Miracle-dz/UniFAR-FTUs huggingface dataset:
Germinal Center T Follicular Helper Cell IL-4 Production Is Dependent on Signaling Lymphocytic Activation Molecule Receptor (CD150)

CD4 T cell help is critical for the generation and maintenance of germinal centers (GCs), and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP [SH2D1A]) expression in CD4 T cells is essential for GC development. However, SAP-deficient mice have only a moderate defect in TFH differentiation, as defined by common TFH surface markers. CXCR5+ TFH cells are found within the GC, as well as along the boundary regions of T/B cell zones. In this study, we show that GC-associated T follicular helper (GC TFH) cells can be identified by their coexpression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. GC TFH cells are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH cell subset and SAP− TFH cells are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that uses SAP signaling, is specifically required for IL-4 production by GC TFH cells. GC TFH cells require IL-4 and -21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by GC CD4 T cells but not in TFH cell and GC TFH cell differentiation.
Exercise and Neuroendocrine Modulation of Macrophage Function

Like all immune cells, Mphi's cannot simply be viewed as individual cells, but as part of a complex network of cells and tissues that communicate in many different ways in an attempt to elicit an appropriate host response to immune and other challenges. Mphi's are important initial effector cells and are highly regulated by other cells (including T and B lymphocytes) and hormones produced by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. Indeed, it may well be that stressors, including exercise, exert their regulatory influence over these cells by activating the SNS, HPA axis, or by influencing other tissues or cells. With this in mind, the overall objective of this review is to introduce and provide current information regarding the role of neuroendocrine factors in mediating exercise-induced changes in macrophage (Mphi) function. Under this broad objective this review will: 1) briefly discuss the cell biology of the Mphi and its role in host defense, 2) explore the potential regulatory influence of selected neuroendocrine hormones (glucocorticoids, catecholamines, growth hormone, prolactin, and beta-endorphin) that may potentially mediate exercise-induced changes in Mphi function, and 3) describe the effects of exercise on the functions of the Mphi.
Prevalence of echocardiographic left-atrial enlargement in hypertension: a systematic review of recent clinical studies.

BACKGROUND Left atrial enlargement (LAE) is a marker of hypertensive heart disease associated with increased cardiovascular risk. We reviewed recent literature about the prevalence of LAE, as assessed by echocardiography, to update our information about the clinical relevance of this cardiac phenotype in human hypertension. METHODS We performed a search of MEDLINE using the key words "left atrial enlargement," "left atrial dilatation," "left atrial size," "hypertension," "echocardiography," and "atrial fibrillation" to identify relevant papers. We considered full articles published in English from January 1, 2000 to July 1, 2012 reporting studies involving adult individuals. RESULTS We analyzed a total of 15 studies, including 10,141 untreated and treated subjects. LAE was defined according to 11 different criteria (4 studies applied two or three criteria), and its prevalence consistently varied among studies, from 16.0-83.0%, with a prevalence in the pooled population of 32%. A gender-based analysis of 9 studies (8,588 patients) showed the prevalence of LAE as being similar in women and men (OR, 1.23; 95% CI, 0.83-1.83; P = 0.30). Data provided by 10 studies (n = 9,354 patients) showed the prevalence of left-ventricular hypertrophy as being significantly higher in patients with LAE (68.2%) than in their counterparts without LAE (41.8%) (OR, 2.97; 95% CI, 2.68-3.29; P < 0.01). CONCLUSIONS Our analysis shows that LAE is present in a relevant fraction of the hypertensive population. Because LAE is an independent predictor of cardiovascular events, the accurate detection of this phenotype may improve the evaluation of risk in hypertensive patients.
Liver test alterations with total parenteral nutrition and nutritional status.

