Miracle-dz/UniFAR-FTUs huggingface dataset:
Cryo-EM Structures of a Gonococcal Multidrug Efflux Pump Illuminate a Mechanism of Drug Recognition and Resistance

Neisseria gonorrhoeae has become a highly antimicrobial-resistant Gram-negative pathogen. Multidrug efflux is a major mechanism that N. gonorrhoeae uses to counteract the action of multiple classes of antibiotics. It appears that gonococci bearing mosaic-like sequences within the gene mtrD, encoding the most predominant and clinically important transporter of any gonococcal multidrug efflux pump, significantly elevate drug resistance and enhance transport function. Here, we report cryo-electron microscopy (EM) structures of N. gonorrhoeae MtrD carrying a mosaic-like sequence that allow us to understand the mechanism of drug recognition. Our work will ultimately inform structure-guided drug design for inhibiting these critical multidrug efflux pumps. ABSTRACT Neisseria gonorrhoeae is an obligate human pathogen and causative agent of the sexually transmitted infection (STI) gonorrhea. The most predominant and clinically important multidrug efflux system in N. gonorrhoeae is the multiple transferrable resistance (Mtr) pump, which mediates resistance to a number of different classes of structurally diverse antimicrobial agents, including clinically used antibiotics (e.g., β-lactams and macrolides), dyes, detergents and host-derived antimicrobials (e.g., cationic antimicrobial peptides and bile salts). Recently, it has been found that gonococci bearing mosaic-like sequences within the mtrD gene can result in amino acid changes that increase the MtrD multidrug efflux pump activity, probably by influencing antimicrobial recognition and/or extrusion to elevate the level of antibiotic resistance. Here, we report drug-bound solution structures of the MtrD multidrug efflux pump carrying a mosaic-like sequence using single-particle cryo-electron microscopy, with the antibiotics bound deeply inside the periplasmic domain of the pump. Through this structural approach coupled with genetic studies, we identify critical amino acids that are important for drug resistance and propose a mechanism for proton translocation. IMPORTANCE Neisseria gonorrhoeae has become a highly antimicrobial-resistant Gram-negative pathogen. Multidrug efflux is a major mechanism that N. gonorrhoeae uses to counteract the action of multiple classes of antibiotics. It appears that gonococci bearing mosaic-like sequences within the gene mtrD, encoding the most predominant and clinically important transporter of any gonococcal multidrug efflux pump, significantly elevate drug resistance and enhance transport function. Here, we report cryo-electron microscopy (EM) structures of N. gonorrhoeae MtrD carrying a mosaic-like sequence that allow us to understand the mechanism of drug recognition. Our work will ultimately inform structure-guided drug design for inhibiting these critical multidrug efflux pumps.
Effect of polysaccharides on the stability and renaturation of soybean trypsin (Kunitz) inhibitor

Thermal denaturation and renaturation of soybean trypsin (Kunitz) inhibitor (STI) were studied by high-sensitivity differential scanning calorimetry in the presence of polysaccharides (dextran, and κ-carrageenans, gum arabic, pectins and dextran sulfate). This study was carried out under conditions of both thermodynamic incompatibility and complex formation of STI and polysaccharides. The presence of polysaccharides did neither influence the denaturation temperature nor the denaturation enthalpy of STI under conditions of their incompatibility with the protein. No polysaccharide (except gum arabic) affected the ability of STI to renature and recover its inhibitory activity after thermal denaturation. At acidic pH values, the protein was shown to form electrostatic complexes with pectins and dextran sulfate. Substantial destabilisation of STI bound to dextran sulfate was observed. In the case of STI/pectin complexes, either a decrease or increase in the stability of STI was observed depending on the complex composition and esterification degree of pectin. The mechanism behind the changes in stability of STI bound to the polysaccharide matrix is discussed. Thermal denaturation of STI in complexes with dextran sulfate and pectin was completely irreversible. This observation indicates a possibility of suppressing antinutritional activities of trypsin inhibitors in soy products.
Human γ‐aminobutyric acid A receptor α2 gene moderates the acute effects of alcohol and brain mRNA expression

