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Introduction Child eating behaviours develop through interactions between the child’s characteristics, psychological factors and the child’s social environment and this affects the child’s diet and weight. To examine the currently existing birth cohort studies examining child eating behaviours, a review was conducted. There are currently no birth cohorts that concurrently examine child eating behaviours, dietary intake, growth and parental feeding practices from birth into early childhood. Therefore, the primary objective of the Longitudinal Assessment of Children’s Eating (LACE) study is to examine the bidirectional and transactional processes of child eating behaviours and parental feeding practices explaining poor dietary intake and excess weight across infancy and early childhood.Methods and analysis The LACE study will be a prospective, longitudinal parent-reported study following infants from younger than 4 months of age across nine waves of data collection: younger than 4 months, 4 months, 6 months, 9 months, 12 months, 18 months, 2 years, 3 years and 5 years. Participants will be included if they are parents of infants younger than 4 months, 18 years or older, fluent in English and living in Australia at baseline. A sample size of 1210 is proposed. Participants will be recruited online via paid social media (Facebook and Instagram) advertisements. The study will examine child eating behaviours, body mass index Z-score, dietary intake, screen time, temperament, parent feeding practices and styles, and demographics. The data will be obtained using the online survey software Qualtrics. Data analyses will be conducted using Stata.Ethics and dissemination Ethical approval was granted by the Deakin University Human Ethics Advisory Group, Faculty of Health (HEAG-H 120_2022). The findings from this study will be disseminated via presentations at scientific conferences and published manuscripts in peer-reviewed journals. Findings will be disseminated to the general public via mainstream media and to participants of the study with a summary of the findings.

Health promotion programs and strategies have the potential to support people to live healthier lives. Dementia, a collective name for brain disorders that impact thinking and memory, affects over 55 million people worldwide. Currently, there is no cure for dementia, so prevention is critical. Health promotion has the potential to reduce dementia by targeting the twelve potentially modifiable risk factors. A project currently being undertaken by the research team aims to strengthen the quality of clinical care and health services that specifically address dementia risk for Australian Aboriginal and Torres Strait Islander peoples. One of the intended strategies supporting the project's aim is the need for appropriate and safe health promotion programs and resources that support dementia risk reduction. Consequently, the aim of this scoping review is to identify and determine the quality and appropriateness of existing health promotion programs and resources aimed at dementia risk reduction developed or modified for Indigenous populations of Canada, the USA, Aotearoa New Zealand, and Australia that could be incorporated into the broader project. The Joanna Briggs Institute method for scoping reviews will be used to identify programs and resources focussed on dementia risk reduction for Indigenous peoples. Searches will be limited to the English language and literature published since January 2010. Databases to be searched include: CINAHL, Medline, PsychInfo, PubMed, Scopus and Google. Data that answers the research questions will be extracted from the literature and recorded on a data charting form. A combination of quantitative and qualitative methods will be used to analyse the findings of the scoping review. Dissemination of the findings through continuing community engagement, conference presentations and publications will be led by Aboriginal and Torres Strait Islander members of the research team.

Tools screening depression and anxiety developed using the Western biomedical paradigm are still used with First Nations Peoples globally, despite calls for cross-cultural adaption. Recent work by this research team found that tools used to screen for depression and anxiety were inappropriate for use with Australian First Nations Peoples living in the Torres Strait and Northern Peninsula Area of Australia. The objective of this Delphi study, the second phase of a broader four-phase project, was to gain consensus from an expert mental health and/or social and emotional wellbeing (SEWB) panel to inform the development of an appropriate screening tool. This Delphi study took place between March and May 2023. Three sequential rounds of anonymous online surveys delivered using QualtricsTM were planned, although only two were needed to reach 75% consensus. The first round sought consensus on whether a new screening tool needed to be developed or whether existing tools could be used. The second round achieved consensus. Twenty-eight experts (47% response rate) participated across the two Delphi rounds. In the second round, 83% of these experts agreed or strongly agreed that a new screening tool, using the holistic First Nations concept of social and emotional wellbeing, be developed. Ninety-four percent of them agreed that it should take a Yarning approach. These findings enabled the development of a new SEWB screening tool that adopted a Yarning (narrative) approach designed for use in primary care and geriatric settings in the region. The new tool has four different Yarning areas: Community engagement and behaviour; Stress worries; Risk; and Feeling strong. Guidelines for tool use are integrated as well as Summary and Recommendation sections. At a macro-level this project responds to the need for new screening tools that are underpinned by First Nations worldviews.

