The Influence of Soil Moisture Regimes and Atmospheric Environments on transpiration and the Energy Status of Water in Plants

Plant responses to different soil moisture regimes have been extensively studied. Because of interactions between the soil, plant and climatic factors, few convincing generalizations concerning the influence of soil water on the transpiration of water by plants have been established. Generally single factors or at most the interaction of two have been studied at any one time. Useful theories describing the conditions of water retention in plant tissues and movement of water through plants have been proposed. Equally useful theories have been suggested for describing the retention and transmission of water in soil. The integration of these theories and their applications to evapotranspiration remains to be elucidated. This indicates a need for studying the total free energy path that causes water transport from soil to atmosphere through plants. Two interrelated categories of processes or factors, atmospheric desiccation and rate of soil water uptake, need to be studied simultaneously. The energy status of plant water, herein called total plant water potential, in conjugation with soil water potential appears to be critically involved in the process of water transfer through the soil-plant-atmosphere system. Plant water potential is the best criterion for detecting the degree of plant water stress. By studying water retention and flow properties of both plants and the supporting soil, one may be able to find relations that will help to predict the behavior of plants as they remove water from soil. For example, water retention characteristics of drought resistant plants may suggest reasons why some desert plants survive desiccating conditions that cause death to more succulent plant species. The major objective of this study was to investigate the influence of soil water potential and atmospheric environment on both the transpiration rates and components of the plant water potential

Synthesis and antimicrobial activities of novel 1,4-benzothiazine derivatives

AbstractA series of 2H,4H-2-[3,5-dimethyl-4-(substituted) phenyl azo pyrazol-1-yl] carbonyl methyl-3-oxo-1,4-benzothiazine derivatives have been synthesized by the reaction of 2H,4H-2-hydrazino carbonyl methyl-3-oxo-1,4-benzothiazine with acetyl acetone derivatives using ultrasound in lesser time with higher yields. All the synthesized compounds were investigated for their antibacterial activities. The result indicated that the compounds show convincing activities against Gram-positive bacteria (Bacillus subtilis and Streptococcus lactis) when compared with standard drug (ampicillin trihydrate). These compounds were also synthesized by conventional method and their structures have been elucidated on the basis of spectral analyses and chemical reactions

Investigation of Supercapacitive Behaviour of Electrodeposited Cobalt Oxide Thin Film by Potentiostatic Mode

Cobalt oxide films were prepared potentiostatically on stainless steel substrates. The as-deposited Co3O4 films were annealed at 400 °C, 500 °C, 600 °C and were analyzed. The structural analysis of films was carried out by X-ray diffraction technique and wettability parameters by Contact angle measurements at different annealed temperatures. The electrochemical supercapacitive behaviour of Cobalt oxide thin film was studied through Electrochemical properties using cyclic voltammetry and galvanostatic charge-discharge analysis which were carried out in 1 M aqueous KOH, 1 M aqueous NaOH and 1 M aqueous Na2SO4 electrolytes at a scan rate of 5 mV∙s – 1 with a three-electrode cell at different annealed temperatures. The film exhibited maximum specific capacitance of 284.4 Fg – 1 at a scan rate of 5 mV∙s – 1, specific energy 4.325 Whkg – 1, specific power 3 kWkg – 1 and coulomb efficiency 53.75 % in 1 M Na2SO4 electrolyte at optimized annealed temperature of 500 °C. In 1 M KOH electrolyte specific capacitance of Cobalt oxide electrode was 182.03 Fg – 1 at a scan rate 5 mV∙s – 1, specific energy 3.570 Whkg – 1, specific power 2.00 kWkg – 1 annealed at 500 °C. In 1 M NaOH electrolyte, annealed at 500 °C, the specific capacitance of Cobalt oxide electrode was 176.33 Fg – 1 at a scan rate 5 mVs – 1, specific energy 4.37 Whkg – 1, specific power 2.33 kWkg – 1

Highly efficient, processive and multifunctional recombinant endoglucanase RfGH5_4 from Ruminococcus flavefaciens FD-1 v3 for recycling lignocellulosic plant biomasses

