Centuries of Heat Waves over India during 20th and 21st Century

An assessment of temperature extremes is made for the Indian subcontinent to identify the changes since 1951 to 2015, and for the future climate periods till 2100 for all the 21 CMIP5 (Coupled Model intercomparision Project phase 5) models and the representative concentration pathways RCP4.5 and RCP8.5 were examined for the period from 1 March to 31 May to characterize the heat waves in future climates and mean maximum and mean minimum bias were evaluated for the Indian subcontinent. Later two highest recorded temperature regions were chosen Northwest & Central India (NW&CIN) and only central India (CIN) box and the features of heat waves such as intensity and frequency were evaluated up to 2100. Corresponding temperature predictions from historical runs for the period 1951–2005 of 21 global CMIP model outputs and statistics were performed with the India Meteorological Department (IMD) gridded maximum temperature data for validation. Statistical metrics of BIAS, RMSE and MAE have indicated low BIAS, high correlation and high IOA (Index of Agreement) validating CMIP climate simulations. By analyzing the statistics of all the 21 models with respect to the observational gridded data from IMD came to conclusion that among all the 21 models 5 models were performing well for Indian region and having good index of agreement with IMD. The frequencies of the days having thresholds of 40 ºC, 42 ºC and 45 ºC for the maximum temperature over India during the pre-monsoon are evaluated up to 21st century. All models are showing that the intensity and frequency of heat waves were increasing significantly for both RCP4.5 and RCP8.5. Specifically, the characteristics of heat waves in terms of intensity, duration and area extent are calculated and compared to heat waves of the current climate.

TrkB-enhancer Facilitates Functional Recovery After Traumatic Brain Injury

Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits. Here we demonstrate that CN2097 significantly reduces the post-traumatic synthesis of proinflammatory mediators and inhibits the posttraumatic activation of JNK in a rodent model of TBI. The recordings of field excitatory post-synaptic potentials in the hippocampal CA1 subfield demonstrate that TBI inhibits the expression of long-term potentiation (LTP) evoked by high-frequency stimulation of Schaffer collaterals, and that CN2097 attenuates this LTP impairment. Lastly, we demonstrate that CN2097 significantly improves the complex auditory processing deficits, which are impaired after injury. The multifunctionality of CN2097 strongly suggests that CN2097 could be highly efficacious in targeting complex secondary injury processes resulting from neurotrauma

Identification of QTLs and candidate genes for high grain Fe and Zn concentration in sorghum [Sorghum bicolor (L.)Moench]

Sorghum is a major food crop in the semi-arid tropics of Africa and Asia. Enhancing the grain iron (Fe) and zinc (Zn) concentration in sorghum using genetic approaches would help alleviate micronutrient malnutrition in millions of poor people consuming sorghum as a staple food. To localize genomic regions associated with grain Fe and Zn, a sorghum F6 recombinant inbred line (RIL) population (342 lines derived from cross 296B PVK 801) was phenotyped in six environments, and genotyped with simple sequence repeat (SSR), DArT (Diversity Array Technology) and DArTSeq (Diversity Array Technology) markers. Highly significant genotype environment interactions were observed for both micronutrients. Grain Fe showed greater variation than Zn. A sorghum genetic map was constructed with 2088 markers (1148 DArTs, 927 DArTSeqs and 13 SSRs) covering 1355.52 cM with an average marker interval of 0.6 cM. Eleven QTLs (individual) and 3 QTLs (across) environments for Fe and Zn were identified. We identified putative candidate genes from the QTL interval of qfe7.1, qzn7.1, and qzn7.2 (across environments) located on SBI-07 involved in Fe and Zn metabolism. These were CYP71B34, and ZFP 8 (ZINC FINGER PROTEIN 8). After validation, the linked markers identified in this study can help in developing high grain Fe and Zn sorghum cultivars in sorghum improvement programs globally

Identification of QTLs and Underlying Candidate Genes Controlling Grain Fe and Zn Concentration in Sorghum [Sorghum bicolor (L).Moench]

