Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytokine production by human peripheral blood mononuclear cells: differential senstivity to glutamine availability.

Human peripheral blood mononuclear cells (PBMCs) were cultured in the presence of different glutamine concentrations (0, 0.1, 0.4, 0.6, 2 mM) and stimulated with concanavalin A (Con A) or bacterial lipopolysaccharide (LPS). The concentrations of T lymphocyte- and monocyte-derived cytokines were measured in the culture medium 24 h later. The availability of glutamine significantly increased the production of interleukin (IL)-2 (2-fold), IL-10 (4-fold) and interferon (IFN)-gamma (4.5-fold) by Con A-stimulated PBMCs. Maximal production of these cytokines occurred at 0.1 mM glutamine and increasing the concentration of glutamine above that did not lead to a further increase in cytokine production. Glutamine availability resulted in small increases (24 to 35%) in the production of IL-1alpha, IL-1beta, IL-6 and tumour necrosis factor (TNF)-alpha by Con A-stimulated PBMCs; again maximal production occurred at a glutamine concentration of 0.1 mM. Glutamine availability did not influence the production of IL-1beta or TNF-alpha by LPS-stimulated PBMCs, while there was a small increase (17 to 32%) in the production of IL-1alpha, IL-6 and IL-10 by these cells at a glutamine concentration of 0.1 mM. It is concluded that glutamine enhances the production of T lymphocyte-derived cytokines with only minimal effects on production of cytokines by monocytes.
Generation and functional characterization of a conditional Pumilio2 null allele

The highly conserved RNA binding protein PUF (Pumilio/FBF) family is present throughout eukaryotes from yeast to mammals, with critical roles in development, fertility and the nervous system. However, the function of the mammalian PUF family members remains underexplored. Our previous study reported that a gene-trap mutation of Pum2 results in a smaller testis but does not impact fertility and viability. Although the gene-trap mutation disrupted the key functional domain of PUM protein–PUM-HD (Pumilio homology domain), but still produced a chimeric Pum2-β-geo protein containing part of PUM2, raising a question if such a chimeric protein may provide any residual function or contribute to the reproductive phenotype. Here, we report the generation of a conditional PUM2 allele, when knocked out, producing no residual PUM2 and hence a complete loss-of-function allele. We also uncovered small but significant reduction of male fertility and viability in the mutants, suggesting requirement of PUM2 for male fertility and viability.
The House Dust Mite Allergen Der p 1, Unlike Der p 3, Stimulates the Expression of Interleukin-8 in Human Airway Epithelial Cells via a Proteinase-activated Receptor-2-independent Mechanism*

We investigated and compared the mechanisms by which two dust mite proteolytic allergens, Der p 1 and Der p 3, and a peptide agonist of proteinase-activated receptor 2 (PAR2AP) trigger interleukin (IL)-8 release from human pulmonary epithelial cells (A549). Although all three stimuli tested induced the up-regulation of IL-8 (mRNA and protein), the Der p 1-mediated signaling events did not exactly match those induced by PAR2AP and Der p 3. First, Der p 1 was less effective in stimulating IL-8 gene transcriptional activity than PAR2AP and Der p 3. Second, Der p 1-mediated IL-8 expression was mainly dependent on NF-κB, whereas Der p 3 and PAR2AP regulated IL-8 expression through the activation of both NF-κB and AP-1. Third, although all three MAP kinases, ERK1/2, p38, and JNK, were activated, Der p 1 induced IL-8 release exclusively via the ERK1/2 signaling pathway, whereas PAR2AP and Der p 3 also involved the other kinases. Fourth, in HeLa cells, Der p 1 was able to up-regulate IL-8 secretion independent of PAR2 expression, and in contrast with PAR2AP and Der p 3, Der p 1 was unable to affect calcium signaling via PAR2 in PAR2-expressing KNRK cells. Finally, cleavage by Der p 1 of a synthetic peptide representing the N-terminal activation-cleavage site of PAR2 did not release a high potency activator of PAR2 as does Der p 3. We conclude that Der p 1 (but not Der p 3)-induced IL-8 production in A549 epithelial cells is independent of PAR2 activation.
Drinking-water quality and issues associated with water vending machines in the city of Los Angeles.

