Does Africa trade less than it should, and if so, why?: The role of market access and domestic factors

"This paper addresses the question of whether Africa is an undertrading continent. We answer this question using a much-improved data set for obtaining predicted trade and by employing methods that correct for bias in estimates of undertrading. Our results indicate that globally Africa is an underexporter in our preferred Heckman specification. This result is robust to the addition of various controls and the application of variants of the gravity model of trade. We also looked for explanations for Africa's undertrading. We found that accounting for transport and communication infrastructure reduced the undertrading effect for Africa, and in some specifications of the gravity model, the under-trading effect vanished altogether. Results from a semiparametric model provided evidence of significant nonlinear impacts from infrastructure, and the effects for a large number of African countries was significant and compared favorably with the marginal effects of infrastructure in countries on other continents and in comparable income brackets. Using this model we also found evidence of complementarity across transport and communication infrastructure, implying that much greater impacts will be likely if the infrastructure are developed jointly rather than in isolation." from Author's AbstractGravity model, Undertrading, Trade related infrastructure, Market access,

Effects of acute alcohol exposure on glutamate neurotransmission in adolescents and adults : a preclinical study

The age at which an individual first uses alcohol is a powerful predictor of alcohol dependence later in life. Brain development and maturation continues during adolescence until adulthood in humans. There are continuous morphological and functional altera tions within the brain areas involved in emotions, learning, decision - making and reward - motivated behavior s and alcohol exposure during this period may modify the development of these regions, increasing the sensitivity of adolescents to some of alcohol’s effects. Thus, adolescents might be or may become more sensitive to the rewarding properties of alcohol than adults. Despite the important role of glutamate neurotransmission for brain development and many other brain functions and despite the fact that et hanol consumption during adolescence may have a detrimental impact on these functions, we know surprisingly little about glutamatergic transmission in the adolescent brain and its modulation by alcohol. Here the acute effects of ethanol on glutamatergic ne urotransmission in nucleus accumbens (NAc) were studied using brain slice electrophysiology and glutamate release and dynamics in the prefrontal cortex (PFC) were studied using enzyme - based microelectrode amperometry. The results of the present thesis reve al several age - dependent differences in glutamatergic neurotransmission in these brain regions. Using extracellular electrophysiology, I found that the inhibitory effect of acute ethanol on glutamatergic transmission (fEPSP/PS) in the NAc was higher in bra in slices from adolescent animals compared to brain slices from adults. As previously reported, the mechanism by which acute ethanol inhibits glutamate neurotransmission was found to be presynaptic inhibition of glutamate release and this effect was blocke d by GABA receptor antagonists. Moreover, acute ethanol was found to inhibit the induction on long - term potentiation ( LTP ) in the NAc. In the PFC, glutamate levels in freely moving animals were measured and it was found that basal levels of glutamate were more than three times higher in adolescent animals than in adults. Spontaneous release of glutamate in terms of glutamate transients was higher in the PFC of adolescent rats than in the PFC of adult rats. The transients were inhibited by ethanol in the ado lescent animals but they were unaffected in the adults. The data in my thesis thereby confirms previous studies suggesting age - dependent differences in glutamatergic neurotransmission in response to ethano l and extend our knowledge about effects of ethan ol on adolescent brain. These age - related differences and differential effects of alcohol on glutamate neurotransmission in adolescent animals may be a contributing factor underlying the increased susceptibility of a young individuals’ brain to develop alcoh olism or other addictions later in life

Effect of yoga and meditation on serum cortisol level in first-year medical students

Background: Yoga is a traditional technique to conserve and purify body, mind and soul. It is a mind-body bridge which involves relaxation, meditation and a set of physical exercises performed in association with breathing. In this new era of evolution, most of the population are depressed or in stress, irrespective of their age and gender.Methods: This study is performed on 1st yr. medical students whose stress level is in higher side due to academic burden. An 55 medical students were selected as participants through counseling and were divided into yoga group (n= 27) and control group (n=28). Their morning serum cortisol level was assessed, and yoga group were instructed to practice yoga (1hr/day for 12 weeks) under supervision of yoga instructor. No such instruction was given to control group.Results: Serum cortisol level is the marker of stress and inflammation. Higher cortisol level means high stress level. Yoga and meditation is documented to reduce stress level in regular practitioners.  Statistical analysis has shown decrease in morning serum cortisol level (572.18±168.03 to 544.98±139.89, 4.8% decrease, P value ˂0.05, significant) in yoga group after study. Control group have shown marked increase in cortisol level (558.89±162.69 to 577.26±254.5, 3.4% increase, P value = 0.74, not significant) after three months of study.Conclusions: This study concludes that practicing Yoga has a significant effect on the reduction of stress and anxiety level in medical students

