Structures of Get3d reveal a distinct architecture associated with the emergence of photosynthesis.

Homologs of the protein Get3 have been identified in all domains yet remain to be fully characterized. In the eukaryotic cytoplasm, Get3 delivers tail-anchored (TA) integral membrane proteins, defined by a single transmembrane helix at their C terminus, to the endoplasmic reticulum. While most eukaryotes have a single Get3 gene, plants are notable for having multiple Get3 paralogs. Get3d is conserved across land plants and photosynthetic bacteria and includes a distinctive C-terminal α-crystallin domain. After tracing the evolutionary origin of Get3d, we solve the Arabidopsis thaliana Get3d crystal structure, identify its localization to the chloroplast, and provide evidence for a role in TA protein binding. The structure is identical to that of a cyanobacterial Get3 homolog, which is further refined here. Distinct features of Get3d include an incomplete active site, a "closed" conformation in the apo-state, and a hydrophobic chamber. Both homologs have ATPase activity and are capable of binding TA proteins, supporting a potential role in TA protein targeting. Get3d is first found with the development of photosynthesis and conserved across 1.2 billion years into the chloroplasts of higher plants across the evolution of photosynthesis suggesting a role in the homeostasis of photosynthetic machinery.

Local government stewardship for TB elimination in Kerala, India.

SETTING: The southern Indian state of Kerala has implemented 'Kerala Tuberculosis Elimination Mission' as 'People's Movement against TB' under the stewardship of local governments (LGs). The state has been certified by the Government of India for being on track to attain the UN Sustainable Development Goals related to TB elimination. OBJECTIVE: To document the role of LG stewardship in the successful implementation of the TB elimination activities in Kerala. DESIGN: 1) Key informant interviews with four state officials, 2) desk review of available documents, 3) in-depth interviews with seven LG leaders, three mid-level programme managers and three health department field staff. RESULTS: LG involvement led to the establishment of solutions based on local problems, enhanced outreach of services to the socially vulnerable individuals, improved treatment support to patients with TB, increased community ownership of TB elimination activities, reduced TB-related stigma and social determinants being addressed. Institutional mechanisms such as LG TB elimination task forces, formal guidance in planning interventions and appreciation of their performance in the form of awards were facilitators for LG involvement. CONCLUSION: LG stewardship can accelerate TB elimination. A good plan for engagement and institutional mechanisms are crucial for LG involvement.

CONTEXTE: L'État du Kérala, situé dans le sud de l'Inde, a mis en place la « Kerala Tuberculosis Elimination Mission ¼ dans le cadre du « People's Movement Against TB ¼, sous l'égide des gouvernements locaux (LG). Le gouvernement indien a certifié que le Kérala était sur la bonne voie pour atteindre les objectifs de développement durable des Nations unies en matière d'élimination de la TB. OBJECTIF: Documenter le rôle de l'intendance des LG dans la bonne mise en œuvre des activités d'élimination de la TB au Kérala. MÉTHODES: 1) Entretiens avec des informateurs clés (quatre responsables gouvernementaux), 2) analyse des documents disponibles, 3) entretiens approfondis avec sept responsables de LG, trois responsables de programme de niveau intermédiaire et trois membres du personnel de terrain du département de la santé. RÉSULTATS: L'implication des LG a permis d'établir des solutions au vu des problèmes locaux, d'améliorer l'accès aux services pour les personnes socialement vulnérables, d'améliorer le soutien au traitement des patients atteints de TB, de renforcer l'appropriation par la communauté des activités d'élimination de la TB, de réduire la stigmatisation liée à la TB et d'agir sur les déterminants sociaux. Les mécanismes institutionnels, tels que les groupes de travail pour l'élimination de la TB mis en place par les LG, les conseils officiels reçus pour planifier les interventions et l'appréciation des performances sous forme de récompenses ont facilité l'implication des LG. CONCLUSION: L'intendance des LG peut permettre d'accélérer l'élimination de la TB. Une bonne planification de l'engagement et des mécanismes institutionnels sont essentiels à l'implication des LG.

The 2019-2020 volcanic eruption of Late'iki (Metis Shoal), Tonga.

Late'iki (previously known as Metis Shoal) is a highly active volcano in the Tofua arc with at least four temporary island-building eruptions and one submarine eruption in the last 55 years. The most recent eruption, commencing in October 2019, resulted in lava effusion and subsequent phreatic explosions, the construction of a short-lived island that was quickly eroded by wave action and possibly further phreatic activity that continued into January 2020. The two-pyroxene dacite from the 2019 eruption is similar to the 1967/8 eruptions suggesting the magma is residual from earlier eruptions and has not undergone further differentiation in the last 50 years. New observations of the 2019 eruption site confirm the lava-dominant character of the volcano summit but a thin veneer of wave-reworked, finely fragmented lava material remains that is interpreted to have been produced by phreatic explosions from hot rock-water interactions during the effusive eruption. A notable absence of quench-fragmented hyaloclastite breccias suggests that non-explosive quench fragmentation processes were minimal at these shallow depths or that hyaloclastite debris has resedimented to greater depths beyond our summit survey area.

