Knowledge-based energy functions for computational studies of proteins

This chapter discusses theoretical framework and methods for developing knowledge-based potential functions essential for protein structure prediction, protein-protein interaction, and protein sequence design. We discuss in some details about the Miyazawa-Jernigan contact statistical potential, distance-dependent statistical potentials, as well as geometric statistical potentials. We also describe a geometric model for developing both linear and non-linear potential functions by optimization. Applications of knowledge-based potential functions in protein-decoy discrimination, in protein-protein interactions, and in protein design are then described. Several issues of knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe

Scaling up Agroforestry to Achieve Food Security and Environmental Protection among Smallholder Farmers in Malawi

Malawi is a land-locked country in southern Africa. Three-fourths of Malawi’s 13 million people rely on smallholder agriculture for their livelihoods. Increasing population, accelerating deforestation, poor soil and water management, and increasing poverty and land degradation directly impact the food security and human health of millions of Malawians. Cropping systems which combine cereal crops, agroforestry and small doses of inorganic fertilizers produce food-crop yields greater than inorganic fertilizers alone on degraded soils, as well as recuperating soil nutrients over a period of years. These agroforestry practices improve the livelihoods of farm families, lower risks associated with fertilizer price increases and drought and at the same time improve biodiversity and nutrient and water cycling in the agro-ecosystem. The World Agroforestry Centre (ICRAF) has a long history of agroforestry research and development in Malawi dating back to the 1980s. In 2007-2011, ICRAF implemented the Malawi Agroforestry Food Security Project (AFSP) through financial support from Irish Aid. ICRAF’s task in AFSP was to build a strong partnership to reach 200,000 farming families in 11 districts. The purpose of AFSP was to combine tested agroforestry practices, effective partnership and informed policies to increase food security and income, and improve livelihood opportunities for rural communities in Malawi, through accelerated adoption of fertilizer trees, fruit trees, fodder trees and fuel-wood trees. To accomplish these purposes, ICRAF provided the farming communities with planting material (tree seeds and seedlings), and the knowledge of how to care for them and effectively combine them with food crops. The beneficiaries of the project saw increases in household food security and nutrition. However, difficulties were encountered in transporting tree seeds and seedlings across eleven districts in a timely fashion, and in managing the flow of reporting and disbursements of funding among such a large group of collaborators. Several solutions were implemented which improved performance in these areas, and which allowed the group to reach very near the targeted number of participants, and to plan for a second phase of the project.Le Malawi est un état enclavé dans le Sud de l’Afrique. Les trois-quarts des 13 millions de Malawites sont de petits exploitants agricoles qui vivent de leur production. L’accroissement de la population, l’accélération de la déforestation, la mauvaise gestion des sols et de l’eau, et l’essor de la pauvreté et de la dégradation des terres ont des conséquences directes sur la sécurité alimentaire et la santé de millions d’habitants du pays. Les systèmes de culture qui associent cultures céréalières, agroforesterie et faibles doses d’engrais non organiques produisent des rendements de cultures vivrières plus importants que ceux obtenus avec des engrais non organiques utilisés seuls sur des sols dégradés, et permettent de récupérer des nutriments du sol au bout d'une certaine période. Ces pratiques d’agroforesterie améliorent les moyens de subsistance des foyers agricoles, réduisent les risques associés à l’augmentation du prix des engrais et à la sécheresse, et améliorent la biodiversité et le cycle des nutriments et de l’eau dans l’écosystème agricole. L’ICRAF (World Agroforestry Centre) travaille depuis les années 1980 sur la recherche et le développement en agroforesterie au Malawi. En 2007-2011, l’ICRAF a lancé au Malawi le projet « Agroforestry Food Security Project » (AFSP), financé par le programme Irish Aid et mis en place par le gouvernement irlandais pour soutenir les pays en développement. Dans le cadre de ce projet, l’ICRAF a eu pour mission d’établir un solide partenariat pour mettre en place l’agroforesterie dans 200 000 foyers agricoles répartis dans 11 districts. L’objectif de l’AFSP était d’associer des pratiques d’agroforesterie ayant fait leurs preuves, un partenariat efficace et des politiques éclairées afin d’améliorer la sécurité alimentaire et les revenus, ainsi que les moyens de subsistance des communautés rurales du Malawi, via l’utilisation de plus en plus massive d’arbres fertilisants, d’arbres fruitiers, d’arbres fourragers et d’arbres donnant du bois combustible. Pour atteindre ces objectifs, l’ICRAF a fourni aux communautés agricoles du matériel de plantation (graines et plants), et leur a expliqué comment s’en occuper et les associer efficacement aux cultures vivrières. Les bénéficiaires du projet ont pu constater une amélioration de la sécurité alimentaire et de la nutrition dans leur foyer. Il a fallu toutefois faire face à certaines difficultés notamment assurer le transport en dû temps des graines et plants dans les onze districts, et gérer le flux de rapports d’information et d’allocations de fonds entre un tel nombre de collaborateurs. Plusieurs solutions ont été mises en œuvre afin d’améliorer les performances dans ces domaines, ce qui a permis au groupe d’atteindre pratiquement l’objectif du nombre de bénéficiaires fixé, et de planifier une seconde phase pour le projet.Malaui es un país rodeado de tierra en el sur de África. Tres cuartos de los 13 millones de pobladores de Malaui dependen de la agricultura a pequeña escala para ganarse el sustento. El aumento de la población, la aceleración de la deforestación, la mala gestión del suelo y el agua y el aumento de la pobreza y la degradación de la tierra afectan directamente a la seguridad alimentaria y la salud humana de millones de Malauitas. Los sistemas de cultivo que combinan cultivos de cereal, agrosilvicultura y pequeñas dosis de fertilizantes inorgánicos producen rendimientos de cultivos alimentarios mayores que los fertilizantes inorgánicos en solitario en suelos degradados, así como la recuperación de los nutrientes del suelo durante un periodo de años. Estas prácticas de agrosilvicultura mejoran las condiciones de subsistencia de las familias de granjeros, reducen los riesgos asociados con aumentos de precio de los fertilizantes y sequías y al mismo tiempo mejoran la biodiversidad y el desarrollo del ciclo de los nutrientes y del agua en el ecosistema agrario. El ICRAF (Word Agroforestry Centre) cuenta con un largo historial de investigación y desarrollo en agrosilvicultura en Malaui que se remonta hasta la década de 1980. En 2007-2011, el ICRAF implementó en Malawi el proyecto de “Agroforestry Food Security” (AFSP) mediante apoyo financiero de Irish Aid. La tarea del ICRAF en AFSP consistía en construir una fuerte sociedad para alcanzar las 200.000 familias dedicadas a la agricultura en 11 distritos. El objetivo de AFSP era combinar prácticas de agrosilvicultura probadas, una sociedad eficaz y políticas fundadas para aumentar la seguridad alimentaria y los ingresos, y mejorar las oportunidades de ganarse el sustento para las comunidades rurales en Malaui, mediante la adopción acelerada de árboles fertilizantes, árboles frutales, árboles forrajeros y árboles madereros para combustible. Para conseguir estos objetivos, el ICRAF proporcionó a las comunidades agrícolas material para plantar (semillas y plantones de árboles), y el conocimiento de cómo cuidarlos y combinarlos de forma eficaz con los cultivos alimentarios. Los beneficiarios del proyecto percibieron un aumento de la seguridad alimentaria y la nutrición doméstica. Sin embargo, surgieron dificultades a la hora de transportar las semillas y plantones de los árboles a través de once distritos a tiempo, y de gestionar el flujo de informes y desembolsos de fondos entre un grupo tan grande de colaboradores. Se implementaron varias soluciones que mejoraron el rendimiento en estas áreas, y que permitieron al grupo alcanzar un número de participantes muy cercano al objetivo, y planificar una segunda fase del proyecto

Evidence for improved DNA repair in long-lived bowhead whale

At more than 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto’s paradox. Here, to understand the mechanisms that underlie the cancer resistance of the bowhead whale, we examined the number of oncogenic hits required for malignant transformation of whale primary fibroblasts. Unexpectedly, bowhead whale fibroblasts required fewer oncogenic hits to undergo malignant transformation than human fibroblasts. However, bowhead whale cells exhibited enhanced DNA double-strand break repair capacity and fidelity, and lower mutation rates than cells of other mammals. We found the cold-inducible RNA-binding protein CIRBP to be highly expressed in bowhead fibroblasts and tissues. Bowhead whale CIRBP enhanced both non-homologous end joining and homologous recombination repair in human cells, reduced micronuclei formation, promoted DNA end protection, and stimulated end joining in vitro. CIRBP overexpression in Drosophila extended lifespan and improved resistance to irradiation. These findings provide evidence supporting the hypothesis that, rather than relying on additional tumour suppressor genes to prevent oncogenesis, the bowhead whale maintains genome integrity through enhanced DNA repair. This strategy, which does not eliminate damaged cells but faithfully repairs them, may be contributing to the exceptional longevity and low cancer incidence in the bowhead whale

Effects of eight neuropsychiatric copy number variants on human brain structure

peer reviewedMany copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions. © 2021, The Author(s)

A New Framework of 17 Hydrological Ecosystem Services (HESS17) for Supporting River Basin Planning and Environmental Monitoring

