Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Immunodeficiency Virus Type 1 Subtypes Have a Distinct Long Terminal Repeat That Determines the Replication Rate in a Host-Cell-Specific Manner

ABSTRACT The long terminal repeat (LTR) transcriptional promoters of different human immunodeficiency virus (HIV) type 1 subtypes were inserted into the LAI molecular clone of subtype B. The viral genotypes represent seven subtypes (A, B, C, D, E, F, and G) and one circulating recombinant form (AG). We performed replication studies with this isogenic set of viruses across six cellular environments. This approach revealed strong cellular environment effects, but the method was not sensitive enough to detect small differences in the replication rate between the subtypes. By conducting pairwise competition experiments between the virus variants in six cellular environments, we could demonstrate significant differences in the replication rates of the subtypes and that LTR-determined viral fitness depends both on the host cell type and the activation state of the cell. In addition, we determined the degree of conservation of the transcription factor-binding sites (TFBS) in the different-subtype LTRs by analyzing sequences from the HIV sequence database. The sequence analyses revealed subtype-specific conservation of certain TFBS. The results indicate that one should consider the possibility of subtype-specific viral replication rates in vivo, which are strongly influenced by the host environment. We argue that the multidimensional host environment may have shaped the genetic structures of the subtype LTRs.
Relationship between reduced nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox gene polymorphism and obstructive sleep apnea-hypopnea syndrome in the Chinese Han population.

BACKGROUND Increased production of reactive oxygen species (ROS) is thought to play a major role in the pathogenesis of obstructive sleep apnea-hypopnea syndrome (OSAHS). The reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex is an important source of ROS. The p22phox subunit is polymorphic with a C242T variant that changes histidine-72 for a tyrosine in the potential heme binding site. This study aimed to investigate the relationship between NADPH oxidase subunit p22phox gene polymorphism and OSAHS. METHODS The genotypes of p22phox polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) assay in 176 unrelated subjects of the Han population in southern region of China (including 107 OSAHS subjects and 69 non-OSAHS subjects), while the plasma concentration of superoxide dismutase (SOD) was detected in the two groups, and p22phox mRNA expression in peripheral blood mononuclear cell (PBMC) was determined with reverse transcription polymerase chain reaction (RT-PCR). RESULTS The phagocyte NADPH oxidase subunit p22phox mRNA expression was significantly increased in the OSAHS group than that in the non-OSAHS group (P < 0.01). Compared with the non-OSAHS control group ((85.31 +/- 9.23) U/ml), the levels of SOD were lower in patients with OSAHS ((59.65 +/- 11.61) U/ml (P < 0.01). There were significant differences in genotypes distribution in p22phox polymorphism between the two groups (P = 0.02). Compared with the non-OSAHS control group, the OSAHS group had a significantly higher T allele frequency in p22phox polymorphism (P = 0.03). There were independent effects of p22phox polymorphism on body mass index (BMI), neck circumference (NC), waist-to-hip ratio (WHR) in the OSAHS group, and the carriers of the T allele of p22phox polymorphism had greater NC, WHR, systolic blood pressure (SBP), diastolic blood pressure (DBP) and apnea-hypopnea index (AHI) (P < 0.05), but the carriers of the T allele had lower SOD (P < 0.01) and lowest SaO(2) (P = 0.04). There was no significant difference in p22phox mRNA expression between the OSAHS groups with or without T allele (P = 0.45). CONCLUSIONS The NADPH oxidase subunit p22phox gene polymorphism may be associated with susceptibility to OSAHS, and it may be an important candidate gene for OSAHS.
Interaction of Mycobacterium leprae with the HaCaT human keratinocyte cell line: new frontiers in the cellular immunology of leprosy

