bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterologous Viral Promoters Incorporated into the Human Cytomegalovirus Genome Are Silenced during Experimental Latency
Authors: Qin Qingsong , Penkert Rhiannon R. , Kalejta Robert F.
Published: July 2013

Human cytomegalovirus (HCMV) lytic phase gene expression is repressed upon entry into myeloid lineage cells where the virus establishes latency. Lytic infection is not initiated because the tegument-delivered transactivator protein pp71 fails to enter the nucleus and inactivate the Daxx-mediated cellular intrinsic defense that silences the viral genome. When pp71 is expressed
de novo
in THP-1 monocytes, it localizes to the nucleus, inactivates the Daxx defense, and initiates lytic infection. We speculated that replacing the native viral promoter that drives pp71 expression with one that is highly and constitutively active in myeloid cells would permit pp71
de novo
expression upon infection and that this newly expressed pp71 would accumulate in the nucleus, inactivate the intrinsic defense, and initiate the cascade of lytic gene expression. Surprisingly, we found that this promoter was still subject to normal silencing mechanisms in THP-1 monocytes and primary CD34
+
cells, two independent myeloid lineage cells. A second constitutively active heterologous viral promoter located in a different region of the HCMV genome was also silenced in THP-1 and CD34
+
cells. Furthermore, these two independent heterologous viral promoters inserted into three different regions of the HCMV genome in three different viral strains all required prior expression of the viral immediate early proteins for activation in fibroblasts. From this, we conclude that incorporation within the HCMV genome impacts the proclivity of heterologous viral promoters to initiate transcription. These observations have mechanistic implications for the expression of viral genes and transgenes during both lytic infection and latency.
Patterns of healthcare use among adolescents attending an urban general practitioner-led urgent care centre
Authors: Gnani Shamini , McDonald Helen , Islam Saiful , Ramzan Farzan , Davison Michele , Ladbrooke Tim , Majeed Azeem , Saxena Sonia
Published: July 2013

Introduction

Adolescence is a time of increasing health and peak fitness, as well as increasing health risks. In the UK, primary care is free at the point of access, yet, adolescents aged 10–19 years are the lowest users of primary care services, and disproportionately high users of emergency services. The effect of new general practitioner (GP)-led urgent care centres in meeting the needs of adolescents are unknown.

Methods

We used routinely collected data to describe the demographics and attendance pattern among adolescents at two new colocated GP-led urgent care centres at Hammersmith and Charing Cross Hospitals, London. We also compared attendance rates with those observed in routine general practice and emergency departments.

Results

Adolescents formed 6.5% (N=14 038) of total urgent care attendances. 13.2% (95% CI 12.9% to 14.1%) was recorded as not being registered with a GP. Commonest reasons for attendance were musculoskeletal conditions and injuries (30.2%), respiratory tract infections (12.5%) and limb fractures (5.1%). Adolescents aged 15–19 years were more likely to attend the centres (30.6 vs 23.4, per 100, p<0.0001) than routine general practice. The opposite was true for adolescents aged 10–14 years.

Conclusions

Adolescents aged 15–19 years are more likely to attend urgent care centres than general practice. The majority attended for conditions commonly seen in primary care including musculoskeletal conditions and injuries, and respiratory tract infections. Primary care services may need to be more responsive to needs of the older adolescent age, if their use of urgent care centres is to be reduced.
Emergency medical services versus private transport of trauma patients in the Sultanate of Oman: a retrospective audit at the Sultan Qaboos University Hospital
Authors: Al-Shaqsi Sultan , Al-Kashmiri Ammar , Al-Hajri Hamood , Al-Harthy Abdullah
Published: July 2013

Aims

This study aims to assess the differences in the outcome of road traffic trauma patients between those transported by emergency medical services (EMS) and those privately transported to the Sultan Qaboos University Hospital in the Sultanate of Oman in 2011.

Methods

This is a retrospective study of road traffic trauma patients admitted to the Sultan Qaboos University Hospital between January to December 2011. Data for all cases were retrieved from the emergency department database. The general linear multivariate regression analysis model was performed to test the differences in outcome. The analysis controlled for age, gender, ethnicity, weekend injury, time of injury, triage status, Injury Severity Score, existence of head injury, need for intensive care unit admission and need for surgical management.

Results

There were 821 trauma cases in 2011. 66.7% were transported by EMS. Male patients represented 65.7% of the cases. There was no significant difference in the characteristics of EMS and non-EMS trauma patients. In terms of inhospital mortality, the relative ratio of inhospital mortality between EMS and non-EMS groups was 0.64 (0.36–1.13), and p value 0.13. There is no significant difference in all other secondary outcomes tested.

