Miracle-dz/UniFAR-FTUs huggingface dataset:
Normal adult climbing fiber monoinnervation of cerebellar Purkinje cells in mice lacking MHC class I molecules

Some immune system proteins have recently been implicated in the development and plasticity of neuronal connections. Notably, proteins of the major histocompatibility complex 1 (MHC class 1) have been shown to be involved in synaptic plasticity in the hippocampus and the development of projection patterns in the visual system. We examined the possible role for the MHC class 1 proteins in one well‐characterized example of synaptic exuberance and subsequent refinement, the climbing fiber (CF) to Purkinje cell (PC) synapse. Cerebella from adult mice deficient for two MHC genes, H2‐D1 and H2‐K1, and for β2‐microglobulin gene were examined for evidence of deficient elimination of supernumerary CF synapses on their PCs. Electrophysiological and morphological evidence showed that, despite the absence of these MHC class 1 molecules, adult PCs in these transgenic mice are monoinnervated as in wild‐type animals. These findings indicate that, at the level of restriction of afferent number at this synapse, functional MHC class 1 proteins are not required. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Long‐term foscarnet therapy not associated with the development of foscarnet‐resistant human immunodeficiency virus type 1 in an acquired immunodeficiency syndrome patient

Sequential human-immunodeficiency virus type 1 (HIV-1) isolates from an acquired immunodeficiency syndrome (AIDS) patient on long-term foscarnet and zidovudine therapy were examined for the emergence of foscarnet resistance. One isolate obtained before therapy, and three post-foscarnet therapy HIV isolates had similar foscarnet sensitivity profiles, despite the emergence of foscarnet-resistant herpes simplex virus type 2 (HSV-2) during the period of therapy. Virion reverse transcriptases from these isolates were also equally inhibited by foscarnet. In contrast, sequential HIV isolates taken pre- and postzidovudine therapy showed a gradual increase in IC50 to this drug. In this patient, long-term foscarnet and zidovudine therapy selected foscarnet-resistant HSV and zidovudine-resistant HIV; in contrast, HIV remained susceptible to foscarnet. Concurrent administration of other anti-HIV drugs (zidovudine and interferon-alpha) may have hindered the development of foscarnet resistant HIV-1 in vivo.
Expression of osteoclast differentiation factor at sites of bone erosion in collagen-induced arthritis.

OBJECTIVE To investigate the cellular mechanism of bone destruction in collagen-induced arthritis (CIA). METHODS After induction of CIA in DA rats, a histologic study of the advanced arthritic lesion was carried out on whole, decalcified joints from the hindpaws of affected animals. To conclusively identify osteoclasts, joint tissue sections were stained for tartrate-resistant acid phosphatase (TRAP) enzyme activity, and calcitonin receptors (CTR) were identified using a specific rabbit polyclonal antibody. The expression of messenger RNA (mRNA) for the osteoclast differentiation factor (also known as receptor activator of nuclear factor kappaB ligand [RANKL]) was investigated using in situ hybridization with a specific riboprobe. RESULTS TRAP-positive and CTR-positive multinucleated cells were invariably detected in arthritic lesions that were characterized by bone destruction. Osteoclasts were identified at the pannus-bone and pannus-subchondral bone junctions of arthritic joints, where they formed erosive pits in the bone. TRAP-positive multinucleated cells were detected within synovium and at the bone erosive front; however, CTR-positive multinucleated cells were present only at sites adjacent to bone. RANKL mRNA was highly expressed in the synovial cell infiltrate in arthritic joints, as well as by osteoclasts at sites of bone erosion. CONCLUSION Focal bone erosion in CIA is attributed to cells expressing definitive features of osteoclasts, including CTR. The expression of RANKL by cells within inflamed synovium suggests a mechanism for osteoclast differentiation and activation at sites of bone erosion. Inhibitors of RANKL may represent a novel approach to treatment of bone loss in rheumatoid arthritis.
In Vitro Comparison of Multinucleated Giant Cell Formation from Human Umbilical Cord and Adult Peripheral Blood Mononuclear Phagocytes