Hydrological ecosystem services (HESS) describe the benefits of water for multiple purposes with an emphasis on environmental values. The value of HESS is often not realized because primary benefits (e.g., food production, water withdrawals) get the most attention. Secondary benefits such as water storage, purification or midday temperature cooling are often overlooked. This results in an incorrect evaluation of beneficial water usage in urban and rural resettlements and misunderstandings when land use changes are introduced. The objective of this paper is to propose a standard list of 17 HESS indicators that are in line with the policy and philosophy of the Consultative Group of International Agricultural Research (CGIAR) and that are measurable with earth observation technologies in conjunction with GIS and hydrological models. The HESS17 framework considered indicators that can be directly related to water flows, water fluxes and water stocks; they have a natural characteristic with minimal anthropogenic influence and must be quantifiable by means of earth observation models in combination with GIS and hydrological models. The introduction of a HESS framework is less meaningful without proper quantification procedures in place. Because of the widely diverging management options, the role of water should be categorized as (i) consumptive use (i.e., evapotranspiration and dry matter production) and (ii) non-consumptive use (stream flow, recharge, water storage). Governments and responsible agencies for integrated water management should recognize the need to include HESS17 in water allocation policies, water foot-printing, water accounting, transboundary water management, food security purposes and spatial land-use planning processes. The proposed HESS17 framework and associated methods can be used to evaluate land, soil and water conservation programs. This paper presents a framework that is non-exhaustive but can be realistically computed and applicable across spatial scales

Scaling up Agroforestry to Achieve Food Security and Environmental Protection among Smallholder Farmers in Malawi

Malawi is a land-locked country in southern Africa. Three-fourths of Malawi’s 13 million people rely on smallholder agriculture for their livelihoods. Increasing population, accelerating deforestation, poor soil and water management, and increasing poverty and land degradation directly impact the food security and human health of millions of Malawians. Cropping systems which combine cereal crops, agroforestry and small doses of inorganic fertilizers produce food-crop yields greater than inorganic fertilizers alone on degraded soils, as well as recuperating soil nutrients over a period of years. These agroforestry practices improve the livelihoods of farm families, lower risks associated with fertilizer price increases and drought and at the same time improve biodiversity and nutrient and water cycling in the agro-ecosystem. The World Agroforestry Centre (ICRAF) has a long history of agroforestry research and development in Malawi dating back to the 1980s. In 2007-2011, ICRAF implemented the Malawi Agroforestry Food Security Project (AFSP) through financial support from Irish Aid. ICRAF’s task in AFSP was to build a strong partnership to reach 200,000 farming families in 11 districts. The purpose of AFSP was to combine tested agroforestry practices, effective partnership and informed policies to increase food security and income, and improve livelihood opportunities for rural communities in Malawi, through accelerated adoption of fertilizer trees, fruit trees, fodder trees and fuel-wood trees. To accomplish these purposes, ICRAF provided the farming communities with planting material (tree seeds and seedlings), and the knowledge of how to care for them and effectively combine them with food crops. The beneficiaries of the project saw increases in household food security and nutrition. However, difficulties were encountered in transporting tree seeds and seedlings across eleven districts in a timely fashion, and in managing the flow of reporting and disbursements of funding among such a large group of collaborators. Several solutions were implemented which improved performance in these areas, and which allowed the group to reach very near the targeted number of participants, and to plan for a second phase of the project

Genetics and community-based restoration can guide conservation of forest fragments for endangered primates

As deforestation progresses in the tropics, wildlife populations are increasingly restricted to forest fragments. Here we study genetic population structure in the endangered Ashy red colobus (Piliocolobus tephrosceles) population in the forest fragments surrounding Kibale National Park, Uganda. Subsequently, we use landscape features (elevation, road data and distance to the park) to design a feasible strategy to restore forest in a fashion suitable for both the dispersal patterns of the species and land use practices of the local people. A lack of association between geographic distance and pairwise genetic relatedness among localities, the presence of first degree relatives across localities, and a low global F value suggest that red colobus individuals have migrated across this landscape in the recent past. Thus, a series of “stepping stone” forests from the fragments to the park will likely maintain viability of red colobus fragment populations. In this area, low-lying valleys are legally protected to prevent flooding and are considered of low-economic value to local people. We identify such valleys for development of community-based forest restoration efforts that will aid in red colobus conservation and provide various ecosystem services. Our study outlines how genetics and community-based restoration can be integrated to provide realistic conservation solutions

Motions of the running horse and cheetah revisited: fundamental mechanics of the transverse and rotary gallop

Mammals use two distinct gallops referred to as the transverse (where landing and take-off are contralateral) and rotary (where landing and take-off are ipsilateral). These two gallops are used by a variety of mammals, but the transverse gallop is epitomized by the horse and the rotary gallop by the cheetah. In this paper, we argue that the fundamental difference between these gaits is determined by which set of limbs, fore or hind, initiates the transition of the centre of mass from a downward–forward to upward–forward trajectory that occurs between the main ballistic (non-contact) portions of the stride when the animal makes contact with the ground. The impulse-mediated directional transition is a key feature of locomotion on limbs and is one of the major sources of momentum and kinetic energy loss, and a main reason why active work must be added to maintain speed in locomotion. Our analysis shows that the equine gallop transition is initiated by a hindlimb contact and occurs in a manner in some ways analogous to the skipping of a stone on a water surface. By contrast, the cheetah gallop transition is initiated by a forelimb contact, and the mechanics appear to have much in common with the human bipedal run. Many mammals use both types of gallop, and the transition strategies that we describe form points on a continuum linked even to functionally symmetrical running gaits such as the tölt and amble