Policies, Political-Economy, and Swidden in Southeast Asia

For centuries swidden was an important farming practice found across the girth of Southeast Asia. Today, however, these systems are changing and sometimes disappearing at a pace never before experienced. In order to explain the demise or transitioning of swidden we need to understand the rapid and massive changes that have and are occurring in the political and economic environment in which these farmers operate. Swidden farming has always been characterized by change, but since the onset of modern independent nation states, governments and markets in Southeast Asia have transformed the terms of swiddeners’ everyday lives to a degree that is significantly different from that ever experienced before. In this paper we identified six factors that have contributed to the demise or transformation of swidden systems, and support these arguments with examples from China (Xishuangbanna), Laos, Thailand, Malaysia, and Indonesia. These trends include classifying swiddeners as ethnic minorities within nation-states, dividing the landscape into forest and permanent agriculture, expansion of forest departments and the rise of conservation, resettlement, privatization and commoditization of land and land-based production, and expansion of market infrastructure and the promotion of industrial agriculture. In addition we note a growing trend toward a transition from rural to urban livelihoods and expanding urban-labor markets

Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model

<p>Abstract</p> <p>Background</p> <p>Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical rapamycin in a mouse model for TSC-related tumors.</p> <p>Methods</p> <p>0.4% and 0.8% rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.</p> <p>Results</p> <p>Treatment with topical rapamycin improved survival and reduced tumor growth. Topical rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected rapamycin.</p> <p>Conclusion</p> <p>Topical rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.</p

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Effect of exploitation and exploration on the innovative as outcomes in entrepreneurial firms

[EN] The main aim of this study is to establish the effect of the Exploitation and Exploration; and the influence of these learning flows on the Innovative Outcome (IO). The Innovative Outcome refers to new products, services, processes (or improvements) that the organization has obtained as a result of an innovative process. For this purpose, a relationship model is defined, which is empirically contrasted, and can explains and predicts the cyclical dynamization of learning flows on innovative outcome in knowledge intensive firms. The quantitative test for this model use the data from entrepreneurial firms biotechnology sector. The statistical analysis applies a method based on variance using Partial Least Squares (PLS). Research results confirm the hypotheses, that is, they show a positive dynamic effect between the Exploration and the Innovative as outcomes. 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State of the Carbon Cycle - Consequences of Rising Atmospheric CO2

The rise of atmospheric CO2, largely attributable to human activity through fossil fuel emissions and land-use change, has been dampened by carbon uptake by the ocean and terrestrial biosphere. We outline the consequences of this carbon uptake as direct and indirect effects on terrestrial and oceanic systems and processes for different regions of North America and the globe. We assess the capacity of these systems to continue to act as carbon sinks. Rising CO2 has decreased seawater pH; this process of ocean acidification has impacted some marine species and altered fundamental ecosystem processes with further effects likely. In terrestrial ecosystems, increased atmospheric CO2 causes enhanced photosynthesis, net primary production, and increased water-use efficiency. Rising CO2 may change vegetation composition and carbon storage, and widespread increases in water use efficiency likely influence terrestrial hydrology and biogeochemical cycling. Consequences for human populations include changes to ecosystem services including cultural activities surrounding land use, agricultural or harvesting practices. Commercial fish stocks have been impacted and crop production yields have been changed as a result of rising CO2. Ocean and terrestrial effects are contingent on, and feedback to, global climate change. Warming and modified precipitation regimes impact a variety of ecosystem processes, and the combination of climate change and rising CO2 contributes considerable uncertainty to forecasting carbon sink capacity in the ocean and on land. Disturbance regime (fire and insects) are modified with increased temperatures. Fire frequency and intensity increase, and insect lifecycles are disrupted as temperatures move out of historical norms. Changes in disturbance patterns modulate the effects of rising CO2 depending on ecosystem type, disturbance frequency, and magnitude of events. We discuss management strategies designed to limit the rise of atmospheric CO2 and reduce uncertainty in forecasts of decadal and centennial feedbacks of rising atmospheric CO2 on carbon storage

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead