bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraspecific variation of a desert shrub species in phenotypic plasticity in response to sand burial
Authors: Xu Liang , Huber Heidrun , During Heinjo J. , Dong Ming , Anten Niels P. R.
Published: May 2013

Shoot elongation is one of the main plastic responses of plants to burial, a ubiquitous stress factor in dry ecosystems. Yet, intraspecific variation in this response to burial and the extent to which this variation is functionally coordinated with variation in other trait responses are largely unknown.

We subjected seedlings of the shrub Caragana intermedia from 18 maternal parents (i.e. different half‐sib families) to repeated partial burial to investigate how burial affects shoot growth, stem mechanical traits and associated plasticity.

Burial increased both stem elongation and diameter growth of plants, but decreased biomass production. Half‐sib families had different rates of shoot elongation, and differed in their response to burial with respect to biomechanical stem properties. Across half‐sib families, the magnitude of these responses in mechanical traits was positively correlated with the magnitude of the stem elongation response.

These results indicate that plasticity in different stem traits in response to sand burial and intraspecific variation therein are functionally coordinated with respect to mechanical stability. The results emphasize the importance of considering functionally coordinated traits when analyzing phenotypic plasticity in plants.
Evidence for wave heating in the solar corona
Authors: Hahn Michael
Published: May 2013

The temperature of the Sun increases over a short distance from a few thousand degrees in the photosphere to over a million degrees in the corona. To understand coronal heating is one of the major problems in astrophysics. There is general agreement that the energy source is convective motion in and below the photosphere. It remains to determine how this mechanical energy is transported outward into the corona and then deposited as heat. Two classes of models have been proposed, namely those that rely on magnetic reconnection and those that rely on waves, particularly Alfvén waves. There is increasing evidence that waves are ubiquitous in the corona. However, a difficulty for wave‐driven models has been that most theories predict Alfvén waves to be undamped in the corona, and therefore they cannot dissipate their energy into heat. Our research has shown unambiguous observational evidence that the waves do damp at sufficiently low heights in the corona to be important for coronal heating.
Functional genomics lead to new therapies in follicular lymphoma
Authors: Oricchio Elisa , Wendel Hans‐Guido
Published: May 2013

Recent technological advances allow analysis of genomic changes in cancer in unprecedented detail. The next challenge is to prioritize the multitude of genetic aberrations found and identify therapeutic opportunities. We recently completed a study that illustrates the use of unbiased genetic screens and murine cancer models to find therapeutic targets among complex genomic data. We genetically dissected the common deletion of chromosome 6q and identified the ephrin receptor A7 (EPHA7) as a tumor suppressor in lymphoma. Notably, EPHA7 encodes a soluble splice variant that acts as an extrinsic tumor suppressor. Accordingly, we developed an antibody‐based strategy to specifically deliver EPHA7 back to tumors that have lost this gene. Recent sequencing studies have implicated EPHA7 in lung cancer and other tumors, suggesting a broader therapeutic potential for antibody‐mediated delivery of this tumor suppressor for cancer therapy. Together, our comprehensive approach provides new insights into cancer biology and may directly lead to the development of new cancer therapies.
Appropriateness of blood product transfusion in the Obstetrics and Gynaecology (O&G) department of a tertiary hospital in West Africa
Authors: Osei E. N. , Odoi A. T. , Owusu‐Ofori S. , Allain J.‐P.
Published: May 2013

Background

Misuse of blood by clinicians has been suggested as an explanation for blood shortages in sub‐Saharan Africa, although this idea is based on little evidence. This study evaluated whether routine halving (restricted) of blood requests was justified.

Study design and methods

On alternate days for 3 months in 2011–2012, restricted or full blood product supply [whole blood (WB), red cell concentrate (RCC)] was provided to the Obstetrics & Gynaecology department (O&G). Patient age, haemoglobin (Hb) level pre‐ and post‐transfusion, clinical condition, blood products request and supply, transfused and returned, clinical outcome were collated.

Results

Five hundred and nineteen patients (249 restricted and 270 full supply) received 1001 blood products (94·6% WB, 6·4% RCC). Clinical conditions were severe peri‐partum bleeding (72·4%) requiring emergency transfusion (82%) whilst 27·6% of total transfusion was for anaemia, 18% being moderate (8–10 g dL−1). Pre‐transfusion Hb level was <6 g dL−1 in 36·7%, 6–8 g dL−1 29·1% and ≥8 g dL−1 in 33·2% of cases. Fifty‐five percent of the transfused blood was stored ≤1 week. Restricted supply triggered requests for additional blood in 40% of cases compared to 10% of cases in full supply mode. Both for restricted or full supply, blood requested and units transfused/patient were similar (restricted 2·3 and 2·1 unit patient−1 and full 2·9 and 2·3 unit patient−1, respectively). Fatal clinical outcome was 3·1% evenly distributed between supply modes and transfusion reactions 0·8%.

