Miracle-dz/UniFAR-FTUs huggingface dataset:
HLA DNA Sequence Variation among Human Populations: Molecular Signatures of Demographic and Selective Events

Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC) genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies. Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model). However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used to explore the genetic history of human populations, and that their analysis allows a more thorough investigation of human MHC molecular evolution.
A continuous-time neural model for sequential action

Action selection, planning and execution are continuous processes that evolve over time, responding to perceptual feedback as well as evolving top-down constraints. Existing models of routine sequential action (e.g. coffee- or pancake-making) generally fall into one of two classes: hierarchical models that include hand-built task representations, or heterarchical models that must learn to represent hierarchy via temporal context, but thus far lack goal-orientedness. We present a biologically motivated model of the latter class that, because it is situated in the Leabra neural architecture, affords an opportunity to include both unsupervised and goal-directed learning mechanisms. Moreover, we embed this neurocomputational model in the theoretical framework of the theory of event coding (TEC), which posits that actions and perceptions share a common representation with bidirectional associations between the two. Thus, in this view, not only does perception select actions (along with task context), but actions are also used to generate perceptions (i.e. intended effects). We propose a neural model that implements TEC to carry out sequential action control in hierarchically structured tasks such as coffee-making. Unlike traditional feedforward discrete-time neural network models, which use static percepts to generate static outputs, our biological model accepts continuous-time inputs and likewise generates non-stationary outputs, making short-timescale dynamic predictions.
The danger theory: 20 years later

The self–non-self theory has dominated immunology since the 1950s. In the 1990s, Matzinger and her colleagues suggested a new, competing theory, called the “danger theory. ” This theory has provoked mixed acclaim: enthusiasm and criticism. Here we assess the danger theory vis-à-vis recent experimental data on innate immunity, transplantation, cancers and tolerance to foreign entities, and try to elucidate more clearly whether danger is well defined.
Hindering milk quality storage deterioration by mild thermization combined with methylated chickpea protein.

Methylated chickpea protein (MCP) or native chickpea protein (NCP) were supplemented to milk (0.5%) and combined with a mild thermization (65oC/ 5 min) treatment before storing at 4oC for 30 days. The influence of these combined treatments was assessed on milk physicochemical, nutritional and sensorial quality during storage. Supplementation of milk samples with MCP (0.5% w/v) significantly (p < 0.05) and considerably reduced the levels of the bacterial counts; i.e. total bacterial, psychrotrophic and Pseudomonas spp. counts by about 1.6-1.9 log CFU ml-1 after 16 days of storage at 4oC. Within the same period, it could control the development of titratable acidity, limit lipolysis, attenuate proteolysis, maintain most of the vitamin contents, keep considerable heat stability, oxidative stability, rennetablity and sensorial properties.
68Ga-PRGD2 PET/CT in the Evaluation of Glioma: A Prospective Study

Integrin αvβ3 is overexpressed in both neovasculature and glioma cells. We aimed to evaluate 68gallium-BNOTA-PRGD2 (68Ga-PRGD2) as a new reagent for noninvasive integrin αvβ3 imaging in glioma patients. With informed consent, 12 patients with suspicious brain glioma, as diagnosed by enhanced magnetic resonance imaging (MRI) scanning, were enrolled to undergo 68Ga-PRGD2 PET/CT and 18F-FDG PET/CT scans before surgery. The preoperative images were compared and correlated with the pathologically determined WHO grade. Next, the expression of integrin αvβ3, CD34, and Ki-67 were determined by immunohistochemical staining of the resected brain tumor tissue. Our findings demonstrated that 68Ga-PRGD2 specifically accumulated in the brain tumors that were rich of integrin αvβ3 and other neovasculature markers, but not in the brain parenchyma other than the choroid plexus. Therefore, 68Ga-PRGD2 PET/CT was able to evaluate the glioma demarcation more specifically than 18F-FDG PET/CT. The maximum standardized uptake values (SUVmax) of 68Ga-PRGD2, rather than those of 18F-FDG, were significantly correlated with the glioma grading. The maximum tumor-to-brain ratios (TBRmax) of both tracers were significantly correlated with glioma grading, whereas 68Ga-PRGD2 seemed to be more superior to 18F-FDG in differentiating high-grade glioma (HGG) from low-grade glioma (LGG). Moreover, 68Ga-PRGD2 PET/CT showed different accumulation patterns for HGG of WHO grades III and IV. This is the first noninvasive integrin imaging study, to the best of our knowledge, conducted in preoperative patients with different grades of glioma, and it preliminarily indicated the effectiveness of this novel method for evaluating glioma grading and demarcation.
Hypertension Accelerates the Progression of Alzheimer-Like Pathology in a Mouse Model of the Disease

