In December of 2019, an outbreak of a novel coronavirus flared in Wuhan, the capital city of the Hubei Province, China. The pathogen has been identified as a novel enveloped RNA beta-coronavirus ...named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus SARS-CoV-2 is associated with a disease characterized by severe atypical pneumonia known as coronavirus 2019 (COVID-19). Typical symptoms of this disease include cough, fever, malaise, shortness of breath, gastrointestinal symptoms, anosmia, and, in severe cases, pneumonia.1 The high-risk group of COVID-19 patients includes people over the age of 60 years as well as people with existing cardiovascular disease and/or diabetes mellitus. Epidemiological investigations have suggested that the outbreak was associated with a live animal market in Wuhan. Within the first few months of the outbreak, cases were growing exponentially all over the world. The unabated spread of this deadly and highly infectious virus is a health emergency for all nations in the world and has led to the World Health Organization (WHO) declaring a pandemic on March 11, 2020. In this report, we consolidate and review the available clinically and preclinically relevant results emanating from in vitro animal models and clinical studies of drugs approved for emergency use as a treatment for COVID-19, including remdesivir, hydroxychloroquine, and lopinavir-ritonavir combinations. These compounds have been frequently touted as top candidates to treat COVID-19, but recent clinical reports suggest mixed outcomes on their efficacies within the current clinical protocol frameworks.
The different (sur)faces of Rap1p Piña, B; Fernández-Larrea, J; García-Reyero, N ...
Molecular genetics and genomics : MGG
268, Številka:
6
Journal Article
Recenzirano
The DNA-binding protein Rap1p fulfills many different functions in the yeast cell. It targets 5% of the promoters, acting both as a transcriptional activator and as a repressor, depending on the DNA ...sequence context. In addition, Rap1p is an essential structural component of yeast telomeres, where it contributes to telomeric silencing. Here we review the evidence indicating that Rap1p function is modulated by the precise architecture of the its binding site and its surroundings: long tracts of telomeric repeats for telomeric functions, specific sequences and orientation for maximal transcriptional activation, and specific DNA recognition sequences for complementary factors in other cases. Many of these functions are probably related to chromatin organization around Rap1p DNA binding sites, resulting from the very tight binding of Rap1p to DNA. We propose that Rap1p alters its structure to bind to different versions of its DNA binding sequence. These structural changes may modulate the function of Rap1p domains, providing different interacting surfaces for binding to specific co-operating factors, and thus contributing to the diversity of Rap1p function.
The Patient Acceptable Symptom State (PASS) is the value beyond which patients consider themselves well. Our aim was to determine the PASS estimate for patients with AS by assessing pain, disease ...activity and functional impairment and evaluate whether the PASS is stable over time.
A 4-week prospective study of patients with AS was carried-out. The PASS was estimated at week 2 and 4 for the following patient reported outcomes: global and nocturnal pain measured on a visual analogue scale, disease activity (BASDAI), and functional impairment (BASFI). We used an anchoring method based on patients answering yes or no to, 'is your current condition satisfactory, when you take your general functioning and your current pain into consideration?' The PASS was defined as the 75th percentile of the score for patients who considered their state satisfactory. Pearson's chi square and binary logistic regression were used to analyse the data.
A total of 200 patients were recruited of whom 110 (55%) were in PASS. The PASS estimates were 60 mm for global pain, 40 mm for night pain, 4.0 for BASDAI and 4.3 for BASFI. These PASS values were stable over time for all criteria except for pain. Significant contributors to PASS were low functional impairment (BASFI; p<0.001), low pain intensity (p=0.02), intensive physical activity (p=0.004) and high educational level (p=0.01).
A high percentage of Moroccan patients with AS (55%) reported being in PASS. PASS threshold for pain was unexpectedly high, possibly suggesting a high level of patients' tolerance to pain.
