Impact of melatonin and tryptophan on water stress tolerance in white lupine (Lupinus termis L.)

Melatonin  has been identified as a signal molecule that regulates plant responses to different abiotic and biotic stresses. Melatonin (MT) and its precursor tryptophan (Try) have a major role in improving plant stress tolerance to different environmental stresses such as water deficiency. The rapid increase in the Egyptian population caused insufficient protein sources, especially those of animal origin, in their diet. The possible solution is to augment the diet with legumes such as white lupine which are relatively rich in protein. Thus, the current experimental work was carried out to find changes in growth, biochemical aspects and yield quantity and quality of white lupine plant with spraying of both MT and Try at different concentrations on plant shoot under water deficit stress conditions. Results showed that water deficit (75 or 50% of water irrigation requirements; WIR) caused significant reduction in growth, photosynthetic pigments, indole acetic acid and yield compared with those received 100% WIR. Seed yield significantly decreased (p < 0.05) by 26.98 and 41.64% by decreasing WIR to 75 and 50%. The decrease was accompanied by significant increase in phenolic contents, hydrogen peroxide, lipid peroxidation and some antioxidant enzymes, while nitrate reductase enzyme was decreased. However, external application of either MT or Try significantly alleviated the adverse effects of water deficit (growth suppression), since MT or Try-treated plants recovered more quickly than untreated plants. Moreover, MT or Try—treated plants had higher photosynthetic pigments, indole acetic acid, phenolic, as well as yield quantity and quality under the three WIR as compared with untreated plants. Melatonin treatment at 100 µM and Tryptophan at 200 µM increased weight of seeds/plant by 78.29 and 52.19%, 71.49 and 43.78% and 41.21 and 13.07% in plants irrigated with 100, 75 and 50% WIR, respectively. Exogenous MT and Try significantly reduced hydrogen peroxide and malondialdehyde content, while markedly increased the activities of antioxidant enzymes and nitrate reductase under different WIR. Finally, the current study concluded that MT and Try treatments alleviated the detrimental effects of water deficiency and accelerated the recovery mainly via improving white lupine plants tolerance in forms of enhancing photosynthetic pigments, indole acetic acid, phenolic and antioxidant capacity.     

3D-Pharmacophore Modeling,Molecular Docking,and Virtual Screening for Discovery of Novel CDK4/6 Selective Inhibitors

Russian Journal of Bioorganic Chemistry - Structure-based pharmacophore mapping, drug-likeness and ADMET profiles were used as tools in our virtual screening process, in addition to molecular...     

Hesperidin suppressed hepatic precancerous lesions via modulation of exophagy in rats

The enormous cost of modern medicines warrants alternative strategies for the better management of hepatocellular carcinoma. Recently, exosomes have been shown to relay the oncogenic information through the horizontal transfer of RNAs between the cells. In this study, we modulated exosomal production and autophagy (exophagy) by the administration of hesperidin and evaluated its effect on the development of hepatic precancerous lesion (HPC) in rats. Diethylnitrosamine and 2-acetylaminofluorene were used in vivo to induce HPC in rats. Rats were allocated into five groups: naïve, HPC, and three hesperidin treated (50, 100, and 200 mg/kg/d; orally) for 4 consecutive days per week for 16 weeks. Liver tissues and blood samples were collected for histopathological, immunohistochemical, and transmission electron microscope examinations, liver function, alfa-fetoprotein level, and isolation of exosomal and autophagy RNAs. Hesperidin administration showed hepato-protective effects and improved the microscopic hepatic features with a decrease in glutathione S-transferase placental precancerous foci and the abundance of exosomes in liver tissues. Hesperidin improved liver function with a significant decrease in alfa-fetoprotein levels. Hesperidin dose-dependently decreased exosomal RAB11A messsenger RNA and long noncoding RNA-RP11-583F2.2 along with the increase in exosomal miR-1298, involved in the exophagy process. In conclusion, hesperidin likely suppresses liver carcinogenesis in rat model via the modulation of exosomal secretion and autophagy.     

