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IntroductionThe increase in atmospheric CO2 concentration, which mainly is attributed to fossil-fuel combustion and deforestation, is often suggested as one of the prime causative factors toward accelerated global warming. This commends for sequestration of atmospheric carbon under terrestrial systems to partially offset fossil-fuel emissions. Concerning the same, agricultural sector presents an extensive opportunity, especially for countries such as India where over 55% of the population is engaged in the agriculture sector.MethodsSequestering atmospheric carbon in agriculture requires the adoption of climate-resilient alternative agriculture practices without compromising food security. The deliberated study highlights the options of alteration in current conventional farming practices and its economic evaluation for sequestrating carbon under two Climate Change (CC) scenarios, viz., RCP 4.5 and 8.5, over three temporal scales, i.e., 2020, 2030, and 2050. Considering the current land-use pattern and existing growth rate in land-use shifting, three land-use policies, namely, Business as Usual (BaU), Optimistic, and Pessimistic scenario, integrated with CC scenarios were contemplated. Six possible futuristic scenarios were generated for the assessment of carbon sequestration and its valuation following the Integrated Valuation of Ecosystem Services and Tradeoff (InVEST) model.ResultsThe results suggested that across the studied region adopting an optimistic policy over BaU and pessimistic scenario, carbon can sequestrate an additional 0.64 to 1.46 Mt. (2.35 to 5.36 million ton CO2e) having an economic value of 193.4 to 504.8 million USD.ResultsMoreover, the outcomes of the study are advocated for the policy of carbon credit in the agriculture sector, which shall contribute toward meeting various nationally determined contributions (NDCs) and sustainable development goals (SDGs) as well.

IntroductionOver the years, smallholder farmers have faced more vulnerability to risk and uncertainty in India due to their dependence on cereal crops. One way to reduce this risk is through diversified agriculture, integrating different practices for efficient resource utilization, and adopting a farming systems approach. An integrated farming system (IFS) is one such technique that provides year-round income from different components of enterprises. However, the decision to adopt IFS may be determined by several characteristics of farmers, which needs to be delineated through impact analysis to harness the benefits of a systems approach.MethodsThis study analyzes the economic effects of integrated farming systems and assesses their determinants, as well as the dietary diversity patterns of farmers in two states of southern India, i.e., Kerala and Tamil Nadu. A multistage sampling technique was used to obtain cross-sectional data from 367 farmers randomly chosen from one district in Kerala and two districts in Tamil Nadu. The participants have Crop + Horticulture + Animal husbandry (45.45%) as their major system, whereas non-participants have Crop + Animal husbandry (44.35%) as their predominant system. Coarsened exact matching and logit regression methods were used to evaluate the economic impacts of IFS and its influencing factors.ResultsThe findings of the study indicate that age, education, livestock holding, access to credit, and plantation area have a positive and significant effect on participation by farmers in the program. The matching results show that adoption of IFS resulted in a significant economic impact, generating an additional gross income of Rs. 36,165 ha−1 and a net income of Rs. 35,852 ha−1 and improving the dietary diversity of farm households by 8.6% as compared to non-adopters.DiscussionThis study suggests that IFS is a promising approach for improving farmers' livelihoods, economic gains, and nutritional security. Therefore, the integrated farming systems models need to be upscaled through the convergence of government schemes in other regions of India to support smallholder farmers' farming.

Healthy water is our prime demand however population explosion and industrialization have threatened the quality of water. Consequently, about a billion people in developing countries including Iran are struggling for a safe and sustainable water supply. Timely water sampling and analyses are critical to access and maintain healthy status. The current study investigates the state of water supply in 29 villages of Sahneh town and provides recommendations for maintaining good health. Water samples were extensively analyzed for the physical and chemical indexes using the EPA standards and the Iran national water standards (Table S1). The mean of pH, total dissolve solid, electrical conductivity, chloride concentration, sulfate, temperature, bicarbonate, total alkalinity, calcium hardness was 8.2, 326.5 mg/L, 422.4 mS/cm, 203 mg/L, 6.4 mg/L, 24.7 °C, 257.2 mg/L, 210.9 mg/L as CaCO3, 233.8 mg/L CaCO3, respectively that are within the permitted limit. Interactions between these factors were statistically analyzed to characterize the water samples. All sampled waters were probable to sediment according to the Langelier index (0.67 ± 0.20), corrosive according to aggressiveness (10.74 ± 0.40) and Puckhorius indexes (6.96 ± 0.63). Water samples also exhibited scaling therefore it is recommended to use cemented pipes for dispensing networks. Moreover, balancing pH, alkalinity, calcium levels and annual testing by the government should be considered to promote good health.