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae affecting the skin and peripheral nerves. Despite M. leprae invasion of the skin and keratinocytes importance in innate immunity, the interaction of these cells in vitro during M. leprae infection is poorly understood. Conventional and fluorescence optical microscopy, transmission electronic microscopy, flow cytometry and ELISA were used to study the in vitro interaction of M. leprae with the HaCaT human keratinocyte cell line. Keratinocytes uptake of M. leprae is described, and modulation of the surface expression of CD80 and CD209, cathelicidin expression and TNF‐α and IL‐1β production of human keratinocytes are compared with dendritic cells and macrophages during M. leprae interaction. This study demonstrated that M. leprae interaction with human keratinocytes enhanced expression of cathelicidin and greatly increased TNF‐α production. The highest spontaneous expression of cathelicidin was by dendritic cells which are less susceptible to M. leprae infection. In contrast, keratinocytes displayed low spontaneous cathelicidin expression and were more susceptible to M. leprae infection than dendritic cells. The results show, for the first time, an active role for keratinocytes during infection by irradiated whole cells of M. leprae and the effect of vitamin D on this process. They also suggest that therapies which target cathelicidin modulation may provide novel approaches for treatment of leprosy.
Measuring the effect of climate change on wars in history

ABSTRACT Since 2005, there have been an increasing number of large-N quantitative studies measuring the effect of climate change on wars in recent history. Those large-N studies are crucial in illuminating the close connection between the physical environment and human societies in a macro (i.e. long-temporal and large-spatial) historic perspective. Grounded on a large number of cases, those studies help evidence and generalize the societal impact of climate change. Nevertheless, this large-N approach is relatively new in academia, and there is not any standard practice as regards how the quantitative analysis of the pre-industrial climate-war nexus should be conducted. Some methodological issues remain open. In this study, those large-N studies of the climate-war nexus in the pre-industrial period are systematically reviewed. Some conceptual and methodological issues pertinent to the understanding and examination of the climate-war nexus are discussed. Suggestions and priorities for future research on the topic are also provided at the end of this paper. This study may provide deeper reflections and produce constructive insights about the relationship between climate change and wars, advancing progress in climate-war research.
The impact of Wisconsin’s Act 10 on municipal management in smaller municipalities: Views from local elected officials

This article examines elected officials’ opinions on Wisconsin’s controversial 2011 collective bargaining reform. Survey results from elected officials serving on city councils and village boards with less than 10,000 residents demonstrate that Act 10 is still viewed through a partisan lens, making its overall impact on municipal governance unsettled. We also find that officials who first came to office prior to Act 10 generally think the law has had a positive fiscal impact. Overall, the authors conclude that Act 10 cannot yet be viewed as a successful governance reform because it is still viewed by local policymakers through a narrow fiscal and partisan lens.
Thiomer nanoparticles: Stabilization via covalent cross-linking

The purpose of this study was the development of stable thiomer nanoparticles for mucosal drug delivery. Chitosan-thioglycolic acid (chitosan-TGA) nanoparticles (NP) were formed via ionic gelation with tripolyphosphate (TPP). In order to stabilize the NP inter- and intra-molecular disulfide bonds were formed via controlled oxidation with hydrogen peroxide (H2O2). Thereafter, stability was investigated in saline and simulated body fluids at pH 2 and pH 5.5 via optical density measurements. The mucoadhesive properties were evaluated in vitro on freshly excised porcine intestinal mucosa via the rotating cylinder method. Particles had a mean size of 158 ± 8 nm and a zeta potential of ~ + 16 mV. Three different degrees of oxidation were adjusted by the addition of H2O2 in final concentrations of 10.60 µmol (chitosan-TGA (ox1)), 21.21 µmol (chitosan-TGA (ox2)), and 31.81 µmol (chitosan-TGA (ox3)) leading to 60%, 75%, and 83% of oxidized thiol groups, respectively. More than 99% of chitosan-TGA (ox3) NP, 70% of chitosan-TGA (ox2) NP, and 50% of chitosan-TGA (ox1) NP were stable over a 60-min period in simulated gastric fluid. In contrast, only 10% of unmodified chitosan and chitosan-TGA NP which were just ionically cross-linked remained stable in the same experiment. The adhesion times of covalently cross-linked chitosan-TGA (ox1), chitosan-TGA (ox2), and chitosan-TGA (ox3) were ~ 41-fold, 31-fold, and 25-fold longer in comparison to unmodified ionically cross-linked chitosan. The method described here might be useful for the preparation of stable nanoparticulate drug delivery systems.
Cell Signaling and the Genesis of Neuropathic Pain

Damage to the nervous system can cause neuropathic pain, which is in general poorly treated and involves mechanisms that are incompletely known. Currently available animal models for neuropathic pain mainly involve partial injury of peripheral nerves. Multiple inflammatory mediators released from damaged tissue not only acutely excite primary sensory neurons in the peripheral nervous system, producing ectopic discharge, but also lead to a sustained increase in their excitability. Hyperexcitability also develops in the central nervous system (for instance, in dorsal horn neurons), and both peripheral and spinal elements contribute to neuropathic pain, so that spontaneous pain may occur or normally innocuous stimuli may produce pain. Inflammatory mediators and aberrant neuronal activity activate several signaling pathways [including protein kinases A and C, calcium/calmodulin-dependent protein kinase, and mitogen-activated protein kinases (MAPKs)] in primary sensory and dorsal horn neurons that mediate the induction and maintenance of neuropathic pain through both posttranslational and transcriptional mechanisms. In particular, peripheral nerve lesions result in activation of MAPKs (p38, extracellular signal–regulated kinase, and c-Jun N-terminal kinase) in microglia or astrocytes in the spinal cord, or both, leading to the production of inflammatory mediators that sensitize dorsal horn neurons. Activity of dorsal horn neurons, in turn, enhances activation of spinal glia. This neuron-glia interaction involves positive feedback mechanisms and is likely to enhance and prolong neuropathic pain even in the absence of ongoing peripheral external stimulation or injury. The goal of this review is to present evidence for signaling cascades in these cell types that not only will deepen our understanding of the genesis of neuropathic pain but also may help to identify new targets for pharmacological intervention. Nerve injury not only leads to immediate sensations of pain, which serves an adaptive function, but can also lead to chronic pain, which is pathological. Although the mechanisms underlying the genesis and maintenance of neuropathic pain—the chronic pain that often, although in humans not always, results from nerve injury—remain incompletely understood, they are known to involve signaling pathways initiated both by inflammatory substances released from the damaged tissues and by aberrant firing of the damaged neurons. These signaling pathways lead to posttranslational modifications of existing proteins that appear to be involved in the genesis of neuropathic pain, as well as to changes in transcriptional activity that appear to be involved in its maintenance. This STKE Review explores the peripheral and central mechanisms underlying the initiation and maintenance of neuropathic pain and discusses the interactions between neurons and glia that are likely to prolong and enhance the pain that results from nerve injury. A deeper understanding of the mechanisms that contribute to neuropathic pain may be expected to lead to more effective methods of treating this chronic and disabling condition.
Legionnaires disease: historical perspective

In the summer of 1976, a mysterious epidemic of fatal respiratory disease in Philadelphia launched an intensive investigation that resulted in the definition of a new family of pathogenic bacteria, the Legionellaceae. In retrospect, members of the family had been isolated from clinical specimens as early as 1943. Unsolved epidemics of acute respiratory disease dating to the 1950s were subsequently attributed to the newly described pathogens. In the intervening years, the Legionellaceae have been firmly established as important causes of sporadic and epidemic respiratory disease. The sources of the infecting bacteria are environmental, and geographic variation in the frequency of infection has been documented. Airborne dissemination of bacteria from cooling towers and evaporative condensers has been responsible for some epidemics, but potable water systems are perhaps more important sources. The mode of transmission from drinking water is unclear. The Legionellaceae are gram-negative, facultative, intracellular pathogens. The resident alveolar macrophage, usually an effective antibacterial defense, is the primary site of growth. Cell-mediated immunity appears to be the most important immunological defense; the role of humoral immunity is less clear. Erythromycin remains the antibiotic of choice for therapy of infected patients, but identification and eradication of environmental sources are also essential for the control of infection.
FOXL2 mutations and genomic rearrangements in BPES

The FOXL2 gene is one of 10 forkhead genes, the mutations of which lead to human developmental disorders, often with ocular manifestations. Mutations in FOXL2 are known to cause blepharophimosis syndrome (BPES), an autosomal dominant eyelid malformation associated (type I) or not (type II) with ovarian dysfunction, leading to premature ovarian failure (POF). In addition, a few mutations have been described in patients with isolated POF. Here, we review all currently described FOXL2 sequence variations and genomic rearrangements in BPES and POF. Using a combined mutation detection approach, it is possible to identify the underlying genetic defect in a major proportion (88%) of typical BPES patients. Of all genetic defects found in our BPES cohort, intragenic mutations represent 81%. They include missense changes, frameshift and nonsense mutations, in‐frame deletions, and duplications, that are distributed along the single‐exon gene. Genomic rearrangements comprising both deletions encompassing FOXL2 and deletions located outside its transcription unit, represent 12% and 5% of all genetic defects in our BPES cohort, respectively. One of the challenges of genetic testing in BPES is the establishment of genotype–phenotype correlations, mainly with respect to the ovarian phenotype. Genetic testing should be performed in the context of genetic counseling, however, and should be systematically complemented by a multidisciplinary clinical follow‐up. Another challenge for health care professionals involved in BPES is the treatment of the eyelid phenotype and the prevention or treatment of POF. Hum Mutat 0, 1–12, 2008. © 2008 Wiley‐Liss, Inc.
Corticospinal control of the thumb–index grip depends on precision of force control: a transcranial magnetic stimulation and functional magnetic resonance imagery study in humans

The corticospinal system (CS) is well known to be of major importance for controlling the thumb–index grip, in particular for force grading. However, for a given force level, the way in which the involvement of this system could vary with increasing demands on precise force control is not well‐known. Using transcranial magnetic stimulation and functional magnetic resonance imagery, the present experiments investigated whether increasing the precision demands while keeping the averaged force level similar during an isometric dynamic low‐force control task, involving the thumb–index grip, does affect the corticospinal excitability to the thumb–index muscles and the activation of the motor cortices, primary and non‐primary (supplementary motor area, dorsal and ventral premotor and in the contralateral area), at the origin of the CS. With transcranial magnetic stimulation, we showed that, when precision demands increased, the CS excitability increased to either the first dorsal interosseus or the opponens pollicis, and never to both, for similar ongoing electromyographic activation patterns of these muscles. With functional magnetic resonance imagery, we demonstrated that, for the same averaged force level, the amplitude of blood oxygen level‐dependent signal increased in relation to the precision demands in the hand area of the contralateral primary motor cortex in the contralateral supplementary motor area, ventral and dorsal premotor area. Together these results show that, during the course of force generation, the CS integrates online top‐down information to precisely fit the motor output to the task's constraints and that its multiple cortical origins are involved in this process, with the ventral premotor area appearing to have a special role.
Demand for Law in the African Private Sector

Abstract This article develops a model for explaining private sector response to law reforms in developing countries. The dependent variable in this model is the demand for law – the extent to which business owners and firm managers engage the formal legal system and attempt to mobilize the law to their advantage when making market decisions. Demand for law is a crucial micro-connection in the causal chain linking law and law reform to market expansion and economic development. The theoretical framework developed here focuses on the interplay between informal and formal social institutions in influencing market decisions made by private sector actors. The article tests hypotheses generated by this framework by analyzing survey data collected from business firms in Dar es Salaam, Tanzania. The results support the hypothesis that demand for law is shaped by informal market institutions, particularly the informal business networks developed and maintained by firms. The analysis further suggests that these “demand-side” variables matter more than “supply-side” variables identified in the social science literature. These findings have important implications for law reform initiatives in developing countries and suggest avenues for further social science research on the relationship between law and economic development.
[Protective effect of capsaicin on against myocardial ischemia-reperfusion injury of rat in vivo].

OBJECTIVE To explore whether the capsaicin offers protective effect and possible mechanism on against myocardial ischemia-reperfusion injury of rat in vivo. METHODS Ligating the left anterior descending coronary artery for 45 min and loosing it for 120 min were performed to establish the rat model of local myocardial ischemia-reperfusion injury in vivo. Forty healthy male rats were randomly divided into control group, capsaicin group, capsazepine group, and S-3144 group. In 10 min and 5 min before ischemia, all drugs for this study were delivered into rat left ventricle (LV) via right carotid artery. Variations of left ventricular function were successively monitored with ECG (electrocardiogram). Levels of creatine kinase MB (CKMB) in serum were determined. Evans-blue and TTC were utilized to identify the area at risk and the infarct size of LV. RESULTS In all groups, the variables of left ventricular developed pressure (LVDP) significantly decreased after ischemia and reperfusion (P < 0.05). Except capsaicin group, heart rates (HR) of three other groups markedly reduced with reperfusion for 120 min as compared to pre-reperfusion (P < 0.05). In capsaicin group, there were significant increases in HR and LVDP with reperfusion for 120 min when compared with the other three groups (P < 0.05). At the end of experiment, the levels of CKMB and infract size were lower in capsaicin group than in the other three groups (P < 0.05), and there was no statistical significance among the other three groups (P > 0.05). CONCLUSION Pretreatment with capsaicin can attenuate myocardial ischemia-reperfusion injury, of which the likely mechanism is by stimulating capsaicin receptor or TRPV1 and further activating substance P receptor in the rat in vivo.
The Utility of Dynamic Flexion-Extension Radiographs in the Initial Evaluation of the Degenerative Lumbar Spine

Study Design. Retrospective radiographic review. Objective. To assess the utility of lateral dynamic flexion-extension radiographs in the initial evaluation of the degenerative lumbar spine. Summary of Background Data. Most surgeons obtain standing anteroposterior (AP) and lateral radiographs in the initial evaluation of patients presenting with lumbar complaints. The potential role of dynamic films in this population has not been established. Methods. Of a 390 radiograph series, 342 met inclusion criteria and were reviewed. After assessment of the AP and lateral radiographs, dynamic films were evaluated to determine if additional information was obtained. Results. Only 2 of the 342 radiographic series had new findings seen on dynamic films not appreciated on the AP and lateral films (a L3–L4 anterolisthesis of 3 mm with flexion and a L5–S1 retrolisthesis of 4 mm with extension). Fifteen additional radiographic series were noted to have a change in the amount of anterolisthesis or retrolisthesis on the dynamic films (changes ranged from 2 to 5 mm). Conclusion. In the population studied, dynamic radiographs did not significantly alter the initial course of clinical management beyond standing AP and lateral lumbar images.
Accounting as a tool of State governance: The tutelage system of ‘Free Africans’ in Brazil between 1818 and 1864

Through the theoretical lenses of Foucault’s governmentality, Latour’s action at a distance and Althusser’s ideology theory, this article shows how accounting regulations allowed the Brazilian government to exercise control over the tutelage system of former slaves (‘Free Africans’) between 1818 and 1864. It finds that the measures undertaken to reinforce the accounting regulations permitted the Brazilian government to control ‘Free Africans’ at a distance while minimizing interference in this process from a British government intent upon abolishing slavery.
Radiation mechanism of H-shaped antenna using parallel resonance mode

It is required to work in various surrounding environments in order that the small antennas used for mobile terminal and RFID tag are located in the vicinity of various objects including the human body and the metal. H-shaped antenna has been proposed to obtain the characteristics not to be changed by circumference environment. The H-shaped antenna has been designed by adjusting offset position and the ratio between the lengths of parallel elements. As a result of examination about the antenna height (h), the shift of input impedance near the metal was the smallest when h=0. 04ε.