bluuebunny/crossref_metadata_2025 huggingface dataset:
Crocodile Head Scales Are Not Developmental Units But Emerge from Physical Cracking
Authors: Milinkovitch Michel C. , Manukyan Liana , Debry Adrien , Di-Poï Nicolas , Martin Samuel , Singh Daljit , Lambert Dominique , Zwicker Matthias
Published: November 2012

How the Crocodile Got Its Scales

Mammalian hairs, avian feathers, and reptile scales differentiate and grow from genetically controlled units. Using three-dimensional (3D) computer graphics and computational biology to study scale generation,

Milinkovitch
et al.

(p.
78
, published online 29 November; see the cover) show that crocodilians' face and jaw scales do not follow this rule but emerge by physical cracking of the developing skin in a tension field. Thus, a crocodile's head scales are not genetically controlled developmental units but are random polygonal domains of keratinized skin that are generated from a self-organizing physical process.
Apatite
4
He/
3
He and (U-Th)/He Evidence for an Ancient Grand Canyon
Authors: Flowers R. M. , Farley K. A.
Published: November 2012

A Grand Old Canyon

In the southwestern United States, the Grand Canyon is a striking example of the power of erosion over time. Over millions of years, flowing river water carved out the canyon that today measures over 1.6 km deep and 29 km long. Most models posit that the majority of the canyon formed 5 to 6 million years ago. Using thermochronometry,
Flowers and Farley
(p.
1616
, published online 29 November) examined the temperature-dependent diffusion of helium within mineral grains representative of the canyon basement, which cools as erosion brings crustal rocks near the surface. After validating the approach across the younger eastern canyon, the model suggests that the western canyon experienced an ancient cooling event induced by erosional processes, such that the canyon likely reached near modern depths by 70 million years ago—nearly 60 million years earlier than generally believed.
Sonication of Explanted Cardiac Implants Improves Microbial Detection in Cardiac Device Infections
Authors: Oliva Alessandra , Nguyen Bich Lien , Mascellino Maria T. , D'Abramo Alessandra , Iannetta Marco , Ciccaglioni Antonio , Vullo Vincenzo , Mastroianni Claudio M.
Published: November 2012

The sonication technique has been shown to be a promising tool for microbiological diagnosis of device-related infections. We evaluated the usefulness of the sonication method for pathogen detection in 80 explanted cardiac components collected from 40 patients, and the results were compared with those of conventional cultures. Forty subjects undergoing cardiac device removal were studied: 20 had cardiac device infection, and 20 subjects underwent elective generator replacement or revision in the absence of infection. Sonication of explanted devices was more sensitive than traditional culture for microbial detection (67% and 50%, respectively;
P
= 0.0005). The bacterial count detected in sonication fluid culture was significantly higher than that detected in traditional culture in both infected (
P
= 0.019) and uninfected (
P
= 0.029) devices. In the infected patients, sonication fluid culture yielded a significantly higher rate of pathogen detection in explanted electrodes than traditional culture (65% versus 45%;
P
= 0.02), while no differences were found in the generators. Ten strains were detected only through sonication fluid culture: 6
Staphylococcus epidermidis
strains, 1
Staphylococcus hominis
strain, 2
Corynebacterium striatum
strains, and 1
Brevundimonas
sp. Neither the type nor the duration of antimicrobial therapy before device removal had an effect on the diagnostic performance of sonication fluid culture (
P
= 0.75 and
P
= 0.56, respectively). In the patients without infection, sonication fluid culture was positive in 8 cases (40%), whereas conventional culture was positive in only 4 (20%). In summary, the sonication technique improves the microbiological diagnosis of explanted cardiac devices.
Receptor Characterization and Susceptibility of Cotton Rats to Avian and 2009 Pandemic Influenza Virus Strains
Authors: Blanco Jorge C. G. , Pletneva Lioubov M. , Wan Hongquan , Araya Yonas , Angel Matthew , Oue Raymonde O. , Sutton Troy C. , Perez Daniel R.
Published: November 2012

Animal influenza viruses (AIVs) are a major threat to human health and the source of pandemic influenza. A reliable small-mammal model to study the pathogenesis of infection and for testing vaccines and therapeutics against multiple strains of influenza virus is highly desirable. We show that cotton rats (
Sigmodon hispidus
) are susceptible to avian and swine influenza viruses. Cotton rats express α2,3-linked sialic acid (SA) and α2,6-linked SA residues in the trachea and α2,6-linked SA residues in the lung parenchyma. Prototypic avian influenza viruses (H3N2, H9N2, and H5N1) and swine-origin 2009 pandemic H1N1 viruses replicated in the nose and in the respiratory tract of cotton rats without prior adaptation and produced strong lung pathology that was characterized by early lung neutrophilia, followed by subsequent pneumonia. Consistent with other natural and animal models of influenza, only the H5N1 virus was lethal for cotton rats. More importantly, we show that the different avian and pandemic H1N1 strains tested are strong activators of the type I interferon (IFN)-inducible MX-1 gene both locally and systemically. Our data indicate that the cotton rat is a suitable small-mammal model to study the infection of animal influenza viruses and for validation of vaccines and therapeutics against these viruses.
Intramuscular Inoculation of Mice with the Live-Attenuated Recombinant Rabies Virus TriGAS Results in a Transient Infection of the Draining Lymph Nodes and a Robust, Long-Lasting Protective Immune Response against Rabies
Authors: Schutsky Keith , Curtis Dana , Bongiorno Emily K. , Barkhouse Darryll A. , Kean Rhonda B. , Dietzschold Bernhard , Hooper D. Craig , Faber Milosz
Published: November 2012

