Miracle-dz/UniFAR-FTUs huggingface dataset:
The response of T4 lysozyme to large‐to‐small substitutions within the core and its relation to the hydrophobic effect

To further examine the structural and thermodynamic basis of hydrophobic stabilization in proteins, all of the bulky non‐polar residues that are buried or largely buried within the core of T4 lysozyme were substituted with alanine. In 25 cases, including eight reported previously, it was possible to determine the crystal structures of the variants. The structures of four variants with double substitutions were also determined. In the majority of cases the “large‐to‐small” substitutions lead to internal cavities. In other cases declivities or channels open to the surface were formed. In some cases the structural changes were minimal (mainchain shifts ≤ 0.3 Å); in other cases mainchain atoms moved up to 2 Å. In the case of Ile 29 → Ala the structure collapsed to such a degree that the volume of the putative cavity was zero. Crystallographic analysis suggests that the occupancy of the engineered cavities by solvent is usually low. The mutants Val 149 → Ala (V149A) and Met 6 → Ala (M6A), however, are exceptions and have, respectively, one and two well‐ordered water molecules within the cavity. The Val 149 → Ala substitution allows the solvent molecule to hydrogen bond to polar atoms that are occluded in the wild‐type molecule. Similarly, the replacement of Met 6 with alanine allows the two solvent molecules to hydrogen bond to each other and to polar atoms on the protein. Except for Val 149 → Ala the loss of stability of all the cavity mutants can be rationalized as a combination of two terms. The first is a constant for a given class of substitution (e.g., − 2.1 kcal/mol for all Leu → Ala substitutions) and can be considered as the difference between the free energy of transfer of leucine and alanine from solvent to the core of the protein. The second term can be considered as the energy cost of forming the cavity and is consistent with a numerical value of 22 cal mol−1 Å−3, Physically, this term is due to the loss of van der Waal's interactions between the bulky sidechain that is removed and the atoms that form the wall of the cavity. The overall results are consistent with the prior rationalization of Leu → Ala mutants in T4 lysozyme by Eriksson et al. (Eriksson et al., 1992, Science 255:178‐183).
Survey of molecular determinants in Gram-positive cocci isolated from hospital settings in Argentina.

BACKGROUND In order to study the resistance mechanisms to aminoglycosides, tetracyclines and erythromycin, we investigated the genetic determinants on 85 Streptococcus spp. , Staphylococcus spp. , and Enterococcus spp. isolates collected from 46 hospitals of Argentina over a two-year period. METHODOLOGY The MICs to amikacin, gentamicin, kanamycin, and streptomycin, tetracycline and erythromycin were determined by the standard broth dilution method according to CLSI recommendations. Detection of resistance genes to the antibiotic tested was assessed by the PCR standard technique whereas the clonal relationships of each species was performed by PFGE. RESULTS Major heterogeneity was detected in aminoglycoside and erythromycin resistances. Indeed, 37.6% of the isolates harbored the aac(6')-aph(2'') genes; 27% harbored the aph(3')-IIIa and ant(6)-Ia genes along with the aac(6')-aph(2'') gene; 7% carried the ant(4')-Ia gene; and 71% harbored one or more of the erm(A), erm(B), erm(TR), mef(A), mef(E) and msr(A) genes. The tetracycline resistance was determined by the tet(M) gene and was found in 23 isolates that were resistant to this antibiotic. Spreading of tet(M) by the Tn916-like transposon was not a frequent event since the integrase of this element was detected only in 3 Streptococcus spp. isolates. Instead, a 370 bp fragment was detected that corresponded to a region of the CW459-like element integrase in 10 of 11 methicillin-resistant Staphylococcus aureus and in 3 group G Streptococcus isolates, a finding that implies a novel mechanism for tetracycline resistance spreading. CONCLUSION This study demonstrates the wide spreading of resistance mechanisms in our nosocomial cocci population and underscores the importance of continuous and efficient epidemiological surveillance.
A SysML based-methodology for modelling disturbances in manufacturing systems using ADACOR holonic control architecture