ABSTRACT: The fetus and newborn infant are highly susceptible to infection by pathogens that are capable of intracellular survival. The invasion of these microbes usually stimulates a granulomatous host defense response in the fetus or neonate. Multinucleated giant cells (MGC) are the predominant cells composing the granuloma and represent the terminally differentiated state of activated macrophages. Because macrophages derived from human umbilical cord blood monocytes demonstrate some deficiencies in activated functions, we tested the ability of these cells to form MGC in vitro. Mononuclear cells from umbilical cord blood and adult peripheral blood were isolated and cultured for 7, 14, or 21 d before stimulation with phorbol myristate acetate (PMA), an agent known to stimulate MGC from mononuclear phagocytes in vitro. Spontaneous MGC formation occurred in both cord and adult blood mononuclear cell cultures by d 7 of incubation, although significantly fewer MGC formed in the cord blood cultures. PMA treatment of adult blood mononuclear cells resulted in a significant increase in MGC formation after 7, 14, or 21 d of culture, but PMA did not significantly increase MGC formation in cord blood cultures until 14 or 21 d of culture. Pretreatment of cord and adult blood mononuclear cells with 1,25-dihydroxyvitamin D3 inhibited PMA-induced MGC formation. However, when a purified population of cord blood, monocyte-derived macrophages were pretreated with 1,25-dihydroxyvitamin D3, PMA significantly increased MGC formation. These data indicate that distinct differences exist between mononuclear phagocytes isolated from cord blood versus adult peripheral blood with respect to in vitro MGC formation and that a unique population of 1,25-dihydroxyvitamin D3-responsive macrophages is derived from cord blood monocytes.
The Effect of Exclusive Breast-feeding on Respiratory Illness in Young Infants in a Maternal Immunization Trial in Bangladesh

Background: Exclusive breast-feeding reduces the risk of respiratory illness in infants younger than 6 months of age in developing countries by approximately half. We evaluated the effect of exclusive breast-feeding on respiratory illness with fever (RIF) in Bangladeshi infants in the context of a randomized maternal influenza immunization trial. Methods: Infants in a maternal vaccine trial in Dhaka, Bangladesh, were prospectively assessed at weekly intervals for 6 months after birth for breast-feeding practices and RIF. We estimated the risk of an RIF episode for infants who were exclusively breast-fed the prior week compared with infants not exclusively breast-fed the prior week using generalized estimating equations. Results: We followed a total of 331 infants from birth to 24 weeks of age. The median weeks infants were exclusively breast-fed was 15 (interquartile range, 6–21). The adjusted independent odds of respiratory illness for exclusively breast-fed infants compared with nonexclusively breast-fed infants was 0.59 (95% confidence interval: 0.45–0.77) for an RIF episode. After adjusting for exclusive breast-feeding, we confirmed the previous report that maternal immunization with influenza vaccine had an independent protective effect against RIF (odds ratio, 0.72; 95% confidence interval: 0.55–0.93). No significant difference in the protective effect of exclusive breast-feeding was seen by maternal influenza immunization status. Conclusions: Exclusive breast-feeding during the first 6 months of life and maternal immunization with influenza vaccine independently and substantially reduced respiratory illness with fever in infants.
Chemical Tools for Studying Lipid-Binding Class A G Protein–Coupled Receptors

Cannabinoid, free fatty acid, lysophosphatidic acid, sphingosine 1-phosphate, prostanoid, leukotriene, bile acid, and platelet-activating factor receptor families are class A G protein–coupled receptors with endogenous lipid ligands. Pharmacological tools are crucial for studying these receptors and addressing the many unanswered questions surrounding expression of these receptors in normal and diseased tissues. An inherent challenge for developing tools for these lipid receptors is balancing the often lipophilic requirements of the receptor-binding pharmacophore with favorable physicochemical properties to optimize highly specific binding. In this study, we review the radioligands, fluorescent ligands, covalent ligands, and antibodies that have been used to study these lipid-binding receptors. For each tool type, the characteristics and design rationale along with in vitro and in vivo applications are detailed.
Restriction of plasmid DNA during transformation but not conjugation in Neisseria gonorrhoeae