Excess use of hazardous agrochemicals and inorganic fertilizers resulted negative impact on environmental outcomes and degraded soil function, biological diversity, and ecosystem services. A 15-year long-term (2004–05 to 2017–18) field experiment was conducted to improve the ecosystem services with soil quality restoration and stabilization of yield through agronomic manipulation in the rice (Oryza sativa)–wheat (Triticum aestivum) system under Indo-Gangetic Plains (IGP). Three crop management practices (i) organic crop management, (ii) inorganic crop management, and (iii) integrated crop management were evaluated at four locations (i) Jabalpur, (ii) Ludhiana, (iii) Pantnagar, and (iv) Modipuram in a factorial randomized block design and replicated thrice at each location. Among the spatial variation, the highest soil quality indicators like soil microbial biomass carbon (0.52 mg g−1), fungal (46.2 CFU × 104 CFU), bacterial (54.2 CFU × 106 CFU), and actinomycetes viable cells (23.0 CFU × 106 CFU), and nutrients (available N and available P) were observed at Pantnagar than other location. The soil pH varied from 7.2 to 8.3, and the lowest bulk density (ρb) was recorded at Jabalpur and Modipuram. Subsequently, higher system productivity (8,196.7 kg ha−1) and net returns were obtained in Pantnagar > Ludhiana, and it was 44.1–63.4% higher than in Modipuram and Jabalpur. Among the crop management, organic crop management significantly improved (p < 0.05) ρb, soil organic carbon, available N, available P, and available K by 3.7%, 33.3%, 16.4%, 37.8%, and 20.3% over inorganic crop management, respectively. Similarly, the highest bacterial, fungal, and actinomycetes viable cell counts were found under the organic plots, followed by integrated plots. In terms of productivity, integrated crop management (ICM) had increased the system productivity by 4.7%–6.7% and net returns by 22.2% and 23.5% over inorganic and organic crop management. Similarly, the highest sustainability yield index (SYI) was recorded in integrated crop management (0.77) as compared to inorganic (0.74) and organic management (0.75). The soil quality index was estimated as 0.60, 0.53, and 0.54 in organic, inorganic, and ICM, respectively. Hence, the study indicated that the application of organic amendments under organic or integrated crop management improves the system’s resiliency and sustainability. Therefore, the study concludes that towards organic approach (integrated application of organic amendments with a gradual reduction in mineral fertilizers) is better suitable for keeping the rice–wheat system productivity and sustainable in the long term.

Heterozygous mutations in FLT3ITD, TET2, and DNMT3A are associated with hematologic malignancies in humans. In patients, cooccurrence of mutations in FLT3ITD combined with TET2 (TF) or FLT3ITD combined with DNMT3A (DF) are frequent. However, in some rare complex acute myeloid leukemia (AML), all 3 mutations cooccur — i.e., FLT3ITD, TET2, and DNMT3A (TFD). Whether the presence of these mutations in combination result in quantitative or qualitative differences in disease manifestation has not been investigated. We generated mice expressing heterozygous Flt3ITD and concomitant for either heterozygous loss of Tet2 (TF) or Dnmt3a (DF) or both (TFD). TF and DF mice did not induce disease early on, in spite of similar changes in gene expression; during the same time frame, an aggressive form of transplantable leukemia was observed in TFD mice, which was mostly associated with quantitative but not qualitative differences in gene expression relative to TF or DF mice. The gene expression signature of TFD mice showed remarkable similarity to the human TFD gene signature at the single-cell RNA level. Importantly, TFD-driven AML responded to a combination of drugs that target Flt3ITD, inflammation, and methylation in a mouse model, as well as in a PDX model of AML bearing 3 mutations.

An inter-organizational certificate course i.e. Certified Farm Advisor (CFA) in Organic Farming was jointly organized by National Institute of Agricultural Extension Management (MANAGE), Hyderabad and ICAR-Indian Institute of Farming Systems Research, Modipuram, Meerut during 2019. The objective of this certificate course was to create a cadre of “Certified Farm Advisors†in appropriate technologies of organic farming and enable them to deliver effective “Technical Advisory Services†and thereby solving the field level problems faced by the organic farmers/entrepreneurs/startups or other related stakeholders. A 15 days CFA module II was organized at ICAR- Indian Institute of Farming Systems Research, Modipuram, Meerut in two batches with 50 trainees from 15 different states and union territories. In the present study, the learning, knowledge and skill levels of the participants were analyzed. Multiple regression analysis showed that, gender, service experience and serving region significantly affected the learning ability of trainees. There was significant improvement in the knowledge and skill of trainees in various aspects of organic farming, viz. organic standards, certification and marketing network (study area A); technology package (study area B) and general knowledge (study area C). Based on the training effectiveness scores (TES), maximum improvement was observed with general knowledge of organic farming with 103.73% improvement. However, study area A and B exhibited 45.41% and 34.88% improvement, respectively. Further, the success of this inter-organizational training programme could serve as a model for streamlining HRD programmes on organic farming in the country.

