The Arabidopsis ARID-HMG DNA-BINDING PROTEIN 15 modulates JA signaling by regulating MYC2 during pollen development.

The intricate process of male gametophyte development in flowering plants is regulated by jasmonic acid (JA) signaling. JA signaling initiates with the activation of the basic-helix-loop-helix (bHLH) transcription factor (TF), MYC2, leading to the expression of numerous JA-responsive genes during stamen development and pollen maturation. However, the regulation of JA signaling during different stages of male gametophyte development remains less understood. This study focuses on the characterization of the plant ARID-HMG DNA-BINDING PROTEIN 15 (AtHMGB15), and its role in pollen development in Arabidopsis (Arabidopsis thaliana). Phenotypic characterization of a T-DNA insertion line (athmgb15-4) revealed delayed bolting, shorter siliques, and reduced seed set in mutant plants compared to the wildtype. Additionally, AtHMGB15 deletion resulted in defective pollen morphology, delayed pollen germination, aberrant pollen tube growth, and a higher percentage of non-viable pollen grains. Molecular analysis indicated the down-regulation of JA biosynthesis and signaling genes in the athmgb15-4 mutant. Quantitative analysis demonstrated that jasmonic acid and its derivatives were approximately tenfold lower in athmgb15-4 flowers. Exogenous application of methyl jasmonate could restore pollen morphology and germination, suggesting that the low JA content in athmgb15-4 impaired JA signaling during pollen development. Furthermore, our study revealed that AtHMGB15 physically interacts with MYC2 to form a transcription activation complex. This complex promotes the transcription of key JA signaling genes, the R2R3-MYB TFs MYB21 and MYB24, during stamen and pollen development. Collectively, our findings highlight the role of AtHMGB15 as a positive regulator of the JA pathway, controlling the spatiotemporal expression of key regulators involved in Arabidopsis stamen and pollen development.

Identification of genome-wide targets and DNA recognition sequence of the Arabidopsis HMG-box protein AtHMGB15 during cold stress response.

AtHMGB15 belongs to a group of ARID-HMG proteins which are plant specific. The presence of two known DNA binding domains: AT rich interacting domain (ARID) and High Mobility Group (HMG)-box, in one polypeptide, makes this protein intriguing. Although proteins containing individual HMG and ARID domains have been characterized, not much is known about the role of ARID-HMG proteins. Promoter analysis of AtHMGB15 showed the presence of various stress responsive cis regulatory elements along with MADS-box containing transcription factors. Our result shows that the expression of AtHMGB15 increased significantly upon application of cold stress. Using ChIP-chip approach, we have identified 6128 and 4689 significantly enriched loci having AtHMGB15 occupancy under control and cold stressed condition respectively. GO analysis shows genes belonging to abiotic stress response, cold response and root development were AtHMGB15 targets during cold stress. DNA binding and footprinting assays further identified A(A/C)--ATA---(A/T)(A/T) as AtHMGB15 binding motif. The enriched probe distribution in both control and cold condition shows a bias of AtHMGB15 binding towards the transcribed (gene body) region. Further, the expression of cold stress responsive genes decreased in athmgb15 knockout plants compared to wild-type. Taken together, binding enrichment of AtHMGB15 to the promoter and upstream to stress loci suggest an unexplored role of the protein in stress induced transcription regulation.

Salicylic acid mediated reduction in grain cadmium accumulation and amelioration of toxicity in Oryza sativa L. cv Bandana.

