Analysis of growth rate and supply response of cocoa in Tamil Nadu, India: Nerlovian adjustment model

The present study focussed on the growth rate of area, production and productivity of cocoa in Tamil Nadu and estimated the impact of cocoa allocation decision, price variation and its supply in selected districts. The study employed the CAGR, Nerlovian model using the secondary data from 2011-12 to 2020-21. A positive significant growth in the area (40.24%) and production (34.60%) was witnessed in the Coimbatore district, while Thanjavur district showed a decline in the growth rate of cocoa. The area response concluded by lagged values of area and price significantly influenced the current year area in Coimbatore. The lagged productions were positively significant for both the districts and inferred that the increase in the price with one per cent level with the respective rise in price variability in Coimbatore district and opposite trend in Thanjavur district. The study suggested improving cocoa productivity and smoothing out variability in domestic prices can help boost farmers’ confidence in cocoa cultivation. The government provided the subsidy for transportation of the beans from one place to another, procurement centres in cocoa growing districts in Tamil Nadu and supplying the HYV to increase production, developing crop insurance schemes for cocoa during uncertain conditions and establishing facilities for the distribution of beans through Farmer Producer Companies (FPO), as well as attracting foreign consumers by improving bean quality

Screening and management of anemia in adolescent girls in lower socioeconomic strata

INTRODUCTION: Adolescence is a time of intense physical, psychosocial and cognitive development. Increased nutritional need at this junction relate to the fact that the adolescents gain upto 50 % of their adult weight, more than 20 % of their adult height and 50% of their adult skeletal mass during this period. The iron needs are high in adolescent girls because of the increased requirements for expansion of blood volume associated with the adolescent growth spurts and the onset of menstruation.[Clinical medicine and Research] India has the highest prevalence of iron deficiency anemia among women in the world especially adolescent girls. 60-70% of Indian adolescent girls are anemic [International centre for research on women and the Institute of health management- pachod] The percentage of Indian adolescent girls who were anemic was reported as 73.7% by Chaturvedi et al, 61.9% in urban areas and 85.4% in rural areas. AIM OF THE STUDY: 1. To assess the Hb status of adolescent girls from lower socio economic strata of society. 2. To identify the attributable causes of anemia in these adolescent girls. 3. To counsel on the impact of anemia and to educate them and the importance of regular iron intake. 4. To appropriately treat anemia in whom it was deducted. 5. To reassess the Hb status at three months interval for 1 year. 6. To encourage the regular intake of iron. 7. To popularise adolescent girls about consuming locally available, economically affordable iron rich foods. MATERIALS AND METHODS: The study was conducted at Institute of Social Obstetrics and Govt. Kasthurba Gandhi Hospital (ISO and Govt. KGH), Triplicane, Chennai, Outpatient Department. period of study: From April 2007 to April 2008. Study Population: 500 Adolescent girls between 12-19 years of age belonging to lower socioeconomic strata were included in the study based on the inclusion and exclusion criteria. Inclusion Criteria: 1. Age between 12 and 19 years of age. 2. Belonging to lower socioeconomic strata. 3. No known hematological lesion. 4. Not pregnant at the time of intervention. 5. Not on IFA Supplementation. Exclusion Criteria: 1. Girls 19yeras of age. 2. Pregnant woman. 3. H/o bleeding tendency. 4. On long time medications which might produce hematological complications. 5. H/o menstrual disturbances. 6. H/o malarial fever in the recent past. 7. Not willing to consume IFA tablets. 8. Not sure about follow up visits. 9. Not willing for changing food habits. SUMMARY: This study conducted at ISO-KGH, Chennai is to screen the adolescent girls in lower socioeconomic status for anemia. Among 500 girls screened, 340 (68%) were found to be anemic under various degrees. All the girls showed significant improvement in Hb levels and reached normal level after IFA supplementation and deworming. Severely anemic girls needed a longer time of IFA supplementation. In this study, lower socioeconomic status, hookworm infestation, increasing age were found to be attributable causes of anemia. There is significant improvement in the knowledge about anemia after counseling. CONCLUSION: Adolescence is an oppurtune time for interventions to address anemia. In addition to growth needs, girls need to improve iron status before pregnancy. Preventing iron deficiency and increasing iron stores in adolescent girls can improve their iron status in preparation for pregnancy and benefit their current health and well being. Treating anemia in adolescent girls is a primordial prevention there by reducing anemia complicating pregnancies and hence maternal mortality and morbidity to a great extent. This study shows the prevalence of anemia in adolescent girls in lower socioeconomic strata. Hence there is an urgent need to improve their iron status by planning intervention programme that would increase the hemoglobin levels through prophylaxis treatment, dietary modification and helminthic control

Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum

Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite homeostasis. To test this hypothesis, we measured whether pyrimidinone-amides, a new class of Hsp70 modulators, could inhibit the replication of the pathogenic P. falciparum stages in human red blood cells. Nine compounds with IC50 values from 30 nM to 1.6 μM were identified. Each compound also altered the ATPase activity of purified P. falciparum Hsp70 in single-turnover assays, although higher concentrations of agents were required than was necessary to inhibit P. falciparum replication. Varying effects of these compounds on Hsp70s from other organisms were also observed. Together, our data indicate that pyrimidinone-amides constitute a novel class of anti-malarial agents. © 2009 Elsevier Ltd. All rights reserved

The Saccharomyces cerevisiae Histone Chaperone Rtt106 Mediates the Cell Cycle Recruitment of SWI/SNF and RSC to the HIR-Dependent Histone Genes

In Saccharomyces cerevisiae, three out of the four histone gene pairs (HTA1-HTB1, HHT1-HHF1, and HHT2-HHF2) are regulated by the HIR co-repressor complex. The histone chaperone Rtt106 has recently been shown to be present at these histone gene loci throughout the cell cycle in a HIR- and Asf1-dependent manner and involved in their transcriptional repression. The SWI/SNF and RSC chromatin remodeling complexes are both recruited to the HIR-dependent histone genes; SWI/SNF is required for their activation in S phase, whereas RSC is implicated in their repression outside of S phase. Even though their presence at the histone genes is dependent on the HIR complex, their specific recruitment has not been well characterized. In this study we focused on characterizing the role played by the histone chaperone Rtt106 in the cell cycle-dependent recruitment of SWI/SNF and RSC complexes to the histone genes.Using GST pull-down and co-immunoprecipitation assays, we showed that Rtt106 physically interacts with both the SWI/SNF and RSC complexes in vitro and in vivo. We then investigated the function of this interaction with respect to the recruitment of these complexes to HIR-dependent histone genes. Using chromatin immunoprecipitation assays (ChIP), we found that Rtt106 is important for the recruitment of both SWI/SNF and RSC complexes to the HIR-dependent histone genes. Furthermore, using synchronized cell cultures, we showed by ChIP assays that the Rtt106-dependent SWI/SNF recruitment to these histone gene loci is cell cycle regulated and restricted to late G1 phase just before the peak of histone gene expression in S phase.Overall, these data strongly suggest that the interaction between the histone chaperone Rtt106 and both the SWI/SNF and RSC chromatin remodeling complexes is important for the cell cycle regulated recruitment of these two complexes to the HIR-dependent histone genes

Plasmodium falciparum-Infected Erythrocytes Induce Granzyme B by NK Cells through Expression of Host-Hsp70

In the early immune response to Plasmodium falciparum-infected erythrocytes (iRBC), Natural Killer (NK) cells are activated, which suggests an important role in innate anti-parasitic immunity. However, it is not well understood whether NK cells directly recognize iRBC or whether stimulation of NK cells depends mainly on activating signals from accessory cells through cell-to-cell contact or soluble factors. In the present study, we investigated the influence of membrane-bound host Heat shock protein (Hsp) 70 in triggering cytotoxicity of NK cells from malaria-naïve donors or the cell line NK92 against iRBC. Hsp70 and HLA-E membrane expression on iRBC and potential activatory NK cell receptors (NKG2C, CD94) were assessed by flow cytometry and immunoblot. Upon contact with iRBC, Granzyme B (GzmB) production and release was initiated by unstimulated and Hsp70-peptide (TKD) pre-stimulated NK cells, as determined by Western blot, RT-PCR and ELISPOT analysis. Eryptosis of iRBC was determined by Annexin V-staining. Our results suggest that presence of Hsp70 and absence of HLA-E on the membrane of iRBC prompt the infected host cells to become targets for NK cell-mediated cytotoxicity, as evidenced by impaired parasite development. Contact of iRBC with NK cells induced release of GzmB. We propose that following GzmB uptake, iRBC undergo eryptosis via a perforin-independent, GzmB-mediated mechanism. Since NK activity toward iRBC could be specifically enhanced by TKD peptide and abrogated to baseline levels by blocking Hsp70 exposure, we propose TKD as an innovative immunostimulatory agent to be tested as an adjunct to anti-parasitic treatments in vivo

