Increasing daily feeding occasions in restricted feeding strategies does not improve performance or well being of fattening pigs

Background  

The natural feeding behaviour of the pig is searching for feed by rooting activities throughout the day; self-feeding pigs randomly space their eating and drinking periods throughout the day consuming ten to twelve meals per day. Pigs in conventional fattening pig production are normally fed 2–3 times daily with the feed consumed within 15 minutes. The aim of this study was to determine if more frequent feedings could improve the performance of conventionally kept fattening pigs.     

Estimation of a monotone percentile residual life function under random censorship

In this paper, we introduce a new estimator of a percentile residual life function with censored data under a monotonicity constraint. Specifically, it is assumed that the percentile residual life is a decreasing function. This assumption is useful when estimating the percentile residual life of units, which degenerate with age. We establish a law of the iterated logarithm for the proposed estimator, and its ‐equivalence to the unrestricted estimator. The asymptotic normal distribution of the estimator and its strong approximation to a Gaussian process are also established. We investigate the finite sample performance of the monotone estimator in an extensive simulation study. Finally, data from a clinical trial in primary biliary cirrhosis of the liver are analyzed with the proposed methods. One of the conclusions of our work is that the restricted estimator may be much more efficient than the unrestricted one.     

Protein 4.1R self-association: identification of the binding domain

Erythroid protein 4.1 (4.1R) stabilizes the spectrin-actin network and anchors it to the plasma membrane. To contribute to the characterization of non-erythroid protein 4.1R, we used sedimentation, pull-down and co-immunoprecipitation assays to investigate the ability of protein 4.1R to establish inter-/intra-molecular associations. We demonstrated that the small 4.1R isoforms of 60 kDa (4.1R60), but not the larger isoforms of 80 and 135 kDa (4.1R80 and 4.1R135), were self-associated, and that a domain contained in all 4.1R isoforms, the core region, was responsible for 4.1R self-association. Results from denaturing-renaturing experiments, in which an initially non-self-associated 4.1R80 isoform became self-associated, suggested that an initially hidden core region was subsequently exposed. This hypothesis was supported by results from pull-down assays, which showed that the core region interacted with the N-terminal end of the FERM (4.1, ezrin, radixin, moesin) domain that is present in 4.1R80 and 4.1R135 isoforms but absent from 4.1R60 isoforms. Consistently, 4.1R80 isoforms bound neither to each other nor to 4.1R60 isoforms. We propose that 4.1R60 isoforms are constitutively self-associated, whereas 4.1R80 and 4.1R135 self-association is prevented by intramolecular interactions.     

Isolation and characterization of heparan sulfate from various murine tissues

Heparan sulfate (HS), is a proteoglycan (PG) found both in the extracellular matrix and on cell surface. It may represent one of the most biologically important glycoconjugates, playing an essential role in a variety of different events at molecular level. The publication of the mouse genome, and the intensive investigations aimed at understanding the proteome it encodes, has motivated us to initiate studies in mouse glycomics focused on HS. The current study is aimed at determining the quantitative and qualitative organ distribution of HS in mice. HS from brain, eyes, heart, lung, liver, kidney, spleen, intestine and skin was purified from 6–8 week old male and female mice. The recovered yield of HS from these organs is compared with the recovered whole body yield of HS. Structural characterization of the resulting HS relied on disaccharide analysis and ¹H-NMR spectroscopy. Different organs revealed a characteristic HS structure. These data begin to provide a structural understanding of the role of HS in cell-cell interactions, cell signaling and sub-cellular protein trafficking as well as a fundamental understanding of certain aspects of protein-carbohydrate interactions.     

Natalizumab Treatment Reduces Fatigue in Multiple Sclerosis. Results from the TYNERGY Trial; A Study in the Real Life Setting

Fatigue is a significant symptom in multiple sclerosis (MS) patients. First-generation disease modifying therapies (DMTs) are at best moderately effective to improve fatigue. Observations from small cohorts have indicated that natalizumab, an antibody targeting VLA-4, may reduce MS-related fatigue. The TYNERGY study aimed to further evaluate the effects of natalizumab treatment on MS-related fatigue. In this one-armed clinical trial including 195 MS patients, natalizumab was prescribed in a real-life setting, and a validated questionnaire, the Fatigue Scale for Motor and Cognitive functions (FSMC), was used both before and after 12 months of treatment to evaluate a possible change in the fatigue experienced by the patients. In the treated cohort all measured variables, that is, fatigue score, quality of life, sleepiness, depression, cognition, and disability progression were improved from baseline (all p values<0.0001). Walking speed as measured by the six-minute walk-test also increased at month 12 (p = 0.0016). All patients were aware of the nature of the treatment agent, and of the study outcomes.