Conclusions

EMS transported trauma patients had a statistically non-significant 36% reduction in mortality compared with privately transported patients admitted to the Sultan Qaboos University Hospital in 2011. Further, research that incorporates prehospital factors such as crash to arrival of EMS services and transport time to definitive healthcare facility should be conducted to evaluate the effectiveness of such a system in trauma care. Since non-EMS transport is likely to continue, public first aid training is critical to reduce mortality and morbidity of road traffic trauma in Oman.
Evolution of the Late Ordovician plaesiomyid brachiopod lineage in Laurentia
Authors: Sproat Colin D. , Jin Jisuo
Published: July 2013

Multivariate analysis of 197 well-preserved specimens among 11 species of late Late Ordovician (Katian and Hirnantian) plaesiomyid brachiopods from North America revealed two trends of morphological changes: (1) increasing globosity and dorsal convexity from the early to late Katian, and (2) coarser, but fewer ribs in species from the paleoequatorial intracratonic seas compared with species from the mid- to high-tropical pericratonic shelves and platforms. Another notable change, albeit not quantified, was the enlargement of cardinal process in plaesiomyids from early to late Katian, characterized by a predominantly trilobed cardinal process in the intracratonic species versus a bilobed cardinal process in pericratonic species. Increases in dorsal convexity and shell globosity are interpreted to have allowed for development of a larger lophophore, improving the capacity and efficiency of filter feeding and gas exchange. Smaller but more frequently bifurcating ribs would have led to more numerous setae near the margin of the shell, resulting in increased sensitivity to environmental stimuli. Increased size and number of lobes of the cardinal process would have allowed for larger diductor muscles to open a larger, heavier shell. In this study, two new species, Plaesiomys periosa sp. nov. and Plaesiomys lenzi sp. nov., are proposed, and two existing species are transferred from Dinorthis to Plaesiomys.
The emerging synthesis of evolution with ecology in fisheries science
Authors: Fraser Dylan J.
Published: July 2013

Fisheries science is currently being transformed through a true integration of ecological and evolutionary perspectives. Many questions are emerging from the recognition that human-induced evolutionary change can elicit ecological change on short time scales, in some cases equal to or exceeding the changes brought on by classical ecological effects. For instance, to what extent does evolutionary change associated with size-selective harvesting, supplementation, captive breeding, aquaculture escapees, and related fisheries activities directly or indirectly affect species demography (persistence, productivity, or recovery), community structure, and ecosystem functioning? Under what conditions do feedbacks between evolution and ecology matter most for managing fisheries activities? Do such feedbacks generate predictable outcomes, and are they reversible? Although as yet, little consensus has been reached on the answers to these questions, it is clear that a synthesis of evolutionary and ecological perspectives holds great promise for improving and generating more biologically realistic modeling, monitoring, rebuilding, and management of fish populations, fish species, and aquatic ecosystems.
Toward developing a direct relation between gross volume increment and stand density
Authors: Dean Thomas J. , Roberts Scott D. , Seymour Robert S.
Published: July 2013

A general form for expressing gross volume increment in terms of stand density is derived and tested with data from spacing trials in red alder (Alnus rubra Bong.), eastern white pine (Pinus strobus L.), longleaf pine (Pinus palustris Mill.), and loblolly pine (Pinus taeda L.). The equation relates the stand sum of individual-tree volume increment per metre height increment to a power function of quadratic mean diameter times tree density. The proposed equation fit the data best when the model included an intercept. Within each species, the fits were unbiased with respect to the independent variables, plantation age, and site height, and with the exception of the youngest ages for red alder and loblolly pine, they were unbiased with respect to the plot sums of individual-tree volume increment divided by individual height increment. Exponents estimated for quadratic mean diameter for each species ranged from 1.58 to 1.80. The resulting equations indicate a linear relationship between the stand sum of individual-tree volume increment per metre height increment and stand density. Scattergrams of gross-volume increment per hectare per year and stand density can be recovered by multiplying the predicted values of the regressions by Lorey’s height. The regressions support the hypothesis that each metre of height growth produces consistent changes in stem size, regardless of initial tree size, age, or site quality, and implies that the change in stem size is a predictable power function of stem diameter for an individual tree or quadratic mean diameter for a stand.
Relationships between carotenoid-based female plumage and age, reproduction, and mate colour in the American Redstart (Setophaga ruticilla)
Authors: Osmond Matthew M. , Reudink Matthew W. , Germain Ryan R. , Marra Peter P. , Nocera Joseph J. , Boag Peter T. , Ratcliffe Laurene M.
Published: July 2013

Most studies investigating the function and evolution of ornaments have focused on males. Variation in ornaments may also reflect individual quality and convey information in females. We examined correlations between female plumage colour and reproductive variables in the sexually dichromatic songbird, the American Redstart (Setophaga ruticilla (L., 1758)). Female American Redstarts display yellow, carotenoid-based plumage patches on their tails, wings, and flanks. Using reflectance spectrometry, we quantified brightness (feather structure) and “yellowness” (hue and chroma) of tail and flank feathers to examine whether female plumage colour varies with age, reproductive success, parental care, and the plumage colour of mates. Female plumage varied with age, with adult (after-second-year) females having brighter tail feathers than first-year females. We failed to find a relationship between female plumage colour and pairing or first-egg dates. However, adult females with brighter tails visited their nests less frequently and first-year females with brighter tails fledged fewer offspring. Adult females with brighter tails also mated with males who provided less care. In addition, adult females with yellower flanks paired with males with brighter flanks and with males who provided less parental care. We suggest that plumage colouration in female American Redstarts can act as a signal of individual age and quality.
NEIGHBOR INTEGRITY OF TRANSFORMATION GRAPHS
Authors: BACAK-TURAN GOKSEN , KIRLANGIC ALPAY
Published: July 2013

