Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination

Incorporating Primary and Secondary Prevention Approaches To Address Childhood Obesity Prevention and Treatment in a Low-Income, Ethnically Diverse Population: Study Design and Demographic Data from the Texas Childhood Obesity Research Demonstration (TX CORD) Study

Background: There is consensus that development and evaluation of a systems-oriented approach for child obesity prevention and treatment that includes both primary and secondary prevention efforts is needed. This article describes the study design and baseline data from the Texas Childhood Obesity Research Demonstration (TX CORD) project, which addresses child obesity among low-income, ethnically diverse overweight and obese children, ages 2–12 years; a two-tiered systems-oriented approach is hypothesized to reduce BMI z-scores, compared to primary prevention alone. Methods: Our study aims are to: (1) implement and evaluate a primary obesity prevention program; (2) implement and evaluate efficacy of a 12-month family-centered secondary obesity prevention program embedded within primary prevention; and (3) quantify the incremental cost-effectiveness of the secondary prevention program. Baseline demographic and behavioral data for the primary prevention community areas are presented. Results: Baseline data from preschool centers, elementary schools, and clinics indicate that most demographic variables are similar between intervention and comparison communities. Most families are low income ( \u3c $25,000) and Hispanic/Latino (73.3– 83.8%). The majority of parents were born outside of the United States. Child obesity rates exceed national values, ranging from 19.0% in preschool to 35.2% in fifth-grade children. Most parents report that their children consume sugary beverages, have a television in the bedroom, and do not consume adequate amounts of fruits and vegetables. Conclusions: Interventions to address childhood obesity are warranted in low-income, ethnically diverse communities. Integrating primary and secondary approaches is anticipated to provide sufficient exposure that will lead to significant decreases in childhood obesity

Incorporating Primary and Secondary Prevention Approaches To Address Childhood Obesity Prevention and Treatment in a Low-Income, Ethnically Diverse Population: Study Design and Demographic Data from the Texas Childhood Obesity Research Demonstration (TX CORD) Study

Background: There is consensus that development and evaluation of a systems-oriented approach for child obesity prevention and treatment that includes both primary and secondary prevention efforts is needed. This article describes the study design and baseline data from the Texas Childhood Obesity Research Demonstration (TX CORD) project, which addresses child obesity among low-income, ethnically diverse overweight and obese children, ages 2–12 years; a two-tiered systems-oriented approach is hypothesized to reduce BMI z-scores, compared to primary prevention alone. Methods: Our study aims are to: (1) implement and evaluate a primary obesity prevention program; (2) implement and evaluate efficacy of a 12-month family-centered secondary obesity prevention program embedded within primary prevention; and (3) quantify the incremental cost-effectiveness of the secondary prevention program. Baseline demographic and behavioral data for the primary prevention community areas are presented. Results: Baseline data from preschool centers, elementary schools, and clinics indicate that most demographic variables are similar between intervention and comparison communities. Most families are low income ( \u3c $25,000) and Hispanic/Latino (73.3– 83.8%). The majority of parents were born outside of the United States. Child obesity rates exceed national values, ranging from 19.0% in preschool to 35.2% in fifth-grade children. Most parents report that their children consume sugary beverages, have a television in the bedroom, and do not consume adequate amounts of fruits and vegetables. Conclusions: Interventions to address childhood obesity are warranted in low-income, ethnically diverse communities. Integrating primary and secondary approaches is anticipated to provide sufficient exposure that will lead to significant decreases in childhood obesity

The Adaptor Function of TRAPPC2 in Mammalian TRAPPs Explains TRAPPC2-Associated SEDT and TRAPPC9-Associated Congenital Intellectual Disability

Background: The TRAPP (Transport protein particle) complex is a conserved protein complex functioning at various steps in vesicle transport. Although yeast has three functionally and structurally distinct forms, TRAPPI, II and III, emerging evidence suggests that mammalian TRAPP complex may be different. Mutations in the TRAPP complex subunit 2 (TRAPPC2) cause X-linked spondyloepiphyseal dysplasia tarda, while mutations in the TRAPP complex subunit 9 (TRAPPC9) cause postnatal mental retardation with microcephaly. The structural interplay between these subunits found in mammalian equivalent of TRAPPI and those specific to TRAPPII and TRAPPIII remains largely unknown and we undertook the present study to examine the interaction between these subunits. Here, we reveal that the mammalian equivalent of the TRAPPII complex is structurally distinct from the yeast counterpart thus leading to insight into mechanism of disease. Principal Findings: We analyzed how TRAPPII- or TRAPPIII- specific subunits interact with the six-subunit core complex of TRAPP by co-immunoprecipitation in mammalian cells. TRAPPC2 binds to TRAPPII-specific subunit TRAPPC9, which in turn binds to TRAPPC10. Unexpectedly, TRAPPC2 can also bind to the putative TRAPPIII-specific subunit, TRAPPC8. Endogenous TRAPPC9-positive TRAPPII complex does not contain TRAPPC8, suggesting that TRAPPC2 binds to either TRAPPC9 or TRAPPC8 during the formation of the mammalian equivalents of TRAPPII or TRAPPIII, respectively. Therefore, TRAPPC2 serves as an adaptor for the formation of these complexes. A disease-causing mutation of TRAPPC2, D47Y, failed to interact with either TRAPPC9 or TRAPPC8, suggesting that aspartate 47 in TRAPPC2 is at or near the site of interaction with TRAPPC9 or TRAPPC8, mediating the formation of TRAPPII and/or TRAPPIII. Furthermore, disease-causing deletional mutants of TRAPPC9 all failed to interact with TRAPPC2 and TRAPPC10. Conclusions: TRAPPC2 serves as an adaptor for the formation of TRAPPII or TRAPPIII in mammalian cells. The mammalian equivalent of TRAPPII is likely different from the yeast TRAPPII structurally. © 2011 Zong et al.published_or_final_versio