Liver test abnormalities are a well-recognized complication in the parenterally fed population. Numerous etiologies for the development of elevated liver tests have been suggested. However, the etiology and clinical significance remain unclear. The aim of this retrospective study was to determine the extent of liver-associated test (LAT) abnormalities in patients receiving total parenteral nutrition (TPN) and to investigate whether the composition of TPN solutions and the magnitude of malnutrition could be used to predict subsequent LAT abnormalities. Medical records of 78 adult patients who received TPN for at least 2 weeks were reviewed. All subjects had normal LAT results before TPN, were not receiving hepatotoxic drugs, and had no underlying liver disease. Aspartate aminotransferase peaked transiently during week 2 and returned to normal during week 4. Alkaline phosphatase and total bilirubin peaked during weeks 4 and 3, respectively. The average nonprotein kilocalorie distribution was approximately 80% dextrose and 20% lipid. Caloric intake ranged from 7% to 23% above estimated needs. The mean nutritional status score was 22 +/- 15, with a possible range of 0 to 75 (0 indicates no malnutrition). The composition of TPN solutions was not significantly associated with the changes in the three LATs during any week of the 4-week study. The nutritional status score was significantly associated (p less than .05) with the change in alkaline phosphatase during week 1. This study confirms that LAT abnormalities occur during TPN, but the composition of the solution has no significant ability to predict subsequent LAT abnormalities. (ABSTRACT TRUNCATED AT 250 WORDS)
Large-scale soil moisture mapping in western Africa using the ERS scatterometer

Water is a critical resource in western Africa, and droughts are a serious threat to the population and the environment. A technique to retrieve soil moisture from ERS scatterometer data is applied over a large region covering southern Mali and Burkina Faso. How the method accounts for the wide range of climatic and physiographic conditions encountered in the study area is discussed. An analysis of monthly soil moisture maps covering six years of data shows that the climatic conditions are well reflected in the remotely sensed data.
Effects of iron deficiency anemia on hemoglobin A1c in type 1 diabetes mellitus

Abstract Background: The relationship between hemoglobin A1c (HbA1c) and iron status in type 1 diabetes mellitus (DM) has not been adequately studied. In this prospective investigation, we aimed to determine the effect of iron deficiency on HbA1c in diabetic patients who also had insufficient iron stores.
Standards for the Optical Detection of Protein Particles

Particles in protein therapeutics, composed of aggregated protein monomers, may cause an immunogenic response in patients. Consequently, industry and the FDA desire more accurate methods for counting and characterizing particles. Unlike many manufacturing impurities, protein particles have a refractive index very close to that of the matrix solution. In this paper, we describe some of the measurement challenges for the common optical methods of brightfield microscopy and light obscuration. The particulate refractive index is a key unknown parameter in the effort to standardize counting of protein particles. At NIST, we are developing two types of reference materials that mimic the properties of protein particles to support the validation of these two optical methods. We have developed a polymer-based protein surrogate based on the partially fluorinated polymer ethylene tetrafluoroethylene (ETFE). Mechanical abrasion of the ETFE followed by size filtration produces a polydisperse suspension of very rugged particles with a morphology quite similar to protein particles. In another approach, we have created artificial polymer particles as small as 3 μm x 4 μm x 40 μm in large quantities using photolithographic methods developed for the semiconductor industry. Future work will focus on reducing the optical contrast of these particles in order to better mimic typical protein particles. These reference materials will provide a stringent test of the sensitivity and morphological measurements of optical particle-counting and particle-characterization instruments. Product of the U.S. government; not subject to U. S. copyright
A secure channel free conjunctive keyword search without random oracle under simple assumption

The public key encryption scheme with conjunctive keyword search (PECKS) is one of the most important techniques used for sensitive users' data outsourced to the third party, especially the cloud storage. However, most existing PECKS schemes need to construct a secure channel, which is usually costly. To solve this problem, some scholars have proposed several secure channel-free PECKS schemes, however, most of these schemes either are provably secure in the random oracle model, or provably secure in the stand model under complicated security assumption. Therefore, the security of these schemes is questionable. In this article, we propose a security-enhanced SCF-PECKS scheme, which is provably secure under the simple Decisional Bilinear Diffie-Hellman (DBDH) assumption in the standard model. Then we give its computational consistency and full security proof. Finally, we improve our SCF-PECKS scheme to resist the keyword guessing attack (KGA) and give its security demonstration.
Tomato-based Functional Food as Interferon Adjuvant in HCV Eradication Therapy