Abstract The product encoded by the X-linked inhibitor of apoptosis (XIAP) gene is a multi-functional protein which not only controls caspase-dependent cell death, but also participates in inflammatory signalling, copper homeostasis, response to hypoxia and control of cell migration. Deregulation of XIAP, either by elevated expression or inherited genetic deletion, is associated with several human disease states. Reconciling XIAP-dependent signalling pathways with its role in disease progression is essential to understand how XIAP promotes the progression of human pathologies. In this study we have created a panel of genetically modified XIAP-null cell lines using TALENs and CRISPR/Cas9 to investigate the functional outcome of XIAP deletion. Surprisingly, in our genetically modified cells XIAP deletion had no effect on programmed cell death, but instead the primary phenotype we observed was a profound increase in cell migration rates. Furthermore, we found that XIAP-dependent suppression of cell migration was dependent on XIAPdependent control of C-RAF levels, a protein kinase which controls cell signalling pathways that regulate the cytoskeleton. These results suggest that XIAP is not necessary for control of the apoptotic signalling cascade, however it does have a critical role in controlling cell migration and motility that cannot be compensated for in XIAP-knockout cells.

Abstract The objective is to find a new pathway for significant reduction in CO2 capture energy consumption. Specifically, nanoporous TiO(OH)2 was used to realize the objective, which was desired as a catalyst to significantly accelerate the decomposition of aqueous NaHCO3, essentially CO2 desorption – the key step of Na2CO3/NaHCO3 based CO2 capture technologies from overall CO2 energy consumption perspective. Effects of several important factors on TiO(OH)2-catalyzed NaHCO3 decomposition were investigated. The quantity of CO2 generated from 0.238 mol/L NaHCO3 at 65 °C with catalyst is ~800% of that generated without the presence of catalyst. When a 12 W vacuum pump was used for carrying the generated CO2 out of reactor, the total amount of CO2 released was improved by ~2,500% under the given experimental conditions. No significant decrease in the catalytic effect of TiO(OH)2 was observed after five cyclic CO2 activated tests. In addition, characterizations with in-situ Fourier transform infrared spectroscopy, thermal gravity analysis and Brunauer-Emmett-Teller of TiO(OH)2 indicate that TiO(OH)2 is quite stable. The discovery in this research could inspire scientists’ interests in starting to focus on a new pathway instead of making huge effort or investment in designing high-capacity but expensive CO2 sorbent for developing practical or cost-effective CO2 technologies.

Abstract Recent data indicate that the metabolism of Mycobacterium tuberculosis (Mtb) inside its host cell is heavily dependent on cholesterol and fatty acids. Mtb exhibits a unique capacity to co-metabolize different carbon sources and the products from these substrates are compartmentalized metabolically. Isocitrate lies at one of the key nodes of carbon metabolism and can feed into either the glyoxylate shunt (via isocitrate lyase) or the TCA cycle (via isocitrate dehydrogenase (ICDH) activity) and we sought to better understand the regulation at this junction. An isocitrate lyase-deficient mutant of Mtb (Δicl1) exhibited a delayed growth phenotype in stearic acid (C18 fatty acid) media and we isolated rescue mutants that had lost this growth delay. We found that mutations in the gene rv2170 promoted Mtb replication under these conditions and rescued the growth delay in a Δicl1 background. The Mtb Rv2170 protein shows lysine acetyltransferase activity, which is capable of post-translationally modifying lysine residues of the ICDH protein leading to a reduction in its enzymatic activity. Our data show that contrary to most bacteria that regulate ICDH activity through phosphorylation, Mtb is capable of regulating ICDH activity by acetylation. This mechanism of regulation is similar to that utilized for mammalian mitochondrial ICDH.

