Undernutrition and Tuberculosis: Public Health Implications.

Almost 800 million people are chronically undernourished worldwide, of whom 98% are in low- and middle-income countries where tuberculosis is endemic. In many tuberculosis-endemic countries, undernutrition is a driver of tuberculosis incidence and associated with a high population attributable fraction of tuberculosis and poor treatment outcomes. Data suggest that undernutrition impairs innate and adaptive immune responses needed to control Mycobacterium tuberculosis infection and may affect responses to live vaccines, such as BCG. Given its impact on tuberculosis, addressing undernutrition will be a vital component of the World Health Organization End TB strategy. This narrative review describes the effect of undernutrition on the immune response, vaccine response, and tuberculosis incidence, severity, and treatment outcomes.

Probing Myosin Ensemble Mechanics in Actin Filament Bundles using Optical Tweezers.

Myosins are motor proteins that hydrolyze ATP to step along actin filament (AF) tracks and are essential in cellular processes such as motility and muscle contraction. To understand their force-generating mechanisms, myosin II has been investigated both at the single-molecule (SM) level and as teams of motors in vitro using biophysical methods such as optical trapping. These studies showed that myosin force-generating behavior can differ greatly when moving from the single-molecule level in a three-bead arrangement to groups of motors working together on a rigid bead or coverslip surface in a gliding arrangement. However, these assay constructions do not permit evaluating the group dynamics of myosin within viscoelastic structural hierarchy as they would within a cell. We have developed a method using optical tweezers to investigate the mechanics of force generation by myosin ensembles interacting with multiple actin filaments. These actomyosin bundles facilitate investigation in a hierarchical and compliant environment that captures motor communication and ensemble force output. The customizable nature of the assay allows for altering experimental conditions to understand how modifications to the myosin ensemble, actin filament bundle, or the surrounding environment result in differing force outputs.

Myosin II Adjusts Motility Properties and Regulates Force Production Based on Motor Environment.

Introduction: Myosin II has been investigated with optical trapping, but single motor-filament assay arrangements are not reflective of the complex cellular environment. To understand how myosin interactions propagate up in scale to accomplish system force generation, we devised a novel actomyosin ensemble optical trapping assay that reflects the hierarchy and compliancy of a physiological environment and is modular for interrogating force effectors. Methods: Hierarchical actomyosin bundles were formed in vitro. Fluorescent template and cargo actin filaments (AF) were assembled in a flow cell and bundled by myosin. Beads were added in the presence of ATP to bind the cargo AF and activate myosin force generation to be measured by optical tweezers. Results: Three force profiles resulted across a range of myosin concentrations: high force with a ramp-plateau, moderate force with sawtooth movement, and baseline. The three force profiles, as well as high force output, were recovered even at low solution concentration, suggesting that myosins self-optimize within AFs. Individual myosin steps were detected in the ensemble traces, indicating motors are taking one step at a time while others remain engaged in order to sustain productive force generation. Conclusions: Motor communication and system compliancy are significant contributors to force output. Environmental conditions, motors taking individual steps to sustain force, the ability to backslip, and non-linear concentration dependence of force indicate that the actomyosin system contains a force-feedback mechanism that senses the local cytoskeletal environment and communicates to the individual motors whether to be in a high or low duty ratio mode. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-022-00731-1.

Determination of vibrational band positions in the E-hook of ß-tubulin.

Raman spectral characterization of the ß-TUBB2A E-hook hexapeptide, EGEDEA, is determined through experimental analysis combined with full geometry optimizations and corresponding harmonic vibrational frequency computations employing DFT methods. The hexapeptide is first broken down into di- and tetrapeptide fragments which are analyzed both quantum chemically and experimentally, and then combined to achieve an energetic minimum of the large EGEDEA hexapeptide. The Raman spectral characterization of EGEDEA band positions are then verified via the literature and comparison to the small fragment's similarly located band positions. The approach employed provides further evidence for the use of fragments as a helpful tool in characterization of the vibrational band positions of large peptides. STATEMENT OF SIGNIFICANCE: To investigate ß-TUBB2A E-hook hexapeptide, a unique approach is employed whereby the hexapeptide is broken into fragments, EG, ED, EA, EGED, and EDEA and analyzed via experimental Raman spectroscopy of the crystalline solids. The experimentally observed vibrational band positions are compared to those computed using and scaled from DFT methods and Pople's 6-311+G(2df,2pd) basis set. The reported vibrational band positions are also confirmed by previously reported bands of similar peptides in the literature. This methodology facilitates differentiation between the behaviors of various side chains and their influence on the structure of the hexapeptide, providing insight into not only the nature of the peptide but also defining regions for potential protein and cytoplasmic interactions, without requiring excessive computing resources or overly-sensitive experimental methods.