Conclusion

Natalizumab, as used in a real-life setting, might improve MS-related fatigue based on the results from this one-armed un-controlled stud. Also other parameters related to patients'' quality of life seemed to improve with natalizumab treatment.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00884481","term_id":"NCT00884481"}}NCT00884481     

Inhibition of calpain blocks pancreatic beta-cell spreading and insulin secretion

In addition to promoting insulin secretion, an increase in cytosolic Ca(2+) triggered by glucose has been shown to be crucial for spreading of beta-cells attached on extracellular matrix (804G matrix). Calpains are Ca(2+)-dependent cysteine proteases involved in an extended spectrum of cellular responses, including cytoskeletal rearrangements and vesicular trafficking. The present work aimed to assess whether calpain is also implicated in the process of Ca(2+)-induced insulin secretion and spreading of rat pancreatic beta-cells. The results indicate calpain dependency of beta-cell spreading on 804G matrix. Indeed, treatment with three distinct calpain inhibitors (N-Ac-Leu-Leu-norleucinal, calpeptin, and ethyl(+)-(2S,3S)-3-[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butyl-carbamoyl]-2-ox-iranecarboxylate) inhibited cell spreading induced by glucose and KCl, whereas cell attachment was not significantly modified. Calpain inhibitors also suppressed glucose- and KCl-stimulated insulin secretion without affecting insulin synthesis. Washing the inhibitor out of the cell culture restored spreading on 804G matrix and insulin secretory response after 24 h. In addition, incubation with calpeptin did not affect insulin secretory response to mastoparan that acts on exocytosis downstream of intracellular calcium [Ca(2+)]i. Finally, calpeptin was shown to affect the [Ca(2+)]i response to glucose but not to KCl. In summary, the results show that inhibition of calpain blocks spreading and insulin secretion of primary pancreatic beta-cells. It is therefore suggested that calpain could be a mediator of Ca(2+)-induced-insulin secretion and beta-cell spreading.     

Importance of the cultivation history for the response of Escherichia coli to oscillations in scale-down experiments

Bioprocess and Biosystems Engineering - Large-scale bioreactors are inhomogeneous systems, in which the fluid phase expresses concentration gradients. They depend on the mass transfer and fluid...     

Population dynamics of a natural red deer population over 200 years detected via substantial changes of genetic variation

Most large mammals have constantly been exposed to anthropogenic influence over decades or even centuries. Because of their long generation times and lack of sampling material, inferences of past population genetic dynamics, including anthropogenic impacts, have only relied on the analysis of the structure of extant populations. Here, we investigate for the first time the change in the genetic constitution of a natural red deer population over two centuries, using up to 200‐year‐old antlers (30 generations) stored in trophy collections. To the best of our knowledge, this is the oldest DNA source ever used for microsatellite population genetic analyses. We demonstrate that government policy and hunting laws may have strong impacts on populations that can lead to unexpectedly rapid changes in the genetic constitution of a large mammal population. A high ancestral individual polymorphism seen in an outbreeding population (1813–1861) was strongly reduced in descendants (1923–1940) during the mid‐19th and early 20th century by genetic bottlenecks. Today (2011), individual polymorphism and variance among individuals is increasing in a constant‐sized (managed) population. Differentiation was high among periods (F_ST > ***); consequently, assignment tests assigned individuals to their own period with >85% probability. In contrast to the high variance observed at nuclear microsatellite loci, mtDNA (D‐loop) was monomorphic through time, suggesting that male immigration dominates the genetic evolution in this population.     

The energetic costs of case construction in the caddisfly Limnephilus rhombicus: direct impacts on larvae and delayed impacts on adults

Caddisflies, whose aquatic larvae build a portable case with silk, are a suitable model organism to test the impacts of resource allocation trade-off during development and examine the evolution of life-history strategies. In the caddisfly Limnephilus rhombicus, adult feeding is minimal. Therefore, the whole resources are acquired during the larval phase and must be allocated to case construction, growth and reproduction. In this study, the larval energetic reserves of L. rhombicus were manipulated by forcing larvae to rebuild their cases in the final larval stage. This allowed us to measure the physiological cost of construction. First, we recorded oxygen consumption during case reconstruction. Second, we measured the sugar, protein and lipid contents of larvae forced to rebuild their case and of larvae required only to re-enter on their case. Larvae had their sugar, protein and lipid content measured after the rebuilding event and 72 h later. The same analyses were carried out with adults immediately after emergence. We found that larvae forced to rebuild a case consumed 1.5 times more oxygen than control larvae. This energy expenditure generated a cost that was estimated to be a loss of larval protein of approximately 35%. Insects were unable to compensate for this loss of proteins during the end of the larval stage, and their metamorphosis to adults was also impacted. Therefore, we suggest that loss of larval protein is linked to silk production and may alter fitness.