OBJECTIVES:Our study goal was to evaluate a set of nutritional indicators among adults with confirmed or suspected active tuberculosis disease in southern India, given the limited literature on this topic. Study objectives were to assess the: I) double burden of malnutrition at individual and population levels; II) relative performance of anthropometric indicators (body mass index, waist circumference) in diabetes screening; and III) associations between vitamin D and metabolic abnormalities. DESIGN:Cross-sectional study. SETTING:Hospital in rural southern India. PARTICIPANTS:Among adult patients (n = 834), we measured anthropometry, body composition, and biomarkers (vitamin D, glycated hemoglobin, hemoglobin) of nutritional status. Subsets of participants provided blood and sputum samples. RESULTS:Among participants, 91.7% had ≥ 1 malnutrition indicator; 34.6% had both undernutrition and overnutrition indicators. Despite the fact that >80% of participants would be considered low-risk in diabetes screening based on low body mass index and waist circumference, approximately one-third had elevated glycated hemoglobin (≥ 5.7%). The lowest quintile of serum 25-hydroxyvitamin D was associated with an increased risk of glycated hemoglobin ≥ 5.7% (adjusted risk ratio 1.61 [95% CI 1.02, 2.56]) compared to the other quintiles, adjusting for age and trunk fat. CONCLUSIONS:Malnutrition and diabetes were prevalent in this patient population; since both can predict poor prognosis of active tuberculosis disease, including treatment outcomes and drug resistance, this emphasizes the importance of dual screening and management of under- and overnutrition-related indicators among patients with suspected or active tuberculosis disease. Further studies are needed to determine clinical implications of vitamin D as a potential modifiable risk factor in metabolic abnormalities, and whether population-specific body mass index and waist circumference cut-offs improve diabetes screening.

Background. Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with intracellular mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC. Methods. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed. Results. Macrophages infected with intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca 2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca 2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in promoting clearance of mycobacteria from infected host cells. Conclusion. These findings provide a novel mechanistic explanation for mycobacterial intracellular persistence, and suggest that targeting interactions between the mycobacteria and host cell pathways may provide a novel avenue for development of anti-TB therapies.

Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in Mtb were previously unknown. Here, we identify and determine that the previously uncharacterized protein Rv3723/LucA, functions to integrate cholesterol and fatty acid uptake in Mtb. Rv3723/LucA interacts with subunits of the Mce1 and Mce4 complexes to coordinate the activities of these nutrient transporters by maintaining their stability. We also demonstrate that Mce1 functions as a fatty acid transporter in Mtb and determine that facilitating cholesterol and fatty acid import via Rv3723/LucA is required for full bacterial virulence in vivo. These data establish that fatty acid and cholesterol assimilation are inexorably linked in Mtb and reveals a key function for Rv3723/LucA in in coordinating thetransport of both these substrates.

The identification of immune correlates that are predictive of disease outcome for tuberculosis remains an ongoing challenge. To address this issue, we evaluated gene expression profiles from peripheral blood mononuclear cells following ex vivo challenge with Mycobacterium tuberculosis, among participants with active TB disease (ATBD, n = 10), latent TB infection (LTBI, n = 10), and previous active TB disease (after successful treatment; PTBD, n = 10), relative to controls (n = 10). Differential gene expression profiles were assessed by suppression-subtractive hybridization, dot blot, real-time polymerase chain reaction, and the comparative cycle threshold methods. Comparing ATBD to control samples, greater fold-increases of gene expression were observed for a number of chemotactic factors (CXCL1, CXCL3, IL8, MCP1, MIP1α). ATBD was also associated with higher IL1B gene expression, relative to controls. Among LTBI samples, gene expression of several chemotactic factors (CXCL2, CXCL3, IL8) was similarly elevated, compared to individuals with PTBD. Our results demonstrated that samples from participants with ATBD and LTBI have distinct gene expression profiles in response to ex vivo M. tuberculosis infection. These findings indicate the value in further characterizing the peripheral responses to M. tuberculosis challenge as a route to defining immune correlates of disease status or outcome.

