Understanding the impacts of environmental, economic, and policy factors on developing economies

The first chapter of this dissertation studies the long-term effects of climate conditions during an individual's birth year on their life cycle. Drawing on data from the India Human Development Survey and monthly rainfall data from the Global Historical Climatology Network, the study focuses on adults born between 1965 and 1978. The analysis reveals that higher rainfall levels during the birth year are associated with improved socioeconomic outcomes in an individual's health, schooling, and income over time. However, the presence of birth-year rainfall volatility has a contrasting negative impact, with men experiencing a stronger effect compared to women due to pre-existing gender inequality in India. Notably, regions relying on rice farming show heightened susceptibility to the influence of rainfall on health and schooling during adulthood. These findings underscore the significance of early-life climate conditions, particularly the importance of adequate nutrition during infancy, in shaping an individual's long-term well-being. In the second chapter, we delve into the evaluation of the IMF's Structural Adjustment Programs (SAP) and their impact on the IMF's yearly growth predictions for member countries. The analysis centers on a dataset consisting of 158 countries during the period from 1990 to 2004. The Structural Adjustment Programs were implemented by the IMF in the early 1980s and required member countries to fulfill specific conditions to receive loan tranches. We find that the IMF tends to overestimate future growth in countries subjected to a higher number of SAP conditions. This research sheds light on the IMF's perception of SAP allocation and its implications for a country's future growth. The effectiveness of SAP remains a contentious topic, and these findings contribute valuable insights into how these programs may impact a country's economic prospects. In the third chapter, the impact of China's Cleaner Production Law on firm behavior and long-term investment decisions is studied using a Synthetic Difference-in-Differences (SDID) framework. We focus on the role of county governments' environmental budgets in shaping firms' investment decisions, highlighting the importance of effective monitoring mechanisms. Although the implementation of environmental laws resulted in changes in firm behavior, we did not find statistically significant reductions in pollution levels after the implementation of the law. This is owing to the fact that pollution levels are affected by multiple variables apart from manufacturing activities. We also run a battery of sensitivity tests to check the validity of our results and find that the main results are consistent across various frameworks

Sulfatase‐mediated manipulation of the astrocyte‐Schwann cell interface

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6‐O‐sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC‐astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC‐S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC‐S1S2s have increased integrin‐dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor‐linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC‐astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase‐mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC‐like in character. This approach may be beneficial for cell transplant‐mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19–3

Syndromics: A Bioinformatics Approach for Neurotrauma Research

Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings

Systemic and Local Cytokine Profile following Spinal Cord Injury in Rats: A Multiplex Analysis

Our study of the changes in cytokine profile in blood serum and in the spinal cord after traumatic spinal cord injury (SCI) has shown that an inflammatory reaction and immunological response are not limited to the CNS, but widespread. This fact was confirmed by changes detected in a cytokine profile in blood serum samples [MIP-1 alpha, interleukin 1 (IL-1) alpha, IL-2, IL-5, IL-1 beta, MCP-1, RANTES]. There were also changes in the levels of MIP-1 alpha, IL-1 alpha, IL-2, IL-5, IL-18, GM-colony-stimulating factor, IL-17 alpha, IFN-gamma, IL-10, IL-13, MCP-1, and GRO KC CINC-1 in samples of the rat injured spinal cord. The results underscore the complex cytokine network imbalance exhibited after SCI and show significant changes in the concentrations of 14 cytokines/chemokines with different inflammatory and immunological activities

Central nervous system injury triggers hepatic CC and CXC chemokine expression that is associated with leukocyte mobilization and recruitment to both the central nervous system and the liver

The administration of interleukin-1ß to the brain induces hepatic CXC chemokine synthesis, which increases neutrophil levels in the blood, liver, and brain. We now show that such hepatic response is not restricted to the CXC chemokines. CCL-2, a CC chemokine, was released by the liver in response to a tumor necrosis factor (TNF)- challenge to the brain and boosted monocyte levels. Furthermore, a clinically relevant compression injury to the spinal cord triggered hepatic chemokine expression of both types. After a spinal cord injury, elevated CCL-2 and CXCL-1 mRNA and protein were observed in the liver by TaqMan reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay as early as 2 to 4 hours. Simultaneously, we observed elevated levels of these chemokines and circulating leukocyte populations in the blood. Leukocytes were recruited to the liver at this early stage, whereas at the site of challenge in the central nervous system, few were observed until 24 hours. Artificial elevation of blood CCL-2 triggered dose-dependent monocyte mobilization in the blood and enhanced monocyte recruitment to the brain after TNF- challenge. Attenuation of hepatic CCL-2 production with corticosteroids resulted in reduced monocyte levels after the TNF- challenge. Thus, combined production of CC and CXC hepatic chemokines appears to amplify the central nervous system response to injury

Immunoreactivity of arcuate nucleus astrocytes in rats after intragastric administration of habanero peppers (Capsicum Chinese Jacq.)

Habanero pepper fruits contain capsaicin (CAP) characterised by a spicy taste. Astrocytes express vanilloid receptor (TRPV1), which interacts with cannabinoids including CAP. Only a few studies revealed that CAP leads to alterations of the arcuate nucleus (ARC) structures. The aim of this study was to analyse the GFAP (GFAP-IR) and S100β (S100β-IR) immunoreactive astrocytes of ARC in adult rats after intragastric administration of habanero pepper fruits. Adult, Wistar rats received a peanut oil – control group (C) – and oil suspension of habanero pepper fruits at a dose of 0.08 g dm/kg b.w. for 7 days – E1 group – and 28 days – E2 group. After euthanasia, the brains were embedded in paraffin blocks using a routine histological technique. Frontal slices of ARC were immunohistochemically stained for GFAP and S100β using specific antibodies in the peroxidase-antiperoxidase method. Astrocytes of ARC were morphologically and morphometrically analysed under a light microscope. The results of the study did not reveal statistically significant changes in the density of GFAP-IR cells in E1 and E2 groups of rats in comparison with group C. A statistically significant increase in the density of S100β-IR astrocytes was observed in the E1 group and a decrease in the E2 group. Astrocytes with expression of both studied proteins were characterised by morphological alterations in ARC in the E2 group. The obtained results suggest an influence of CAP contained in habanero pepper fruits on the reactivity of astroglia, which may have an impact on the astrocyte-neuron interactions in order to maintain a proper activity of nervous cells in ARC