Biofortification is one of sustainable options for combating micronutrient-malnutrition. For identifying genomic regions associated with grain Fe and Zn in sorghum, RIL population (342 individuals) from cross 296B × PVK 801 was phenotyped for two years at three locations and genotyped with SSRs and DArTs. Highly significant genotype×environment interactions were observed for both micronutrients; grain Fe showed greater variation than Zn. Sorghum genetic map was constructed with 2088 markers (1148 DArTs, 927 DArT Seqs and 13 SSRs) covering 1355.52 cM with an average marker interval of 0.6cM. A total of 18 QTLs controlling Fe and Zn were found stable across environments. Three QTLs for Fe and 15 for Zn were identified with phenotypic variance explained (PVE) values ranging from 3.94 to 5.09% and 3.17 to 9.42%, respectively. Of these 18 stable QTLs, 11 were located on chromosome SBI-07. Favorable alleles for 11 QTLs (co-located) for Fe and Zn on chromosome SBI-07 were contributed by parent PVK801-P23. QTLs were analyzed in-silico to identify underlying candidate genes, 62 candidate genes involved in Fe/Zn metabolism were identified within QTL interval; twenty-three were found in QTL with highest phenotypic effect (PVE 9.42%). Sorghum genes underlying Fe/Zn QTLs were used to analyze gene synteny with rice and maize. Synteny sequence level between sorghum-rice ranged from 44% to 97%, while sorghum-maize ranged from 49% to 99%. QTLs/candidate/novel genes along with the marker/genetic resources identified through this study can help in developing high Fe and Zn lines in cost-effective and efficient manner

Genetic Variability, Genotype × Environment Interaction, Correlation, and GGE Biplot Analysis for Grain Iron and Zinc Concentration and Other Agronomic Traits in RIL Population of Sorghum (Sorghum bicolor L. Moench)

The low grain iron and zinc densities are well documented problems in food crops, affecting crop nutritional quality especially in cereals. Sorghum is a major source of energy and micronutrients for majority of population in Africa and central India. Understanding genetic variation, genotype × environment interaction and association between these traits is critical for development of improved cultivars with high iron and zinc. A total of 336 sorghum RILs (Recombinant Inbred Lines) were evaluated for grain iron and zinc concentration along with other agronomic traits for 2 years at three locations. The results showed that large variability exists in RIL population for both micronutrients (Iron = 10.8 to 76.4 mg kg−1 and Zinc = 10.2 to 58.7 mg kg−1, across environments) and agronomic traits. Genotype × environment interaction for both micronutrients (iron and zinc) was highly significant. GGE biplots comparison for grain iron and zinc showed greater variation across environments. The results also showed that G × E was substantial for grain iron and zinc, hence wider testing needed for taking care of G × E interaction to breed micronutrient rich sorghum lines. Iron and zinc concentration showed high significant positive correlation (across environment = 0.79; p 0.60, in individual environments) for Fe and Zn and other traits studied indicating its suitability to map QTL for iron and zinc

Galectin-3C Inhibits Tumor Growth and Increases the Anticancer Activity of Bortezomib in a Murine Model of Human Multiple Myeloma

Galectin-3 is a human lectin involved in many cellular processes including differentiation, apoptosis, angiogenesis, neoplastic transformation, and metastasis. We evaluated galectin-3C, an N-terminally truncated form of galectin-3 that is thought to act as a dominant negative inhibitor, as a potential treatment for multiple myeloma (MM). Galectin-3 was expressed at varying levels by all 9 human MM cell lines tested. In vitro galectin-3C exhibited modest anti-proliferative effects on MM cells and inhibited chemotaxis and invasion of U266 MM cells induced by stromal cell-derived factor (SDF)-1α. Galectin-3C facilitated the anticancer activity of bortezomib, a proteasome inhibitor approved by the FDA for MM treatment. Galectin-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. Delivery of galectin-3C intravenously via an osmotic pump in a subcutaneous U266 cell NOD/SCID mouse model of MM significantly inhibited tumor growth. The average tumor volume of bortezomib-treated animals was 19.6% and of galectin-3C treated animals was 13.5% of the average volume of the untreated controls at day 35. The maximal effect was obtained with the combination of galectin-3C with bortezomib that afforded a reduction of 94% in the mean tumor volume compared to the untreated controls at day 35. In conclusion, this is the first study to show that inhibition of galectin-3 is efficacious in a murine model of human MM. Our results demonstrated that galectin-3C alone was efficacious in a xenograft mouse model of human MM, and that it enhanced the anti-tumor activity of bortezomib in vitro and in vivo. These data provide the rationale for continued testing of galectin-3C towards initiation of clinical trials for treatment of MM