Background. Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with persistent mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC. Methods. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed. Results. Macrophages infected with persistent intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that persistent intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in promoting clearance of mycobacteria from infected host cells. Conclusion. These findings provide a novel mechanistic explanation for mycobacterial intracellular persistence, and suggest that targeting interactions between the mycobacteria and host cell pathways may provide a novel avenue for development of anti-TB therapies.

Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles- that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100 Å pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.

BACKGROUND:Household air pollution in low income countries is an important cause of mortality from respiratory infection. We hypothesised that chronic smoke exposure is detrimental to alveolar macrophage function, causing failure of innate immunity. We report the relationship between macrophage function and prior smoke exposure in healthy Malawians. METHODS:Healthy subjects exposed daily to cooking smoke at home volunteered for bronchoalveolar lavage. Alveolar macrophage particulate content was measured as a known correlate of smoke exposure. Phagocytosis and intraphagosomal function (oxidative burst and proteolysis) were measured by a flow cytometric assay. Cytokine responses in macrophages were compared following re-exposure in vitro to wood smoke, before and after glutathione depletion. RESULTS:Volunteers had a range of alveolar macrophage particulate loading. The macrophage capacity for phagosomal oxidative burst was negatively associated with alveolar macrophage particulate content (n = 29, r2 = 0.16, p = 0.033), but phagocytosis per se and proteolytic function were unaffected. High particulate content was associated with lower baseline CXCL8 release (ratio 0.51, CI 0.29-0.89) and lower final concentrations on re-exposure to smoke in vitro (ratio 0.58, CI 0.34-0.97). Glutathione depletion augmented CXCL8 responses by 1.49x (CI 1.02-2.17) compared with wood smoke alone. This response was specific to smoke as macrophages response to LPS were not modulated by glutathione. CONCLUSION:Chronic smoke exposure is associated with reduced human macrophage oxidative burst, and dampened inflammatory cytokine responses. These are critical processes in lung defence against infection and likely to underpin the relationship between air pollution and pneumonia.

The formation and maintenance of granulomas is central to the host response to Mycobacterium tuberculosis (Mtb) infection. It is widely accepted that the lungs of patients with tuberculosis (TB) usually contain multiple infection foci, and that the granulomas evolve and differentiate independently, resulting in considerable heterogeneity. Although gene expression profiles of human blood cells have been proposed as biomarkers of Mtb infection and/or active disease, the immune profiles of discrete lesion types has not been studied extensively. Using histology, immunopathology and genome-wide transcriptome analysis, we explored the immunological profile of human lung TB granulomas. We show that although the different granulomas share core similarities in their immunological/inflammatory characteristics, they also exhibit significant divergence. Despite similar numbers of CD68+ macrophages in the different lesions, the extent of immune reactivity, as determined by the density of CD3+ T cells in the macrophage rich areas, and the extent of fibrosis, shows considerable variation. Both quantitative and qualitative differences among significantly differentially expressed genes (SDEG) were noted in each of the lesion types studied. Further, network/pathway analysis of SDEG revealed differential regulation of inflammatory response, immune cell trafficking, and cell mediated immune response in the different lesions. Our data highlight the formidable challenges facing ongoing efforts to identify peripheral blood biomarkers due to the diversity of lesion types and complexity of local immune responses in the lung.

