Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytokine expression in normal, atopic, and asthmatic subjects using the combination of sputum induction and the polymerase chain reaction.

BACKGROUND--The importance of cytokines in the asthmatic inflammatory response is becoming apparent. The aim of this study was to determine whether the non-invasive method of induced sputum combined with the polymerase chain reaction would allow the detection of messenger RNA (mRNA) encoding a range of cytokines on a qualitative basis. METHODS--Four groups were studied comprising 10 normal subjects, six atopic, 10 mild and five moderately severe asthmatic subjects. Sputum was induced by the inhalation of nebulised 3.5% saline and total RNA extracted from the expectorated cells. Expression of cytokine message within induced sputum was examined by reverse transcription and the polymerase chain reaction (PCR) using primers specific for a range of cytokines (IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, RANTES, TNF alpha, IFN alpha, IFN gamma). Presence or absence of the signal was determined at 35 and 70 cycles of PCR by electrophoretic size fractionation on ethidium bromide stained agarose gels. RESULTS--Cytokine message was detectable in sputum by this method. All samples showed a positive result for actin control. Analysis of signal for the cytokines in all subjects showed that, at 70 cycles, IL-1, IL-5, IL-8, and TNF alpha were detected in more subjects than would be expected by chance. IL-5 mRNA was detected in more of the asthmatic patients (moderate 80%, mild 40%) than in the atopic subjects (33%), who in turn showed expression of this cytokine in more individuals than nonatopic subjects (10%). CONCLUSIONS--The combination of sputum induction and PCR appears to be a useful, non-invasive tool to explore the chronic inflammation of asthma and possibly other lung disorders. It should enable differences between normal and asthmatic subjects to be identified for future confirmation by quantitative techniques.
An Extensive Antigenic Footprint Underpins Immunodominant TCR Adaptability against a Hypervariable Viral Determinant

Mutations in T cell epitopes are implicated in hepatitis C virus (HCV) persistence and can impinge on vaccine development. We recently demonstrated a narrow bias in the human TCR repertoire targeted at an immunodominant, but highly mutable, HLA-B*0801–restricted epitope (1395HSKKKCDEL1403 [HSK]). To investigate if the narrow TCR repertoire facilitates CTL escape, structural and biophysical studies were undertaken, alongside comprehensive functional analysis of T cells targeted at the natural variants of HLA-B*0801–HSK in different HCV genotypes and quasispecies. Interestingly, within the TCR–HLA-B*0801–HSK complex, the TCR contacts all available surface-exposed residues of the HSK determinant. This broad epitope coverage facilitates cross-genotypic reactivity and recognition of common mutations reported in HCV quasispecies, albeit to a varying degree. Certain mutations did abrogate T cell reactivity; however, natural variants comprising these mutations are reportedly rare and transient in nature, presumably due to fitness costs. Overall, despite a narrow bias, the TCR accommodated frequent mutations by acting like a blanket over the hypervariable epitope, thereby providing effective viral immunity. Our findings simultaneously advance the understanding of anti-HCV immunity and indicate the potential for cross-genotype HCV vaccines.
SPATIO-TEMPORAL PATTERN OF AGRO ECOSYSTEM NET PRIMARY PRODUCTIVITY OF INDIA : A PRELIMINARY ANALYSIS USING SPOT VGT DATA

Indian landmass with 1.45% of the world’s total geographical area accounts for approximately 2.7–5.5% to the global NPP estimates with agriculture contributing to more than sixty percent. This paper reports the spatio-temporal pattern of agricultural NPP in India using SPOT VGT 10-day composite NPP product for 2002-03 to 2004-05 agricultural years. Detailed analysis was carried out for the Indo-Gangetic Region to analyse the temporal pattern of NPP for major cropping systems like rice-wheat, cotton-wheat, rice-rice, rice-potato etc. Results showed that total average crop year (June-May) NPP of Indian landmass was a little higher than 2000 TgC (Terra gram carbon) with more than 60 per cent contribution from agricultural vegetation. Annual rate of fixation for India in a normal monsoon year was high in forest ecosystems (a little more than 1300 gC/m) than cropland (a little more than 750 gC/m). Average rate of fixation varied from 900 to 1100 gC/m for rice-rice, rice-potato and sugarcane-based cropping systems in the Indo-Gangetic Plain (IGP). Significant year-to-year variation (22-25 per cent) in annual NPP was observed depending upon weather condition as it varied from 1881.64 TgC in 2002-03 (a monsoon deficit year) to 2515.22 TgC in 2004-05 (a normal monsoon year). Both agriculture and forest NPP showed a decline of 20-26 per cent in abnormal years.
Neural Basis of Video Gaming: A Systematic Review