Neisseria gonorrhoeae strains WR302 and PGH3-2 were characterized with respect to their restriction-modification phenotype. WR302 DNA was cleaved by HaeIII, indicating the lack of methylation at the GGCC sequence. PGH3-2 produced NgoSI (an isoschizomer of NgoII). WR302 produced a restriction enzyme with a recognition sequence different from that of NgoI, NgoII, or NgoIII. Plasmid pFT180 isolated from WR302 was unable to transform PGH3-2, whereas plasmid pFT180 isolated from PGH3-2 was able to transform PGH3-2 at a very high frequency. When plasmid pFT180 isolated from WR302 was methylated in vitro with meth M. HaeIII, this plasmid was able to transform PGH3-2. NgoSI was able to restrict WR302 DNA in vitro, whereas it was incapable of restricting PGH3-2 DNA in vitro. When the self-transmissible R factor pFT6 was mobilized from WR302 to PGH3-2 by conjugation, a 1-order-of-magnitude difference in transfer frequencies was observed, as compared with an isogenic cross. The data indicate that host-mediated restriction can prevent the gonococcus from acquiring DNA via transformation but not via conjugation.
Dissociation in Foster Preschoolers: A Replication and Assessment Study

ABSTRACT This study replicated the Child Behavior Checklist factor structure of traumatic sequelae in maltreated children that was established by A. C. Hulette and colleagues (in press; see also A. Cholankeril et al., 2007). The factors represent dissociation and posttraumatic stress disorder symptomatology. The present study also examined the extent to which these 2 factor scores varied depending on specific maltreatment experiences. Results indicated that children who experienced both physical and sexual abuse in addition to neglect had significantly higher levels of dissociation than children who experienced (a) sexual abuse alone or with neglect, (b) physical abuse alone or with neglect, or (c) only neglect. The current study provides evidence that children who experience multiple forms of maltreatment are more likely to be dissociative, perhaps due to a greater need for a coping mechanism to manage the distress of that maltreatment.
Laparoendoscopic Rendezvous Versus Preoperative ERCP and Laparoscopic Cholecystectomy for the Management of Cholecysto-Choledocholithiasis: Interim Analysis of a Controlled Randomized Trial

Background:Although the ideal management of cholecysto-choledocholi-thiasis is controversial, the 2-stage approach [endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy, and common bile duct (CBD) clearance followed by laparoscopic cholecystectomy] remains the standard way of management worldwide. One-stage approach using the so-called laparoendoscopic rendezvous (LERV) technique offers some advantages, mainly by reducing the hospital stay and the risk of post-ERCP pancreatitis. Objective:To compare the LERV 1-stage approach with the standard 2-stage approach consisting of preoperative ERCP followed by laparoscopic cholecystectomy for the treatment of cholecysto-choledocholithiasis. Setting:Controlled randomized trial, University/Teaching Hospital. Methods:Patients with cholecysto-choledocholithiasis were randomized either to LERV or to the 2-stage approach. Both elective and emergency cases were included in the study. Primary endpoint was to detect difference in overall hospital stay, whereas secondary endpoints were (i) to detect differences in morbidity (especially post-ERCP pancreatitis) and (ii) success of CBD clearance. This is an interim analysis of the first 100 randomized patients. Results:Hospital stay was significantly shorter in the LERV group; median 4 (2–19) days versus 5.5 (3–22) days, P = 0.0004. There was no difference in morbidity and success of CBD clearance between the 2 groups. Post-ERCP amylase value was found significantly lower in the LERV group: median 65 (16–1159) versus 91 (30–1846), P = 0.02. Conclusions:Interim analysis of the results suggests the superiority of the LERV technique in terms of hospital stay and post-ERCP hyperamylasemia.
Structural requirements for protection by small amino acids against hypoxic injury in kidney proximal tubules 1

Kidney proximal tubules are resistant to hypoxic injury if glycine or L‐alanine is present in their incubation medium. Protection does not depend on the concentration or turnover of ATP in cells. We have investigated structure‐function relationships that govern this protective activity. Among more than 45 amino acids and analogs examined, only glycine, L‐alanine, d‐alanine, β‐alanine, and the neuronal glycine binding site agonist, 1‐aminocyclopropane‐1‐carboxylic acid, were active. The protective effect could not be explained by amino acid metabolism. Ultrastructural features in protected cells were preserved to a degree which suggested that processes responsible for degradation during hypoxia were retarded. These results are consistent with stringent requirements of amino acid molecular structure for protection against hypoxia, and suggest the involvement of highly specific, acceptor‐ligand effects on a process critical for maintaining cellular integrity. —Weinberg, J. M. ; Venkatachalam, M. A. ; Garza‐Quintero, R. ; Roeser, N. F. ; Davis, J. A. Structural requirements for protection by small amino acids against hypoxic injury in kidney proximal tubules. FASEB J. 4: 3347–3354; 1990.
Investigations of the CLOCK and BMAL1 Proteins Binding to DNA: A Molecular Dynamics Simulation Study

