Unveiling the occurrence of COVID-19 in a diverse Bangladeshi population during the pandemic.

Introduction: COVID-19 pandemic hit Bangladesh with relatively low intensity, unlike its neighbors India and European countries and USA. Methods: The present report included data of 8,480 individuals tested for COVID-19 RT-PCR of the workers and officials from readymade garments (RMG) industry in Chandra area in Gazipur. The present data looked into the clinic-demographic factors associated with the susceptibility of the condition. Result: The data elucidated the susceptibility of the individuals to SARS-CoV-2 based on age, gender, pre-existing health conditions, and the presence of symptoms. It was observed that individuals aged over 60 had the highest rate of COVID-19 positivity, and men exhibited a higher infection rate compared to women. Regardless of age, fever and cough were the most frequently reported symptoms. Two-thirds of the individuals included in this report appeared to be asymptomatic carriers. The prevalence of comorbidities among individuals who tested positive for COVID-19 was notably higher, and this exhibited a gender-specific pattern. Discussion: Although our study provides important epidemiological insights into the initial year of the pandemic among Bangladeshi populations, it can also add value for future drug and vaccine development. However, it is essential to acknowledge the limitations like - restriction of public movement, unavailability of vehicle yielding a selection bias, due to the lockdown conditions imposed owing to the pandemic and the diverse characteristics of the participants. The report emphasizes the significance of figuring out how age, gender, and underlying health conditions impact susceptibility to and transmission of COVID-19, thereby providing valuable insights for public health strategies and future research initiatives.

Evaluation of the potentials of rice varieties and water management practices for reducing human health risks associated with polluted river water irrigated rice in Bangladesh.

The consumption of arsenic and trace-metal-contaminated rice is a human health concern worldwide, particularly in Bangladesh. In this study, the effects of rice varieties and water management practices on the concentrations of arsenic and trace metals in rice grains were investigated to reduce human health risks related to rice consumption. In addition, the performance of risk reduction using the optimum combination of rice variety and water management practices was quantitatively assessed using Monte Carlo simulation, in which non-carcinogenic and carcinogenic risk distributions under the status quo and the optimum combination were compared. The experimental results revealed that Dular and BRRI dhan45 (rice varieties) cultivated under alternate wetting and drying (AWD) and continuous flooding (CF) conditions showed the lowest hazard quotient (HQ) values for copper, cadmium, and arsenic and the lowest target cancer risk (TR) for arsenic. In Dular and BRRI dhan45 (AWD and CF) varieties, the proportion of the population for which HQs exceeded 1.0 (the reference value) tended to decrease (except for arsenic), compared with populations for which the rice varieties and water management practices were not specified. These results suggest that the use of optimum combinations of rice varieties and water management practices could reduce non-carcinogenic and carcinogenic risks associated with arsenic and trace metals uptake via rice grain consumption by the Bangladeshi people.

Recycled Household Ash in Rice Paddies of Bangladesh for Sustainable Production of Rice Without Altering Grain Arsenic and Cadmium.

In Bangladesh most agronomic biomass (straw, husk, dried dung) is burnt for domestic cooking use. Consequently, the soil is continuously stripped of mineral nutrients and carbon (C) substrate. Here we investigate if recycling of household ash (ash) as fertilizer can sustainably improve soil fertility as well as minimise accumulation of toxic elements (As, Cd) in rice grain. Large scale field trials across two geographic regions (Barind, Madhupur) and two seasons (wet, dry) and with application of 3 fertiliser treatments (NPKS, ash, NPKS + ash) were conducted. At the end of each season, the impact of region*season*treatment on soil microbial comunities, rice yield, and grain quality (As, Cd, nutrient elements) was assessed. When compared to conventional field application rates of NPKS (control), application of ash boosted rice yield by circa. 20% in both regions during wet and dry season, with no effect on rice grain carcinogenic inorganic arsenic (iAs), dimethylarsonic acid (DMA) or cadmium (Cd), but with potential to increase zinc (Zn). For soil microbial communities, a significant region and season effect as well as correlation with elements in rice grain was observed, amongst these Cd, Zn, iAs and DMA. This study illustrates that application of ash can reduce the requirement for expensive chemical fertiliser, whilst at the same time increasing rice yield and maintaining grain quality, making farming in Bangladesh more sustainable and productive. The study also implies that the combined impact of region, season, and soil microbes determines accumulation of elements in rice grain. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-023-00539-y.