A single intramuscular application of the live but not UV-inactivated recombinant rabies virus (RABV) variant TriGAS in mice induces the robust and sustained production of RABV-neutralizing antibodies that correlate with long-term protection against challenge with an otherwise lethal dose of the wild-type RABV. To obtain insight into the mechanism by which live TriGAS induces long-lasting protective immunity, quantitative PCR (qPCR) analysis of muscle tissue, draining lymph nodes, spleen, spinal cord, and brain at different times after TriGAS inoculation revealed the presence of significant copy numbers of RABV-specific RNA in muscle, lymph node, and to a lesser extent, spleen for several days postinfection. Notably, no significant amounts of RABV RNA were detected in brain or spinal cord at any time after TriGAS inoculation. Differential qPCR analysis revealed that the RABV-specific RNA detected in muscle is predominantly genomic RNA, whereas RABV RNA detected in draining lymph nodes is predominantly mRNA. Comparison of genomic RNA and mRNA obtained from isolated lymph node cells showed the highest mRNA-to-genomic-RNA ratios in B cells and dendritic cells (DCs), suggesting that these cells represent the major cell population that is infected in the lymph node. Since RABV RNA declined to undetectable levels by 14 days postinoculation of TriGAS, we speculate that a transient infection of DCs with TriGAS may be highly immunostimulatory through mechanisms that enhance antigen presentation. Our results support the superior efficacy and safety of TriGAS and advocate for its utility as a vaccine.
Tombusvirus Y-Shaped Translational Enhancer Forms a Complex with eIF4F and Can Be Functionally Replaced by Heterologous Translational Enhancers
Authors: Nicholson Beth L. , Zaslaver Olga , Mayberry Laura K. , Browning Karen S. , White K. Andrew
Published: November 2012

Certain plus-strand RNA plant viruses that are uncapped and nonpolyadenylated rely on RNA elements in their 3′ untranslated region, termed 3′-cap-independent translational enhancers (3′CITEs), for efficient translation of their proteins. Here, we have investigated the properties of the Y-shaped class of 3′CITE present in the tombusvirus
Carnation Italian ringspot virus
(CIRV). While some types of 3′CITE have been found to function through recruitment of translation initiation factors to the viral genome, no
trans
-acting translation-related factors have yet been identified for the Y-shaped 3′CITE. Our results indicate that the CIRV 3′CITE complexes with eIF4F and eIFiso4F, with the former mediating translation more efficiently than the latter. In nature, some classes of 3′CITE are present in several different viral genera, suggesting that these elements hold a high degree of modularity. Here, we test this concept by engineering chimeric viruses containing heterologous 3′CITEs and show that the Y-shaped class of 3′CITE in CIRV can be replaced by two alternative types of 3′CITE, i.e., a
Panicum mosaic virus
-like 3′CITE or an I-shaped 3′CITE, without any major loss in
in vitro
translation or replication efficiency in protoplasts. The heterologous 3′CITEs also mediated whole-plant infections of
Nicotiana benthamiana
, where distinct symptoms were observed for each of the alternative 3′CITEs and 3′CITE evolution occurred during serial passaging. Our results supply new information on Y-shaped 3′CITE function and provide insights into 3′CITE virus-host compatibilities.
Analysis of Viral Membranes Formed in Cells Infected by a Vaccinia Virus L2-Deletion Mutant Suggests Their Origin from the Endoplasmic Reticulum
Authors: Maruri-Avidal Liliana , Weisberg Andrea S. , Bisht Himani , Moss Bernard
Published: November 2012

Assembly of the poxvirus immature virion (IV) membrane is a poorly understood event that occurs within the cytoplasm. At least eight viral proteins participate in formation of the viral membrane. Of these, A14, A17, and D13 are structural components whereas A6, A11, F10, H7, and L2 participate in membrane biogenesis. L2, the object of this study, is conserved in all chordopoxviruses, expressed early in infection, and associated with the endoplasmic reticulum (ER) throughout the cell and at the edges of crescent-shaped IV precursors. Previous studies with an inducible L2 mutant revealed abortive formation of the crescent membrane. However, possible low-level L2 synthesis under nonpermissive conditions led to ambiguity in interpretation. Here, we constructed a cell line that expresses L2, which allowed the creation of an L2-deletion mutant. In noncomplementing cells, replication was aborted prior to formation of mature virions and two types of aberrant structures were recognized. One consisted of short crescents, at the surface of dense masses of viroplasm, which were labeled with antibodies to the A11, A14, A17, and D13 proteins. The other structure consisted of “empty” IV-like membranes, also labeled with antibodies to the viral proteins, which appeared to be derived from adjacent calnexin-containing ER. A subset of 25 proteins examined, exemplified by components of the entry-fusion complex, were greatly diminished in amount. The primary role of L2 may be to recruit ER and modulate its transformation to viral membranes in juxtaposition with the viroplasm, simultaneously preventing the degradation of viral proteins dependent on viral membranes for stability.
Neurotropic Arboviruses Induce Interferon Regulatory Factor 3-Mediated Neuronal Responses That Are Cytoprotective, Interferon Independent, and Inhibited by Western Equine Encephalitis Virus Capsid
Authors: Peltier Daniel C. , Lazear Helen M. , Farmer Jocelyn R. , Diamond Michael S. , Miller David J.
Published: November 2012

