266 research outputs found
Lower Liassic Formations of the Central High-Atlas near Rich (Morocco) : lithostratigraphic
Dans le Haut-Atlas central (Maroc) entre Midelt et Er-Rachidia affleure une épaisse série du Lias inférieur,
organisĂ©e en 3 formations successives : a) la formation dâIdikel, b) la formation de lâAberdouz et c) la formation de
lâOuchbis. Les variations latĂ©rales de faciĂšs et lâusage abusif de la nomenclature des formations posent beaucoup de
problĂšmes dâapplication et de corrĂ©lation. Certains auteurs ont essayĂ© de rĂ©duire le nombre de formations alors que
dâautres ont crĂ©Ă© de nouvelles formations simplement sur la base de variations latĂ©rales peu importantes. Ainsi, lâapplication
de la nomenclature prĂ©cĂ©dente sur une sĂ©rie liasique de la rĂ©gion de Foum Zidet nâest pas homogĂšne dâun auteur
Ă lâautre et peut par consĂ©quent conduire Ă des erreurs cartographiques, palĂ©obiogĂ©ographiques et de reconstitution des
Ă©tapes de lâĂ©volution du bassin. Pour remĂ©dier Ă ce problĂšme, nous proposons de :
1) subdiviser la formation dâIdikel de Studer [1980] en deux formations successives : la formation dâIdikel (partie
infĂ©rieure de Studer [1980]), laquelle sâorganise en une succession de cycles pĂ©ritidaux et comporte deux membres : a)
membre inférieur à dolomies, pseudomorphes de gypse et des calcaires et b) membre supérieur avec des calcaires dolomitiques
en gros bancs Ă fenestrae ;
2) dĂ©finir une nouvelle formation : la formation de Foum Zidet (partie supĂ©rieure de la formation dâIdikel de Studer
[1980]) avec trois membres successifs : a) membre inférieur formé par des calcaires bioclastiques à mollusques, brachiopodes
et spongiaires, b) membre médian à calcaires lités en petits bancs et c) membre supérieur à monticules de
spongiaires interdigités avec les calcaires lités. Vers le sud au tunnel de la Légion la formation de Foum Zidet est représentée
par des bioconstructions à hußtres et des calcaires lités ;
3) prĂ©ciser les caractĂ©ristiques de la formation de lâAberdouz, surtout au sens de variation latĂ©rale Ă proximitĂ© de
la plate-forme carbonatĂ©e oĂč celle-ci sâenrichit progressivement en intercalations calcaires oobioclastiques.
Cette nouvelle subdivision du Lias inférieur est cartographiable au 1/50 000 et traduit les étapes significatives de
lâĂ©volution du bassin haut-atlasique central : La formation dâIdikel ainsi redĂ©finie sâest dĂ©posĂ©e aprĂšs le stade de rifting
initial (Trias-Lias basal) à sédimentation détritique rouge et au cours de la premiÚre incursion marine à dépÎt carbonaté
(dolomies et calcaires du Sinémurien inférieur) et sous un climat aride (membre inférieur) à semi-aride (membre supérieur).
Dans un mileu pĂ©ritidal, lâĂ©paisseur de la formation dâIdikel traduit directement la subsidence centrĂ©e vers lâaxe
du bassin. La limite entre la formation dâIdikel et la formation de Foum Zidet correspond Ă un Ă©largissement du bassin
au cours dâun Ă©pisode de subsidence diffĂ©rentielle et de transgression majeure accompagnĂ©e de migration des organismes
marins. Les membres de la formation de Foum Zidet (essentiellement Sinémurien supérieur) reflÚtent les variations
palaéoocéanographiques (courants, influence des sédiments importés, cycles de nutrition) pendant un stade marin-eutrophique.
Vers le Pliensbachien et Ă la limite entre la formation de Foum Zidet et la formation de lâAberdouz, sâinstallent
des conditions biodétritiques/hémipélagiques et oligotrophes auxquelles succÚde un milieu hémipélagique, témoin des
cycles orbitaux de Milankovitch (formation de lâOuchbis)
Long-Range Modulation of Chain Motions within the Intrinsically Disordered Transactivation Domain of Tumor Suppressor p53
ABSTRACT: The tumor suppressor p53 is a hub protein with a multitude of binding partners, many of which target its intrinsically disordered N-terminal domain, p53-TAD. Partners, such as the N-terminal domain of MDM2, induce formation of local structure and leave the remainder of the domain apparently disordered. We investigated segmental chain motions in p53-TAD using fluorescence quenching of an extrinsic label by tryptophan in combination with fluorescence correlation spectroscopy (PET-FCS). We studied the loop closure kinetics of four consecutive segments within p53-TAD and their response to protein binding and phosphorylation. The kinetics was multiexponential, showing that the conformational ensemble of the domain deviates from random coil, in agreement with previous findings from NMR spectroscopy. Phosphorylations or binding of MDM2 changed the pattern of intrachain kinetics. Unexpectedly, we found that upon binding and phosphorylation chain motions were altered not only within the targeted segments but also in remote regions. Long-range interactions can be induced in an intrinsically disordered domain by partner proteins that induce apparently only local structure or by post-translational modification
Autochthonous hepatitis E as a cause of acute-on-chronic liver failure and death: histopathology can be misleading but transaminases may provide a clue.
Acute decompensation and death have been observed in patients with acute hepatitis E virus (HEV) infection and preexisting liver cirrhosis. However, the clinical, laboratory and histological features need to be fully characterised.
Some of us recently described the histological presentation of hepatitis E in a large panel of liver tissue specimens. Here, we conducted a case-control study to investigate the clinical and laboratory features of the subset of patients with HEV-related acute-on-chronic liver failure (ACLF) and death. Each patient was matched to three control patients with histologically confirmed severe alcoholic hepatitis based on sex, age, total bilirubin, INR, serum creatinine and MELD score on admission.