In a communication network, the vulnerability measures are essential to guide the designer in choosing an appropriate topology. They measure the stability of the network to disruption of operation after the failure of certain stations or communication links. If a station or operative is captured in a spy network, then the adjacent stations will be betrayed and are therefore useless in the whole network. In this sense, Margaret B. Cozzens and Shu-Shih Y. Wu modeled a spy network as a graph and then defined the neighbor integrity of a graph to obtain the vulnerability of a spy network [10]. The neighbor integrity of a graph G, is defined to be [Formula: see text], where S is any vertex subversion strategy of G and c(G/S) is the maximum order of the components of G/S. In this paper, we investigate the transformation graphs G-+-, G+--, G++-, G---, G+-+, G-++, G--+and G+++of a graph G, and determine their neighbor integrity.
CONSTRUCTING ODD VARIABLE BOOLEAN FUNCTIONS WITH OPTIMAL ALGEBRAIC IMMUNITY
Authors: TU ZIRAN , JIANG YUPENG , ZENG XIANGYONG
Published: July 2013

Based on Carlet-Feng functions, we present a method to construct odd variable Boolean functions with optimal algebraic immunity in this paper. The proposed functions can have the highest algebraic degree and a lower bound on the nonlinearity is also established.
DETERMINATION OF THE CKM MATRIX ELEMENTS |Vxb|
Authors: RICCIARDI GIULIA
Published: July 2013

We review the current status of |Vcb|, |Vub| and |Vtb|, the absolute values of the matrix elements in the CKM third column.
ON THEORY OF REGULAR ACCELERATING UNIVERSE IN RIEMANN–CARTAN SPACETIME
Authors: MINKEVICH A. V.
Published: July 2013

Isotropic cosmology built in the Riemann–Cartan spacetime is investigated. Properties of homogeneous isotropic cosmological models filled with usual gravitating matter and scalar fields are studied in the beginning of cosmological expansion near the limiting energy density. It is shown that cosmological models are regular not only with respect to the Hubble parameter and the energy density but also with respect to the torsion and curvature tensors.
A MODEL CONSTRUCTION OF SELF-SIMILARITY BASED DOUBLE PARTON DISTRIBUTION FUNCTIONS FOR PROTON–PROTON COLLISION AT LHC
Authors: CHOUDHURY D. K. , JAHAN AKBARI
Published: July 2013

We construct a model for double parton distribution functions (dPDFs) based on the notion of self-similarity, pursued earlier for small x physics at HERA. The most general form of dPDFs contains total 13 parameters to be fitted from data of proton–proton collision at LHC. It is shown that the constructed dPDF does not factorize into two single PDFs in conformity with QCD expectation, and it satisfies the condition that at the kinematic boundary x1+x2= 1 (where x1and x2are the longitudinal fractional momenta of two partons), the dPDF vanishes.
LONG-RANGE VAN DER WAALS INTERACTION
Authors: TAO JIANMIN , PERDEW JOHN P. , RUZSINSZKY ADRIENN
Published: July 2013

Van der Waals interaction is an elusive many-body effect arising from instantaneous charge fluctuations. Fundamental understanding of this effect plays an important role in computational chemistry, physics and materials science. In this article, recent advances in the evaluation of van der Waals coefficients, in particular the higher-order ones, are reviewed.
INHOMOGENEITY INDUCED CONDUCTIVITY FLUCTUATION IN YBa2Cu3O7-δ/BaTiO3–CoFe2O4 COMPOSITE
Authors: SAHOO MOUSUMIBALA , BEHERA DHRUBANANDA
Published: July 2013

Polycrystalline (1-x) YBa 2 Cu 3 O 7-y + x BaTiO 3– CoFe 2 O 4(x = 0.0, 0.2, 0.4, 0.6 wt. %) superconductors were prepared by solid state route. XRD analysis reveals no significant change in "b" parameter and increase in "a" and "c" parameters. SEM micrographs show no change in grain size of the samples. With the increase of BaTiO 3– CoFe 2 O 4 (BTO–CFO) addition it has been analyzed that the superconducting transition temperatures (Tc) determined from standard four-probe method was decreased and dropped sharply with higher wt.% addition. Excess conductivity fluctuation analysis using Aslamazov–Larkin model fitting reveals transition of two dominant regions (2D and 3D) above Tc. The decrease in 2D–3D crossover temperature T LD (Lawerence–Doniach temperature) in the mean field region has been observed as a consequent dominance of 3D region to increase in wt.% in the composite. The increasing value of ρwl and ρ0 and the decreasing trend in the value of zero-resistance critical temperature (Tc0) indicates that the connectivity between grains decreases gradually with the addition of magneto–electric composite BTO–CFO.
RESILIENCE AND ECONOMIC EMPOWERMENT: A QUALITATIVE INVESTIGATION OF ENTREPRENEURIAL INDONESIAN WOMEN
Authors: LOH JENNIFER M. I. , DAHESIHSARI RAYINI
Published: July 2013