Predominant postglomerular vascular resistance response to reflex renal sympathetic nerve activation during ANG II clamp in rabbits

We have shown previously that a moderate reflex increase in renal sympathetic nerve activity (RSNA) elevated glomerular capillary pressure, whereas a more severe increase in RSNA decreased glomerular capillary pressure. This suggested that the nerves innervating the glomerular afferent and efferent arterioles could be selectively activated, allowing differential control of glomerular capillary pressure. A caveat to this conclusion was that intrarenal actions of neurally stimulated ANG II might have contributed to the increase in postglomerular resistance. This has now been investigated. Anesthetized rabbits were prepared for renal micropuncture and RSNA recording. One group (ANG II clamp) received an infusion of an angiotensin-converting enzyme inhibitor (enalaprilat, 2 mg/kg bolus plus 2 mg.kg(-1).h(-1)) plus ANG II ( approximately 20 ng.kg(-1).min(-1)), the other vehicle. Measurements were made before (room air) and during 14% O(2). Renal blood flow decreased less during ANG II clamp compared with vehicle [9 +/- 1% vs. 20 +/- 4%, interaction term (P(GT)) < 0.05], despite a similar increase in RSNA in response to 14% O(2) in the two groups. Arterial pressure and glomerular filtration rate were unaffected by 14% O(2) in both groups. Glomerular capillary pressure increased from 33 +/- 1 to 37 +/- 1 mmHg during ANG II clamp and from 33 +/- 2 to 35 +/- 1 mmHg in the vehicle group before and during 14% O(2), respectively (P(GT) < 0.05). During ANG II clamp, postglomerular vascular resistance was still increased in response to RSNA during 14% O(2), demonstrating that the action of the renal nerves on the postglomerular vasculature was independent of the renin-angiotensin system. This further supports our hypothesis that increases in RSNA can selectively control pre- and postglomerular vascular resistance and therefore glomerular ultrafiltration.     

Reproductive Biology and Behavior of <Emphasis Type="Italic">Tranosema rostrale</Emphasis> (Hymenoptera: Ichneumonidae), a Parasitoid of Low-Density Spruce Budworm (Lepidoptera: Tortricidae) Populations

Tranosema rostrale (Brischke) (Hymenoptera: Ichneumonidae) is an important parasitoid of low-density spruce budworm Choristoneura fumiferana (Clemens) (Lepidoptera: Tortricidae) populations. To investigate the effectiveness of this parasitoid in attacking low-density spruce budworm populations, we conducted a detailed laboratory study on its reproductive biology and behavior including mating behavior, potential fecundity, longevity, host searching, and oviposition behavior. We found that the occurrence of mating increases with the number of males present in the cage but that it drastically decreases when females mated previously. Females may mate multiple times with different males in one breeding session and mating duration is significantly longer when a male mates the second time with the same female. Dissections of T. rostrale’s oviducts showed that it is a synovigenic species emerging with about 17 % of its lifetime egg load and develops most of its eggs in the first three days after emergence at 20 °C. Sugar, but not pollen, significantly increased the insect’s longevity compared to water. Spruce budworm larvae, silk from larvae and damaged balsam fir foliage triggered probing in T. rostrale females significantly more often than larval feces. The sequence of the parasitoid’s behaviors leading to successful attack is described as antennation, probing, insertion of the ovipositor, oviposition, and subsequent disinterest or resuming of the sequence. Defense mechanisms of the host larva such as vigorous movements, biting, and/or regurgitation and behavioral countermeasures by T. rostrale are described in detail.     

Formation and calcification of modern gypsum-dominated stromatolites,EMISAL, Fayium,Egypt

Recent gypsum stromatolites are forming along the margin as well as on the pond floor of the EMISAL saltworks, Fayium, Egypt. Gypsum precipitates are classified according to their morphology, fabrics, and crystal size into (1) subaqueous bottom gypsum crusts, (2) selenitic gypsum facies, (3) stromatolitic gypsum dome facies, and (4) gypsolite facies. Two types of microbial mats, lithifying and non-lithifying, can be identified. The lithifying mat is shallow and composed of an alternation of gypsum and microbial layers that are seasonally controlled. The non-lithifying mat, formed in the deeper part of the pond, is a greenish-brown slime-rich layer that exhibits a frothy macro texture and produces a firm gelatinous film covering the sediment surface. Calcium carbonate (mostly aragonite) particles, identified by light and scanning electron microscopy, and X-ray diffraction occur within the deeper part of the lithified mat and are associated with living and degrading biofilm. Precipitation of aragonite is associated with the dissolution of gypsum, which may have resulted from bacterial sulphate reduction. The latter process increases alkalinity and ultimately results in the replacement of gypsum by aragonite.     