This work dealt with a modeling and a PQ theory-based control of a vehicle-to-grid (V2G) three-phase battery electric vehicle (BEV) charger. This studied system consists of a bidirectional ac-dc ...three-phase power converter associated with an EV battery pack via an LC filter. The control of the studied system is performed in order to meet all control objectives, namely: (i) Guaranteeing a unity power factor (UPF) during the grid-to-vehicle (G2V) operating mode; (ii) Regulating the reactive power injected during the V2G operating mode; and (iii) Ensuring the battery charging and the battery discharging, safely. To achieve all these objectives, a backstepping controller using the PQ theory has been designed. Therefore, an imbricate-loops structure has been adopted to regulate the reactive power injected into the power grid and to ensure the charging and discharging of the battery. The achievement of all the objectives of the proposed nonlinear controller was confirmed by numerical simulations performed using the MATLAB/Simulink software.
This paper deals with the problem of controlling an interleaved buck converter (IBC) associated with a Proton Exchange Membrane Electrolyzer (PEM-EL) used in electrical energy storage applications. ...The control objective is to regulate the electrolyzer voltage to its reference and to ensure an asymptotic stability of the closed loop system. The point is that the internal voltage of the double layer charge capacitor of the electrolyzer is not accessible for measurement. So, an output feedback controller, combining an observer and a sliding mode controller (SMC), is developed. The observer is also used to estimate all inductor currents of the IBC making the solution cheaper and more reliable. It is shown using a formal analysis and numerical simulations, that the proposed output feedback controller meets all control objectives.
The applications of the Salient-Pole permanent magnet synchronous motor (PMSM) increase greatly due to their advantages such as high efficiency, high power factor, higher power density, high inertia ...torque ratio and long life on other types kinds of motors such as DC motors and induction motors. The present work deals with the problem of controlling Salient-Pole PMSM for traction in hybrid vehicles. The control objectives are twofold: i) tight regulation of the rotation speed motor to its desired value whatever the road profile, ii) asymptotic stability of the closed loop system. To this end, a Backstepping technique is used. It is shown using formal analysis and simulations that the proposed controller perfectly achieves all the control objectives.
The yeast transcriptional regulator Rap1p binds to the DNA consensus sequence ACACCCAYACAYYY. We have previously shown that DNA-binding sites in which all four Y (Y=T or C) positions were Ts (UASrpg ...sequences) synergized more efficiently to activate transcription than sequences in which all Ys were Cs (telomere sequences) F.-Z. Idrissi, J. Fernández-Larrea and B. Piña (1998) J. Mol. Biol. 284, 925-935. Here we provide evidence that the DNA consensus sequence for Rap1p behaves as a combination of two ACAYYY half-sites with different functionality, the presence of Ts in the second half-site being the determinant for the transcriptional behaviour of the UASrpg sequences. DNA structure in the different complexes with Rap1p varied from being relatively uniform to appear rather distorted, this also being dependent on the presence of Ts in the second half-site. These distortions did not cause sharp bends or kinks in the DNA molecule. Computer analysis suggests that high-affinity binding of Rap1p to UASrpg sequences requires a rearrangement of the C-terminal Myb domain of the protein. We propose that the structural alterations in Rap1p-DNA complexes, both in the DNA and in the protein, affect the transcription potential of the complex in an allosteric manner. We also propose that the dimeric nature of the Rap1 DNA-binding domain is a key structural feature that explains the disparate functions of its DNA-binding sites in vivo.
Genetic analysis of endocytosis in yeast early pointed to the essential role of actin in the uptake step. Efforts to identify the machinery involved demonstrated the important contribution of Arp2/3 ...and the myosins-I. Analysis of the process using live-cell fluorescence microscopy and electron microscopy have recently contributed to refine molecular models explaining clathrin and actin-dependent endocytic uptake. Increasing evidence now also indicates that actin plays important roles in post-internalization events along the endocytic pathway in yeast, including transport of vesicles, motility of endosomes and vacuole fusion. This review describes the present knowledge state on the roles of actin in endocytosis in yeast and points to similarities and differences with analogous processes in mammals.
