Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities

In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more proinflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy

Histological and transcriptome-wide level characteristics of fetal myofiber hyperplasia during the second half of gestation in Texel and Ujumqin sheep

<p>Abstract</p> <p>Background</p> <p>Whether myofibers increase with a pulsed-wave mode at particular developmental stages or whether they augment evenly across developmental stages in large mammals is unclear. Additionally, the molecular mechanisms of myostatin in myofiber hyperplasia at the fetal stage in sheep remain unknown. Using the first specialized transcriptome-wide sheep oligo DNA microarray and histological methods, we investigated the gene expression profile and histological characteristics of developing fetal ovine longissimus muscle in Texel sheep (high muscle and low fat), as a myostatin model of natural mutation, and Ujumqin sheep (low muscle and high fat). Fetal skeletal muscles were sampled at 70, 85, 100, 120, and 135 d of gestation.</p> <p>Results</p> <p>Myofiber number increased sharply with a pulsed-wave mode at certain developmental stages but was not augmented evenly across developmental stages in fetal sheep. The surges in myofiber hyperplasia occurred at 85 and 120 d in Texel sheep, whereas a unique proliferative surge appeared at 100 d in Ujumqin sheep. Analysis of the microarray demonstrated that immune and hematological systems' development and function, lipid metabolism, and cell communication were the biological functions that were most differentially expressed between Texel and Ujumqin sheep during muscle development. Pathways associated with myogenesis and the proliferation of myoblasts, such as calcium signaling, chemokine (C-X-C motif) receptor 4 signaling, and vascular endothelial growth factor signaling, were affected significantly at specific fetal stages, which underpinned fetal myofiber hyperplasia and postnatal muscle hypertrophy. Moreover, we identified some differentially expressed genes between the two breeds that could be potential myostatin targets for further investigation.</p> <p>Conclusions</p> <p>Proliferation of myofibers proceeded in a pulsed-wave mode at particular fetal stages in the sheep. The myostatin mutation changed the gene expression pattern in skeletal muscle at a transcriptome-wide level, resulting in variation in myofiber phenotype between Texel and Ujumqin sheep during the second half of gestation. Our findings provide a novel and dynamic description of the effect of myostatin on skeletal muscle development, which contributes to understanding the biology of muscle development in large mammals.</p

Muscle Interstitial Cells: A Brief Field Guide to Non-satellite Cell Populations in Skeletal Muscle

Skeletal muscle regeneration is mainly enabled by a population of adult stem cells known as satellite cells. Satellite cells have been shown to be indispensable for adult skeletal muscle repair and regeneration. In the last two decades, other stem/progenitor cell populations resident in the skeletal muscle interstitium have been identified as "collaborators" of satellite cells during regeneration. They also appear to have a key role in replacing skeletal muscle with adipose, fibrous, or bone tissue in pathological conditions. Here, we review the role and known functions of these different interstitial skeletal muscle cell types and discuss their role in skeletal muscle tissue homeostasis, regeneration, and disease, including their therapeutic potential for cell transplantation protocols

COMPUTER-AIDED CLASSIFICATION OF INTERSTITIAL LUNG DISEASES VIA MDCT: 3D ADAPTIVE MULTIPLE FEATURE METHOD (3D AMFM)

Rationale and Objectives. Computer-aided detection algorithms applied to multidetector row CT (MDCT) lung image data sets have the potential to significantly alter clinical practice through the early, quantitative detection of pulmonary pathology. In this project, we have further developed a computer-aided detection tool, the adaptive multiple feature method (AMFM), for the detection of interstitial lung diseases based on MDCT-generated volumetric data. Materials and Methods. We performed MDCT (Siemens Sensation 16 or 64 120 kV, B50f convolution kernel, and <= 0.75-mm slice thickness) on 20 human volunteers recruited from four cohorts studied under an National Institutes of Health-sponsored Bioengineering Research Partnership Grant: 1) normal never smokers; 2) normal smokers; 3) those with emphysema, and 4) those with interstitial lung disease (total: 11 males, 9 females; age range 20-75 years, mean age 40 years). A total of 1,184 volumes of interest (VOIs; 21 x 21 pixels in plane) were marked by a senior radiologist and a senior pulmonologist as emphysema (EMPH, n = 287); ground-glass (GG, n = 147), honeycombing (HC, n = 137), normal nonsmokers (NN, n = 287), and normal smokers (NS, n = 326). For each VOI, we calculated 24 volumetric features, including statistical features (first-order features, run-length, and co-occurrence features), histogram, and fractal features. We compared two methods of classification (a Support Vector Machine (SVM) and a Bayesian classifier) using a 10-fold cross validation method and McNemar&apos;s test. Results. The sensitivity of five patterns in the form of Bayesian/SVM was: EMPH: 91/93%; GG: 89/86%; HC: 93/90%; NN: 90/73%; and NS: 75/82%. The specificity of five patterns in the form of Bayesian/support vector machine was: EMPH: 98/98%; GG: 98/98%; HC: 99/99%; NN: 90/94%; and NS: 96/91%. Conclusion. We conclude that volumetric features including statistical features, histogram and fractal features can be successfully used in differentiation of parenchymal pathology associated with both emphysema and interstitial lung diseases. Additionally, support vector machine and Bayesian methods are comparable classifiers for characterization of interstitial lung diseases on MDCT images.X1183sciescopu

Nutritional challenges for the elderly

[No Abstract]<br /

Clinical and radiological results of arthroscopically treated tibial spine fractures in childhood

The objective of this study is to report the clinical and radiological long-term follow-up evaluation of young patients arthroscopically treated for anterior tibial eminence fracture. Ten patients (mean age: 13.5 years) were treated between 1992 and 2006. At follow-up they were clinically and radiologically evaluated. Moreover, they underwent assessment with the International Knee Documentation Committee (IKDC) forms, Lysholm and Tegner knee scales and measurement with the KT-1000 arthrometer. At a mean follow-up of 85.8 months, all of the patients reported a subjective good-excellent outcome. Objectively, the Lachman test was negative in seven patients and positive in three patients; six patients (60%) registered a slight (+) to mild (++) pivot-glide test. The mean value of KT-1000 arthrometer measurements was 3 mm; all knee scales showed satisfactory results. Radiological exam always showed good healing of the fracture. Fractures of the tibial spine often lead to anterior and rotational knee laxity. However, despite this instrumental finding, patients usually do not report any type of restriction in their functional or sports activities