Cell-intrinsic innate immune responses mediated by the transcription factor interferon regulatory factor 3 (IRF-3) are often vital for early pathogen control, and effective responses in neurons may be crucial to prevent the irreversible loss of these critical central nervous system cells after infection with neurotropic pathogens. To investigate this hypothesis, we used targeted molecular and genetic approaches with cultured neurons to study cell-intrinsic host defense pathways primarily using the neurotropic alphavirus western equine encephalitis virus (WEEV). We found that WEEV activated IRF-3-mediated neuronal innate immune pathways in a replication-dependent manner, and abrogation of IRF-3 function enhanced virus-mediated injury by WEEV and the unrelated flavivirus St. Louis encephalitis virus. Furthermore, IRF-3-dependent neuronal protection from virus-mediated cytopathology occurred independently of autocrine or paracrine type I interferon activity. Despite being partially controlled by IRF-3-dependent signals, WEEV also disrupted antiviral responses by inhibiting pattern recognition receptor pathways. This antagonist activity was mapped to the WEEV capsid gene, which disrupted signal transduction downstream of IRF-3 activation and was independent of capsid-mediated inhibition of host macromolecular synthesis. Overall, these results indicate that innate immune pathways have important cytoprotective activity in neurons and contribute to limiting injury associated with infection by neurotropic arboviruses.
Acute lower back pain mapped by dermatomal scarification in urban Malawi
Authors: Lo Tammy , Tindall Alistair
Published: November 2012

Lower back pain is a problem that affects many and generates an economic burden on the National Health Service. In modern days, although it is tempting to rely on specialist imaging for the initial investigation of back pain, it is often unnecessary. Comprehensive clinical examination is immediately available and should detect neurological impairments where they exist. A 32-year-old man from Malawi presented to clinic with lower back pain radiating to the right leg. Inspection revealed traditional scarification marks along the classical path of lumbar nerve root, which coincided with his L5 dermatomal pain. The distribution of his ‘Mphini’ along the typical path of lumbar nerve was identical to his myelography. This report strongly illustrates that in the Western medical setting, accurate history and examination would have allowed correct interpretation of these symptoms and correctly indicated the need for myelography.
Pancreatic pseudocyst formation due to non-traumatic pancreatitis in a 3-year-old child
Authors: Chaudhari Hemang D , Bhatt Chhaya J , Desai Aditi B , Patel Nupur K
Published: November 2012

A pancreatic pseudocyst is a localised collection of pancreatic secretions that lacks a true epithelial lining and is walled off by granulation tissue. A rare case of pancreatic pseudocyst formation due to non-traumatic pancreatitis in a 3-year-old boy is described. The child was presented with fever, abdominal pain and vomiting for a period of 5 days. Ultrasonography and CT scan examinations were performed and biochemical and haematological investigations were undertaken. A pancreatic pseudocyst was identified and operatively managed by cystogastrostomy.
Pop-provoked paralysis: silent Graves’ disease presenting as thyrotoxic periodic paralysis
Authors: Sehmer Benjamin , Arnason Terra
Published: November 2012

A 48-year-old Filipino man presented after several episodes of worsening limb paralysis that occurred after drinking cola beverages. In the emergency department he was found to be hypokalaemic, and although he exhibited no symptoms of thyrotoxicosis he was biochemically hyperthyroid. Thyroid stimulating hormone receptor antibody serology was positive indicating Graves’ disease as the underlying cause of his hyperthyroidism. Intravenous potassium supplementation resulted in complete resolution of symptoms, and a diagnosis of thyrotoxic periodic paralysis was made. He was started on a regimen of propylthiouracil and propranolol and subsequently given radioiodine as the definitive treatment for Graves’ disease. There were no recurrent attacks of paralysis once a stable euthyroid state was achieved, and the patient was able to resume cola consumption without issue.
Stem cells, angiogenesis and muscle healing: a potential role in massage therapies?
Authors: Best Thomas M , Gharaibeh Burhan , Huard Johnny
Published: November 2012

Skeletal muscle injuries are among the most common and frequently disabling injuries sustained by athletes.

Repair of injured skeletal muscle is an area that continues to present a challenge for sports medicine clinicians and researchers due, in part, to complete muscle recovery being compromised by development of fibrosis leading to loss of function and susceptibility to re-injury.

Injured skeletal muscle goes through a series of coordinated and interrelated phases of healing including degeneration, inflammation, regeneration and fibrosis. Muscle regeneration initiated shortly after injury can be limited by fibrosis which affects the degree of recovery and predisposes the muscle to reinjury. It has been demonstrated in animal studies that antifibrotic agents that inactivate transforming growth factor (TGF)-β1 have been effective at decreasing scar tissue formation. Several studies have also shown that vascular endothelial growth factor (VEGF) can increase the efficiency of skeletal muscle repair by increasing angiogenesis and, at the same time, reducing the accumulation of fibrosis. We have isolated and thoroughly characterised a population of skeletal muscle-derived stem cells (MDSCs) that enhance repair of damaged skeletal muscle fibres by directly differentiating into myofibres and secreting paracrine factors that promote tissue repair. Indeed, we have found that MDSCs transplanted into skeletal and cardiac muscles have been successful at repair probably because of their ability to secrete VEGF that works in a paracrine fashion. The application of these techniques to the study of sport-related muscle injuries awaits investigation. Other useful strategies to enhance skeletal muscle repair through increased vascularisation may include gene therapy, exercise, neuromuscular electrical stimulation and, potentially, massage therapy. Based on recent studies showing an accelerated recovery of muscle function from intense eccentric exercise through massage-based therapies, we believe that this treatment modality offers a practical and non-invasive form of therapy for skeletal muscle injuries. However, the biological mechanism(s) behind the beneficial effect of massage are still unclear and require further investigation using animal models and potentially randomised, human clinical studies.
Public perceptions and behaviours related to the risk of infection with Aedes mosquito-borne diseases: a cross-sectional study in Southeastern France
Authors: Raude Jocelyn , Chinfatt Kimberly , Huang Peiching , Betansedi Charles Olivier , Katumba Kenneth , Vernazza Nicole , Bley Daniel
Published: November 2012

Objectives

To explore public perceptions and behaviours related to the risk of flavivirus and alphavirus infection in Southeastern regions of France following the recent colonisation of the Asian tiger mosquito,Aedes albopictus, and the identification of four autochthonous cases of dengue and chikungunya fever in these regions.