The development of female entrepreneurs in Indonesia is an integral part of Muslim women's economic contributions and empowerment. However, there is a lack of reliable research about female entrepreneurship and how gender may affect the experiences of business ownership in Indonesia. Therefore, the aim of this study is to explore the challenges encountered by these women entrepreneurs on a daily basis. Qualitative in-depth interviews were conducted with 30 female Indonesian entrepreneurs. Participants were recruited using theoretical and maximum variation sampling techniques. Content analysis was then used to analyze the data. Results revealed high levels of variations, both within and between women, suggesting that the quality of business entrepreneurship and success depended largely on the personal characteristics of these women, rather than on any system of formal education or training. This study also found that many women displayed resilient coping strategies when dealing with business failures. As a consequence, they were able to thrive despite restrictive social, cultural and political constraints. The paper highlights the importance of the experiences of female entrepreneurs in a developing country and the need to integrate the development of female entrepreneurship as a part of women empowerment effort.
DOMESTIC GENERALIZED MULTICOIL ENLARGEMENTS OF CONCEALED CANONICAL ALGEBRAS
Authors: MALICKI PIOTR
Published: July 2013

In this paper, we prove that the class of artin algebras such that ( rad ∞( mod A))3 = 0 and the Auslander–Reiten quiver of A admits a sincere family of almost cyclic coherent components coincides with the class of domestic generalized multicoil enlargements of concealed canonical algebras.
AN INTEGRATED DATA CHARACTERISTIC TESTING SCHEME FOR COMPLEX TIME SERIES DATA EXPLORATION
Authors: TANG LING , YU LEAN , LIU FANGTAO , XU WEIXUAN
Published: July 2013

In this paper, an integrated data characteristic testing scheme is proposed for complex time series data exploration so as to select the most appropriate research methodology for complex time series modeling. Based on relationships across different data characteristics, data characteristics of time series data are divided into two main categories: nature characteristics and pattern characteristics in this paper. Accordingly, two relevant tasks, nature determination and pattern measurement, are involved in the proposed testing scheme. In nature determination, dynamics system generating the time series data is analyzed via nonstationarity, nonlinearity and complexity tests. In pattern measurement, the characteristics of cyclicity (and seasonality), mutability (or saltation) and randomicity (or noise pattern) are measured in terms of pattern importance. For illustration purpose, four main Chinese economic time series data are used as testing targets, and the data characteristics hidden in these time series data are thoroughly explored by using the proposed integrated testing scheme. Empirical results reveal that the natures of all sample data demonstrate complexity in the phase of nature determination, and in the meantime the main pattern of each time series is captured based on the pattern importance, indicating that the proposed scheme can be used as an effective data characteristic testing tool for complex time series data exploration from a comprehensive perspective.
CONTRAST-ENHANCED PHOTOACOUSTIC IMAGING USING INDOCYANINE GREEN-CONTAINING NANOPARTICLES
Authors: ZHONG JUNPING , YANG SIHUA
Published: July 2013

Contrast agents are attracting a great deal of attention in photoacoustic imaging. Here we introduce an exogenous contrast agent that provides high photoacoustic signal amplitude at the near-infrared wavelength. Our agents consist of Indocyanine green (ICG) and phospholipid–polyethylene glycol (PL–PEG), entitled ICG–PL–PEG nanoparticles. These nanoparticles have overcome numerous limitations of ICG, such as poor aqueous stability, concentration-dependent aggregation and lack of target specificity. ICG–PL–PEG nanoparticles are biocompatible and relatively nontoxic. All the components of ICG–PL–PEG nanoparticles have been approved for human use. Upon pulsed laser irradiation, the nanoparticles are more efficient in producing photoacoustic waves than ICG alone. The results showed that ICG–PL–PEG nanoparticles act as good contrast agents for photoacoustic imaging. These unique ICG–PL–PEG nanoparticles have great potential in clinical applications.
LOW TEMPERATURE THERMOELECTRIC PROPERTIES AND AGING PHENOMENA OF NANOSTRUCTURED p-TYPEBi2-XSbXTe3(x = 1.46, 1.48, 1.52 AND 1.55)
Authors: HITCHCOCK DALE , LIU YEN-LIANG , LIU YUFEI , TRITT TERRY M. , HE JIAN , LIU CHIA-JYI
Published: July 2013

Over the past decade the widely used p-type ( Bi2-xSbx) Te3bulk thermoelectric materials have been subject to various nanostructuring processes for higher thermoelectric performance. However, these nanostructuring processing were conducted on compositions optimized for bulk materials (x ~ 1.52–1.55). This leads to the question of whether the optimal composition for bulk materials is the same for their nanoscale counterparts. In this work we hydrothermally grew Bi2-xSbxTe3nanopowders (nominally, x = 1.46, 1.48, 1.52 and 1.55) and measured their thermoelectric properties on cold-pressed vacuum-sintered pellets (74–78% of the theoretical density) below 300 K. The measurements were conducted 18 months apart to probe the aging phenomena, with the samples stored in ambient conditions. We have found that (i) the peak of thermopower shifts to lower temperatures upon nanostructuring but it shifts back to higher temperatures upon aging; (ii) the electrical conductivity degrades by a factor of 1.5–2.3 upon aging while the temperature dependence is largely retained; and (iii) the ZT of freshly made samples is sensitive to the x value, a maximum ZT ~ 1.25(~ 0.62) at ~ 270 K (~ 255 K) was attained in the freshly made sample x = 1.55(x = 1.46), respectively; while the ZT of aged samples is significantly lowered by a factor of 2–4 but lesser x-dependent. These observations have been discussed in the context of charge buildup and compensation at grain boundaries.
MARTENSITIC TRANSFORMATION AND MAGNETIC PROPERTIES OF NiMnAl:Fe, Co FERROMAGNETIC SHAPE MEMORY ALLOYS
Authors: FENG LIN , ZHANG WENXING , LIU ENKE , WANG WENHONG , WU GUANGHENG
Published: July 2013

