Physiological Impact of Ergot Alkaloid Consumption in Ruminant Livestock

Ergot alkaloids in feeds and forages are a worldwide concern. Consumption of ergot alkaloids by ruminant livestock can range from extreme cases that threaten the life of the animal to more frequent and chronic outcomes where livestock productivity is decreased. Consumption of ergot alkaloids alters ruminant physiology such that it outwardly manifests in lower animal intake and gain, decreased reproductive efficiency, and a compromised circulatory system. This talk will cover current research that is improving our understanding of how ergot alkaloids alter cell and tissue physiology that results in the compromised growth and reproduction observed at the whole animal level

COMPARISON OF SUCROSE CATABOLISM IN ROOTS OF THREE BETA VULGARIS L. GENOTYPES WITH DIFFERENT YIELD AND SUCROSE ACCUMULATING CAPACITIES

ABSTRACT Sucrose catabolism is a major determinant of sink strength in nearly all plants and affects sucrose partitioning to growing sinks as well as sink size and carbohydrate content. Three enzyme families are responsible for nearly all sucrose catabolism in sugarbeet roots: acid invertase, alkaline invertase and sucrose synthase. Previous work suggested that sucrose synthase may have a role in sink strength and root size in sugarbeet. To examine this observation more thoroughly, sucrose catabolism was compared in three Beta vulgaris genotypes with contrasting capacities for root yield and sucrose accumulation. Soluble acid invertase, cell wall acid invertase, alkaline invertase and sucrose synthase activities were compared at five stages of root development in a fodder beet hybrid (high yield, low sucrose content), a commercial sugarbeet hybrid (typical yield and sucrose content) and the sugarbeet breeding line, L 19 (low yield, high sucrose content). Sucrose, glucose and fructose concentrations and mass accumulation were also determined. Generally, sucrolytic activity was greatest in the high yielding fodder beet and lowest in the low yielding L 19 breeding line at any stage of development. Sucrose synthase activity was the predominant sucrolytic activity at all stages of development examined, and accounted for 90% or more of the total sucrolytic activity in fodder beet and sugarbeet hybrid roots by six weeks after planting and in L 19 eight weeks after planting. Total sucrose synthase activity was positively correlated with nonextractable dry matter accumulation. Differences in sucrose concentration between genotypes were observed, although sucrose concentration or accumulation was not highly correlated with any of the major sucrolytic enzymes examined

The historical vanishing of the Blazhko effect of RR Lyr from GEOS and Kepler surveys

RR Lyr is one of the most studied variable stars. Its light curve has been regularly monitored since the discovery of the periodic variability in 1899. Analysis of all observed maxima allows us to identify two primary pulsation states defined as pulsation over a long (P0 longer than 0.56684 d) and a short (P0 shorter than 0.56682 d) primary pulsation period. These states alternate with intervals of 13-16 yr, and are well defined after 1943. The 40.8 d periodical modulations of the amplitude and the period (i.e. Blazhko effect) were noticed in 1916. We provide homogeneous determinations of the Blazhko period in the different primary pulsation states. The Blazhko period does not follow the variations of P0 and suddenly diminished from 40.8 d to around 39.0 d in 1975. The monitoring of these periodicities deserved and deserves a continuous and intensive observational effort. For this purpose we have built dedicated, transportable and autonomous small instruments, Very Tiny Telescopes (VTTs), to observe the times of maximum brightness of RR Lyr. As immediate results the VTTs recorded the last change of P0 state in mid-2009 and extended the time coverage of the Kepler observations, thus recording a maximum O-C amplitude of the Blazhko effect at the end of 2008, followed by the historically smallest O-C amplitude in late 2013. This decrease is still ongoing and VTT instruments are ready to monitor the expected increase in the next few years.Comment: 10 pages, 6 figures. Accepted for publication in MNRAS. Contents of appendix B may be requested to first autho

Re: A review of continuous vs intermittent androgen deprivation therapy: Redefining the gold standard in the treatment of advanced prostate cancer. Myths, facts and new data on a ?perpetual dispute?

Objectives: To review the literature and present new data of continuous androgen deprivation therapy (ADT) vs intermittent androgen deprivation (IAD) as therapies for prostate cancer in terms of survival and quality of life and clarify practical issues in the use of IAD. Materials and Methods: We conducted a systematic search on Medline and Embase databases using “prostatic neoplasm” and “intermittent androgen deprivation” as search terms. We reviewed meta-analyses, randomised controlled trials, reviews, clinical trials and practise guidelines written in English from 2000 and onwards until 01/04/2013. Ten randomized controlled trials were identified. Seven of them published extensive data and results randomizing 4675 patients to IAD versus CAD. Data from the other three randomized trials were limited. Results: Over the last years studies confirmed that IAD is an effective alternative approach to hormonal deprivation providing simultaneously several potential benefits in terms of quality of life and cost effectiveness. Thus, in patients with non metastatic, advanced prostate cancer IAD could be used as standard treatment, while in metastatic prostate cancer IAD role still remains ambiguous. Conclusions: Nowadays, revaluation of the gold standard of ADT in advanced prostate cancer appears essential. Recent data established that IAD should no longer be considered as investigational, since its effectiveness has been proven, especially in patients suffering from non-metastatic advanced prostate cancer