Drug repositioning: current scenario and future prospective for rewriting saga of drug development

Drug development is a process that demands huge investment of resources and time with only 1 drug candidate successful in reaching market among 10,000 screened taking time duration of 10-15 years and millions of dollars. This high attrition rates discourage investors and researchers. The pharmaceutical industry is shifting its attention away from de novo drug research and towards discovering novel targets and indications for already-approved drugs. In order to accelerate the drug development process with reduced risk of failure and relatively lower costs, pharmaceutical companies have adopted drug repositioning as an alternative. Therefore, a good strategy for drug development would be drug repositioning or drug repurposing, which is to identify, investigate, and exploit new therapeutic uses of already-available, on-market drugs, as well as those that have been withdrawn due to toxicities or that remain on shelves in various stages of development. The outbreak of SARS-COV-19 shows that humanity is constantly vulnerable to epidemics and new microbial attacks and that there is no time to create disease-specific therapies. Consequently, it would seem advantageous to use what is already accessible. Novel therapeutic indications that have previously been approved by the market can reduce investment costs significantly in terms of money, resources, and most importantly, time, as long as they meet PKPD and toxicity standards. Sponsors and pharmaceutical corporations get enthusiastic about additional investments and initiatives related to drug development as a consequence. The upcoming therapeutic revolution, especially with the aid of artificial intelligence, is indicated by the successful applications of several already-available drugs against COVID-19 and the various phases of repurposed drugs against TB, colorectal cancer, Alzheimer’s disease, cervical cancer, and Parkinsonism

The development and application of a process model for R&D project management in a high tech firm: A field study

a b s t r a c t In R&D organizations of high tech firms, multiple R&D projects are executed concurrently and timeliness of project completion -i.e., developing the right products at the right times -is a matter of serious concern. Given that the priority of R&D projects and the interdependencies between the projects in a high tech firm change dynamically, high tech R&D project management is a complex and challenging endeavor. To improve the understanding and management of high tech R&D projects, this paper reports the findings of a field study where we, first, develop and empirically estimate a model that relates project priority over time with the generative mechanisms of market pull and technical challenge associated with R&D projects. Next, we develop and demonstrate the application of a process model within which the time-varying project priority model is embedded. The process model makes it possible to allocate fixed resources among competing projects with time-varying interdependencies, thereby improving the timeliness of project completion. This research was conducted in collaboration with a major U.S. high tech firm. The corporate R&D center of the firm served as the research setting for the field study. We present an application of the process model to delineate the evolution of the R&D organization with the merger of its (technology driven) parent firm with another (market driven) high tech manufacturing firm. The application of the process model generates theoretical insights that are used to develop testable propositions. Implications of the study findings and directions for future research are discussed

Parabrachial Interleukin-6 reduces body weight and food intake and increases thermogenesis to regulate energy metabolism

Chronic low-grade inflammation and increased serum levels of the cytokine IL-6 accompany obesity. For brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. Here, we show that brain-produced IL-6 is decreased in obese mice and rats in a neuroanatomically and sex-specific manner. Reduced IL-6 mRNA localized to lateral parabrachial nucleus (lPBN) astrocytes, microglia, and neurons, including paraventricular hypothalamus-innervating lPBN neurons. IL-6 microinjection into lPBN reduced food intake and increased brown adipose tissue (BAT) thermogenesis in male lean and obese rats by increasing thyroid and sympathetic outflow to BAT. Parabrachial IL-6 interacted with leptin to reduce feeding. siRNA-mediated reduction of lPBN IL-6 leads to increased weight gain and adiposity, reduced BAT thermogenesis, and increased food intake. Ambient cold exposure partly normalizes the obesity-induced suppression of lPBN IL-6. These results indicate that lPBN-produced IL-6 regulates feeding and metabolism and pinpoints (patho)physiological contexts interacting with lPBN IL-6This research was funded by the Swedish Research Council ( 2014-2945 to K.P.S.; 2017-00792 to I.W.A.; and 2013-7107 to Patrik Rorsman), the Novo Nordisk Foundation Excellence project grant (to K.P.S. and I.W.A.), the Ragnar Söderberg Foundation (to K.P.S.), Harald Jeanssons Stiftelse and Greta Jeanssons Stiftelse (to K.P.S.), Magnus Bergvalls Stiftelse (to K.P.S.), the Wallenberg Foundation and the Center for Molecular and Translational Medicine (to K.P.S.), postdoctoral stipendium from The Swedish Brain Foundation (to D.M.), the ERC ( BFU2015-70664-R and StG-281408 ) (to R.N.), and the NIH ( DK-21397 ) (to H.J.G.)S