A series of Ni 50-x Fe x Mn 34 Al 16(0 ≦ x ≦ 18) and Ni 38 Fe 12-z Co z Mn 34 Al 16(3 ≦ z ≦ 6) ribbons were prepared by the melt-spinning method. With Fe substitution for Ni in Ni 50 Mn 34 Al 16 ribbons, the magnetization of the austenitic phase increases greatly while that of the martensitic phase increases little. Thus, in the magnetic field of 5 T a large magnetization change (22 Am2/kg) during the martensitic transformation is observed in Ni 38 Fe 12 Mn 34 Al 16 ribbon. The effect of Fe substitution for Ni on the magnetic modulation was investigated, which is attributed to the change of the magnetic interaction between Mn – Mn atoms. By substituting Co for Fe in Ni 38 Fe 12 Mn 34 Al 16 ribbons, a magnetic-field-induced martensite-austenite transformation is observed in Ni 38 Fe 9 Co 3 Mn 34 Al 16 ribbon.
Regulation of intramembranous absorption and amniotic fluid volume by constituents in fetal sheep urine
Authors: Anderson Debra F. , Jonker Sonnet S. , Louey Samantha , Cheung Cecilia Y. , Brace Robert A.
Published: July 2013

Our objective was to test the hypothesis that fetal urine contains a substance(s) that regulates amniotic fluid volume by altering the rate of intramembranous absorption of amniotic fluid. In late gestation ovine fetuses, amniotic fluid volumes, urine, and lung liquid production rates, swallowed volumes and intramembranous volume and solute absorption rates were measured over 2-day periods under control conditions and when urine was removed and continuously replaced at an equal rate with exogenous fluid. Intramembranous volume absorption rate decreased by 40% when urine was replaced with lactated Ringer solution or lactated Ringer solution diluted 50% with water. Amniotic fluid volume doubled under both conditions. Analysis of the intramembranous sodium and chloride fluxes suggests that the active but not passive component of intramembranous volume absorption was altered by urine replacement, whereas both active and passive components of solute fluxes were altered. We conclude that fetal urine contains an unidentified substance(s) that stimulates active intramembranous transport of amniotic fluid across the amnion into the underlying fetal vasculature and thereby functions as a regulator of amniotic fluid volume.
20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension
Authors: Ding Yan , Wu Cheng-Chia , Garcia Victor , Dimitrova Irina , Weidenhammer Adam , Joseph Gregory , Zhang Frank , Manthati Vijay L. , Falck John R. , Capdevila Jorge H. , Schwartzman Michal L.
Published: July 2013

20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6( Z),15( Z)-dienoic acid (20-HEDE) prevented 5α-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14−/− mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 ± 1 vs. 15 ± 1 μm) and M/L (0.29 ± 0.03 vs. 0.17 ± 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12–20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 ± 4 vs. 92 ± 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 ± 1 vs. 16 ± 1 μm; M/L: 0.39 ± 0.04 vs. 0.23 ± 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels.
Erythropoietin ameliorates podocyte injury in advanced diabetic nephropathy in thedb/dbmouse
Authors: Loeffler Ivonne , Rüster Christiane , Franke Sybille , Liebisch Marita , Wolf Gunter
Published: July 2013

Podocyte damage and accumulation of advanced glycation end products (AGEs) are characteristics of diabetic nephropathy (DN). The pathophysiology of AGE-challenged podocytes, such as hypertrophy, apoptosis, and reduced cell migration, is closely related to the induction of the cell cycle inhibitor p27Kip1and to the inhibition of neuropilin 1 (NRP1). We have previously demonstrated that treatment with erythropoietin is associated with protective effects for podocytes in vitro. db/ db mice with overt DN aged 15–16 wk were treated with either placebo, epoetin-β, or continuous erythropoietin receptor activator (CERA) for 2 wk. db/ db mice compared with nondiabetic db/ m control mice revealed the expected increases in body weight, blood glucose, albumin-to-creatinine ratio, and AGE accumulation. Whereas there were no differences in body weight, hyperglycemia and AGEs were observed among diabetic mice that received epoetin-β compared with CERA and placebo treatment, indicating that epoetin-β/CERA treatment does not interfere with the development of diabetes in this model. However, the albumin-to-creatinine ratio was significantly lower in db/ db mice treated with epoetin-β or CERA. Furthermore, kidney weights in db/ db mice were increased compared with db/ m control mice, indicating renal hypertrophy, whereas the increase in renal weight in epoetin-β- or CERA-treated db/ db mice was significantly lower than in placebo-treated control mice. Induction of p27Kip1and suppression of NRP1 were significantly reduced in the epoetin-β treatment group versus the CERA treatment group. Furthermore, erythropoietin treatment diminished the diabetes-induced podocyte loss. Together, independently from hematopoetic effects, epoetin-β or CERA treatment was associated with protective changes in DN, especially that NRP1 and p27Kip1expressions as well as numbers of podocytes returned to normal levels. Our data show, for the first time, that medication of overt DN with erythropoietin for a short time can ameliorate albuminuria and podocyte loss.
Long-term wheel running compromises diaphragm function but improves cardiac and plantarflexor function in the mdx mouse
Authors: Selsby Joshua T. , Acosta Pedro , Sleeper Meg M. , Barton Elisabeth R. , Sweeney H. Lee
Published: July 2013

