Necessary conditions for linear noncooperative N-player delta differential games on time scales

We present necessary conditions for linear noncooperative N-player delta dynamic games on a generic time scale. Necessary conditions for an open-loop Nash-equilibrium and for a memoryless perfect state Nash-equilibrium are proved.Comment: Partially presented at the "Fifth Symposium on Nonlinear Analysis" (SNA 2007), Torun, Poland, September 10-14, 200

A symmetric quantum calculus

We introduce the $\alpha,\beta$-symmetric difference derivative and the $\alpha,\beta$-symmetric N\"orlund sum. The associated symmetric quantum calculus is developed, which can be seen as a generalization of the forward and backward $h$-calculus.Comment: Submitted 26/Sept/2011; accepted in revised form 28/Dec/2011; to Proceedings of International Conference on Differential & Difference Equations and Applications, in honour of Professor Ravi P. Agarwal, to be published by Springer in the series Proceedings in Mathematics (PROM

Historical Perspective and Innovations in Penile Urethroplasty

Penile urethral strictures are common and impact on quality of life and health-care costs. Management of penile urethral strictures is complex and depends on the physical characteristics of the stricture. Contemporary studies show no difference between urethral dilation and internal urethrotomy in terms of long-term outcomes. Overall, long-term success rates range from 20 to 30%. However, their recurrence rate is greater for men with longer strictures, penile urethral strictures, multiple strictures, presence of infection, or history of prior procedures, which make them less cost-effective. Surgical urethroplasty is associated with higher long-term success rates, averaging from 85 to 90%, mostly in virgin or noncomplex cases. Historically, modern urethral reconstruction has evolved from 1950s with the revolutionary introduction of Johanson’s technique for staged urethral reconstruction. Since then, many techniques have been developed and employed for urethroplasty, depending on the location, length, and character of the stricture. Successful management of urethral strictures requires detailed knowledge of anatomy, pathophysiology, proper patient selection, and reconstructive techniques

Temperature responsiveness of gilthead sea bream bone; an in vitro and in vivo approach

This study aimed to characterize the molecules involved in osteogenesis in seabream and establish using in vitro/in vivo approaches the responsiveness of selected key genes to temperature. The impact of a temperature drop from 23 to 13 degrees C was evaluated in juvenile fish thermally imprinted during embryogenesis. Both, in vitro/in vivo, Fib1a, appeared important in the first stages of bone formation, and Col1A1, ON and OP, in regulating matrix production and mineralization. OCN mRNA levels were up-regulated in the final larval stages when mineralization was more intense. Moreover, temperature-dependent differential gene expression was observed, with lower transcript levels in the larvae at 18 degrees C relative to those at 22 degrees C, suggesting bone formation was enhanced in the latter group. Results revealed that thermal imprinting affected the long-term regulation of osteogenesis. Specifically, juveniles under the low and low-to-high-temperature regimes had reduced levels of OCN when challenged, indicative of impaired bone development. In contrast, gene expression in fish from the high and high-to-low-temperature treatments was unchanged, suggesting imprinting may have a protective effect. Overall, the present study revealed that thermal imprinting modulates bone development in seabream larvae, and demonstrated the utility of the in vitro MSC culture as a reliable tool to investigate fish osteogenesis."Ministerio de Economia y Competitividad" (MINECO) [BES-2015-074654]; Portuguese Science Foundation (FCT) [SFRH/BPD/111512/2015, SFRH/BD/81625/2011]; MINECO, Spain [AGL2010-17324, AGL2014-57974-R]; "Generalitat de Catalunya" (XRAq); Generalitat de Catalunya [2014SGR-01371]; FCT, Portugal [CCMAR/Multi/04326/2013]; European Union [LIFECYCLE EU-FP7 222719]info:eu-repo/semantics/publishedVersio

A spontaneous increase in intracellular Ca2+ in metaphase II human oocytes in vitro can be prevented by drugs targeting ATP-sensitive K+ channels