Identification of genomic loci regulating grain iron content in aus rice under two irrigation management systems.

Iron (Fe) deficiency is one of the common causes of anaemia in humans. Improving grain Fe in rice, therefore, could have a positive impact for humans worldwide, especially for those people who consume rice as a staple food. In this study, 225-269 accessions of the Bengal and Assam Aus Panel (BAAP) were investigated for their accumulation of grain Fe in two consecutive years in a field experiment under alternative wetting and drying (AWD) and continuous flooded (CF) irrigation. AWD reduced straw Fe by 40% and grain Fe by 5.5-13%. Genotype differences accounted for 35% of the variation in grain Fe, while genotype by irrigation interaction accounted for 12% of the variation in straw and grain Fe in year 1, with no significant interactions detected in year 2. Twelve rice accessions were identified as having high grain Fe for both years regardless of irrigation treatment, half of which were from BAAP aus subgroup 3 which prominently comes from Bangladesh. On average, subgroup 3 had higher grain Fe than the other four subgroups of aus. Genome-wide association mapping identified 6 genomic loci controlling natural variation of grain Fe concentration in plants grown under AWD. For one QTL, nicotianamine synthase OsNAS3 is proposed as candidate for controlling natural variation of grain Fe in rice. The BAAP contains three haplotypes of OsNAS3 where one haplotype (detected in 31% of the individuals) increased grain Fe up to 11%. Haplotype analysis of this gene in rice suggests that the ability to detect the QTL is enhanced in the BAAP because the high Fe allele is balanced in aus, unlike indica and japonica subgroups.

Blood phenylalanine reduction reverses gene expression changes observed in a mouse model of phenylketonuria.

Phenylketonuria (PKU) is a genetic deficiency of phenylalanine hydroxylase (PAH) in liver resulting in blood phenylalanine (Phe) elevation and neurotoxicity. A pegylated phenylalanine ammonia lyase (PEG-PAL) metabolizing Phe into cinnamic acid was recently approved as treatment for PKU patients. A potentially one-time rAAV-based delivery of PAH gene into liver to convert Phe into tyrosine (Tyr), a normal way of Phe metabolism, has now also entered the clinic. To understand differences between these two Phe lowering strategies, we evaluated PAH and PAL expression in livers of PAHenu2 mice on brain and liver functions. Both lowered brain Phe and increased neurotransmitter levels and corrected animal behavior. However, PAL delivery required dose optimization, did not elevate brain Tyr levels and resulted in an immune response. The effect of hyperphenylalanemia on liver functions in PKU mice was assessed by transcriptome and proteomic analyses. We observed an elevation in Cyp4a10/14 proteins involved in lipid metabolism and upregulation of genes involved in cholesterol biosynthesis. Majority of the gene expression changes were corrected by PAH and PAL delivery though the role of these changes in PKU pathology is currently unclear. Taken together, here we show that blood Phe lowering strategy using PAH or PAL corrects both brain pathology as well as previously unknown lipid metabolism associated pathway changes in liver.

Cholinesterase inhibitory activity of tinosporide and 8-hydroxytinosporide isolated from Tinospora cordifolia: In vitro and in silico studies targeting management of Alzheimer's disease.

Tinosporide and 8-hydroxytinosporide isolated from Tinospora cordifolia were evaluated for acetylcholinesterase (AChE) and butylcholinesterase (BuChE) inhibitory activities. The structure of the compound was confirmed by spectroscopic analysis, whereas cholinesterase inhibition was investigated by Ellman method using donepezil as standard drug and the data were presented as IC50 (µg/ml ± SEM). Furthermore, donepezil, tinosporide and 8-hydroxytinosporide were executed for docking analysis. The results from the isolated compounds TC-16R confirmed as tinosporide promisingly inhibited AChE with IC50 value of 13.45 ± 0.144, whereas TC-19R confirmed as 8-hydroxytinosporide moderately inhibited AChE with IC50 value of 46.71 ± 0.511. In case of BuChE inhibition, the IC50 values were found to be 408.50 ± 17.197 and 317.26 ± 6.918 for tinosporide and 8-hydroxytinosporide, respectively. The in silico studies revealed that the ligand tinosporide fit with the binding sites and inhibited AChE. Overall, the study findings suggested that tinosporide would be a complementary noble molecule of donepezil which is correlated with its pharmacological activity through in vitro studies, while 8-hydroxytinosporide modestly inhibited BuChE and the results are very close to the standard donepezil.