Conclusions

O&G clinicians order blood according to clinical need and transfuse 85% of the products supplied. Product supply did not significantly affect use although the appropriateness of transfusion was difficult to assess.
The role of lipid metabolism in the acquisition of desiccation tolerance in Craterostigma plantagineum: a comparative approach
Authors: Gasulla Francisco , vom Dorp Katharina , Dombrink Isabel , Zähringer Ulrich , Gisch Nicolas , Dörmann Peter , Bartels Dorothea
Published: May 2013

Dehydration leads to different physiological and biochemical responses in plants. We analysed the lipid composition and the expression of genes involved in lipid biosynthesis in the desiccation‐tolerant plant Craterostigma plantagineum. A comparative approach was carried out with Lindernia brevidens (desiccation tolerant) and two desiccation‐sensitive species, Lindernia subracemosa and Arabidopsis thaliana. In C. plantagineum the total lipid content remained constant while the lipid composition underwent major changes during desiccation. The most prominent change was the removal of monogalactosyldiacylglycerol (MGDG) from the thylakoids. Analysis of molecular species composition revealed that around 50% of 36:x (number of carbons in the acyl chains: number of double bonds) MGDG was hydrolysed and diacylglycerol (DAG) used for phospholipid synthesis, while another MGDG fraction was converted into digalactosyldiacylglycerol via the DGD1/DGD2 pathway and subsequently into oligogalactolipids by SFR2. 36:x‐DAG was also employed for the synthesis of triacylglycerol. Phosphatidic acid (PA) increased in C. plantagineum, L. brevidens, and L. subracemosa, in agreement with a role of PA as an intermediate of lipid turnover and of phospholipase D in signalling during desiccation. 34:x‐DAG, presumably derived from de novo assembly, was converted into phosphatidylinositol (PI) in C. plantagineum and L. brevidens, but not in desiccation‐sensitive plants, suggesting that PI is involved in acquisition of desiccation tolerance. The accumulation of oligogalactolipids and PI in the chloroplast and extraplastidial membranes, respectively, increases the concentration of hydroxyl groups and enhances the ratio of bilayer‐ to non‐bilayer‐forming lipids, thus contributing to protein and membrane stabilization.
Fibrinogen concentrate in dilutional coagulopathy: a dose study in pigs
Authors: Martini Judith , Maisch Sonja , Pilshofer Lisa , Streif Werner , Martini Wenjun , Fries Dietmar
Published: May 2013

Dilutional coagulopathy can be reversed with fibrinogen concentrate. Effects of different fibrinogen dosages on clot function are not defined; high doses may increase the risk of thromboemboembolism. This study investigated the effect of six fibrinogen dosages on coagulation profile and blood loss in coagulopathic pigs.

Forty‐two pigs underwent a 60% hemodilution (HD) with hydroxyethylstarch (HES 130/0.4). After a standardized bone injury, animals randomly received 37.5, 75, 150, 300, 450 or 600 mg/kg fibrinogen (FGTW, LFB) or 500 ml of saline. Four hours later, a standardized liver injury was performed. Animals were then observed for two hours or until death. Blood loss was measured after death; Hemodynamic and coagulation parameters (thromboelastometry) were measured at baseline (BL), after HD, 15’, 1, 2, 4 hours after fibrinogen administration and 2 hours after liver injury or right before the animals’ death. Occurrence of thrombosis was examined in histological slides of internal organs. Statistical significance was set at p < 0.05.

Doses of 150 mg/kg fibrinogen and higher reversed dilutional coagulopathy: Maximum clot firmness (MCF) was decreased after hemodilution (36 ± 3 mm vs. 65 ± 4 mm at BL, p < 0.05) and returned to BL after fibrinogen administration (69 ± 5 mm). Blood loss was significantly decreased with increased fibrinogen dosages: 42 ± 19 (sham), 34 ± 14 (75 mg/kg), 29 ± 13 (150 mg/kg), 28 ± 10 ml/kgbw (600 mg/kg).

Fibrinogen (150‐600 mg/kg) normalized clot firmness and decreased blood loss. No signs of hypercoagulability or thromboembolism were detected after high dosages.
Integrating MBE materials with graphene to induce novel spin-based phenomena
Authors: Swartz Adrian G. , McCreary Kathleen M. , Han Wei , Wong Jared J. I. , Odenthal Patrick M. , Wen Hua , Chen Jen-Ru , Kawakami Roland K. , Hao Yufeng , Ruoff Rodney S. , Fabian Jaroslav
Published: May 2013

Magnetism in graphene is an emerging field that has received much theoretical attention. In particular, there have been exciting predictions for induced magnetism through proximity to a ferromagnetic insulator as well as through localized dopants and defects. Here, the authors discuss their experimental work using molecular beam epitaxy to modify the surface of graphene and induce novel spin-dependent phenomena. First, they investigate the epitaxial growth of the ferromagnetic insulator EuO on graphene and discuss possible scenarios for realizing exchange splitting and exchange fields by ferromagnetic insulators. Second, they investigate the properties of magnetic moments in graphene originating from localized pz-orbital defects (i.e., adsorbed hydrogen atoms). The behavior of these magnetic moments is studied using nonlocal spin transport to directly probe the spin-degree of freedom of the defect-induced states. They also report the presence of enhanced electron g-factors caused by the exchange fields present in the system. Importantly, the exchange field is found to be highly gate dependent, with decreasing g-factors with increasing carrier densities.
Enhanced light output from light emitting diodes with two-dimensional cone-shape nanostructured surface
Authors: Wang Benzhong , Chua Soo-Jin
Published: May 2013

A simple, inexpensive and high throughput approach for creating two-dimensional cone-shaped nanostructures is reported. A self-assembled array of polystyrene nanospheres is employed as the primary mask to fabricate such structures on AlGaInP red light emitting diodes, resulting in over two times increase of light output power. An orderly array of cones show higher intensity emitted in the forward direction than one that is randomly arranged.
Targeting the TLR Co-Receptor CD14 with TLR2-Derived Peptides Modulates Immune Responses to Pathogens
Authors: Raby Anne-Catherine , Holst Benjamin , Le Bouder Emmanuel , Diaz Constantino , Ferran Edgardo , Conraux Laurence , Guillemot Jean-Claude , Coles Barbara , Kift-Morgan Ann , Colmont Chantal S. , Szakmany Tamas , Ferrara Pascual , Hall Judith E. , Topley Nicholas , Labéta Mario O.
Published: May 2013

Toll-like receptor–mediated responses to pathogens can be modulated by targeting the TLR co-receptor CD14.
Now You See Me, Now You Don’t
Authors: Chow Edward Kai-Hua
Published: May 2013

Computer-aided design helps nanoparticles escape recognition and uptake by macrophages.
A prospective study on dinghy sailors’ training habits and injury incidence with a comparison between elite sailor and club sailor during a 12-month period
Authors: Bøymo-Having Lena , Grävare Magnus , Grävare Silbernagel Karin
Published: May 2013

Background

Sailing is an Olympic sport practiced by both men and women of all ages. Despite being a popular sport, we have found no prospective studies investigating the injury incidence and training quantity such as found for other sports. The purpose of this study was to do an inventory over dinghy sailors’ training habits, injury incidence and type of injury.

Methods

In this prospective cohort study, 45 sailors (17 women and 28 men), age 17–31 years, were included. 24 sailors belonged to the SWE Sailing Team and 21 were club sailors. All the participants kept a training diary, and once a month for 12 months they reported their training and injuries through a web-based questionnaire. Each time a sailor reported an injury, they were contacted by the researchers and an injury form was completed.

Results

The SWE Sailing Team performed significantly (p=0.006) more physical training than the club sailor. There was no significant difference (p=0.7) in hours of sail training. A total of 144 injuries were reported. The most common injury location was the knee (19%), followed by the lower leg (13%) and shoulder (12%). 30% of the injuries occurred during physical training, 17% during sail training and 12% during sail racing.

Conclusions

The most common injury location was the knee. The largest proportion of injuries occurred during physical training and unspecified activities. The least number of injuries occurred during sail racing. The injury location was different between the older more experienced sailor (more upper extremity injuries) compared with the younger sailors (more trunk injuries).
Case–control and prospective studies of dietary α-linolenic acid intake and prostate cancer risk: a meta-analysis
Authors: Carleton Amanda J , Sievenpiper John L , de Souza Russell , McKeown-Eyssen Gail , Jenkins David J A
Published: May 2013

Objective

α-Linolenic acid (ALA) is considered to be a cardioprotective nutrient; however, some epidemiological studies have suggested that dietary ALA intake increases the risk of prostate cancer. The main objective was to conduct a systematic review and meta-analysis of case–control and prospective studies investigating the association between dietary ALA intake and prostate cancer risk.

Design

A systematic review and meta-analysis were conducted by searching MEDLINE and EMBASE for relevant prospective and case–control studies.

Included studies

We included all prospective cohort, case–control, nested case-cohort and nested case–control studies that investigated the effect of dietary ALA intake on the incidence (or diagnosis) of prostate cancer and provided relative risk (RR), HR or OR estimates.

Primary outcome measure

Data were pooled using the generic inverse variance method with a random effects model from studies that compared the highest ALA quantile with the lowest ALA quantile. Risk estimates were expressed as RR with 95% CIs. Heterogeneity was assessed by χ2and quantified by I2.

Results

Data from five prospective and seven case–control studies were pooled. The overall RR estimate showed ALA intake to be positively but non-significantly associated with prostate cancer risk (1.08 (0.90 to 1.29), p=0.40; I2=85%), but the interpretation was complicated by evidence of heterogeneity not explained by study design. A weak, non-significant protective effect of ALA intake on prostate cancer risk in the prospective studies became significant (0.91 (0.83 to 0.99), p=0.02) without evidence of heterogeneity (I2=8%, p=0.35) on removal of one study during sensitivity analyses.

Conclusions

This analysis failed to confirm an association between dietary ALA intake and prostate cancer risk. Larger and longer observational and interventional studies are needed to define the role of ALA and prostate cancer.
Nocturnal sweating—a common symptom of obstructive sleep apnoea: the Icelandic sleep apnoea cohort
Authors: Arnardottir Erna Sif , Janson Christer , Bjornsdottir Erla , Benediktsdottir Bryndis , Juliusson Sigurdur , Kuna Samuel T , Pack Allan I , Gislason Thorarinn
Published: May 2013

Objectives

To estimate the prevalence and characteristics of frequent nocturnal sweating in obstructive sleep apnoea (OSA) patients compared with the general population and evaluate the possible changes with positive airway pressure (PAP) treatment. Nocturnal sweating can be very bothersome to the patient and bed partner.

Design

Case–control and longitudinal cohort study.

Setting

Landspitali—The National University Hospital, Iceland.

Participants

The Icelandic Sleep Apnea Cohort consisted of 822 untreated patients with OSA, referred for treatment with PAP. Of these, 700 patients were also assessed at a 2-year follow-up. The control group consisted of 703 randomly selected subjects from the general population.

Intervention

PAP therapy in the OSA cohort.

Main outcome measures

Subjective reporting of nocturnal sweating on a frequency scale of 1–5: (1) never or very seldom, (2) less than once a week, (3) once to twice a week, (4) 3–5 times a week and (5) every night or almost every night. Full PAP treatment was defined objectively as the use for ≥4 h/day and ≥5 days/week.

