Lessons from the breeding program of rohu

For the first time in India, selective breeding work has been initiated at the Central Institute of Freshwater Aquaculture, Bhubaneswar, India in collaboration with the Institute of Aquaculture Research (AKVAFORSK), Norway. Rohu has been chosen as the model species because it enjoys the highest consumer preference among Indian major carps (IMC) although its performance was observed to be slower than other IMC. As this was the first ever selection work on any Indian major carp, many procedures and techniques for successful implementation of the programs were standardized (i.e. production of full-sib groups, establishment of model hatchery for selective breeding of carps, rearing of full-sib groups in partitioned nursery ponds, individual tagging with the Passive Integrated Transponder (PIT) tag, communal rearing, sampling, data analysis, field testing and dissemination of improved rohu). After four generations of selection, an average of 17 per cent higher growth per generation was observed in improved rohu.Biotechnology, Genetics, Food fish, Genetic drift, Genetic diversity, Aquatic animals, DNA, Selective breeding, Breeding success, Research programmes, India, Labeo rohita

Importance of highly selective LC–MS/MS analysis for the accurate quantification of tamoxifen and its metabolites: focus on endoxifen and 4-hydroxytamoxifen

The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen. This effect is assumed to be concentration-dependent and therefore quantitative analysis of tamoxifen and metabolites for clinical studies and therapeutic drug monitoring is increasing. We investigated the large discrepancies in reported mean endoxifen and 4-hydroxytamoxifen concentrations. Two published LC–MS/MS methods are used to analyse a set of 75 serum samples from patients treated with tamoxifen. The method from Teunissen et al. (J Chrom B, 879:1677–1685, 2011) separates endoxifen and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A, 1082:6–14, 2005) however lacks selectivity, resulting in a factor 2–3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We emphasize the use of highly selective LC–MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples

The Active Tamoxifen Metabolite Endoxifen (4OHNDtam) Strongly Down-Regulates Cytokeratin 6 (CK6) in MCF-7 Breast Cancer Cells

Introduction: Tamoxifen is an anti-estrogen drug used in treatment of Estrogen Receptor (ER) positive breast cancer. Effects and side effects of tamoxifen is the sumof tamoxifen and all itsmetabolites. 4-Hydroxytamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen) both have ER affinity exceeding that of the parent drug tamoxifen. 4OHNDtam is considered the main active metabolite of tamoxifen. Ndesmethyltamoxifen (NDtam) is the major tamoxifen metabolite. It has low affinity to the ER and is not believed to influence tumor growth. However, NDtam might mediate adverse effects of tamoxifen treatment. In this study we investigated the gene regulatory effects of the three metabolites of tamoxifen in MCF-7 breast cancer cells. Material and Methods: Using concentrations that mimic the clinical situation we examined effects of 4OHtam, 4OHNDtam and NDtam on global gene expression in 17β-estradiol (E2) treated MCF-7 cells. Transcriptomic responses were assessed by correspondence analysis, differential expression, gene ontology analysis and quantitative real time PCR (Q-rt-PCR). E2 deprivation and knockdown of Steroid Receptor Coactivator-3 (SRC-3)/Amplified in Breast Cancer 1 (AIB1) mRNA in MCF-7 cells were performed to further characterize specific effects on gene expression. Results: 4OHNDtam and 4OHtamcausedmajor changes in gene expression compared to treatment with E2 alone, with a stronger effect of 4OHNDtam. NDtam had nearly no effect on the global gene expression profile. Treatment ofMCF-7 cells with 4OHNDtam led to a strong down-regulation of the CytoKeratin 6 isoforms (KRT6A, KRT6B and KRT6C). The CytoKeratin 6 mRNAs were also down-regulated inMCF-7 cells after E2 deprivation and after SRC-3/ AIB1 knockdown. Conclusion: Using concentrations that mimic the clinical situation we report global gene expression changes that were most pronounced with 4OHNDtam and minimal with NDtam. Genes encoding CytoKeratin 6, were highly down-regulated by 4OHNDtam, as well as after E2 deprivation and knockdown of SRC-3/AIB1, indicating an estrogen receptor-dependent regulation.publishedVersio

Дослідження «великого терору» у науково-документальній серії книг «Реабілітовані історією»