Research Areas: Biochemistry & Molecular Biology ; Chemistry ; Polymer ScienceGene encoding endoglucanase, RfGH5_4 from R. flavefaciens FD-1 v3 was cloned, expressed in Escherichia coli BL21(DE3) cells and purified. RfGH5_4 showed molecular size 41 kDa and maximum activity at pH 5.5 and 55 ◦C. It was stable between pH 5.0–8.0, retaining 85% activity and between 5 ◦C–45 ◦C, retaining 75% activity, after 60 min. RfGH5_4 displayed maximum activity (U/mg) against barley β-D-glucan (665) followed by carboxymethyl cellulose (450), xyloglucan (343), konjac glucomannan (285), phosphoric acid swollen cellulose (86), beechwood xylan (21.7) and carob galactomannan (16), thereby displaying the multi-functionality. Catalytic efficiency (mL.mg− 1 s − 1 ) of RfGH5_4 against carboxymethyl cellulose (146) and konjac glucomannan (529) was significantly high. TLC and MALDI-TOF-MS analyses of RfGH5_4 treated hydrolysates of cellulosic and hemicellulosic polysaccharides displayed oligosaccharides of degree of polymerization (DP) between DP2-DP11. TLC, HPLC and Processivity-Index analyses revealed RfGH5_4 to be a processive endoglucanase as initially, for 30 min it hydrolysed cellulose to cellotetraose followed by persistent release of cellotriose and cellobiose. RfGH5_4 yielded sufficiently high Total Reducing Sugar (TRS, mg/g) from saccharification of alkali pre-treated sorghum (72), finger millet (62), sugarcane bagasse (38) and cotton (27) in a 48 h saccharification reaction. Thus, RfGH5_4 can be considered as a potential endoglucanase for renewable energy applications.info:eu-repo/semantics/publishedVersio

DNA repair targeted therapy: The past or future of cancer treatment?

The repair of DNA damage is a complex process that relies on particular pathways to remedy specific types of damage to DNA. The range of insults to DNA includes small, modest changes in structure including mismatched bases and simple methylation events to oxidized bases, intra- and interstrand DNA crosslinks, DNA double strand breaks and protein-DNA adducts. Pathways required for the repair of these lesions include mismatch repair, base excision repair, nucleotide excision repair, and the homology directed repair/Fanconi anemia pathway. Each of these pathways contributes to genetic stability, and mutations in genes encoding proteins involved in these pathways have been demonstrated to promote genetic instability and cancer. In fact, it has been suggested that all cancers display defects in DNA repair. It has also been demonstrated that the ability of cancer cells to repair therapeutically induced DNA damage impacts therapeutic efficacy. This has led to targeting DNA repair pathways and proteins to develop anti-cancer agents that will increase sensitivity to traditional chemotherapeutics. While initial studies languished and were plagued by a lack of specificity and a defined mechanism of action, more recent approaches to exploit synthetic lethal interaction and develop high affinity chemical inhibitors have proven considerably more effective. In this review we will highlight recent advances and discuss previous failures in targeting DNA repair to pave the way for future DNA repair targeted agents and their use in cancer therapy

Structure-Guided Optimization of Replication Protein A (RPA)–DNA Interaction Inhibitors

Replication protein A (RPA) is the major human single stranded DNA (ssDNA)-binding protein, playing essential roles in DNA replication, repair, recombination, and DNA-damage response (DDR). Inhibition of RPA–DNA interactions represents a therapeutic strategy for cancer drug discovery and has great potential to provide single agent anticancer activity and to synergize with both common DNA damaging chemotherapeutics and newer targeted anticancer agents. In this letter, a new series of analogues based on our previously reported TDRL-551 (4) compound were designed to improve potency and physicochemical properties. Molecular docking studies guided molecular insights, and further SAR exploration led to the identification of a series of novel compounds with low micromolar RPA inhibitory activity, increased solubility, and excellent cellular up-take. Among a series of analogues, compounds 43, 44, 45, and 46 hold promise for further development of novel anticancer agents

Design and Structure-Guided Development of Novel Inhibitors of the Xeroderma Pigmentosum Group A (XPA) Protein–DNA Interaction

XPA is a unique and essential protein required for the nucleotide excision DNA repair pathway and represents a therapeutic target in oncology. Herein, we are the first to develop novel inhibitors of the XPA–DNA interaction through structure-guided drug design efforts. Ester derivatives of the compounds 1 (X80), 22, and 24 displayed excellent inhibitory activity (IC50 of 0.82 ± 0.18 μM and 1.3 ± 0.22 μM, respectively) but poor solubility. We have synthesized novel amide derivatives that retain potency and have much improved solubility. Furthermore, compound 1 analogs exhibited good specificity for XPA over RPA (replication protein A), another DNA-binding protein that participates in the nucleotide excision repair (NER) pathway. Importantly, there were no significant interactions observed by the X80 class of compounds directly with DNA. Molecular docking studies revealed a mechanistic model for the interaction, and these studies could serve as the basis for continued analysis of structure–activity relationships and drug development efforts of this novel target