Results

Frequent nocturnal sweating (≥3× a week) was reported by 30.6% of male and 33.3% of female OSA patients compared with 9.3% of men and 12.4% of women in the general population (p<0.001). This difference remained significant after adjustment for demographic factors. Nocturnal sweating was related to younger age, cardiovascular disease, hypertension, sleepiness and insomnia symptoms. The prevalence of frequent nocturnal sweating decreased with full PAP treatment (from 33.2% to 11.5%, p<0.003 compared with the change in non-users).

Conclusions

The prevalence of frequent nocturnal sweating was threefold higher in untreated OSA patients than in the general population and decreased to general population levels with successful PAP therapy. Practitioners should consider the possibility of OSA in their patients who complain of nocturnal sweating.
Longitudinal trends in regulated rivers: a review and synthesis within the context of the serial discontinuity concept
Authors: Ellis Lucy Eunsun , Jones Nicholas Edward
Published: May 2013

Dams alter the geomorphology, water quality, temperature regime, and flow regime of lotic systems influencing the resources and habitat of fish, benthic invertebrates, and lower trophic levels. Since the inception of the river continuum concept and the serial discontinuity concept (SDC), biotic and abiotic impacts below impoundments have been the focus of many lotic studies. However, recovery gradients below dams are rarely examined in sufficient detail and no current synthesis of longitudinal impacts in regulated rivers exists. This understanding is needed to build ecological relationships in regulated rivers to inform environmental flows science and management. In this review, we provide evidence for SDC predictions on physical, chemical, and biological recovery in regulated rivers. Additionally, we determine how these changes are reflected in the benthic community. Our review suggests that two recovery gradients exist in regulated rivers: (1) a longer, thermal gradient taking up to hundreds of kilometres downstream; and (2) a shorter, resource subsidy gradient recovering within 1–4 km downstream of an impoundment. Total benthic invertebrate abundance varies considerably, with both increases and reductions observed at near-dam sites and varying in recovery downstream. Much of this variability stems from the degree of flow alteration and resource subsidies from the upstream reservoir. In contrast, benthic diversity is often reduced below dams irrespective of dam location and operation with little recovery observed downstream. The community at near-dam sites is largely composed of filter-feeding invertebrates which are quickly replaced downstream, while stoneflies are reduced below impoundments with limited downstream recovery. Despite a lack of formal testing, studies support SDC predictions. The SDC still provides a useful theoretical framework for hypothesis testing, and future studies should further expand the SDC to include empirical estimation within the context of the landscape.
SKILL-BIASED EXPORT GROWTH: ACCOUNTING FOR THE CHANGES IN LABOR CONTENTS ACROSS ETHNIC GROUPS IN MALAYSIA (1991–2000)
Authors: SAARI M. YUSOF , PEI JIANSUO
Published: May 2013

This paper quantifies the extent to which trade liberalization in Malaysia between 1991 and 2000 has contributed to the expansion in the most skilled labor, which in turn can validate the trade-enhanced quality upgrading hypothesis. By using an input–output structural decomposition analysis (SDA), results confirm the theoretical predication that skills help to upgrade the quality of exporting commodities, by documenting that trade growth is associated with increases in the use of the higher skilled labor. We observe that Chinese and Indian ethnic groups contribute the most to the quality upgrading of exporting commodities, more so than the Malays, which imply productivity differentials among the ethnic groups.
ESTIMATING THE UNCERTAINTY OF THE BEHAVIOR OF A PWM POWER CONVERTER BY ANALYZING A SET OF EXPERIMENTAL BIFURCATION DIAGRAMS
Authors: KOLOKOLOV YURY , MONOVSKAYA ANNA
Published: May 2013

One of the main faults of a PWM power converter is linked to losing the operating process stability because of bifurcations. A bifurcation diagram contains information on the evolution of the behavior of a PWM power converter that could be theoretically used to prevent the bifurcations. Surprisingly, applying the bifurcation analysis is not yet typical in engineering practice. One of the reasons seems to be in the fundamental properties of the PWM power converter dynamics caused by the unavoidable uncertainty of its behavior near a bifurcation point. We propose a new approach to estimating this uncertainty. By analyzing a set of experimental bifurcation diagrams, our approach allows to determine both the location of the uncertainty zone and the quantitative regularities of the behavior within this zone. The proposed approach can be applied to design and maintenance, including fault diagnosis, and also to scientific research of the nonlinear dynamics regularities. Our results are experimentally verified by using the "PWM DC drive" setup.
BIOMECHANICAL CONSEQUENCE OF EXTENSOR POLLICIS LONGUS TENDON RELOCATION
Authors: Tanaka Martin L. , Wiesler Ethan R. , Chloros George D.
Published: May 2013