Nowadays, industrials are looking for models and methods that are not only capable to support efficient production performances, but also reactive systems facing an increasing set of unpredicted events and perturbations. For this reason, manufacturing control systems must include mechanisms that cope with the complexity and unpredictability related with disturbances and perturbations that may appear in the system. In this paper we propose a methodology based on SysML language and holonic architecture “ADACOR” for modelling the sources of disturbance and its management in manufacturing systems. In the proposed methodology we show how we use SysML diagrams to estimate the future performances in a reactive mode and how to switch between the scheduling and control in the case of unpredictability. In order to validate the proposed methodology, a case study has been conducted on a welding cell. As a result, we noticed that the unpredictable events are controlled in such a way that we assure a continuous production.
Impact of a treatment of Beauveria bassiana (Deuteromycota: Hyphomycetes) on honeybee (Apis mellifera) colony health and on Varroa destructor mites (Acari: Varroidae)

In 2 experiments bee colonies in southern France were treated with conidia of a Beauveria bassiana isolate collected from Varroa mites in the region. Objectives were to evaluate treatment effect on colony weight, adult bee mass, and capped brood and honey, and on Varroa fall onto sticky boards. Treatments included conidia formulated with either wax powder or wheat flour, flour alone, or control. Treatment did not affect colony health. Colonies treated with conidia and wax powder had higher mite fall compared to controls while those treated with conidia and wheat flour did not. The proportion fallen, infected mites in both conidia treatments was higher than controls for up to a week. Higher mite fall and infection rates were observed in treated hives in the 2nd, smaller experiment. The relationships between dosage and proportion fallen, infected mites, and between ambient temperature and infection duration, were examined. Future experiments will explore Varroa control using conidia.ZusammenfassungIn zwei Experimenten wurden Honigbienenvölker in Südfrankreich mit Konidiensporen eines aus Varroamilben der Region gesammelten Isolates behandelt. Ziel war die Erfassung der Auswirkung der Behandlung auf das Gewicht der Völker, das Gesamtgewicht an adulten Bienen, auf die verdeckelte Brut und auf die Honigmenge, sowie auf den Totenfall von Varroamilben auf klebrige Bodeneinlagen. Die Behandlungen umfassten Formulierungen von Konidiensporen entweder mit Wachspulver oder mit Weizenmehl, sowie Weizenmehl alleine und unbehandelte Kontrollvölker. Die Behandlungen hatten keinen Einfluss auf die Gesundheit der Bienenvölker. Die mit Konidiensporen und Wachspulver behandelten Völker hatten einen höheren Milbentotenfall als die Kontrollvölker, bei den mit Konidiensporen und Weizenmehl behandelten Völkern war dies nicht der Fall. Der Anteil an infizierten Milben im Totenfall war bei beiden Behandlungen mit Konidiensporen über den Zeitraum von etwa einer Woche höher als bei den Kontrollen. Ein erhöhter Milbentotenfall und erhöhte Infektionsraten wurden auch in dem zweiten, kleineren Experiment gefunden. Die Beziehung zwischen der Dosierung und dem Anteil infizierter Milben im Totenfall und zwischen der Umgebungstemperatur und der Infektionsdauer wurden untersucht. Zukünftige Experimente sollen die Möglichkeit einer Behandlung der Varroose mittels Konidiensporen untersuchen.
Mechanisms of programmed cell death signaling in hair cells and support cells post-electrode insertion trauma

