Microarray analyses to identify differentially expressed genes for assessing meat quality in swine

In order to identify candidate genes and molecular mechanisms that influence meat quality and production in pigs, microarray experiments were carried out to find differences in gene expression levels between two pools of six individuals, constituting the extreme tails of the Gaussian distribution of seven adjusted phenotypes of 100 Landrace and Large White animals. The phenotypes considered in this study were: muscle compactness, marbling, colour uniformity, fat covering, colour, dorsal fat, thickness, ham fat thickness. 437 differentially expressed ESTs (Expressed Sequence Tags) were found, clustering in different pathways according to their ontology. In particular, 73 functional categories were identified and ten of them could have a role in meat quality. Among the ESTs belonging to these pathways, seven of them were selected to be validated in quantitative real-time RT-PCR

Effects of A -site ordering on the Mn local structure and polar phases of R Ba Mn 2 O 6 ( R = La , Nd, Sm, and Y)

We have investigated the temperature dependence of the Mn local structure in A-site ordered RBaMn2O6 (R = La, Nd, Sm, and Y) perovskites, in parallel with their disordered counterparts, R0.5Ba0.5MnO3, by means of x-ray emission (XES) and x-ray absorption spectroscopy (XAS) The end member LaBaMn2O6 shows a nearly regular MnO6 octahedron independent of temperature. With decreasing the R ionic radius in the ordered samples, the XAS results indicate that a local distortion develops in the MnO6 octahedron at the low-temperature charge-localized and polar phases. For NdBaMn2O6, this local distortion is tiny, indicating the absence of charge segregation at the Mn site. This is followed by a bigger local distortion anticipated for SmBaMn2O6 in its respective charge-localized and polar phase and finally, the biggest local distortion for the smallest A-site cation ordered compound, YBaMn2O6, for which it even persists above the polar charge-localization transition temperatures. The high-resolution XAS spectra confirm the presence of charge segregation between two nonequivalent Mn sites in the low-temperature polar phase of Sm and Y ordered samples. Thus, our XAS study suggests a displacive mechanism for the charge-localization and polar transitions in the Nd and Sm ordered samples while a combination of displacive and order-disorder contributions is revealed for YBaMn2O6. Besides, calorimetric measurements confirm the combination of the two mechanisms, order-disorder and displacive, for the ordered Sm and Y compounds. On the other hand, the A-site disordered R0.5Ba0.5MnO3 samples with R cations smaller than Nd present a significant static (temperature-independent) local disorder, which explains why polar charge-localization transitions are not developed in these samples. Finally, we correlate our results about the Mn local structure and character of the transitions with the macroscopic magnetic and electric behavior of both A-site ordered and disordered compounds

Prognostic factors and treatment-effect modifiers in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with Type 1 SMA do not achieve major motor milestones, and death from respiratory failure typically occurs before 2 years. Individuals with Types 2 and 3 SMA exhibit milder phenotypes and have better functional and survival outcomes. Herein, a systematic literature review was conducted to identify factors that influence the prognosis of Types 1, 2 and 3 SMA. In untreated infants with Type 1 SMA, absence of symptoms at birth, a later symptom onset and a higher survival of motor neuron 2 (SMN2) copy number are all associated with increased survival. Disease duration, age at treatment initiation and, to a lesser extent, baseline function were identified as potential treatment-modifying factors for survival, emphasizing that early treatment with disease-modifying therapies (DMT) is essential in Type 1 SMA. In patients with Types 2 and 3 SMA, factors considered prognostic of changes in motor function were SMN2 copy number, age and ambulatory status. Individuals aged 6-15 years were particularly vulnerable to developing complications (scoliosis and progressive joint contractures) which negatively influence functional outcomes and may also affect the therapeutic response in patients. Age at the time of treatment initiation emerged as a treatment-effect modifier on the outcome of DMTs. Factors identified in this review should be considered prior to designing or analyzing studies in an SMA population, conducting population matching or summarizing results from different studies on the treatments for SMA

Genetic modifiers of Duchenne muscular dystrophy and dilated cardiomyopathy

OBJECTIVE: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset. METHODS: A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up. RESULTS: Patients were followed up to an average age of 15.9 \ub1 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027). CONCLUSIONS: We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts

Towards interoperability in the european poetry community: the standardization of philological concepts

This paper stems from the Poetry Standardization and Linked Open Data project (POSTDATA). As its name reveals, one of the main aims of POSTDATA is to provide a means to publish European poetry (EP) data as Linked Open Data (LOD). Thus, developing a metadata application profile (MAP) as a common semantic model to be used by the EP community is a crucial step of this project. This MAP will enhance interoperability among the community members in particular, and among the EP community and other contexts in general (e.g. bibliographic records). This paper presents the methodology followed in the process of defining the concepts of the domain model of this MAP, as well as some issues that arise when labeling philological terms.info:eu-repo/semantics/publishedVersio

Conservation of energy and momenta in nonholonomic systems with affine constraints

We characterize the conditions for the conservation of the energy and of the components of the momentum maps of lifted actions, and of their `gauge-like' generalizations, in time-independent nonholonomic mechanical systems with affine constraints. These conditions involve geometrical and mechanical properties of the system, and are codified in the so-called reaction-annihilator distribution

Findings from the Longitudinal CINRG Becker Natural History Study

BACKGROUND: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype. OBJECTIVE: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials. METHODS: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes. RESULTS: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter. CONCLUSIONS: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset

Long-term follow-up of patients with type 2 and non-ambulant type 3 spinal muscular atrophy (SMA) treated with olesoxime in the OLEOS trial

In a previous Phase 2 study, olesoxime had a favorable safety profile. Although the primary endpoint was not met, analyses suggested that olesoxime might help in the maintenance of motor function in patients with Types 2/3 SMA. This open-label extension study (OLEOS) further characterizes the safety, tolerability and efficacy of olesoxime over longer therapy durations. In OLEOS, no new safety risks were identified. Compared to matched natural history data, patients treated with olesoxime demonstrated small, non-significant changes in motor function over 52 weeks. Motor function scores were stable for 52 weeks but declined over the remainder of the study. The greatest decline in motor function was seen in patients ≤15 years old, and those with Type 2 SMA had faster motor function decline versus those with Type 3 SMA. Previous treatment with olesoxime in the Phase 2 study was not protective of motor function in OLEOS. Respiratory outcomes were stable in patients with Type 3 SMA >15 years old but declined in patients with Type 2 SMA and in patients with Type 3 SMA ≤15 years old. Overall, with no stabilization of functional measures observed over 130 weeks, OLEOS did not support significant benefit of olesoxime in patients with SMA

Risdiplam in Type 1 Spinal Muscular Atrophy

BACKGROUND: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. METHODS: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. RESULTS: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. CONCLUSIONS: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.)