Barrier-to-autointegration factor (BAF) involvement in prelamin a-related chromatin organization changes

Chromatin disorganization is one of the major alterations linked to prelamin A processing impairment. In this study we demonstrate that BAF is necessary to modulate prelamin A effects on chromatin structure. We show that when prelamin A and BAF cannot properly interact no prelamin A-dependent effects on chromatin occur; similar to what is observed in human Nestor Guillermo Progeria Syndrome cells harboring a BAF mutation, in HEK293 cells expressing a BAF mutant unable to bind prelamin A, or in siRNA mediated BAF-depleted HEK293 cells expressing prelamin A. BAF is necessary to induce histone trimethyl-H3K9 as well as HP1-alpha and LAP2-alpha nuclear relocalization in response to prelamin A accumulation. These findings are enforced by electron microscopy evaluations showing how the prelamin A-BAF interaction governs overall chromatin organization. Finally, we demonstrate that the LAP2-alpha nuclear localization defect observed in HGPS cells involves the progerin-BAF interaction, thus establishing a functional link between BAF and prelamin A pathological forms

Extracellular matrix and nuclear abnormalities in skeletal muscle of a patient with Walker–Warburg syndrome caused by POMT1 mutation

AbstractWalker–Warburg syndrome (WWS) is an autosomal recessive disorder characterized by congenital muscular dystrophy, structural eye abnormalities and severe brain malformations. We performed an immunohistochemical and electron microscopy study of a muscle biopsy from a patient affected by WWS carrying a homozygous frameshift mutation in O-mannosyltransferase 1 gene (POMT1). α-Dystroglycan glycosylated epitope was not detected in muscle fibers and intramuscular peripheral nerves. Laminin α2 chain and perlecan were reduced in muscle fibers and well preserved in intramuscular peripheral nerves. The basal lamina in several muscle fibers showed discontinuities and detachment from the plasmalemma. Most nuclei, including myonuclei and satellite cell nuclei, showed detachment or complete absence of peripheral heterochromatin from the nuclear envelope. Apoptotic changes were detected in 3% of muscle fibers. The particular combination of basal lamina and nuclear changes may suggest that a complex pathogenetic mechanism, affecting several subcellular compartments, underlies the degenerative process in WWS muscle

Artificial biochemical networks: a different connectionist paradigm.

Connectionist models are usually based on artificial neural networks. However, there is another route towards parallel distributed processing. This is by considering the origins of the intelligence displayed by the single celled organisms known as protoctists. Such intelligence arises by means of the biochemical interactions within the animal. An artificial model of this might therefore be termed an artificial biochemical network or ABN. This paper describes the attributes of such networks and illustrates their abilities in pattern recognition problems and in generating time-varying signals of a type which can be used in many control tasks. The flexibility of the system is explained using legged robots as an example. The networks are trained using back propagation and evolutionary algorithms such as genetic algorithms

Artificial biochemical networks.

Connectionist approaches to Artificial Intelligence are almost always based on Artificial Neural Networks. However, there is another route towards Parallel Distributed Processing, taking as its inspiration the intelligence displayed by single celled creatures called Protoctists (Protists). This is based on networks of interacting proteins. Such networks may be used in Pattern Recognition and Control tasks and are more flexible than most neuron models. In this paper they are demonstrated in Image Recognition applications and in Legged Robot control. They are trained using a Genetic Algorithm and Back Propagation

Unusual presentation of extra-nodal double-hit follicular lymphoma: a case report

Background: To the best of our knowledge, this case represents the first report of an extranodal double-hit follicular lymphoma (DH-FL) as an intestinal polypoid lesion. Case presentation: A 72-year-old woman presents with constipation. Colonoscopy reveals a sessile polypoid lesion of the colon bearing morphological, immunohistochemical and molecular hallmarks of DH-FL. Complete clinical staging and bone marrow biopsy showed no signs of disseminated disease. The patient, after two years of follow-up is still free of disease confirming the indolent behaviour of this limited lesion. Conclusions: A synoptic view at all the features of the patient and not merely at the molecular hallmarks of a disease are essential to establish the correct clinical approach

Ankrd2 in Mechanotransduction and Oxidative Stress Response in Skeletal Muscle: New Cues for the Pathogenesis of Muscular Laminopathies

Ankrd2 (ankyrin repeats containing domain 2) or Arpp (ankyrin repeat, PEST sequence, and proline-rich region) is a member of the muscle ankyrin repeat protein family. Ankrd2 is mostly expressed in skeletal muscle, where it plays an intriguing role in the transcriptional response to stress induced by mechanical stimulation as well as by cellular reactive oxygen species. Our studies in myoblasts from Emery-Dreifuss muscular dystrophy 2, a LMNA-linked disease affecting skeletal and cardiac muscles, demonstrated that Ankrd2 is a lamin A-binding protein and that mutated lamins found in Emery-Dreifuss muscular dystrophy change the dynamics of Ankrd2 nuclear import, thus affecting oxidative stress response. In this review, besides describing the latest advances related to Ankrd2 studies, including novel discoveries on Ankrd2 isoform-specific functions, we report the main findings on the relationship of Ankrd2 with A-type lamins and discuss known and potential mechanisms involving defective Ankrd2-lamin A interplay in the pathogenesis of muscular laminopathies