Switching in bacterial gene expression networks

An ability of a bacterium to appropriately respond to its environmental cues ultimately decides its fate. Bacteria deal with the fluctuating environment as a population instead of individual cells. By allowing individual cells to stochastically switch between multiple phenotypes, the cell population can make sure some cells are always fit for the environmental change. The underlying genetic circuitry plays a key role in eliciting multiple phenotypes by an isogenic population of bacteria. Understanding the underlying mechanism requires careful and systematic approach. In this study, we investigated two very well-known systems: the motility in Salmonella enterica serovar Typhimurium and the sugar utilization in Escherichia coli. Many bacteria are motile only when nutrients are scarce. By contrast, Salmonella enterica is motile only when nutrients are plentiful, suggesting this bacterium uses motility for purposes other than foraging, most likely host colonization. We investigated how nutrients affect motility in S. enterica and found that nutrients tune the fraction of motile cells. In particular, we observed co-existing populations of motile and non-motile cells, where the distribution was determined by the concentration of nutrients in the growth medium. Interestingly, S. enterica does not respond to a single nutrient but apparently a complex mixture of them. We investigated the mechanism governing this behavior and found that it results from two antagonizing regulatory proteins, FliZ and YdiV. We further demonstrated that the response is bistable: namely, that genetically identical cells can exhibit different phenotypes under identical growth conditions. We further characterized the differences within class 2 and class 3 gene expression and showed that a secretion-dependent feedback loop involving flagellar specific sigma factor, σ28, is responsible for partitioning cells into two fractions. Together, these results uncover a new facet to the regulation of the flagellar genes in S. enterica and further demonstrate how bacteria employ phenotypic diversity as general mechanism for adapting to change in their environment. We then investigated the sugar utilization system in E. coli. Glucose is known to inhibit the transport and metabolism of many sugars in Escherichia coli. This mechanism leads to its preferential consumption. Far less, however, is known about the preferential utilization of non-glucose sugars in E. coli. One notable exception is arabinose and xylose. Previous studies have shown that E. coli will consume arabinose ahead of xylose. Selective utilization results from arabinose-bound AraC binding to the promoter of the xylose metabolic genes and inhibiting their expression. This mechanisms, however, has not been explored in single cells. Both the arabinose and xylose utilization systems are known to exhibit a bimodal induction response to their cognate sugar, where mixed populations of cells either expressing the metabolic genes or not are observed at intermediate sugar concentrations. This suggests that arabinose can only inhibit xylose metabolism in arabinose-induced cells. To understand how crosstalk between these systems affects their response, we investigated E. coli during growth on mixtures of arabinose and xylose at single-cell resolution. Our results show that mixed, multimodal populations of arabinose and xylose-induced cells occur at some intermediate sugar concentrations. We also found that xylose can inhibit the expression of the arabinose metabolic genes and that this repression is due to XylR. We further found that xylose-bound XylR binds to the divergent promoter region of the regulator araC and the arabinose metabolic genes and inhibit expression. These results demonstrate that a strict hierarchy does not exist between arabinose and xylose as previously thought and this may aid in the design of E. coli strains capable of simultaneous sugar consumption

Corporate governance reform and risk-taking:evidence from a quasi-natural experiment in an emerging market

Existing studies suggest that stricter Corporate Governance Reform (CGR) reduces corporate risk-taking, primarily due to higher compliance costs and expanded liabilities of insiders or managers. We revisit the relationship between CGR and risk-taking in an emerging market set-up characterized by weaker market forces of corporate scrutiny and greater insider ownership, which encourages firms to pursue investment conservatism. Using a quasi-natural experiment, we find that stricter CGR leads to greater corporate risk-taking. We further show that risk-taking is an important channel through which CGR enhances firm value. Our findings support the view that stricter CGR can have a positive effect on corporate risk-taking and corporate investment decisions in an evolving regulatory environment

Geopolitical risk and M&A: the role of national governance institutions

Examining nineteen emerging economies from 1990 to 2018, we identify a positive effect of geopolitical risk on mergers and acquisition (M&A) deal frequency, driven mainly by an increase in domestic M&A. However, we find a negative effect of geopolitical risk on the M&A deal size, highlighting the deadweight cost created by the geopolitical risk. The quality of national governance moderates the deterring effect of geopolitical risk

Access to internal capital, creditor rights and corporate borrowing: does group affiliation matter?

We examine whether the effect of increased creditor rights on corporate borrowing depends on firm's access to internal capital. By exploiting a creditor protection reform in India, empirical outcomes strongly indicate that strengthening of creditor rights leads to increased corporate borrowing among firms that have constrained access to internal capital compared to business group affiliated firms, which have relatively easier access to internal capital. Further, the increased corporate borrowing by firms with constrained access to internal capital, in the post-reform period, is associated with a greater expansion of real investments, improved operational performance, and better market valuation. Taken together, these findings indicate that expanding creditor rights may aid in improving allocative efficiency

The distribution of onion virulence gene clusters among Pantoea spp.

