HspX protein as a candidate vaccine against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis>: an overview

Background

Tuberculosis (TB) is a contagious infectious disease caused by Mycobacterium tuberculosis (Mtb). This disease with two million deaths per year has the highest mortality rate among bacterial infections. The only available vaccine against TB is BCG vaccine. BCG is an effective vaccine against TB in childhood, however, due to some limitations, has not proper efficiency in adults. Also, BCG cannot produce an adequately protective response against reactivation of latent infections.

Objective

In the present study we will review the most recent findings about contribution of HspX protein in the vaccines against tuberculosis.

Methods

Therefore, many attempts have been made to improve BCG or to find its replacement. Most of the subunit vaccines for TB in various phases of clinical trials were constructed as prophylactic vaccines using Mtb proteins expressed in the replicating stage. These vaccines might prevent active TB but not reactivation of latent tuberculosis infection (LTBI). A literature search was performed on various online databases (PubMed, Scopus, and Google Scholar) regarding the roles of HspX protein in tuberculosis vaccines.

Results

Ideal subunit post-exposure vaccines should target all forms of TB infection, including active symptomatic and dormant (latent) asymptomatic forms. Among these subunit vaccines, HspX is the most important latent phase antigen of M. tuberculosis with a strong immunological response. There are many studies that have evaluated the immunogenicity of this protein to improve TB vaccine.

Conclusion

According to the studies, HspX protein is a good candidate for development of subunit vaccines against TB infection.

     

Is HPA axis reactivity in childhood gender-specific? A systematic review

Background

In adults, hypothalamus–pituitary–adrenal (HPA) axis activity shows sexual dimorphism, and this is thought to be a mechanism underlying sex-specific disease incidence. Evidence is scarce on whether these sex differences are also present in childhood. In a meta-analysis, we recently found that basal (non-stimulated) cortisol in saliva and free cortisol in 24-h urine follow sex-specific patterns. We explored whether these findings could be extended with sex differences in HPA axis reactivity.

Methods

From inception to January 2016, PubMed and EMBASE.com were searched for studies that assessed HPA axis reactivity in healthy girls and boys aged ≤18 years. Articles were systematically assessed and reported in the categories: (1) diurnal rhythm, (2) cortisol awakening response (CAR), (3) protocolled social stress tests similar or equal to the Trier Social Stress Test for children (TSST-C), (4) pharmacological (ACTH and CRH) stress tests, and (5) miscellaneous stress tests.

Results

Two independent assessors selected 109 out of 6158 records for full-text screening, of which 81 studies (with a total of 14,591 subjects) were included. Studies showed that girls had a tendency towards a more variable diurnal rhythm (12 out of 29 studies), a higher CAR (8 out of 18 studies), and a stronger cortisol response to social stress tests (9 out of 21 studies). We found no evidence for sex differences in cortisol response after a pharmacological challenge or to miscellaneous stress tests.

Discussion

Sex differences in HPA axis reactivity appear to be present in childhood, although evidence is not unequivocal. For a better evaluation of sex differences in HPA axis reactivity, standardization of protocols and reports of stress tests is warranted.

     

The effect of family policies and public health initiatives on breastfeeding initiation among 18 high-income countries: a qualitative comparative analysis research design

Background

The objective of this study is to examine the effects of macro-level factors – welfare state policies and public health initiatives – on breastfeeding initiation among eighteen high-income countries.

Methods

This study utilizes fuzzy-set Qualitative Comparative Analysis methods to examine the combinations of conditions leading to both high and low national breastfeeding initiation rates among eighteen high-income countries.

Results

The most common pathway leading to high breastfeeding initiation is the combination of conditions including a high percentage of women in parliament, a low national cesarean section rate, and either low family spending, high rates of maternity leave, or high rates of women working part-time. The most common pathway leading to low breastfeeding initiation includes the necessary condition of low national adherence to the Baby-Friendly Hospital Initiative.