Herbicide resistance in little seed canary grass (Phalaris minor Retz.) in wheat is the major sustainability issue, which puts the rice-wheat (R-W) system in north-western Indo-Gangetic Plains (IGP) under serious threat. To assess the resistance level, a questionnaires based survey with a systematic approach was conducted during rabi 2017-18 in five districts (Yamuna Nagar, Kaithal, Karnal, Fatehabad and Rohtak) of Haryana. The study revealed that at present, farmers of Haryana are closely back to square one, similar to the situation of herbicide resistance in P. minor like 1990's and currently, no herbicide is satisfactorily effective against resistant P. minor. Farmers are using every possible combination of herbicides in a hit and trial way. In 2017-18, half of the farmers (50%) went for the second spray, 13% applied the third spray, and even 3% of farmers opted for the fourth spray. The same pattern followed in the case of herbicide dose; in 2017-18, 38% of farmers opted for 2-4 X-dose, 16% of farmers for 4-6 X-dose, 3% of farmers for 6-8 X-dose, and even one percent farmers applied 8-10 X-dose. Negative relationship between percent control with higher dose (X) (Chi-Square value 72.560a, DF = 12 and p =

FLT3 internal tandem duplication (FLT3-ITD) mutations account for ~25% of adult acute myeloid leukemia cases and are associated with poor prognosis. Venetoclax, a selective BCL-2 inhibitor, has limited monotherapy activity in relapsed/refractory acute myeloid leukemia with no responses observed in a small subset of FLT3-ITD+ patients. Further, FLT3-ITD mutations emerged at relapse following venetoclax monotherapy and combination therapy suggesting a potential mechanism of resistance. Therefore, we investigated the convergence of FLT3-ITD signaling on the BCL-2 family proteins and determined combination activity of venetoclax and FLT3-ITD inhibition in preclinical models. In vivo, venetoclax combined with quizartinib, a potent FLT3 inhibitor, showed greater anti-tumor efficacy and prolonged survival compared to monotherapies. In a patient-derived FLT3-ITD+ xenograft model, cotreatment with venetoclax and quizartinib at clinically relevant doses had greater anti-tumor activity in the tumor microenvironment compared to quizartinib or venetoclax alone. Use of selective BCL-2 family inhibitors further identified a role for BCL-2, BCL-XL and MCL-1 in mediating survival in FLT3-ITD+ cells in vivo and highlighted the need to target all three proteins for greatest anti-tumor activity. Assessment of these combinations in vitro revealed synergistic combination activity for quizartinib and venetoclax but not for quizartinib combined with BCL-XL or MCL-1 inhibition. FLT3-ITD inhibition was shown to indirectly target both BCL-XL and MCL-1 through modulation of protein expression, thereby priming cells toward BCL-2 dependence for survival. These data demonstrate that FLT3-ITD inhibition combined with venetoclax has impressive anti-tumor activity in FLT3-ITD+ acute myeloid leukemia preclinical models and provides strong mechanistic rational for clinical studies.

Background and Aims: Post-dural puncture headache (PDPH) is one of the complications following spinal anaesthesia (SA) and accidental dural puncture (ADP). In our institute, we routinely practice epidural analgesia (EA) for supra-major surgeries. Our previous audit on EA revealed 4% incidence of ADP. This lead us to a clinical initiative to follow-up patients with dural puncture (DP) to note the incidence, presentation, associated symptoms and treatment of PDPH. Herewith, we present the retrospective analysis over a 2-year period. Methods: Following institutional review board approval, the follow-up notes of patients who had DP from May 2011 to April 2013 were analysed retrospectively (using SPSS 20 version) with respect to the needle size, level of DP, reinsertion of epidural catheter, details of ongoing analgesics, incidence and severity of PDPH and treatment received. Results: In 2 years, we found that the incidence of PDPH in the patients who received SA was 3.9% and 25% in the ADP group. There was a positive association between needle size, type and PDPH, and it was seen more in the 20–40 age group. The commonest presentation of PDPH was occipital/frontal headache within 96 h and lasted for a mean of 3 days. All patients received pharmacological treatment. Seventy-one per cent of patients (25) were either on coffee or caffeine tablets. One case of intractable PDPH responded well to oral pregabalin 75 mg. Conclusion: PDPH severity and incidence following ADP in our centre is lower than the reported incidence from obstetric centres and can be effectively controlled with drug treatment only.