Dystrophin-deficient muscles suffer from free radical injury, mitochondrial dysfunction, apoptosis, and inflammation, among other pathologies that contribute to muscle fiber injury and loss, leading to wheelchair confinement and death in the patient. For some time, it has been appreciated that endurance training has the potential to counter many of these contributing factors. Correspondingly, numerous investigations have shown improvements in limb muscle function following endurance training in mdx mice. However, the effect of long-term volitional wheel running on diaphragm and cardiac function is largely unknown. Our purpose was to determine the extent to which long-term endurance exercise affected dystrophic limb, diaphragm, and cardiac function. Diaphragm specific tension was reduced by 60% ( P < 0.05) in mice that performed 1 yr of volitional wheel running compared with sedentary mdx mice. Dorsiflexor mass (extensor digitorum longus and tibialis anterior) and function (extensor digitorum longus) were not altered by endurance training. In mice that performed 1 yr of volitional wheel running, plantarflexor mass (soleus and gastrocnemius) was increased and soleus tetanic force was increased 36%, while specific tension was similar in wheel-running and sedentary groups. Cardiac mass was increased 15%, left ventricle chamber size was increased 20% (diastole) and 18% (systole), and stroke volume was increased twofold in wheel-running compared with sedentary mdx mice. These data suggest that the dystrophic heart may undergo positive exercise-induced remodeling and that limb muscle function is largely unaffected. Most importantly, however, as the diaphragm most closely recapitulates the human disease, these data raise the possibility of exercise-mediated injury in dystrophic skeletal muscle.
Dissociating oculomotor contributions to spatial and feature-based selection
Authors: Jonikaitis Donatas , Theeuwes Jan
Published: July 2013

Saccades not only deliver the high-resolution retinal image requisite for visual perception, but processing stages associated with saccade target selection affect visual perception even before the eye movement starts. These presaccadic effects are thought to arise from two visual selection mechanisms: spatial selection that enhances processing of the saccade target location and feature-based selection that enhances processing of the saccade target features. By measuring oculomotor performance and perceptual discrimination, we determined which selection mechanisms are associated with saccade preparation. We observed both feature-based and space-based selection during saccade preparation but found that feature-based selection was neither related to saccade initiation nor was it affected by simultaneously observed redistribution of spatial selection. We conclude that oculomotor selection biases visual selection only in a spatial, feature-unspecific manner.
Evidence for reticulospinal contributions to coordinated finger movements in humans
Authors: Honeycutt Claire Fletcher , Kharouta Michael , Perreault Eric Jon
Published: July 2013

The reticulospinal tract was recently shown to have synaptic connections to the intrinsic muscles of the fingers in nonhuman primates, indicating it may contribute to hand function long thought to be controlled exclusively through corticospinal pathways. Our objective was to obtain evidence supporting the hypothesis that these same anatomical connections exist in humans. startReact, an involuntary release of a planned movement via the startle reflex, provides a noninvasive means to examine the reticulospinal tract in humans. We found that startReact was triggered during coordinated grasp but not individuated finger movements. This result suggests that the reticulospinal tract does have connections to the intrinsic muscles of the fingers in humans but its functional role is limited to coordinated movement of the whole hand. These results do not diminish the well-established role of corticospinal pathways in the control of hand movement. Indeed, they cement the significance of corticospinal pathways in individuated finger movement control. Still, these results point to an updated and expanded view of distal hand control where reticulospinal and corticospinal pathways work in parallel to generate a large repertoire of diverse, coordinated movement in the hand. Finally, the presence of reticulospinal pathways to the muscles of the hand makes this pathway an attractive therapeutic target for clinical populations where the corticospinal tract is absent or injured.
JAK-STAT Blockade Inhibits Tumor Initiation and Clonogenic Recovery of Prostate Cancer Stem-like Cells
Authors: Kroon Paula , Berry Paul A. , Stower Michael J. , Rodrigues Greta , Mann Vincent M. , Simms Matthew , Bhasin Deepak , Chettiar Somsundaram , Li Chenglong , Li Pui-Kai , Maitland Norman J. , Collins Anne T.
Published: July 2013