Cerebrovascular impairment is frequent in patients with Alzheimer disease and is believed to influence clinical manifestation and severity of the disease. Cardiovascular risk factors, especially hypertension, have been associated with higher risk of developing Alzheimer disease. To investigate the mechanisms underlying the hypertension, Alzheimer disease cross talk, we established a mouse model of dual pathology by infusing hypertensive doses of angiotensin II into transgenic APPPS1 mice overexpressing mutated human amyloid precursor and presenilin 1 proteins. At 4.5 months, at the early stage of disease progression, only hypertensive APPPS1 mice presented impairment of temporal order memory performance in the episodic-like memory task. This cognitive deficit was associated with an increased number of cortical amyloid deposits (223±5 versus 207±5 plaques/mm2; P<0.05) and a 2-fold increase in soluble amyloid levels in the brain and in plasma. Hypertensive APPPS1 mice presented several cerebrovascular alterations, including a 25% reduction in cerebral microvessel density and a 30% to 40% increase in cerebral vascular amyloid deposits, as well as a decrease in vascular endothelial growth factor A expression in the brain, compared with normotensive APPPS1 mice. Moreover, the brain levels of nitric oxide synthase 1 and 3 and the nitrite/nitrate levels were reduced in hypertensive APPPS1 mice (by 49%, 34%, and 33%, respectively, compared with wild-type mice; P<0.05). Our results indicate that hypertension accelerates the development of Alzheimer disease–related structural and functional alterations, partially through cerebral vasculature impairment and reduced nitric oxide production.
Subclinical hypothyroidism and cognitive function in people over 60 years: a systematic review and meta-analysis

Subclinical hypothyroidism (SCH), defined as elevated thyroid stimulating hormone (TSH) and normal thyroid hormone levels, and cognitive impairment are both common in older people. While the relation between overt hypothyroidism and cognitive impairment is well established, data on the association between SCH and cognitive impairment are conflicting. This systematic review and meta-analysis was performed to assess available evidence on the association of SCH with cognition in community dwelling, relatively healthy older adults. PubMed, EMBASE, Web of Science, COCHRANE, CINAHL, PsycINFO, and Academic Search Premier (January 1966 to April 1, 2015) were searched without language restrictions, as were references of key articles, for studies on the association between SCH and cognition in older adults (>60 years). These studies were reviewed by two independent reviewers according to predefined criteria for eligibility and methodological quality, and data were extracted using standardized forms. Of the 844 reports initially identified, 270 remained after exclusion of duplicates. Of the 270, 15 studies comprising 19,944 subjects, of whom 1,199 had subclinical hypothyroidism were included. Data from the 15 studies was pooled, and meta-analyzed cross-sectionally for global cognition [assessed by Mini-Mental State Examination (MMSE)], executive function, and memory, using random effects models. Pooled effect size (ES) for MMSE was −0.01 (95% CI −0.09, 0.08), with heterogeneity (I2) of 55.1%. Pooled ES was < 0.001 (95% CI −0.10, 0.09) for executive function (I2 = 13.5%), and 0.01 (95% CI −0.12, 0.14) for memory (I2 = 46.9%). In addition, prospective analysis including four studies showed pooled ES of 0.033 (95% CI −0.001 − 0.067) for MMSE (I2 < 0.001%), indicating that subclinical hypothyroidism was not significantly associated with accelerated cognitive decline. This systematic review and meta-analysis provides no evidence that supports an association between SCH and cognitive impairment in relatively healthy older adults.
Maternal and sibling microchimerism in twins and triplets discordant for neonatal lupus syndrome-congenital heart block.

OBJECTIVE Neonatal lupus syndrome-congenital heart block (NLS-CHB) is an acquired autoimmune disease in which maternal autoantibodies are necessary but not sufficient for disease. Maternal myocardial cells have been found in the hearts of patients with NLS-CHB, suggesting that maternal microchimerism may also play a role. In this study we asked whether levels of microchimerism in the blood are associated with NLS-CHB in discordant twins and triplets. METHODS Human leucocyte antigen (HLA)-specific and Y-chromosome-specific real-time quantitative polymerase chain reaction (PCR) was used to quantitatively assay maternal and sibling microchimerism in peripheral blood. Because of HLA allele sharing in families, it was not always possible to distinguish between multiple sources of microchimerism. RESULTS In one family, maternal and/or sibling microchimerism was detected in two triplets who had CHB, but not in the triplet with transient hepatitis. Levels ranged from 4 to 948 genome-equivalents of foreign deoxyribonucleic acid per million host genome-equivalents (gEq/million). Over the first year levels of sibling microchimerism decreased in the triplet with complete CHB and increased in the triplet who progressed from first- to second-degree CHB. In a second family, maternal and/or sibling microchimerism was detected in the healthy twin (1223 gEq/million) but not in the twin with CHB. CONCLUSIONS Maternal and/or sibling microchimerism was detectable in the blood of infant twins and triplets discordant for NLS. Microchimerism in the blood was not specific for NLS-CHB, although in one family levels correlated with disease. Thus, microchimerism in the blood and/or tissues may be involved in the pathogenesis or progression of NLS-CHB, but additional factors must also contribute. Further investigation is warranted.
(Methanol-κO)bis{2-methoxy-6-[(4-methylphenyl)iminiomethyl]phenolato-κ2 O,O′}tris(nitrato-κ2 O,O′)cerium(III)