Lenalidomide reduces microglial activation and behavioral deficits in a transgenic model of Parkinson’s disease

BACKGROUND: Parkinson’s disease (PD) is one of the most common causes of dementia and motor deficits in the elderly. PD is characterized by the abnormal accumulation of the synaptic protein alpha-synuclein (α-syn) and degeneration of dopaminergic neurons in substantia nigra, which leads to neurodegeneration and neuroinflammation. Currently, there are no disease modifying alternatives for PD; however, targeting neuroinflammation might be a viable option for reducing motor deficits and neurodegeneration. Lenalidomide is a thalidomide derivative designed for reduced toxicity and increased immunomodulatory properties. Lenalidomide has shown protective effects in an animal model of amyotrophic lateral sclerosis, and its mechanism of action involves modulation of cytokine production and inhibition of NF-κB signaling. METHODS: In order to assess the effect of lenalidomide in an animal model of PD, mThy1-α-syn transgenic mice were treated with lenalidomide or the parent molecule thalidomide at 100 mg/kg for 4 weeks. RESULTS: Lenalidomide reduced motor behavioral deficits and ameliorated dopaminergic fiber loss in the striatum. This protective action was accompanied by a reduction in microgliosis both in striatum and hippocampus. Central expression of pro-inflammatory cytokines was diminished in lenalidomide-treated transgenic animals, together with reduction in NF-κB activation. CONCLUSION: These results support the therapeutic potential of lenalidomide for reducing maladaptive neuroinflammation in PD and related neuropathologies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-015-0320-x) contains supplementary material, which is available to authorized users

Formulation and evaluation of a topical niosomal gel containing a combination of benzoyl peroxide and tretinoin for antiacne activity

Ankush Gupta,1,* Sima Singh,1,* Niranjan G Kotla,1 Thomas J Webster2,3 1Department of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 3Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia *These authors contributed equally to this work Abstract: A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. One of the best options for successful drug delivery to the affected area of skin is the use of elastic vesicles (niosomes) which can be transported through the skin through channel-like structures. In this study, a combination of tretinoin (keratolytic agent) and benzoyl peroxide (BPO) (a potent antibacterial) was given by using niosomes as promising carriers for the effective treatment of acne by acting on a pathogenic site. In this section, niosomal gel formulation encapsulated drugs have been evaluated for in vitro, ex vivo, and in vivo, for their predetermined characteristics; and finally the stability of the niosome gel was tested at different temperature conditions for understanding of the storage conditions required for maintaining the quality of formulation attributes. The prepared niosome was found to be in the range of 531 nm with a zeta potential of -43 mV; the entrapment efficiencies of tretinoin (TRA) and BPO niosomes were found to be 96.25%±0.56% and 98.75%±1.25%, respectively. The permeated amount of TRA and BPO from the niosomal gel after 24 hours was calculated as 6.25±0.14 µg/cm2 and 5.04±0.014 µg/cm2, respectively. A comparative drug retention study in Wistar rat skin using cream, an alcoholic solution, and a niosomal gel showed 11.54 µg, 2.68 µg, and 15.54 µg amounts of TRA and 68.85 µg, 59.98 µg, and 143.78 µg amounts of BPO were retained in the layers of skin, respectively. In vivo studies of the niosomal gel and antiacne cream of TRA and BPO showed that the niosomal gel was more efficacious than the antiacne cream because niosomal gels with a 4.16-fold lower dose of BPO provided the same therapeutic index at targeted sites in comparison to the antiacne cream. Keywords: antiacne combination therapy, rabbit ear pinna model, retention efficiency, therapeutic inde