Population Attributable Risk of Tuberculosis Vulnerabilities in Kerala, India.

BACKGROUND: A robust disaggregated understanding of the determinants of tuberculosis (TB) in each local setting is essential for effective health system and policy action to control TB. OBJECTIVES: The objective of the study was to identify population attributable risk (PAR) for TB disease based on the locally available evidences for Kerala, India. METHODS: Systematic review was done for risk factors of TB in the state. The second set of searches was done to understand the prevalence of the identified risk factors in general population in Kerala. With all available studies and reports, an expert group consensus was made to finalize state-specific prevalence of risk factors. Population attributable fractions were calculated for identified risk factors. RESULTS: PAR for TB disease in Kerala obtained was 24% for undernutrition, 15% for diabetes, 15% for tobacco use, and 1% for HIV. CONCLUSION: Kerala state's PAR for TB was comparatively lower for HIV but higher for diabetes mellitus. Similar exercises for summarizing population risk factors need to happen at all states for making plans to effectively combat TB.

The first state-level public health program for obstructive airway disease in India: An early field-level evaluation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the second leading cause of mortality in India; however, there are no programs for COPD in India at primary care level. Kerala became the first state in India to implement a program at primary care for COPD, called the Step Wise Approach to Airway Syndrome program. OBJECTIVE: The objective of the study was to evaluate and document the implementation status of a program for obstructive airway disease (OAD) in Trivandrum district of Kerala state in India and compare the treatment characteristics of patients with OAD seeking care from the centers implementing and not implementing this program for OADs. METHODS: A cross-sectional study was done as early evaluation of a program for OAD implemented in Kerala state, India, from October 2018 to February 2019. RESULTS: A reflection of the health-seeking behavior due to better facilities at the FHCs. There was no difference in the hospital visits or emergency department visits between the two groups. However, there was a statistically significant difference in the average number of visits per patient to health center for taking injectable drugs and visits for nebulization. Forty-nine (94%) of the COPD and 36 (100%) of the asthma patients underwent spirometry from implementing center itself. A higher proportion of patients receiving care from implementing centers (30.9%) never had to buy inhalers from outside. CONCLUSION: This is the first time that a public health programme for chronic respiratory disease management at primary care level was evaluated in India. The study has provided valuable insights on the need for strengthening the training for health care providers as well as patient education in bringing about a change in patient attitudes.

Structure and regulation of SWEET transporters in plants: An update.

Sugar will eventually be exported transporters (SWEETs), a novel family of sugar transporters found in both eukaryotes and prokaryotes, facilitate sugar flux across the cell membrane. Although these transporters were first discovered in plants, their homologs have been reported in different organisms. SWEETs have critical roles in various developmental processes, including phloem loading, nectar secretion, and pathogen nutrition. The structure of bacterial homologs, called SemiSWEETs, has been well studied thus far. Here, we provide an overview of SWEET protein structure and dynamic function by analyzing the solved crystal structures and predicted models that are available for a few SWEETs in a monocot plant (rice) and dicot plant (Arabidopsis thaliana). Despite the advancement in structure-related studies, the regulation of SWEETs remains unknown. In light of reported regulatory mechanisms of a few other sugar transporters, we propose the regulation of SWEETs at the post-translational level. We then enumerate the potential post-translational modification sites in SWEETs using computational tools. Overall, in this review, we critically analyze SWEET protein structure in plants to predict the post-translational regulation of SWEETs. Such findings have a direct bearing on plant nutrition and defense and targeting the regulation at these levels will be important in crop improvement.

Lung Health Care pilot project trims patient pill load and antibiotic prescription in primary health care settings in Kerala, India.

INTRODUCTION: Kerala, the southern Indian state piloted Lung Health Care Project (LHCP) which is a locally adopted version of WHO recommended Practical Approach to Lung health (PAL). The current study assessed the impact of the project on the prescribing practices of doctors and consumption of antibiotics and other drugs. METHODS: This study compared performance of primary health care institutions with regard to drug prescriptions and consumptions before and after the implementation of the project. Chronic respiratory disease (CRD) patients in institutions implemented the project were interviewed in the OPD at exit and their prescriptions were documented at baseline and after six months. Focus group discussions were conducted with doctors to explore the reasons behind changes in drug consumption pattern. RESULTS: In the project implementing institutions, mean number of drugs prescribed for CRDs was 3.88 (SD 1.50) and 2.73 (SD 1.18) at baseline and after six months respectively (p < 0.001). Adjusted odds ratio for prescribing an antibiotic and injection to a CRD patient during impact assessment at institutions implementing project was 0.34 (95% CI 0.15-0.75 p 0.008) and 0.39 (95% CI 0.20-0.74 p 0.004) respectively, as compared to baseline. The factors which helped in reducing antibiotic and injection use as felt by the doctors were presence of a protocol, good quality trainings, supportive supervision and monitoring, availability of alternate drugs and good participation of staff nurses especially in-patient education. CONCLUSION: Strict adherence to diagnostic and management algorithms of Lung health care project in a primary health care setting in India helped in reducing pill burden to patients and prescription of antibiotics and injections.

Analysis of tail-anchored protein translocation pathway in plants.

Tail-anchored (TA) proteins are a special class of membrane proteins that carry out vital functions in all living cells. Targeting mechanisms of TA proteins are investigated as the best example for post-translational protein targeting in yeast. Of the several mechanisms, Guided Entry of Tail-anchored protein (GET) pathway plays a major role in TA protein targeting. Many in silico and in vivo analyses are geared to identify TA proteins and their targeting mechanisms in different systems including Arabidopsis thaliana. Yet, crop plants that grow in specific and/or different conditions are not investigated for the presence of TA proteins and GET pathway. This study majorly investigates GET pathway in two crop plants, Oryza sativa subsp. Indica and Solanum tuberosum, through detailed in silico analysis. 508 and 912 TA proteins are identified in Oryza sativa subsp. Indica and Solanum tuberosum respectively and their localization with respect to endoplasmic reticulum (ER), mitochondria, and chloroplast has been delineated. Similarly, the associated GET proteins are identified (Get1, Get3 and Get4) and their structural inferences are elucidated using homology modelling. Get3 models are based on yeast Get3. The cytoplasmic Get3 from O. sativa is identified to be very similar to yeast Get3 with conserved P-loop and TA binding groove. Three cytoplasmic Get3s are identified for S. tuberosum. Taken together, this is the first study to identify TA proteins and GET components in Oryza sativa subsp. Indica and Solanum tuberosum, forming the basis for any further experimental characterization of TA targeting and GET pathway mechanisms in crop plants.

A retrospective analysis of serial measurement of serum cholinesterase in acute poisoning with organophosphate compounds.

OBJECTIVES: Retrospective analysis of the utility of serial measurements of serum acetylcholinesterase (AChE) in predicting the duration of stay in the intensive care unit (ICU), duration of mechanical ventilation (MV) and outcome of the patient from MV in organophosphate (OP) compound poisoning patients. MATERIALS AND METHODS: The medical records of patients who presented to tertiary care hospital with symptomatic insecticidal poisoning from January 2009 to December 2010 were utilized for the study purpose. Forty four patients with history of poisoning were admitted during this period. Out of these 37 patients with history of OP poisoning, without any underlying diseases and whose serial AChE activity levels were available were included in the study. Data regarding clinical manifestation at presentation, AChE activity results and its interpretation, details of patient management and data on outcomes of patients were noted. RESULTS: Serum acetycholinesterase levels below 1,250IU/L, 1,789IU/L and 2,764IU/L on day three, day four and five respectively indicates longer duration of stay in the ICU. Patients with serum AChE levels below 975IU/L, 876IU/L, 1,245IU/L, 1,395IU/L and 1,875IU/L on day one, two, three, four and five respectively take a longer time to be out of mechanical ventilation. Levels below 870IU/L, 1,110IU/L, 1,020IU/L and 885IU/L on day two, three, four and five respectively indicate poor prognosis of the patient and mortality. CONCLUSION: We conclude that the serial measurements of serum acetylcholinesterase levels can be useful in predicting the length of ICU stay, duration of mechanical ventilation and the prognosis of the patient with OP poisoning.

Metabolic recovery in goldfish: A comparison of recovery from severe hypoxia exposure and exhaustive exercise.

Severe hypoxia exposure and exhaustive exercise in goldfish both elicit a strong activation of substrate-level phosphorylation with the majority of the metabolic perturbations occurring in the white muscle. Approximately half of the muscle glycogen breakdown observed during severe hypoxia exposure was accounted for by ethanol production and loss to the environment, which limited the extent of muscle glycogen recovery when animals were returned to normoxic conditions. Ethanol production in goldfish is not solely a response to anoxia/hypoxia exposure however, as a transient increase in ethanol production was observed during the early stages of recovery from exhaustive exercise. These data suggest that ethanol production is a ubiquitous "anaerobic" end product, which accumulates whenever metabolic demands exceed mitochondrial oxidative potential. Exhaustive exercise and hypoxia exposure both caused a 7 to 8 micromol g(-1) wet mass increase in muscle [lactate] and the rates of recovery following these perturbations were similar. The rates of muscle PCr and pHi recovery after hypoxia exposure and exhaustive exercise were similar with levels returning to controls values within 0.5 h. Surprisingly, liver [glycogen] was not depleted during exposure to severe hypoxia, however, during recovery from both hypoxia and exercise dramatically different responses in liver [glycogen] were noted. During the early stages of recovery, liver [glycogen] transiently increased to high levels after exhaustive exercise, while during recovery from hypoxia there was a transient decrease in liver glycogen over the same time frame. Overall, this points to the liver playing a dramatically different role in facilitating recovery from exercise compared with hypoxia exposure.