Conclusion

This research suggests that there is a connection between broad level welfare state polices, public health initiatives, and breastfeeding initiation. Compliance with the WHO/UNICEF initiatives depends on welfare regime policies and overall support for women in both productive and reproductive labor.

     

Cell Counting and Viability Assessment of 2D and 3D Cell Cultures: Expected Reliability of the Trypan Blue Assay

Background

Whatever the target of an experiment in cell biology, cell counting and viability assessment are always computed. The Trypan Blue (TB) assay was proposed about a century ago and is still the most widely used method to perform cell viability analysis. Furthermore, the combined use of TB with a haemocytometer is also considered the standard approach to estimate cell population density. There are numerous research articles reporting the use of TB assays to compute cell number and viability of 2D and 3D cultures. However, the literature still lacks studies regarding the reliability of the TB assay in terms of assessment of its repeatability and reproducibility.

Methods

We compared the TB assay's measurements obtained by two biologists who analysed 105 different samples in double-blind for a total of 210 counts performed. We measured: (a) the repeatability of the count performed by the same operator; (b) the reproducibility of counts performed by the two operators.

Results

There were no significant differences in the results obtained with 2D and 3D cell cultures: we estimated an approximate variability of 5% when the TB assay was used to assess the viability of the culture, and a variability of around 20% when it was used to determine the cell population density.

Conclusions

The main aim of this study was to make researchers aware of potential measurement errors when TB is used with a haemocytometer for counting and viability measurements in 2D and 3D cultures. We believe that these results can help researchers to determine whether the expected reliability of the TB assay is compliant with their applications.

     

Atripla<Superscript>R</Superscript>/anti-TB combination in TB/HIV patients. Drug in focus

Background

Co-administration of anti-tuberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and several antiretroviral drugs is complicated by pharmacokinetic drug-drug interaction.

Method

Pubmed and Google search following the key words tuberculosis, HIV, emtricitabine, tenofovir efavirenz, interaction were used to find relevant information on each drug of the fixed dose combination Atripla^R

Results

Information on generic name, trade name, pharmacokinetic parameter, metabolism and the pharmacokinetic interaction with Anti-TB drugs of emtricitabine, tenofovir, and efavirenz was obtained.

Conclusion

Fixed dose combination of emtricitabine/tenofovir/efavirenz (ATRIPLA^R) which has been approved by Food and Drug Administration shows promising results as far as safety and efficacy is concerned in TB/HIV co-infection patients, hence can be considered effective and safe antiretroviral drug in TB/HIV management for adult and children above 3 years of age.

     

Sex-specific effects of dietary fatty acids on saliva cortisol and social behavior in guinea pigs under different social environmental conditions

Background

Unbalanced dietary intakes of saturated (SFAs) and polyunsaturated (PUFAs) fatty acids can profoundly influence the hypothalamic-pituitary-adrenal (HPA)-axis and glucocorticoid secretions in relation to behavioral performances. The beneficial effects of higher dietary PUFA intakes and PUFA:SFA ratios may also affect social interactions and social-living per se, where adequate physiological and behavioral responses are essential to cope with unstable social environmental conditions.

Methods

Effects of diets high in PUFAs or SFAs and a control diet were investigated in male and female guinea pigs after 60 days of supplementation. Plasma fatty acid patterns served as an indicator of the general fatty acid status. HPA-axis activities, determined by measuring saliva cortisol concentrations, social behaviors, and hierarchy ranks were analyzed during group housing of established single-sexed groups and during challenging social confrontations with unfamiliar individuals of the other groups.

Results

The plasma PUFA:SFA ratio was highest in PUFA supplemented animals, with female levels significantly exceeding males, and lowest in SFA animals. SFA males and females showed increased saliva cortisol levels and decreased aggressiveness during group housing, while sociopositive behaviors were lowest in PUFA males. Males generally showed higher cortisol increases in response to the challenging social confrontations with unfamiliar individuals than females. While increasing cortisol concentrations were detected in control and PUFA animals, no such effect was found in SFA animals. During social confrontations, PUFA males showed higher levels of agonistic and sociopositive behaviors and also gained higher dominance ranks among males, which was not detected for females.