In Vivo Targeting Replication Protein A for Cancer Therapy

Replication protein A (RPA) plays essential roles in DNA replication, repair, recombination, and the DNA damage response (DDR). Retrospective analysis of lung cancer patient data demonstrates high RPA expression as a negative prognostic biomarker for overall survival in smoking-related lung cancers. Similarly, relative expression of RPA is a predictive marker for response to chemotherapy. These observations are consistent with the increase in RPA expression serving as an adaptive mechanism that allows tolerance of the genotoxic stress resulting from carcinogen exposure. We have developed second-generation RPA inhibitors (RPAis) that block the RPA-DNA interaction and optimized formulation for in vivo analyses. Data demonstrate that unlike first-generation RPAis, second-generation molecules show increased cellular permeability and induce cell death via apoptosis. Second-generation RPAis elicit single-agent in vitro anticancer activity across a broad spectrum of cancers, and the cellular response suggests existence of a threshold before chemical RPA exhaustion induces cell death. Chemical RPA inhibition potentiates the anticancer activity of a series of DDR inhibitors and traditional DNA-damaging cancer therapeutics. Consistent with chemical RPA exhaustion, we demonstrate that the effects of RPAi on replication fork dynamics are similar to other known DDR inhibitors. An optimized formulation of RPAi NERx 329 was developed that resulted in single-agent anticancer activity in two non-small cell lung cancer models. These data demonstrate a unique mechanism of action of RPAis eliciting a state of chemical RPA exhaustion and suggest they will provide an effective therapeutic option for difficult-to-treat lung cancers

Discovery and development of novel DNA-PK inhibitors by targeting the unique Ku–DNA interaction

DNA-dependent protein kinase (DNA-PK) plays a critical role in the non-homologous end joining (NHEJ) repair pathway and the DNA damage response (DDR). DNA-PK has therefore been pursued for the development of anti-cancer therapeutics in combination with ionizing radiation (IR). We report the discovery of a new class of DNA-PK inhibitors that act via a novel mechanism of action, inhibition of the Ku-DNA interaction. We have developed a series of highly potent and specific Ku-DNA binding inhibitors (Ku-DBi's) that block the Ku-DNA interaction and inhibit DNA-PK kinase activity. Ku-DBi's directly interact with the Ku and inhibit in vitro NHEJ, cellular NHEJ, and potentiate the cellular activity of radiomimetic agents and IR. Analysis of Ku-null cells demonstrates that Ku-DBi's cellular activity is a direct result of Ku inhibition, as Ku-null cells are insensitive to Ku-DBi's. The utility of Ku-DBi's was also revealed in a CRISPR gene-editing model where we demonstrate that the efficiency of gene insertion events was increased in cells pre-treated with Ku-DBi's, consistent with inhibition of NHEJ and activation of homologous recombination to facilitate gene insertion. These data demonstrate the discovery and application of new series of compounds that modulate DNA repair pathways via a unique mechanism of action

The Groebke-Blackburn-Bienayme Reaction

Imidazo[1,2a]pyridine is a well‐known scaffold in many marketed drugs, such as Zolpidem, Minodronic acid, Miroprofen and DS‐1 and it also serves as a broadly applied pharmacophore in drug discovery. The scaffold revoked a wave of interest when Groebke, Blackburn and Bienaymé reported independently a new three component reaction resulting in compounds with the imidazo[1,2‐a]‐heterocycles as a core structure. During the course of two decades the Groebke Blackburn Bienaymé (GBB‐3CR) reaction has emerged as a very important multicomponent reaction (MCR), resulting in over a hundred patents and a great number of publications in various fields of interest. Now two compounds derived from GBB‐3CR chemistry received FDA approval. To celebrate the first 20 years of GBB‐chemistry , we present an overview of the chemistry of the GBB‐3CR, including an analysis of each of the three starting material classes, solvents and catalysts. Additionally, a list of patents and their applications and a more in‐depth summary of the biological targets that were addressed, including structural biology analysis, is given