Goals: The authors conducted a study to verify whether supplementation with an antioxidant-rich tomato-based functional food reduces anemia during pegylated interferon and ribavirin therapy for chronic hepatitis C. Background: Oxidative stress plays a major role in the physiopathology of hemolytic anemia during ribavirin therapy. The efficacy of antioxidant supplementation with vitamins C and E as pure compounds, is still controversial. Methods: A functional food with a high content of natural antioxidants and with high carotenoid bioavailability was developed. The authors enrolled 92 patients with chronic hepatitis C, treated with standard combination therapy. Forty-six of them received a daily dose (100 g) of functional food (group 1), and 46 did not (group 2). The effect of antioxidant activity was assessed comparing compliance with the full dose of ribavirin and hemoglobin levels during the first 3 months of treatment. Results: Only 8.7% of patients in group 1 had to reduce their daily ribavirin dose, whereas ribavirin reduction was necessary for 30.4% of patients in group 2 (P = 0.09). Hemoglobin levels showed significant differences at 15, 30, and 90 days during the observation time. Conclusion: Results demonstrated that the authors’ functional food reduces the severity of ribavirin-related anemia and improves the tolerance to the full dose of ribavirin in patients with chronic hepatitis C.
Impairment of double‐strand breaks repair and aberrant splicing of ATM and MRE11 in leukemia–lymphoma cell lines with microsatellite instability

Mutations of DNA double‐strand breaks (DSB) repair genes, ATM, MRE11, RAD50, NBS1 and ATR, are postulated to play a role in the development of gastrointestinal malignancies with an impaired mismatch repair (MMR) function. In the present study, mutations of these genes together with the presence of microsatellite instability (MSI) were examined in 50 leukemia–lymphoma cell lines. MSI was detected in 13 (26%) lines. Mutations of intronic mononucleotide repeats in ATM and MRE11 were found in nine and six lines, respectively, whereas mutations of mononucleotide repeats of RAD50 were found in only one line, and none were found in either NBS1 or ATR. Frequencies of ATM and MRE11 mutations were significantly higher in MSI‐positive than MSI‐negative lines. These mutations generated aberrant splicing in both genes. The intensity of the aberrant transcript of ATM (497del22) was stronger in five lines harboring mononucleotide mutations of 2 bp or more than in the lines without or with a 1‐bp mutation. The intensity of the aberrant transcript of MRE11 (315del88) was stronger in four lines with mononucleotide mutations than in lines without. The expression levels of ATM and MRE11 transcripts in MSI‐positive lines were significantly higher than those in MSI‐negative lines. MSI‐positive cell lines showed delay or abrogation of DSB repair. The present study suggests that impairment of the MMR system causes aberrant transcripts in the DSB repair genes ATM and MRE11. This might result in inactivation of the DSB repair system, thus inducing an acceleration of genome instability and accumulation of genetic damage. (Cancer Sci 2006; 97: 226–234)
Irreversible Inactivation of Protein Kinase C by a Peptide-Substrate Analog (*)