Genome-wide association mapping of sodium and potassium concentration in rice grains and shoots under alternate wetting and drying and continuously flooded irrigation.

KEY MESSAGE: Identification of a large number of QTL and candidate genes for sodium accumulation in a field grown population of rice derived from the aus subpopulation. Rice (Oryza sativa L.) is a globally important cereal crop. Sodium (Na+) and potassium (K+) are the major monovalent ions which affect rice growth, and exploring their uptake mechanisms will be useful for understanding rice biology. Since the balance of Na+ and K+ plays a significant role in adaptation of rice to salinity, that biology might inform the search for tolerance. In this study, the Na+ and K+ concentration and Na+/K+ ratio in grains and shoots were analyzed in the Bengal and Assam Aus Panel grown in field conditions under continuously flooded (CF) and alternate wetting and drying (AWD) irrigation. Overall, AWD irrigation significantly reduced the Na+ concentration and increased the K+ concentration in shoots and grains compared to the plants grown under CF. Genome-wide association mapping was conducted on Na+, K+ concentration and Na+/K+ ratio with 2 million SNPs using an efficient mixed model. Only QTLs which contained more than two significant SNPs (p < 0.0001) and where at least one of these significant SNPs passed a 10% false discovery rate were reported. A total of 106 QTLs were identified as being associated with Na+ concentration and Na+/K+ ratio across all traits and field conditions, with 48 QTLs found in multiple traits and/or water conditions. Four notable QTLs (one each on chromosomes 1 and 11, two on chromosome 2) and the haplotype variants of four candidate genes (OsHKT1;5, OsNHX2, LOC_Os02g32490 and OsFAD2_1) are discussed. The QTLs/candidate genes identified here could be useful for breeding rice that accumulates lower concentrations of sodium.

Living with arsenic in the environment: An examination of current awareness of farmers in the Bengal basin using hybrid feature selection and machine learning.

High levels of arsenic in drinking water and food materials continue to pose a global health challenge. Over 127 million people alone in Bangladesh (BD) and West Bengal (WB) state of India are exposed to elevated levels of arsenic in drinking water. Despite decades of research and outreach, arsenic awareness in communities continue to be low. Specifically, very few studies reported arsenic awareness among low-income farming communities. A comprehensive approach to assess arsenic awareness is a key step in identifying research and development priorities so that appropriate stakeholder engagement may be designed to tackle arsenic menace. In this study, we developed a comprehensive arsenic awareness index (CAAI) and identified key awareness drivers (KADs) of arsenic to help evaluate farmers' preferences in dealing with arsenic in the environment. The CAAI and KADs were developed using a questionnaire survey in conjunction with ten machine learning (ML) models coupled with a hybrid feature selection approach. Two questionnaire surveys comprising of 73 questions covering health, water and community, and food were conducted in arsenic-affected areas of WB and BD. Comparison of CAAIs showed that the BD farmers were generally more arsenic-aware (CAAI = 7.7) than WB farmers (CAAI = 6.8). Interestingly, the reverse was true for the awareness linked to arsenic in the food chain. Application of hybrid feature selection identified 15 KADs, which included factors related to stakeholder interventions and cropping practices instead of commonly perceived factors such as age, gender and income. Among ML algorithms, classification and regression trees and single C5.0 tree could estimate CAAIs with an average accuracy of 84%. Both communities agreed on policy changes on water testing and clean water supply. The CAAI and KADs combination revealed a contrasting arsenic awareness between the two farming communities, albeit their cultural similarities. Specifically, our study shows the need for increasing awareness of risks through the food chain in BD, whereas awareness campaigns should be strengthened to raise overall awareness in WB possibly through media channels as deemed effective in BD.

Genetic loci regulating cadmium content in rice grains.