γ‐aminobutyric acid A (GABAA) receptors moderate several of the behavioral effects of alcohol. In fact, recent studies have shown an association between the gene for the α2‐subunit of the GABAA receptor (GABRA2) and alcoholism. In the present study, we examined the functional relevance of the GABRA2 gene in alcohol dependence by assessing brain GABRA2 mRNA and GABAAα2‐subunit protein levels in post‐mortem prefrontal cortical tissue collected from control and alcohol‐dependent individuals. In addition, using an endophenotype approach, we tested whether the GABRA2 gene moderates sensitivity to the acute effects of alcohol in two independent samples from distinct human alcohol challenge studies. Results indicated that GABRA2 mRNA levels significantly differed by GABRA2 genotype. GABRA2 single nucleotide polymorphisms (rs573400, rs279871 and rs279858) were significantly associated with sensitivity to the acute effects of alcohol. Specifically, there was a significant main effect of GABRA2 × breath alcohol concentration on several measures of subjective responses to alcohol, including the hedonic value of alcohol. Importantly, reanalysis of a previous intravenous alcohol administration study confirmed the results of the oral alcohol challenge study. In summary, these results extend previous findings and provide new insights into the putative biobehavioral mechanisms that may moderate the association between the GABRA2 gene, sensitivity to the acute effects of alcohol and ultimately alcohol dependence.
Assessment of Measurement Reliability for the IPN Test in Cardiac Patients

Cardiological diagnostics use maximal and submaximal tests with increasing load. Maximal stress tests are currently considered the gold standard. The Institut für Prävention und Nachsorge, Cologne (IPN) test may be an alternative when maximal patient load is not indicated. The universality of the test is well-documented in sport, but the reliability of this test is unknown. The aim of this study was to assess between-trial and between-day reliability for parameters assessed by the IPN stress test in cardiological patients. : In a study of 24 patients aged 39 to 79 years with cardiovascular diseases, the IPN cycle ergometer short test was performed (submaximal performance test). The reliability of heart rate, systolic and diastolic pressure, absolute power at submaximal load, relative performance at submaximal load and target heart rate were assessed. Good (Interclass Correlation Coefficient (ICC) values ranged from 0.832 to 0.894) and excellent (ICC values ranged from 0.904 to 0.969) between-trial reliability was noted. Between-day reliability was good (ICC values from 0.777 to 0.895) and excellent (ICC values from 0.922 to 0.950). The obtained results suggest that the IPN test may be a reliable tool for use in the assessment of cardiological patients, avoiding the implementation of maximal efforts when excessive patient load is not recommended.
The Quality Assessment of Different Geolocalisation Methods for a Sensor System to Monitor Structural Health of Monumental Objects

Cultural heritage objects are affected by a wide range of factors causing their deterioration and decay over time such as ground deformations, changes in hydrographic conditions, vibrations or excess of moisture, which can cause scratches and cracks formation in the case of historic buildings. The electromagnetic spectroscopy has been widely used for non-destructive structural health monitoring of concrete structures. However, the limitation of this technology is a lack of geolocalisation in the space for multispectral architectural documentation. The aim of this study is to examine different geolocalisation methods in order to determine the position of the sensor system, which will then allow to georeference the results of measurements performed by this device and apply corrections to the sensor response, which is a crucial element required for further data processing related to the object structure and its features. The classical surveying, terrestrial laser scanning (TLS), and Structure-from-Motion (SfM) photogrammetry methods were used in this investigation at three test sites. The methods were reviewed and investigated. The results indicated that TLS technique should be applied for simple structures and plain textures, while the SfM technique should be used for marble-based and other translucent or semi-translucent structures in order to achieve the highest accuracy for geolocalisation of the proposed sensor system.
Hybridization between Calopteryx splendens and C. haemorrhoidalis confirmed by morphological and genetic analyses