Design

Cross-sectional telephone survey using a proportional random digit dialling selection method.

Setting

Interviews were conducted from 28 November 2011 to 29 January 2012 using a computer-assisted telephone interviewing system.

Participants

1506 French speaking adults aged 18 years or older residing in French Mediterranean regions.

Results

Protective health behaviours were found to be performed less frequently among men (AOR=0.65, 95% CI 0.52% to 0.80%), residents with lower educational status (AOR=0.61, 95% CI 0.43% to 0.85% for respondents with primary school education; AOR=0.69, 95% CI 0.53% to 0.90% for those with some secondary school education), and those living in regions where the Aedes mosquito is objectively rare (AOR=0.60, 95% CI 0.36% to 0.98% for Aude; AOR=0.63, 95% CI 0.44% to 0.89% for Herault; AOR=0.56, 95% CI 0.34% to 0.93% for Eastern Pyrenees). Empirical results also suggest that behavioural responses to infection risk are greater shaped by the perceived exposure to Aedes, notably the perceived frequency of mosquito bites (AOR=2.07, 95% CI 1.84% to 2.32%) and visual identification of Aedes mosquitoes in one's immediate environment (AOR=1.98, 95% CI 1.45% to 2.71%) rather than by other common predictors of protective behaviours.

Conclusions

These findings may help with the development of innovative instruments designed to make more visible and personal the threat of flavivirus and alphavirus infections induced by the presence ofA albopictusin order to promote significant behavioural changes among populations at risk.
Interpretation of postmortem forensic toxicology results for injury prevention research
Authors: Drummer Olaf H , Kennedy Briohny , Bugeja Lyndal , Ibrahim Joseph Elias , Ozanne-Smith Joan
Published: November 2012

Forensic toxicological data provides valuable insight into the potential contribution of alcohol and drugs to external-cause deaths. There is a paucity of material that guides injury researchers on the principles that need to be considered when examining the presence and contribution of alcohol and drugs to these deaths. This paper aims to describe and discuss strengths and limitations of postmortem forensic toxicology sample selection, variations in analytical capabilities and data interpretation for injury prevention research. Issues to be considered by injury researchers include: the circumstances surrounding death (including the medical and drug use history of the deceased person); time and relevant historical factors; postmortem changes (including redistribution and instability); laboratory practices; specimens used; drug concentration; and attribution of contribution to death. This paper describes the range of considerations for testing and interpreting postmortem forensic toxicology, particularly when determining impairment or toxicity as possible causal factors in injury deaths. By describing these considerations, this paper has application to decisions about study design and case inclusion in injury prevention research, and to the interpretation of research findings.
Effects of urethane on reflex activity of lower urinary tract in decerebrate unanesthetized rats
Authors: Yoshiyama Mitsuharu , Roppolo James R. , Takeda Masayuki , de Groat William C.
Published: November 2012

Effects of urethane on lower urinary tract function were examined in decerebrate unanesthetized rats. During single slow infusion (0.04 ml/min) cystometrograms (CMGs), urethane (0.3 g/kg) increased micturition pressure threshold (PT) by 73%, postvoid residual volume (RV) by 425%, and decreased voiding efficiency (VE) by 57%, but did not change maximal voiding pressure (MVP), closing peak pressure (CPP), bladder compliance, bladder contraction duration (BCD), or volume threshold (VT) for inducing micturition. Lower doses (0.01–0.1 g/kg) did not alter any parameter. During continuous fast infusion (0.21 ml/min) CMGs, urethane at doses of 0.6–1.2 g/kg (iv) markedly decreased CPP by 69–85%, whereas only the largest dose (1.2 g/kg iv) decreased MVP and external urethral sphincter electromyogram activity by 42 and by 80%, respectively. Doses of 0.001–0.6 g/kg did not alter the intercontraction interval and BCD. Taken together, these results suggest that urethral activity, which is essential for efficient voiding, is more sensitive to the suppressive effect of urethane than afferent or efferent mechanisms controlling the bladder. The threshold dose of MK-801 (0.3 mg/kg), an NMDA antagonist, required to decrease MVP and increase VT in urethane (1.2 g/kg)-anesthetized rats, only increased VT in rats treated with a subanesthetic dose of urethane (0.3 g/kg), suggesting a higher sensitivity of the afferent vs. efferent limb of the micturition reflex pathway to urethane-MK-801 interactions. Because effects of urethane persisted after removal of the forebrain, they must be mediated by actions on the brain stem, spinal cord, or peripheral nervous system.
Differential effects of mild central hypovolemia with furosemide administration vs. lower body suction on dynamic cerebral autoregulation
Authors: Ogawa Yojiro , Aoki Ken , Kato Jitsu , Iwasaki Ken-ichi
Published: November 2012

