of SAA in osteoclastogenesis and suggest that SAA is an important endogenous modulator that regulates bone homeostasis.open

Visual masking: past accomplishments, present status, future developments

Visual masking, throughout its history, has been used as an investigative tool in exploring the temporal dynamics of visual perception, beginning with retinal processes and ending in cortical processes concerned with the conscious registration of stimuli. However, visual masking also has been a phenomenon deemed worthy of study in its own right. Most of the recent uses of visual masking have focused on the study of central processes, particularly those involved in feature, object and scene representations, in attentional control mechanisms, and in phenomenal awareness. In recent years our understanding of the phenomenon and cortical mechanisms of visual masking also has benefited from several brain imaging techniques and from a number of sophisticated and neurophysiologically plausible neural network models. Key issues and problems are discussed with the aim of guiding future empirical and theoretical research

A Place to Rest Your (Burnt) Bones? Mortuary Houses in Early Anglo-Saxon England

This is an Accepted Manuscript of an article published by Taylor & Francis in Archaeological Journal on 5th October 2017, available online: doi: 10.1080/00665983.2017.1366704This article presents a fresh interpretation of square and rectangular mortuary structures found in association with deposits of cremated material and cremation burials in a range of early Anglo-Saxon (fifth-/sixth-century AD) cemeteries across southern and eastern England. Responding to a recent argument that they could be traces of pyre structures, a range of ethnographic analogies are drawn upon, and the full-range of archaeological evidence is synthesized, to re-affirm and extend their interpretation as unburned mortuary structures. Three interleaving significances are proposed: (i) demarcating the burial place of specific individuals or groups from the rest of the cemetery population, (ii) operating as ‘columbaria’ for the above-ground storage of the cremated dead (i.e. not just to demarcate cremation burials), and (iii) providing key nodes of commemoration between funerals as the structures were built, used, repaired and eventually decayed within cemeteries. The article proposes that timber ‘mortuary houses’ reveal that groups in early Anglo-Saxon England perceived their cemeteries in relation to contemporary settlement architectures, with some groups constructing and maintaining miniaturized canopied buildings to store and display the cremated remains of the dead

Design of A Crop-appropriate Irrigation System for Digital Agriculture During the Pandemic, Crisis of Public Health

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