The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3

Proteins related to the ubiquitin-proteasome system play an important role during the differentiation and ciliogenesis of photoreceptor cells. Mutations in several genes involved in ubiquitination and proteostasis have been identified as causative of inherited retinal dystrophies (IRDs) and ciliopathies. USP48 is a deubiquitinating enzyme whose role in the retina is still unexplored although previous studies indicate its relevance for neurosensory organs. In this work, we describe that a pool of endogenous USP48 localises to the basal body in retinal cells and provide data that supports the function of USP48 in the photoreceptor cilium. We also demonstrate that USP48 interacts with the IRD-associated proteins ARL3 and UNC119a, and stabilise their protein levels using different mechanisms. Our results suggest that USP48 may act in the regulation/stabilisation of key ciliary proteins for photoreceptor function, in the modulation of intracellular protein transport, and in ciliary trafficking to the photoreceptor outer segment.     

A Novel Homozygous Variant in DYSF Gene Is Associated with Autosomal Recessive Limb Girdle Muscular Dystrophy R2/2B

Mutations in the DYSF gene, encoding dysferlin, are responsible for Limb Girdle Muscular Dystrophy type R2/2B (LGMDR2/2B), Miyoshi myopathy (MM), and Distal Myopathy with Anterior Tibialis onset (MDAT). The size of the gene and the reported inter and intra familial phenotypic variability make early diagnosis difficult. Genetic analysis was conducted using Next Gene Sequencing (NGS), with a panel of 40 Muscular Dystrophies associated genes we designed. In the present study, we report a new missense variant c.5033G>A, p.Cys1678Tyr ({"type":"entrez-nucleotide","attrs":{"text":"NM_003494","term_id":"1675063869"}}NM_003494) in the exon 45 of DYSF gene related to Limb Girdle Muscular Dystrophy type R2/2B in a 57-year-old patient affected with LGMD from a consanguineous family of south Italy. Both healthy parents carried this variant in heterozygosity. Genetic analysis extended to two moderately affected sisters of the proband, showed the presence of the variant c.5033G>A in both in homozygosity. These data indicate a probable pathological role of the variant c.5033G>A never reported before in the onset of LGMDR2/2B, pointing at the NGS as powerful tool for identifying LGMD subtypes. Moreover, the collection and the networking of genetic data will increase power of genetic-molecular investigation, the management of at-risk individuals, the development of new therapeutic targets and a personalized medicine.     

Exposure to polycyclic aromatic hydrocarbons through consumption of edible marine species in Catalonia, Spain

The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs; naphthalene, acenaphtylene, acenaphtene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, indeno[1,2,3-c,d]pyrene, dibenzo[a,h]anthracene, and benzo[g,h,i]perylene) were determined by gas chromatography-mass spectrometry in samples of 14 edible marine species (sardine, tuna, anchovy, mackerel, swordfish, salmon, hake, red mullet, sole, cuttlefish, squid, clam, mussel, and shrimp) collected in March and April 2005. These species are widely consumed by the population of Catalonia, Spain. PAH intake was also estimated for eight age and sex groups of this population. Mussel, clam, and shrimp had the highest PAH concentrations (22.4, 21.5, and 15.9 ng/g of fresh weight, respectively). In contrast, sole (2.5 ng/g of fresh weight) and cuttlefish and squid (both 3.0 ng/g of fresh weight) had the lowest mean concentrations. The highest PAH intake was found in women and girls (5.3 and 5.2 ng/kg/day, respectively), but female adolescents and female seniors had the lowest PAH intakes (3.3 ng/kg/day in both groups). The intake of benzo[a]pyrene and six other PAHs that are probably human carcinogens through consumption of these marine species would be associated with 0.27/10(6) increase in the risk of development of cancer over a 70-year life span.     

Views on contentious practices in dairy farming: The case of early cow-calf separation