Maximizing Science Return from Future Rodent Experiments on the International Space Station (ISS): Tissue Preservation

To better understand how mammals adapt to long duration habitation in space, a system for performing rodent experiments on the ISS is under development; Rodent Research-1 is the first flight and will include validation of both on-orbit animal support and tissue preservation. To evaluate plans for on-orbit sample dissection and preservation, we simulated conditions for euthanasia, tissue dissection, and prolonged sample storage on the ISS, and we also developed methods for post-flight dissection and recovery of high quality RNA from multiple tissues following prolonged storage in situ for future science. Mouse livers and spleens were harvested under conditions that simulated nominal, on-orbit euthanasia and dissection operations including storage at -80 C for 4 months. The RNA recovered was of high quality (RNA Integrity Number, RIN(is) greater than 8) and quantity, and the liver enzyme contents and activities (catalase, glutathione reductase, GAPDH) were similar to positive controls, which were collected under standard laboratory conditions. We also assessed the impact of possible delayed on-orbit dissection scenarios (off-nominal) by dissecting and preserving the spleen (RNAlater) and liver (fast-freezing) at various time points post-euthanasia (from 5 min up to 105 min). The RNA recovered was of high quality (spleen, RIN (is) greater than 8; liver, RIN (is) greater than 6) and liver enzyme activities were similar to positive controls at all time points, although an apparent decline in select enzyme activities was evident at the latest time (105 min). Additionally, various tissues were harvested from either intact or partially dissected, frozen carcasses after storage for approximately 2 months; most of the tissues (brain, heart, kidney, eye, adrenal glands and muscle) were of acceptable RNA quality for science return, whereas some tissues (small intestine, bone marrow and bones) were not. These data demonstrate: 1) The protocols developed for future flight experiments will support science return despite delayed preservation post-euthanasia or prolonged storage, and 2) Many additional tissues for gene expression analysis can be obtained by dissection following prolonged storage of the tissue in situ at -80 C. These findings have relevance both to high value, ground-based experiments when sample collection capability is severely constrained, and to all future spaceflight experiments that entail on-orbit sample recovery by the ISS crew

Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events

Abstract Background In a phase III trial in patients with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid in reducing skeletal-related events (SREs; radiation to bone, pathologic fracture, surgery to bone, or spinal cord compression). This study reassessed the efficacy of denosumab using symptomatic skeletal events (SSEs) as a prespecified exploratory end point. Patients and methods Patients with CRPC, no previous bisphosphonate exposure, and radiographic evidence of bone metastasis were randomized to subcutaneous denosumab 120 mg plus i.v. placebo every 4 weeks (Q4W), or i.v. zoledronic acid 4 mg plus subcutaneous placebo Q4W during the blinded treatment phase. SSEs were defined as radiation to bone, symptomatic pathologic fracture, surgery to bone, or symptomatic spinal cord compression. The relationship between SSE or SRE and time to moderate/severe pain was assessed using the Brief Pain Inventory Short Form. Results Treatment with denosumab significantly reduced the risk of developing first SSE [HR, 0.78; 95% confidence interval (CI) 0.66–0.93; P = 0.005] and first and subsequent SSEs (rate ratio, 0.78; 95% CI 0.65–0.92; P = 0.004) compared with zoledronic acid. The treatment differences in the number of patients with SSEs or SREs were similar (n = 48 and n = 45, respectively). Among patients with no/mild pain at baseline, both SSEs and SREs were associated with moderate/severe pain development (P < 0.0001). Fewer patients had skeletal complications, particularly fractures, when defined as SSE versus SRE. Conclusion In patients with CRPC and bone metastases, denosumab reduced the risk of skeletal complications versus zoledronic acid regardless of whether the end point was defined as SSE or SRE

A new method for analyzing ground-state landscapes: ballistic search

A ``ballistic-search'' algorithm is presented which allows the identification of clusters (or funnels) of ground states in Ising spin glasses even for moderate system sizes. The clusters are defined to be sets of states, which are connected in state-space by chains of zero-energy flips of spins. The technique can also be used to estimate the sizes of such clusters. The performance of the method is tested with respect to different system sizes and choices of parameters. As an application the ground-state funnel structure of two-dimensional +or- J spin glasses of systems up to size L=20 is analyzed by calculating a huge number of ground states per realization. A T=0 entropy per spin of s_0=0.086(4)k_B is obtained.Comment: 10 pages, 11 figures, 35 references, revte

Theodicy and End-of-Life Care

Acknowledgments The section on Islamic perspective is contributed by information provided by Imranali Panjwani, Tutor in Theology & Religious Studies, King's College London.Peer reviewedPublisher PD