The study reported in this paper sampled 40 water vending machines distributed throughout the city of Los Angeles, California, in the water servicing area of the Los Angeles Department of Water and Power. The authors examined water samples for temperature, turbidity, chlorine content, fungal growth, coliform bacteria, fecal coliform bacteria, Pseudomonas spp. , Pseudomonas aeruginosa, and heterotrophic plate counts using plate count agar and R2A agar. Roughly 48 percent of the original 40 samples were sampled in a second or third round, and these subsequent samples were examined for coliform bacteria, fecal coliform bacteria, Pseudomonas spp. , Pseudomonas aeruginosa, and both heterotrophic plate counts. Observations were made of vending-machine external conditions, identifying information, and permits. Statistically significant associations were found between operator accessibility and poor machine conditions, operator accessibility and permits, and operator accessibility and the servicing interval. Statistically significant associations also were found between operator accessibility and presence of fungi, Pseudomonas spp. , and Pseudomonas aeruginosa, and between presence of fungi and the servicing interval. In addition, statistically significant associations indicate that the quality of machine maintenance is a factor in microbial levels. The microbial content of the water suggested a need for further research into potential health effects in susceptible populations.
Modeling and reducing power consumption in large IT systems

This paper proposes a new energy optimization methodology using the Potluck Problem concept for large and complex IT systems. The proposed methodology involves analyzing the historical time-series data about resource utilization in the IT system, and finding interesting temporal patterns therefrom. Based on the analysis, a system of predictors is constructed wherein each predictor provides an estimate of demand for resources in the IT system for a future time period. These estimates are then used in the Potluck Problem solution strategy to obtain final demand predictions. This approach has been tested for efficacy using data from an actual large IT system. Before-and-after comparison is done for computing energy savings had the resources in the IT system been provisioned in accordance with our approach, in comparison with what actually transpired. Following these calculations, policies are designed with an aim to reduce the aggregate power consumption of the IT system.
Clinical and radiographic presentations of pulmonary cryptococcosis in immunocompetent patients

Pulmonary cryptococcosis is often noted in immunocompromized patients, especially in HIV-seropositive patients and post-transplant patients. Only a few case reports and small-scale studies on pulmonary cryptococcosis in immunocompetent patients have been published in the English literature. However, there are several areas of uncertainty in this group of patients including image presentations and management strategy. This retrospective study including 17 patients is designed to share our 7 y of experience in clarifying the characteristics of pulmonary cryptococcosis in immunocompetent patients, including initial symptoms, diagnostic criteria, pulmonary imaging, treatment and outcome in a tertiary teaching hospital in Taiwan.
Infant Demand and Milk Supply. Part 1: Infant Demand and Milk Production in Lactating Women

This first part of a two-part commentary examines evidence for the notion that human milk production is at least in part controlled by the infant's appetite. The studies that we review, of milk production by breastfeeding and expressing mothers, strongly support this hypothesis. Therefore, in established lactation and with a demand feeding regime, a mother's milk production is likely to be a reflection of her infant's appetite, rather than her ability to produce milk, which may in fact be several-fold higher. However, previous studies of human milk production have not provided a clear insight into how the lactating breast matches milk production to infant demand.
Identification and characterization of embryonic stem cell‐derived pacemaker and atrial cardiomyocytes

The aim of this study was to identify and functionally characterize cardiac subtypes during early stages of development. For this purpose, transgenic embryonic stem cells were generated using the α‐myosin heavy chain promoter driving the expression of the enhanced green fluorescent protein (EGFP). EGFP‐positive clusters of cells were first observed as early as 7 days of development, thus, even before the initiation of the contractile activity. Flow cytometry and single‐cell fluorescence measurements evidenced large diversities of EGFP intensity. Patch‐clamp experiments showed EGFP expression exclusively in pacemaker and atrial but not ventricular cells. The highest fluorescence intensities were detected in pacemaker‐like cardiomyocytes. In accordance, multielectrode‐array recordings of whole embryoid bodies confirmed that the pacemaker center coincided with strongly EGFP‐positive areas. The cardiac subtypes displayed already at this early stage differential characteristics of electrical activity and ion channel expression. Thus, quantitation of the α‐myosin heavy chain driven reporter gene expression allows identification and functional characterization of early cardiac subtypes.
Immunocytochemical analysis of bipolar cells in the macaque monkey retina