Hybridization between Calopteryx haemorrhoidalis and any of its congeners has not been reported until now. We observed spontaneous matings between male C. splendens and female C. haemorrhoidalis at a locality in Central Italy, together with some putative hybrid individuals that had a mixed phenotype. Here, we report the morphological and molecular characterization of five suspected hybrids collected from this population during 2001 (n=1), 2012 (n=2) and 2013 (n=2). A discriminant analysis based on 13 morphological variables correctly separated both parental species (with 100% assignation success) and classified the hybrid from 2001 as splendens phenotype and those from 2012 and 2013 as haemorrhoidalis. Genotype data (microsatellite loci) was used to confirm the hybrid origin of these specimens, although there were differences between the individual from 2001 and those from 2012 and 2013; the 2001 individual had alleles that were present in both parent species, suggesting it is an F1 hybrid, but the individuals collected in 2012 and 2013 had private alleles at eight (out of 12) loci and only a small portion of the genome in common with C. splendens, which suggests that introgression is occurring in this population. Similarities in mitochondrial DNA sequences indicate that the 2001 hybrid and the 2012–2013 hybrids have splendens and haemorrhoidalis maternal origins respectively, which, in contrast with behavioural observations, indicates that interspecific matings in both directions are possible. This is the first demonstration that C. haemorrhoidalis can hybridize with other congeners to produce viable offspring.
Genome-Wide Dissection of the CRF Gene Family in Brassica napus Indicates that BnaCRF8s Specifically Regulate Root Architecture and Phosphate Homeostasis against Phosphate Fluctuation in Plants

Phosphorus (P) is an essential macronutrient required for plant growth and development. The involvement of cytokinin response factors (CRFs) in phosphate (Pi) homeostasis and lateral root (LR) initiation in Arabidopsis has been revealed. However, little is known in oil crops. Here, we performed genome-wide dissection of the CRF family in Brassica napus to identify 44 members, which were evolutionally classified into 6 subgroups. Among them, four BnaCRF8 genes were strongly upregulated by P deprivation, and were selected to be further investigated. Time course qRT-PCR analyses showed that four BnaCRF8 genes were enhanced dramatically after 12 h of P stress. Analyses of the subcellular localization in tobacco leaves indicated that BnaA7.CRF8 and BnaC2.CRF8 were localized in the nucleus. The expression of BnaCRF8 genes had constant negative effects on primary root growth and LR initiation and growth, and it reduced Pi acquisition and plant growth in Arabidopsis. Moreover, the expression of Pi homeostasis-related genes was modulated in BnaA7.CRF8 overexpression plants. These results suggest that BnaCRF8 genes might negatively regulate root architecture and plant growth through transcriptional modification of Pi homeostasis-related components. Overall, this study suggests that upregulation of BnaCRF8 genes might be a smart adaptive strategy to cope with continuous Pi deficiency in the environment.
The nonsignificance of distance pairing for the regular segregation of the sex chromosomes in Hemerobius marginatus male. (Hemerobidae, Neuroptera)

Pachytene nuclei in Hemerobius marginatus male showed five autosomal bivalents and loosely paired X and Y chromosomes. In part of the cells, the paired condition was retained until late prometaphase. In these cells, the segregation of sex chromosomes was determined by the bivalent condition. In another part of the cells, sex chromosomes appeared as spatially well separated univalents at diakinesis, followed by their congression separately to the equator at the beginning of prometaphase, after which they were pulled near the poles by spindle fibers during the stabilization process of metaphase structure. On the basis of the behaviour of univalent sex chromosoms during prometaphase, it was concluded that no pairing occurring late at prometaphase was involved in the determination of their segregation. During metaphase I, the X and Y chromosomes did not reorientate, but showed stabilized positions near opposite poles, i.e., distance pairing. Nondisjunction of sex chromosomes occurred in only 0.6% of metaphase I cells. The determination of the segregation of univalent sex chromosomes was explained by the model according to which nonrandom desynapsis movement of chromosomes is responsible for their initial orientation to opposite spindle poles at the beginning of prometaphase.
Structural analysis of the human inter-ş-trypsin inhibitor light-chain gene