Performances of the DS synthetic breed of sheep (50% D’man and 50% Sardi genes) were compared to those of the contemporary parental breeds using records collected between 1998 and 2000. Results from ...reproductive traits showed that breeds differed for weight at breeding, litter size at birth and at 90 days, and litter weight at birth (
P<0.01), but were similar for fertility, litter weight at 90 days and gestation length (
P>0.05). Performances of DS ewes were, in general, intermediate to those of the parental breeds. DS ewes were lower than the average of the parental breeds for weight at mating by 3%, litter size at birth by 0.9%, litter size at 90 days by 3.5%, and litter weight at birth by 10.2%. Milk production during the 2-month lactation was identical for Sardi, D’man, and DS breeds (
P>0.05). DS lambs were intermediate to those of D’man and Sardi lambs for weight at birth, 30 and 90 days, whereas preweaning growth was higher. DS lambs were 9.4% lighter at birth but 0.6 and 2.3% heavier at 30 and 90 days than the average of the parental D’man and Sardi breeds. Likewise, carcass characteristics of DS lambs were close to those of the best parental breed. Lamb survival to 90 days, fattening growth and feed efficiency did not differ among breeds (
P>0.05). It was concluded that the DS synthetic breed could be considered as a purebred flock or maternal breed for market lamb production.
Introduction: Les paragangliomes sont de rares tumeurs neuroendocrines de ladulte, le plus souvent benignes, developpees aux depens du systeme nerveux autonome le long des axes vasculaires majeurs. ...Localises le plus frequemment au niveau cervico-facial, ils representent 0,6% des tumeurs de cette region. Le diagnostic est le plus souvent porte par la clinique evocatrice et le bilan dimagerie radiologique. La radiotherapie est une option therapeutique majeure des paragangliomes, particulierement pour les tumeurs inextirpables, permettant un bon controle de la maladie tout en evitant la iatrogenicite de la chirurgie. Materiel et Methode: Nous rapportons les resultats dune etude retrospective de 06 patients ayant ete pris en charge pour un paragangliome inoperable de la tete et du cou entre 2017 et 2020 au service donco-radiotherapie de lHopital dOnco-Hematologie du CHU de Marrakech. Resultats : La moyenne dage des patients etait de 59 ans avec des extremes allant de 41 a 88 ans, avec un sex ratio a 1. Le tableau clinique etait domine par les acouphenes et bourdonnements doreille (66%), lhypoacousie, la paralysie faciale et les troubles de la deglutition (50%). Dautres symptomes etaient retrouves a type dotorragies, otalgies pulsatiles, algies faciale (33%). A lexamen clinique etaient retrouves le plus souvent une masse parotidienne et une paralysie faciale (50%). Les symptomes rapportes etaient apparus dans un delai allant de 06 mois a 13 ans precedant la consultation. Le diagnostic a ete pose par le bilan dimagerie realise chez la quasi-totalite de nos patients (83%) : une tomodensitometrie chez 66% des patients, une imagerie par resonance magnetique chez 66% des patients, couplee a une sequence dangiographie chez une patiente. La localisation la plus frequente etait le foramen jugulaire (66%), une extension a langle ponto-cerebelleux etait retrouvee dans 50% des cas, et au niveau de los petreux dans 50% des cas. Une biopsie de la tumeur a ete realisee chez un patient, ayant permis une confirmation du diagnostic par une etude anatomopathologique et immunohistochimique. Lextension loco-regionale importante a indique une radiotherapie conformationnelle exclusive a la dose de 54 Gy en fractionnement habituel de 2 Gy par seance. Cinq patients (83%) ont reçu la totalite de leur traitement. Une diminution de la symptomatologie a ete obtenue chez lensemble des patients traites notamment une diminution des troubles neurosensoriels, ainsi quune stabilisation de levolution de la maladie. Une patiente a ete perdue de vue. Il na pas ete rapporte de complications importantes ou de sequelles de traitement par radiotherapie. Discussion et Conclusion: Grace aux nouvelles avancees technologiques, la radiotherapie externe conventionnelle constitue une excellente alternative therapeutique a la chirurgie dans le traitement des paragangliomes de la tete et du cou, offrant un taux de controle local au moins equivalent avec un faible profil de toxicite. Les donnees publiees concernant la radiotherapie stereotaxique et la protontherapie pour cette localisation suggerent des resultats encore plus prometteurs. Davantage de recul et de publications permettraient dasseoir definitivement la place preponderante de ces techniques dans larsenal therapeutique des paragangliomes benins de la tete et du cou.
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