Background: Video gaming is an increasingly popular activity in contemporary society, especially among young people, and video games are increasing in popularity not only as a research tool but also as a field of study. Many studies have focused on the neural and behavioral effects of video games, providing a great deal of video game derived brain correlates in recent decades. There is a great amount of information, obtained through a myriad of methods, providing neural correlates of video games. Objectives: We aim to understand the relationship between the use of video games and their neural correlates, taking into account the whole variety of cognitive factors that they encompass. Methods: A systematic review was conducted using standardized search operators that included the presence of video games and neuro-imaging techniques or references to structural or functional brain changes. Separate categories were made for studies featuring Internet Gaming Disorder and studies focused on the violent content of video games. Results: A total of 116 articles were considered for the final selection. One hundred provided functional data and 22 measured structural brain changes. One-third of the studies covered video game addiction, and 14% focused on video game related violence. Conclusions: Despite the innate heterogeneity of the field of study, it has been possible to establish a series of links between the neural and cognitive aspects, particularly regarding attention, cognitive control, visuospatial skills, cognitive workload, and reward processing. However, many aspects could be improved. The lack of standardization in the different aspects of video game related research, such as the participants' characteristics, the features of each video game genre and the diverse study goals could contribute to discrepancies in many related studies.
Global Versus Local MPC Algorithms in Freeway Traffic Control With Ramp Metering and Variable Speed Limits

This paper compares global and local model predictive control (MPC) algorithms in a traffic network controlled by intelligent transportation system (ITS) signals (ramp metering and variable speed limits). It will be shown that local techniques have a suboptimal behavior and that centralized techniques are difficult to implement in real time. To deal with this problem, a local MPC with only one communication cycle at each sampling time is proposed. This controller improves the local controller performance, and although it is suboptimal with regard to the centralized controller behavior, it can be implemented in real time.
Clinical, radiological, and biochemical features of a bilateral buttock amyloidoma emerging after 27 years of hemodialysis

Deposition of amyloid in the buttock is a rare complication of dialysis related amyloidosis (DRA), but this localization is even rarer in other types of amyloidoses. We report here the clinical, radiological, and biochemical features of a patient who incurred into this complication after 27 years of hemodialysis. Imaging of the amyloid deposition by magnetic resonance imaging (MRI) documents the amyloid infiltration in the muscles of the buttock region and highlights a peculiar feature of amyloid fibrils deposition in the subcutaneous fat. The amyloid deposition is confirmed by biochemical and microscopic analysis of fibrils extracted from a biopsy specimen. Review of literature and the features of this case lead to speculation that the peculiar involvement of the buttock region including muscles and subcutaneous fat in DRA might derive from the propagation of amyloid initially deposited in the hip joint.
Trimethylamine N-oxide alleviates the severe aggregation and ER stress caused by G98R αA-crystallin

Purpose: Crystallins are major functional and structural proteins in mammalian lens. Their expression, distribution, and protein–protein interaction affect lens development and fiber cell differentiation. Mutated crystallins lead to structural and functional changes of lens structure and could lead to opacity formation and cataract development. The purpose of this study was to investigate the biological effects of the cataract-causing G98R mutation on the αA-crystallin (CRYAA) protein and to test the capability of chemical chaperone trimethylamine N-oxide (TMAO) to reverse such effects. Methods: Myc/His-tagged, human, full-length, wild-type (WT) or G98R CRYAA was expressed in human lens epithelial B3 cells and treated or not treated with TMAO. Triton X-100 (Tx) solubility and cellular localization of CRYAA were examined by western blotting and confocal immunofluorescence, respectively. Ubiquitin proteasome-associated degradation was assayed by MG132 treatment. Endoplasmic reticulum (ER) stress, unfolded protein response, and apoptosis were analyzed by the expression of phosphorylated protein kinase-like ER-kinase, binding immunoglobulin protein (BiP), C/EBP homologous protein/growth arrest and DNA damage-inducible gene 153 (CHOP/GADD153), and caspase-3 and immunocytochemistry. Changes in heat shock and stress signaling were investigated. Results: When transfected in lens epithelial B3 cells, unlike WT CRYAA located in the cytoplasm, the G98R CRYAA mutant formed aggregates inside the ER and the protein was predominantly Tx-insoluble. ER stress was induced by G98R CRYAA expression, and cells underwent apoptosis, as shown by a more frequent appearance of fragmented nuclei. Treatment with TMAO reduced Tx-insoluble mutant protein in time- and dose-dependent manners. Other chemical chaperones, 4-phenylbutyric acid, dimethysulfoxide, and glycerol, were much less effective than TMAO. ER-associated aggregates were reduced after TMAO treatment, and the protein was degraded through the ubiquitin–proteasome pathway. This alleviated ER stress and resulted in less apoptosis. Moreover, TMAO treatment induced a moderate upregulation of heat shock protein 70, indicating its effect on heat-shock response to modulate protein folding and assembly. No change was found for nontransfected cells after TMAO treatment. Conclusion: The natural osmolyte and chemical chaperone TMAO reduced the aggregation of G98R CRYAA. This alleviated ER stress and rescued the affected cells from apoptosis. Our results showed that the chemical chaperone reduces mutant CRYAA aggregates in lens cells. We suggest a potential chemical-based strategy to reduce lens opacity formation.
BREEDING BIOLOGY OF THE LOGGERHEAD SHRIKE LANIUS LUDOVICIANUS IN CENTRAL MEXICO