The long-term efficacy of stormwater treatment systems requires continuous pollutant removal without substantial re-release. Hence, the division of incoming pollutants between temporary and permanent removal pathways is fundamental. This is pertinent to nitrogen, a critical water body pollutant, which on a broad level may be assimilated by plants or microbes and temporarily stored, or transformed by bacteria to gaseous forms and permanently lost via denitrification. Biofiltration systems have demonstrated effective removal of nitrogen from urban stormwater runoff, but to date studies have been limited to a 'black-box' approach. The lack of understanding on internal nitrogen processes constrains future design and threatens the reliability of long-term system performance. While nitrogen processes have been thoroughly studied in other environments, including wastewater treatment wetlands, biofiltration systems differ fundamentally in design and the composition and hydrology of stormwater inflows, with intermittent inundation and prolonged dry periods. Two mesocosm experiments were conducted to investigate biofilter nitrogen processes using the stable isotope tracer 15NO3(-) (nitrate) over the course of one inflow event. The immediate partitioning of 15NO3(-) between biotic assimilation and denitrification were investigated for a range of different inflow concentrations and plant species. Assimilation was the primary fate for NO3(-) under typical stormwater concentrations (∼1-2 mg N/L), contributing an average 89-99% of 15NO3(-) processing in biofilter columns containing the most effective plant species, while only 0-3% was denitrified and 0-8% remained in the pore water. Denitrification played a greater role for columns containing less effective species, processing up to 8% of 15NO3(-), and increased further with nitrate loading. This study uniquely applied isotope tracing to biofiltration systems and revealed the dominance of assimilation in stormwater biofilters. The findings raise important questions about nitrogen release upon plant senescence, seasonally and in the long term, which have implications on the management and design of biofiltration systems.

Dysfunctional pulmonary homeostasis and repair, including diseases such as pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), and tumorigenesis have been increasing over the past decade, a fact that heavily implicates environmental influences. Several investigations have suggested that in response to increased transforming growth factor--beta (TGFβ) signaling, the alveolar type II (ATII) epithelial cell undergoes phenotypic changes that may contribute to the complex pathobiology of PF. We have previously demonstrated that increased tissue stiffness associated with PF is a potent extracellular matrix (ECM) signal for epithelial cell activation of TGFβ. The work reported here explores the relationship between tissue stiffness and exposure to environmental stimuli in the activation of TGFβ. We hypothesized that exposure of ATII cells to fine particulate matter (PM2.5) will result in enhanced cell contractility, TGFβ activation, and subsequent changes to ATII cell phenotype. ATII cells were cultured on increasingly stiff substrates with or without addition of PM2.5. Exposure to PM2.5 resulted in increased activation of TGFβ, increased cell contractility, and elongation of ATII cells. Most notably, on 8 kPa substrates, a stiffness greater than normal but less than established fibrotic lung, addition of PM2.5 resulted in increased cortical cell stiffness, enhanced actin staining and cell elongation; a result not seen in the absence of PM2.5. Our work suggests that PM2.5 exposure additionally enhances the existing interaction between ECM stiffness and TGFβ that has been previously reported. Furthermore, we show that this additional enhancement is likely a consequence of intracellular reactive oxygen species (ROS) leading to increased TGFβ signaling events. These results highlight the importance of both the micromechanical and biochemical environment in lung disease initiation and suggest that individuals in early stages of lung remodeling during fibrosis may be more susceptible than healthy individuals when exposed to environmental injury adjuvants.

Emerging research supports the feasibility and viability of conducting clinical swallow examinations (CSE) for patients with dysphagia via telerehabilitation. However, minimal data has been reported to date regarding the implementation of such services within the clinical setting or the user perceptions of this type of clinical service. A mixed methods study design was employed to examine the outcomes of a weekly dysphagia assessment clinic conducted via telerehabilitation and examine issues relating to service delivery and user perceptions. Data was collected across a total of 100 patient assessments. Information relating to primary patient outcomes, session statistics, patient perceptions, and clinician perceptions was examined. Results revealed that session durations averaged 45 minutes, there was minimal technical difficulty experienced, and clinical decisions made regarding primary patient outcomes were comparable between the online and face to face clinicians. Patient satisfaction was high and clinicians felt that they developed good rapport, found the system easy to use, and were satisfied with the service in over 90% of the assessments conducted. Key factors relating to screening patient suitability, having good general organization, and skilled staff were identified as facilitators for the service. This trial has highlighted important issues for consideration when planning or implementing a telerehabilitation service for dysphagia management.