Of 5 patients who died in a context of HEV-related ACLF, 3 (60%) were male and the median age was 66 years (range 51–76). Median alanine aminotransferase (ALT) at presentation was 2610 U/l (range 705–3134) and aspartate aminotransferase (AST) 2818 U/l (range 1176–8611). Liver function was heavily altered in all patients. Histological analyses revealed steatohepatitis on a background of cirrhosis, suggestive of an alcoholic or nonalcoholic origin. Based on histopathology, alcoholic hepatitis was initially suspected in two patients and corticosteroid treatment was initiated. Ribavirin was started in four patients. Median time from hospitalisation to death was 17 days (range 6–25 days). AST levels in patients with HEV-related ACLF were significantly higher as compared to the matched patients with severe alcoholic hepatitis.
Typical histopathological features of viral hepatitis may be absent in ACLF caused by HEV infection. HEV infection should be sought in acute decompensation of cirrhosis and ACLF even in the absence of histological changes suggesting viral infection
Dominant Glint Based Prey Localization in Horseshoe Bats: A Possible Strategy for Noise Rejection
Rhinolophidae or Horseshoe bats emit long and narrowband calls. Fluttering insect prey generates echoes in which amplitude and frequency shifts are present, i.e. glints. These glints are reliable cues about the presence of prey and also encode certain properties of the prey. In this paper, we propose that these glints, i.e. the dominant glints, are also reliable signals upon which to base prey localization. In contrast to the spectral cues used by many other bats, the localization cues in Rhinolophidae are most likely provided by self-induced amplitude modulations generated by pinnae movement. Amplitude variations in the echo not introduced by the moving pinnae can be considered as noise interfering with the localization process. The amplitude of the dominant glints is very stable. Therefore, these parts of the echoes contain very little noise. However, using only the dominant glints potentially comes at a cost. Depending on the flutter rate of the insect, a limited number of dominant glints will be present in each echo giving the bat a limited number of sample points on which to base localization. We evaluate the feasibility of a strategy under which Rhinolophidae use only dominant glints. We use a computational model of the echolocation task faced by Rhinolophidae. Our model includes the spatial filtering of the echoes by the morphology of the sonar apparatus of Rhinolophus rouxii as well as the amplitude modulations introduced by pinnae movements. Using this model, we evaluate whether the dominant glints provide Rhinolophidae with enough information to perform localization. Our simulations show that Rhinolophidae can use dominant glints in the echoes as carriers for self-induced amplitude modulations serving as localization cues. In particular, it is shown that the reduction in noise achieved by using only the dominant glints outweighs the information loss that occurs by sampling the echo
Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains
Characterization of the length dependence of end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding of early steps in protein folding. Here, loop-closure in poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular dynamics simulation. For chains containing more than 10 peptide bonds loop-closing rate constants on the 20â100 nanosecond time range exhibit a power-law length dependence. However, this scaling breaks down for shorter peptides, which exhibit slower kinetics arising from a perturbation induced by the dye reporter system used in the experimental setup. The loop-closure kinetics in the longer peptides is found to be determined by the formation of intra-peptide hydrogen bonds and transient ÎČ-sheet structure, that accelerate the search for contacts among residues distant in sequence relative to the case of a polypeptide chain in which hydrogen bonds cannot form. Hydrogen-bond-driven polypeptide-chain collapse in unfolded peptides under physiological conditions found here is not only consistent with hierarchical models of protein folding, that highlights the importance of secondary structure formation early in the folding process, but is also shown to speed up the search for productive folding events
Single Molecule Conformational Memory Extraction: P5ab RNA Hairpin
Extracting kinetic models from single
molecule data is an important
route to mechanistic insight in biophysics, chemistry, and biology.
Data collected from force spectroscopy can probe discrete hops of
a single molecule between different conformational states. Model extraction
from such data is a challenging inverse problem because single molecule
data are noisy and rich in structure. Standard modeling methods normally
assume (i) a prespecified number of discrete states and (ii) that
transitions between states are Markovian. The data set is then fit
to this predetermined model to find a handful of rates describing
the transitions between states. We show that it is unnecessary to
assume either (i) or (ii) and focus our analysis on the zipping/unzipping
transitions of an RNA hairpin. The key is in starting with a very
broad class of non-Markov models in order to let the data guide us
toward the best model from this very broad class. Our method suggests
that there exists a folding intermediate for the P5ab RNA hairpin
whose zipping/unzipping is monitored by force spectroscopy experiments.
This intermediate would not have been resolved if a Markov model had
been assumed from the onset. We compare the merits of our method with
those of others
Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer
This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000âmgâmâ2 bid on days 1â14 and oxaliplatin 130âmgâmâ2 on day 1), followed by RT (1.8âGy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825âmgâmâ2 bid on days 22â35 and 43â56, and oxaliplatin 50âmgâmâ2 on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13â36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer
Wing pathology of white-nose syndrome in bats suggests life-threatening disruption of physiology
White-nose syndrome (WNS) is causing unprecedented declines in several species of North American bats. The characteristic lesions of WNS are caused by the fungus Geomyces destructans, which erodes and replaces the living skin of bats while they hibernate. It is unknown how this infection kills the bats. We review here the unique physiological importance of wings to hibernating bats in relation to the damage caused by G. destructans and propose that mortality is caused by catastrophic disruption of wing-dependent physiological functions. Mechanisms of disease associated with G. destructans seem specific to hibernating bats and are most analogous to disease caused by chytrid fungus in amphibians
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