Abstract Conclusion: Programmed cell death (PCD) initially starts in the support cells (SCs) after electrode insertion trauma (EIT), followed by PCD in hair cells (HCs). Activation of caspase-3 was observed only in SCs. Protecting both SCs and HCs with selective otoprotective drugs at an early stage post implantation may help to preserve residual hearing. Objectives: Cochlear implant EIT can initiate sensory cell losses via necrosis and PCD within the organ of Corti, which can lead to a loss of residual hearing. PCD appears to be a major factor in HC loss post-EIT. The current study aimed to: (1) determine the onset of PCD in both SCs and HCs within the traumatized organ of Corti; and (2) identify the molecular mechanisms active within the HCs and SCs that are undergoing PCD. Methods: Adult guinea pigs were assigned to one of two groups: (1) EIT and (2) unoperated contralateral ears as controls. Immunostaining of dissected organ of Corti surface preparations for phosphorylated-Jun, cleaved caspase-3, and 4-hydroxy-2,3-nonenal (HNE) were performed at 6, 12, and 24 h post-EIT and for contralateral control ears. Results: At 6 h post-EIT the SCs immunolabeled for the presence of phosphorylated-Jun and activated caspase-3. Phosphorylated p-Jun labeling was observed at 12 h in both the HCs and SCs of middle and basal cochlear turns. Cleaved caspase-3 was not observed in HCs of any cochlear turn at up to 24 h post-EIT. Lipid peroxidation (HNE immunostaining) was first observed at 12 h post-EIT in both the HCs and SCs of the basal turn, and reached the apical turn by 24 h post-EIT.
Genetic and environmental effects on conduct disorder and alcohol dependence symptoms and their covariation at age 14.

BACKGROUND Alcohol misuse and conduct disorder (CD) are strongly associated in adolescents. Is their association due to shared genetic and environmental liabilities? We addressed that question with data obtained from structured interviews of 14-year-old Finnish twins. METHODS A total of 1854 twins completed face-to-face interviews. Univariate models, allowing for sex limitation, were fit to symptom counts for Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised diagnoses of CD and alcoholism to examine their genetic and environmental influences. Then, bivariate models evaluated the extent to which genetic and environmental influences contributed to the covariation between symptom counts for the two disorders. RESULTS A total of 822 twins (44% of the sample) reported one or more symptoms of CD; alcohol dependence symptoms were much less common, reported by only 12%. The correlation between the two symptom counts was 0.50. Models fit to the twin data demonstrated that CD symptoms were under significant genetic influence in both boys and girls, although those influences were predominantly sex specific. In contrast, alcohol dependence symptoms were, at this age, under sex-specific effects of common environments, with no evidence of genetic influences. Accordingly, the substantial covariation between alcohol dependence symptoms and those of CD was attributed entirely to shared environmental effects. CONCLUSIONS At age 14, genetic influences on alcohol dependence symptoms are negligible, and the correlated liabilities between these symptoms and those of CD are to be found in environmental factors that are common to both.
Synthesis of a major integral membrane polypeptide of rat liver peroxisomes on free polysomes.

The manner of synthesis and assembly of the peroxisomal membrane proteins is unknown. Understanding these processes is essential to an understanding of the formation of the organelle. We have investigated the biogenesis of the previously identified major 21.7-kDa integral peroxisomal membrane polypeptide [Fujiki, Y. , Fowler, S. , Shio, H. , Hubbard, A. L. & Lazarow, P. B. (1982) J. Cell Biol. 93, 103-110]. This protein was purified to apparent homogeneity and used to elicit a rabbit antiserum. In immunoblotting analysis, antibody bound only to the 22-kDa membrane polypeptide present exclusively in peroxisomal membranes. Total rat liver RNA was translated in a nuclease-treated rabbit reticulocyte cell-free protein-synthesizing system. The in vitro translation product, isolated by means of the antibody and Staphylococcus aureus cells, comigrated with the mature 22-kDa polypeptide in NaDodSO4/PAGE. Analysis of the translation products of RNAs from free and membrane-bound polysomes indicated that the mRNA for the 22-kDa membrane polypeptide is found predominantly in free polysomes. The results imply post-translational insertion of the membrane polypeptide into the peroxisomal membrane without proteolytic processing and suggest that peroxisomes, like mitochondria and chloroplasts, form by fission from preexisting organelles.
A Layered Segmentation Algorithm of Fingerprint