Diuretic-induced mild hypovolemia with hemoconcentration reportedly improves dynamic cerebral autoregulation, whereas central hypovolemia without hemoconcentration induced by lower body negative pressure (LBNP) has no effect or impairs dynamic cerebral autoregulation. This discrepancy may be explained by different blood properties, by degrees of central hypovolemia, or both. We investigated the effects of equivalent central hypovolemia induced by furosemide administration or LBNP application on dynamic cerebral autoregulation to test our hypothesis that mild central hypovolemia due to furosemide administration enhances dynamic cerebral autoregulation in contrast to LBNP. Seven healthy male subjects received 0.4 mg/kg furosemide and LBNP, with equivalent decreases in central venous pressure (CVP). Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between beat-to-beat mean arterial blood pressure (MAP) and mean cerebral blood flow velocity (MCBFV). CVP decreased by ∼3–4 mmHg with both furosemide administration (∼26 mg) and LBNP (approximately −20 mmHg). Steady state MCBFV remained unchanged with both techniques, whereas MAP increased significantly with furosemide administration. Coherence and transfer function gain in the low and high frequency ranges with hypovolemia due to furosemide administration were significantly lower than those due to LBNP (ANOVA interaction effects, P < 0.05), although transfer function gain in the very low frequency range did not change. Our results suggest that although the decreases in CVP were equivalent between furosemide administration and LBNP, the resultant central hypovolemia differentially affected dynamic cerebral autoregulation. Mild central hypovolemia with hemoconcentration resulting from furosemide administration may enhance dynamic cerebral autoregulation compared with LBNP.
Synaptic transmission at parasympathetic neurons of the major pelvic ganglion from normal and diabetic male mice
Authors: Tompkins John D. , Vizzard Margaret A. , Parsons Rodney L.
Published: November 2012

Bladder and erectile dysfunction are common urologic complications of diabetes and are associated with reduced parasympathetic autonomic control. To determine whether disruption of ganglionic neurotransmission contributes to the loss of function, we investigated synaptic transmission at parasympathetic, major pelvic ganglion (MPG) neurons in control and chronically (20 wk) diabetic mice. In contrast to what has been reported for sympathetic neurons, diabetes did not cause an interruption of synaptic transmission at parasympathetic MPG neurons from streptozotocin-treated C57BL/6J (STZ) or db/db mice. Cholinergically mediated excitatory postsynaptic potentials (EPSPs) were suprathreshold during 5-s trains of 5-, 10-, and 20-Hz stimuli. Asynchronous neurotransmitter release, observed as miniature EPSPs (mEPSPs) during and after stimulation, permitted quantitative assessment of postganglionic, cholinergic receptor sensitivity. mEPSP amplitude following tetanic stimulation (recorded at −60 mV) was reduced in STZ (4.95 ± 0.4 vs. 3.71 ± 0.3 mV, P = 0.03), but not db/db mice. The number of posttetanic mEPSPs was significantly greater in db/db mice at all frequencies tested. Assessment of basic electrophysiological properties revealed that parasympathetic MPG neurons from db/db mice had less negative membrane potentials, lower input resistances, and shorter afterhyperpolarizations relative to their control. MPG neurons from STZ had longer afterhyperpolarizations but were otherwise similar to controls. Membrane excitability, measured by the membrane responsiveness to long-duration (1 s), suprathreshold depolarizing pulses, was unchanged in either model. The present study indicates that, while parasympathetic neurotransmission at the MPG is intact in chronically diabetic mice, obese, type 2 diabetic animals exhibit an altered presynaptic regulation of neurotransmitter release.
Targeting Folate Receptors to Treat Invasive Urinary Bladder Cancer
Authors: Dhawan Deepika , Ramos-Vara José A. , Naughton James F. , Cheng Liang , Low Philip S. , Rothenbuhler Ryan , Leamon Christopher P. , Parker Nikki , Klein Patrick J. , Vlahov Iontcho R. , Reddy Joseph A. , Koch Michael , Murphy Linda , Fourez Lindsey M. , Stewart Jane C. , Knapp Deborah W.
Published: November 2012

Folate receptors (FR) may be of use for targeted delivery of cytotoxic drugs in invasive urothelial carcinoma (iUC), for which improved therapy is needed. FR expression and function in iUC were explored and the antitumor activity and toxicity of a folate-targeted vinblastine conjugate were evaluated in dogs with naturally occurring iUC, an excellent model for human iUC. FR immunohistochemistry was carried out on iUC and normal human and dog bladder tissues together with nuclear scintigraphy in dogs to monitor iUC folate uptake. Dose escalation of a folate-targeted vinblastine compound, EC0905, was conducted in dogs with biopsy-confirmed, FR-positive iUC. FRs were detected by immunohistochemistry (PU17) in most primary iUC and many nodal and lung metastases from dogs, and scintigraphy confirmed folate uptake in both primary and metastatic lesions. The maximum tolerated dose of EC0905 in dogs was 0.25 mg/kg IV weekly, with neutropenia at higher doses. Tumor responses included partial remission (≥50% reduction in tumor volume) in five dogs and stable disease (<50% change in tumor volume) in four dogs. Immunoreactivity to PU17 was similar in humans (78% of primary iUC, 80% of nodal metastases). Less immunoreactivity to mab343 (22% of cases) occurred. FR-β was noted in 21% of human iUC cases. Our findings suggest folate-targeted therapy holds considerable promise for treating iUC, where FR-β may be important in addition to FR-α. Cancer Res; 73(2); 875–84. ©2012 AACR.
Spontaneous Recovery of Ventilator-Associated Pneumothorax
Authors: Wu Shin-Hwar , Horng Ming-Hwarng , Lin Kai-Huang , Hsu Wu-Huei
Published: November 2012

