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141.
The higher rate of non-synonymous over synonymous substitutions (dN/dS) of the X chromosome compared with autosomes is often interpreted as a consequence of X hemizygosity. However, other factors, such as gene expression, are also known to vary between X and autosomes. Analysing 4800 orthologues in six mammals, we found that gene expression levels, associated with GC content, fully account for the variation in dN/dS between X and autosomes with no detectable effect of hemizygosity. We also report an extensive variance in dN/dS and gene expression between autosomes. 相似文献
142.
Neurite growth acceleration of adult Dorsal Root Ganglion neurons illuminated by low‐level Light Emitting Diode light at 645 nm 下载免费PDF全文
Marion Burland Lambert Paris Patrice Quintana Jean‐Michel Bec Lucie Diouloufet Chamroeun Sar Hassan Boukhaddaoui Benoit Charlot Jefferson Braga Silva Michel Chammas Victor Sieso Jean Valmier Fabrice Bardin 《Journal of biophotonics》2015,8(6):480-488
The effect of a 645 nm Light Emitting Diode (LED) light irradiation on the neurite growth velocity of adult Dorsal Root Ganglion (DRG) neurons with peripheral axon injury 4–10 days before plating and without previous injury was investigated. The real amount of light reaching the neurons was calculated by taking into account the optical characteristics of the light source and of media in the light path. The knowledge of these parameters is essential to be able to compare results of the literature and a way to reduce inconsistencies. We found that 4 min irradiation of a mean irradiance of 11.3 mW/cm2 (corresponding to an actual irradiance reaching the neurons of 83 mW/cm2) induced a 1.6‐fold neurite growth acceleration on non‐injured neurons and on axotomized neurons. Although the axotomized neurons were naturally already in a rapid regeneration process, an enhancement was found to occur while irradiating with the LED light, which may be promising for therapy applications.
143.
Y‐craniosynostosis by premature fusion of the metopic and coronal sutures: A new nosological entity or a variety of Saethre‐Chotzen syndrome? 下载免费PDF全文
144.
Caryn S. Ross-Innes Irene Debiram-Beecham Maria O'Donovan Elaine Walker Sibu Varghese Pierre Lao-Sirieix Laurence Lovat Michael Griffin Krish Ragunath Rehan Haidry Sarmed S. Sami Philip Kaye Marco Novelli Babett Disep Richard Ostler Benoit Aigret Bernard V. North Pradeep Bhandari Adam Haycock Danielle Morris Stephen Attwood Anjan Dhar Colin Rees Matthew D. D. Rutter Peter D. Sasieni Rebecca C. Fitzgerald 《PLoS medicine》2015,12(1)
BackgroundBarrett''s esophagus (BE) is a commonly undiagnosed condition that predisposes to esophageal adenocarcinoma. Routine endoscopic screening for BE is not recommended because of the burden this would impose on the health care system. The objective of this study was to determine whether a novel approach using a minimally invasive cell sampling device, the Cytosponge, coupled with immunohistochemical staining for the biomarker Trefoil Factor 3 (TFF3), could be used to identify patients who warrant endoscopy to diagnose BE.ConclusionsThe Cytosponge-TFF3 test is safe and acceptable, and has accuracy comparable to other screening tests. This test may be a simple and inexpensive approach to identify patients with reflux symptoms who warrant endoscopy to diagnose BE. 相似文献
145.
Diana Moreira Vasco Rodrigues Maria Abengozar Luis Rivas Eduardo Rial Mireille Laforge Xiaoling Li Marc Foretz Benoit Viollet Jér?me Estaquier Anabela Cordeiro da Silva Ricardo Silvestre 《PLoS pathogens》2015,11(3)
Metabolic manipulation of host cells by intracellular pathogens is currently recognized to play an important role in the pathology of infection. Nevertheless, little information is available regarding mitochondrial energy metabolism in Leishmania infected macrophages. Here, we demonstrate that during L. infantum infection, macrophages switch from an early glycolytic metabolism to an oxidative phosphorylation, and this metabolic deviation requires SIRT1 and LKB1/AMPK. SIRT1 or LBK1 deficient macrophages infected with L. infantum failed to activate AMPK and up-regulate its targets such as Slc2a4 and Ppargc1a, which are essential for parasite growth. As a result, impairment of metabolic switch caused by SIRT1 or AMPK deficiency reduces parasite load in vitro and in vivo. Overall, our work demonstrates the importance of SIRT1 and AMPK energetic sensors for parasite intracellular survival and proliferation, highlighting the modulation of these proteins as potential therapeutic targets for the treatment of leishmaniasis. 相似文献
146.
