Miracle-dz/UniFAR-FTUs huggingface dataset:
The 5A Apolipoprotein A-I Mimetic Peptide Displays Antiinflammatory and Antioxidant Properties In Vivo and In Vitro

Objectives—The apolipoprotein (apo)A-I mimetic peptide 5A is highly specific for ATP-binding cassette transporter (ABC)A1-mediated cholesterol efflux. We investigated whether the 5A peptide shares other beneficial features of apoA-I, such as protection against inflammation and oxidation. Methods—New Zealand white rabbits received an infusion of apoA-I, reconstituted high-density lipoprotein (HDL) containing apoA-I ([A-I]rHDL), or the 5A peptide complexed with phospholipids (1-palmitoyl-2-linoleoyl phosphatidylcholine [PLPC]), before inserting a collar around the carotid artery. Human coronary artery endothelial cells (HCAECs) were incubated with (A-I)rHDL or 5A/PLPC before stimulation with tumor necrosis factor &agr;. Results—ApoA-I, (A-I)rHDL, and 5A/PLPC reduced the collar-mediated increase in (1) endothelial expression of cell adhesion molecules vascular cell adhesion molecule-1 and intercellular adhesion molecule-1; (2) O&OV0254;2 production, as well as the expression of the Nox4 catalytic subunits of the NADPH oxidase; and (3) infiltration of circulating neutrophils into the carotid intima–media. In HCAECs, both 5A/PLPC and (A-I)rHDL inhibited tumor necrosis factor-&agr;–induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, as well as the nuclear factor &kgr;B signaling cascade and O&OV0254;2 production. The effects of the 5A/PLPC complex were no longer apparent in HCAECs knocked down for ABCA1. Conclusion—Like apoA-I, the 5A peptide inhibits acute inflammation and oxidative stress in rabbit carotids and HCAECs. In vitro, the 5A peptide exerts these beneficial effects through interaction with ABCA1.
Disulfiram Reactivates Latent HIV-1 in a Bcl-2-Transduced Primary CD4+ T Cell Model without Inducing Global T Cell Activation

ABSTRACT Highly active antiretroviral therapy (HAART) can reduce plasma HIV-1 levels to below the detection limit. However, due to the latent reservoir in resting CD4+ cells, HAART is not curative. Elimination of this reservoir is critical to curing HIV-1 infection. Agents that reactivate latent HIV-1 through nonspecific T cell activation are toxic. Here we demonstrate in a primary CD4+ T cell model that the FDA-approved drug disulfiram reactivates latent HIV-1 without global T cell activation. The extent to which disulfiram reactivates latent HIV-1 in patient cells is unclear, but the drug alone or in combination may be useful in future eradication strategies.
The Giant, Horizontal, and Asymptotic Branches of Galactic Globular Clusters. I. The Catalog, Photometric Observables, and Features

A catalog including a set of the most recent color-magnitude diagrams (CMDs) is presented for a sample of 61 Galactic globular clusters (GGCs). We used this database to perform a homogeneous systematic analysis of the evolved sequences (namely, the red giant branch [RGB], horizontal branch [HB], and asymptotic giant branch [AGB]). Based on this analysis, we present (1) a new procedure to measure the level of the zero-age horizontal branch (VZAHB) and a homogeneous set of distance moduli obtained by adopting the HB as standard candle; (2) an independent estimate for RGB metallicity indicators and new calibrations of these parameters in terms of both spectroscopic ([Fe/H]CG97) and global metallicity ([M/H], including also the α-element enhancement), such that the set of equations presented can be used to simultaneously derive a photometric estimate of the metal abundance and the reddening from the morphology and the location of the RGB in the (V, B-V) CMD; and (3) the location of the RGB bump (in 47 GGCs) and the AGB bump (in nine GGCs). The dependence of these features on metallicity is discussed. We find that by using the latest theoretical models and the new metallicity scales, the earlier discrepancy between theory and observations (∼0.4 mag) completely disappears.
Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab)

Objective:The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. Methods:Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. Results:PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. Conclusion:Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans.
Cardiorespiratory‐resolved magnetic resonance imaging: Measuring respiratory modulation of cardiac function