It has been estimated that up to 90% of human exposure to cadmium is through food, and that cadmium within rice grains can be a major contributor to that dietary source. In this study genome wide association mapping was conducted on the Bengal and Assam Aus Panel (BAAP) of rice to identify quantitative trait loci and candidate genes for lowering grain cadmium. Field experiments were conducted over two years under two different irrigation systems: continually flooded and alternate wetting and drying (AWD). There was significant effects of water treatment, genotype, and genotype by water treatment interaction. Importantly, AWD increased grain cadmium, on average, by 49.6% and 108.8% in year 1 and 2 respectively. There was between 4.6 and 28 fold variation in cadmium concentration. A total of 58 QTLs were detected but no loci are clearly specific to one water regime despite approximately 20% of variation attributable to genotype by water regime interaction. A number of QTLs were consistent across most water treatments and years. These included QTLs on chromosome 7 (7.23-7.61, 8.93-9.04, and 29.12-29.14 Mbp), chromosome 5 (8.66-8.72 Mbp), and chromosome 9 (11.46-11.64 Mbp). Further analysis of the loci on chromosome 7 (8.93-9.04 Mbp), identified the candidate gene OsNRAMP1, where cultivars with a deletion upstream of the gene had higher concentrations of cadmium compared to the cultivars that did not have the deletion. The distribution of alleles within the BAAP suggest this QTL is easily detected in this population because it is composed of aus cultivars. Local genome cluster analysis suggest high Cd alleles are uncommon, but should be avoided in breeding. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1007/s10681-020-02752-1).

Arsenic dynamics in paddy soil under traditional manuring practices in Bangladesh.

Fertilization with organic matter (farm yard manure and/or rice straw) is thought to enhance arsenic (As) mobilization into soil porewaters, with subsequent As assimilation by rice roots leading to enhanced translocation to the grain. Here, interlinked experiments (field manuring and soil batch culture) were conducted to find the effect of organic matter at a field application rate practiced in Bangladesh (5 t/ha) on As mobilization in soil for paddies impacted by As contaminated groundwater irrigation, a widespread phenomenon in Bangladesh where the experiments were conducted. Total As concentration in a paddy soil (Sonargaon) ranged from 21.9 to 8.1 mg/kg down the soil profile and strongly correlated with TOC content. Arsenic, Fe, Mn, and DOC release into soil solution, and As speciation, are intimately linked to OM amendment, soil depth and temporal variation. Organic matter amendments lead to increased mobilization of As into both soil porewaters and standing surface waters. The As speciation in the porewater was dominated by inorganic As (Asi) (arsenite and arsenate), with traces amounts of methylated species (DMAV and MMAV) only being found with OM amendment. It was noted in field trials that OM fertilization greatly enhanced As mobility to surface waters, which may have major implications for the fate of As in paddy agronomic ecosystems.

Genetic loci regulating arsenic content in rice grains when grown flooded or under alternative wetting and drying irrigation.

BACKGROUND: Rice is a global staple crop, being the main calorific component of many people living subsistence livelihoods. Rice can accumulate toxic elements such as arsenic, with the crop water management strongly affecting uptake. This study utilises the Bengal and Assam Aus Panel to conduct genome wide association (GWA) mapping for arsenic in shoots and grains of rice grown over 2 years under continually flooded (CF) and alternate wetting and drying (AWD). The aim was to assess genotype by water management interaction, identify quantitative trait loci (QTL) for arsenic accumulation, and propose candidate genes for lowering grain arsenic. RESULTS: AWD significantly reduced grain arsenic across all cultivars on average by 15.7 and 15.1% in year 1 and 2 respectively and shoot arsenic by 27.0% compared to the plants grown under CF. There was a weak cultivar by treatment interaction for grain for arsenic. All traits were strongly influenced by cultivar. GWA mapping identified a large number of 74 individual QTLs for arsenic, with six QTLs showing stability across years and/or water treatments. Three of the loci (one on chromosome 3, one on chromosome 4, and one on chromosome 5) were investigated in detail using an approach of clustering cultivars that had similar haplotypes for the QTL regions and then looking at the phenotypic values across the clusters. Two of the identified QTLs co-localised with known genes involved in arsenic accumulation, including Lsi2 which has not previously been reported to underlie a grain arsenic QTL. CONCLUSIONS: This study has identified a number of novel QTLs for arsenic accumulation, as well as cultivars that consistently accumulate less arsenic over multiple field traits. The use of a haplotype clustering approach after GWA mapping has allowed for the effect, in terms of arsenic accumulation, to be determined for cultivars that share similar genomic sequence. Allocating nine high yielding Bangladeshi cultivars to these clusters has identified the potential of utilising these QTLs in breeding programmes; for example, incorporation of the QTL on chromosome 5 should decrease grain arsenic in elite high yielding Bangladeshi cultivars by 10% in all high yielding cultivars studied.