Benoit Visseaux Charlotte Charpentier Gilles Collin Mélanie Bertine Gilles Peytavin Florence Damond Sophie Matheron Eric Lefebvre Fran?oise Brun-Vézinet Diane Descamps ANRS CO HIV- Cohort 《PloS one》2015,10(8)
Background
Maraviroc activity against HIV-2, a virus naturally resistant to different HIV-1 antiretroviral drugs, has been recently demonstrated. The aim of this study was to assess HIV-2 susceptibility to cenicriviroc, a novel, once-daily, dual CCR5 and CCR2 antagonist that has completed Phase 2b development in HIV-1 infection.Methods
Cenicriviroc phenotypic activity has been tested using a PBMC phenotypic susceptibility assay against four R5-, one X4- and one dual-tropic HIV-2 clinical primary isolates. All isolates were obtained by co-cultivation of PHA-activated PBMC from distinct HIV-2-infected CCR5-antagonist-naïve patients included in the French HIV-2 cohort and were previously tested for maraviroc susceptibility using the same protocol. HIV-2 tropism was determined by phenotypic assay using Ghost(3) cell lines.Results
Regarding the 4 R5 HIV-2 clinical isolates tested, effective concentration 50% EC50 for cenicriviroc were 0.03, 0.33, 0.45 and 0.98 nM, similar to those observed with maraviroc: 1.13, 0.58, 0.48 and 0.68 nM, respectively. Maximum percentages of inhibition (MPI) of cenicriviroc were 94, 94, 93 and 98%, similar to those observed with maraviroc (93, 90, 82, 100%, respectively). The dual- and X4-tropic HIV-2 strains were resistant to cenicriviroc with EC50 >1000 nM and MPI at 33% and 4%, respectively.Conclusions
In this first study assessing HIV-2 susceptibility to cenicriviroc, we observed an in vitro activity against HIV-2 R5-tropic strains similar to that observed with maraviroc. Thus, cenicriviroc may offer a once-daily treatment opportunity in the limited therapeutic arsenal for HIV-2. Clinical studies are warranted. 相似文献147.
148.
Marianne Suter Paolo Salvioni Ramon F Thali Roland Scholz Kari Vaahtomeri Yolanda Auchli Helene Rechsteiner René A Brunisholz Benoit Viollet Tomi P Mäkelä Theo Wallimann Dietbert Neumann Wilhelm Krek 《The EMBO journal》2010,29(2):469-481
The mobilization of metabolic energy from adipocytes depends on a tightly regulated balance between hydrolysis and resynthesis of triacylglycerides (TAGs). Hydrolysis is stimulated by β‐adrenergic signalling to PKA that mediates phosphorylation of lipolytic enzymes, including hormone‐sensitive lipase (HSL). TAG resynthesis is associated with high‐energy consumption, which when inordinate, leads to increased AMPK activity that acts to restrain hydrolysis of TAGs by inhibiting PKA‐mediated activation of HSL. Here, we report that in primary mouse adipocytes, PKA associates with and phosphorylates AMPKα1 at Ser‐173 to impede threonine (Thr‐172) phosphorylation and thus activation of AMPKα1 by LKB1 in response to lipolytic signals. Activation of AMPKα1 by LKB1 is also blocked by PKA‐mediated phosphorylation of AMPKα1 in vitro. Functional analysis of an AMPKα1 species carrying a non‐phosphorylatable mutation at Ser‐173 revealed a critical function of this phosphorylation for efficient release of free fatty acids and glycerol in response to PKA‐activating signals. These results suggest a new mechanism of negative regulation of AMPK activity by PKA that is important for converting a lipolytic signal into an effective lipolytic response. 相似文献
149.
150.
Humans have developed a particular innate immunity system against African trypanosomes, and only two Trypanosoma brucei clones (T. b. gambiense, T. b. rhodesiense) can resist this defence and cause sleeping sickness. The main players of this immunity are the primate‐specific apolipoprotein L‐I (apoL1) and haptoglobin‐related protein (Hpr). These proteins are both associated with two serum complexes, a minor subfraction of HDLs and an IgM/apolipoprotein A‐I (apoA1) complex, respectively, termed trypanosome lytic factor (TLF) 1 and TLF2. Although the two complexes appear to lyse trypanosomes by the same mechanism, they enter the parasite through various modes of uptake. In case of TLF1 one uptake process was characterized. When released in the circulation, haemoglobin (Hb) binds to Hpr, hence to TLF1. In turn the TLF1–Hpr–Hb complex binds to the trypanosome haptoglobin (Hp)–Hb receptor, whose original function is to ensure haem uptake for optimal growth of the parasite. This binding triggers efficient uptake of TLF1 and subsequent trypanosome lysis. While Hpr is involved as TLF ligand, the lytic activity is due to apoL1, a Bcl‐2‐like pore‐forming protein. We discuss the in vivo relevance of this uptake pathway in the context of other potentially redundant delivery routes. 相似文献