A technique for cardiac‐ and respiratory‐resolved MRI is described. A retrospectively gated‐segmented acquisition scheme similar to that used in conventional cine cardiac imaging was used to collect image data that spanned both the cardiac and respiratory cycles. Raw k‐space data were regridded in a cardiorespiratory phase space to allow image reconstruction at target cardiac and respiratory phases. The approach can be applied with various k‐space trajectories and pulse sequences, and was implemented in this study with both a Cartesian steady‐state free precession (SSFP) sequence and a radial phase‐contrast (PC) pulse sequence. Free‐breathing short‐axis SSFP images of the heart were reconstructed at multiple respiratory and cardiac phases to illustrate separation of cardiac and respiratory motion without artifacts. A respiratory‐resolved radial PC experiment was used to quantify the volumetric flow rates in the inferior vena cava (IVC), pulmonary artery (PA), and aorta (Ao) in five free‐breathing normal volunteers and a positive‐pressure ventilated dog. Total flow (ml/min) in each vessel was quantified as a function of respiratory phase (peak/minimum output = 1.85 ± 0.29 (IVC), 1.36 ± 0.15 (PA), 1.24 ± 0.09 (Ao)). Peak flow occurred during inspiration for the IVC and PA, and during expiration for the Ao, and there was a complete pattern reversal for the positive‐pressure ventilated dog. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.
Order-optimal caching in hierarchical networks

The decentralized caching is studied in hierarchical networks, where users request contents through intermediate nodes (helpers) from a file server. By placing contents randomly and independently in each node and carefully designing the data delivery, the correlations of the pre-stored contents across layers can be utilized to reduce the transmission rate in each layer. A hybrid caching scheme is developed by exploiting the cross-layer storage correlations as well as the single-layer and cross-layer multicast opportunities. It is observed that the achievable rate region of the hybrid caching scheme is strictly better than the caching scheme in [1]. Furthermore, the order-optimality of the hybrid caching scheme is demonstrated by achieving the performance within constant multiplicative and additive factors of the information-theoretic optimum. In particular, the multiplicative and additive factors are carefully quantified to be 48 and 4, respectively.
Fish monogeneans from a shallow, eutrophic Oświn Lake in Poland.

BACKGROUND A study was carried out in a shallow, eutrophic Oświn Lake, within Seven Islands Reserve (north-eastern Poland), in order to determine the infection of fish with monogeneans as sensitive indicators of water quality. This paper presents comparative analysis of the occurrence of Monogenea in fishes from two, distinctly separated pools of the lake, differing in environmental conditions. The impact of fish size and sampling season on the infection parameters was also analyzed. MATERIAL AND METHODS In 1998 and 1999, a total of 1091 fish representing 8 dominant species were examined. Samples were collected four times a year (in May, July, August, and October) simultaneously from the eastern and western parts of the lake. RESULTS 16 species of Monogenea (and some unidentified specimeus) occurred in the fish examined, most of them from the Dactylogyridae family: Dactylogyrus sphyrna, D. auriculatus, D. intermedius, D. anchoratus, D. falcatus, D. tincae, D. wunderi, D. zandti, D. difformis, D. nanus, D. distinguendus, D. crucifer, D. caballeroi. Furthermore, Tetraonchus monenteron (Tetraonchidae), Gyrodactylus elegans (Gyrodactylidae), and Paradiplozoon megan (Diplozoidae) were detected. Monogenea occurred abundantly on the gills of pike, roach, rudd, white bream, carp bream and crucian carp, but rather sporadically in tench and perch. The highest species variety and diversity of monogenean guilds were detected in carp bream and roach. It was proved that D. crucifer and D. difformis were significantly more abundant in the western pool compared to the eastern one. Infection of fish with Dactylogyridae was season-dependent, contrary to the infection of pike with T. monenteron. Intensity of infection of white bream with D. sphyrna and roach with D. crucifer increased with fish body length; such a relationship did not appear for the other monogeneans and their hosts. CONCLUSION Presence of common Monogenea in the fish examined, lack of rare species, poor diversity of monogenean guilds and relatively low infection rate could be connected with the low stability of the lake environment. Location-dependent occurrence of D. crucifer and D. difformis indicated that the exchange between fish groups from the eastern and western parts of the lake is limited.
Aging with HIV in Africa: the challenges of living longer

The global response to the HIV epidemic and the successful scale-up of antiretroviral therapy (ART) represents one of the greatest public health achievements of this century. The HIV response was initially defined by a focus on mothers and children and as treatment expanded and resources increased globally new groups received particular attention including sex workers drug users and migrants. One group that has so far received little attention in the HIV response in developing countries has been older adults. Several opportunities to highlight the emerging trend of the aging of the HIV epidemic and the potential impact of this trend on the HIV response has been missed. Aids2031 the group established by UNAIDS to chart the actions needed to address the trajectory of the HIV epidemic over the coming decades has emphasized the need for a shift in the response from â€˜crisis management to sustained strategic response. â€™ However the group does not discuss the substantial changes to the HIV response that will likely become necessary as the large-scale delivery of ART will change the age composition of HIV-infected populations over the coming decades. The findings discussed in this article show that the current neglect of the elderly in HIV prevention efforts is unwarranted and that HIV prevention interventions targeted at the specific needs of older adults are needed.
AMP-kinase α2 subunit gene PRKAA2 variants are associated with total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol in normal women