The malarial exported PFA0660w is an Hsp40 co-chaperone of PfHsp70-x

Plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. Molecular chaperones of the heat shock protein (Hsp) family are prominent members of the exportome, including a number of Hsp40s and a Hsp70. PFA0660w, a type II Hsp40, has been shown to be exported and possibly form a complex with PfHsp70-x in the infected erythrocyte cytosol. However, the chaperone properties of PFA0660w and its interaction with human and parasite Hsp70s are yet to be investigated. Recombinant PFA0660w was found to exist as a monomer in solution, and was able to significantly stimulate the ATPase activity of PfHsp70-x but not that of a second plasmodial Hsp70 (PfHsp70-1) or a human Hsp70 (HSPA1A), indicating a potential specific functional partnership with PfHsp70-x. Protein binding studies in the presence and absence of ATP suggested that the interaction of PFA0660w with PfHsp70-x most likely represented a co-chaperone/chaperone interaction. Also, PFA0660w alone produced a concentrationdependent suppression of rhodanese aggregation, demonstrating its chaperone properties. Overall, we have provided the first biochemical evidence for the possible role of PFA0660w as a chaperone and as co-chaperone of PfHsp70-x. We propose that these chaperones boost the chaperone power of the infected erythrocyte, enabling successful protein trafficking and folding, and thereby making a fundamental contribution to the pathology of malaria

Exploring the Trypanosoma brucei Hsp83 Potential as a Target for Structure Guided Drug Design

Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp), while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF). Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC) and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite

Expression of a malarial Hsp70 improves defects in chaperone-dependent activities in ssa1 mutant yeast

Plasmodium falciparum causes the most virulent form of malaria and encodes a large number of molecular chaperones. Because the parasite encounters radically different environments during its lifecycle, many members of this chaperone ensemble may be essential for P. falciparum survival. Therefore, Plasmodium chaperones represent novel therapeutic targets, but to establish the mechanism of action of any developed therapeutics, it is critical to ascertain the functions of these chaperones. To this end, we report the development of a yeast expression system for PfHsp70-1, a P. falciparum cytoplasmic chaperone. We found that PfHsp70-1 repairs mutant growth phenotypes in yeast strains lacking the two primary cytosolic Hsp70s, SSA1 and SSA2, and in strains harboring a temperature sensitive SSA1 allele. PfHsp70-1 also supported chaperone-dependent processes such as protein translocation and ER associated degradation, and ameliorated the toxic effects of oxidative stress. By introducing engineered forms of PfHsp70-1 into the mutant strains, we discovered that rescue requires PfHsp70-1 ATPase activity. Together, we conclude that yeast can be co-opted to rapidly uncover specific cellular activities mediated by malarial chaperones. © 2011 Bell et al

HP1-Mediated Formation of Alternative Lengthening of Telomeres-Associated PML Bodies Requires HIRA but Not ASF1a

Approximately 10% of cancers use recombination-mediated Alternative Lengthening of Telomeres (ALT) instead of telomerase to prevent telomere shortening. A characteristic of cells that utilize ALT is the presence of ALT-associated PML nuclear bodies (APBs) containing (TTAGGG)n DNA, telomere binding proteins, DNA recombination proteins, and heterochromatin protein 1 (HP1). The function of APBs is unknown and it is possible that they are functionally heterogeneous. Most ALT cells lack functional p53, and restoration of the p53/p21 pathway in these cells results in growth arrest/senescence and a substantial increase in the number of large APBs that is dependent on two HP1 isoforms, HP1α and HP1γ. Here we investigated the mechanism of HP1-mediated APB formation, and found that histone chaperones, HIRA and ASF1a, are present in APBs following activation of the p53/p21 pathway in ALT cells. HIRA and ASF1a were also found to colocalize inside PML bodies in normal fibroblasts approaching senescence, providing evidence for the existence of a senescence-associated ASF1a/HIRA complex inside PML bodies, consistent with a role for these proteins in induction of senescence in both normal and ALT cells. Moreover, knockdown of HIRA but not ASF1a significantly reduced p53-mediated induction of large APBs, with a concomitant reduction of large HP1 foci. We conclude that HIRA, in addition to its physical and functional association with ASF1a, plays a unique, ASF1a-independent role, which is required for the localization of HP1 to PML bodies and thus for APB formation