Interleukin-6 in the central amygdala is bioactive and co-localised with glucagon-like peptide-1 receptor

Neuronal circuits involving the central amygdala (CeA) are gaining prominence as important centres for regulation of metabolic functions. As a part of the subcortical food motivation circuitry, CeA is associated with food motivation and hunger. We have previously shown that interleukin (IL)-6 can act as a downstream mediator of the metabolic effects of glucagon-like peptide-1 (GLP-1) receptor (R) stimulation in the brain, although the sites of these effects are largely unknown. In the present study, we used the newly generated and validated RedIL6 reporter mouse strain to investigate the presence of IL-6 in the CeA, as well as possible interactions between IL-6 and GLP-1 in this nucleus. IL-6 was present in the CeA, mostly in cells in the medial and lateral parts of this structure, and a majority of IL-6-containing cells also co-expressed GLP-1R. Triple staining showed GLP-1 containing fibres co-staining with synaptophysin close to or overlapping with IL-6 containing cells. GLP-1R stimulation enhanced IL-6 mRNA levels. IL-6 receptor-alpha (IL-6R alpha) was found to a large part in neuronal CeA cells. Using electrophysiology, we determined that cells with neuronal properties in the CeA could be rapidly stimulated by IL-6 administration in vitro. Moreover, microinjections of IL-6 into the CeA could slightly reduce food intake in vivo in overnight fasted rats. In conclusion, IL-6 containing cells in the CeA express GLP-1R, are close to GLP-1-containing synapses, and demonstrate increased IL-6 mRNA in response to GLP-1R agonist treatment. IL-6, in turn, exerts biological effects in the CeA, possibly via IL-6R alpha present in this nucleus

Hindbrain insulin controls feeding behavior

Objective: Pancreatic insulin was discovered a century ago, and this discovery led to the first lifesaving treatment for diabetes. While still controversial, nearly one hundred published reports suggest that insulin is also produced in the brain, with most focusing on hypothalamic or cortical insulin-producing cells. However, specific function for insulin produced within the brain remains poorly understood. Here we identify insulin expression in the hindbrain's dorsal vagal complex (DVC), and determine the role of this source of insulin in feeding and metabolism, as well as its response to diet-induced obesity in mice. Methods: To determine the contribution of Ins2-producing neurons to feeding behavior in mice, we used the cross of transgenic RipHER-cre mouse and channelrhodopsin-2 expressing animals, which allowed us to optogenetically stimulate neurons expressing Ins2 in vivo. To confirm the presence of insulin expression in Rip-labeled DVC cells, in situ hybridization was used. To ascertain the specific role of insulin in effects discovered via optogenetic stimulation a selective, CNS applied, insulin receptor antagonist was used. To understand the physiological contribution of insulin made in the hindbrain a virogenetic knockdown strategy was used.Results: Insulin gene expression and presence of insulin-promoter driven fluorescence in rat insulin promoter (Rip)-transgenic mice were detected in the hypothalamus, but also in the DVC. Insulin mRNA was present in nearly all fluorescently labeled cells in DVC. Diet-induced obesity in mice altered brain insulin gene expression, in a neuroanatomically divergent manner; while in the hypothalamus the expected obesity-induced reduction was found, in the DVC diet-induced obesity resulted in increased expression of the insulin gene. This led us to hypothesize a potentially divergent energy balance role of insulin in these two brain areas. To determine the acute impact of activating insulin-producing neurons in the DVC, optic stimulation of light-sensitive channelrhodopsin 2 in Rip-transgenic mice was utilized. Optogenetic photoactivation induced hyperphagia after acute activation of the DVC insulin neurons. This hyperphagia was blocked by central application of the insulin receptor antagonist S961, suggesting the feeding response was driven by insulin. To determine whether DVC insulin has a necessary contribution to feeding and meta-bolism, virogenetic insulin gene knockdown (KD) strategy, which allows for site-specific reduction of insulin gene expression in adult mice, was used. While chow-fed mice failed to reveal any changes of feeding or thermogenesis in response to the KD, mice challenged with a high-fat diet consumed less food. No changes in body weight were identified, possibly resulting from compensatory reduction in thermogenesis. Conclusions: Together, our data suggest an important role for hindbrain insulin and insulin-producing cells in energy homeostasis. (c) 2022 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</p