Allen's Rule documents a century-old biological observation that strong positive correlations exist among latitude, ambient temperature, and limb length in mammals. Although genetic selection for thermoregulatory adaptation is frequently presumed to be the primary basis of this phenomenon, important but overlooked research has shown appendage outgrowth also markedly influenced by environmental temperature. Alteration blood flow via vasoconstriction/vasodilation current default hypothesis...

Abstract Aberrantly activated signal transducer and activator of transcription 3 (Stat3) is implicated in the development various human cancers. Y705 phosphorylation conventionally thought to be required for Stat3 signal-dependent activation seems play an essential role some malignancies. Recently, it was shown that through novel noncanonical mechanisms, including at S727. Here, we investigate S727 its subsequent effects prostate cancer development, independent phosphorylation, using mutated...

The BMI1 oncogene promotes prostate cancer (PC) progression. High B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) expression predicts poor prognosis in PC patients. Recent evidence suggests that may also play a role docetaxel chemoresistance. However, mechanisms and clinical significance of BMI1-related chemoresistance have not been investigated. For this purpose, was silenced 2 cell lines (LNCaP DU 145). Cell proliferation apoptosis after treatment were measured....

Abstract There is mounting evidence that tumors are initiated by a rare subset of cells called cancer stem (CSCs). CSCs generally quiescent, self-renew, form at low numbers, and give rise to the heterogeneous cell types found within tumor. isolated from multiple tumor differentiate both in vivo vitro when cultured serum, yet factors responsible for their differentiation have not been identified. Here we show vitronectin component human serum driving through an integrin αVβ3-dependent...

ABSTRACT Limbs of animals raised at warm ambient temperature are significantly and permanently longer than those siblings housed in the cold. These highly reproducible lab results closely parallel ecogeographical tenet described by Allen's extremity size rule, which states that appendage length correlates with latitude. It is unclear what mechanisms underlie these differences pattern they emerge, since morphology traditionally thought to reflect naturally selected genomic adaptations for...

Abstract The developmental anatomy of the proximal femur is complex. In some mammals, including humans, femoral head and greater trochanter emerge as separate ossification centres within a common chondroepiphysis remain throughout ontogeny. other species, these secondary coalesce to form single osseous epiphysis much like humerus. These differences in ontogeny have not been previously addressed, yet are critical an understanding mineralization architecture across wide range mammals may key...

Didactic lessons are only one part of the multimodal teaching strategies used in gross anatomy courses today. Increased emphasis is placed on providing more opportunities for students to develop lifelong learning and critical thinking skills during medical training. In a pilot program designed promote engaged independent anatomy, self‐study modules were introduced supplement human instruction at Joan C. Edwards School Medicine Marshall University. Modules use three‐dimensional constructs...

The proximal and distal growth plates of the principal long bones do not contribute equally to longitudinal growth. Most forelimb elongation occurs at shoulder wrist, while most hindlimb knee. This study examined whether insulin-like factor-I (IGF-I), a potent regulator, could underlie this variation via differential receptor expression. spatiotemporal distribution IGF-I (IGF-IR) was mapped in (overall within regional zones) from immature mice using immunohistochemistry. Growth activity...

Linear growth failure results from a broad spectrum of systemic and local disorders that can generate chronic musculoskeletal disability. Current bone lengthening protocols involve invasive surgeries or drug regimens, which are only partially effective. Exposure to warm ambient temperature during increases limb length, suggesting targeted heat could noninvasively enhance elongation. We tested the hypothesis daily exposure on one side body unilaterally femoral tibial lengths. Mice (N = 20)...

Ambient temperature and physical activity modulate bone elongation in mammals, but mechanisms underlying this plasticity are a century-old enigma. Longitudinal growth occurs cartilaginous plates, which receive nutritional support via delivery of solutes from the vasculature. We tested hypothesis that chronic exercise warm promote lengthening by increasing solute to plate, measured real time using vivo multiphoton microscopy. housed 68 weanling female mice at cold (16°C) or (25°C)...

Solute delivery to avascular cartilaginous plates is critical bone elongation, and impaired transport of nutrients growth factors in cartilage matrix could underlie many skeletal abnormalities. Advances imaging technology have revolutionized our ability visualize vivo, but quantitative methods are still needed. We developed analytical standards for measuring solute delivery, defined by amount rate intravenous tracer entry, murine using multiphoton microscopy. employed an acute temperature...

This report presents the results of an epidemiologic case-control study. The study includes 58 cases and 116 controls from both sexes, selected Admission Register Hospital Death Registry Office local city authorities. Controls have been matched to by age, sex, place residence source selection. demonstrated no increased risk associated with coffee consumption. Habitual smokers present a 2.3 times higher than nonsmokers. estimated relative for occupation standardized age smoking habit, is 5.5....

Cartilage histomorphometry is often performed on decalcified, paraffin-embedded bone sections, which provide versatility in staining applications from basic morphology to immunohistochemistry. Safranin O a cationic dye that binds proteoglycans cartilage and routinely used assess growth plate dynamics and/or fracture repair at bone-cartilage interfaces. When with counterstain such as fast green, safranin can offer exquisite differentiation of surrounding bone. However, various decalcification...

Growth hormone is known to stimulate connective tissue, but the degree which it influences skin biomechanical properties unclear. This study tested hypothesis that human growth transgene expression changes material and structural composition of adult mouse skin. Fracture toughness elastic modulus were measured on freshly dissected dorsal fixed samples analyzed histologically. Transgenics had higher moduli than their sex-matched non transgenic littermates, male transgenics demonstrated...

Limb length inequality results from many types of musculoskeletal disorders. Asymmetric weight bearing a limb discrepancy less than 2% can have debilitating consequences such as back problems and early onset osteoarthritis. Existing treatments include invasive surgeries and/or drug regimens that are often only partially effective. As noninvasive alternative, we previously developed once daily limb-heating model using targeted heat on one side the body for two weeks to unilaterally increase...

Advances in understanding the molecular regulation of longitudinal growth have led to development novel drug therapies for plate disorders. Despite progress, a major unmet challenge is delivering therapeutic agents avascular-cartilage plates. Dense extracellular matrix and lack penetrating blood vessels create semipermeable “barrier,” which hinders transport at vascular-cartilage interface. To overcome this obstacle, we used hindlimb heating model manipulate bone circulation 5-wk-old female...

Bones elongate through endochondral ossification in cartilaginous growth plates located at ends of primary long bones. Linear ensues from a cascade biochemical signals initiated by actions systemic and local regulators on plate chondrocytes. Although cellular processes are well defined, there is fundamental gap understanding how physically transported surrounding blood vessels into dense, avascular cartilage matrix. Intravital imaging using vivo multiphoton microscopy one promising strategy...

Abstract Environmental temperature can have a surprising impact on extremity growth in homeotherms, but the underlying mechanisms remained elusive for over century. Limbs of animals raised at warm ambient are significantly and permanently longer than those littermates housed cooler temperature. These remarkably consistent lab results closely resemble ecogeographical tenet described by Allen's “extremity size rule,” that appendage length correlates with latitude. This phenotypic plasticity...

Bone elongation occurs in cartilaginous growth plates, which rely on surrounding blood vessels for nutrition. New imaging modalities that enable real‐time study of vascular access to plates have potential fundamentally advance understanding physiological regulation. Our lab employs vivo multiphoton microscopy measure environmental effects entrance systemically‐introduced fluorescent tracers into tibial 5 week old mice. We previously found temperature‐ and exercise‐related changes small...