An Overview of Brain-Derived Neurotrophic Factor and Implications for Excitotoxic Vulnerability in the Hippocampus

The present paper examines the nature and function of brain-derived neurotrophic factor (BDNF) in the hippocampal formation and the consequences of changes in its expression. The paper focuses on literature describing the role of BDNF in hippocampal development and neuroplasticity. BDNF expression is highly sensitive to developmental and environmental factors, and increased BDNF signaling enhances neurogenesis, neurite sprouting, electrophysiological activity, and other processes reflective of a general enhancement of hippocampal function. Such increases in activity may mediate beneficial effects such as enhanced learning and memory. However, the increased activity also comes at a cost: BDNF plasticity renders the hippocampus more vulnerable to hyperexcitability and/or excitotoxic damage. Exercise dramatically increases hippocampal BDNF levels and produces behavioral effects consistent with this phenomenon. In analyzing the literature regarding exercise-induced regulation of BDNF, this paper provides a theoretical model for how the potentially deleterious consequences of BDNF plasticity may be modulated by other endogenous factors. The peptide galanin may play such a role by regulating hippocampal excitability

Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk:analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants

BACKGROUND: Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. docosahexaenoic acid (DHA) and total omega-3 PUFA) and omega-6 PUFA (i.e. linoleic acid and total omega-6 PUFA) on the risk of CVDs using Mendelian randomization. METHODS: We conducted the largest genome-wide association study (GWAS) of circulating PUFA to date including a sample of 114,999 individuals and incorporated these data in a two-sample Mendelian randomization framework to investigate the involvement of circulating PUFA on a wide range of CVDs in up to 1,153,768 individuals of European ancestry (i.e. coronary artery disease, ischemic stroke, haemorrhagic stroke, heart failure, atrial fibrillation, peripheral arterial disease, aortic aneurysm, venous thromboembolism and aortic valve stenosis). RESULTS: GWAS identified between 46 and 64 SNPs for the four PUFA traits, explaining 4.8–7.9% of circulating PUFA variance and with mean F statistics >100. Higher genetically predicted DHA (and total omega-3 fatty acids) concentration was related to higher risk of some cardiovascular endpoints; however, these findings did not pass our criteria for multiple testing correction and were attenuated when accounting for LDL-cholesterol through multivariable Mendelian randomization or excluding SNPs in the vicinity of the FADS locus. Estimates for the relation between higher genetically predicted linoleic acid (and total omega-6) concentration were inconsistent across different cardiovascular endpoints and Mendelian randomization methods. There was weak evidence of higher genetically predicted linoleic acid being related to lower risk of ischemic stroke and peripheral artery disease when accounting by LDL-cholesterol. CONCLUSIONS: We have conducted the largest GWAS of circulating PUFA to date and the most comprehensive Mendelian randomization analyses. Overall, our Mendelian randomization findings do not support a protective role of circulating PUFA concentration on the risk of CVDs. However, horizontal pleiotropy via lipoprotein-related traits could be a key source of bias in our analyses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02399-w

Charm production in nonresonant e(+)e(-) annihilations at √s =10.55 GeV

This is the publisher's version also available electronically from http://journals.aps.org/prd/abstract/10.1103/PhysRevD.37.1719We report results on the differential and total cross sections for inclusive production of the charmed particles D*+, D*(0), D(0), D(+), D(s), and Λc in e(+)e(-) annihilations at √s=10.55 GeV. Widely used quark fragmentation models are discussed and compared with the measured charmed-particle momentum distributions. This comparison, as well as that with measurements at other center-of-mass energies, shows the need to take QCD corrections into account and their importance for a correct interpretation of the model parameters. The observed rate of D(0) and D(+) production is compared to the expected total charm production cross section. We measure the probability of a charmed meson being produced as a vector meson and the D*(+) decay branching fraction into D(0)π+

Effect of Iron Chelation Therapy on Recovery From Deep Coma in Children With Cerebral Malaria

Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy. To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine—pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis. The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52). Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria. (N Engl J Med 1992; 327:1473–7.), CEREBRAL malaria, one of the most severe complications of infection with Plasmodium falciparum, is especially common among young children. Despite therapy with parenteral antimalarial agents and attentive management of complications, the mortality rate is 15 to 50 percent and gross neurologic sequelae persist in about 10 percent of the children who survive.1 2 3 It is estimated that in sub-Saharan Africa alone, over 1 million children die from severe forms of malaria annually.4 , 5 Cerebral malaria is diagnosed when asexual forms of P. falciparum are found in the blood of a patient with signs of an acute, diffuse symmetric encephalopathy not attributable to