Interleukin (IL)-6 overexpression and constitutive STAT3 activation occur in many cancers, including prostate cancer. However, their contribution to prostate stem and progenitor cells has not been explored. In this study, we show that stem-like cells from patients with prostate cancer secrete higher levels of IL-6 than their counterparts in non-neoplastic prostate. Tumor grade did not influence the levels of expression or secretion. Stem-like and progenitor cells expressed the IL-6 receptor gp80 with concomitant expression of pSTAT3. Blockade of activated STAT3, by either anti-IL-6 antibody siltuximab (CNTO 328) or LLL12, a specific pSTAT3 inhibitor, suppressed the clonogenicity of the stem-like cells in patients with high-grade disease. In a murine xenograft model used to determine the in vivo effects of pSTAT3 suppression, LLL12 treatment effectively abolished outgrowth of a patient-derived castrate-resistant tumor. Our results indicate that the most primitive cells in prostate cancer require pSTAT3 for survival, rationalizing STAT3 as a therapeutic target to treat advanced prostate cancer. Cancer Res; 73(16); 5288–98. ©2013 AACR.
Simple Clinical Risk Score Identifies Patients with Serrated Polyps in Routine Practice
Authors: Bouwens Mariëlle W.E. , Winkens Bjorn , Rondagh Eveline J.A. , Driessen Ann L. , Riedl Robert G. , Masclee Ad A.M. , Sanduleanu Silvia
Published: July 2013

Large, proximal, or dysplastic (LPD) serrated polyps (SP) need accurate endoscopic recognition and removal as these might progress to colorectal cancer. Herewith, we examined the risk factors for having ≥1 LPD SP. We developed and validated a simple SP risk score as a potential tool for improving their detection. We reviewed clinical, endoscopic, and histologic features of serrated polyps in a study of patients undergoing elective colonoscopy (derivation cohort). A self-administered questionnaire was obtained. We conducted logistic regression analyses to identify independent risk factors for having ≥1 LPD SP and incorporated significant variables into a clinical score. We subsequently tested the performance of the SP score in a validation cohort. We examined 2,244 patients in the derivation and 2,402 patients in the validation cohort; 6.3% and 8.2% had ≥1 LPD SP, respectively. Independent risk factors for LPD SPs were age of more than 50 years [OR 2.2; 95% confidence interval (CI), 1.3–3.8; P = 0.004], personal history of serrated polyps (OR 2.6; 95% CI, 1.3–4.9; P = 0.005), current smoking (OR 2.2; 95% CI, 1.4–3.6; P = 0.001), and nondaily/no aspirin use (OR 1.8; 95% CI, 1.1–3.0; P = 0.016). In the validation cohort, a SP score ≥5 points was associated with a 3.0-fold increased odds for LPD SPs, compared with patients with a score <5 points. In the present study, age of more than 50 years, a personal history of serrated polyps, current smoking, and nondaily/no aspirin use were independent risk factors for having LPD SPs. The SP score might aid the endoscopist in the detection of such lesions. Cancer Prev Res; 6(8); 855–63. ©2013 AACR.
Successful Nd:YAG Laser Therapy for Hair Removal in the Oral Cavity after Plastic Reconstruction Using Hairy Donor Sites
Authors: Kaune Kjell M. , Haas Ellen , Jantke Maren , Kramer Franz-Josef , Gruber Rudolf , Thoms Kai-Martin , Schön Michael P. , Zutt Markus
Published: July 2013

Background: Concepts of reconstruction of intraoral structures may often include the transfer of flaps composed of external skin with hairs. Given that intraoral hair growth following myocutaneous flaps can cause discomfort, there is a need for effective treatments to relieve cancer patients of these symptoms. Objective: To describe the successful epilation of hairy intraoral flaps using Nd:YAG laser emitting a wavelength of 1,064 nm. Methods: We performed an interdisciplinary prospective clinical study with 9 patients suffering from intraoral hair growth after plastic reconstruction of a hairy donor site due to cancer. Eight male and one female patients were treated with 1-4 sessions of Nd:YAG laser at 5-15-week intervals. Results: Laser treatment resulted in effective hair reduction in 8/9 patients regardless of flap type. In 5/9 patients a hair clearance of >90% could be achieved, whereas laser treatment was ineffective in one male with white hair. Patients were very satisfied with the outcome and no side effects could be observed. Conclusion: Nd:YAG laser therapy appears to be a successful therapeutic option for patients suffering from growth of dark hair in the oral cavity after plastic reconstruction using a hairy donor site.
Alopecia Areata: Infiltration of Th17 Cells in the Dermis, Particularly around Hair Follicles
Authors: Tanemura Atsushi , Oiso Naoki , Nakano Mayuko , Itoi Saori , Kawada Akira , Katayama Ichiro
Published: July 2013

Background: The precise pathogenesis of alopecia areata remains unknown, although this disease seems to be triggered by helper T cell infiltration in hair follicles. Recent studies of psoriasis and vitiligo have demonstrated the involvement of Th17 cells. Psoriasis and vitiligo occasionally develop concomitantly or inversely in patients with alopecia areata. Objective: The aim of this study was to determine whether Th17 cells are present in the affected lesions of alopecia areata. Methods: We performed immunofluorescent staining of representative immunocompetent cells that had infiltrated into the skin of the scalp in 4 individuals with alopecia areata (single patchy alopecia areata, multiple patchy alopecia areata, alopecia totalis and alopecia universalis). Results: We found the infiltration of CD4+IL-17A+ Th17 cells in the dermis, particularly around hair follicles, in all 4 cases. Conclusions: These findings suggest the possibility that alopecia areata is induced by a Th17 cell-associated autoimmune mechanism.
New Surgical Technique for the Treatment of Buried Penis: Results and Comparison with a Traditional Technique in 75 Patients
Authors: Spinoit Anne-Françoise , De Prycker Stefanie , Groen Luitzen-Albert , van Laecke Erik , Hoebeke Piet
Published: July 2013