Protein kinase C (PKC) is a phospholipid-dependent isozyme family that plays a pivotal role in mammalian signal-transduction pathways that mediate cell growth and differentiation and pathological developments, such as the acquisition of drug resistance by cancer cells. Several peptide-substrate analogs have been shown to reversibly inhibit PKC with high potency and selectivity, but peptide-substrate analogs that antagonize PKC by forming a covalent complex with the enzyme have not been reported. The development of active site-directed irreversible inactivators of PKC could provide new insights into the catalytic mechanism and might ultimately lead to the design of novel therapeutics targeted at PKC. In this report, we show that the peptide-substrate analog Arg-Lys-Arg-Cys-Leu-Arg-Arg-Leu (RKRCLRRL) irreversibly inactivates PKC in a dithiothreitol-sensitive manner. The inactivation mechanism most consistent with our results is the formation of a covalent linkage between the inhibitor-peptide and the enzyme at its active-site. Limited proteolysis of PKC produces a catalytic-domain fragment that is independent of the phospholipid cofactor. RKRCLRRL antagonized the histone kinase activity of PKC and its catalytic-domain fragment with similar efficacies, achieving >50% inactivation at an RKRCLRRL concentration of 10 μM. In contrast, RKRCLRRL analogs with single amino acid substitutions at Cys were non-inhibitory. The inactivated complex of the catalytic-domain fragment and RKRCLRRL was stable upon dilution, and the inactivation of PKC and the catalytic-domain fragment by RKRCLRRL was quenched by dithiothreitol, providing evidence that the enzyme and the synthetic peptide may be covalently linked in an inactivated complex by a disulfide bond. Substrates and substrate analogs protected the catalytic-domain fragment against inactivation by RKRCLRRL, providing evidence that inactivation entailed binding of RKRCLRRL at the active-site of the enzyme. S-Thiolation is the formation of mixed disulfides between proteins and low molecular weight thiols. PKC is thought to have a highly reactive Cys residue in its active-site, and Cys residues that are flanked by basic residues, as is the case in RKRCLRRL, display enhanced reactivity. Our results support an inactivation mechanism that entails S-thiolation of the active-site of PKC by RKRCLRRL. This is the first report of irreversible inactivation of PKC by an active site-directed peptide.
In vitro interactions of immune lymphocytes and Cryptococcus neoformans

CBA/J mice immunized subcutaneously with emulsions of heat-killed Cryptococcus neoformans in complete Freund adjuvant displayed delayed-type hypersensitivity to cryptococcal culture filtrate antigen and developed sensitized splenic lymphoid cells which inhibited the growth of C. neoformans in vitro. The in vitro assay of growth inhibition served to investigate further the kinetics of the effect of sensitized lymphoid cells on the pathogen. There was a close correlation between the delayed-type hypersensitivity response in mice and inhibition of growth of C. neoformans by lymphoid cells. Sensitized splenic lymphocytes capable of inhibiting the growth of the cryptococci were detected at day 6 after immunization and reached maximum levels by days 8 through 16. Inhibition of growth was highest with effector-to-target cell ratios of 300:1 or greater. Inhibition of growth of C. neoformans by sensitized lymphoid cells was detectable as early as 4 h after effector and target cells were mixed and increased gradually, reaching a maximum at 24 h, but dropped significantly by 48 h. By supplementing the reaction mixtures with fresh medium or additional sensitized effector cells during incubation, the inhibition of growth of C. neoformans could be maintained through 48 h. C. neoformans-sensitized effector lymphoid populations not only inhibited the growth of the pathogen in vitro but also restricted C. neoformans proliferation in various vital organs upon transfer to naive recipient animals, indicating that the in vitro growth inhibition assay may be a means of assessing the resistance of animals to C. neoformans. The effector cells from sensitized animals were nylon wool-nonadherent Thy-1+ and Ia+ lymphocytes.
Donor morbidity after living donation for liver transplantation.

BACKGROUND & AIMS Reports of complications among adult right hepatic lobe donors have been limited to single centers. The rate and severity of complications in living donors were investigated in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). METHODS A retrospective observational study design was used. Participants included all potential living donors evaluated between 1998 and 2003. Complication severity was graded using the Clavien scoring system. RESULTS Of 405 donors accepted for donation, 393 underwent donation, and 12 procedures were aborted. There were 245 donors (62%) who did not experience complications; 82 (21%) had 1 complication, and 66 (17%) had 2 or more. Complications were scored as grade 1 (minor; n = 106, 27%), grade 2 (potentially life threatening; n = 103, 26%), grade 3 (life threatening; n = 8, 2%), and grade 4 (leading to death; n = 3, 0.8%). Common complications included biliary leaks beyond postoperative day 7 (n = 36, 9%), bacterial infections (n = 49, 12%), incisional hernia (n = 22, 6%), pleural effusion requiring intervention (n = 21, 5%), neuropraxia (n = 16, 4%), reexploration (n = 12, 3%), wound infections (n = 12, 3%), and intraabdominal abscess (n = 9, 2%). Two donors developed portal vein thrombosis, and 1 had inferior vena caval thrombosis. Fifty-one (13%) donors required hospital readmission, and 14 (4%) required 2 to 5 readmissions. CONCLUSIONS Adult living liver donation was associated with significant donor complications. Although most complications were of low-grade severity, a significant proportion were severe or life threatening. Quantification of complication risk may improve the informed consent process, perioperative planning, and donor care.
Development of a Rabbit Model to Investigate the Effects of Acute Nitrogen Dioxide Intoxication