The extensor pollicis longus (EPL) tendon is responsible for thumb extension and normally passes over Lister's tubercle which acts as a pulley. During procedures in which access to the radiocarpal joint is required through a dorsal approach, the EPL tendon must be relocated toward the radial side of the wrist. However, in the clinical setting, we have observed that some patients have limited thumb extension following relocation surgery. In order to better understand this effect, a rigid body mathematical model was developed to evaluate the effect of EPL tendon relocation on thumb extension. Simulated thumb extensions were performed for both the natural and relocated positions and the model was calibrated and verified with cadaveric experimental data. Relocating the EPL tendon increased the moment arm resulting in an improved mechanical advantage. However, it also shortened the path causing tendon slack and reduced muscle force generation. When these two effects were combined, thumb extension decreased with tendon relocation and the thumb extension force was reduced. These results support clinical studies and observations that suggest displacement of the EPL tendon would result in loss of function or deformity. These results are a first step toward developing a quantitative understanding of the effect of EPL relocation. Further studies including more advanced models and clinical trials are needed before definite conclusions can be made regarding the implications of this research.
THE RELATIONSHIP OF TWO XANTHINE OXIDASE SINGLE NUCLEOTIDE POLYMORPHISMS TO HYPERURICEMIA, GOUT, AND DOSE OF XANTHINE OXIDASE INHIBITOR
Authors: Carroll Matthew B. , DeCastro-Pretelt Mauricio , Hust Nicole , Smith Freddie , Belema Tigist , Schramko Mary L. , Harris Chylander C. , Bashford Michael T.
Published: May 2013

Background: There is evidence linking xanthine oxidase (XO) single nucleotide polymorphisms (SNPs) to multiple medical conditions. The relationship of XO SNPs to hyperuricemia/gout is limited. An in vitro study of serum from healthy adults found two XO SNPs at 2107A > G and 3662A > G associated with a two-fold higher activity of the enzyme. Materials and Methods: The main outcomes of this study were to determine if the presence of either 2107A > G or 3662A > G XO SNP led to the occurrence of hyperuricemia, gout, or necessitated a higher dose of XO inhibitor (XOI) to achieve a treatment goal of less than 6 mg/dL. A total of 72 patients were enrolled in the hyperuricemia/gout group; 41 in the control group. XO SNPs were amplified and sequenced. Patient interviews and chart reviews gathered demographic data, use of XOI, comorbidities, and serum uric acid levels. Results: The 2107A > G SNP was detected in six patients with hyperuricemia/gout and two patients in the control group. There was no association between either XO SNP with the occurrence of hyperuricemia/gout (p = 0.709). A higher dose of allopurinol was needed to achieve a treatment serum uric acid goal of less than 6 mg/dL (p = 0.049). The 3662A > G SNP was not identified in any patients in the either group of the study. Conclusion: While the presence of 2107A > G SNP had no relationship to hyperuricemia or gout in our cohort it did affect the dose of allopurinol needed to achieve a treatment goal of less than 6 mg/dL. The 3662A > G SNP was not identified in our sample.
COMPUTER-BASED IDENTIFICATION OF NORMAL AND ALCOHOLIC EEG SIGNALS USING WAVELET PACKETS AND ENERGY MEASURES
Authors: FAUST OLIVER , YU WENWEI , KADRI NAHRIZUL ADIB
Published: May 2013

This paper describes a computer-based identification system of normal and alcoholic Electroencephalography (EEG) signals. The identification system was constructed from feature extraction and classification algorithms. The feature extraction was based on wavelet packet decomposition (WPD) and energy measures. Feature fitness was established through the statistical t-test method. The extracted features were used as training and test data for a competitive 10-fold cross-validated analysis of six classification algorithms. This analysis showed that, with an accuracy of 95.8%, the k-nearest neighbor (k-NN) algorithm outperforms naïve Bayes classification (NBC), fuzzy Sugeno classifier (FSC), probabilistic neural network (PNN), Gaussian mixture model (GMM), and decision tree (DT). The 10-fold stratified cross-validation instilled reliability in the result, therefore we are confident when we state that EEG signals can be used to automate both diagnosis and treatment monitoring of alcoholic patients. Such an automatization can lead to cost reduction by relieving medical experts from routine and administrative tasks.
INDECOMPOSABLE SURFACE BUNDLES OVER SURFACES
Authors: BAYKUR R. İNANÇ , MARGALIT DAN
Published: May 2013

For each pair of integers g ≥ 2 and h ≥ 1, we explicitly construct infinitely many fiber sum and section sum indecomposable genus g surface bundles over genus h surfaces whose total spaces are pairwise homotopy inequivalent.
Muscle-specificPikfyvegene disruption causes glucose intolerance, insulin resistance, adiposity, and hyperinsulinemia but not muscle fiber-type switching
Authors: Ikonomov Ognian C. , Sbrissa Diego , Delvecchio Khortnal , Feng Han-Zhong , Cartee Gregory D. , Jin Jian-Ping , Shisheva Assia
Published: May 2013

The evolutionarily conserved kinase PIKfyve that synthesizes PtdIns5P and PtdIns(3,5)P2has been implicated in insulin-regulated GLUT4 translocation/glucose entry in 3T3-L1 adipocytes. To decipher PIKfyve's role in muscle and systemic glucose metabolism, here we have developed a novel mouse model with Pikfyve gene disruption in striated muscle (MPIfKO). These mice exhibited systemic glucose intolerance and insulin resistance at an early age but had unaltered muscle mass or proportion of slow/fast-twitch muscle fibers. Insulin stimulation of in vivo or ex vivo glucose uptake and GLUT4 surface translocation was severely blunted in skeletal muscle. These changes were associated with premature attenuation of Akt phosphorylation in response to in vivo insulin, as tested in young mice. Starting at 10–11 wk of age, MPIfKO mice progressively accumulated greater body weight and fat mass. Despite increased adiposity, serum free fatty acid and triglyceride levels were normal until adulthood. Together with the undetectable lipid accumulation in liver, these data suggest that lipotoxicity and muscle fiber switching do not contribute to muscle insulin resistance in MPIfKO mice. Furthermore, the 80% increase in total fat mass resulted from increased fat cell size rather than altered fat cell number. The observed profound hyperinsulinemia combined with the documented increases in constitutive Akt activation, in vivo glucose uptake, and gene expression of key enzymes for fatty acid biosynthesis in MPIfKO fat tissue suggest that the latter is being sensitized for de novo lipid anabolism. Our data provide the first in vivo evidence that PIKfyve is essential for systemic glucose homeostasis and insulin-regulated glucose uptake/GLUT4 translocation in skeletal muscle.
Effects of intraportal exenatide on hepatic glucose metabolism in the conscious dog
Authors: Edgerton Dale S. , An Zhibo , Johnson Kathryn M. S. , Farmer Tiffany , Farmer Ben , Neal Doss , Cherrington Alan D.
Published: May 2013