Transfer of visual information from photoreceptors to ganglion cells within the retina is mediated by specialized groups of bipolar cells. At least 10 different morphological types of bipolar cells have been distinguished in Golgi studies of primate retina. In the present study, bipolar cell populations in the macaque monkey retina were identified by their differential immunoreactivity to a spectrum of antibody markers. This enabled their spatial density and photoreceptor connections to be analysed. An antibody against the β isozyme of protein kinase C (PKCAβ) labelled many cone bipolar cells. Invaginating (presumed ON) cone bipolar cells and rod bipolar cells were prefentially labelled with a monoclonal antibody raised against rabbit olfactory bulb. Flat (presumed OFF) bipolar cells were labelled with an antiserum against the glutamate transporter protein (GLT‐1).
Prion Protein Gene M129V Polymorphism and Variability in Age at Migraine Onset

Prion protein, a sialoglycoprotein with neuroprotective properties on oxidative stress damage, has been related with the mechanisms leading to migraine. In the present case‐control study, we investigated the correlation between the common methionine/valine polymorphism at codon 129 within the prion protein gene (PRNP) and migraine. Genotyping of PRNP V129M variant was performed in 384 migraine patients and 185 age‐, sex‐, and race‐ethnicity‐matched healthy controls. The frequencies of the PRNP V129M genotype did not differ significantly between migraineurs and controls. The frequencies of 129VV genotype were significantly higher in patients with earlier age at migraine onset. No correlation was found between PRNP 129 genotype and demographics, and other clinical migraine features. Our data suggest that the PRNP 129VV polymorphism is not a direct migraine risk factor but is significantly associated with an earlier onset of the disease.
Characterization of the Rat Star Gene That Encodes the Predominant 3.5-Kilobase Pair mRNA

The steroidogenic acute regulatory protein (STAR) participates in steroidogenesis through the mitochondrial transfer of cholesterol to cytochrome P450scc. The rat adrenal Star gene is transcribed as a 3.5-kilobase pair (kb) and 1.6-kb mRNA with the larger mRNA predominating (∼85% of total) in vivo. Hypophysectomy (HPX) produced a 3–5-fold decrease in Star mRNA along with a loss of adrenal steroids, whereas P450scc mRNA decreased by less than 2-fold. Adrenocorticotropic hormone (ACTH) treatment of HPX rats maximally stimulated steroidogenesis rates within 5 min with over 10-fold elevation of steady state blood levels occurring within 10 min. For intact rats there was a 5–10-fold larger increase, paralleling previously observed elevations of cholesterol-cytochrome P450scc association and metabolism in subsequently isolated adrenal mitochondria. ACTH did not increase either total STAR protein or a group of modified forms until at least 30 min after completion of acute stimulation, indicating that elevated translation of STAR protein cannot alone mediate this acute stimulation. Parallel slow changes in STAR protein and corticosterone formation after ACTH treatment are consistent with participation of STAR forms as co-regulators of these hormonal responses. ACTH stimulation of HPX rats increasedStar mRNA by 2.5-fold within 20 min and by 4.5-fold after 1 h, thus preceding the rise in the STAR protein. A 3.5-kbStar cDNA clone isolated from a rat adrenal cDNA library exhibited a 0.9-kb open reading frame and a 2.5-kb 3′-untranslated region (3′-UTR). The open reading frame sequence differed at only 12 amino acids from that of the mouseStar. The rat Star gene seven exons with exon 7 encoding the entire 2.5 kb of 3′-UTR of the 3.5-kb mRNA. The 3′-UTR sequence suggests that 1.6- and 3.5-kb mRNA are formed by an alternative usage of different polyadenylation signals. Multiple UUAUUUA(U/A)(U/A) motifs also suggest additional regulation through this extended 3′-UTR. Although elevation of STAR protein by ACTH does not cause the acute increase in adrenal cholesterol metabolism, changes in the turnover or distribution of an active STAR subfraction cannot be excluded.
The Bacillus cereus GerN and GerT Protein Homologs Have Distinct Roles in Spore Germination and Outgrowth, Respectively