Contamination of agricultural fields with Cadmium (Cd) due to several agricultural practices is increasing worldwide. The rice plants can easily take up Cd and accumulate it into different parts, including the grains, posing a threat to human health even at low concentration exposure. Several phytohormones, including Salicylic acid (SA) have been investigated since long for its alleviating properties under various biotic and abiotic stress conditions. In the present study, 100 µM SA application to ameliorate 25 µM Cd stress was studied for 72 h in hydroponics in Oryza sativa cv. Bandana seedlings. Pot experiments were done with same treatment condition and plants were grown till maturity. SA application to Cd exposed rice seedlings alleviated the stress condition, which was established by several physiological, biochemical, histochemical and gene expression analysis. SA treatment to Cd stressed seedlings showed elevated photosynthetic pigment content, on-protein thiol content and relieved the Cd induced growth inhibition considerably. It lowered the accumulation of ROS like, O2- and H2O2 with a regulated antioxidative enzymatic activity. SA application in Cd exposed rice seedlings had upregulated expression of OsHMA3 and OsPCS1 whereasOsNRAMP2 gene was downregulated. Co-application of SA and Cd led to higher yield and improved agronomic traits in comparison to only Cd exposed plants under pot experimentation. Daily intake of Cd and Carcinogenic risk were also reduced by 99.75% and 99.99% respectively in the SA treated Cd stressed plants. SA positively affected the growth and tolerance of rice seedlings to Cd stress. Hence, SA addition to Cd contaminated soil can ensure rice cultivation without posing health risk to consumers.

The global neurosurgical workforce: a mixed-methods assessment of density and growth.

OBJECTIVE: In 2000, the global density of neurosurgeons was estimated at 1 per 230,000 population, which remains the most recent estimate of the global neurosurgeon workforce density. In 2004, the World Health Organization (WHO) estimated that there were 33,193 neurosurgeons worldwide, including trainees. There have been no updates to this estimate in the past decade. Moreover, only WHO region-level granularity regarding neurosurgeon distribution exists; country-level estimates are limited. The neurosurgery workforce is a crucial component to meeting the growing burden of neurosurgical diseases, which not only represent high absolute incidences and prevalences, but also represent correspondingly high disability-adjusted life years affecting hundreds of millions of people worldwide. Combining the lack of knowledge about the availability of the neurosurgical workforce and the increasing demand for neurosurgical services underscores the need for a system of neurosurgical workforce density surveillance. METHODS: This study involved 3 key steps: 1) global survey/literature review to obtain the number of working neurosurgeons per WHO-recognized country, 2) regression to interpolate any missing data, and 3) calculation of workforce densities and comparison to available historical data by WHO region. RESULTS: Data for 198 countries were collected (158) or interpolated (40). The global total number of neurosurgeons was estimated at 49,940. Overall, neurosurgeon density ranged from 0 to 58.95 (standardized to per 1,000,000 population) with a median of 3.56 (IQR 0.29-8.26). Thirty-three countries were found to have no neurosurgeons (zero). The highest density, 58.95, was in Japan, where 7495 neurosurgeons are taking care of a population of 127,131,800. CONCLUSIONS: In 2015, the Lancet Commission on Global Surgery estimated that 143 million additional surgical procedures are needed in low- and middle-income countries each year, and a subsequent study revealed that approximately 15% of those surgical procedures are neurosurgical. Based on our results, we can conclude that there are approximately 49,940 neurosurgeons currently, worldwide. The availability of neurosurgeons appears to have increased in all geographic regions over the past decade, with Southeast Asia experiencing the greatest growth. Such remarkable expansion should be assessed to determine factors that could play a role in other regions where the acceleration of growth would be beneficial.

Neurosurgical Care: Availability and Access in Low-Income and Middle-Income Countries.

BACKGROUND: An estimated 5 billion people worldwide lack access to basic surgical care. In particular, the vast majority of low-income and middle-income countries (LMICs) currently struggle to provide adequate neurosurgical services. Significant barriers exist, including limited access to trained medical, nursing, and allied health staff; lack of equipment; and availability of services at reasonable distance and at reasonable cost to patients. An accurate assessment of current neurosurgical capacity in LIMCs is an essential first step in tackling this deficit. OBJECTIVE: To quantify the neurosurgical operational capacity and assess access to neurosurgical services in LMICs, by taking into account the location of workforce and services. METHODS: A total of 141 LMICs were contacted and asked to report the number of currently practicing neurosurgeons, access to computed tomographic and magnetic resonance imaging, and availability of neurosurgical equipment (microscope, endoscope, bipolar diathermy, high-speed neurosurgical drill). A proposed World Federation of Neurosurgeons classification was used to stratify cities based on the level of neurosurgical care that could be provided. The data were geocoded and analyzed in Redivis (Redivis Inc.) to assess the percentage of the population covered within a 2-hour travel time of a city offering differing levels of neurosurgical care. RESULTS: 68 countries provided complete data (response rate, 48.2%). Eleven countries reported having no practicing neurosurgeons. The average percentage of the population with access to neurosurgical services within a 2-hour window is 25.26% in sub-Saharan Africa, 62.3% in Latin America and the Caribbean, 29.64% in East Asia and the Pacific, 52.83% in South Asia, 79.65% in the Middle East and North Africa, and 93.3% in Eastern Europe and Central Asia. CONCLUSIONS: There are several challenges to the provision of adequate neurosurgical services in low-resource settings. This study used mapping techniques to determine the current global neurosurgical workforce capacity and distribution. We have used our findings to identify areas for improvement. These include increasing and improving neurosurgical training programs worldwide, recruiting students and young physicians into the field, and retaining existing neurosurgeons within their home countries.

