Water stress causes differential effects on germination indices, total soluble sugar and proline content in wheat (Triticum aestivum L.) genotypes

Different cultivars differ inherently in their response to drought and those cultivars best adapted to growth in arid and semiarid conditions form the most uniform and vigorous stands when grown under water deficits. The seeds of five wheat cultivars (GA-2002, Chakwal-97, Uqab-2000, Chakwal-50 and Wafaq-2001) were subjected to five different levels of osmotic stress; 0 bars (distilled water, control), -2, -4, -6 and -8 bars to assess the effect of osmotic stress on germination percentage, mean germination time, coleoptile length, proline and sugar amounts. The investigations were performed as factorial experiments under complete randomized design (CRD). Germination percentage, mean germination time and coleoptile length were shown to decrease with increasing osmotic stress, whereas a progressive increase in proline and sugar content were observed with increasing osmotic stress. The response of five cultivars examined under various levels of osmotic stress differed dramatically. Chakwal-50 and GA-2002 were amongst best performers, showing high germination rate, longest coleoptile length, highest proline values and sugar contents when compared with other cultivars under stress conditions. These were proven to be the most tolerant cultivars. Performance of  Wafaq-2001 and Uqab-2000 were poor when compared to the other cultivars under limited water stress conditions.Key words: Wheat, Triticum aestivum, water stress, osmotic stress, proline, sugar, seedling, germination

Dual Targeting of PDGFRα and FGFR1 Displays Synergistic Efficacy in Malignant Rhabdoid Tumors

© 2016 The Author(s) Subunits of the SWI/SNF chromatin remodeling complex are mutated in a significant proportion of human cancers. Malignant rhabdoid tumors (MRTs) are lethal pediatric cancers characterized by a deficiency in the SWI/SNF subunit SMARCB1. Here, we employ an integrated molecular profiling and chemical biology approach to demonstrate that the receptor tyrosine kinases (RTKs) PDGFRα and FGFR1 are coactivated in MRT cells and that dual blockade of these receptors has synergistic efficacy. Inhibitor combinations targeting both receptors and the dual inhibitor ponatinib suppress the AKT and ERK1/2 pathways leading to apoptosis. MRT cells that have acquired resistance to the PDGFRα inhibitor pazopanib are susceptible to FGFR inhibitors. We show that PDGFRα levels are regulated by SMARCB1 expression, and assessment of clinical specimens documents the expression of both PDGFRα and FGFR1 in rhabdoid tumor patients. Our findings support a therapeutic approach in cancers with SWI/SNF deficiencies by exploiting RTK coactivation dependencies

Incomplete posttranslational prohormone modifications in hyperactive neuroendocrine cells

Contains fulltext : 76028.pdf (publisher's version ) (Open Access)8 p

Dissection of Pol II Trigger Loop Function and Pol II Activity–Dependent Control of Start Site Selection In Vivo

Structural and biochemical studies have revealed the importance of a conserved, mobile domain of RNA Polymerase II (Pol II), the Trigger Loop (TL), in substrate selection and catalysis. The relative contributions of different residues within the TL to Pol II function and how Pol II activity defects correlate with gene expression alteration in vivo are unknown. Using Saccharomyces cerevisiae Pol II as a model, we uncover complex genetic relationships between mutated TL residues by combinatorial analysis of multiply substituted TL variants. We show that in vitro biochemical activity is highly predictive of in vivo transcription phenotypes, suggesting direct relationships between phenotypes and Pol II activity. Interestingly, while multiple TL residues function together to promote proper transcription, individual residues can be separated into distinct functional classes likely relevant to the TL mechanism. In vivo, Pol II activity defects disrupt regulation of the GTP-sensitive IMD2 gene, explaining sensitivities to GTP-production inhibitors, but contrasting with commonly cited models for this sensitivity in the literature. Our data provide support for an existing model whereby Pol II transcriptional activity provides a proxy for direct sensing of NTP levels in vivo leading to IMD2 activation. Finally, we connect Pol II activity to transcription start site selection in vivo, implicating the Pol II active site and transcription itself as a driver for start site scanning, contravening current models for this process