1 In previous studies a rat inhalation model was developed to investigate the effects of intervention after acute NO2 exposure. The object of the present study was to investigate whether acute NO2 intoxication induced comparable effects in rabbits as it does in rats. Where the effects of intervention in both species are similar, then the conclusions drawn from these studies may have more relevance for the treatment of man. 2 Biochemical variables in bronchoalveolar lavage and supernatant from lung homogenate, which may be relevant for the evaluation of lung injury and repair, were investigated and compared with histology. 3 After NO 2 exposure for 10 min, the pulmonary effects observed became more pronounced with increasing NO2 concentrations (0, 125, 175, 250, 400, 600 or 800 ppm) [1 ppm NO2 is 1.88 mg m-3]. The effects in rabbits were found to be broadly comparable with those in rats. 4 To achieve severe lung injury in rabbits without mortality, enabling investigations of the effects of intervention over several days, exposure to a NO2 concentration of 600 ppm for 10 min was most appropriate, while a concentration of 175 ppm NO2 was needed to attain comparable effects in rats. 5 The repair phase starts later, namely at 3 days after exposure in rats, compared to 5 days in rabbits.
Analysis of the puc Operon Promoter fromRhodobacter capsulatus

ABSTRACT Expression of the Rhodobacter capsulatus puc operon, which codes for structural polypeptides of the light-harvesting-II peripheral antenna complex, is highly regulated in response to alterations in oxygen tension and light intensity. To obtain an understanding of the puc promoter region we report the high-resolution 5′ mapping of the puc mRNA transcriptional start site and DNA sequence analysis of the puc upstream regulatory sequence (pucURS). A ς70-type promoter sequence was identified (pucP1) which has a high degree of sequence similarity with carotenoid and bacteriochlorophyll biosynthesis promoters. Inspection of the DNA sequence also indicated the presence of two CrtJ and four integration host factor (IHF) binding sites. Transcriptional fusions of the pucURS fused tolacZ also confirmed that puc promoter activity is regulated by the transcriptional regulators IHF, CrtJ, and RegA. Gel retardation analysis using cell extracts indicates that mutations in IHF and RegA disrupt protein binding to DNA fragments containing thepucURS.
Cutaneous photoprotection from ultraviolet injury by green tea polyphenols.

BACKGROUND In animal models, extracts from green tea have been shown to be remarkably effective at reducing the severity of adverse human health effects of overexposure to ultraviolet (UV) radiation. Although sunscreens and other photoprotective measures have traditionally been used for this purpose, there is a need for additional measures and natural products are increasingly being explored for that purpose. OBJECTIVE Our purpose was to evaluate the effect of polyphenols from green tea on parameters associated with acute UV injury. METHODS Areas of skin of normal volunteers were treated with an extract of green tea or one of its constituents. Thirty minutes later, the treated sites were exposed to a 2 minimal erythema dose solar simulated radiation. UV-treated skin was examined clinically for UV-induced erythema, histologically for the presence of sunburn cells or Langerhans cell distributions, or biochemically for UV-induced DNA damage. RESULTS Application of green tea extracts resulted in a dose-dependent inhibition of the erythema response evoked by UV radiation. The (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) polyphenolic fractions were most efficient at inhibiting erythema, whereas (-)-epigallocatechin (EGC) and (-)-epicatechin (EC) had little effect. On histologic examination, skin treated with green tea extracts reduced the number of sunburn cells and protected epidermal Langerhans cells from UV damage. Green tea extracts also reduced the DNA damage that formed after UV radiation. CONCLUSION Polyphenolic extracts of green tea are effective chemopreventive agents for many of the adverse effects of sunlight on human health and may thus serve as natural alternatives for photoprotection.