Modifying the Parboiling of Rice to Remove Inorganic Arsenic, While Fortifying with Calcium.

Using village-based rice processing plants in rural Bangladesh, this study considered how parboiling rice could be altered to reduce the content of the carcinogen inorganic arsenic. Parboiling is normally conducted with rough rice (i.e., where the husk is intact) that is soaked overnight at ambient temperatures, and then either steamed or boiled for ∼10 min, followed by drying. Across 13 geographically dispersed facilities it was found that a simple alteration parboiling wholegrain, instead of rough rice, decreased the inorganic arsenic content by 25% ( P = 0.002) in the final polished grain. Also, parboiling wholegrain had little impact on milling quality of the final polished rice. The wholegrain parboiling approach caused statistically significant median enrichment of calcium, by 213%; and a reduction in potassium, by 40%; with all other nutrient elements tested being unaffected. Milled parboiled rough rice had an enriched inorganic arsenic compared to nonparboiled milled rice, but parboiling of wholegrain rice did not enrich inorganic arsenic in the final milled product. Polished rice produced from the parboiling of both rough and wholegrain rice significantly reduced cadmium compared to nonparboiled polished rice, by 25%. This study also identified that trimethylarsine oxide and tretramethylarsonium are widely elevated in the husk and bran of rice and, therefore, gives new insights into the biogeochemical cycling of arsenic in paddy ecosystems.

Genome Wide Association Mapping of Grain and Straw Biomass Traits in the Rice Bengal and Assam Aus Panel (BAAP) Grown Under Alternate Wetting and Drying and Permanently Flooded Irrigation.

Growing demand for staple crops like rice will need to be achieved predominately through agricultural intensification and more efficient use of inputs. To meet this demand it is essential that the genetic diversity within rice is fully utilized. The aus subpopulation is considered an underappreciated resource within that diversity. A new rice panel, the Bengal and Assam Aus Panel (BAAP) of 266 aus accessions was generated with ∼2 million informative SNPs obtained using skim sequencing at ∼4× depth. The BAAP was grown in the field in Bangladesh in the 'boro' season under both continuously flooded and Alternate Wetting and Drying (AWD) irrigation during 2013 and 2014 in Mymensingh and during 2014 in Madhupur. Heading date, grain mass, straw biomass and harvest index were measured. The majority (94%) of BAAP accessions flowered within a relatively small window of 10 days. The AWD irrigation treatment generally caused an increase in grain mass, but no significant genotype by treatment interactions were detected for this trait. Shoot biomass was the only trait that showed evidence of genotype by treatment interaction. The average LD (Linkage Disequilibrium) decay across the genome was 243 Kbp. Genome wide association mapping revealed 115 quantitative trait loci (QTLs). There was little evidence of QTLs specific to the irrigation treatment, and only a few QTLs co-localized with known genes. However, some QTLs were detected across multiple sites and years. These QTLs should be targets for breeding, and include a region around 2.2 Mbp on chromosome 1, a large region in the middle of chromosome 7 and two regions on chromosome 11 (∼10 Mbp and ∼29 Mbp). The BAAP appears to be a valuable addition to the growing collection of GWA mapping populations of rice.

Biomass and elemental concentrations of 22 rice cultivars grown under alternate wetting and drying conditions at three field sites in Bangladesh.

As the global population grows, demand on food production will also rise. For rice, one limiting factor effecting production could be availability of fresh water, hence adoption of techniques that decrease water usage while maintaining or increasing crop yield are needed. Alternative wetting and drying (AWD) is one of these techniques. AWD is a method by which the level of water within a rice field cycles between being flooded and nonflooded during the growth period of the rice crop. The degree to which AWD affects cultivars differently has not been adequately addressed to date. In this study, 22 rice cultivars, mostly landraces of the aus subpopulation, plus some popular improved indica cultivars from Bangladesh, were tested for their response to AWD across three different field sites in Bangladesh. Grain and shoot elemental concentrations were determined at harvest. Overall, AWD slightly increased grain mass and harvest index compared to plants grown under continually flooded (CF) conditions. Plants grown under AWD had decreased concentrations of nitrogen in their straw compared to plants grown under CF. The concentration of elements in the grain were also affected when plants were grown under AWD compared to CF: Nickel, copper, cadmium and iron increased, but sodium, potassium, calcium, cobalt, phosphorus, molybdenum and arsenic decreased in the grains of plants grown under AWD. However, there was some variation in these patterns across different sites. Analysis of variance revealed no significant cultivar × treatment interaction, or site × cultivar × treatment interaction, for any of the plant mass traits. Of the elements analyzed, only grain cadmium concentrations were significantly affected by treatment × cultivar interactions. These data suggest that there is no genetic adaptation amongst the cultivars screened for response to AWD, except for grain cadmium concentration and imply that breeding specifically for AWD is not needed.