Gendered performances in sport: an embodied approach

Despite significant advances in recent years, gender inequalities remain apparent within the context of sport participation and engagement. One of the problems, however, when addressing gender issues in sport is the continued assumption by many sport practitioners that the experiences of women and men will always be different because of perceived physiological characteristics. Adopting a focus based solely upon perceived gendered differences often overlooks the importance of recognising individual experience and the prevailing social influences that impact upon participation, such as age, class, race and ability. An embodied approach, as well as seeking to move beyond mind/body dualisms, incorporates the physiological with the social and psychological. Therefore, it is suggested that while considerations of gender remain important, they need to be interpreted alongside other interconnecting and influential (at varying times and occasions) social and physical factors. It is argued that taking the body as a starting point opens up more possibilities to manoeuvre through the mine field that is gender and sport participation. The appeal of an embodied approach to the study of gender and sport is in its accommodation of a wider multi-disciplinary lens. Particularly, by acknowledging the subjective, corporeal, lived experiences of sport engagement, an embodied approach offers a more flexible starting point to negotiate the theoretical and methodological challenges created by restrictive discourses of difference

Anhydrobiosis-Associated Nuclear DNA Damage and Repair in the Sleeping Chironomid: Linkage with Radioresistance

Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET) ions (4He). In contrast, low-LET radiation (gamma-rays) of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3–4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to damage caused by desiccation and ionizing radiation

Organization of sensory feature selectivity in the whisker system

Our sensory receptors are faced with an onslaught of different environmental inputs. Each sensory event or encounter with an object involves a distinct combination of physical energy sources impinging upon receptors. In the rodent whisker system, each primary afferent neuron located in the trigeminal ganglion innervates and responds to a single whisker and encodes a distinct set of physical stimulus properties – features – corresponding to changes in whisker angle and shape and the consequent forces acting on the whisker follicle. Here we review the nature of the features encoded by successive stages of processing along the whisker pathway. At each stage different neurons respond to distinct features, such that the population as a whole represents diverse properties. Different neuronal types also have distinct feature selectivity. Thus, neurons at the same stage of processing and responding to the same whisker nevertheless play different roles in representing objects contacted by the whisker. This diversity, combined with the precise timing and high reliability of responses, enables populations at each stage to represent a wide range of stimuli. Cortical neurons respond to more complex stimulus properties – such as correlated motion across whiskers – than those at early subcortical stages. Temporal integration along the pathway is comparatively weak: neurons up to barrel cortex are sensitive mainly to fast (tens of milliseconds) fluctuations in whisker motion. The topographic organization of whisker sensitivity is paralleled by systematic organization of neuronal selectivity to certain other physical features, but selectivity to touch and to dynamic stimulus properties is distributed in “salt-and-pepper” fashion

Extracorporeal Membrane Oxygenation for Acute Pediatric Respiratory Failure

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The use of extracorporeal membrane oxygenation (ECMO) to support children with acute respiratory failure has steadily increased over the past several decades, with major advancements having been made in the care of these children. There are, however, many controversies regarding indications for initiating ECMO in this setting and the appropriate management strategies thereafter. Broad indications for ECMO include hypoxia, hypercarbia, and severe air leak syndrome, with hypoxia being the most common. There are many disease-specific considerations when evaluating children for ECMO, but there are currently very few, if any, absolute contraindications. Venovenous rather than veno-arterial ECMO cannulation is the preferred configuration for ECMO support of acute respiratory failure due to its superior side-effect profile. The approach to lung management on ECMO is variable and should be individualized to the patient, with the main goal of reducing the risk of VILI. ECMO is a relatively rare intervention, and there are likely a minimum number of cases per year at a given center to maintain competency. Patients who have prolonged ECMO runs (i.e., greater than 21 days) are less likely to survive, though no absolute duration of ECMO that would mandate withdrawal of ECMO support can be currently recommended