The human inter-α-trypsin inhibitor (ITI) light-chain gene, which codes for the two proteins α1-microglobulin (protein HC) and ITI-derived human inhibitor of 30 kDa (HI-30), was isolated from a human genomic library. This gene, present as a single copy in the human genome, is composed of 10 exons and 9 introns distributed over 20 kbp. A single transcriptional initiation site was identified in the 5′-flanking region which contained promoter elements, but no typical TATA box. However a sequence equivalent to the TATA box is present on both sense and anti-sense strands in the 5′-flanking region of the first exon coding for HI-3C. The exon-intron organization suggets that the region coding for protein HC and other members of the lipocalin superfamily evolved from a common ancestral gene that is probabaly differnt from that coding for HI-30 These data suggest that two distinct ancestral genes could have existed and fused during evolution. Several direct and one inverted repeats are also found within this gene, as well as potential glucorticoid-receptor binding sites.
Fructose- and Sorbitol-reduced Diet Improves Mood and Gastrointestinal Disturbances in Fructose Malabsorbers

Background: Fructose malabsorption is characterized by the inability to absorb fructose efficiently. As a consequence fructose reaches the colon where it is broken down by bacteria to short fatty acids, CO2 and H2. Bloating, cramps, osmotic diarrhea and other symptoms of irritable bowel syndrome are the consequences and can be seen in about 50% of fructose malabsorbers. We have previously shown that fructose malabsorption is associated with early signs of mental depression and low serum tryptophan concentrations. It was therefore of interest whether a fructose-reduced diet could not only improve gastrointestinal complaints but also depressive signs seen in fructose malabsorbers. Methods: Fifty-three adults (12 males, 41 females), who were identified as fructose malabsorbers according to their breath-H2 concentrations, filled out a Beck's depression inventory-questionnaire, and a questionnaire with arbitrary scales for measurement of meteorism, stool frequency and quality of life for a 4-week period before dietary intervention and 4 weeks after dietary change as for fructose- and sorbitol-reduced diet. Results: Depression scores were reduced by 65.2% after 4 weeks of diet (P < 0.0001), and there was a significant reduction of meteorism (P < 0.0001) and stool frequency (P < 0.01). Improvement of signs of depression and of meteorism was more pronounced in females than in males. Conclusion: Fructose- and sorbitol-reduced diet in subjects with fructose malabsorption does not only reduce gastrointestinal symptoms but also improves mood and early signs of depression.
Covariances Between Traits Deriving From Successive Allocations of a Resource

The sign and magnitude of covariances between traits involved in a trade-off depend upon two factors: the trade-off pattern between the amounts of resource devoted to the traits and the transformation from amount of resource to trait. Let a single resource be divided over many traits, leading to a complicated pattern of trade-offs between the traits. A trade-off pattern can be modelled as a «tree», with resource acquisition as the trunk, each allocation decision as a dichotomous «branching point» and the amount of resource devoted to a trait at the outer end of the branches. In a «major» allocation, the fractions of resource going to each of the two alternative'branches'are appreciable. In the presence of variation in acquisition and in the allocations, the covariances between the amounts of resource allocated to the traits are shown to depend upon their position relative to the allocation tree and upon allocation magnitudes
On the Core-Shell Nanoparticle in Fractional Dimensional Space