Incretins improve glucose metabolism through multiple mechanisms. It remains unclear whether direct hepatic effects are an important part of exenatide's (Ex-4) acute action. Therefore, the objective of this study was to determine the effect of intraportal delivery of Ex-4 on hepatic glucose production and uptake. Fasted conscious dogs were studied during a hyperglycemic clamp in which glucose was infused into the hepatic portal vein. At the same time, portal saline (control; n = 8) or exenatide was infused at low (0.3 pmol·kg−1·min−1, Ex-4-low; n = 5) or high (0.9 pmol·kg−1·min−1, Ex-4-high; n = 8) rates. Arterial plasma glucose levels were maintained at 160 mg/dl during the experimental period. This required a greater rate of glucose infusion in the Ex-4-high group (1.5 ± 0.4, 2.0 ± 0.7, and 3.7 ± 0.7 mg·kg−1·min−1between 30 and 240 min in the control, Ex-4-low, and Ex-4-high groups, respectively). Plasma insulin levels were elevated by Ex-4 (arterial: 4,745 ± 428, 5,710 ± 355, and 7,262 ± 1,053 μU/ml; hepatic sinusoidal: 14,679 ± 1,700, 15,341 ± 2,208, and 20,445 ± 4,020 μU/ml, 240 min, area under the curve), whereas the suppression of glucagon was nearly maximal in all groups. Although glucose utilization was greater during Ex-4 infusion (5.92 ± 0.53, 6.41 ± 0.57, and 8.12 ± 0.54 mg·kg−1·min−1), when indices of hepatic, muscle, and whole body glucose uptake were expressed relative to circulating insulin concentrations, there was no indication of insulin-independent effects of Ex-4. Thus, this study does not support the notion that Ex-4 generates acute changes in hepatic glucose metabolism through direct effects on the liver.
Role of vasopressin in maintenance of potassium homeostasis in severe hemorrhage
Authors: Uyehara Catherine F. T. , Sarkar Joy
Published: May 2013

Uncontrolled elevation in plasma potassium within minutes of rapid blood volume loss is associated with mortality and distinguishes nonsurvivors of severe hemorrhage from survivors. In a pig model of severe hemorrhage, we discovered that along with a sharp increase in plasma potassium coincident with a shut down of urine flow, nonsurvivors also had an insufficient vasopressin response to hemorrhage. In contrast, survivors did have elevated vasopressin levels in response to hemorrhage and maintained plasma potassium within normal limits. While it has been demonstrated for some time that vasopressin can influence secretion of potassium in the distal nephron, the magnitude of this effect and conditions under which this contributes to physiological modulation of potassium excretion has yet to be defined. In this review, we assess the evidence that would suggest that vasopressin plays a key role in modulating potassium excretion and is important in the regulation of potassium homeostasis during hemorrhage.
Silicon: A Review of Its Potential Role in the Prevention and Treatment of Postmenopausal Osteoporosis
Authors: Price Charles T. , Koval Kenneth J. , Langford Joshua R.
Published: May 2013

Physicians are aware of the benefits of calcium and vitamin D supplementation. However, additional nutritional components may also be important for bone health. There is a growing body of the scientific literature which recognizes that silicon plays an essential role in bone formation and maintenance. Silicon improves bone matrix quality and facilitates bone mineralization. Increased intake of bioavailable silicon has been associated with increased bone mineral density. Silicon supplementation in animals and humans has been shown to increase bone mineral density and improve bone strength. Dietary sources of bioavailable silicon include whole grains, cereals, beer, and some vegetables such as green beans. Silicon in the form of silica, or silicon dioxide (SiO2), is a common food additive but has limited intestinal absorption. More attention to this important mineral by the academic community may lead to improved nutrition, dietary supplements, and better understanding of the role of silicon in the management of postmenopausal osteoporosis.
Vascular Endothelial Cell Function in Catastrophic Antiphospholipid Syndrome: A Case Report and Review of the Literature
Authors: Routy B. , Huynh T. , Fraser R. , Séguin C.
Published: May 2013

Catastrophic antiphospholipid syndrome (CAPS) is a rare autoimmune condition, which has been associated with a high mortality rate. However, with current management that includes a combination of anticoagulation, glucocorticoid administration, and plasma exchange, mortality rate has declined. Despite survival improvement with new generation immunosuppressive agents, their mechanisms of action are poorly defined, and CAPS is still considered a high-risk complication in patients known with antiphospholipid antibody syndrome. Herein, we present a case of a 79-year-old male who presented with a myocardial infarct and renal failure secondary to CAPS following a splenectomy for immune thrombocytopenia. Regardless of rapid combination of first-line treatment and rituximab therapy, the patient developed lethal cardiogenic shock secondary to mitral valve papillary muscle necrosis. Discussion of the pathophysiology and avenues of future therapies in CAPS are reported.
Obstacle Avoidance amongst Parkinson Disease Patients Is Challenged in a Threatening Context
Authors: Doan Jon B. , de Bruin Natalie , Pellis Sergio M. , Suchowersky Oksana , Whishaw Ian Q. , Brown Lesley A.
Published: May 2013

