Regeneration in denervated toad (bufo viridis) gastrocnemius muscle and the promotion of the process by low energy laser irradiation

Background: It is known that while denervated skeletal muscles have the ability to regenerate, maturation of regenerated myofibres does not take place under these conditions. Denervation also causes elevation of “invasive” and satellite cells, but the role of these cells in the regeneration process after injury to the denervated muscle is still unknown. Low energy lasers have recently been found to modulate and accelerate physiological processes in cells. The aim of the present study was to compare regeneration in denervated and innervated amphibian muscles and to investigate whether this process in denervated muscles can be stimulated by low energy laser irradiation prior to injury in these muscles. Methods: Denervated gastrocnemius muscles of toads were irradiated with He-Ne laser (6.0 mW, 31.2 J/cm²) 7 days postdenervation (control muscle received red light irradiation at the same wavelength). Nine days after denervation cold injury was performed on the site of irradiation of both groups of muscles. At 14 days postinjury all muscles were removed and processed for histology and histomorphometric analysis of mononucleated cells, myotubes, and young myofibres in the regenerated zone. Results: The volume fraction (percent of total injured zone) of the various histological structures in the injured zones 14 days after cold injury in the denervated (9 days prior to injury) muscles did not differ from innervated injured muscles at the same time interval postinjury. The mononucleated cells and myotubes in the laser irradiated muscles comprised 49 ± 4% and 6 plusmn; 1% of the injured area, respectively, which was significantly lower than their volume fraction (67 plusmn; 2% and 11 plusmn; 2%, respectively) in the control muscles. The young myofibres populated 34 plusmn; 4% of the total injured area in the denervated and laser irradiated muscles which was significantly higher than their volume fraction (12 ± 2%) in control denervated muscles. Conclusions: It is concluded that initial stages of regeneration can also take place in skeletal denervated and injured muscles of amphibians. The kinetics of the regeneration process are identical in denervated and innervated muscles. The process of regeneration in denervated muscles can be markedly enhanced if the muscle is irradiated by low energy laser prior to injury, probably by activation (stimulation of proliferation and/or differentiation) cells in the muscles that are “recruited” and participate in the process of regeneration. © 1995 Wiley-Liss, Inc.     

Teacher–student neural coupling during teaching and learning

Human communication is remarkably versatile, enabling teachers to share highly abstracted and novel information with their students. What neural processes enable such transfer of information across brains during naturalistic teaching and learning? Here, a teacher was scanned in functional magnetic resonance imaging while giving an oral lecture with slides on a scientific topic followed by a review lecture. Students were then scanned while watching either the intact Lecture and Review (N = 20) or a temporally scrambled version of the lecture (N = 20). Using intersubject correlation, we observed widespread Teacher–Student neural coupling spanning sensory cortex and language regions along the superior temporal sulcus as well as higher-level regions including posterior medial cortex (PMC), superior parietal lobule, and dorsolateral and dorsomedial prefrontal cortex. Teacher–student alignment in higher-level areas was not observed when learning was disrupted by temporally scrambling the lecture. Moreover, teacher–student coupling in PMC was significantly correlated with learning: the more closely the student’s brain mirrored the teacher’s brain, the more the student improved their learning score. Together, these results suggest that the alignment of neural responses between teacher and students may reflect effective communication of complex information across brains in classroom settings.     

Toward an accelerated adoption of data-driven findings in medicine

Medicine, Health Care and Philosophy - To accelerate the adoption of a new method with a high potential to replace or extend an existing, presumably less accurate, medical scoring system,...     

Topoisomerase IIalpha expression in ductal carcinoma in situ of the breast: a preliminary study

Ductal carcinoma in situ (DCIS) of the breast, a precursor lesion of invasive breast cancer, is a heterogeneous disease in terms of histomorphologic features and biologic behavior. Our aim was to assess the proliferative activity, expressed as topoisomerase IIalpha (Topo IIalpha) immunoreactivity and c-erbB-2 expression in relation to morphologic features and architectural pattern of DCIS. The study included 26 DCIS, which were reclassified according to the recommendations of Consensus Conference. Topo-IIalpha and c-erbB-2 immunoreactivity were detected on paraffin sections. Topo IIalpha was consistently negative in normal ductal epithelium. Topo IIalpha-labeling index (Topo IIalpha-LI) was 0.7+/-0.6% for grade I, 4.3+/-3.9% for grade II, and 13.4+/-8.9 for grade III lesions (P<.01). For mixed nuclear grade DCIS, Topo IIalpha-LI was 6.8+/-4.8. There was no difference in Topo IIalpha-LI between different architectural patterns in low- and intermediate-grade lesions. In high nuclear grade DCIS, there was a progressive increase in Topo IIalpha-LI from solid toward cribriform and comedo-type DCIS. Positive c-erbB-2 immunoreactivity was found in 46% of DCIS, being highest in DCIS with high nuclear grade (78%) and in lesions with extensive necrosis. Topo IIalpha-LI was significantly higher in c-erbB-2-positive lesions (Topo IIalpha-LI- 12.4+/-8.5) as compared with negative lesions (Topo IIalpha-LI- 3.9+/-4.5, P<. 0001). Overexpression of c-erbB-2 and Topo IIalpha is associated with poorly differentiated lesions. Proliferative activity in individual ducts of DCIS depended primarily on the nuclear grade and was independent of architectural patterns of individual ducts in architecturally heterogeneous lesions.     

Fine mapping of a region on chromosome 8p gives evidence for a QTL contributing to individual differences in an anxiety-related personality trait: TPQ harm avoidance.

