Dominant BIN1-related centronuclear myopathy (CNM) revealed by lower limb myalgia and moderate CK elevation

We report a BIN1-related CNM family with unusual clinical phenotype. The proband, a 56-year-old man suffered of lower limbs myalgia since the age of 52. Clinical examination showed short stature, mild symmetric eyelid ptosis without ophthalmoplegia, scapular winging and Achilles tendon retraction. A muscle weakness was not noted. CK levels were up to 350 UI/L. Deltoid muscle biopsy showed nuclear centralization and clustering, deep sarcolemmal invaginations and type 1 fiber hypotrophy. Whole body MRI revealed fatty infiltration of posterior legs compartments, lumbar paraspinal and serratus muscles. Myotonic dystrophy type1 and 2, Pompe disease and MTM1 and DNM2-related CNM were ruled out. By sequencing BIN1, we identified a heterozygous pathogenic mutation [c.107C > A (p.A36E)], and we demonstrate that the mutation strongly impairs the membrane tubulation property of the protein. One affected sister carried the same mutation. Her clinical examination and muscle MRI revealed a similar phenotype. Our findings expand the clinical and genetic spectrum of the autosomal dominant CNM associated with BIN1 mutations

Decoding information for grasping from the macaque dorsomedial visual stream

Neurodecoders have been developed by researchers mostly to control neuroprosthetic devices, but also to shed new light on neural functions. In this study, we show that signals representing grip configurations can be reliably decoded from neural data acquired from area V6A of the monkey medial posterior parietal cortex. Two Macaca fascicularis monkeys were trained to perform an instructed-delay reach-to-grasp task in the dark and in the light toward objects of different shapes. Population neural activity was extracted at various time intervals on vision of the objects, the delay before movement, and grasp execution. This activity was used to train and validate a Bayes classifier used for decoding objects and grip types. Recognition rates were well over chance level for all the epochs analyzed in this study. Furthermore, we detected slightly different decoding accuracies, depending on the task's visual condition. Generalization analysis was performed by training and testing the system during different time intervals. This analysis demonstrated that a change of code occurred during the course of the task. Our classifier was able to discriminate grasp types fairly well in advance with respect to grasping onset. This feature might be important when the timing is critical to send signals to external devices before the movement start. Our results suggest that the neural signals from the dorsomedial visual pathway can be a good substrate to feed neural prostheses for prehensile actions

Serine hydroxymethyltransferase: origin of substrate specificity

All forms of serine hydroxymethyltransferase, for which a primary structure is known, have five threonine residues near the active-site lysyl residue (K229) that forms the internal aldimine with pyridoxal phosphate. For Escherichia coli serine hydroxymethyltransferase each of these threonine residues has been changed to an alanine residue. The resulting five mutant enzymes were purified and characterized with respect to kinetic and spectral properties. The mutant enzymes T224A and T227A showed no significant changes in kinetic and spectral properties compared to the wild-type enzyme. The T225A and T230A enzymes exhibited differences in K(m) and k(cat) values but exhibited the same spectral properties as the wild-type enzyme. The four threonine residues at positions 224, 225, 227, and 230 do not play a critical role in the mechanism of the enzyme. The T226A enzyme had nearly normal affinity for substrates and coenzymes but had only 3% of the catalytic activity of the wild-type enzyme. The spectrum of the T226A enzyme in the presence of amino acid substrates showed a large absorption maximum at 343 nm with only a small absorption band at 425 nm, unlike the wild-type enzyme whose enzyme-substrate complexes absorb at 425 nm. Rapid reaction studies showed that when amino acid substrates and substrate analogues were added to the T226A enzyme, the internal aldimine absorbing at 422 nm was rapidly converted to a complex absorbing at 343 nm in a second-order process. This was followed by a very slow first-order formation of a complex absorbing at 425 nm. Variation of the initial rapid second-order process as a function of pH suggested that the anionic form of the amino acid forms the first complex with the enzyme. The results are interpreted as being due to the rapid formation of a gem-diamine complex between amino acids and T226A enzyme with a rate-determining formation of the external aldimine. This suggests that Thr-226 plays an important role in converting the gem-diamine complex to the external aldimine complex. Variation of the kinetic constants with amino acid structure suggests that the T226A enzyme distinguishes between substrates and substrate analogues in the formation of the gem-diamine complex

