bluuebunny/crossref_metadata_2025 huggingface dataset:
Cabergoline in the Treatment of Male Orgasmic Disorder—A Retrospective Pilot Analysis
Authors: Hollander Adam B. , Pastuszak Alexander W. , Hsieh Tung-Chin , Johnson William G. , Scovell Jason M. , Mai Christina K. , Lipshultz Larry I.
Published: March 2016

Introduction

Male orgasmic disorder is common, with few treatment options. Cabergoline is a dopamine agonist that acts centrally to normalize serum prolactin that could improve orgasmic dysfunction.

Aims

To determine whether cabergoline increases the potential for orgasm in men with orgasmic disorder.

Methods

A retrospective chart review of men treated in a single andrology clinic for delayed orgasm or anorgasmia in a pilot study using cabergoline 0.5 mg twice weekly was performed. Duration of treatment and response were noted. Medical records were examined for other factors including history of prostatectomy and concomitant androgen supplementation.

Main Outcome Measures

Subjective improvement in orgasmic function resulting from cabergoline treatment.

Results

Of 131 men treated with cabergoline for orgasmic disorder, 87 (66.4%) reported subjective improvement in orgasm and 44 (33.6%) reported no change in orgasm. Duration of therapy (P = .03) and concomitant testosterone therapy (P = .02) were associated with a significant positive response to cabergoline treatment. No differences were found between injectable and non-injectable testosterone formulations (P = .90), and neither age (P = .90) nor prior prostatectomy (P = .41) influenced the outcome of cabergoline treatment. Serum testosterone levels before (P = .26) and after (P = .81) treatment were not significantly different in responders vs non-responders.

Conclusion

Cabergoline is a potentially effective and easy-to-administer treatment for male orgasmic disorder, the efficacy of which appears to be independent of patient age or orgasmic disorder etiology. Prospective randomized trials are needed to determine the true role of cabergoline in the treatment of this disorder.
Long-Term Follow-Up of Individuals Undergoing Sex-Reassignment Surgery: Somatic Morbidity and Cause of Death
Authors: Simonsen Rikke Kildevæld , Hald Gert Martin , Kristensen Ellids , Giraldi Annamaria
Published: March 2016

Introduction

Studies of mortality and somatic well-being after sex-reassignment surgery (SRS) of transsexual individuals are equivocal. Accordingly, the present study investigated mortality and somatic morbidity using a sample of transsexual individuals who comprised 98% (n = 104) of all surgically reassigned transsexual individuals in Denmark.

Aims

To investigate somatic morbidity before and after SRS and cause of death and its relation to somatic morbidity after SRS in Danish individuals who underwent SRS from 1978 through 2010.

Methods

Somatic morbidity and mortality in 104 sex-reassigned individuals were identified retrospectively by data from the Danish National Health Register and the Cause of Death Register.

Main Outcome Measures

Somatic morbidity and cause of death.

Results

Overall, 19.2% of the sample were registered with somatic morbidity before SRS and 23.1% after SRS (P = not significant). In total, 8.6% had somatic morbidity before and after SRS. The most common diagnostic category was cardiovascular disease, affecting 18 individuals, 9 before and 14 after SRS, and 5 of those 14 who were affected after SRS had cardiovascular disease before and after SRS. Ten individuals died after SRS at an average age of 53.5 ± 7.9 years (male to female) and 53.5 ± 7.3 years (female to male).

Conclusion

Of 98% of all Danish transsexuals who officially underwent SRS from 1978 through 2010, one in three had somatic morbidity and approximately 1 in 10 had died. No significant differences in somatic morbidity or mortality were found between male-to-female and female-to-male individuals. Despite the young average age at death and the relatively larger number of individuals with somatic morbidity, the present study design does not allow for determination of casual relations between, for example, specific types of hormonal or surgical treatment received and somatic morbidity and mortality.
Three-dimensional modeling of pulsed soundings using a fast Fourier transform
Authors: Epov M.I. , Shurina E.P. , Shtabel E.P. , Shtabel N.V.
Published: March 2016

A method for three-dimensional modeling of pulsed soundings using a fast Fourier transform is developed: instead of the time-domain problem, it is proposed to solve a set of frequency-domain problems obtained by processing the original excitation pulse by a fast Fourier transform. The error of the proposed method compared to the method of solving the time-domain problem is numerically estimated for a model problem with a sinusoidal signal.
Paleoseismological studies in the epicentral area of the 1911 Kemin earthquake (northern Tien Shan)
Authors: Deev E.V. , Korzhenkov A.M.
Published: March 2016

