Kinematic Behaviour of a Novel Pedicle Screw-Rod Fixation System for the Canine Lumbosacral Joint

Objective: To determine the biomechanical behaviour of a novel distraction-stabilization system, consisting of an intervertebral distraction bolt, polyaxial screws and connecting rods, in the canine lumbosacral spine. Study design: Biomechanical study. Sample population: Cadaveric canine lumbosacral spines (L4-Cd3) (N=8) Methods: Cadaveric lumbosacral spines were harvested, stripped of musculature, mounted on a 4-point bending jig, and tested in extension, flexion and lateral bending using non-destructive compressive axial loads (0-150N). Angular displacement was recorded from reflective optical trackers rigidly secured to L6, L7 and S1. Data for primary and coupled motion were collected from intact spines; after destabilization at L7-S1, and following surgical stabilisation with the new implant system. Results: As compared with the intact spine, laminectomy resulted in a modest increase in angular displacement at L6-L7 and a marked increase at L7-S1. Instrumentation significantly reduced motion at the operated level (L7-S1) with a concomitant increase at the adjacent level (L6-L7). Conclusion: The combination of a polyaxial pedicle screw-rod system and intervertebral spacer provides a versatile solution of surgical stabilisation of the lumbosacral joint following surgical decompression in the canine lumbosacral spine. The increase in motion at L6-L7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this question. Clinical relevance: These results support the feasibility of using this new implant system for the management of degenerative lumbosacral disease in dogs. The increase in motion at L6-L7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this question

The Large Zinc Finger Protein ZAS3 Is a Critical Modulator of Osteoclastogenesis

Mice deficient in the large zinc finger protein, ZAS3, show postnatal increase in bone mass suggesting that ZAS3 is critical in the regulation of bone homeostasis. Although ZAS3 has been shown to inhibit osteoblast differentiation, its role on osteoclastogenesis has not been determined. In this report we demonstrated the role of ZAS3 in bone resorption by examining the signaling mechanisms involved in osteoclastogenesis.Comparison of adult wild-type and ZAS3 knockout (ZAS3-/-) mice showed that ZAS3 deficiency led to thicker bones that are more resistant to mechanical fracture. Additionally, ZAS3-/- bones showed fewer osteoclasts and inefficient M-CSF/sRANKL-mediated osteoclastogenesis ex vivo. Utilizing RAW 264.7 pre-osteoclasts, we demonstrated that overexpression of ZAS3 promoted osteoclastogenesis and the expression of crucial osteoclastic molecules, including phospho-p38, c-Jun, NFATc1, TRAP and CTSK. Contrarily, ZAS3 silencing by siRNA inhibited osteoclastogenesis. Co-immunoprecipitation experiments demonstrated that ZAS3 associated with TRAF6, the major receptor associated molecule in RANK signaling. Furthermore, EMSA suggested that nuclear ZAS3 could regulate transcription by binding to gene regulatory elements.Collectively, the data suggested a novel role of ZAS3 as a positive regulator of osteoclast differentiation. ZAS3 deficiency caused increased bone mass, at least in part due to decreased osteoclast formation and bone resorption. These functions of ZAS3 were mediated via activation of multiple intracellular targets. In the cytoplasmic compartment, ZAS3 associated with TRAF6 to control NF-kB and MAP kinase signaling cascades. Nuclear ZAS3 acted as a transcriptional regulator for osteoclast-associated genes. Additionally, ZAS3 activated NFATc1 required for the integration of RANK signaling in the terminal differentiation of osteoclasts. Thus, ZAS3 was a crucial molecule in osteoclast differentiation, which might potentially serve as a target in the design of therapeutic interventions for the treatment of bone diseases related to increased osteoclast activity such as postmenopausal osteoporosis, Paget's disease, and rheumatoid arthritis

Household Contamination with Salmonella enterica1

Household contamination with Salmonella enterica increases when occupational exposure exists (cattle farms with known salmonellosis in cattle, a salmonella research laboratory, or a veterinary clinic experiencing an outbreak of salmonellosis). Fifteen of 55 (27.2%) vacuum cleaner bags from households with occupational exposure to S. enterica were positive versus 1 of 24 (4.2% without known exposure. Use of a carpet cleaner and several cleaners/disinfectants reduced, but failed to eliminate, S. enterica from artificially contaminated carpet

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Mitochondria and Energetic Depression in Cell Pathophysiology