Elevated Trimethylarsine Oxide and Inorganic Arsenic in Northern Hemisphere Summer Monsoonal Wet Deposition.

For arsenic speciation, the inputs for wet deposition are not well understood. Here we demonstrate that trimethylarsine oxide (TMAO) and inorganic arsenic are the dominant species in monsoonal wet deposition in the summer Indian subcontinent, Bangladesh, with inorganic arsenic dominating, accounting for ∼80% of total arsenic in this medium. Lower concentrations of both species were found in monsoonal wet deposition in the winter Indian subcontinent, Sri Lanka. The only other species present was dimethylarsinic acid (DMAA), but this was usually below limits of detection (LoD). We hypothesize that TMAO and inorganic arsenic in monsoonal wet deposition are predominantly of marine origin. For TMAO, the potential source is the atmospheric oxidation of marine derived trimethylarsine. For inorganic arsenic, our evidence suggests entrainment of water column inorganic arsenic into atmospheric particulates. These conclusions are based on weather trajectory analysis and on the strong correlations with known wet deposition marine derived elements: boron, iodine, and selenium. The finding that TMAO and inorganic arsenic are widely present and elevated in monsoonal wet deposition identifies major knowledge gaps that need to be addressed regarding the understanding of arsenic's global cycle.

Interaction of Quercetin of Onion with Axon Guidance Protein Receptor, NRP-1 Plays Important Role in Cancer Treatment: An In Silico Approach.

Neuropilin-1 (NRP-1) is a transmembrane glycoprotein receptor whose distinct sites bind semaphorins and vascular endothelial growth factor family members to mediate the role of these ligands in neuronal axon guidance and angiogenesis, respectively. Similarly, Eph receptors and ephrin ligands play critical roles in various biological functions, and deregulated activation of Eph/ephrin signaling in humans is thought to lead to tumorigenesis. Therefore, in this paper, an attempt was made to elucidate the inhibition potential of nine bioactive compounds from four different native spices of Bangladesh against this couple of receptors via molecular docking study. The molecular docking study was carried out using Vina docking protocol. Finally, the receptor-ligand interaction analysis was carried out using the Discovery Studio Client package. Quercetin and diosgenin of onion showed favorable binding with NRP-1 with low binding energy of -7.8 and -7.2 kcal/mol, respectively, in comparison with the control inhibitor (-6.1 kcal/mol). The study suggests that ligand interaction with the residues Asp 48, Thr 44, Thr 77, Tyr 81, Trp29, Ile 143 of NRP-1 and Lys 653, Phe 765, Ser 763, Thr 699, Ile 683 of Eph might be critical for the inhibitory activity of these receptors. The study provides evidence for consideration of quercetin and diosgenin of onion as valuable small ligand molecules for targeting NRP-1 receptor in treatment and prevention of neurological disorders as well as cancer.

Analyses of Genetic Variations of Glutathione S-Transferase Mu1 and Theta1 Genes in Bangladeshi Tannery Workers and Healthy Controls.

Glutathione S-transferases (GSTs) belong to a group of multigene detoxification enzymes, which defend cells against oxidative stress. Tannery workers are at risk of oxidative damage that is usually detoxified by GSTs. This study investigated the genotypic frequencies of GST Mu1 (GSTM1) and GST Theta1 (GSTT1) in Bangladeshi tannery workers and healthy controls followed by their status of oxidative stress and total GST activity. Of the 188 individuals, 50.0% had both GSTM1 and GSTT1 (+/+), 12.2% had GSTM1 (+/-), 31.4% had GSTT1 (-/+) alleles, and 6.4% had null genotypes (-/-) with respect to both GSTM1 and GSTT1 alleles. Among 109 healthy controls, 54.1% were double positive, 9.2% had GSTM1 allele, 32.1% had GSTT1 allele, and 4.6% had null genotypes. Out of 79 tannery workers, 44.3% were +/+, 16.8% were +/-, 30.5% were -/+, and 8.4% were -/-. Though the polymorphic genotypes or allelic variants of GSTM1 and GSTT1 were distributed among the study subjects with different frequencies, the differences between the study groups were not statistically significant. GST activity did not vary significantly between the two groups and also among different genotypes while level of lipid peroxidation was significantly higher in tannery workers compared to controls irrespective of their GST genotypes.