Fingerprint image segmentation heavily influences the performance of fingerprint verification systems. The task of generic segmentation algorithm is only to find the background and the foreground. But the layered segmentation method in this paper is not only to distinguish the background and the foreground but also to be helpful for the matching of fingerprint by endowing different weight to the minutiae in different area. The traditional methods that usually use only one feature to segment diversified images are broadly introduced. In this paper, we introduce a new approach to segment the fingerprint image that uses both the information of gray level of fingerprint image and the direction information from fingerprint image. This approach can segment the fingerprint image to three kinds of area according to the definition of every block of image. The segmentation method described above has been tested on the fingerprint images from the FVC2004 database. The fingerprint is segmented to the background, the clear area of the foreground and the dim area which can be renewed in the foreground using different criteria of estimation in different steps. The effect of this segmentation achieves the anticipative aim that we want to get.
Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats

Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward‐related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain‐derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10 mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real‐time quantitative reverse transcription‐polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine‐treated rats exhibited more place conditioning as compared with saline‐treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine‐induced CPP significantly increased the number of Ki67 and DCX‐labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine‐induced reward‐related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context‐induced drug relapse.
Tachycardia evoked by disinhibition of the dorsomedial hypothalamus in rats is mediated through medullary raphe

Activation of neurons in the region of the dorsomedial hypothalamus (DMH) appears to generate the sympathetically mediated tachycardia seen in experimental stress in rats. The purpose of this study was to assess the role of neurons in the area of the medullary raphe pallidus (RP) in the tachycardia caused by stimulation of the DMH. The cardiovascular response to microinjection of the GABAA receptor antagonist bicuculline methiodide (BMI) 10 pmol (100 nl)−1 into the DMH was assessed before, and after, injection of the GABAA receptor agonist muscimol 80 pmol (100 nl)−1 or saline vehicle 100 nl into the RP in urethane‐anaesthetized rats. Tachycardia evoked by microinjection of BMI into the DMH was mimicked by microinjection of BMI 30 pmol (75 nl)−1 into the RP. This DMH‐induced tachycardia was markedly suppressed after injection of muscimol into the RP, but the response was unaffected by injection of saline into the same region. Thus, DMH‐induced tachycardia is mediated through activation of neurons in the area of the RP, suggesting that these neurons may play a previously unrecognized role in stress‐induced cardiac stimulation.
γ‐COP Appendage Domain – Structure and Function

COPI‐coated vesicles mediate retrograde transport from the Golgi back to the ER and intra‐Golgi transport. The cytosolic precursor of the COPI coat, the heptameric coatomer complex, can be thought of as composed of two subcomplexes. The first consists of the β‐, γ‐, δ‐ and ζ‐COP subunits which are distantly homologous to AP clathrin adaptor subunits. The second consists of the α‐, β′‐ and ε‐COP subunits. Here, we present the structure of the appendage domain of γ‐COP and show that it has a similar overall fold as the α‐appendage of AP2. Again, like the α‐appendage the γ‐COP appendage possesses a single protein/protein interaction site on its platform subdomain. We show that in yeast this site binds to the ARFGAP Glo3p, and in mammalian γ‐COP this site binds to a Glo3p orthologue, ARFGAP2. On the basis of mutations in the yeast homologue of γ‐COP, Sec21p, a second binding site is proposed to exist on the γ‐COP appendage that interacts with the α,β′,ε COPI subcomplex.
Multi-scale simulation of plant tissue deformation using a model for individual cell mechanics