The circadian locomotor output cycles kaput (CLOCK), and brain and muscle ARNT-like 1 (BMAL1) proteins are important transcriptional factors of the endogenous circadian clock. The CLOCK and BMAL1 proteins can regulate the transcription-translation activities of the clock-related genes through the DNA binding. The hetero-/homo-dimerization and DNA combination of the CLOCK and BMAL1 proteins play a key role in the positive and negative transcriptional feedback processes. In the present work, we constructed a series of binary and ternary models for the bHLH/bHLH-PAS domains of the CLOCK and BMAL1 proteins, and the DNA molecule, and carried out molecular dynamics simulations, free energy calculations and conformational analysis to explore the interaction properties of the CLOCK and BMAL1 proteins with DNA. The results show that the bHLH domains of CLOCK and BMAL1 can favorably form the heterodimer of the bHLH domains of CLOCK and BMAL1 and the homodimer of the bHLH domains of BMAL1. And both dimers could respectively bind to DNA at its H1-H1 interface. The DNA bindings of the H1 helices in the hetero- and homo-bHLH dimers present the rectangular and diagonal binding modes, respectively. Due to the function of the α-helical forceps in these dimers, the tight gripping of the H1 helices to the major groove of DNA would cause the decrease of interactions at the H1-H2 interfaces in the CLOCK and BMAL1 proteins. The additional PAS domains in the CLOCK and BMAL1 proteins affect insignificantly the interactions of the CLOCK and BMAL1 proteins with the DNA molecule due to the flexible and long loop linkers located at the middle of the PAS and bHLH domains. The present work theoretically explains the interaction mechanisms of the bHLH domains of the CLOCK and BMAL1 proteins with DNA.
Presentation of Hypoparathyroidism: Etiologies and Clinical Features.

CONTEXT Understanding the etiology, diagnosis, and symptoms of hypoparathyroidism may help to improve quality of life and long-term disease outcomes. This paper summarizes the results of the findings and recommendations of the Working Group on Presentation of Hypoparathyroidism. EVIDENCE ACQUISITION Experts convened in Florence, Italy, in May 2015 and evaluated the literature and recent data on the presentation and long-term outcomes of patients with hypoparathyroidism. EVIDENCE SYNTHESIS The most frequent etiology is surgical removal or loss of viability of parathyroid glands. Despite precautions and expertise, about 20-30% of patients develop transient and 1-7% develop permanent postsurgical hypoparathyroidism after total thyroidectomy. Autoimmune destruction is the main reason for nonsurgical hypoparathyroidism. Severe magnesium deficiency is an uncommon but correctable cause of hypoparathyroidism. Several genetic etiologies can result in the loss of parathyroid function or action causing isolated hypoparathyroidism or a complex syndrome with other symptoms apart from those of hypoparathyroidism or pseudohypoparathyroidism. Neuromuscular signs or symptoms due to hypocalcemia are the main characteristics of the disease. Hyperphosphatemia can contribute to major long-term complications such as ectopic calcifications in the kidney, brain, eye, or vasculature. Bone turnover is decreased, and bone mass is increased. Reduced quality of life and higher risk of renal stones, renal calcifications, and renal failure are seen. The risk of seizures and silent or symptomatic calcifications of basal ganglia is also increased. CONCLUSIONS Increased awareness of the etiology and presentation of the disease and new research efforts addressing specific questions formulated during the meeting should improve the diagnosis, care, and long-term outcome for patients.
Paradoxical Effect of Reduced Costimulation in T Cell-Mediated Colitis12