Clinicopathological features and prognosis of triple negative breast cancer in Kuwait: A comparative/perspective analysis

Aim

The aim of this study was to determine the incidence of TNBC in Kuwait, to analyze the clinicopathologic features and prognosis of this type of breast cancer, and compare it with reports from other regions of the world.

Background

Triple negative breast cancer (TNBC) is defined as a subtype that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). There is a growing evidence of the heterogeneity of such entity on the molecular level that may cause discrete outcomes.

Methods

We analyzed the clinicopathologic features of 363 TNBC cases which were diagnosed in Kuwait from July 1999 to June 2009. The disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan–Meier method. Comparison was done with reports from USA, Europe, Middle and Far East.

Results

Among 2986 patients diagnosed with breast cancer in Kuwait, 363 patients (12.2%) were TNBC. The median age was 48 years, 57.2% had lymph nodes (LN) metastasis, 56.9% were of grade III tumor and 41.9% had stage II disease. 81% developed recurrences and 75% of deaths occurred by 2.5 years after treatment. There is marked variation of clinicopathologic features according to country of patients’ cohort.

Conclusion

The incidence of TNBC in our study is similar to other studies. TNBC patients showed an early major recurrence surge peaking at approximately year 2.5. Regional variation of clinicopathologic features indicates a need for molecular studies to define underlying molecular features and its impact on survival.     

Evaluation of mRNA expression level of the ATP synthase membrane subunit c locus 1 (ATP5G1) gene in patients with schizophrenia

BackgroundSchizophrenia is a serious, complex mental disorder. The impairment of oxidative phosphorylation has a detrimental consequence on CNS function. Different ATP synthase subunits have been involved in the pathological process of various neurodegenerative disorders. Our goal was to evaluate the mRNA expression level of the ATP synthase membrane subunit c locus 1 (ATP5G1, also named ATP5MC1) gene in patients with schizophrenia.MethodsDetermination of the expression levels of ATP5G1 in plasma and peripheral blood mononuclear cells (PBMCs) were performed by real-time PCR in 90 controls and 90 patients with schizophrenia.ResultsPatients had significantly decreased ATP5G1 mRNA expression levels in both plasma and PBMCs compared to controls. The receiver operating characteristic curve was applied to detect a cut-off value of ATP5G1 expression in plasma and PBMCs. The ATP5G1 relative expression in PBMCs had better performance with a cut-off value ≤ 21 (AUC = 0.892, P < 0.001), sensitivity of 94.44%, and specificity of 72.22% in discriminating between schizophrenic patients. ATP5G1 expression in PBMCs was an independent predictor in schizophrenia.ConclusionThis study revealed a down-regulation of ATP5G1 expression in schizophrenia, precisely expression in PBMCs. That might give insight into the role of ATP5G1 gene in the pathogenesis of schizophrenia.     

Synthesis of A New Intercalating Nucleic Acid 6H-INDOLO[2,3-b] Quinoxaline Oligonucleotides to Improve Thermal Stability Of Hoogsteen-Type Triplexes

A new intercalating nucleic acid monomer X was obtained in high yield starting from alkylation of 4-iodophenol with (S)-(+)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol under Mitsunobu conditions followed by hydrolysis with 80% aqueous acetic acid to give a diol which was coupled under Sonogashira conditions with trimethylsilylacetylene (TMSA) to achieve the TMS protected (S)-4-(4-((trimethylsilyl)ethynyl)phenoxy)butane-1,2-diol. Tetrabutylammonium flouride was used to remove the silyl protecting group to obtain (S)-4-(4-ethynylphenoxy)butane-1,2-diol which was coupled under Sonogashira conditions with 2-(9-bromo-6H-indolo[2,3-b]quinoxalin-6-yl)-N,N-dimethylethanamine to achieve (S)-4-(4-((6-(2-(dimethylamino)ethyl)-6H-indolo[2,3-b]quinoxalin-9-yl)ethynyl)phenoxy)butane-1,2-diol. This compound was tritylated with 4,4′-dimethoxytrityl chloride followed by treatment with 2-cyanoethyltetraisopropylphosphordiamidite in the presence of N,N′-diisopropyl ammonium tetrazolide to afford the corresponding phosphoramidite. This phosphoramidite was used to insert the monomer X into an oligonucleotide which was used for thermal denaturation studies of a corresponding parallel triplex.