The Loggerhead Shrike Lanius ludovicianus has an exceptionally broad distribution in North America, with the southernmost populations found in central Mexico. The species has experienced severe declines throughout its range, and thus, is of conservation concern, particularly in USA and Canada. Life history data is scarce for Mexico, where both resident and migratory populations are found. In this study we provide information on the breeding biology of a population of Loggerhead Shrikes near the southern limit of its distribution in central Mexico. Based on data from 70 nests over three breeding seasons (2007–2009), we estimated the average nest density as 0.85 nests/ha with most nests built in mesquite trees Prosopis laevigata. Average clutch initiation date was March 28, with variation among years. The breeding period averaged 3.5 months, starting at the end of February, and extending to early June. The laying period averaged 4.6 days, incubation averaged 18 days, and the average brooding period 16.6 days, for a total average of 39.2 days from egg laying to the end of brooding. Clutch size averaged 4.1 eggs (range 2–5) with a mode of four eggs. The nesting success for the three years combined was 64.3% (range 54.5–68.9%). Daily survival rate was estimated to be 0.749 using logistic exposure. The average number of fledglings at successful nests was 1.5. Predation was the main cause of nest failure, accounting for 35.7% of all active nests. In general, life history traits of this Mexican Loggerhead Shrike population are like those reported for breeding populations in more northern parts of its range; however, clutch size was smaller and average incubation period was significantly longer, probably because of latitudinally-related environmental factors.
A data-driven model of biomarker changes in sporadic Alzheimer's disease

Young et al. reformulate an event-based model for the progression of Alzheimer's disease to make it applicable to a heterogeneous sporadic disease population. The enhanced model predicts the ordering of biomarker abnormality in sporadic Alzheimer's disease independently of clinical diagnoses or biomarker cut-points, and shows state-of-the-art diagnostic classification performance.
Prediction of Substrates for Glutathione Transferases by Covalent Docking

Enzymes in the glutathione transferase (GST) superfamily catalyze the conjugation of glutathione (GSH) to electrophilic substrates. As a consequence they are involved in a number of key biological processes, including protection of cells against chemical damage, steroid and prostaglandin biosynthesis, tyrosine catabolism, and cell apoptosis. Although virtual screening has been used widely to discover substrates by docking potential noncovalent ligands into active site clefts of enzymes, docking has been rarely constrained by a covalent bond between the enzyme and ligand. In this study, we investigate the accuracy of docking poses and substrate discovery in the GST superfamily, by docking 6738 potential ligands from the KEGG and MetaCyc compound libraries into 14 representative GST enzymes with known structures and substrates using the PLOP program [JacobsonProteins2004, 55, 35115048827]. For X-ray structures as receptors, one of the top 3 ranked models is within 3 Å all-atom root mean square deviation (RMSD) of the native complex in 11 of the 14 cases; the enrichment LogAUC value is better than random in all cases, and better than 25 in 7 of 11 cases. For comparative models as receptors, near-native ligand–enzyme configurations are often sampled but difficult to rank highly. For models based on templates with the highest sequence identity, the enrichment LogAUC is better than 25 in 5 of 11 cases, not significantly different from the crystal structures. In conclusion, we show that covalent docking can be a useful tool for substrate discovery and point out specific challenges for future method improvement.
Patterns of Late Cenozoic exhumation deduced from apatite and zircon U‐He ages from Fiordland, New Zealand

