Proteome Mapping of Adult Zebrafish Marrow Neutrophils Reveals Partial Cross Species Conservation to Human Peripheral Neutrophils

Neutrophil granulocytes are pivotal cells within the first line of host defense of the innate immune system. In this study, we have used a gel-based LC-MS/MS approach to explore the proteome of primary marrow neutrophils from adult zebrafish. The identified proteins originated from all major cellular compartments. Gene ontology analysis revealed significant association of proteins with different immune-related network and pathway maps. 75% of proteins identified in neutrophils were identified in neutrophils only when compared to neutrophil-free brain tissue. Moreover, cross-species comparison with human peripheral blood neutrophils showed partial conservation of immune-related proteins between human and zebrafish. This study provides the first zebrafish neutrophil proteome and may serve as a valuable resource for an understanding of neutrophil biology and innate immunity

Study of Segmentation Techniques for Medical Images

Segmentation techniques are widely used in for the application of Medical Images. These techniques play a crucial role by automating or facilitating the delineation of anatomical structures and other regions of interest . Image Segmentation is particularly dicult due to restrictions imposed by biological variation and image acquisition . Goal of medical image segmentation is to perform operations on medical images to identify patterns in the use of interaction and develop qualitative criteria to evaluate interactive segmentation methods and extract information from it .Techniques available for segmentation are specic to application and the segment of biological detail to be studied . Number of techniques require wide use of Algorithms specically for certain segmentation procedure of medical images . From the Medical Image processing point of view the classication of segmentation techniques is on gray level and texture based techniques. Approaches have been proposed to segment CT and MR Images. In the following chapters we discuss the reviewed methods with respect to all information provided by the user and the parameters for the computational part. Medical image segmentation techniques require some form of expert supervision to provide accurate and consistent identication of anatomic structures. A novel segmentation technique was developed that combines a knowledge-based segmentation system with a contour model. This method exploits the guidance of a higher level process to robustly perform the segmentation of kind of anatomic structures. Knowledge about the anatomic structures to be segmented is dened statistically in terms of probability density functions of parameters of location, size, and image intensity. The active contour based technique outperform the standard segmentation methods due to its capacity to fully enforce the available a priori knowledge concerning the anatomic structure of interest. The active contour algorithm is suitable for integration with high-level image understanding frameworks, and providing a robust low-level segmentation tool. Studies are required to determine whether the proposed algorithm is indeed capable of providing consistently superior segmentation

Indium-doped ZnOas efficient photosensitive material for sunlight driven hydrogen generation and DSSC applications: integrated experimental and computational approach

Electricity generation using simple and cheap dye-sensitized solar cells and photocatalytic water splitting to produce future fuel, hydrogen, directly under natural sunlight fascinated the researchers worldwide. Herein, synthesis of indium-doped wurtzite ZnO nanostructures with varying molar percentage of indium from 0.25 to 3.0% with concomitant characterization indicating wurtzite structure is reported. The shift of (002) reflection plane to higher 2θ degree with increase in indium-doping thus is a clear evidence of doping of indium in zinc oxide nanoparticles. Surface morphological as well as microstructural studies of In@ZnO exhibited generation of ZnO nanoparticles and nanoplates of diameter 10–30 nm. The structures have been correlated well using computational density functional (DFT) studies. Diffuse reflectance spectroscopy depicted the extended absorbance of these materials in the visible region. Hence, the photocatalytic activity towards hydrogen generation from water under natural sunlight as well as efficient DSSC fabrication of these newly synthesized materials has been demonstrated. In-doped ZnO exhibited enhanced photocatalytic activity towards hydrogen evolution (2465 μmol/h/g) via water splitting under natural sunlight. DSSC fabricated using 2% In-doped ZnO exhibited an efficiency of 3.46% which is higher than other reported In-doped ZnO based DSSCs

Future research directions in pneumonia

Copyright © 2018 by the American Thoracic Society. Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group’s specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Integration of state and sense: modulation of pheromone perception by hormones and social environment

Animals modify their behaviors in response to changes in their external social environment and internal physiological state to maximize their chances of survival and reproduction. This behavioral flexibility allows animals to have different responses to the same sensory stimulus depending on the needs of the animals and their environment. To understand how such flexibility arises in the nervous system, we studied how social environment can modulate mating behavior in the vinegar fly, Drosophila melanogaster. We found that when mature male flies are raised in an environment of high population density, they enhance their courtship display towards females. A similar enhancement is not observed in immature males, suggesting that there is an interaction between signals arising from the internal state (reproductive maturity) and the external environment (population density) of the fly. We identified the neural substrate of this behavioral modulation as plasticity in a single type of aphrodisiac pheromone sensing neuron that enhances its pheromone sensitivity only in mature males raised in dense housing conditions. Neuronal sensitization is induced by a synergistic interaction between juvenile hormone, a signal for reproductive maturity, and activity-dependent signaling pathways. Further, the adaptive responses of pheromone sensing neurons are sexually dimorphic in nature - they are observed in males but not in females. Sex differences in neuronal plasticity are regulated by FruitlessM, a male-specific transcription factor that regulates pheromone sensitivity in these neurons. Our findings indicate that FruitlessM likely functions as a genomic coincidence detector—integrating internal reproductive maturity and external population density—to modulate mating behavior in a sexually dimorphic manner. Mechanistic studies into cellular and molecular basis of behavioral flexibility are largely possible due to the availability of genetic tools that allow precise manipulations of neural circuits. In a parallel effort, we expanded the fly toolkit by developing a new method to alter gene expression in a spatially and temporally controlled manner, and demonstrated its utility in mapping and manipulating neuronal circuits underlying odor preference behavior. We anticipate that the development of these tools will further advance our understanding of how internal state and environmental context modulate behaviors in an integrated fashion

Integration of state and sense: modulation of pheromone perception by hormones and social environment

Animals modify their behaviors in response to changes in their external social environment and internal physiological state to maximize their chances of survival and reproduction. This behavioral flexibility allows animals to have different responses to the same sensory stimulus depending on the needs of the animals and their environment. To understand how such flexibility arises in the nervous system, we studied how social environment can modulate mating behavior in the vinegar fly, Drosophila melanogaster. We found that when mature male flies are raised in an environment of high population density, they enhance their courtship display towards females. A similar enhancement is not observed in immature males, suggesting that there is an interaction between signals arising from the internal state (reproductive maturity) and the external environment (population density) of the fly. We identified the neural substrate of this behavioral modulation as plasticity in a single type of aphrodisiac pheromone sensing neuron that enhances its pheromone sensitivity only in mature males raised in dense housing conditions. Neuronal sensitization is induced by a synergistic interaction between juvenile hormone, a signal for reproductive maturity, and activity-dependent signaling pathways. Further, the adaptive responses of pheromone sensing neurons are sexually dimorphic in nature - they are observed in males but not in females. Sex differences in neuronal plasticity are regulated by FruitlessM, a male-specific transcription factor that regulates pheromone sensitivity in these neurons. Our findings indicate that FruitlessM likely functions as a genomic coincidence detector—integrating internal reproductive maturity and external population density—to modulate mating behavior in a sexually dimorphic manner. Mechanistic studies into cellular and molecular basis of behavioral flexibility are largely possible due to the availability of genetic tools that allow precise manipulations of neural circuits. In a parallel effort, we expanded the fly toolkit by developing a new method to alter gene expression in a spatially and temporally controlled manner, and demonstrated its utility in mapping and manipulating neuronal circuits underlying odor preference behavior. We anticipate that the development of these tools will further advance our understanding of how internal state and environmental context modulate behaviors in an integrated fashion