Introduction: Buried penis is a pathology for which several reconstructive techniques are described. We report our technique and its outcome. Patients and Methods: 75 patients underwent repair of buried penis by one surgeon (P.H.) between 1997 and 2011. The first 17 patients (mean age 2.6 years) underwent skin-sparing circumcision. The next 58 patients (47 children, mean age 4.4 years; 11 adults, mean age 38 years) underwent our new technique. Its key point consists in releasing dartos tissue and in anchoring the corpora cavernosa to dartos bundles at the penile base. Outcome was evaluated by reoperation rate, complications and satisfaction according to surgeon/patients/parents. Results: The results of skin-sparing circumcision performed in 17 children at 1 year were reported as good by the surgeon in 62.5% (n = 10) and in 82.4% (n = 14) by patients. Reoperation for recurrence occurred in 29.4% (n = 5) patients. Complications treated conservatively were reported in 35.3% (n = 6) of the children. The new technique was performed in 58 patients (47 children, 11 adults). The results were reported as good by the surgeon in 96.6% (n = 56) and in 91.4% (n = 53) by patients. Reoperation occurred in 4 patients (6.9%). Conclusions: The outcome of the new technique is superior to skin-sparing circumcision regarding complication/reoperation rate and cosmesis according to patients/parents/surgeon.
Myocardin Regulates Vascular Response to Injury Through miR-24/-29a and Platelet-Derived Growth Factor Receptor-β
Authors: Talasila Amarnath , Yu Haixiang , Ackers-Johnson Matthew , Bot Martine , van Berkel Theo , Bennett Martin R. , Bot Ilze , Sinha Sanjay
Published: July 2013

Objective—

Myocardin, a potent transcriptional coactivator of serum response factor, is involved in vascular development and promotes a contractile smooth muscle phenotype. Myocardin levels are reduced during vascular injury, in association with phenotypic switching of smooth muscle cells (SMCs). However, the direct role of myocardin in vascular disease is unclear.

Approach and Results—

We show that re-expression of myocardin prevents the vascular injury response in murine carotid arteries, with reduced neointima formation due to decreased SMC migration and proliferation. Myocardin reduced SMC migration by downregulating platelet-derived growth factor receptor-β (PDGFRB) expression. Pdgfrb was regulated by myocardin-induced miR-24 and miR-29a expression, and antagonizing these microRNAs restored SMC migration. Furthermore, using miR-24 and miR-29a mimics, we demonstrated that miR-29a directly regulates
Pdgfrb
expression at the 3′ untranslated region while miR-24 has an indirect effect on
Pdgfrb
levels. Myocardin heterozygous-null mice showed an augmented neointima formation with increased SMC migration and proliferation, demonstrating that endogenous levels of myocardin are a critical regulator of vessel injury responses.

Conclusions—

Our results extend the function of myocardin from a developmental role to a pivotal regulator of SMC phenotype in response to injury, and this transcriptional coactivator may be an attractive target for novel therapeutic strategies in vascular disease.
Endothelial Von Willebrand Factor Promotes Blood–Brain Barrier Flexibility and Provides Protection From Hypoxia and Seizures in Mice
Authors: Suidan Georgette L. , Brill Alexander , De Meyer Simon F. , Voorhees Jaymie R. , Cifuni Stephen M. , Cabral Jessica E. , Wagner Denisa D.
Published: July 2013

Objective—

Aberrant blood–brain barrier (BBB) permeability is a hallmark pathology of many central nervous system diseases. von Willebrand factor (VWF) is stored in endothelial Weibel–Palade bodies from where it is released on activation into plasma and basement membrane. The role of VWF in endothelial homeostasis is unclear. The goal of this study was to assess the role of VWF in disease models associated with increased BBB permeability.

Approach and Results—

We did not find any differences in BBB permeability to Evans blue dye at baseline between wild-type and VWF
−/−
animals. We next used 2 models presenting with increased BBB permeability, hypoxia/reoxygenation and pilocarpine-induced status epilepticus, to assess the response of VWF
−/−
animals. In both models, VWF
−/−
mice maintained a tighter BBB than wild–type mice. VWF
−/−
mice fared worse in both conditions, with ≈100% of VWF
−/−
mice dying within 120 minutes after pilocarpine administration, whereas >80% of wild-type animals survived. Investigation into the status of tight junction proteins revealed that VWF
−/−
mice expressed more claudin-5 at baseline. In vitro work confirmed that the presence of subendothelial VWF is inhibitory to claudin-5 expression.

Conclusions—

VWF deficiency confers partial preservation of BBB integrity after hypoxia/reoxygenation and seizures. Surprisingly, this decrease in BBB permeability did not result in protection of animals because they demonstrated more severe pathology in both models compared with wild-type animals. These data suggest that a rigid BBB is detrimental (to the organism) during certain disease states and that VWF release may provide desired flexibility under stress.