STUDY QUESTION: Could drugs targeting ATP-sensitive K+ (KATP) channels prevent any spontaneous increase in intracellular Ca2+ that may occur in human metaphase II (MII) oocytes under in vitro conditions? SUMMARY ANSWER: Pinacidil, a KATP channel opener, and glibenclamide, a KATP channel blocker, prevent a spontaneous increase in intracellular Ca2+ in human MII oocytes. WHAT IS KNOWN ALREADY: The quality of the oocyte and maintenance of this quality during in vitro processing in the assisted reproductive technology (ART) laboratory is of critical importance to successful embryo development and a healthy live birth. Maintenance of Ca2+ homeostasis is crucial for cell wellbeing and increased intracellular Ca2+ levels is a well-established indicator of cell stress. STUDY DESIGN, SIZE, DURATION: Supernumerary human oocytes (n = 102) collected during IVF/ICSI treatment that failed to fertilize were used from October 2013 to July 2015. All experiments were performed on mature (MII) oocytes. Dynamics of intracellular Ca2+ levels were monitored in oocytes in the following experimental groups: (i) Control, (ii) Dimethyl sulfoxide (DMSO; used to dissolve pinacidil, glibenclamide and 2,4-Dinitrophenol (DNP)), (iii) Pinacidil, (iv) Glibenclamide, (v) DNP: an inhibitor of oxidative phosphorylation, (vi) Pinacidil and DNP and (vii) Glibenclamide and DNP. PARTICIPANTS/MATERIALS/SETTINGS/METHODS: Oocytes were collected under sedation as part of routine treatment at an assisted conception unit from healthy women (mean ± SD) age 34.1 ± 0.6 years, n = 41. Those surplus to clinical use were donated for research. Oocytes were loaded with Fluo-3 Ca2+-sensitive dye, and monitored by laser confocal microscopy for 2 h at 10 min intervals. Time between oocyte collection and start of Ca2+ monitoring was 80.4 ± 2.1 h. MAIN RESULTS AND THE ROLE OF CHANCE: Intracellular levels of Ca2+ increased under in vitro conditions with no deliberate challenge, as shown by Fluo-3 fluorescence increasing from 61.0 ± 11.8 AU (AU = arbitrary units; n = 23) to 91.8 ± 14.0 AU (n = 19; P <0.001) after 2 h of monitoring. Pinacidil (100 µM) inhibited this increase in Ca2+ (85.3 ± 12.3 AU at the beginning of the experiment, 81.7 ± 11.0 AU at the end of the experiment; n = 13; P = 0.616). Glibenclamide (100 µM) also inhibited the increase in Ca2+ (74.7 ± 10.6 AU at the beginning and 71.8 ± 10.9 AU at the end of the experiment; n = 13; P = 0.851. DNP (100 mM) induced an increase in intracellular Ca2+ that was inhibited by glibenclamide (100 µM; n = 9) but not by pinacidil (100 µM; n = 5). LIMITATIONS, REASONS FOR CAUTION: Owing to clinical and ethical considerations, it was not possible to monitor Ca2+ in MII oocytes immediately after retrieval. MII oocytes were available for our experimentation only after unsuccessful IVF or ICSI, which was, on average, 80.4 ± 2.1 h (n = 102 oocytes) after the moment of retrieval. As the MII oocytes used here were those that were not successfully fertilized, it is possible that they may have been abnormal with impaired Ca2+ homeostasis and, furthermore, the altered Ca2+ homeostasis might have been associated solely with the protracted incubation. WIDER IMPLICATIONS OF THE FINDINGS: These results show that maintenance of oocytes under in vitro conditions is associated with intracellular increase in Ca2+, which can be counteracted by drugs targeting KATP channels. As Ca2+ homeostasis is crucial for contributing to a successful outcome of ART, these results suggest that KATP channel openers and blockers should be tested as drugs for improving success rates of ART

Comparative genomics allowed the identification of drug targets against human fungal pathogens

<p>Abstract</p> <p>Background</p> <p>The prevalence of invasive fungal infections (IFIs) has increased steadily worldwide in the last few decades. Particularly, there has been a global rise in the number of infections among immunosuppressed people. These patients present severe clinical forms of the infections, which are commonly fatal, and they are more susceptible to opportunistic fungal infections than non-immunocompromised people. IFIs have historically been associated with high morbidity and mortality, partly because of the limitations of available antifungal therapies, including side effects, toxicities, drug interactions and antifungal resistance. Thus, the search for alternative therapies and/or the development of more specific drugs is a challenge that needs to be met. Genomics has created new ways of examining genes, which open new strategies for drug development and control of human diseases.</p> <p>Results</p> <p><it>In silico </it>analyses and manual mining selected initially 57 potential drug targets, based on 55 genes experimentally confirmed as essential for <it>Candida albicans </it>or <it>Aspergillus fumigatus </it>and other 2 genes (<it>kre2 </it>and <it>erg6</it>) relevant for fungal survival within the host. Orthologs for those 57 potential targets were also identified in eight human fungal pathogens (<it>C. albicans</it>, <it>A. fumigatus</it>, <it>Blastomyces dermatitidis</it>, <it>Paracoccidioides brasiliensis</it>, <it>Paracoccidioides lutzii, Coccidioides immitis</it>, <it>Cryptococcus neoformans </it>and <it>Histoplasma capsulatum</it>). Of those, 10 genes were present in all pathogenic fungi analyzed and absent in the human genome. We focused on four candidates: <it>trr1 </it>that encodes for thioredoxin reductase, <it>rim8 </it>that encodes for a protein involved in the proteolytic activation of a transcriptional factor in response to alkaline pH, <it>kre2 </it>that encodes for α-1,2-mannosyltransferase and <it>erg6 </it>that encodes for Δ(24)-sterol C-methyltransferase.</p> <p>Conclusions</p> <p>Our data show that the comparative genomics analysis of eight fungal pathogens enabled the identification of four new potential drug targets. The preferred profile for fungal targets includes proteins conserved among fungi, but absent in the human genome. These characteristics potentially minimize toxic side effects exerted by pharmacological inhibition of the cellular targets. From this first step of post-genomic analysis, we obtained information relevant to future new drug development.</p