Draxin from neocortical neurons controls the guidance of thalamocortical projections into the neocortex.

The thalamocortical tract carries sensory information to the neocortex. It has long been recognized that the neocortical pioneer axons of subplate neurons are essential for thalamocortical development. Herein we report that an axon guidance cue, draxin, is expressed in early-born neocortical neurons, including subplate neurons, and is necessary for thalamocortical development. In draxin(-/-) mice, thalamocortical axons do not enter the neocortex. This phenotype is sufficiently rescued by the transgenic expression of draxin in neocortical neurons. Genetic interaction data suggest that draxin acts through Deleted in colorectal cancer (DCC) and Neogenin (Neo1), to regulate thalamocortical projections in vivo. Draxin promotes the outgrowth of thalamic axons in vitro and this effect is abolished in thalamic neurons from Dcc and Neo1 double mutants. These results suggest that draxin from neocortical neurons controls thalamocortical projections into the neocortex, and that this effect is mediated through the DCC and Neo1 receptors.

Akhirin regulates the proliferation and differentiation of neural stem cells in intact and injured mouse spinal cord.

Although the central nervous system is considered a comparatively static tissue with limited cell turnover, cells with stem cell properties have been isolated from most neural tissues. The spinal cord ependymal cells show neural stem cell potential in vitro and in vivo in injured spinal cord. However, very little is known regarding the ependymal niche in the mouse spinal cord. We previously reported that a secreted factor, chick Akhirin, is expressed in the ciliary marginal zone of the eye, where it works as a heterophilic cell-adhesion molecule. Here, we describe a new crucial function for mouse Akhirin (M-AKH) in regulating the proliferation and differentiation of progenitors in the mouse spinal cord. During embryonic spinal cord development, M-AKH is transiently expressed in the central canal ependymal cells, which possess latent neural stem cell properties. Targeted inactivation of the AKH gene in mice causes a reduction in the size of the spinal cord and decreases BrdU incorporation in the spinal cord. Remarkably, the expression patterns of ependymal niche molecules in AKH knockout (AKH-/-) mice are different from those of AKH+/+, both in vitro and in vivo. Furthermore, we provide evidence that AKH expression in the central canal is rapidly upregulated in the injured spinal cord. Taken together, these results indicate that M-AKH plays a crucial role in mouse spinal cord formation by regulating the ependymal niche in the central canal.

The combinatorial guidance activities of draxin and Tsukushi are essential for forebrain commissure formation.

We have shown that draxin is a repulsive axon guidance molecule for a variety of neuron classes and that genetic deletion of draxin in mice results in the absence of all forebrain commissures. Moreover, we also identified a secreted molecule, Tsukushi (TSK), that belongs to the small leucine-rich proteoglycan family (SLRP) and inhibits signaling molecules, such as BMP and Wnt. TSK knockout mice show malformation of the corpus callosum (CC) and agenesis of the anterior commissure (AC), suggesting the importance of TSK function in forebrain commissure formation. There is a possibility that the combined function of these two proteins is essential for the formation of these commissures. In this study, we investigate this possibility by generating draxin/TSK doubly heterozygous mice and comparing their forebrain commissure phenotypes with those of singly heterozygous mice. We found that, although draxin and TSK did not interact directly, their genetic interaction was evident from the significantly higher prevalence of CC malformation and agenesis of the AC in the draxin/TSK doubly heterozygous mice. Importantly, in this study, we demonstrated a new function of TSK in guiding anterior olfactory neuronal (AON) and cortical axons. TSK bound to and provided growth inhibitory signals dose-dependently to AON and cortical axons in outgrowth assay. TSK also induced growth cone collapse when applied acutely to these cultured neurons. Furthermore, TSK and draxin had additive effects in inhibiting cortical and AON neurite outgrowth. Thus, based on a combination of genetic analyses and in vitro experiments, we propose that the combined guidance activities of draxin and TSK regulate forebrain commissure formation.