Background: The usual management of ventilator-associated pneumothorax (VPX) is tube thoracostomy. However, this recommendation is based on tradition rather than on solid evidence. Although it has been applied successfully to other types of pneumothoraces, observation has not been used in the management of VPX. Objectives: In this study, we investigated whether observation is a valid treatment strategy for VPX. Methods: We retrospectively analyzed data of 471 patients with VPX (2003-2010) and found that 27 did not receive tube thoracostomy. Most of those patients (89%) had documented do-not-resuscitate orders and had refused tube thoracostomy. For comparison, 54 patients with tube thoracostomy, matched by age and do-not-resuscitate status, were chosen as controls. Among patients without tube thoracostomy, we compared attribute differences between those recovered and those not recovered. Results: Thirteen patients (48%) without tube thoracostomy experienced spontaneous recovery of their pneumothoraces. This rate of chest tube-free recovery was higher than that of patients with tube thoracostomy (48 vs. 17%; p = 0.003). The patients did not differ in in-hospital mortality rate, time to ventilator discontinuation or survival. By univariate logistic regression, spontaneous recovery was associated with VPX caused by needle puncture, lack of respiratory distress, large tidal volume and low oxygen requirement following pneumothorax, as well as by physician recommendation against intubation. Conclusion: Observation under physician surveillance is an effective option of managing many VPXs, especially those caused by needle puncture, when patients are not in respiratory distress or when patients have acceptable tidal volumes and oxygen requirements following pneumothorax.
Dental Caries from a Molecular Microbiological Perspective
Authors: Nyvad B. , Crielaard W. , Mira A. , Takahashi N. , Beighton D.
Published: November 2012

Dental caries results from an imbalance of the metabolic activity in the dental biofilm. The microbial communities of teeth have traditionally been studied by standard cultural approaches. More recently, cloning and sequencing of the 16S rRNA gene have been used to characterize the microbial composition of the oral biofilm, but the methodological limitations of this approach have now been recognized. Next-generation high-throughput sequencing methods have the potential to reveal the composition and functioning of the biofilm by means of metagenomic and metatranscriptomic analyses. Currently available high-throughput sequencing approaches are reviewed and discussed in relation to studying the biofilm associated with dental caries. Important in understanding the dynamic processes in caries is the metabolic activity of the biofilm; metabolome analysis is a new tool that might enable us to assess such activity. As caries is a localized disease, it is essential that biofilm samples are taken from precisely determined tooth sites; pooling samples is not appropriate. This paper presents the case that culture-based studies are important, but that the fullest understanding of the role of the biofilm in the caries process will only come from an integrated approach determining biological function and metabolic output.
Distinct roles for the α, β and γ1 isoforms of protein phosphatase 1 in the outside-in αIIbβ3 integrin signalling-dependent functions
Authors: Khatlani Tanvir , Kailasam Lavanya , Alrehani Nawaf , Pradhan Subhashree , Vijayan Vinod K.
Published: November 2012

Although protein kinases and phosphatases participate in integrin αIIbβ3 signalling, whether integrin functions are regulated by the catalytic subunit of protein phosphatase 1 (PP1c) isoforms are unclear. We show that siRNA mediated knockdown of all PP1c isoforms (α, β and γ1) in 293 αIIbβ3 cells decreased adhesion to immobilised fibrinogen and fibrin clot retraction. Selective knockdown of only PP1cγ1 did not alter adhesion or clot retraction, while depletion of PP1cβ decreased both functions. Unexpectedly, knockdown of PP1cα enhanced αIIbβ3 adhesion to fibrinogen and clot retraction. Protein interaction studies revealed that all PP1c isoforms can interact with the integrin αIIb subunit. Phospho-profiling studies revealed an enhanced activation of mitogen- activated protein kinase (MAPK) p38 in the PP1cα depleted cells. Enhanced adhesive phenotype displayed by the PP1cα-depleted 293 αIIbβ3 cells was blocked by pharmacological inhibition of p38. Conversely, the decreased adhesion of PP1cα overexpressing cells was rescued by the expression of constitutively active p38α or p38γ. Thus, PP1c isoforms have distinct contribution to the outside-in αIIbβ3 signalling- dependent functions in 293 αIIbβ3 cells. Moreover, PP1cα negatively regulates integrin function by suppressing the p38 pathway.
Risk of recurrence in patients with pulmonary embolism: Predictive role of D-dimer and of residual perfusion defects on lung scintigraphy
Authors: Cenci Caterina , Antonucci Emilia , Grifoni Elisa , Arcangeli Chiara , Prisco Domenico , Abbate Rosanna , Miniati Massimo , Poli Daniela
Published: November 2012