We examined whether people with Parkinson disease (PD) have difficulty negotiating a gait obstruction in threatening (gait path and obstacle raised above floor) and nonthreatening (gait path and obstacle at floor level) contexts. Ten PD patients were tested in both Meds OFF and Meds ON states, along with 10 age-matched controls. Participants completed 18 gait trials, walking 4.7 m at a self-selected speed while attempting to cross an obstacle 0.15 m in height placed near the centre point of the walkway. Kinematic and kinetic parameters were measured, and obstacle contact errors were tallied. Results indicated that PD patients made more obstacle contacts than control participants in the threatening context. Successful crossings by PD patients in the threatening condition also exhibited kinematic differences, with Meds OFF PD patients making shorter crossing steps, with decreased initiation and crossing velocities. The findings from this study lend support to the theory that PD patients rely on directed attention to initiate and control movement, while providing indication that the motor improvements provided by current PD pharmacotherapy may be limited by contextual interference. These movement patterns may be placing PD patients at risk of obstacle contact and falling.
Identification and Selective Degradation of Neopeptide-Containing Truncated Mutant Proteins in the Tumors with High Microsatellite Instability
Authors: Kim Won Kyu , Park Misun , Park Minhee , Kim Yun Ji , Shin Nara , Kim Hyun Ki , You Kwon Tae , Kim Hoguen
Published: May 2013

Purpose: Frameshift mutations in coding mononucleotide repeats (cMNR) are common in tumors with high microsatellite instability (MSI-H). These mutations generate mRNAs containing abnormal coding sequences and premature termination codons (PTC). Normally, mRNAs containing PTCs are degraded by nonsense-mediated mRNA decay (NMD). However, mRNAs containing PTCs located in the last exon are not subject to degradation by NMD (NMD-irrelevant). This study aimed to discover whether genes with frameshift mutations in the last exon generate truncated mutant proteins.

Experimental Design: We identified 66 genes containing cMNRs in the last exon by bioinformatic analysis. We found frequent insertion/deletion mutations in the cMNRs of 29 genes in 10 MSI-H cancer cell lines and in the cMNRs of 3 genes in 19 MSI-H cancer tissues. We selected 7 genes (TTK, TCF7L2, MARCKS, ASTE1, INO80E, CYHR1, and EBPL) for mutant mRNA expression analysis and 3 genes (TTK, TCF7L2, and MARCKS) for mutant protein expression analysis.

Results: The PTC-containing NMD-irrelevant mRNAs from mutated genes were not degraded. However, only faint amounts of endogenous mutant TTK and TCF7L2 were detected, and we failed to detect endogenous mutant MARCKS. By polysome analysis, we showed that mRNAs from genomic mutant MARCKS constructs are normally translated. After inhibiting 3 protein degradation pathways, we found that only inhibition of the proteasomal pathway facilitated the rescue of endogenous mutant TTK, TCF7L2, and MARCKS.

Conclusions: Our findings indicate that cancer cells scavenge potentially harmful neopeptide-containing mutant proteins derived from NMD-irrelevant abnormal mRNAs via the ubiquitin–proteasome system, and these mutant proteins may be important substrates for tumor-specific antigens. Clin Cancer Res; 19(13); 3369–82. ©2013 AACR.
Spontaneous Remission of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Elderly
Authors: Mizuno T. , Ishigaki M. , Nakajima K. , Matsue T. , Fukushima M. , Minato H. , Nojima N. , Atsushi Saito , Ishigami K. , Atsumi H. , Ito T. , Iguchi M. , Usuda D. , Okamura H. , Urashima S. , Asano M. , Fukuda A. , Izumi Y. , Takekoshi N. , Kanda T.
Published: May 2013

A 94-year-old female patient presented with anorexia and left axillar lymphadenopathy on admission. Her past history was angina pectoris at 83 years of age and total gastrectomy due to gastric cancer at 87 years. The family history revealed that her son had had a malignant lymphoma, the histopathological diagnosis of which was diffuse large B-cell lymphoma. A physical examination showed both cervical, axillar, and inguinal lymphadenopathy without tenderness. She had elevated lactate dehydrogenase, ferritin, and soluble interleukin-2 receptor (sIL-2R). Whole-body computed tomography confirmed the cervical, axillary, and inguinal lymphadenopathy. Gallium-68 imaging revealed positive accumulation in these superficial lymph nodes. A right inguinal lymph node biopsy showed features of Epstein-Barr virus-associated lymphoproliferative disorder. Immunohistological studies on this lymph node biopsy showed CD20-positive large cells, CD3-positive small cells, and CD30-partly-positive large cells. In situ hybridization showed Epstein-Barr virus-positive, LMP-partly-positive, and EBNA2-negative cells. She refused chemotherapy as her son had died from hematemesis during chemotherapy. She received intravenous hyperalimentation for 1 month after admission. No palpable lymph nodes were identified by physical examination or computed tomography 3 months after admission, and regression of lactate dehydrogenase, ferritin, and sIL-2R was observed. She recovered from anorexia and was discharged. She died from pneumonia 10 months later after initial symptoms of anorexia. The autopsy showed no superficial lymphadenopathy.
Transglutaminase-1 Mutations in Omani Families with Lamellar Ichthyosis
Authors: Al-Naamani Aisha , Al-Waily Ahmed , Al-Kindi Mohammed , Al-Awadi Maha , Al-Yahyaee Said Ali
Published: May 2013

