Selection signatures of fat tail in sheep

The investigation of the genes with a role in lipid metabolism enjoy considerable scientific and commercial interest because of the strong correlations between fat deposition and the risk of cardiovascular disease. The fat tail characteristic of sheep is the adaptive response to harsh environment, and beyond representing a valuable energy reserve for facing future climate changes provides clues for elucidating the physiology of fat deposition. Studies on various sheep populations detected fat-tail signatures on chromosomes 2, 3, 5, 6, 7 and 13. Fat-tailed sheep represent about 25% of the world\u2019s sheep population, and the genes with a role in this phenotype are likely not the same for every breed, since the wild ancestor of sheep had a thin tail, and the fat tail was selected by humans in longstanding husbandry practices in different regions. In the present work, a genome-wide scan using ~50,000 Single Nucleotide Polymorphisms was performed to identify selection signatures for the f at tail in the Barbaresca sheep, an Italian breed originating from North Africa. Fst values of differentiation, and \u3c72 test of significance of allele frequency were calculated, for each marker, between the Barbaresca and each of 13 Italian thin-tailed breeds. Strong signals of selection were detected for all 13 breeds on chromosome 6, in a region encoding the SLIT homolog 2 gene, this gene acting as a molecular guidance cue in cellular migration. The signature on chromosome 7 was very strong only in some of the breeds used for comparison: the detected signal was located in proximity of the Vertnin gene, a candidate for variation in vertebral number, and was already revealed in Iranian and Mediterranean fat-tailed breeds, but not in the Chinese sheep, so confirming the complexity of the fat-tail phenotype, which is associated in some breeds to long and pendulous tail, while, in other breeds, to the short tail

Molecular characterization of the NRAMP1 gene in buffalo

NRAMP1 (natural-resistance-associated macrophage protein) gene influences the initial phase of bacterial cellular infections, regulating macrophage activation. Recent literature on buffalo has attempted to associate the genotypes at the polymorphic microsatellite, that is located in the 3'-UTR of the gene, with either susceptibility to brucellosis or improved macrophage function. However, contradictory results were reported. In the present work, we have sequenced the whole coding region, as well as part of the introns and UTRs, of the NRAMP1 gene in 49 Mediterranean buffaloes, including both serologically positive and negative animals to Brucella abortus test. We have detected 12 mutations. Nineteen haplotypes were built from the detected variant alleles, so demonstrating the high variability of this gene in buffalo, but no significant differences in haplotype frequencies were found between serologically positive/negative animals

Structure of cattle, sheep, goat and buffalo populations using single nucleotide polymorphisms in genes affecting lipid metabolism

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Neuronal assembly dynamics in supervised and unsupervised learning scenarios

The dynamic formation of groups of neurons—neuronal assemblies—is believed to mediate cognitive phenomena at many levels, but their detailed operation and mechanisms of interaction are still to be uncovered. One hypothesis suggests that synchronized oscillations underpin their formation and functioning, with a focus on the temporal structure of neuronal signals. In this context, we investigate neuronal assembly dynamics in two complementary scenarios: the first, a supervised spike pattern classification task, in which noisy variations of a collection of spikes have to be correctly labeled; the second, an unsupervised, minimally cognitive evolutionary robotics tasks, in which an evolved agent has to cope with multiple, possibly conflicting, objectives. In both cases, the more traditional dynamical analysis of the system’s variables is paired with information-theoretic techniques in order to get a broader picture of the ongoing interactions with and within the network. The neural network model is inspired by the Kuramoto model of coupled phase oscillators and allows one to fine-tune the network synchronization dynamics and assembly configuration. The experiments explore the computational power, redundancy, and generalization capability of neuronal circuits, demonstrating that performance depends nonlinearly on the number of assemblies and neurons in the network and showing that the framework can be exploited to generate minimally cognitive behaviors, with dynamic assembly formation accounting for varying degrees of stimuli modulation of the sensorimotor interactions

Protein load impairs factor H binding promoting complement-dependent dysfunction of proximal tubular cells

Intrarenal complement activation plays an important role in the progression of chronic kidney disease. A key target of the activated complement cascade is the proximal tubule, a site where abnormally filtered plasma proteins and complement factors combine to promote injury. This study determined whether protein overloading of human proximal tubular cells (HK-2) in culture enhances complement activation by impairing complement regulation. Addition of albumin or transferrin to the cells incubated with diluted human serum as a source of complement caused increased apical C3 deposition. Soluble complement receptor-1 (an inhibitor of all 3 activation pathways) blocked complement deposition while the classical and lectin pathway inhibitor, magnesium chloride–EGTA, was, ineffective. Media containing albumin as well as complement had additive proinflammatory effects as shown by increased fractalkine and transforming growth factor-β mRNA expression. This paralleled active C3 and C5b-9 generations, effects not shared by transferrin. Factor H, one of the main natural inhibitors of the alternative pathway, binds to heparan sulfate proteoglycans. Both the density of heparan sulfate and factor H binding were reduced with protein loading, thereby enhancing the albumin- and serum-dependent complement activation potential. Thus, protein overload reduces the ability of the tubule cell to bind factor H and counteract complement activation, effects instrumental to renal disease progression