The area of the Chon-Aksu and Kichi-Aksu grabens abounds in seismic deformation produced by historic and prehistoric events, among which the great Kemin (Kebin) earthquake of 1911, with a magnitude of Ms ≈ 8 and a shaking intensity of I0 = 10–11, generated by the Aksu fault. Trenching across a fault scarp of the 1911 event has revealed signatures of reverse slip resulted from another earthquake that occurred about 3000 years ago. Traces of a large event at ~12,700 yr BP appear in sediments of a tectonically dammed lake. The trenching results, along with radiocarbon dating and published evidence, show the Late Pleistocene–Holocene history of the Aksu fault to comprise prolonged quiescence periods separated by large earthquakes or earthquake clusters at 19,500–20,000, 12,700, 4000–3000, and <850 yr BP (including the 1911 Kemin shock).
Jerks and conductivity anisotropy of lower mantle
Authors: Plotkin V.V.
Published: March 2016

Conductivity anisotropy of the lower mantle presumably caused by phase change of dielectric magnesiowüstite at depths of 1500–2000 km is detectable from jerks. Jerks are induced by currents in the fluid outer core, propagate upward from the CMB through anisotropic conducting mantle, and appear on the Earth’s surface. The surface jerk patterns are studied theoretically from the potential of the geomagnetic field presented as a sum of magnetic and electric modes. Equations for the fields of both modes and their relationship in a weakly anisotropic earth are obtained by the perturbation method. The field potential is expanded into a series of spherical harmonics, and the equations are solved in the frequency and time domains. The surface jerk responses can be inverted to retrieve anisotropy parameters; the goal function in the inversion may correspond to misfit between the model and experimental values either along the horizontal or vertical components.
Epidemiologic Investigation of Injuries Associated With the 2013 Fertilizer Plant Explosion in West, Texas
Authors: Metzger Kristi , Akram Hammad , Feldt Bonnie , Stone Kahler , Alvey Stephanie , Henley Sandi , Hernandez Alicia , Melville Sharon , Haywood Tracy , Zane David
Published: March 2016

Objective

On April 17, 2013, a fire and subsequent explosion occurred at the West Fertilizer Company plant in West, Texas, and caused extensive damage to the adjacent neighborhood. This investigation described the fatal and nonfatal injuries caused by the explosion.

Methods

Persons injured by the fertilizer plant explosion were identified through death certificates, medical examination reports, medical records, and survivor interviews. Data on patient characteristics, type of injury, and location of injury were collected.

Results

Medical record review indicated that 252 individuals sought medical care for nonfatal injuries directly related to the explosion immediately after the explosion. Fifteen patients died of injuries sustained by the blast. Almost one-quarter of patients were admitted for treatment of injuries. Injuries sustained in the explosion included abrasions/contusions, lacerations/penetrating trauma, traumatic brain injuries/concussions, tinnitus/hearing problems, eye injuries, and inhalational injuries. Patients located closer to the explosion were more likely to be admitted to the hospital for treatment of injuries than were those who were located further away.

Conclusion

Explosions of this magnitude are rare, but can inflict severe damage to a community and its residents. This investigation could be a useful planning resource for other communities, public health agencies, first responders, and medical facilities. (Disaster Med Public Health Preparedness. 2016;10:583–590)
Surface phase defects induced downstream laser intensity modulation in high-power laser facility
Authors: Zhang Xin , Zhou Wei , Dai Wanjun , Hu Dongxia , Deng Xuewei , Huang Wanqing , Zhou Lidan , Yuan Qiang , Huang Xiaoxia , Wang De’en , Yang Ying
Published: March 2016

Optics surface phase defects induced intensity modulation in high-power laser facility for inertial confinement fusion research is studied. Calculations and experiments reveal an exact mapping of the modulation patterns and the optics damage spot distributions from the surface phase defects. Origins are discussed during the processes of optics manufacturing and diagnostics, revealing potential improvements for future optics manufacturing techniques and diagnostic index, which is meaningful for fusion level laser facility construction and its operation safety.
α-Tocopherol in breast milk of women with preterm delivery after a single postpartum oral dose of vitamin E
Authors: Pires Medeiros Jeane Franco , Ribeiro Karla Danielly da Silva , Lima Mayara Santa Rosa , das Neves Renata Alexandra Moreira , Lima Amanda Cibely Pinheiro , Dantas Raquel Costa Silva , da Silva Alyne Batista , Dimenstein Roberto
Published: March 2016