Prenatal exposure to bisphenol A and/or diethylhexyl phthalate alters stress responses in rat offspring in a sex- and dose-dependent manner

Background: Prenatal exposures to endocrine disrupting chemicals (EDCs) are correlated with adverse behavioral outcomes, but the effects of combinations of these chemicals are unclear. The aim of this study was to determine the dose-dependent effects of prenatal exposure to EDCs on male and female behavior.Methods: Pregnant Sprague-Dawley rats were orally dosed with vehicle, bisphenol A (BPA) (5 μg/kg body weight (BW)/day), low-dose (LD) diethylhexyl phthalate (DEHP) (5 μg/kg BW/day), high-dose (HD) DEHP (7.5 mg/kg BW/day), a combination of BPA and LD-DEHP (B + D (LD)), or a combination of BPA and HD-DEHP (B + D (HD)) on gestational days 6–21. Adult offspring were subjected to the Open Field Test (OFT), Elevated Plus Maze (EPM), and Shock Probe Defensive Burying test (SPDB) in adulthood. Body, adrenal gland, and pituitary gland weights were collected at sacrifice. Corticosterone (CORT) was measured in the serum.Results: Female EDC-exposed offspring showed anxiolytic effects in the OFT, while male offspring were unaffected. DEHP (HD) male offspring demonstrated a feminization of behavior in the EPM. Most EDC-exposed male offspring buried less in the SPDB, while their female counterparts showed reduced shock reactivity, indicating sex-specific maladaptive alterations in defensive behaviors. Additionally, DEHP (LD) males and females and B + D (LD) females displayed increased immobility in this test. DEHP (LD) alone and in combination with BPA led to lower adrenal gland weights, but only in male offspring. Finally, females treated with a mixture of B + D (HD) had elevated CORT levels.Conclusion: Prenatal exposure to BPA, DEHP, or a mixture of the two, affects behavior, CORT levels, and adrenal gland weights in a sex- and dose-dependent manner

The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians:A Mendelian randomization study

Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk

The scene of the crime: inventing the serial killer

This article examines the meanings of the crime scene in serial killings, and the tensions between the real and the imagined in the circulation of those meanings. Starting with the Whitechapel Murders of 1888 it argues that they, as well as forming an origin for the construction of the identity of 'the serial killer', initiate certain ideas about the relationship of subjects to spaces and the existence of the self in the modern urban landscape. It suggests that these ideas come to play an integral part in the contemporary discourse of serial killing, both in the popular imagination and in professional analysis. Examining the Whitechapel Murders, more recent cases and modern profiling techniques, it argues that popular and professional representations of crime scenes reveal more of social anxieties about the nature of the public and the private than they do about serial killers. It suggests that 'the serial killer' is not a coherent type, but an invention produced from the confusions of persons and places. Copyright 2006 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution

A new era for studies on cross-Strait relations: introduction

After more than half a century’s separation, interaction between China and Taiwan has increased and has progressively changed from a politico-economic interaction to a more civic interaction. Scholars working on cross-Strait relations have recently begun to pay attention to the civic influence of Taiwanese businesses on the relationship. Some emphasize the importance of sub-governmental interactions in the process of cross-Strait integration. Others assert that Taiwanese businesses can exercise economic leverage to constrain the Chinese government in cross-Strait policymaking. These scholars stress bottom–up processes by observing current phenomena, then deducing the emerging pattern of cross-Strait relations that may be influenced by business activities. Taking account of changing trends in scholarly discussions of the cross-Strait relationship, this special issue of China Information presents current research in this field. Unlike studies on top–down processes that affect political and economic interactions between China and Taiwan, several contributions in the special issue highlight bottom–up mechanisms affecting such interactions by examining the identity of Taiwanese businesspeople and migrants, as well as the activities and implications of Taiwanese charitable organizations operating in China. This issue focuses not only on the impact of China on Taiwan, but also the impact of Taiwanese investments, migrants, and exports on Chinese society