The stratification of recurrence risk after a first episode of venous thromboembolism (VTE) is an important topic of research, especially in patients with pulmonary embolism (PE). Elevated D-dimer levels and residual vein obstruction (RVO) at compression ultrasonography have been studied as predictors of recurrence after withdrawing oral anticoagulant treatment (OAT). It is still unknown if residual perfusion defects (PD) on lung scintigraphy are related to recurrent PE. In the present study, we evaluated the association of PD with PE recurrence. The relationship between PD, elevated D-dimer levels, and RVO was also investigated. We prospectively followed 236 consecutive patients who survived a first episode of objectively confirmed PE, with or without deep-vein thrombosis. After at least three months of OAT, treatment was withdrawn in 139 patients. D-dimer levels were evaluated at one month of OAT withdrawal, RVO was measured, and perfusion lung scan (P-scan) was performed to evaluate PD. During follow-up, 20 patients experienced a recurrent episode of VTE. Elevated D-dimer levels were significantly associated with VTE recurrence, (p=0.003). RVO was present in 22% of the patients with recurrence and in 7.5% of those without (p=0.07). No significant association was found between PD >10% and VTE recurrence, D-dimer, or RVO. In conclusion, we confirmed the positive predictive value of elevated D-dimer levels for recurrent VTE. Residual PD on lung scintigraphy are neither predictive of recurrence nor related to D-dimer levels or RVO.
Association of the
miR-146a
,
miR-149
,
miR-196a2
, and
miR-499
Polymorphisms With Ischemic Stroke and Silent Brain Infarction Risk
Authors: Jeon Young Joo , Kim Ok Joon , Kim Su Yeoun , Oh Seung Hun , Oh Doyeun , Kim Ok Jun , Shin Byoung Soo , Kim Nam Keun
Published: November 2012

Objective—

MicroRNAs play a role in atherosclerosis-related diseases, such as cerebrovascular or cardiovascular disease. However, the effect of
miR-146a
,
miR-149
,
miR-196a2
, and
miR-499
polymorphisms on stroke and silent brain infarction (SBI) susceptibility has not been reported.

Methods and Results—

Using polymerase chain reaction-amplified DNA, microRNA polymorphisms were analyzed in 678 patients with ischemic stroke, 373 patients with SBI, and 553 control subjects. The
miR-146a
C>G polymorphism and
miR-146a
G/
-149
T/
-196a2
C/
-499
G allele combination was significantly associated with ischemic stroke prevalence. For SBI prevalence, there were no statistically significant genetic markers. However, some allele combinations were associated with increased SBI incidence (C-T-C-G and G-T-T-A of
miR-146a
/
-149
/
-196a2
/
-499
). In subgroup analyses,
miR-146a
C>G increased stroke risk in female, normotensive, and nondiabetic groups. There were significant combined effects between microRNA polymorphisms and homocysteine/folate levels on ischemic stroke and SBI prevalence.

Conclusion—

The
miR-146a
G allele and
miR-146a
G/
-149
T/
-196a2
C/
-499
G allele combination were associated with ischemic stroke pathogenesis. The combined effects between microRNA polymorphisms and homocysteine/folate levels may contribute to stroke and SBI prevalence.
Adrenal-Specific Scavenger Receptor BI Deficiency Induces Glucocorticoid Insufficiency and Lowers Plasma Very-Low-Density and Low-Density Lipoprotein Levels in Mice
Authors: Hoekstra Menno , van der Sluis Ronald J. , Van Eck Miranda , Van Berkel Theo J.C.
Published: November 2012

Objective—

We determined the physiological consequences of adrenocortical-specific deletion of scavenger receptor BI (SR-BI) function in C57BL/6 wild-type mice.

Methods and Results—

One adrenal from 10-day-old SR-BI knockout (KO) mice or wild-type controls was transplanted under the renal capsule of adrenalectomized C57BL/6 recipient mice. The fasting plasma corticosterone level increased over time in transplanted mice. Corticosterone values in SR-BI KO transplanted mice remained ≈50% lower (
P
<0.001) as compared with wild-type transplanted mice, which coincided with adrenocortical lipid depletion. A 6.5-fold higher (
P
<0.01) plasma adrenocorticotropic hormone level was present in SR-BI KO transplanted mice reminiscent of primary glucocorticoid insufficiency. On feeding with cholic acid-containing high cholesterol/high fat diet, SR-BI KO transplanted mice exhibited a 26% (
P
<0.05) reduction in their liver triglyceride level. Hepatic myosin regulatory light chain interacting protein/inducible degrader of the low-density lipoprotein receptor mRNA expression was 48% (
P
<0.01) decreased in adrenal-specific SR-BI KO mice, which was paralleled by a marked decrease (–46%;
P
<0.01) in proatherogenic very-low-density and low-density lipoprotein levels.

Conclusion—

Adrenal-specific disruption of SR-BI function induces glucocorticoid insufficiency and lowers plasma very-low-density and low-density lipoprotein levels in atherogenic diet-fed C57BL/6 mice. These findings further highlight the interaction between adrenal high-density lipoprotein-cholesterol uptake by SR-BI, adrenal steroidogenesis, and the regulation of hepatic lipid metabolism.
Time-Mean Flow as the Prevailing Contribution to the Poleward Heat Flux across the Southern Flank of the Antarctic Circumpolar Current: A Case Study in the Fawn Trough, Kerguelen Plateau
Authors: Sekma H. , Park Y.-H. , Vivier F.
Published: November 2012

The major mechanisms of the oceanic poleward heat flux in the Southern Ocean are still in debate. The long-standing belief stipulates that the poleward heat flux across the Antarctic Circumpolar Current (ACC) is mainly due to mesoscale transient eddies and the cross-stream heat flux by time-mean flow is insignificant. This belief has recently been challenged by several numerical modeling studies, which stress the importance of mean flow for the meridional heat flux in the Southern Ocean. Here, this study analyzes moored current meter data obtained recently in the Fawn Trough, Kerguelen Plateau, to estimate the cross-stream heat flux caused by the time-mean flow and transient eddies. It is shown that the poleward eddy heat flux in this southern part of the ACC is negligible, while that from the mean flow is overwhelming by two orders of magnitude. This is due to the unusual anticlockwise turning of currents with decreasing depth, which is associated with significant bottom upwelling engendered by strong bottom currents flowing over the sloping topography of the trough. The circumpolar implications of these local observations are discussed in terms of the depth-integrated linear vorticity budget, which suggests that the six topographic features along the southern flank of the ACC equivalent to the Fawn Trough case would yield sufficient poleward heat flux to balance the oceanic heat loss in the subpolar region. As eddy activity on the southern flank of the ACC is too weak to transport sufficient heat poleward, the nonequivalent barotropic structure of the mean flow in several topographically constricted passages should accomplish the required task.
Associations Between Timing in the Baseball Pitch and Shoulder Kinetics, Elbow Kinetics, and Ball Speed
Authors: Urbin M.A. , Fleisig Glenn S. , Abebe Asheber , Andrews James R.
Published: November 2012