Deforestation reduces rainfall and agricultural revenues in the Brazilian Amazon.

It has been suggested that rainfall in the Amazon decreases if forest loss exceeds some threshold, but the specific value of this threshold remains uncertain. Here, we investigate the relationship between historical deforestation and rainfall at different geographical scales across the Southern Brazilian Amazon (SBA). We also assess impacts of deforestation policy scenarios on the region's agriculture. Forest loss of up to 55-60% within 28 km grid cells enhances rainfall, but further deforestation reduces rainfall precipitously. This threshold is lower at larger scales (45-50% at 56 km and 25-30% at 112 km grid cells), while rainfall decreases linearly within 224 km grid cells. Widespread deforestation results in a hydrological and economic negative-sum game, because lower rainfall and agricultural productivity at larger scales outdo local gains. Under a weak governance scenario, SBA may lose 56% of its forests by 2050. Reducing deforestation prevents agricultural losses in SBA up to US$ 1 billion annually.

Brazil's sugarcane embitters the EU-Mercosur trade talks.

The Brazilian government's decision to open the Amazon biome to sugarcane expansion reignited EU concerns regarding the sustainability of Brazil's sugar sector, hindering the ratification of the EU-Mercosur trade agreement. Meanwhile, in the EU, certain conventional biofuels face stricter controls, whilst uncertainty surrounding the commercialisation of more sustainable advanced-biofuels renders bioethanol as a short- to medium-term fix. This paper examines Brazil's land-use changes and associated greenhouse gas emissions arising from an EU driven ethanol import policy and projections for other 13 biocommodities. Results suggest that Brazil's sugarcane could satisfy growing ethanol demand and comply with EU environmental criteria, since almost all sugarcane expansion is expected to occur on long-established pasturelands in the South and Midwest. However, expansion of sugarcane is also driven by competition for viable lands with other relevant commodities, mainly soy and beef. As a result, deforestation trends in the Amazon and Cerrado biomes linked to soy and beef production could jeopardize Brazil's contribution to the Paris agreement with an additional 1 ± 0.3 billion CO2eq tonnes above its First NDC target by 2030. Trade talks with a narrow focus on a single commodity could thus risk unsustainable outcomes, calling for systemic sustainability benchmarks, should the deal be ratified.

Brazil's Market for Trading Forest Certificates.

Brazil faces an enormous challenge to implement its revised Forest Code. Despite big losses for the environment, the law introduces new mechanisms to facilitate compliance and foster payment for ecosystem services (PES). The most promising of these is a market for trading forest certificates (CRAs) that allows landowners to offset their restoration obligations by paying for maintaining native vegetation elsewhere. We analyzed the economic potential for the emerging CRA market in Brazil and its implications for PES programs. Results indicate a potential market for trading 4.2 Mha of CRAs with a gross value of US$ 9.2±2.4 billion, with main regional markets forming in the states of Mato Grosso and São Paulo. This would be the largest market for trading forests in the world. Overall, the potential supply of CRAs in Brazilian states exceeds demand, creating an opportunity for additional PES programs to use the CRA market. This expanded market could provide not only monetary incentives to conserve native vegetation, but also environmental co-benefits by fostering PES programs focused on biodiversity, water conservation, and climate regulation. Effective implementation of the Forest Code will be vital to the success of this market and this hurdle brings uncertainty into the market. Long-term commitment, both within Brazil and abroad, will be essential to overcome the many challenges ahead.