Type-III intermittency in a four-level coherently pumped laser

We study a homogeneously broadened four-level model for a coherently pumped laser with pump and laser fields having crossed linear polarizations. For a parameter range of the type explored in the experiments by Tang et al. [Phys. Rev. A 44, R35 (1991)] the system exhibits a family of type-III-intermittency transitions to chaos in which the onset of intermittency is preceded by period-2, period-3, or period-4 states. We find similarities but also differences between the results of our theory and their experimental results

Management of asymptomatic arrhythmias: a European Heart Rhythm Association (EHRA) consensus document, endorsed by the Heart Failure Association (HFA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Cardiac Arrhythmia Society of Southern Africa (CASSA), and Latin America Heart Rhythm Society (LAHRS).

Asymptomatic arrhythmias are frequently encountered in clinical practice. Although studies specifically dedicated to these asymptomatic arrhythmias are lacking, many arrhythmias still require proper diagnostic and prognostic evaluation and treatment to avoid severe consequences, such as stroke or systemic emboli, heart failure, or sudden cardiac death. The present document reviews the evidence, where available, and attempts to reach a consensus, where evidence is insufficient or conflicting

A preliminary investigation on the effect of extracorporeal shock wave therapy as a treatment for neurogenic heterotopic ossification following traumatic brain injury. Part I: Effects on pain

“This is an Accepted Manuscript of an article published by Taylor & Francis in Brain Injury on 24 March 2017, available online: http://www.tandfonline.com/10.1080/02699052.2017.1283059.”Copyright © 2017 Taylor & Francis Group, LLC This author manuscript is made available following 12 month embargo from date of publication (24 March 2017) in accordance with publisher’s copyright policyIntroduction: Neurogenic heterotopic ossification (NHO) is a complication of a neurological injury following traumatic brain injury (TBI) and may be present around major synovial joints. It is often accompanied by severe pain, which may lead to limitation in activities of daily living. Currently, a common intervention for NHO is surgery, which has been reported to carry many additional risks. This study was designed to assess the effect of extracorporeal shock wave therapy (ESWT) on pain in patients with TBI with chronic NHO. Methods: A series of single-case studies (n = 11) was undertaken with patients who had TBI and chronic NHO at the hip or knee. Each patient received four applications of high-energy EWST delivered to the affected joint over 8 weeks. Two-weekly follow-up assessments were carried out, and final assessments were made 3 and 6 months post-intervention. Pain was measured using the Faces Rating Scale, and X-rays were taken at baseline and 6-months post-intervention to physiologically measure the size of the NHO. Results: The application of high-energy ESWT was associated with significant overall reduction of pain in patients with TBI and NHO (Tau-0.412, 95% confidence interval −0.672 to −0.159, p = 0.002). Conclusions: ESWT is a novel non-invasive intervention for reducing pain resulting from NHO in patients with TBI

Genome-Wide Association Data Reveal a Global Map of Genetic Interactions among Protein Complexes

This work demonstrates how gene association studies can be analyzed to map a global landscape of genetic interactions among protein complexes and pathways. Despite the immense potential of gene association studies, they have been challenging to analyze because most traits are complex, involving the combined effect of mutations at many different genes. Due to lack of statistical power, only the strongest single markers are typically identified. Here, we present an integrative approach that greatly increases power through marker clustering and projection of marker interactions within and across protein complexes. Applied to a recent gene association study in yeast, this approach identifies 2,023 genetic interactions which map to 208 functional interactions among protein complexes. We show that such interactions are analogous to interactions derived through reverse genetic screens and that they provide coverage in areas not yet tested by reverse genetic analysis. This work has the potential to transform gene association studies, by elevating the analysis from the level of individual markers to global maps of genetic interactions. As proof of principle, we use synthetic genetic screens to confirm numerous novel genetic interactions for the INO80 chromatin remodeling complex

Multipurpose silicon photonics signal processor core

[EN] Integrated photonics changes the scaling laws of information and communication systems offering architectural choices that combine photonics with electronics to optimize performance, power, footprint, and cost. Application-specific photonic integrated circuits, where particular circuits/chips are designed to optimally perform particular functionalities, require a considerable number of design and fabrication iterations leading to long development times. A different approach inspired by electronic Field Programmable Gate Arrays is the programmable photonic processor, where a common hardware implemented by a two-dimensional photonic waveguide mesh realizes different functionalities through programming. Here, we report the demonstration of such reconfigurable waveguide mesh in silicon. 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