ABSTRACT The GerT protein of Bacillus cereus shares 74% amino acid identity with its homolog GerN. The latter is a Na+/H+-K+ antiporter that is required for normal spore germination in inosine. The germination properties of single and double mutants of B. cereus ATCC 10876 reveal that unlike GerN, which is required for all germination responses that involve the GerI germinant receptor, the GerT protein does not have a significant role in germination, although it is required for the residual GerI-mediated inosine germination response of a gerN mutant. In contrast, GerT has a significant role in outgrowth; gerT mutant spores do not outgrow efficiently under alkaline conditions and outgrow more slowly than the wild type in the presence of high NaCl concentrations. The GerT protein in B. cereus therefore contributes to the success of spore outgrowth from the germinated state during alkaline or Na+ stress.
The Neuronal Ceroid‐Lipofuscinoses. Recent Advances

The neuronal ceroid lipofuscinoses (NCLs) represent a group of neurodegenerative disorders characterised by progressive visual failure, neurodegeneration, epilepsy and the accumulation of an autofluorescent lipopigment in neurons and other cells. The main childhood subtypes are infantile (INCL;CLN1), classical late infantile (LINCL;CLN2) and juvenile NCL (J NCL; CLN3), distinguished on the basis of age of onset, clinical course and ultrastructural morphology, and recently genetic analysis. In addition several variant forms of the disease complex have been described as well as a rare adult onset form. Advances in both genetics and biochemistry have led to the identification of the genes for the three main subtypes of childhood NCL and their corresponding protein products and to mapping of two additional genes for two variant forms. The disease causing genes in both INCL and classical LINCL have been shown to encode lysosomal enzymes whilst the JNCL gene codes for a protein whose function is as yet unknown.
Can choice feeding improve performances and N-retention of broilers compared to a standard three-phase feeding schedule?

1. An experiment was conducted to investigate if broilers can improve their performances and N-retention using choice feeding (CF). 2. Treatment 1 consisted of a standard three-phase feeding regime (SF). Treatments 2–7 were CF treatments with a high (HP) and a low protein (LP) feed offered simultaneously to the birds. Choice feeding started at day 1 or 8 and feeds were offered in mash form or as pellets. 3. When choice feeding was started at day 1 and the HP diet was mash, growth rates were increased (+4·2%) compared to SF, whereas all other CF treatments showed similar or significantly lower final body weights compared to SF. Feed conversion was increased for all CF strategies. 4. Highest yield and breast meat percentages were obtained if the low protein diet was pelleted. The amount of N excreted was increased for most choice feeding treatments as a result of the increased N-intakes and the less efficient growth. 5. Broilers were able to make a choice between two feeds differing in protein/amino acid contents starting as early as day 1, but choices were influenced by feed form. The results confirmed that very high protein/amino acid concentrations in the starter period are desirable to improve growth rates in fast-growing chickens.
Creutzfeldt–Jakob disease and oxidative stress

Objectives– Substantial evidence supports the hypothesis that oxygen free radicals are involved in various neurodegenerative disorders. To assess the presence of oxidative stress in Creutzfeldt–Jakob disease (CJD) we examined the concentrations of malondialdehyde (MDA) as an established marker of lipid peroxidation. Material and methods– MDA was quantified by high performance liquid chromatography (HPLC) in cerebrospinal fluid (CSF; n=12) and in serum (n=11) samples of CJD patients and healthy controls (n=15). Results– Mean values in healthy controls: 2.56 nmol/ml±0.46 (CSF) and 1.94 nmol/ml±0.67 (serum); mean values in CJD patients: 2.64 nmol/ml±0.67 (CSF) and 1.68 nmol/ml±0.79 (serum). No significant (P>0.05) difference between CJD patients and controls was observed. Conclusions– The results indicated that the CSF and serum of CJD patients showed no higher endogenous levels of MDA as compared to normal healthy controls. These findings provide no evidence for an additional role of oxidative stress in the pathogenetic mechanism underlying CJD neurodegeneration.
Family history as a risk factor for rheumatoid arthritis: a case-control study.