Survey of Emergency and Essential Surgical, Obstetric and Anaesthetic Services Available in Bangladeshi Government Health Facilities.

OBJECTIVE: Evaluate the capacity of government-run hospitals in Bangladesh to provide emergency and essential surgical, obstetric and anaesthetic services. METHODS: Cross-sectional survey of 240 Bangladeshi Government healthcare facilities using the World Health Organisation Situational Analysis Tool to Assess Emergency and Essential Surgical Care (SAT). This tool evaluates the ability of a healthcare facility to provide basic surgical, obstetric and anaesthetic care based on 108 queries that detail the infrastructure and population demographics, human resources, surgical interventions and reason for referral, and available surgical equipment and supplies. For this survey, the Bangladeshi Ministry of Health sent the SAT to sub-district, district/general and teaching hospitals throughout the country in April 2013. RESULTS: Responses were received from 240 healthcare facilities (49.5% response rate): 218 sub-district and 22 district/general hospitals. At the sub-district level, caesarean section was offered by 55% of facilities, laparotomy by 7% and open fracture repair by 8%. At the district/general hospital level, 95% offered caesarean section, 86% offered laparotomy and 77% offered open fracture treatment. Availability of anaesthesia services, general equipment and supplies reflected this trend, where district/general hospitals were better equipped than sub-district hospitals, though equipment and infrastructure shortages persist. CONCLUSION: There has been overall impressive progress by the Bangladeshi Government in providing essential surgical services. Areas for improvement remain across all key areas, including infrastructure, human resources, surgical interventions offered and available equipment. Investment in surgical services offers a cost-effective opportunity to continue to improve the health of the Bangladeshi population and move the country towards universal healthcare coverage.

Hippocampal and amygdala volumes in an older bipolar disorder sample.

BACKGROUND: Brain volumetric magnetic resonance imaging (MRI) studies of adult bipolar disorder samples, compared with healthy controls, have reported conflicting results in hippocampal and amygdala volumes. Among these, few have studied older bipolar samples, which would allow for examination of the effects of greater duration in mood episodes on brain volumes. The aim of this study was to compare hippocampal and amygdala volumes in older bipolar patients with controls. METHODS: High-resolution MRI scans were used to determine hippocampal and amygdala volumes that were manually traced using established protocols in 18 euthymic patients with DSM-IV bipolar I disorder (mean age 57 years) and 21 healthy controls (mean age 61 years). Analysis of covariance (ANCOVA) was used to explore group differences while controlling for intracranial volume (ICV), age, sex, and years of education. RESULTS: While gray matter, white matter, and cerebrospinal fluid volumes did not differ between the groups, bipolar disorder patients had smaller ICV (t = 2.54, p = 0.015). After correcting for ICV, the bipolar group had smaller hippocampal (left hippocampus F = 13.944, p = 0.001; right hippocampus F = 10.976, p = 0.002; total hippocampus F = 13.566; p = 0.001) and right amygdala (F = 13.317, p = 0.001) volumes. Total hippocampal volume was negatively associated with the duration of depressive (r = -0.636; p = 0.035) and manic (r = -0.659; p = 0.027) episodes, but not lithium use. Amygdala volumes were not associated with the duration of mood episodes. CONCLUSIONS: Older bipolar disorder patients had smaller hippocampal and amygdala volumes. That smaller hippocampal volume was associated with the duration of mood episodes may suggest a neuroprogressive course related to the severity of the disorder.