Background: 5′-AMP-activated protein kinase (AMPK) inactivates critial ensymes in fatty acid and cholesterol synthesis. We hypothesised that the serum lipid profile may be influenced by genetic variation in the AMPK catalytic α2 subunit. Method: We examined association of 5 tagging SNPs (tSNPs) in the PRKAA2 gene with serum lipids in 2777 normal Caucasian females (mean age 47.4±12.5 years). Results: All tSNPs were associated with total- and LDL-cholesterol, (p<0.001 to 0.034), explaining variances of 0.13–0.59% and 0.11–0.55% respectively. One haplotype (frequency 34.7%) showed lower total- and LDL-cholesterol compared with the most common haplotype (frequency 45.7%) (p≤0.001), explaining 0.78% of total- and 0.75% of LDL-cholesterol. Another haplotype (frequency 10.5%) was significantly associated with lower HDL-cholesterol (p = 0.005), explaining 0.59% of variance. Conclusions:PRKAA2 gene variants are significantly associated with serum lipoproteins in a large sample of normal female Caucasians.
The Yin and Yang of Microglia

Microglia, the resident immune cells of the mammalian central nervous system (CNS), play a pivotal role in both physiological and pathological conditions such as the restoration of CNS integrity and the progression of neurodegenerative disorders. Extensive data have been published that describe neuroinflammation by microglial activation to have detrimental consequences on the developing and mature brain. On the other hand, a properly directed and limited inflammatory response is known to be a natural healing process after an insult in several other tissues. Thus, it is not surprising that research results illustrating benefits of neuroinflammation have been emerging over the past decade. Inflammation-mediated benefits for CNS outcomes include mechanisms such as neuroprotection, mobilization of neural precursors for repair, remyelination and axonal regeneration. Here, we review data that highlight the dual aspects of microglia with a focus on the developing brain, i.e. as aggressors potentiating damage and as helpers in the recovery process following CNS damage.
Identification of microdeletions in candidate genes for cleft lip and/or palate.

BACKGROUND Genome-wide association studies are now used routinely to identify genes implicated in complex traits. The panels used for such analyses can detect single nucleotide polymorphisms and copy number variants, both of which may help to identify small deleted regions of the genome that may contribute to a particular disease. METHODS We performed a candidate gene analysis involving 1,221 SNPs in 333 candidate genes for orofacial clefting, using 2,823 samples from 725 two- and three-generation families with a proband having cleft lip with or without cleft palate. We used SNP genotyping, DNA sequencing, high-resolution DNA microarray analysis, and long-range PCR to confirm and characterize the deletion events. RESULTS This dataset had a high duplicate reproducibility rate (99.98%), high Mendelian consistency rate (99.93%), and low missing data rate (0.55%), which provided a powerful opportunity for deletion detection. Apparent Mendelian inconsistencies between parents and children suggested deletion events in 15 individuals in 11 genomic regions. We confirmed deletions involving CYP1B1, FGF10, SP8, SUMO1, TBX1, TFAP2A, and UGT7A1, including both de novo and familial cases. Deletions of SUMO1, TBX1, and TFAP2A are likely to be etiologic. CONCLUSIONS These deletions suggest the potential roles of genes or regulatory elements contained within deleted regions in the etiology of clefting. Our analysis took advantage of genotypes from a candidate-gene-based SNP survey and proved to be an efficient analytical approach to interrogate genes potentially involved in clefting. This can serve as a model to find genes playing a role in complex traits in general.
Behavioral flexibility predicts increased ability to resist excessive methamphetamine self‐administration

Drug addiction is often associated with cognitive deficits and behavioral inflexibility that may contribute to the development and maintenance of addictive behaviors by reducing addicts' ability to control their behavior toward the drug. In this study, we investigated the relationships between pre‐drug levels of behavioral flexibility and the risk to develop uncontrolled methamphetamine (METH) self‐administration. First, we measured individual performance in an inter‐dimensional set‐shifting procedure in which animals have to switch between an external visual rule and an internal side rule in order to obtain food pellets. Then we allowed rats to self‐administer METH for twenty long 14‐hour sessions, and we investigated the relationships between behavioral flexibility and measures of control over drug intake. Rats rapidly acquired to self‐administer high levels of METH which resulted in moderate weight loss. After several sessions of self‐administration, whereas some rats progressively increased their METH intake, other rats showed very long voluntary pauses between drug injections and showed no escalation in METH self‐administration. Interestingly, we found that behavioral flexibility is correlated with METH self‐administration and that more flexible rats take less METH and do not escalate drug taking. These results suggest that traits of behavioral flexibility may protect against the development of excessive and dysregulated drug taking. Conversely, the inability to adapt behavioral responses as a function of the environmental contingencies may contribute to the risks to develop addiction to METH.
Differentiation of bone marrow-derived mesenchymal stem cells in diabetic patients into islet-like insulin-producing cells: a new era in the treatment of diabetes