У статті автор аналізує результати дослідження «великого терору» 1937–1938 рр. у контексті реалізації Державної програми науково-документальної серії книг «Реабілітовані історією».В статье автор анализирует результаты исследования «большого террора» 1937–1938 гг. в контексте реализации Государственной программы научно-документальной серии книг «Реабилитированные историей».The author analyzes the results of a study of the «great terror» 1937–1938 in the context of implementing the State Program for Research, a documentary series of books «Rehabilitated history»

Relationship between Ketones, Ghrelin, and, Appetite on Isocaloric Diets with Varying Carbohydrate Quality and Amount: Results from a Randomized Controlled Trial in People with Obesity (CARBFUNC)

Background - Low-carbohydrate high-fat (LCHF) diets may suppress the increase in appetite otherwise seen after diet-induced fat loss. However, studies of diets without severe energy restriction are lacking, and the effects of carbohydrate quality relative to quantity have not been directly compared. Objectives - To evaluated short- (3 mo) and long-term (12 mo) changes in fasting plasma concentrations of total ghrelin, β-hydroxybutyrate (βHB), and subjective feelings of appetite on 3 isocaloric eating patterns within a moderate caloric range (2000–2500 kcal/d) and with varying carbohydrate quality or quantity. Methods - We performed a randomized controlled trial of 193 adults with obesity, comparing eating patterns based on “acellular” carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), “cellular” carbohydrate sources (minimally processed foods with intact cellular structures), or LCHF principles. Outcomes were compared by an intention-to-treat analysis using constrained linear mixed modeling. This trial was registered at clinicaltrials.gov as NCT03401970. Results - Of the 193 adults, 118 (61%) and 57 (30%) completed 3 and 12 mo of follow-up. Throughout the intervention, intakes of protein and energy were similar with all 3 eating patterns, with comparable reductions in body weight (5%−7%) and visceral fat volume (12%−17%) after 12 mo. After 3 mo, ghrelin increased significantly with the acellular (mean: 46 pg/mL; 95% CI: 11, 81) and cellular (mean: 54 pg/mL; 95% CI: 21, 88) diets but not with the LCHF diet (mean: 11 pg/mL; 95% CI: −16, 38). Although βHB increased significantly more with the LCHF diet than with the acellular diet after 3 m (mean: 0.16 mmol/L; 95% CI: 0.09, 0.24), this did not correspond to a significant group difference in ghrelin (unless the 2 high-carbohydrate groups were combined [mean: −39.6 pg/mL; 95% CI: −76, −3.3]). No significant between-group differences were seen in feelings of hunger. Conclusions - Modestly energy-restricted isocaloric diets differing in carbohydrate cellularity and amount showed no significant differences in fasting total ghrelin or subjective hunger feelings. An increase in ketones with the LCHF diet to 0.3–0.4 mmol/L was insufficient to substantially curb increases in fasting ghrelin during fat loss

The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

A strategy for the conservation of biodiversity on mid-ocean ridges from deep-sea mining

Mineral exploitation has spread from land to shallow coastal waters and is now planned for the offshore, deep seabed. Large seafloor areas are being approved for exploration for seafloor mineral deposits, creating an urgent need for regional environmental management plans. Networks of areas where mining and mining impacts are prohibited are key elements of these plans. We adapt marine reserve design principles to the distinctive biophysical environment of mid-ocean ridges, offer a framework for design and evaluation of these networks to support conservation of benthic ecosystems on mid-ocean ridges, and introduce projected climate-induced changes in the deep sea to the evaluation of reserve design. We enumerate a suite of metrics to measure network performance against conservation targets and network design criteria promulgated by the Convention on Biological Diversity. We apply these metrics to network scenarios on the northern and equatorial Mid-Atlantic Ridge, where contractors are exploring for seafloor massive sulfide (SMS) deposits. A latitudinally distributed network of areas performs well at (i) capturing ecologically important areas and 30 to 50% of the spreading ridge areas, (ii) replicating representative areas, (iii) maintaining along-ridge population connectivity, and (iv) protecting areas potentially less affected by climate-related changes. Critically, the network design is adaptive, allowing for refinement based on new knowledge and the location of mining sites, provided that design principles and conservation targets are maintained. This framework can be applied along the global mid-ocean ridge system as a precautionary measure to protect biodiversity and ecosystem function from impacts of SMS mining