Mitochondrial dysfunction is a hallmark of almost all diseases. Acquired or inherited mutations of the mitochondrial genome DNA may give rise to mitochondrial diseases. Another class of disorders, in which mitochondrial impairments are initiated by extramitochondrial factors, includes neurodegenerative diseases and syndromes resulting from typical pathological processes, such as hypoxia/ischemia, inflammation, intoxications, and carcinogenesis. Both classes of diseases lead to cellular energetic depression (CED), which is characterized by decreased cytosolic phosphorylation potential that suppresses the cell’s ability to do work and control the intracellular Ca2+ homeostasis and its redox state. If progressing, CED leads to cell death, whose type is linked to the functional status of the mitochondria. In the case of limited deterioration, when some amounts of ATP can still be generated due to oxidative phosphorylation (OXPHOS), mitochondria launch the apoptotic cell death program by release of cytochrome c. Following pronounced CED, cytoplasmic ATP levels fall below the thresholds required for processing the ATP-dependent apoptotic cascade and the cell dies from necrosis. Both types of death can be grouped together as a mitochondrial cell death (MCD). However, there exist multiple adaptive reactions aimed at protecting cells against CED. In this context, a metabolic shift characterized by suppression of OXPHOS combined with activation of aerobic glycolysis as the main pathway for ATP synthesis (Warburg effect) is of central importance. Whereas this type of adaptation is sufficiently effective to avoid CED and to control the cellular redox state, thereby ensuring the cell survival, it also favors the avoidance of apoptotic cell death. This scenario may underlie uncontrolled cellular proliferation and growth, eventually resulting in carcinogenesis

Technological elites, the meritocracy, and postracial myths in Silicon Valley

Entre as modernas elites tecnológicas digitais, os mitos da meritocracia e da façanha intelectual são usados como marcadores de raça e gênero por uma supremacia branca masculina que consolida recursos de forma desproporcional em relação a pessoas não brancas, principalmente negros, latinos e indígenas. Os investimentos em mitos meritocráticos suprimem os questionamentos de racismo e discriminação, mesmo quando os produtos das elites digitais são infundidos com marcadores de raça, classe e gênero. As lutas históricas por inclusão social, política e econômica de negros, mulheres e outras classes desprotegidas têm implicado no reconhecimento da exclusão sistêmica, do trabalho forçado e da privação de direitos estruturais, além de compromissos com políticas públicas dos EUA, como as ações afirmativas, que foram igualmente fundamentais para reformas políticas voltadas para participação e oportunidades econômicas. A ascensão da tecnocracia digital tem sido, em muitos aspectos, antitética a esses esforços no sentido de reconhecer raça e gênero como fatores cruciais para inclusão e oportunidades tecnocráticas. Este artigo explora algumas das formas pelas quais os discursos das elites tecnocráticas do Vale do Silício reforçam os investimentos no pós racialismo como um pretexto para a re-consolidação do capital em oposição às políticas públicas que prometem acabar com práticas discriminatórias no mundo do trabalho. Por meio de uma análise cuidadosa do surgimento de empresas de tecnologias digitais e de uma discussão sobre como as elites tecnológicas trabalham para mascarar tudo, como inscrições algorítmicas e genéticas de raça incorporadas em seus produtos, mostramos como as elites digitais omitem a sua responsabilidade por suas reinscrições pós raciais de (in)visibilidades raciais. A partir do uso de análise histórica e crítica do discurso, o artigo revela como os mitos de uma meritocracia digital baseados em um “daltonismo racial” tecnocrático emergem como chave para a manutenção de exclusões de gênero e raça.Palavras-chave: Tecnologia. Raça. Gênero.Among modern digital technology elites, myths of meritocracy and intellectual prowess are used as racial and gender markers of white male supremacy that disproportionately consolidate resources away from people of color, particularly African Americans, Latino/as and Native Americans. Investments in meritocratic myths suppress interrogations of racism and discrimination even as the products of digital elites are infused with racial, class, and gender markers. Longstanding struggles for social, political, and economic inclusion for African Americans, women, and other legally protected classes have been predicated upon the recognition of systemic exclusion, forced labor, and structural disenfranchisement, and commitments to US public policies like affirmative action have, likewise, been fundamental to political reforms geared to economic opportunity and participation. The rise of the digital technocracy has, in many ways, been antithetical to these sustained efforts to recognize race and gender as salient factors structuring technocratic opportunity and inclusion. This paper explores some of the ways in which discourses of Silicon Valley technocratic elites bolster investments in post-racialism as a pretext for re-consolidations of capital, in opposition to public policy commitments to end discriminatory labor practices. Through a careful analysis of the rise of digital technology companies, and a discussion of how technology elites work to mask everything from algorithmic to genetic inscriptions of race embedded in their products, we show how digital elites elide responsibility for their post-racial re-inscriptions of racial visibilities (and invisibilities). Using historical and critical discourse analysis, the paper reveals how myths of a digital meritocracy premised on a technocratic colorblindness emerge key to perpetuating gender and racial exclusions.Keywords: Technology. Race. Gender