Objective: To determine the molecular basis of familial ichthyosis in three Omani families. Subjects and Methods: Nine patients from three consanguineous families, A, B, and C, were born with typical features of lamellar ichthyosis subtype including collodion membrane and maintained ectropion, and epidermal scaling through their childhood. The 4 patients from family B had more severe symptoms requiring neonatal critical care and subsequent regular treatment with emollients, eye lubricants, and low-dose acitretin. DNA was extracted from peripheral blood by standard methods. The samples were initially genotyped to screen known loci linked to recessive ichthyosis on chromosomes 2q33-32 (ABCA12), 14q11 (TGM1), and 19p12-q12 using commercially supplied polymorphic fluorescent microsatellite markers. TGM1 was analyzed by direct sequencing for disease-associated mutations. Results: Two known pathogenic mutations in TGM1 were detected: p.Gly278Arg in families A and B and p.Arg396His in family C. These two mutations were segregating in an autosomal recessive mode of inheritance. Conclusion: Two known pathogenic TGM1 mutations were detected in three large consanguineous Omani families with lamellar ichthyosis. This study confirmed the geographic distribution of known mutations to an apparently unrelated population.
Comparison and Reproducibility of Techniques for Fluid Status Assessment in Chronic Hemodialysis Patients
Authors: Basso Flavio , Milan Manani Sabrina , Cruz Dinna N. , Teixeira Catarina , Brendolan Alessandra , Nalesso Federico , Zanella Monica , Ronco Claudio
Published: May 2013

Background: Several methods have been developed to assess the hydration status in chronic hemodialysis (HD) patients. The aim of this study was to compare body bioimpedance spectroscopy (BIS) with ultrasound (US) lung comet score (ULCs), B-type natriuretic peptide (BNP) and inferior vena cava diameter (IVCD) by US for the estimation of dry weight before and after HD and to analyze all methods in terms of fluid status variations induced by HD. An additional aim of this study was to establish the interoperator reproducibility of these methods. Methods: Two nephrologists evaluated BIS, ULCs, IVCD during inspiration (min) and expiration (max), the inferior vena cava collapsibility index (IVCCI) as well as BNP before and after HD in 30 patients. The same operators measured BIS, ULCs and IVCD in 28 HD patients in a blinded fashion. Results: There was a significant reduction in BIS, ULCs, IVCD and BNP after HD (p < 0.001), but a less significant reduction in IVCCI (p = 0.13). There was a significant correlation between BIS and ULCs, BNP and indexed IVCD (IVCDi)min (p < 0.05) before and after HD, and between BIS and IVCDimax only before HD. Conclusion: All methods were able to describe hyperhydration before and after HD, except for IVCCI after HD. All techniques correlated with BIS before HD. After HD, ULCs correlated better with BIS than IVCD in terms of evaluation of fluid status. It could be expected that the ULCs can give a real-time evaluation of interstitial water. The reproducibility of the measurement of BIS, IVCD and ULCs between the two operators was high.
Preoperative Serum Albumin Levels Predict 1-Year Postoperative Survival of Patients Undergoing Heart Transplantation
Authors: Kato Tomoko S. , Cheema Faisal H. , Yang Jonathan , Kawano Yumeko , Takayama Hiroo , Naka Yoshifumi , Farr Maryjane , Lederer David J. , Baldwin Matthew R. , Jin Zhezhen , Homma Shunichi , Mancini Donna M. , Schulze P. Christian
Published: May 2013

Background—

Serum albumin concentration has been recognized as a marker of nutrition, severity of inflammation, and hepatic function in patients with various chronic diseases. The purpose of this study was to investigate the impact of pretransplant serum albumin concentration on post-transplant outcome in heart transplant recipients.

Methods and Results—

Preoperative laboratory variables, including albumin concentration and donor-related information, were obtained from 822 consecutive patients undergoing heart transplant at Columbia University Medical Center between 1999 and 2010. The association between pretransplant albumin concentration and post-transplant 1-year survival was analyzed. Available data from the United Network for Organ Sharing (n=13 671) were also analyzed to evaluate the impact of preoperative albumin levels on post-transplant outcome. In our cohort, multivariable analysis revealed that preoperative albumin (mg/dL; hazard ratio, 0.46;
P
<0.0001) and preoperative total bilirubin (mg/dL; hazard ratio, 1.26;
P
=0.0002) were associated with post-transplant 1-year mortality. This implied that for every 1 mg/dL increase in albumin concentration, the post-transplant 1-year mortality rate decreased by 54%. The Kaplan–Meier analysis based on our patients cohort and the United Network for Organ Sharing dataset showed lower survival rate at 1-year post-transplant in patients with albumin levels ≤3.5 mg/dL compared with those with >3.5 mg/dL (our patients, 91.3 versus 72.4%;
P
<0.0001; United Network for Organ Sharing, 88.4 versus 84.8%;
P
<0.0001).

Conclusions—

Pretransplant serum albumin concentration is a strong prognostic marker for post-transplant survival in heart transplant recipients.