The public has become increasingly interested in the welfare of food animals, but the food animal industries possess few mechanisms for public engagement. Here we present results from a web-based forum designed to allow stakeholders to share views on controversial issues in dairying. In response to the question “Should dairy calves be separated from the cow within the first few hours after birth?” participants were able to indicate “yes,” “no,” or “neutral” and either write a reason in support of their view or select reasons provided by other participants. Four independent groups of participants were recruited (a total of 163 people); 31% said they had no involvement in the dairy industry; the remaining 69% (with some involvement in the industry) were students or teachers (33%), animal advocates (13%), producers (11%), veterinarians (9%) and other dairy industry professionals (3%). Overall, little consensus existed among participants across groups; 44% chose “yes,” 48% “no,” and 9% “neutral.” Responses varied with demographics, with opposition to early separation higher among females, animal advocates, and those with no involvement with the dairy industry. A fifth group was recruited at a dairy industry conference (an additional 28 participants); 46% chose “yes,” 32% “no,” and 21% “neutral.” Across all 5 groups, opponents and supporters often referenced similar issues in the reasons they provided. Opponents of early separation contended that it is emotionally stressful for the calf and cow, it compromises calf and cow health, it is unnatural, and the industry can and should accommodate cow-calf pairs. In contrast, supporters of early separation reasoned that emotional distress is minimized by separating before bonds develop, that it promotes calf and cow health, and that the industry is limited in its ability to accommodate cow-calf pairs. These results illustrate the potential of web-based forums to identify areas of agreement and conflict among stakeholders, providing a basis for the development of practices that address shared concerns.     

Strengthening Brady’s Paraconsistent 4-Valued Logic BN4 with Truth-Functional Modal Operators

?ukasiewicz presented two different analyses of modal notions by means of many-valued logics: (1) the linearly ordered systems ?3,..., Open image in new window ,..., \(\hbox {L}_{\omega }\); (2) the 4-valued logic ? he defined in the last years of his career. Unfortunately, all these systems contain “?ukasiewicz type (modal) paradoxes”. On the other hand, Brady’s 4-valued logic BN4 is the basic 4-valued bilattice logic. The aim of this paper is to show that BN4 can be strengthened with modal operators following ?ukasiewicz’s strategy for defining truth-functional modal logics. The systems we define lack “?ukasiewicz type paradoxes”. Following Brady, we endow them with Belnap–Dunn type bivalent semantics.     

Quality and antioxidant properties of a reduced-sugar pomegranate juice jelly with an aqueous extract of pomegranate peels

In the present study, the production of a reduced-sugar pomegranate juice jelly supplemented with an aqueous extract of pomegranate peel (PE) is described. Influence of different carbohydrate polymers (guar (G), xanthan (X) and tragacanth (T) gums) on rheological properties was studied. Combination GXT presented the most similar rheological behaviour to commercial jelly. Jelly (J) and jelly with PE (JE) were stored at 4 °C over an 8 week period for physical, chemical, antioxidant, microbiological and sensory analysis. J and JE showed similar values for °Brix, colour and Aw, though the pH of JE was lower than J. Thiol and phenolic compounds were higher in JE than in J. Antioxidant activity (radical scavenging activity and autoxidation of linoleic acid) was higher in JE than in J at 0 weeks, and were decreasing with time. Pomegranate juice with additives was generally less accepted than J and JE.     

Random walks with statistical shape prior for cochlea and inner ear segmentation in micro-CT images

A cochlear implant is an electronic device which can restore sound to completely or partially deaf patients. For surgical planning, a patient-specific model of the inner ear must be built using high-resolution images accurately segmented. We propose a new framework for segmentation of micro-CT cochlear images using random walks, where a region term estimated by a Gaussian mixture model is combined with a shape prior initially obtained by a statistical shape model (SSM). The region term can then take advantage of the high contrast between the background and foreground, while the shape prior guides the segmentation to the exterior of the cochlea and to less contrasted regions inside the cochlea. The prior is obtained via a non-rigid registration regularized by a statistical shape model. The SSM constrains the inner parts of the cochlea and ensures valid output shapes of the inner ear.     

Design and behavior study of a grammar-guided genetic programming algorithm for mining association rules

This paper presents a proposal for the extraction of association rules called G3PARM (Grammar-Guided Genetic Programming for Association Rule Mining) that makes the knowledge extracted more expressive and flexible. This algorithm allows a context-free grammar to be adapted and applied to each specific problem or domain and eliminates the problems raised by discretization. This proposal keeps the best individuals (those that exceed a certain threshold of support and confidence) obtained with the passing of generations in an auxiliary population of fixed size n. G3PARM obtains solutions within specified time limits and does not require the large amounts of memory that the exhaustive search algorithms in the field of association rules do. Our approach is compared to exhaustive search (Apriori and FP-Growth) and genetic (QuantMiner and ARMGA) algorithms for mining association rules and performs an analysis of the mined rules. Finally, a series of experiments serve to contrast the scalability of our algorithm. The proposal obtains a small set of rules with high support and confidence, over 90 and 99% respectively. Moreover, the resulting set of rules closely satisfies all the dataset instances. These results illustrate that our proposal is highly promising for the discovery of association rules in different types of datasets.