The presence of the brown bear (Ursus arctos, L.) in the north eastern Alps (Friuli Venezia Giulia region) in relation to the Alpine metapopulation

The North Eastern Alps (Friuli Venezia Giulia Region) represent a peripheral area of presence of the Dinaric population (for the North Dinaric population, Slovenia, 400-450 individuals estimated) of the Brown Bear; in this area in the last years some individuals has started to come from Trentino population (40-45 individuals estimated) and to use this areas. In previous 114 researches this area has been considered one of the most suitable areas, in the alps, for supporting the alpine brown bear population and for enhancing the creation of the alpine metapopulation. From 2004 to the 2013 in mountains areas of the Friuli Venezia Giulia has been studied (2500 km2) the presence of the Brown Bear with different techniques: the genetic sampling (by opportunistic and systematic methods), photo interpretation and behavioral analysis and radiotelemetry. The genetic samplings have been obtained by the hair traps (50 permanent hair traps plus 80 temporary and moving hair traps) and by opportunistic techniques. By the genetic analysis it has detected the presence, from 2004, of 21 different genotypes (4 from Trentino and 17 from the Dinaric population, 3 of them studied by telemetry), all of them were males. The number of genotypes detected in different year has showed a cyclic pattern, with a increment in the last year, due to dispersing individuals from Dinaric source population; in different years, from 3 to 8 (2013), different genotypes have been detected, with a evident turnover. The median time of presence (years of sampling), for each genotypes, was 2 years, and only 6 genotypes have been sampled for 3 or more years (1 from Trentino); 10 genotypes have been sampled in only one year. Despite to the increment of the Trentino population and the high density of the Dinaric populations, in the north eastern alps the process of immigration and colonization appears to be slow and intermittent and seems correlated more to the demographic aspects (i.e localization and philopatry of the females, now present only in the Alpine and Dinaric areas of Slovenia and on the right side of Adige river, in Trentino), management of the Dinaric population, dispersal behavior and presence of not permeable infrastructure (high way Ljubljana-Trieste) rather than the ecological values of the areas

Effect of freeze-dryer design on heat transfer variability investigated using a 3D mathematical model

International audienceIn the freeze-drying process, vials located at the border of the shelf usually present higher heat flow rates which in turn result in higher product temperatures than central vials. This phenomenon, named edge vial effect, can result in product quality variability within the same batch of vials and between batches at different scales. Our objective was to investigate the effect of various freeze-dryer design features on the heat transfer variability. A 3D mathematical model previously developed in COMSOL Multiphysics and experimentally validated was used to simulate heat transfer of a set of vials located at the edge and in the centre of the shelf. The design features considered were the loading configurations of the vials, the thermal characteristics of the rail, the walls and the shelves and some relevant dimensions of the drying chamber geometry. The presence of the rail in the loading configuration and the value of the shelf emissivity strongly impacted on the heat flow rates received by the vials. Conversely, the heat transfer was not significantly influenced by modifications of the thermal conductivity of the rail, the emissivity of the walls and by the geometry of the drying chamber. The developed model revealed to be a powerful tool to predict the heat transfer variability between edge and central vials for the cycle development and scale-up and to compare various freeze-dryer design features

Presence and distribution of the brown bear (Ursus arctos) in Friuli Venezia Giulia, from 2004 to 2011, through the non-invasive genetic monitoring ad conservation implications

