Trial and error versus errorless learning of functional skills in patients with acute stroke

Objective: To compare the effectiveness of errorless learning versus trial and error learning for teaching activities of daily living to patients with acute stroke with or without explicit memory impairments. Design: Randomized crossover. Setting: Rehabilitation hospital. Participants: 33 adult subjects following an acute stroke. Intervention: Subjects were taught to prepare a wheelchair for a transfer and to put on a sock with a sock-donner. Tasks were taught using errorless learning or trial and error learning. Explicit memory was assessed using the Neurobehavioral Cognitive Status Exam. Main Outcome Measures: Days until subject was able to demonstrate retention of the task, and success or failure at carry-over to a similar task. Results: No significant differences were found in days to retention for either functional task when taught using errorless learning or trial and error learning in subjects with or without explicit memory impairments. Carry-over was significantly better when trial and error learning was used for learning sock donning. Conclusions: When choosing the best learning method for patients undergoing rehabilitation for stroke, the nature of the task should be considered. Additional research is needed to identify the best approach for teaching activities of daily living and facilitating carry-over of learning in individuals with acute stroke

Mycobacterial trehalose dimycolate reprograms macrophage global gene expression and activates matrix metalloproteinases.

Trehalose 6,6′-dimycolate (TDM) is a cell wall glycolipid and an important virulence factor of mycobacteria. In order to study the role of TDM in the innate immune response to Mycobacterium tuberculosis, microarray analysis was used to examine gene regulation in murine bone marrow-derived macrophages in response to 90-μm-diameter polystyrene microspheres coated with TDM. A large number of genes, particularly those involved in the immune response and macrophage function, were up- or downregulated in response to these TDM-coated beads compared to control beads. Genes involved in the immune response were specifically upregulated in a myeloid differentiation primary response gene 88 (MyD88)-dependent manner. The complexity of the transcriptional response also increased greatly between 2 and 24 h. Matrix metalloproteinases (MMPs) were significantly upregulated at both time points, and this was confirmed by quantitative real-time reverse transcription-PCR (RT-PCR). Using an in vivo Matrigel granuloma model, the presence and activity of MMP-9 were examined by immunohistochemistry and in situ zymography (ISZ), respectively. We found that TDM-coated beads induced MMP-9 expression and activity in Matrigel granulomas. Macrophages were primarily responsible for MMP-9 expression, as granulomas from neutrophil-depleted mice showed staining patterns similar to that for wild-type mice. The relevance of these observations to human disease is supported by the similar induction of MMP-9 in human caseous tuberculosis (TB) granulomas. Given that MMPs likely play an important role in both the construction and breakdown of tuberculous granulomas, our results suggest that TDM may drive MMP expression during TB pathogenesis

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A unique anisotropic R

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148373/1/mrm27621.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148373/2/mrm27621_am.pd

JAK2 as a novel mediator of the pro-fibrotic effects of TGFβ in systemic sclerosis

OBJECTIVE.: Tissue fibrosis caused by a pathological activation of SSc fibroblasts is a major hallmark of systemic sclerosis (SSc). The aims of the present study were to investigate whether JAK2 contributes to the pathologic activation of fibroblasts in SSc and to evaluate the anti-fibrotic potential of JAK2 inhibition for the treatment of systemic sclerosis. METHODS.: Activation of JAK2 in human skin and in experimental fibrosis was determined by immunohistochemistry. JAK2 signaling was inhibited with the selective JAK2 inhibitor TG 101209 or by siRNA. Bleomycin-induced dermal fibrosis and tight-skin 1 (Tsk-1) mice were used to evaluate the anti-fibrotic potential of a specific JAK2 inhibition in vivo. RESULTS.: Increased activation of JAK2 was detected in the skin of SSc patients, particularly in fibroblasts. The activation of JAK2 was TGFβ dependent and persisted in cultured SSc fibroblasts. Inhibition of JAK2 reduced the basal collagen synthesis selectively in SSc fibroblasts but not in resting healthy dermal fibroblasts. Moreover, inhibition of JAK2 prevented the stimulatory effects of TGFβ on fibroblasts. Treatment with TG 101209 did not only prevent bleomycin-induced fibrosis, but also effectively reduced skin fibrosis in Tsk-1 mice. CONCLUSION.: We demonstrated that JAK2 is activated in a TGFβ dependent manner in SSc. Considering the potent anti-fibrotic effects of JAK2 inhibition, our study might have direct translational implications, because inhibitors of JAK2 are currently evaluated in clinical trials for myeloproliferative disorders and would be also available for evaluation in SSc patients

Structure, Dynamics, and Kinetics of Weak Protein-Protein Complexes from NMR Spin Relaxation Measurements of Titrated Solutions

International audienc