On the parallelism between the mechanisms behind chromatography and drug delivery: the role of interactions with a stationary phase

A huge number of studies and work in the drug delivery literature are focused on understanding and modeling transport phenomena, the pivotal point for a good device design. The rationalization of all phenomena involved is fundamental, but several concerns arise leaving many issues unsolved. In order to change the point of view we decided to focus our attention on the parallelisms between two fields that seem to be very far from each other: chromatography and drug release. Taking advantages of the studies conducted by many researchers using chromatographic columns we decided to explain all the phenomena involved in drug delivery considering sodium ibuprofen (IP) molecules as analytes and hydrogel as a stationary phase. In particular, we considered not only diffusion, but also drug–polymer interactions as adsorption on the stationary phase and drug–drug interactions as aggregation of analytes. The hydrogel investigated is a promising formulation made of agarose and carbomer 974p (AC) loaded with IP, a non-steroidal common anti-inflammatory drug. The self-diffusion coefficient of IP in AC formulations was measured by using an innovative method based on a magic angle spinning NMR spectroscopic technique to produce high resolution (liquid-like) spectra. This method (HR-MAS NMR) is used in combination with pulsed field gradient spin echo (PGSE) liquid-state techniques. The model predictions satisfactorily match with the experimental data obtained in water and the gel environment, indicating that the model presented here, despite its simplicity, is able to describe the key phenomena governing the device behavior and could be used to rationalize the experimental activity

Efficacy and safety of dalbavancin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and other infections in a real-life setting: data from an Italian observational multicentric study (DALBITA study)

Objectives: We evaluated the efficacy and safety of dalbavancin in ABSSSI and ‘other sites’ infections’ (OTA). Methods: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016–2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting. Results: 206 patients enrolled (males 50%, median age 62 [IQR 50–76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI vs 90.7% OTA (p = 0.003) and 46.3% ABSSSI vs 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure. Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hospitalization (13.5 days, 5.5–22 vs 3, 0–11.7; p<0.0001) and received longer previous (18 days, 9–30 vs 11, 7–19; p = 0.007)/concomitant antibiotic treatments (21 days, 14–52 vs 11, 8–14; p < 0.0001), compared to ABSSSI. ABSSSI and OTA showed similar efficacy (85.5% vs 75%, p = 0.459) and safety (no AE: 81.5% vs 64.3%, p = 0.258); efficacy was independent of previous/concomitant therapies. Conclusions: Dalbavancin demonstrated a success rate of >80%, with similar efficacy/safety in ABSSSI and off-label indications. The preferential use of dalbavancin as second-line or combination therapy would seem to suggest the need for in-depth studies focused on its off-label use

Casein SNP in Norwegian goats: additive and dominance effects on milk composition and quality

<p>Abstract</p> <p>Background</p> <p>The four casein proteins in goat milk are encoded by four closely linked casein loci (<it>CSN1S1</it>, <it>CSN2</it>, <it>CSN1S2 </it>and <it>CSN3</it>) within 250 kb on caprine chromosome 6. A deletion in exon 12 of <it>CSN1S1</it>, so far reported only in Norwegian goats, has been found at high frequency (0.73). Such a high frequency is difficult to explain because the national breeding goal selects against the variant's effect.</p> <p>Methods</p> <p>In this study, 575 goats were genotyped for 38 Single Nucleotide Polymorphisms (SNP) located within the four casein genes. Milk production records of these goats were obtained from the Norwegian Dairy Goat Control. Test-day mixed models with additive and dominance fixed effects of single SNP were fitted in a model including polygenic effects.</p> <p>Results</p> <p>Significant additive effects of single SNP within <it>CSN1S1 </it>and <it>CSN3 </it>were found for fat % and protein %, milk yield and milk taste. The allele with the deletion showed additive and dominance effects on protein % and fat %, and overdominance effects on milk quantity (kg) and lactose %. At its current frequency, the observed dominance (overdominance) effects of the deletion allele reduced its substitution effect (and additive genetic variance available for selection) in the population substantially.</p> <p>Conclusions</p> <p>The selection pressure of conventional breeding on the allele with the deletion is limited due to the observed dominance (overdominance) effects. Inclusion of molecular information in the national breeding scheme will reduce the frequency of this deletion in the population.</p

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA &lt; 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged &gt; 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p &lt; 0.001]. By multivariate analysis, females (p &lt; 0.01) and PWID (p &lt; 0.001), presented a longer time to ART initiation, while older people (p &lt; 0.001), people with higher educational levels (p &lt; 0.001), unemployed (p = 0.02) and students (p &lt; 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability