Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin Reverses the High-Fat Diet–Induced Increase in Brain Aβ and Improves Memory in an Animal Model of Alzheimer Disease

Defects in insulin production and signaling are suspected to share a key role in diabetes and Alzheimer disease (AD), two age-related pathologies. In this study, we investigated the interrelation between AD and diabetes using a high-fat diet (HFD) in a mouse model of genetically induced AD-like neuropathology (3xTg-AD). We first observed that cerebral expression of human AD transgenes led to peripheral glucose intolerance, associated with pancreatic human Aβ accumulation. High-fat diet enhanced glucose intolerance, brain soluble Aβ, and memory impairment in 3xTg-AD mice. Strikingly, a single insulin injection reversed the deleterious effects of HFD on memory and soluble Aβ levels, partly through changes in Aβ production and/or clearance. Our results are consistent with the development of a vicious cycle between AD and diabetes, potentiating both peripheral metabolic disorders and AD neuropathology. The capacity of insulin to rapidly break the deleterious effects of this cycle on soluble Aβ concentrations and memory has important therapeutic implications.
Habituation of the infant arousal response.

STUDY OBJECTIVES Arousal is considered to be an important protective response in a sleeping infant and its depression could leave an infant vulnerable to a life threatening stimulus. We found previously that arousal to a non-respiratory (tactile) stimulus occurs in a sequence of events that begins with spinal, followed by brainstem responses, and then a cortical electroencephalographic (EEG) arousal response. We hypothesized that repeated stimuli would depress the arousal responses by habituation and that spinal and brainstem responses would be more resistant to habituation than cortical responses. PARTICIPANTS We studied 22 normal infants. INTERVENTIONS The infants underwent polysomnographic monitoring during a daytime nap. Tactile stimuli was applied to the infants foot at 5-second intervals. MEASUREMENTS AND RESULTS We found that spinal, brainstem, and cortical responses occurred on the first trial of each test. Repeated trials during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep resulted in a decrease in the incidence of each individual response and eventually elimination of the arousal responses. Cortical responses were eliminated first, followed by brainstem responses and finally spinal responses. The elimination of each of the responses occurred more rapidly during REM sleep that during NREM sleep. CONCLUSIONS Habituation of the infant arousal sequence occurs with repeated tactile stimulation. There is a serial habituation of responses from the cortical to the spinal level, which occurs more rapidly during REM sleep. Rapid habituation to innocuous stimuli is probably beneficial in avoiding detrimental sleep disruptions. However, in situations requiring the protective functions of arousal, such habituation could be detrimental to an infant.
Proliferation and differentiation markers in snuff-induced oral mucosal lesions.

BACKGROUND Regular use of snuff is known to cause whitish oral mucosal lesions of variable severity at the usual quid placement site. The main aim of this study was to elucidate cellular mechanisms involved in snuff-induced epithelial changes. METHODS Expression patterns for markers of cell proliferation (PCNA, Ki-67), cell cycle regulation (p53, p21), keratin changes (pankeratin, CK18, CK19), cell stress (HSP 70) and collagen type IV in 14 snuff-induced oral mucosal lesions and 12 control samples were analyzed by immunohistochemistry (IHC). RESULTS On light microscopy, all snuff-induced lesions were characterized by a hyperkeratinized and thickened epithelium. Some vacuolized cells, markers of cell degeneration, were frequently seen (in 9/14 of the samples) in the superficial layers in epithelia. Expression of PCNA and Ki-67 was found in a statistically significantly fewer cells in snuff-induced lesions (P < 0.001) than in the controls. This indicates that epithelia in snuff-induced lesions are not thickened as a result of increased cellular proliferation, but by protracted turnover of differentiating cells. Of cell cycle markers, p21 was found be up-regulated in 4/14 snuff-induced lesions, probably by p53-independent pathways. Only two snuff-induced lesions showed p53 positivity. However, the number of stained cells with p53 and p21 was not statistically different from that in controls. Expression of CK18, but not any alterations in CK19 expression, was seen in 5 of 14 snuff-induced lesions. Snuff also seems to stimulate the expression of collagen type IV, possibly by basal cells, as indicated by the thickened staining of the basal lamina. CONCLUSIONS The findings of this study showing suppressed cellular proliferation and infrequent p53 dysfunction in snuff lesions may partly explain why dysplastic changes are seldom seen in mucosal lesions induced by the Scandinavian type of snuff.
Why Canada Goes to War: Explaining Combat Participation in US-led Coalitions

Abstract Canada has taken part in six wars since 1945, all of which have been conducted under US leadership. Despite such military interventionism, there have been no systematic comparative analyses of Canada's decisions to take part in US-led wars. The objective of this article is to develop and test a theoretical framework about why Canada goes to war. More specifically, it seeks to account for variations in Canada's provision of combat forces to multinational interventions led by the United States. It assesses leading theoretical explanations by examining five post–Cold War cases: the wars in Kosovo, Afghanistan and Libya; the war against ISIS; and the refusal to take part in the invasion of Iraq. The article concludes that Canada's willingness to go to war is shaped primarily by a desire to maintain transatlantic alliance unity and enhance Canada's alliance credibility. Threats to national security, the legitimacy of the intervention, government ideology and public opinion are not found to consistently or meaningfully shape Canadian decisions to take part in US-led wars. Résumé Le Canada a participé à six guerres, depuis 1945, au sein de coalitions multinationales dirigées par les États-Unis. Malgré cet interventionnisme militaire, peu d’études ont cherché à cerner les motivations qui amènent le Canada à faire la guerre. L'objectif de cet article est d'offrir un cadre analytique capable d'expliquer pourquoi le Canada fait la guerre. Il propose une comparaison structurée et ciblée de six décisions de prendre part, ou non, à des opérations de combat au sein d'une coalition militaire dirigée par les États-Unis, au Kosovo, en Irak, en Afghanistan, en Libye et contre le groupe État islamique. L'article démontre que le Canada semble faire la guerre principalement pour deux raisons complémentaires : afin d'assurer l'unité de l'Alliance transatlantique ainsi que son statut d'allié fiable. En contrepartie, les menaces contre la sécurité nationale, la légitimité de l'intervention militaire, l'idéologie du gouvernement et l'opinion publique n'ont pas influé de manière systématique ou significative sur la décision de faire la guerre.
Understanding causes of volatility in onion prices in India

Purpose Post-2008 global food crisis the prices of perishable high-value food commodities, such as vegetables and fruits, in India have risen faster and become more volatile compared to that of cereals. The welfare consequences of price shocks though are well understood yet the policy responses to manage these remain blurred because of a lack of clarity on their causes. Focusing on onions that comprise an important constituent of the Indian diet, the purpose of this paper is to explore causes of high price volatility. Design/methodology/approach Using high-frequency time series data on wholesale prices and arrivals of onions in major markets and other relevant variables, this paper analyzes causes of price volatility from several angles, that is production shocks, seasonality in production and market arrivals, internal trade, export policies and market power of intermediaries on the supply chain. Findings Despite markets being integrated and no significant climatic shocks to production there exists a strong element of uncertainty in market arrivals of onions, pointing toward the market power immediate downstream the production or alternatively anti-competition trade practices in major markets as a cause of high price volatility. The measures to manage price volatility, such as an increase in minimum export prices and bans on exports, are also not found to have an immediate cooling effect on prices. Research limitations/implications The agricultural policy should provide for a system of market intelligence to monitor anti-competitive trade practices along the supply chain, and to take proactive trade control measures to prevent frequent ups and downs in domestic prices. In addition, it should provide for incentives for developing efficient supply chains and for the cultivation of onions in the regions that have agronomic potential but it has remained underexploited due to one or the other constraint. Social implications Excessive volatility in food prices impacts farmers, consumers, processors, and traders and even political system. It may distort production and investment decisions of farmers and intermediaries on the value chains, leading to inefficient allocation of resources. The poor consumers may be forced to reduce food and non-food productive expenditures. If persists for a longer period, it may lead to political instability too. Originality/value Several studies have analyzed volatility in food prices and causes thereof. However, rarely any of these has examined volatility in prices of perishable high-value food commodities. This paper is an attempt toward filling this gap.
Societal costs and morbidity of pertussis in adolescents and adults.

BACKGROUND Since the 1980s, the reported incidence of pertussis among adolescents and adults has been steadily increasing. To understand whether the benefits of an acellular pertussis vaccine formulated for adolescents and adults might offset its costs, policy makers will need information about morbidity and societal (medical and nonmedical) costs of pertussis. METHODS Adolescents (age, 10-17 years) and adults (age, >or=18 years) with confirmed pertussis illness were identified by the Massachusetts enhanced pertussis surveillance system. We evaluated medical costs in a cohort of patients who had confirmed pertussis during the period of January 1998 through December 2000; nonmedical costs, by means of prospective interviews, in a cohort of patients who had confirmed pertussis during the period of December 2001 through January 2003; and morbidity in both cohorts. Our main outcome measures were mean costs per case, in 2002 US dollars. RESULTS In the analysis of medical costs, 1679 adolescents and 936 adults were found to have mean costs of 242 dollars and 326 dollars, respectively (P<.05). In interviews with 314 adolescents and 203 adults, adults had significantly higher nonmedical costs (447 dollars) than those of adolescents (155 dollars). A total of 83% of adolescents missed a mean of 5.5 days from school (range, 0.4-32 days), and 61% of adults missed a mean of 9.8 days from work (range, 0.1-180 days) because of pertussis. Thirty-eight percent of adolescents and 61% of adults were still coughing at the time of the interview, which occurred an average of 106 days and 94 days, respectively, after cough onset. CONCLUSIONS Pertussis causes significant morbidity in and costs for adolescents and adults, with time losses comprising the largest proportion of the cost. Societal costs should be considered when making decisions about potential vaccine use in the future.
Trait Impulsivity and Change in Mental Health Problems After Violent Crime Victimization

Violent crime victimization can have serious mental health consequences, but what it is that makes victims at risk of mental health problems or delayed recovery from such problems is largely unknown. Previous research has focused on, amongst other things, the disabling impact of personality factors involved in the regulation of emotions. Using data from the Dutch Longitudinal Internet Studies for the Social Sciences (LISS) panel (n = 2628), this study explored whether the association between violent crime victimization and change in mental health problems over a 1-year time span also varies by trait impulsivity (TI)—a personality factor involved in regulating behavior. TI may serve as a risk factor for mental health problems, but research into this topic is scarce and inconsistent. Results suggested that low TI subjects are prone to experience an increase in mental health problems following victimization. As a possible explanation for this finding, it was speculated that subjects with low TI do not perceive themselves at risk of victimization and thus see this positive assumption shattered when victimization does occur. Results were further discussed in terms of study limitations and strengths and implications for future research.
Ecological Genetics and Natural Selection in Molluscs

Polymorphic snails of the genus Cepaea have been widely used for research in ecological genetics. Natural selection by selective predation is important in controlling morph frequencies in some populations of C. nemoralis in England. The importance of environmental selection in affecting other patterns of local genetic differentiation of population structure (area effects) is a matter of controversy. Some authors emphasize divergent evolution of whole gene pools between area effects, while others feel that climatic selection acting on individual loci is important. Analysis of 500,000 C. nemoralis snails from throughout Europe shows that there is a strong positive association between gene frequencies at the shell color locus and mean summer temperature, but that no climatic correlations are obvious at other loci. Another species, C. vindobonensis, which has a much simpler system of polymorphism than does C. nemoralis, was investigated in Yugoslavia, in a region where there is known to be intense microclimatic differentiation because of the accumulation of cold air in frost hollows. There was a striking tendency for snails with lightly pigmented shell bands to be found in places with a warm microclimate. Physiological and behavioral experiments demonstrate that this is due primarily to differential energy absorption from sunshine by the different shell phenotypes. As in C. nemoralis, other C. vindobonensis phenotypes show no detectable association with the environment. It is possible that genes whose frequencies cannot be related to environmental selection may have evolved strong linkage interactions with other genes in the population's gene pool. Selection by the ecological environment and the genetic environment may therefore both be important in controlling the genetic structure of snail populations.
Analyzing the effect of financial development on economic growth – the Jordanian experience

This study came to inspect the impact of the development of both financial market and banking system on the economic growth of Jordan based on the annual data covering the period 1993–2017. Through the use of many methodologies: Johansen cointegration test, (VECM), and Granger causality test, where real GDP was used as an indicator of economic growth, the real market value of stocks (Market Capitalization) (LCAP) and Share Turnover (LTURN) are indicators for the financial market, Money supply in the broad concept (LM2), and Local domestic credit (LCR) are indicators for the banking sector.The results of this study reported that the study variables are stationary, and in the level of order 2, they are integrated, and a long-run relationship between the study variables existed according to the Johansen co-integration test. VECM model result and the target model result confirm a short-run causality running from the all variables toward GDP. Granger causality test underline a single directional causality running from variables of our study to GDP and denote the short-run impact between LCAP, LTURN, LM2, LCR, and LGDP. The analysis of the variance decomposition shows that the development of the banking system affects economic growth almost equally with the impact of the development of the financial market. The results go to the same line of supply-leading hypothesis.
A Mouse Herpesvirus Induces Relapse of Experimental Autoimmune Arthritis by Infection of the Inflammatory Target Tissue1

It is not known what is required for successive relapses in autoimmune diseases or evolution to a progressive chronic disease. Autoimmune arthritis caused by passive transfer of autoantibodies against glucose 6-phosphate isomerase is transient and therefore lends itself well to test for what might extend the disease. Herpesviruses have long been suspected of contributing to human autoimmune disease. We infected mice with a murine gamma-herpesvirus (MHV-68). In immunodeficient mice, transient arthritis was followed by a relapse. This was due to lytic viral infection of synovial tissues demonstrated by PCR, immunohistochemistry, and electron microscopy. Latent infection could be reactivated in the synovium of normal mice when treated with Cytoxan and this was associated with increased clinical arthritis. We conclude that herpesviruses may play an ancillary pathogenic role in autoimmune arthritis by infection of the inflammatory target tissue.
Environmental contaminants in bald eagle eggs from the Aleutian archipelago

We collected 136 fresh and unhatched eggs from bald eagle (Haliaeetus leucocephalus) nests and assessed productivity on eight islands in the Aleutian archipelago, 2000 to 2002. Egg contents were analyzed for a broad spectrum of organochlorine (OC) contaminants, mercury (Hg), and stable isotopes of carbon (δ13C) and nitrogen (δ15N). Concentrations of polychlorinated biphenyls (∑PCBs), p,p'‐dichlorodiphenyldichloroethylene (DDE), and Hg in bald eagle eggs were elevated throughout the archipelago, but the patterns of distribution differed among the various contaminants. Total PCBs were highest in areas of past military activities on Adak and Amchitka Islands, indicating local point sources of these compounds. Concentrations of DDE and Hg were higher on Amchitka Island, which was subjected to much military activity during World War II and the middle of the 20th century. Concentrations of ∑PCBs also were elevated on islands with little history of military activity (e.g., Amlia, Tanaga, Buldir), suggesting non–point sources of PCBs in addition to point sources. Concentrations of DDE and Hg were highest in eagle eggs from the most western Aleutian Islands (e.g., Buldir, Kiska) and decreased eastward along the Aleutian chain. This east‐to‐west increase suggested a Eurasian source of contamination, possibly through global transport and atmospheric distillation and/or from migratory seabirds. Eggshell thickness and productivity of bald eagles were normal and indicative of healthy populations because concentrations of most contaminants were below threshold levels for effects on reproduction. Contrary to our predictions, contaminant concentrations were not correlated with stable isotopes of carbon (δ13C) or nitrogen (δ15N) in eggs. These latter findings indicate that contaminant concentrations were influenced more by point sources and geographic location than trophic status of eagles among the different islands.
Population pharmacokinetics of stavudine (d4T) in patients with AIDS or advanced AIDS-related complex

The population pharmacokinetics and bioavailability of oral stavudine (d4T; 2',3'-dideoxy-3'-deoxythymidine) was determined in 81 patients with AIDS or AIDS-related complex (ARC) enrolled in phase I and phase I/II dose-ranging trials. Each patient underwent inpatient pharmacokinetic studies following administration of the first oral stavudine dose; 59 patients were restudied after chronic therapy for an average of 19 days. Thirty-three of these patients also received a single intravenous stavudine dose prior to starting an oral regimen. A two-compartment model with first-order absorption and elimination was used as the structural pharmacokinetic model. A basic model provided the following population parameter estimates (interpatient variability expressed in parentheses as percent coefficient of variation): clearance/bioavailability = 30.9 (24.5%) liters/h; volume of distribution/bioavailability = 8.42 (not modeled) liters; volume of distribution at steady state/bioavailability = 68.9 (105%) liters; intercompartmental clearance/bioavailability = 12.4 (26%) liters/h; and first-order absorption rate constant = 1.32 (78.9%) liters/h. In the subset of 33 patients receiving both intravenous and oral doses, the bioavailability of stavudine was estimated to be 99.1% (18.5%). Total body weight, stage of disease (AIDS versus ARC), and an oral stavudine dose of > or = 200 mg were found to have a statistically significant but a clinically marginal effect on the estimate of the oral clearance of stavudine. This analysis shows the high degree of bioavailability of stavudine in patients with AIDS and ARC and the relatively low degree of interpatient variability in oral drug clearance compared with those of other nucleosides. Population pharmacokinetic analysis is a useful tool for assessing the combined effects of several patient variables on the pharmacokinetic properties of drugs in human immunodeficiency virus-infected patients.
Transient focal cerebral ischemia-induced neurogenesis in the dentate gyrus of the adult mouse.

OBJECT Throughout the life of a mammal, new neurons are produced each day from resident progenitor cells located in the hippocampal dentate gyrus (DG). The availability of transgenic and knockout mice enables the evaluation of specific molecular mediators of this phenomenon. To facilitate such studies the authors characterized the proliferation, survival, and maturation of progenitor cells in the DG of adult mice following transient focal cerebral ischemia. METHODS Anesthesia was induced in adult C57BL/6 mice by administering halothane. The middle cerebral artery (MCA) was then occluded for 120 minutes by applying an endovascular suture. The marker used to detect the presence of proliferating cells, 5-bromodeoxyuridine (BrdU; 50 mg/kg) was administered intraperitoneally twice daily on Days 2 through 6 after the MCA occlusion. Cohorts of mice were killed on Days 7 and 21, after which their brains were sectioned and BrdU-positive cells were detected using immunohistochemical analysis. The phenotype of the BrdU-positive cells was identified by fluorescent triple labeling by using antibodies specific for neuronal and astroglial markers together with anti-BrdU antibodies. The infarction was confirmed by applying cresyl violet staining. Compared with sham-operated control animals, there was a 4.6-fold (p < 0.05) increase in BrdU-positive cells in the ipsilateral DG at Day 7 postischemia. Twenty-one percent of the newly proliferated cells survived to Day 21 postischemia. At this time, the newly proliferated cells expressed the immature and mature neuron markers doublecortin and NeuN, respectively, but none expressed the astroglial marker glial fibrillary acidic protein. CONCLUSIONS Focal ischemia induces neurogenesis in the DG of the mouse brain; this may be critical for postischemic brain repair.