Pantoea ananatis is a gram-negative bacterium and the primary causal agent of center rot of onions in Georgia. Previous genomic studies identified two virulence gene clusters, HiVir and alt, associated with center rot. The HiVir gene cluster is required to induce necrosis on onion tissues via synthesis of pantaphos, (2-hydroxy[phosphonomethyl) maleate), a phosphonate phytotoxin. The alt gene cluster aids in tolerance to thiosulfinates generated during onion tissue damage. Whole genome sequencing of other Pantoea species suggests that these gene clusters are present outside of P. ananatis. To assess the distribution of these gene clusters, two PCR primer sets were designed to detect the presence of HiVir and alt. Two hundred fifty-two strains of Pantoea spp. were phenotyped using the red onion scale necrosis (RSN) assay and were genotyped using PCR for the presence of these virulence genes. A diverse panel of strains from three distinct culture collections comprised of 24 Pantoea species, 41 isolation sources, and 23 countries, collected from 1946–2019, was tested. There is a significant association between the alt PCR assay and Pantoea strains recovered from symptomatic onion (P < 0.001). There is also a significant association of a positive HiVir PCR and RSN assay among P. ananatis strains but not among Pantoea spp., congeners. This may indicate a divergent HiVir cluster or different pathogenicity and virulence mechanisms. Last, we describe natural alt positive [RSN C /HiVir C /alt C ] P. ananatis strains, which cause extensive bulb necrosis in a neck-to-bulb infection assay compared to alt negative [RSN C /HiVir C /alt] P. ananatis strains. A combination of assays that include PCR of virulence genes [HiVir and alt] and an RSN assay can potentially aid in identification of onion-bulb-rotting pathogenic P. ananatis strains.The Vidalia Onion Committee, United States Department of Agriculture (USDA), ANII, Uruguay), CSIC Grupos de Investigación I + D 2000 (CSIC, Udelar, Uruguay), Specialty Crops Research Initiative Award from the USDA, and National Institute of Food and Agriculture.http://www.frontiersin.org/Plant_Scienceam2022BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Changing Ways of Marrying: A study of the Dhimal Marriage Ritual of Damak, Nepal

This thesis, entitled “Changing ways of marrying: A study of the Dhimal marriage ritual of Damak, Nepal” focuses on changes in the marriage patterns of Dhimal indigenous people. Dhimal represent one of the oldest indigenous groups of Nepal, residing in the easternmost lowland since time immemorial. For the study, the choice was made for Damak municipality, which is inhabited mainly by the Dhimal and it is regarded as the fastest growing city of eastern Nepal. The main issue revealed by the study is the massive impacts of modernization, westernization, and urbanization on Dhimal indigenous people of Damak, processes that are expeditiously breaking up age-old tradition and customs. The government’s developmental plans and assimilation projects in the name of ‘one nation’ and ‘one language’ also erode the traditional culture. Further, there are some inevitable factors of political and economic nature, as well as migration, urbanization, education, mass media etc. These factors are also responsible for the cultural changes, in general, and marriage patterns, in particular. Marriage is an important social institution of the Dhimal society and thus integral part of its traditions. It is a valuable ritual among them because it brings community together. Until and unless the community provides moral support, a Dhimal marriage does not get validity. Therefore, for Dhimal people, marriage is not just about the two persons and the two families; it is also about their community. The rituals are a way of celebrating community and reinforce ethnic identity as much as a way of bonding the two people and families. But with the passage of time, the ritualistic forms and ritualists parts of their marriage have changed with the influence of modernization and globalization. Since Dhimal marriage is directly related to the community, the impact on marriage rituals entails an impact Dhimal traditions, culture and ethnic identity, indeed what makes them a distinct community. Thus, any negative impacts occurring in marriage mean breaking the identity and unity among the Dhimal people. That is what I am interested to show with this study. The leading research questions target the past and present social customs, norms and values of the traditional Dhimal community specifically as they relate to customs associated with marrying. What are the observable changes that have occurred in their marriage system now? And how are these linked to the social and cultural relationships and practices that are characteristic of Dhimal society? These questions are addressed throughout the whole thesis based on qualitative field work data collected in Damak Municipality in Nepal in June 2014. Several tools and techniques are used in order to answer the questions in this study. Modernization and ritual theories have been employed to analyse the findings. (Key Words: Community making practice, Dhimal People, Dhimal Caste Development Centre, Impact, Marriage Rituals, Responsible factors for Dhimal’s changes, Modernization, tradition, culture