Background:

A baseball pitcher’s ability to maximize ball speed while avoiding shoulder and elbow injuries is an important determinant of a successful career. Pitching injuries are attributed to microtrauma brought about by the repetitive stress of high-magnitude shoulder and elbow kinetics.

Hypothesis:

Over a number of pitches, variations in timing peak angular velocities of trunk segment rotations will be significantly associated with ball speed and upper extremity kinetic parameters.

Study Design:

Descriptive laboratory study.

Methods:

Kinematic and kinetic data were derived from 9 to 15 fastball pitches performed by 16 active, healthy collegiate (n = 8) and professional (n = 8) pitchers via 3-dimensional motion capture (240 Hz). Each pitch was decomposed into 4 phases corresponding to the time between peak angular velocities of sequential body segment rotations. Four mixed models were used to evaluate which phases varied significantly in relation to ball speed, peak shoulder proximal force, peak shoulder internal rotation torque, and peak elbow varus torque. Mixed-model parameter coefficient estimates were used to quantify the influence of these variations in timing on ball speed and upper extremity kinetics.

Results:

All 4 mixed models were significant ( P < .05). The time from stride-foot contact to peak pelvis angular velocity varied significantly in relation to all upper extremity kinetic parameters and ball speed. Increased time in this phase correlated with decreases in all parameters. Decreased ball speed also correlated with increased time between peak upper torso and elbow extension angular velocities. Decreased shoulder proximal force also correlated with increased time between peak pelvis and upper torso angular velocities.

Conclusion:

There are specific phases that vary in relation to ball speed and upper extremity kinetic parameters, reinforcing the importance of effectively and consistently timing segmental interactions. For the specific interactions that varied significantly, increased phase times were associated with decreased kinetics and ball speed.

Clinical Relevance:

Although increased time within specific phases correlates with decreases in the magnitude of upper extremity kinetics linked to overuse injuries, it also correlates with decreased ball speed. Based on these findings, it may appear that minimizing the risk of injury (ie, decreased kinetics) and maximizing performance quality (ie, increased ball speed) are incompatible with one another. However, there may be an optimal balance in timing that is effective for satisfying both outcomes.
Biomechanical comparison of supplemental posterior fixations for two-level anterior lumbar interbody fusion
Authors: Wang Mei , Tang Shu-Jie , McGrady Linda M , Rao Raj D
Published: November 2012

Posterior instrumentations have been used to supplement anterior lumbar interbody fusion with cages. Biomechanical studies on single-level anterior lumbar interbody fusion show that stand-alone cages supplemented with posterior translaminar facet or transfacet screw fixation exhibit comparable stability to those supplemented with pedicle screw/rod fixation, while stability of multilevel anterior lumbar interbody fusion remains mostly unknown. The objectives of this study are to compare the stabilization of three supplemental posterior fixations to two-level anterior lumbar interbody fusion, including translaminar facet fixation, transfacet screw fixation, and pedicle screw/rod fixation. Flexibility tests were conducted on fresh-frozen calf spines with moment up to 8.5 N m in flexion, extension, lateral bending, and axial rotation. Each specimen was tested at three stages: intact, anterior lumbar interbody fusion using Polyetheretherketone (PEEK) interbody cage at L3–L4 and L4–L5, and the same anterior lumbar interbody fusion plus one of the three supplemental posterior fixations. The addition of the supplemental posterior fixation increased stiffness at the fusion levels significantly in flexion (9.9 times), extension (5.4 times), and lateral bending (4.1 times). The pedicle screw/rod and translaminar screw fixations provide approximately 40% higher stiffness than the transfacet screw in lateral bending. The pedicle screw/rod fixation also displayed a trend of superior fixation in extension. Supplemental posterior fixation significantly improved stability of two-level anterior lumbar interbody fusion when compared to the stand-alone cages. Pedicle screw/rod system is still the “gold standard” in providing supplemental stability. However, both translaminar facet screws and transfacet screws are good alternatives to provide adequate fixation.
Framing the 2007 National Basketball Association finals: An analysis of commentator discourse
Authors: Scott Olan KM , Hill Brad , Zakus Dwight
Published: November 2012

Television broadcasters often exhibit bias in the reporting of sport events. Through framed discourse, networks embed multiple storylines to build and maintain audiences over the duration of an event. Research has typically focused on mega-events occurring every four years. This study, through content analysis of American Broadcast Company’s announcer discourse of a smaller annual event, the 2007 National Basketball Association finals series, found that the framing function of the media continued to be employed. Findings also revealed significant associations existed for play-by-play and colour commentary on the two competing teams that would serve to reinforce viewer beliefs. Commentary on the winning team emphasized skill, speed and creativity, whereas star players became the focus of the losing team. Sport marketers can gain practical utility for use of framing in broadcasts by providing commentators with prepared frames that could support viewer beliefs or expectations.