New apatite and zircon (U‐Th)/He ages from the Fiordland region of New Zealand's South Island expand on earlier results and provide new constraints on patterns of Late Cenozoic exhumation and cooling across this region. Zircon (U‐Th)/He cooling ages, in combination with increased density of apatite ages, show that in addition to a gradual northward decrease in cooling ages that was seen during an earlier phase of this study, there is also a trend toward younger cooling ages to the east. Distinct breaks in cooling age patterns on southwestern Fiordland appear to be correlated to the location of previously mapped faults. The northward decrease in ages may reflect asynchronous cooling related to migration in the locus of exhumation driven by subduction initiation, or it may reflect synchronous regional exhumation that exposed different structural levels across Fiordland, or some combination of these effects. In either case, differential exhumation accommodated by major and minor faults that dissect Fiordland basement rocks apparently played an important role in producing the resulting age patterns.
Deconstructing a complex obsidian “source‐scape”: A geoarchaeological and geochemical approach in northwestern Patagonia

Northwestern Patagonia is located in a tectonically active part of the southern Andes (Argentina), which has facilitated the formation of obsidian, including pyroclastic deposits that have been affected by geomorphic processes, resulting in a complex obsidian landscape. To date, the geomorphic relocation of obsidian in the landscape has not been a focus of systematic research, and this hampers our understanding of prehistoric human mobility. We present an updated assessment of the regional availability of different obsidian types based on results from our research program, which combines geoarchaeological survey and geochemical characterization to understand the properties and distribution of obsidian. This robust “source‐scape” provides the foundation for reconstructing patterns of lithic provisioning and discard. Our results suggest that interpretations of obsidian availability across the landscape should be more nuanced than is typically acknowledged. Based on our improved “source‐scape,” we discuss the patterns observed in an archaeological X‐ray fluorescence database. When compared with the geoarchaeological reconstruction of obsidian availability, the archaeological record conforms to a distance‐decay pattern. Contrary to previous interpretations, we suggest that the distribution of obsidian types is not isomorphic with human home ranges. This geoarchaeological research program provides a basis for integrating the archaeological record of different Andean regions.
Ecophysiological Traits Associated with Drought in Mediterranean Tree Seedlings: Individual Responses versus Interspecific Trends in Eleven Species

Species differ regarding their drought tolerance and individuals of a given species can modify their morphology and physiology in response to drought. However, since evolutionary and ecological selective pressures differ, individual and interspecific responses to drought might not match. We determined summer survival and a number of ecophysiological variables in two factorial experiments with seedlings of eleven tree species present in Mediterranean ecosystems, grown under slowly imposed water stress and control conditions. Plants experiencing drought exhibited reduced growth, low specific leaf area, chlorophyll content, and photosynthetic rate when compared to the controls, and species-specific drought tolerance was associated with an analogous set of trait values. However, while species with high leaf area ratio and shoot-root ratio exhibited greater drought tolerance, drought induced the reversed response within species. Contrary to expectations, water use efficiency was lower in drought-tolerant species and decreased in water-stressed individuals compared to the control plants. There was a distinctive phylogenetic signal in the functional grouping of species, with oaks, pines, and other genera being clearly different from each other in their drought tolerance and in their functional responses to drought. However, all relationships between ecophysiological variables and drought tolerance were significant after accounting for phylogenetic effects, with the exception of the relationship between drought tolerance and photochemical efficiency. Our results show that drought tolerance is not achieved by a single combination of trait values, and that even though evolutionary processes and individual responses tend to render similar results in terms of functional traits associated with drought, they do not necessarily match.
Myosin Va Plays a Role in Nitrergic Smooth Muscle Relaxation in Gastric Fundus and Corpora Cavernosa of Penis

The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction.
Alamethicin Suppresses Methanogenesis and Promotes Acetogenesis in Bioelectrochemical Systems

ABSTRACT Microbial electrosynthesis (MES) systems with mixed cultures often generate a variety of gaseous and soluble chemicals. Methane is the primary end product in mixed-culture MES because it is the thermodynamically most favorable reduction product of CO2. Here, we show that the peptaibol alamethicin selectively suppressed the growth of methanogens in mixed-culture MES systems, resulting in a shift of the solution and cathode communities to an acetate-producing system dominated by Sporomusa, a known acetogenic genus in MES systems. Archaea in the methane-producing control were dominated by Methanobrevibacter species, but no Archaea were detected in the alamethicin-treated reactors. No methane was detected in the mixed-culture reactors treated with alamethicin over 10 cycles (∼3 days each). Instead, acetate was produced at an average rate of 115 nmol ml−1 day−1, similar to the rate reported previously for pure cultures of Sporomusa ovata on biocathodes. Mixed-culture control reactors without alamethicin generated methane at nearly 100% coulombic recovery, and no acetate was detected. These results show that alamethicin is effective for the suppression of methanogen growth in MES systems and that its use enables the production of industrially relevant organic compounds by the inhibition of methanogenesis.