The antibiotic, fosmidomycin (FSM) targets the methylerythritol phosphate (MEP) pathway of isoprenoid synthesis by inhibiting the essential enzyme, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (Dxr) and is lethal to intracellular parasites and bacteria. The obligate intracellular bacterial pathogen, Chlamydia trachomatis, alternates between two developmental forms: the extracellular, infectious elementary body (EB), and the intracellular, replicative form called the reticulate body (RB). Several stressful growth conditions including iron deprivation halt chlamydial cell division and cause development of a morphologically enlarged, but viable form termed an aberrant body (AB). This phenotype constitutes the chlamydial developmental state known as persistence. This state is reversible as removal of the stressor allows the chlamydiae to re-enter and complete the normal developmental cycle. Bioinformatic analysis indicates that C. trachomatis encodes a homolog of Dxr, but its function and the requirement for isoprenoid synthesis in chlamydial development is not fully understood. We hypothesized that chlamydial Dxr (DxrCT) is functional and that the methylerythritol phosphate (MEP) pathway is required for normal chlamydial development. Thus, FSM exposure should be lethal to C. trachomatis. Overexpression of chlamydial Dxr (DxrCT) in Escherichia coli under FSM exposure and in a conditionally lethal dxr mutant demonstrated that DxrCT functions similarly to E. coli Dxr. When Chlamydia-infected cultures were exposed to FSM, EB production was significantly reduced. However, titer recovery assays, electron microscopy, and peptidoglycan labeling revealed that FSM inhibition of isoprenoid synthesis is not lethal to C. trachomatis, but instead induces persistence. Bactoprenol is a critical isoprenoid required for peptidoglycan precursor assembly. We therefore conclude that FSM induces persistence in Chlamydia by preventing bactoprenol production necessary for peptidoglycan precursor assembly and subsequent cell division.

ABSTRACT Peptidoglycan is a sugar/amino acid polymer unique to bacteria and essential for division and cell shape maintenance. The d-amino acids that make up its cross-linked stem peptides are not abundant in nature and must be synthesized by bacteria de novo. d-Glutamate is present at the second position of the pentapeptide stem and is strictly conserved in all bacterial species. In Gram-negative bacteria, d-glutamate is generated via the racemization of l-glutamate by glutamate racemase (MurI). Chlamydia trachomatis is the leading cause of infectious blindness and sexually transmitted bacterial infections worldwide. While its genome encodes a majority of the enzymes involved in peptidoglycan synthesis, no murI homologue has ever been annotated. Recent studies have revealed the presence of peptidoglycan in C. trachomatis and confirmed that its pentapeptide includes d-glutamate. In this study, we show that C. trachomatis synthesizes d-glutamate by utilizing a novel, bifunctional homologue of diaminopimelate epimerase (DapF). DapF catalyzes the final step in the synthesis of meso-diaminopimelate, another amino acid unique to peptidoglycan. Genetic complementation of an Escherichia coli murI mutant demonstrated that Chlamydia DapF can generate d-glutamate. Biochemical analysis showed robust activity, but unlike canonical glutamate racemases, activity was dependent on the cofactor pyridoxal phosphate. Genetic complementation, enzymatic characterization, and bioinformatic analyses indicate that chlamydial DapF shares characteristics with other promiscuous/primordial enzymes, presenting a potential mechanism for d-glutamate synthesis not only in Chlamydia but also numerous other genera within the Planctomycetes-Verrucomicrobiae-Chlamydiae superphylum that lack recognized glutamate racemases. IMPORTANCE Here we describe one of the last remaining “missing” steps in peptidoglycan synthesis in pathogenic Chlamydia species, the synthesis of d-glutamate. We have determined that the diaminopimelate epimerase (DapF) encoded by Chlamydia trachomatis is capable of carrying out both the epimerization of DAP and the pyridoxal phosphate-dependent racemization of glutamate. Enzyme promiscuity is thought to be the hallmark of early microbial life on this planet, and there is currently an active debate as to whether “moonlighting enzymes” represent primordial evolutionary relics or are a product of more recent reductionist evolutionary pressures. Given the large number of Chlamydia species (as well as members of the Planctomycetes-Verrucomicrobiae-Chlamydiae superphylum) that possess DapF but lack homologues of MurI, it is likely that DapF is a primordial isomerase that functions as both racemase and epimerase in these organisms, suggesting that specialized d-glutamate racemase enzymes never evolved in these microbes.

Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs), and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK) whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis.

Background: Stunting is one of key factor of chronic under- nutrition is a major health problem in South Asia. It consequences increased morbidity & mortality during childhood. Objectives: This study aims to explore the socio-economic deter- minants of stunting among under-five children of rural tribal In- dia. Methodology: It was cross sectional study and carried out in rural community in Jhalawar District in children’s aged 6-59 months of age during period of February 2014 to April 2014 in 570 study samples. Results: There were almost equal numbers of male and females participated and it was observed that stunting was positively asso- ciated with birth weight, birth order, ANC visit at health care fa- cilities & family monthly income while inversely associated with age of baby, birth interval, EBF, PNC visit at health care facilities, & family size. Logistic regression analysis showed association with gender, working status of mother, history of TB in family member, ANC care, illiteracy of parents, mass media, overcrowding, and type of water supply. Conclusion: Our analysis confirms the multifactorial nature of child stunting. It emphasizes the programmes should specifically target higher-risk groups such as young children, residents of ru- ral community, less educated fathers, poor family social life, low- quality household environment, various morbidity and low birth weight.

Stem cell factor (SCF) mediated KIT receptor activation plays a pivotal role in mast cell growth, maturation and survival. However, the signaling events downstream from KIT are poorly understood. Mast cells express multiple regulatory subunits of class 1(A) PI3Kinase (PI3K) including p85α, p85β, p50α, and p55α. While it is known that PI3K plays an essential role in mast cells; the precise mechanism by which these regulatory subunits impact specific mast cell functions including growth, survival and cycling are not known. We show that loss of p85α impairs the growth, survival and cycling of mast cell progenitors (MCp). To delineate the molecular mechanism (s) by which p85α regulates mast cell growth, survival and cycling, we performed microarray analyses to compare the gene expression profile of MCps derived from WT and p85α-deficient mice in response to SCF stimulation. We identified 151 unique genes exhibiting altered expression in p85α-deficient cells in response to SCF stimulation compared to WT cells. Functional categorization based on DAVID bioinformatics tool and Ingenuity Pathway Analysis (IPA) software relates the altered genes due to lack of p85α to transcription, cell cycle, cell survival, cell adhesion, cell differentiation, and signal transduction. Our results suggest that p85α is involved in mast cell development through regulation of expression of growth, survival and cell cycle related genes.

We hypothesized that analysis of single nucleotide polymorphism arrays (SNP-A) and new molecular defects may provide new insight in the pathogenesis of systemic mastocytosis (SM). SNP-A karyotyping was applied to identify recurrent areas of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family. Overall survival (OS) was analyzed using the Kaplan-Meier method. We studied a total of 26 patients with SM. In 67% of SM patients, SNP-A karyotyping showed new chromosomal abnormalities including uniparental disomy of 4q and 2p spanning TET2/KIT and DNMT3A. Mutations in TET2, DNMT3A, ASXL1 and CBL were found in 23%, 12%, 12%, and 4% of SM patients, respectively. No mutations were observed in EZH2 and IDH1/IDH2. Significant differences in OS were observed for SM mutated patients grouped based on the presence of combined TET2/DNMT3A/ASXL1 mutations independent of KIT (P = 0.04) and sole TET2 mutations (P

Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs), and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK) whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis.

Hyperactivation of the mTOR pathway impairs hematopoietic stem cell (HSC) functions and promotes leukemogenesis. mTORC1 and mTORC2 differentially control normal and leukemic stem cell functions. mTORC1 regulates p70 ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding (eIF4E-binding) protein 1 (4E-BP1), and mTORC2 modulates AKT activation. Given the extensive crosstalk that occurs between mTORC1 and mTORC2 signaling pathways, we assessed the role of the mTORC1 substrate S6K1 in the regulation of both normal HSC functions and in leukemogenesis driven by the mixed lineage leukemia (MLL) fusion oncogene MLL-AF9. We demonstrated that S6K1 deficiency impairs self-renewal of murine HSCs by reducing p21 expression. Loss of S6K1 also improved survival in mice transplanted with MLL-AF9- positive leukemic stem cells by modulating AKT and 4E-BP1 phosphorylation. Taken together, these results suggest that S6K1 acts through multiple targets of the mTOR pathway to promote self-renewal and leukemia progression. Given the recent interest in S6K1 as a potential therapeutic target in cancer, our results further support targeting this molecule as a potential strategy for treatment of myeloid malignancies., Introduction Aberrant regulation of the intracellular signaling pathways that underlie normal hematopoietic stem cell (HSC) renewal and differentiation is one of the pathogenic hallmarks of human leukemia. mTOR plays an [...]