Worm control practice against gastro-intestinal parasites in Norwegian sheep and goat flocks

<p>Abstract</p> <p>Background</p> <p>Anthelmintic treatment is the most common way of controlling nematode infections in ruminants. However, several countries have reported anthelmintic resistance (AR), representing a limitation for sustainable small ruminant production. The knowledge regarding worm control management represents a baseline to develop a guideline for preventing AR. The aim of the present study was therefore to improve our knowledge about the worm control practices in small ruminant flocks in Norway.</p> <p>Methods</p> <p>A questionnaire survey regarding worm control practices was performed in small ruminant flocks in Norway. Flocks were selected from the three main areas of small ruminant farming, i.e. the coastal, inland and northern areas. A total of 825 questionnaires, comprising 587 sheep flocks (return rate of 51.3%) and 238 goat flocks (52.6%) were included.</p> <p>Results</p> <p>The results indicated that visual appraisal of individual weight was the most common means of estimating the anthelmintic dose used in sheep (78.6%) and goat (85.1%) flocks. The mean yearly drenching rate in lambs and ewes were 2.5 ± 1.7 and 1.9 ± 1.1, respectively, whereas it was 1.0 (once a year) in goats. However, these figures were higher in sheep in the coastal area with a rate of 3.4 and 2.2 in lambs and ewes, respectively. Benzimidazoles were the predominant anthelmintic class used in sheep flocks (64.9% in 2007), whereas benzimidazoles and macrocyclic lactones were both equally used in dairy goat flocks. In the period of 2005-2007, 46.3% of the sheep flocks never changed the anthelmintic class. The dose and move strategy was practiced in 33.2% of the sheep flocks.</p> <p>Conclusions</p> <p>The present study showed that inaccurate weight calculation gives a risk of under-dosing in over 90% of the sheep and goat flocks in Norway. Taken together with a high treatment frequency in lambs, a lack of anthelmintic class rotation and the common use of a dose-and-move strategy, a real danger for development of anthelmintic resistance (AR) seems to exist in Norwegian sheep and goat flocks. This risk seems particularly high in coastal areas where high treatment frequencies in lambs were recorded.</p

Prevalence of anthelmintic resistance in gastrointestinal nematodes of sheep and goats in Norway

In the period of 2008–2009, the efficacies of the benzimidazole (BZ) albendazole and the macrocyclic lactone (ML) ivermectin against gastrointestinal nematodes (GIN) of small ruminants were evaluated by means of the fecal egg count reduction (FECR) test and by post-treatment identification of surviving third stage (L3) larvae after coproculture. Sheep (n = 28) and goat (n = 28) flocks from three areas of Norway were randomly selected to assess the prevalence of anthelmintic resistance (AR), whereas only lambs from non-randomly selected sheep flocks (n = 32) with a farm management that could select for AR were investigated the second year. Only flocks with a mean excretion of nematode eggs per gram feces (EPG) ≥150 at time of treatment were included in the survey. In total, 48 (80%) and 13 (46.4%) of the selected sheep and goat flocks, respectively, fulfilled the inclusion criteria. The proportions of flocks classified as resistant (i.e., FECR <95% and with a lower 95% confidence interval of <90%) for the BZ drug albendazole were 10.5% and 31.0% in the randomly and non-randomly selected sheep flocks, respectively. When restricting the area to Rogaland County, eight flocks out of ten (80%) non-randomly selected sheep flocks showed BZ resistance. The efficacy of ML was 100% in all surveyed sheep and goat flocks. In post-treatment coprocultures from the non-randomly selected flocks, the main nematode genera were Teladorsagia/Trichostrongylus in five flocks, Haemonchus in two flocks, and a mixture of these genera in the remaining two flocks. In the goat flocks, the pre-treatment infection levels of GIN were low compared to what was found in the sheep flocks. Still, in one flock, AR against BZ in Teladorsagia/Trichostrongylus was found. New strategies and recommendations to face the emerging AR situation in Rogaland County in order to limit the spread of resistant nematodes within and into other areas are urgently needed