ESTs from a wild Arachis species for gene discovery and marker development

BACKGROUND: Due to its origin, peanut has a very narrow genetic background. Wild relatives can be a source of genetic variability for cultivated peanut. In this study, the transcriptome of the wild species Arachis stenosperma accession V10309 was analyzed. RESULTS: ESTs were produced from four cDNA libraries of RNAs extracted from leaves and roots of A. stenosperma. Randomly selected cDNA clones were sequenced to generate 8,785 ESTs, of which 6,264 (71.3%) had high quality, with 3,500 clusters: 963 contigs and 2537 singlets. Only 55.9% matched homologous sequences of known genes. ESTs were classified into 23 different categories according to putative protein functions. Numerous sequences related to disease resistance, drought tolerance and human health were identified. Two hundred and six microsatellites were found and markers have been developed for 188 of these. The microsatellite profile was analyzed and compared to other transcribed and genomic sequence data. CONCLUSION: This is, to date, the first report on the analysis of transcriptome of a wild relative of peanut. The ESTs produced in this study are a valuable resource for gene discovery, the characterization of new wild alleles, and for marker development. The ESTs were released in the [GenBank:EH041934 to EH048197]

Kaempferol: a key emphasis to its anticancer potential

A marked decrease in human cancers, including breast cancer, bone cancer, and cervical cancer, has been linked to the consumption of vegetable and fruit, and the corresponding chemoprotective e ect has been associated with the presence of several active molecules, such as kaempferol. Kaempferol is a major flavonoid aglycone found in many natural products, such as beans, bee pollen, broccoli, cabbage, capers, cauliflower, chia seeds, chives, cumin, moringa leaves, endive, fennel, and garlic. Kaempferol displays several pharmacological properties, among them antimicrobial, anti-inflammatory, antioxidant, antitumor, cardioprotective, neuroprotective, and antidiabetic activities, and is being applied in cancer chemotherapy. Specifically, kaempferol-rich food has been linked to a decrease in the risk of developing some types of cancers, including skin, liver, and colon. The mechanisms of action include apoptosis, cell cycle arrest at the G2/M phase, downregulation of epithelial-mesenchymal transition (EMT)-related markers, and phosphoinositide 3-kinase/protein kinase B signaling pathways. In this sense, this article reviews data from experimental studies that investigated the links between kaempferol and kaempferol-rich food intake and cancer prevention. Even though growing evidence supports the use of kaempferol for cancer prevention, further preclinical and clinical investigations using kaempferol or kaempferol-rich foods are of pivotal importance before any public health recommendation or formulation using kaempferol.info:eu-repo/semantics/publishedVersio

Marker development for quality protein maize breeding and an interaction study between Opaque-2 and Ask2 genes

Quality Protein Maize (QPM) kernels contain twice the amounts of lysine and tryptophan compared to normal corn kernels. Although the opaque-2 (o2) mutation is the underlying cause of this beneficial change, other genes such as Aspartate kinase-2 (Ask2) affect the amino acid content in the endosperm to a lesser degree. To date, reports on the interaction between both loci are scarce and there are no high-throughput assays for the identification of the alleles of these genes. The objectives of this research were: 1) to study the interaction between the o2 and Ask2 genes with respect to the accumulation of amino acids in the endosperm in an F2 population, 2) to identify conserved SNPs into the o2 gene that can be used as markers, 3) to estimate the frequency of an SNP of Ask2 associated with the accumulation of lysine in the endosperm in CIMMYT germplasm, and 4) to develop high-throughput marker assays for these SNPs. The interaction study showed a preponderant effect of o2 on the accumulation of 11 amino acids (P ≤ 0.01). Ask2 appeared only to act with o2 to enhance marginally lysine, histidine and methionine levels in the double recessive homozygotes. Sequencing of amplicons at the o2 locus led to the identification of an SNP in exon 1 that discriminated all QPM (C) genotypes from non-QPM (T) genotypes. Validation of this SNP through KASP™ assays indicated that it was 92 % assertive in differentiating the o2 genotypes. In contrast, the frequency of the Ask2 SNP in CIMMYT QPM germplasm was low; however, an SSCP marker developed using this SNP detected five variants indicating that other unknown base changes may confer positive lysine-increasing responses. These markers could aid the marker-assisted selection of QPM cultivars