OBJECTIVE To investigate the risk of rheumatoid arthritis (RA) in the first degree relatives and to investigate whether the sex of the parent influences the pattern of inheritance. METHODS An interview based case-control study, with subjects serially matched for age and sex. We analyzed 126 cases (hospital cases) and 94 controls (derived from the same hospitals), who gave information for family history of RA. Data concerning RA history among siblings and parents were computerized and analyzed univariately and multivariately. RESULTS The odds ratio (OR) for developing RA is 4.4 (p < 0.001) if a first degree relative reported having the disease and 5.4 (p < 0.01) if a female first degree relative reported having the disease. For females the OR is 7.0 (p < 0.01) if the first degree relative is female. When the analysis was restricted to parents only, it was found that mothers with RA predispose their daughters and sons to develop RA more (OR = 8.6, p < 0.01, for daughters and 4.8, p < 0.05, for both sexes) than fathers (OR = 1.1 and 1.9, respectively). CONCLUSION This case-control study confirms the familial clustering of RA and suggests that mothers confer susceptibility to RA on their offspring more often than fathers.
Nup98 promotes antiviral gene expression to restrict RNA viral infection in Drosophila

Significance The innate immune system is a highly conserved mode of defense that induces gene expression programs to restrict microbial infections. However, much remains unknown about how the target genes are poised for their rapid induction. Using a Drosophila model, we demonstrate that Nup98 plays an essential antiviral role in insects against human insect-borne viruses. Although Nup98 is known for its role in nuclear-cytoplasmic transport, our data suggest that this antiviral function is not at the nuclear pore, rather at promoters controlling expression of a subset of virus-induced genes. Our findings suggest that the Nup98 primes virus-stimulated genes by regulating the occupancy of active RNA polymerase at these promoters poising them for rapid induction, thereby coordinating a robust and complex antiviral response. In response to infection, the innate immune system rapidly activates an elaborate and tightly orchestrated gene expression program to induce critical antimicrobial genes. While many key players in this program have been identified in disparate biological systems, it is clear that there are additional uncharacterized mechanisms at play. Our previous studies revealed that a rapidly-induced antiviral gene expression program is active against disparate human arthropod-borne viruses in Drosophila. Moreover, one-half of this program is regulated at the level of transcriptional pausing. Here we found that Nup98, a virus-induced gene, was antiviral against a panel of viruses both in cells and adult flies since its depletion significantly enhanced viral infection. Mechanistically, we found that Nup98 promotes antiviral gene expression in Drosophila at the level of transcription. Expression profiling revealed that the virus-induced activation of 36 genes was abrogated upon loss of Nup98; and we found that a subset of these Nup98-dependent genes were antiviral. These Nup98-dependent virus-induced genes are Cdk9-dependent and translation-independent suggesting that these are rapidly induced primary response genes. Biochemically, we demonstrate that Nup98 is directly bound to the promoters of virus-induced genes, and that it promotes occupancy of the initiating form of RNA polymerase II at these promoters, which are rapidly induced on viral infection to restrict human arboviruses in insects.
Comparative proteomics analysis of plasma proteins during the transition period in dairy cows with or without subclinical mastitis after calving.

The transition period is the most critical time of the cow's lactation cycle that is associated with the onset of mastitis. In this study, changes of plasma proteins in cows (n = 12) with or without subclinical mastitis after calving were determined by two-dimensional electrophoresis (2-DE), which detected 18 spots with variations in protein spots abundance. These spots were identified by liquid chromatography coupled with tandem mass spectrometry. The changes in protein profile from day 21 before calving to day 1 after calving were similar in cows with or without subclinical mastitis. Abundance of α1 acid glycoprotein (AGP) and hap- toglobin was dramatically increased at parturition, while transthyretin was down-regulated at parturition, and apolipoprotein E and immunoglobulin gamma 1 were up-regulated at postpartum compared with prepartum in periparturient dairy cows. In cows infected with subclinical mastitis, AGP, haptoglobin, and serum amyloid A were dramatically increased and continued to be elevated in plasma from day 1 to day 21 after calving compared with cows free of mastitis. Changes of protein in plasma at parturition may serve as an immune system response to parturition and lactation process at the protein level and suggest that these altered proteins would not serve as a potential marker for predicting if the periparturient dairy cows are susceptible to subclinical mastitis.