We present a micro–macro method for the simulation of large elastic deformations of plant tissue. At the microscopic level, we use a mass–spring model to describe the geometrical structure and basic properties of individual plant cells. The macroscopic domain is discretized using standard finite elements, in which the macroscopic material properties (the stress–strain relation) are not given in analytical form, but are computed using the microscopic model in small subdomains, called representative volume elements (RVEs), centered around the macroscopic quadrature points. The boundary conditions for these RVEs are derived from the macroscopic deformation gradient. The computation of the macroscopic stress tensor is based on the definition of virial stress, as defined in molecular dynamics. The anisotropic Eulerian elasticity tensor is estimated using a forward finite difference approximation for the Truesdell rate of the Cauchy stress tensor. We investigate the influence of the size of the RVE and the boundary conditions. This multi-scale method converges to the solution of the full microscopic simulation, for both globally and adaptively refined finite element meshes, and achieves a significant speedup compared to the full microscopic simulation.
Use of residual feed intake as a selection criterion on the performance and relative development costs of replacement beef heifers

ABSTRACT Two heifers groups differing in residual feed intake (RFI) were compared with a third control (CON; n = 20) group of randomly selected heifers for performance, reproductive efficiency, and system economics to first calving and repeatability of RFI ranking, with all 3 groups selected from the same cohort. Following weaning, 70 Angus heifers (initial BW = 260 ± 3 kg; 6 mo of age) from a single cohort were fed a forage-based diet (10.0% CP; 65.2% TDN) for 93 d (period 1) where BW, DMI, ADG, G:F, and RFI were evaluated. After period 1 RFI testing, 40 heifers were classified into 2 groups [20 efficient heifers (low RFI; RFI = −1.01 ± 0.10 kg/d) and 20 inefficient heifers (high RFI; RFI = 0.77 ± 0.08 kg/d)] and then selected for a second feeding trial (period 2) and compared with the 20 CON heifers. All 60 heifers in period 2 (BW = 322 ± 2.9 kg; 10 mo of age) were fed for 93 d on a similar forage-based diet (11.0% CP; 66.5% TDN). Low-RFI heifers had the lowest (P = 0.01) RFI value of −0.33 kg/d, followed by CON and high-RFI heifers, −0.09 and 0.42 kg/d, respectively. Control heifers tended (P = 0.08) to have lower ADG (0.83 kg/d) compared with low-RFI (0.92 kg/d) or high-RFI heifers (0.91 kg/d), and low-RFI heifers tended (P = 0.08) to have greater G:F (0.10 ± 0.003) than either CON (0.9 ± 0.003) or high-RFI heifers (0.09 ± 0.003). Spearman rank correlation for RFI between period 1 and 2 was 0.58 (P
Encapsulation of Olive Leaves Extracts in Biodegradable PLA Nanoparticles for Use in Cosmetic Formulation

The aim of the current work was to encapsulate olive leaves extract in biodegradable poly(lactic acid) nanoparticles, characterize the nanoparticles and define the experimental parameters that affect the encapsulation procedure. Moreover, the loaded nanoparticles were incorporated in a cosmetic formulation and the stability of the formulation was studied for a three-month period of study. Poly(lactic acid) nanoparticles were prepared by the nanoprecipitation method. Characterization of the nanoparticles was performed using a variety of techniques: size, polydispersity index and ζ-potential were measured by Dynamic Light Scattering; morphology was studied using Scanning Electron Microscopy; thermal properties were investigated using Differential Scanning Calorimetry; whereas FT-IR spectroscopy provided a better insight on the encapsulation of the extract. Encapsulation Efficiency was determined indirectly, using UV-Vis spectroscopy. The loaded nanoparticles exhibited anionic ζ-potential, a mean particle size of 246.3 ± 5.3 nm (Pdi: 0.21 ± 0.01) and equal to 49.2%, while olive leaves extract release from the nanoparticles was found to present a burst effect at the first 2 hours. Furthermore, the stability studies of the loaded nanoparticles’ cosmetic formulation showed increased stability compared to the pure extract, in respect to viscosity, pH, organoleptic characteristics, emulsions phases and grid.