Conclusions

While SFAs seemingly impaired cortisol responses and social behaviors, PUFAs enabled adequate behavioral responses in male individuals under stressful new social environmental conditions. This sex-specific effect was possibly related to a general sex difference in the n-3 PUFA bioavailability and cortisol responses, which may indicate that males are more susceptible to changing environmental conditions, and shows how dietary fatty acids can shape social systems.

     

Dibutyryl-cAMP affecting fat deposition of finishing pigs by decreasing the inflammatory system related to insulin sensitive or lipolysis

Background

The mechanism of db-cAMP regulating fat deposition and improving lean percentage is unclear and needs to be further studied.

Methods

Eighteen 100-day-old Duroc × Landrance × Large White barrows (49.75?±?0.75 kg) were used for experiment 1, and 15 eighteen 135-day-old barrows (78.34?±?1.22 kg) were used for experiment 2 to investigate the effects of dietary dibutyryl-cAMP (db-cAMP) on fat deposition in finishing pigs. Pigs were fed with a corn-soybean meal-based diet supplemented with 0 or 15 mg/kg db-cAMP, and both experiments lasted 35 days, respectively.

Results

The results showed that db-cAMP decreased the backfat thickness, backfat percentage, and diameter of backfat cells without changing the growth performance or carcass characteristics in both experiments, and this effect was more marked in experiment 1 than in experiment 2; db-cAMP enhanced the activity of the growth hormone–insulin-like growth factor-1 (GH-IGF-1) axis and pro-opiomelanocortin (POMC) system in both experiments, which suppressed the accumulation of backfat deposition; microarray analysis showed that db-cAMP suppressed the inflammatory system within the adipose tissue related to insulin sensitivity, which also reduced fat synthesis.

Conclusions

In summary, the effect of db-cAMP on suppressing fat synthesis and accumulation is better in the earlier phase than in the later phase of finishing pigs, and db-cAMP plays this function by increasing the activity of the GH-IGF-1 axis and POMC system, while decreasing the inflammatory system within the adipose tissue related to insulin sensitive or lipolysis.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

A mathematical model for Zika virus transmission dynamics with a time-dependent mosquito biting rate

Background

Mathematical modeling has become a tool used to address many emerging diseases. One of the most basic and popular modeling frameworks is the compartmental model. Unfortunately, most of the available compartmental models developed for Zika virus (ZIKV) transmission were designed to describe and reconstruct only past, short-time ZIKV outbreaks in which the effects of seasonal change to entomological parameters can be ignored. To make an accurate long-term prediction of ZIKV transmission, the inclusion of seasonal effects into an epidemic model is unavoidable.

Methods

We developed a vector-borne compartmental model to analyze the spread of the ZIKV during the 2015–2016 outbreaks in Bahia, Brazil and to investigate the impact of two vector control strategies, namely, reducing mosquito biting rates and reducing mosquito population size. The model considered the influences of seasonal change on the ZIKV transmission dynamics via the time-varying mosquito biting rate. The model was also validated by comparing the model prediction with reported data that were not used to calibrate the model.

Results

We found that the model can give a very good fit between the simulation results and the reported Zika cases in Bahia (R-square?=?0.9989). At the end of 2016, the total number of ZIKV infected people was predicted to be 1.2087 million. The model also predicted that there would not be a large outbreak from May 2016 to December 2016 due to the decrease of the susceptible pool. Implementing disease mitigation by reducing the mosquito biting rates was found to be more effective than reducing the mosquito population size. Finally, the correlation between the time series of estimated mosquito biting rates and the average temperature was also suggested.

Conclusions

The proposed ZIKV transmission model together with the estimated weekly biting rates can reconstruct the past long-time multi-peak ZIKV outbreaks in Bahia.