B7-1 and B7-2 play different roles in the pathogenesis of autoimmunity, but this is controversial. We analyzed colitis induced by transfer of CD45RBhighCD4+ T cells to RAG−/− recipients lacking B7-1 and/or B7-2. Surprisingly, disease was greatly accelerated in RAG−/− recipients deficient for either B7-1 or B7-2, especially in the B7-2−/− recipients. This accelerated colitis induction correlated with increased T cell division in vivo and production of Th1 cytokines. Although colitis pathogenesis following T cell transfer was inhibited in the absence of CD40L expression, CD40-CD40L interactions were not required in the B7-2−/− RAG−/− recipients. In vitro priming by APCs lacking either B7-1 or B7-2 caused decreased IL-2 production, which led to decreased CTLA-4 expression, although T cells primed in this way could respond vigorously upon restimulation by producing increased IL-2 and proinflammatory cytokines. Consistent with this mechanism, we demonstrate that blocking IL-2 early after T cell transfer accelerated colitis. Our data therefore outline a mechanism whereby synergistic costimulation by B7-1 and B7-2 molecules during priming is required for optimal IL-2 production. The consequent inhibitory effect of full CTLA-4 expression, induced by IL-2, may slow colitis, even in the absence of regulatory T cells.
Analysis of pol Gene Heterogeneity, Viral Quasispecies, and Drug Resistance in Individuals Infected with Group O Strains of Human Immunodeficiency Virus Type 1

ABSTRACT Nucleotide sequences of the reverse transcriptase (RT) coding region have been compared in four new human immunodeficiency virus type 1 (HIV-1) group O isolates. Phylogenetic analysis of thispol region highlights a cluster of these four HIV-1 group O sequences with seven other group O isolates (5% intracluster nucleotide sequence diversity) similar to clusters classified as subtypes in HIV-1 group M (an average of 4.9% intrasubtype sequence diversity). Based on these analyses, this group O cluster has been designated subtype A-O. A longitudinal study of a heterosexual couple infected with group O (ESP1 and ESP2) allowed a detailed analysis of RT sequences (amino acids 28 to 219). Directed evolution and a slightly higher mutation frequency was observed in the RT sequences of patient ESP2, treated with antiretroviral drugs, than that from the untreated patient ESP1. Antiretroviral treatment also selected for specific substitutions, M184V and T215Y in the RT coding region, conferring resistance to 3′-dideoxy-3′-thiacytidine and zidovudine, respectively. A Gly98 to Glu RT substitution identified in the treated patient suggests a possible reversion of a nonnucleoside RT inhibitor-resistant phenotype. Using RT clones from this longitudinal study, both heteroduplex tracking assay and cloning-sequencing techniques were employed for an extensive genetic analysis of pol gene quasispecies. Amino acid substitutions (i.e., Phe-77 to Leu, Lys-101 to Glu, and Val-106 to Iso) associated with antiretroviral resistance were identified in RT clones from HIV-1 group O-infected patients not subjected to drug therapy or treated with unrelated drugs. Finally, phylogenetic relationships between RT clones of the treated ESP2 patient and those of the untreated ESP1 patient show how drug pressure can direct evolution of viral pol gene quasispecies independently of direct drug-resistant substitutions.
Risk Factors for Bacterial Vaginosis Incidence in Young Adult Thai Women

Objective: To determine risk factors for incident bacterial vaginosis (BV) in young Thai women. Study Design: Prospective data from a cohort of 1522 women aged 18 to 35 years, who were enrolled in a study of hormonal contraception and HIV acquisition, were used to evaluate potential risk factors for BV, as diagnosed by Amsel criteria. Results: The median prevalence of BV from 3 to 24 months of follow-up visits was 2.5%. The BV incidence was 10.0 per 100-woman years. Statistically significant factors in multivariable analysis were sex during menstruation [hazard ratio (HR), 1.80; 95% CI, 1.11–2.92], male partners having sex with other women (HR, 2.3; 95% CI, 1.45–2.98), cigarette smoking (HR, 1.79; 95% CI, 1.08–2.98), and trichomoniasis (HR, 15.68; 95% CI, 4.95–49.68). Intravaginal practices were not associated with incident BV in unadjusted or adjusted analysis. Conclusions: This study supports the association between sexual behaviors and the incident BV. Failure to detect an association between intravaginal practices and incident BV warrants further studies in high-risk populations or in women with a higher prevalence of intravaginal practices.