The investigation of core-shell nanoparticles has been greatly exciting in biomedical applications, as this remains of prime importance in targeted drug delivery, sensing, etc. In the present work, the polarizability and scattering features of nanoparticles comprised of nano-sized dielectric/metallic core-shell structures were investigated in the fractional dimensional (FD) space, which essentially relates to the confinement of charged particles. For this purpose, three different kinds of metals—namely aluminum, gold and silver—were considered to form the shell, having a common silicon dioxide (SiO2) nanoparticle as the core. It is noteworthy that the use of noble metal-SiO2 mediums interface remains ideal to realize surface plasmon resonance. The core-shell nanoparticles were considered to have dimensions smaller than the operating wavelength. Under such conditions, the analyses of polarizability and the scattering and absorption cross-sections, and also, the extinction coefficients were taken up under Rayleigh scattering mechanism, emphasizing the effects of a varying FD parameter. Apart from these, the tuning of resonance peaks and the magnitude of surface plasmons due to FD space parameter were also analyzed. It was found that the increase of FD space parameter generally results in blue-shifts in the resonance peaks. Apart from this, the usage of gold and silver shells brings in fairly large shifts in the peak positions of wavelengths, which allows them to be more suitable for a biosensing purpose.
COCOS: A Scalable Architecture for Containerized Heterogeneous Systems

Nowadays software systems are organized around several and heterogeneous components. For example, a modern application can be composed of different microservices, along with dedicated components for machine learning analytics and recurring batch processing jobs. While containers offer a means to deploy the system and tackle heterogeneity, these components have different execution models, can exploit different resource types (e.g., CPUs and GPUs) and result in completely different execution times (milliseconds vs hours). This complexity calls for a new, scalable architecture to allow the systems to operate efficiently. This paper presents COCOS, an architecture, based on containers and control-theory, that is able to manage large and heterogeneous software systems. The architecture is based on a three-level hierarchy of controllers that cooperatively enforce user-defined requirements on execution times and consumed resources. The paper also shows a prototype implementation of COCOS based on Kubernetes, a well-known container orchestrator. The evaluation shows the efficiency of COCOS when dealing with microservices, Spark jobs and machine learning applications.
Description of a New Spotted-Thorax Drosophila (Diptera: Drosophilidae) Species and its Evolutionary Relationships Inferred by a Cladistic Analysis of Morphological Traits

ABSTRACT A phylogenetic approach based on morphological characters is the only alternative applicable in cases where molecular data are unavailable. During a taxonomic inventory of Drosophilidae in 12 localities of Ecuador (South America), we discovered a new species of cactophilic spotted-thorax Drosophila Fallen that here we formally describe as Drosophila machalilla Acurio 2013. To classify this new species, we analyzed the terminalia of male and female adults, finding similarities with flies of two neotropical spotted-thorax species groups of Drosophila, namely rep leta and peruensis. Flies or DNA sequence data are unavailable for the latter species group, hindering a molecular approach. Thus, to accurately classify the new species, we carried out a maximum parsimony cladistic analysis using 52 morphological characters from nine representative taxa of virilis, willistoni, repleta, and peruensis species groups. The results indicate that D. machalilla sp. nov. belongs neither to the repleta group nor to the peruensis group and suggest that a new species group should be erected to house D. machalilla and Drosophila atalaia Vilela & Sene (1982, previously considered a member of the peruensis species group).
Preliminary identification and characterisation of leptin gene polymorphism in Indian goats

The leptin gene could be considered as a hotspot gene. Its role in meat and milk production makes it a candidate for the search of molecular markers related to meat production and meat quality in goats. Leptin gene polymorphism has not been thoroughly studied in Indian goat breeds. Thus for the first time, we report complete gene sequence, its variation including single nucleotide polymorphism (SNPs) in indigenous goats. In the present study, we discovered seven novel SNPs which were never reported previously by direct sequencing of gene in a panel of seven goat breeds differing in phenotype (weight and size) and geographical distribution. Whole leptin gene sequence of 4.8 kb of indigenous goat has been submitted in NCBI database (accession number GU944974). Bioinformatics analysis of the genomic sequences identified a total of 22 variations as compared to exotic goat (AM 114397.2) of which seven were SNPs. These novel SNPs were found in Exon 2 (g.1029T > C), Intron 2 (g.1621G > A) and 3′UTR (g.3968T > C, g.3971C > T, g.4026G > A, g.4105G > A and g.4225T > C). These leptin gene variants can be screened in the larger goat population for association studies with meat quality traits and marker-assisted selection.