The asymmetric unit of title compound, [Ce(NO3)3(C15H15NO2)2(CH3OH)], consists of two Schiff base 2-methoxy-6-[(4-methylphenyl)iminiomethyl]phenolate (HL) ligands, three nitrate anions and a methanol ligand. The CeIII ion is 11-coordinated: three nitrate radical anions coordinate to the CeIII ion through O atoms, two HL ligands chelate the CeIII ion through the O atoms of the phenolate and methoxy groups, and one methanol molecule coordinates to CeIII ion through its O atom. The O atom of one nitrate anion is disordered over two sites of equal occupancy. The protonated imine N atoms are involved in intramolecular hydrogen bonds with the phenoxide groups. C—H⋯O interactions are also observed.
An improved search technique for optimal winner determination in combinatorial auctions

Combinatorial auctions allow bidders to bid their synergistic values. Because of complementarities between different assets, bidders give their preferences not just for particular items but also for sets or bundles of items. This form of auction shows great potential under some given circumstances but is still in its infancy. The difficulty lies in finding the optimal price that is the price of a revenue maximizing set of winning bids. Determining the revenue maximizing set of winning bids is NP-complete. In this paper, we review some of the existing approaches as detailed by Sandholm in one of his recent studies. We propose a heuristic, which is a lower bound on the maximal revenue, or an inadmissible heuristic. We then present an algorithm called, "iterative threshold search (ITS) - hybrid". We show using this algorithm that, although inadmissible, such a heuristic near the optimal can be a better choice in practice than a surely admissible or upper bound heuristic. We establish through experiments that this new heuristic coupled with the proposed search algorithm improves the performance result significantly over the one presented by Sandholm.
Divergence of feeding channels within the soil food web determined by ecosystem type

Understanding trophic linkages within the soil food web (SFW) is hampered by its opacity, diversity, and limited niche adaptation. We need to expand our insight between the feeding guilds of fauna and not just count biodiversity. The soil fauna drive nutrient cycling and play a pivotal, but little understood role within both the carbon (C) and nitrogen (N) cycles that may be ecosystem dependent. Here, we define the structure of the SFW in two habitats (grassland and woodland) on the same soil type and test the hypothesis that land management would alter the SFW in these habitats. To do this, we census the community structure and use stable isotope analysis to establish the pathway of C and N through each trophic level within the ecosystems. Stable isotope ratios of C and N from all invertebrates were used as a proxy for trophic niche, and community-wide metrics were obtained. Our empirically derived C/N ratios differed from those previously reported, diverging from model predictions of global C and N cycling, which was unexpected. An assessment of the relative response of the different functional groups to the change from agricultural grassland to woodland was performed. This showed that abundance of herbivores, microbivores, and micropredators were stimulated, while omnivores and macropredators were inhibited in the grassland. Differences between stable isotope ratios and community-wide metrics, highlighted habitats with similar taxa had different SFWs, using different basal resources, either driven by root or litter derived resources. Overall, we conclude that plant type can act as a top-down driver of community functioning and that differing land management can impact on the whole SFW.
Murine Anorectic Response to Deoxynivalenol (Vomitoxin) Is Sex-Dependent

Deoxynivalenol (DON, vomitoxin), a common trichothecene mycotoxin found in cereal foods, dysregulates immune function and maintenance of energy balance. The purpose of this study was to determine if sex differences are similarly evident in DON’s anorectic responses in mice. A bioassay for feed refusal, previously developed by our lab, was used to compare acute i.p. exposures of 1 and 5 mg/kg bw DON in C57BL6 mice. Greater anorectic responses were seen in male than female mice. Male mice had higher organ and plasma concentrations of DON upon acute exposure than their female counterparts. A significant increase in IL-6 plasma levels was also observed in males while cholecystokinin response was higher in females. When effects of sex on food intake and body weight changes were compared after subchronic dietary exposure to 1, 2.5, and 10 ppm DON, males were found again to be more sensitive. Demonstration of male predilection to DON-induced changes in food intake and weight gain might an important consideration in future risk assessment of DON and other trichothecenes.
Effects of Chronic Ethanol Feeding on Clonidine-Evoked Reductions in Blood Pressure, Heart Rate, and Their Variability: Time-Domain Analyses