Shoulder disorders are common, debilitating, and represent a considerable burden on society. As primary contact practitioners, physiotherapists play a large role in the management and rehabilitation of people with these conditions. For those living outside of urban areas, however, access to physiotherapy can be limited. The aim of this study was to evaluate the validity and reliability of using a telerehabilitation system to collect physical examination findings and correctly identify disorders of the shoulder. Twenty-two participants with 28 shoulder disorders were recruited and underwent a face-to-face physical examination and a remote telerehabilitation examination. Examination findings and diagnoses from the two modes of assessment were used to determine validity and reliability of the new method. Diagnostic agreement and agreement on individual findings between the two methods were found to be consistent with the reliability of conventional assessment methods. This study provides important preliminary findings on the validity and reliability of musculoskeletal examinations conducted via telerehabilitation.

The role of the major histocompatibility complex (MHC) in the immune response makes it an attractive candidate gene for associations with disease resistance and susceptibility. This study describes genetic variability in the BoLA-DRB3 in Iranian buffaloes. Heminested PCR-RFLP method was used to identify the frequency of BoLA-DRB3 alleles. The BoLA-DRB3 locus is highly polymorphic in the study herd (12 alleles). Almost 63.50% of the alleles were accounted for by four alleles (BoLA-DRB3.2 *48, *20, *21, and obe) in Iranian buffalo. The DRB3.2 *48 allele frequency (24.20%) was higher than the others. The frequencies of the DRB3.2 *20 and DRB3.2 *21 are 14.52 and 14.00, respectively, and obe and gbb have a new pattern. Significant distinctions have been found between Iranian buffalo and other cattle breed studied. In the Iranian buffaloes studied alleles associated with resistance to various diseases are found.

The endoplasmic reticulum (ER) stress pathway known as the Unfolded Protein Response (UPR) is an adaptive survival pathway that protects cells from the buildup of misfolded proteins, but under certain circumstances it can lead to apoptosis. ER stress has been causally associated with macrophage apoptosis in advanced atherosclerosis of mice and humans. Because atherosclerosis shares certain features with tuberculosis (TB) with regard to lesional macrophage accumulation, foam cell formation, and apoptosis, we investigated if the ER stress pathway is activated during TB infection.Here we show that ER stress markers such as C/EBP homologous protein (CHOP; also known as GADD153), phosphorylated inositol-requiring enzyme 1 alpha (Ire1α) and eukaryotic initiation factor 2 alpha (eIF2α), and activating transcription factor 3 (ATF3) are expressed in macrophage-rich areas of granulomas in lungs of mice infected with virulent Mycobacterium tuberculosis (Mtb). These areas were also positive for numerous apoptotic cells as assayed by TUNEL. Microarray analysis of human caseous TB granulomas isolated by laser capture microdissection reveal that 73% of genes involved in the UPR are upregulated at the mRNA transcript level. The expression of two ER stress markers, ATF3 and CHOP, were also increased in macrophages of human TB granulomas when assayed by immunohistochemistry. CHOP has been causally associated with ER stress-induced macrophage apoptosis. We found that apoptosis was more abundant in granulomas as compared to non-granulomatous tissue isolated from patients with pulmonary TB, and apoptosis correlated with CHOP expression in areas surrounding the centralized areas of caseation.In summary, ER stress is induced in macrophages of TB granulomas in areas where apoptotic cells accumulate in mice and humans. Although macrophage apoptosis is generally thought to be beneficial in initially protecting the host from Mtb infection, death of infected macrophages in advanced granulomas might favor dissemination of the bacteria. Therefore future work is needed to determine if ER-stress is causative for apoptosis and plays a role in the host response to infection.

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, heritable condition typified by progression of extensive ossification within skeletal muscle, ligament and tendon together with defects in skeletal development. The condition is easily diagnosed by the presence of shortened great toes and there is severe advancement of disability with age. FOP has been shown to result from a point mutation (c.617G>A) in the ACVR1 gene in almost all patients reported. Very recently two other mutations have been described in three FOP patients. We present here evidence for two further unique mutations (c.605G>T and c.983G>A) in this gene in two FOP patients with some atypical digit abnormalities and other clinical features. The observation of disparate missense mutations mapped to the GS and kinase domains of the protein supports the disease model of mild kinase activation and provides a potential rationale for phenotypic variation.