Background The availability of donors for transplantation of human &bgr;-cells as a form of treatment for type II diabetes is limited. Introduction of differentiated human bone marrow-derived mesenchymal stem cells (MSCs) would allow transplantation of an autologous source of &bgr;-cells. This would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Materials and methods Bone marrow cells were obtained from three adult type II diabetic volunteers and three nondiabetic donors. After 3 days in culture, adherent MSCs were expanded for two passages. At passage 3, differentiation was carried out in a three-staged procedure. Cells were cultured in a glucose-rich medium containing activation and growth factors including B27, betacellulin, activin A, and nicotinamde. These cells were evaluated for endocrine characteristics by flow cytometry and morphology. Differentiated cells were transplanted under the kidney capsule of diabetic nude mice and their diabetic status was tested by oral glucose tolerance tests. Results Following differentiation, cells expressed the hormones insulin, glucagon, and somatostatin. No differences in cell characteristics were noted between diabetic and nondiabetic donors. Hormones were detectable by immunomicroscopy in some cells. Transplantation into diabetic mice resulted in secretion of human insulin, near-normalization of glucose levels, and improvements in glucose intolerance. When the MSC-bearing kidneys were removed, rapid return of diabetic state was noted. Histology of the removed kidneys identified insulin-positive cells in the graft. Conclusion Human MSCs from diabetic and nondiabetic donors can be differentiated in vitro to form insulin-producing cells that can restore normoglycemia in diabetic mice. This source of material for autologous transplantation offers new opportunities for the treatment of diabetes.
Supporting successful interpretations of covariation data: Beneficial effects of variable symmetry and problem context

People often have difficulty interpreting covariation data presented in contingency tables. The present study investigates adults’ success and strategy use in interpreting covariation data as a function of two factors that may influence performance: symmetry and context. We hypothesised that symmetrical problems, which involve comparing two candidate causes, would elicit more adequate interpretations than asymmetrical problems, which involve comparing the presence and absence of one candidate cause. We also hypothesised that problems with grounded, concrete contexts would elicit more adequate interpretations than abstract problems. College students (N = 109) interpreted contingency tables in four conditions that varied in symmetry and context. Both factors influenced correct interpretations. A latent class analysis revealed three distinct strategies: (a) compute conditional probabilities (40%), (b) compare-two cells (23%), and (c) anchor and compare (37%), a novel strategy in which reasoners integrate data from all four cells in a stimulus-driven but incorrect way. Participants’ use of the conditional-probabilities strategy was higher in the symmetrical than the asymmetrical conditions, and higher in the concrete than the abstract conditions. Thus, even in a sample of college students, interpreting covariation data is a skill that is not fully consolidated, but instead depends on problem structure and context.
An Explanation for the Gender Gap in Perceptions of Discrimination among African Americans

Studies indicate that African American men report more personal experiences with discrimination than do African American women. According to the subordinate male target hypothesis, this gender difference reflects an underlying reality in which African American men are the primary targets of anti-Black discrimination. From the perspective of intersectionality theory, African American women and men experience racial discrimination differently; and therefore greater reports of discrimination among African American men might be a result of measurement bias that favors the experiences of African American men vis-à-vis African American women. To assess these perspectives, the authors analyze data from the 1995 Detroit Area Study and the 2001–2003 National Survey of American Life. The authors use multiple-group confirmatory factor analytic models with latent means and categorical outcomes to observe the degree to which gender bias in measurement accounts for disparities in perceived discrimination among African American women and men. The results show that gender bias in the measures most often used to assess unfair treatment in social surveys is responsible for the gender gap in certain kinds of perceived discrimination among African Americans. Measures of everyday discrimination are mostly gender balanced, but measurement bias is responsible for a large portion of the gap in perceptions of major life discrimination and the entire gap when major life discrimination is attributed to race. The results highlight the importance of intersectionality theory for assessing discrimination, and the authors argue that revisions in the measurement of perceived discrimination are required to better reflect the experiences of African American women.
PREVELANCE OF GLYCEMIC CONTROL IN EGYPT

Mohamed Shawky ElSayed. Background:Diabetes mellitus (DM) is a metabolic disorder characterised by chronic high blood glucose levels with disturbance of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin resistance or both. The global prevalence of DM among adults aged 20– 79years would increase from 6.4% (affecting 285 million adults) in 2010 to 7.7% (439 million adults) by 2030. From year 2010 to 2030, there would be a 69% increase in numbers of adults with DM in developing countries and a 20% increase in developed countries. Studies by (Porapakkham et al.,2008) and (Margaret et al.,2013) the proportions of population affected by DM were increasing inthe countries, which have higher proportion of ageing societies.