The effects of chronic ethanol administration on the acute hemodynamic effects of clonidine were investigated in conscious radiotelemetered spontaneously hypertensive rats (SHRs). Changes evoked by clonidine (30 μg/kg i.p.) in blood pressure, heart rate, and their variability were evaluated in ethanol [2.5 or 5% (w/v), 12 weeks] and pair-fed control rats. The blood pressure variability was determined as the standard deviation of the mean arterial pressure (SDMAP). Two heart rate variability indices were used, the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive beat-to-beat differences in R-R interval durations (rMSSD). Compared with control rats, ethanol (2.5 and 5%)-fed rats exhibited concentration-related reductions in mean arterial pressure (MAP) and SDMAP versus no change in heart rate variability. In control rats, clonidine caused a significant reduction in MAP that continued for at least 5 h and was associated with significant reductions in SDMAP, SDRR, and rMSSD, responses that are consistent with the inhibition of central sympathetic tone. The hypotensive effect of clonidine was attenuated by ethanol in a concentration-related manner. The maximum reductions in MAP elicited by clonidine in ethanol (2.5 and 5%)-fed rats amounted to –23.4 ± 2.8 and –15.1 ± 1.5 mm Hg, respectively, compared with –35.4 ± 1.2 mm Hg in control rats. The clonidine-induced reductions in SDMAP, SDRR, and rMSSD were also significantly attenuated by ethanol. These findings suggest that the attenuation of MAP and heart rate variability responses elicited by clonidine in ethanol-fed SHRs reflects alterations in the sympathovagal balance, which may be implicated in the antagonistic hemodynamic interaction between the two drugs.
Dissipation of jet bulk kinetic energy in powerful blazars

Aims. We investigate the dissipation of the bulk kinetic energy of a relativistic jet at different distances from the central power-house and analyse in detail how the dissipated energy is radiated away. Methods. We assume that the location of the dissipation region is a function of the bulk Lorentz factor Γ of the jet, being closer to the centre for smaller Γ . This assumption is naturally fulfilled in the internal shock scenario. The dissipated energy is partially used to accelerate electrons and to amplify the magnetic field. This process creates a source inside the jet (blob). Such blobs may efficiently produce synchrotron and inverse Compton emission. Results. We find that even if the blobs or shells responsible for the blazar activity carry the same energy (in bulk kinetic form), the fact that they move at different Γ can produce dramatic variations in different bands, even if the bolometric luminosity is instead very similar. This is due to the relative importance of the synchrotron, self-Compton, and external Compton radiation processes, which greatly change by changing Γ and the compactness of the source, even if the total radiated energy is constant. We then find that the jet can produce most of its radiative output at small distances from the putative black hole and its accretion disk, this implies a low level of emitted MeV-GeV flux. Our findings, which we apply for illustrative purposes to the blazar 3C 454.3, will be easily testable by the coming γ -ray satellite, such as AGILE and GLAST.
Rise in Prostate-Specific Antigen in Men with Untreated Low-Grade Prostate Cancer Is Slower During Spring-Summer

To test the hypothesis that the rate of rise in prostate-specific antigen (PSA) is slower during the spring-summer than during the rest of the year, we used PSA data from a prospective single-arm cohort study of men who had been followed to characterize a watchful observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The rate of PSA increase was calculated as the visit-to-visit slope of log(PSA) against time, from 1 calendar-quarter visit to the next. The nonparametric Friedman test confirmed differences in rate of PSA rise among the calendar quarters (P = 0.041). Post hoc analysis showed the rate of PSA increase during Q2 was significantly slower than in each one of the other calendar quarters (Q1 versus Q2, P = 0.025; Q3 versus Q2, P = 0.002; Q4 versus Q2, P = 0.013), with no differences among quarters Q1, Q3, and Q4. These results are consistent with the vitamin D hypothesis that the higher 25-hydroxyvitamin D levels associated with spring and summer have a desirable effect on prostate biology. The therapeutic implication is that vitamin D supplementation in the range of 2000 IU/d, a dose comparable to the effect of summer, can benefit men monitored for rising PSA.