After having disappeared at the beginning of 1900, the brown bear has started in a late 1960s a slow process of recolonization of the north-eastern Alps, through an expansion of Dinaric population. At the end of the 1990s the University of Udine began the occasional monitoring of the species and from 2004 non-invasive genetic monitoring became systematic. In the last 8 years 217 hair traps have been activated in the region to monitore: Natisone Valleys, the Julian and Carnic Alps and Prealps. Twenty-six hair traps were monitored in all years, whereas 40 were observed only in 2004, 2007 and 2011. The 26 hair traps constantly monitored from 2004 to 2011 showed 17% of average success of hair’s collecting (brown bear samples collected/day control: BBSD). The 40 hair traps, monitored in the window period, showed 12% of BBSD. The BBSD value varied in relation to both season (highest in spring) and year, with a dramatic decline from 2008, and interaction between year and area. From 2004, 13 genotypes, through systematic hair traps monitoring, were identified, while only 2 genotypes were sampled opportunistically. It was observed a high turnover of the genotypes: only 7 genotypes were sampled for more than 2 years (47% of total), 4 genotypes (27% of the total) were sampled for 3 years or more. The annual attendance of bear have been constant from 2004 to 2007, with 5-6 genotypes present every year. In the period between 2008 and 2010 there was a drastic decrease in the successful collection at the hair traps, with and average of 1-2 animals genotyped per year. However, opportunistic samples have increased in the recent times, probably due to the arrivals of 3 genotypes from Trentino (KJ2G2 in 2009 and DG2 and MJ4 in 2011). The year 2011 showed a further increase in the presence of bears with 5 animals genotyped in Friuli Venezia Giulia. Three of these animals belonged to the Slovenian population, while the other 2 genotypes were from the Trentino population. The results seem to confirm the exchange of some individuals between the Dinaric and central alpine population. As an example, the dinaric bear M5 was genotyped in Friuli Venezia Giulia in 2008 and then sampled in 2009 and captured in 2010 in Trentino and finally slot in Slovenia in 2011. The distribution in the alpine and prealpine areas has changed year by year: from the 2004 to 2007 the Natisone Valley and the Julian prealpine areas along the border with Slovenia were the areas more used, whilst from 2009 there was an apparent higher presence of bears in the Carnian Prealps and Alps, and in the Julian Alps. This shift could be due to human disturbance (i.e hunting management), control of the species carried out in neighbouring Slovenia, with a decreasing of immigrant from dinaric populations, and new immigration of bears from the central Alps. The present work has highlighted the necessity for a trans-regional and cross-border management of the species, especially in consideration to the population control applied in Slovenia, which seem to limit the Dinaric population expansion in the Alps, and furthermore the philopatry behaviour of bear females, which implies the absence of females in Friuli Venezia Giulia and induces a movement bach to Slovenia (at least 3 bears genotyped in Italy were shot in Slovenia). All these elements seem to exert important limitations to the consolidation and stabilization of the population of brown bears in north-eastern Alps. From the methodological point of view the protocol of systematic non-invasive genetic monitoring, shared at the trans-regional and trans-boundary level, is fundamental to monitore the dynamics and distribution of bear; the protocol should follow a systematic experimental design and should be integrated with a efficient opportunistic data collection

Feshbach resonances in ultracold K(39)

We discover several magnetic Feshbach resonances in collisions of ultracold K(39) atoms, by studying atom losses and molecule formation. Accurate determination of the magnetic-field resonance locations allows us to optimize a quantum collision model for potassium isotopes. We employ the model to predict the magnetic-field dependence of scattering lengths and of near-threshold molecular levels. Our findings will be useful to plan future experiments on ultracold potassium atoms and molecules.Comment: 7 pages, 6 figure

Observation of an Efimov spectrum in an atomic system

In 1970 V. Efimov predicted a puzzling quantum-mechanical effect that is still of great interest today. He found that three particles subjected to a resonant pairwise interaction can join into an infinite number of loosely bound states even though each particle pair cannot bind. Interestingly, the properties of these aggregates, such as the peculiar geometric scaling of their energy spectrum, are universal, i.e. independent of the microscopic details of their components. Despite an extensive search in many different physical systems, including atoms, molecules and nuclei, the characteristic spectrum of Efimov trimer states still eludes observation. Here we report on the discovery of two bound trimer states of potassium atoms very close to the Efimov scenario, which we reveal by studying three-particle collisions in an ultracold gas. Our observation provides the first evidence of an Efimov spectrum and allows a direct test of its scaling behaviour, shedding new light onto the physics of few-body systems.Comment: 10 pages, 3 figures, 1 tabl

Jacobi Identity for Vertex Algebras in Higher Dimensions

Vertex algebras in higher dimensions provide an algebraic framework for investigating axiomatic quantum field theory with global conformal invariance. We develop further the theory of such vertex algebras by introducing formal calculus techniques and investigating the notion of polylocal fields. We derive a Jacobi identity which together with the vacuum axiom can be taken as an equivalent definition of vertex algebra.Comment: 35 pages, references adde