TB research at UT-Houston--a review of cord factor: new approaches to drugs, vaccines and the pathogenesis of tuberculosis.

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950\u27s providing compelling evidence that cord factor (trehalose 6,6 dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time to have immediate impact. We can now recognize that the physical and biologic properties of cord factor are unprecedented in science, especially its ability to switch between two sets of biologic activities with changes in conformation. While TDM remains on organisms, it protects them from killing within macrophages, reduces antibiotic effectiveness and inhibits the stimulation of protective immune responses. If it comes off organisms and associates with lipid, TDM becomes a driver of tissue damage and necrosis. Studies emanating from cord factor research have produced (1) a rationale for improving vaccines, (2) an approach to new drugs that overcome natural resistance to antibiotics, (3) models of caseating granulomas that reproduce multiple manifestations of human tuberculosis. (4) evidence that TDM is a key T cell antigen in destructive lesions of tuberculosis, and (5) a new understanding of the pathology and pathogenesis of postprimary tuberculosis that can guide more informative studies of long standing mysteries of tuberculosis

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Social inequality and food insecurity in Nepal: Risks and responses

This chapter analyses efforts to address food security and recovery in post- confl ict northern Uganda. This is achieved by exploring how local government actors, humanitarians and local communities try to build on recovery interventions and agricultural rehabilitation programming, and the consequences of their efforts for the food security of the local community. Its major focus is the shift from temporary relief to recovery (i.e., production, infrastructure and restarting basic services) amidst several challenges. The chapter shows that a convergence of multiple humanitarian aims, national development policies, and donor priorities presents a muddle that does not refl ect the farmers' own recovery processes and the constraints they face in bringing land back into cultivation in general. The role of sitting allowances is analysed as a way to create a modestly enabling environment combining and adapting these various norms to the local context.</p

Introduction and Overview

This chapter provides an overview of 23 chapters included in the book. The book aims to present recent knowledge on issues and topics related to agriculture, livestock, and forestry systems across the three agroecological regions of Nepal. Chapters in the book are grouped into four themes: (a) Agriculture, horticulture, and post-harvest management; (b) livestock and fisheries; (c) forest ecosystems, community forestry, and agroforestry, and (d) crosscutting topics. Chapters demonstrate how various components of the food systems—including agronomy, horticulture, agrobiodiversity, soil science, plant health, food toxins and food safety, seed innovation systems, post-harvest management, livestock production, ownership and health, aquaculture and fisheries production, urban agriculture, transhumance systems, and socioeconomics—have been researched and managed to provide foundations for food systems innovations in Nepal. The book also catalogues a wide range of solutions: need of increased investment in R&D to develop new climate resilient technologies and practices and promotion of locally adapted species and varieties for increased and sustained productivity of cereals, fruits, and vegetables, and aquaculture and livestock; development of market linkages with China, India, and other countries; development of robust national seed system; conservation and multiplication of native and neglected species and landraces; effective soil fertility management and soil health improvement; use of plant clinics for pest management; promotion of conservation agriculture and regenerative agriculture practices; promotion of urban agriculture; correcting infective institutional arrangements to minimize food toxins and post-harvest losses; adoption of multisectoral and collaborative one-health approach for integrated animal–human–environmental health; protecting transhumance systems in mountains; integrating ecosystem services in forest and agrobiodiversity management; active harvesting of trees and forest products; promotion of integrated agroforestry systems; managing water–energy–food nexus for research and policy planning and implementation; applications of simulation modelling in closing yield gaps and in climate change studies; and gender and socially inclusive technology development. Whilst these solutions are not entirely new, this book has unravelled why these solutions have not gained traction or how these can be taken forward in more contextually grounded way, not only in Nepal but generally in other countries with similar farming systems and terrestrial environmental issues

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present