     

Plant growth-promoting bacterium <Emphasis Type="Italic">Pseudomonas fluorescens</Emphasis> FR1 secrets a novel type of extracellular polyhydroxybutyrate polymerase involved in abiotic stress response in plants

Objectives

Identification of novel microbial factors contributing to plant protection against abiotic stress.

Results

The genome of plant growth-promoting bacterium Pseudomonas fluorescens FR1 contains a short mobile element encoding a novel type of extracellular polyhydroxybutyrate (PHB) polymerase (PhbC) associated with a type I secretion system. Genetic analysis using a phbC mutant strain and plants showed that this novel extracellular enzyme is related to the PHB production in planta and suggests that PHB could be a beneficial microbial compound synthesized during plant adaptation to cold stress.

Conclusion

Extracellular PhbC can be used as a new tool for improve crop production under abiotic stress.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Crosstalk between catecholamines and erythropoiesis

Background

Erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lineages.

Objective

This study focuses on the biological links interconnecting erythroid development and the sympathetic nervous system. The emerging evidence that underscores the role of catecholamines in the regulation of erythropoietin and other erythropoiesis cytokines are thoroughly reviewed, in addition to elements such as iron and the leptin hormone that are involved in erythropoiesis.

Methods

Relevant English-language studies were identified and retrieved from the PubMed search engine (1981–2017) using the following keywords: “Erythropoiesis”, “Catecholamines”, “Nervous system”, and “Cytokines.”

Results

Chronic social stress alters and suppresses erythroid development. However, the physiological release of catecholamines is an additional stimulator of erythropoiesis in the setting of anemia. Therefore, the severity and timing of catecholamine secretion might distinctly regulate erythroid homeostasis.

Conclusion

Understanding the relationship of catecholamines with different elements of the erythroid islands will be essential to find the tightly regulated production of red blood cells (RBCs) in both chronic and physiological catecholamine activation.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.

     

KniMet: a pipeline for the processing of chromatography–mass spectrometry metabolomics data

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.

     

NMRProcFlow: a graphical and interactive tool dedicated to 1D spectra processing for NMR-based metabolomics

Introduction

Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.

Objectives

The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.

Methods

NMRProcFlow was developed to be a graphical and interactive 1D NMR (¹H & ¹³C) spectra processing tool.

Results

NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.

Conclusion

Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.

     

Stress-induced cortisol is associated with generation of non-negative interpretations during cognitive reappraisal

Background

Enhanced processing of emotional stimuli after stress exposure is reported to be associated with stress-induced cortisol. Because enhanced emotional information processing could make cognitive emotion regulation more difficult, it was hypothesized that stress-induced cortisol would be associated with non-negative interpretation generation associated with the cognitive reappraisal processes.

Methods

A total of 36 participants (Mean age?=?21.3 years, SD?=?1.8) watched video clips of depression-related stressful situations before and after the administration of a stress induction task. They were then asked to generate as many non-negative interpretations as possible to reduce the depressive mood. Saliva samples were obtained before and after the stress induction task to measure change in the cortisol level.

Results

Participants were allocated post-hoc to either a responder (n?=?19) or non-responder group (n?=?17) based on the cortisol response to the stress induction task. The number of non-negative interpretations generated following the stress induction task was reduced only in the cortisol responders. The number of post-stress non-negative interpretations was fewer in the responder group when compared by sex, baseline cortisol level, and the number of pre-stress non-negative interpretations, statistically controlled.

Conclusions

Although baseline cortisol and sex may have impacted the results, the results suggest that stress-induced cortisol is associated with difficulty in non-negative interpretation generation during the cognitive reappraisal process.

     

Responses of rice to chronic and acute iron toxicity: genotypic differences and biofortification aspects

Background and aims

Iron (Fe) toxicity is a wide-spread stress in lowland rice production. The aim of this study was to differentiate between responses to acute Fe stress during the vegetative stage and chronic Fe stress throughout the growing period.