The chromosome 8p region is of interest in human behavioral genetics since it harbors a susceptibility region not only for schizophrenia but also for anxiety-related personality traits such as harm avoidance and neuroticism. Towards verifying our preliminary linkage finding of a QTL for TPQ harm avoidance at chromosome 8p, we have now genotyped altogether 24 micro-satellite markers in 377 families. Using three methods (maximum likelihood binomial or MLB, MERLIN, and an associated one parameter model), we observed significant results (P values from 0.002 to 0.0004) for linkage to harm avoidance in this region. A peak multipoint LOD score of 2.76 (P value 0.0002) was obtained with the MLB method. The region-wide empirical P value was 0.002 [0.001-0.0046]. Although, the peak position varied somewhat according to the method (D8S1048 for MLB, D8S1463 for the two other methods), for three methods D8S1810 ( approximately 60 cM) is within 1-2 cM of the peak for harm avoidance. This marker is of particular interest since it is proximate (<0.5 cM) of the core haplotype that in several recent studies show significant association with schizophrenia near neuroregulin 1. Although association studies with microsatellite markers need to be interpreted cautiously, using the Haplotype Trend Regression test one marker, D8S499 ( approximately 60 cM), showed an empirical P value of 2 x 10(-5) for allele 3, which confers a decreased harm avoidance score. Altogether, the current linkage and association results suggest the possibility that the same locus near the neuroregulin 1 gene on chromosome 8p confers risk for both an anxiety-related personality trait as well as schizophrenia. We hypothesize that this common genetic factor may contribute to emotional liability during early development, which constitutes a predisposing factor for major psychosis.     

Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression

Allicin, a major ingredient of fresh garlic extract that is produced during the crushing of garlic cloves, exerts various beneficial biological effects, including a broad spectrum of antimicrobial activity, antihyperlipidaemic and antihypertensive effects. However, how allicin affects the immune system is less well known, and its effect on human T cells has never been studied. Here, we examined the in-vitro effects of allicin on the functioning of T cells related to their entry to inflamed extravascular sites. We found that allicin (20-100 microm) inhibits the SDF-1alpha (CXCL12)-induced T cell migration through fibronectin (FN), and that this inhibition is mediated by the down-regulation of (i) the reorganization of cortical actin and the subsequent T cell polarization, and (ii) T cell adhesion to FN. Moreover, allicin also inhibited T cell adhesion to endothelial cells and transendothelial migration. The mechanisms underlying these inhibitory effects of allicin are associated with its ability to down-regulate the phosphorylation of Pyk2, an intracellular member of the focal adhesion kinases, and to reduce the expression of the VCAM-1- and FN-specific alpha4beta1-integrin (VLA-4). The ability of allicin to down-regulate these chemokine-induced and VLA-4-mediated T cell functions explains its beneficial biological effects in processes where T cells play an important role and suggests that allicin may be used therapeutically with chronic inflammatory diseases.     

Diet salinity and vasopressin as reproduction modulators in the desert-dwelling golden spiny mouse (Acomys russatus)

The time for reproduction in mammals largely depends on the availability of water and food in their habitat. Therefore, in regions where rains are limited to definite seasons of the year, mammals presumably will restrict their breeding correspondingly. But while mammals living in predictable ecosystems would benefit by timing their season to an ultimate predictable cue, such as photoperiod, in unpredictable ecosystems (e.g., deserts) they will need to use a more proximate signal. We suggest a mechanism by which water shortage (low water content in plants) could act as a proximate cue for ending the reproductive season. The golden spiny mouse (Acomys russatus), a diurnal rodent living in extreme deserts, may face an increased dietary salt content as the summer progresses and the vegetation becomes dry. Under laboratory conditions, increased diet salinity lead to reproductive hiatus in females, notable in imperforated vagina, and a significant decrease in the ovaries, uteri, and body masses. In females treated with vasopressin (VP), a hormone expressed during water stress, the uteri and body masses have decreased significantly, and the ovaries exhibited an increased number of atretic follicles. VP has also led to a significant decrease in relative medullary thickness (RMT) of the kidney. It is thus suggested that VP could act as a modulator linking the reproductive system with water economy in desert rodents, possibly through its act on the energetic pathways.     

The genetic and clinical outcome of isolated fetal muscular ventricular septal defect (VSD)

Introduction: Our objective was to evaluate the incidence of chromosomal aberration (both microscopic and submicroscopic) and the clinical outcome of fetuses with isolated muscular ventricular septal defect (VSD).

Material and methods: The study included 40 pregnant women whose fetuses were diagnosed with isolated muscular ventricular septal defect (mVSD). Of these, 30 patients underwent amniocentesis and 10 declined. All samples were tested by chromosomal microarray analysis (CMA). Of the 40 women in the study, 32 gave birth and the clinical outcome of the children was retrieved from the patients’ medical records.

Results: Of the 30 patients who underwent amniocentesis, one was detected with mosaic Klinefelter syndrome and one was detected with a pathogenic copy number variant unrelated to the VSD. Clinical follow-up was performed on 26 children after birth. The first postnatal echocardiography did not detect a VSD in 13 (50%) of the followed-up children. Spontaneous closure occurred in another eight (30.8%) children during the postnatal follow-up period. In only five children (19.2%) VSD was still detected by echocardiography after the first year of life.

Discussion: Isolated muscular VSD diagnosed prenatally does not appear to be a significant risk factor for chromosomal abnormalities and has a favorable clinical outcome.