Methods

Six rice genotypes were tested in a semi-artificial greenhouse setup, in which acute (almost 1500 mg L^?1 Fe in soil solution during the vegetative stage) and chronic (200 to 300 mg L^?1 Fe throughout the season) Fe toxicity were simulated.

Results

Acute Fe stress induced early development of heavy leaf bronzing, whereas moderate symptoms occurred in the chronic treatment throughout the season. Grain yields were only reduced in the chronic stress treatment (?23 %) due to reductions in spikelet fertility, grain number and grain weight. Symptom formation during the early growth stages did not reflect yield responses in all genotypes. Only one genotype showed increases in grain Fe concentrations (24 % in the acute stress and 44 % in the chronic stress) compared to the control.

Conclusions

Contrasting genotypes responded differently to acute and chronic Fe toxicity, and one genotype showed consistent tolerance and the ability to translocate excess Fe into grains. These traits can be useful in the adaptive breeding of rice for Fe toxic environments.

     

Interaction between contrasting rice genotypes and soil physical conditions induced by hydraulic stresses typical of alternate wetting and drying irrigation of soil

Background and aims

Drought events, agricultural practices and plant communities influence microbial and soil abiotic parameters which can feedback to fodder production. This study aimed to determine which soil legacies influence plant biomass production and nutritional quality, and its resistance and recovery to extreme weather events.

Methods

In a greenhouse experiment, soil legacy effects on Lolium perenne were examined, first under optimal conditions, and subsequently during and after drought. We used subalpine grassland soils previously cultivated for two years with grass communities of distinct functional composition, and subjected to combinations of climatic stress and simulated management.

Results

The soil legacy of climatic stress increased biomass production of Lolium perenne and its resistance and recovery to a new drought. This beneficial effect resulted from higher nutrient availability in soils previously exposed to climatic stresses due to lower competitive abilities and resistance of microbial communities to a new drought. This negative effect on microbial communities was strongest in soils from previously cut and fertilized grasslands or dominated by conservative grasses.

Conclusion

In subalpine grasslands more frequent climatic stresses could benefit fodder production in the short term, but threaten ecosystem functioning and the maintenance of traditional agricultural practices in the long term.

     

Comparison of two prepill cortisol concentrations in dogs with hypercortisolism treated with trilostane

Background

The ideal method for monitoring trilostane therapy in dogs with hypercortisolism is still open to debate. Recently, determination of the pre-trilostane (prepill) cortisol concentration has been proposed to be more repeatable than either post-trilostane or post-ACTH cortisol. The aim of this study was to compare two prepill cortisol concentrations in dogs with hypercortisolism during trilostane therapy. Sixteen client-owned dogs with naturally occurring hypercortisolism were prospectively included and cortisol concentrations were measured twice, 1?h apart, before the morning trilostane dose (prepill 1 and 2 cortisol).

Results

A total of 47 prepill cortisol measurement pairs were included. Compared to prepill 1, prepill 2 cortisol was higher in 15, equal in 8 and lower in 24 pairs. Group agreement between prepill 1 and 2 cortisol was 70% (moderate agreement - weighted kappa 0.55). In 30% of the pairs, group assignment was discrepant, implying a different therapeutic decision. In some dogs certain circumstances (e.g. excessive barking, difficulties during blood collection, excitement at arrival) were identified as potential factors explaining the discrepancy between prepill 1 and 2 cortisol measurements.

Conclusions

In a substantial number of dogs treated with trilostane, the two prepill cortisol concentrations differed. Part of this difference might be ascribable to stressful events during test performance. When using prepill cortisol measurements to monitor trilostane therapy, recording of any incident during handling that might affect cortisol release might be helpful to make a reliable decision about a trilostane dose adaptation.

     

Stress amplifies sex differences in primate prefrontal profiles of gene expression

Background

Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults.

Methods

Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys.

Results

Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex.

Conclusions

Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.