We evaluated the effect of maternal vitamin E supplementation on the α-tocopherol concentrations of colostrum, transitional milk and mature milk of women who had given birth prematurely. This longitudinal randomised-controlled trial divided eighty-nine women into two groups: a control group and a supplemented group. Blood and breast milk were collected from all the participants after delivery. Next, each woman in the supplemented group received 400 IU of RRR-α-tocopheryl acetate. Further breast milk samples were collected 24 h after the first collection, as well as 7 and 30 d after delivery. α-Tocopherol concentrations were determined by HPLC. The baseline α-tocopherol concentrations in the maternal serum of the two groups were similar: 1159·8 (sd 292·4) μg/dl (27·0 (SD 6·8) μmol/l) for the control group and 1128·3 (sd 407·2) μg/dl (26·2 (SD 9·5) μmol/l) for the supplemented group. None of the women was vitamin E deficient. Breast milk α-tocopherol concentrations increased by 60 % 24 h after supplementation in the intervention group and did not increase at all in the control group. α-Tocopherol concentration of the transitional milk in the supplemented group was 35 % higher compared with the control group. α-Tocopherol concentrations of the mature milk in both groups were similar. Maternal supplementation with 400 IU of RRR-α-tocopherol increased the vitamin E concentrations of the colostrum and transitional milk, but not of the mature milk. This study presents relevant information for the design of strategies to prevent and combat vitamin E deficiency in the risk group of preterm infants.
Greater flavonoid intake is associated with improved CVD risk factors in US adults
Authors: Kim Kijoon , Vance Terrence M. , Chun Ock K.
Published: March 2016

Epidemiological studies have reported that diets high in flavonoids are associated with a reduced risk of CVD. However, evidence on the association of dietary flavonoid intake with CVD risk factors is still scarce. The present study aimed to investigate the association of dietary flavonoid intake with CVD risk factors among US adults in the National Health and Nutrition Examination Survey (NHANES) 2007–2012. A total of 4042 US adults aged 19 years and older from the NHANES 2007–2012 participated in this cross-sectional, population-based study. Intakes of total and individual flavonoids were estimated from 2-d 24-h diet recall data by matching with the expanded US Department of Agriculture flavonoid, isoflavone and proanthocyanidin databases. After adjusting for covariates, increased HDL-cholesterol was associated with higher total flavonoid intake (0·54 % change). TAG and TAG:HDL-cholesterol ratio were inversely associated with anthocyanidin (−1·25 % change for TAG; −1·60 % change for TAG:HDL-cholesterol ratio) and total flavonoid intakes (−1·31 % change for TAG; −1·83 % change for TAG:HDL-cholesterol ratio), respectively. Insulin and homoeostasis model assessment for insulin resistance (HOMA-IR) were inversely associated with flavone (for insulin, −3·18 % change; 95 % CI −5·85, −0·44; for HOMA-IR, −3·10 % change; 95 % CI −5·93, −0·19) and isoflavone intakes (for insulin, −3·11 % change; 95 % CI −5·46, −0·70; for HOMA-IR, −4·01 % change; 95 % CI −6·67, −1·27). BMI was negatively associated with anthocyanidin intake (−0·60 % change). This study showed that higher flavonoid intake was associated with improved CVD risk factors. Further research is warranted to confirm the findings from this study as these associations were moderate in strength.
Relationship between general nutrition knowledge and diet quality in Australian military personnel
Authors: Kullen Charina J. , Farrugia Jamie-Lee , Prvan Tania , O’Connor Helen T.
Published: March 2016

A balanced diet informed by sound nutrition knowledge is key for operational readiness and the health of military personnel. Unfortunately, research suggests that military personnel have inadequate dietary intakes. This study assessed general nutrition knowledge, diet quality and their association in Australian military personnel. A convenience sample of male military personnel (n211) including Army soldiers and officers completed a validated general nutrition knowledge questionnaire (GNKQ) and FFQ. The GNKQ assessed knowledge of dietary guidelines (Section A), sources of nutrients (Section B), choosing everyday foods (Section C) and diet–disease relationships (Section D). The Australian Recommended Food Score (ARFS) was used to assess diet quality from FFQ data. Statistical analyses included theχ2test, Spearman’s correlation test,ttest, median test, ANCOVA and ordinal logistic regression. The mean total GNKQ score was 52·7 %. Participants performed best on Section A (58·5 %) followed by Sections B (57·3 %) and C (57·0 %) and worst on Section D (31·0 %). Overall, officers scored significantly higher than soldiers (58·7v. 51·9 %,P=0·001). Age was weakly but positively correlated with GNKQ total scores (r0·307;P<0·0005), with no significant effects seen for level of education (P=0·463) or living arrangement (P=0·167). Overall ARFS was 37·6 (sd7·7) (50·8 %) with officers scoring significantly higher than soldiers (54·7v. 50·3 %,P=0·040). No demographic variables influenced total ARFS. The total GNKQ score had a significant, positive but weak relationship with total ARFS (r0·179;P=0·009). Given the importance of nutrition to personnel health and operational readiness, initiatives to improve nutrition knowledge and diet quality are recommended in this population, especially in soldiers.
Trade in Environmental Goods: A Review of the WTO Appellate Body's Ruling in US‒Countervailing Measures (China)
Authors: BREWSTER RACHEL , BRUNEL CLAIRE , MAYDA ANNA MARIA
Published: March 2016

In this paper we claim that, in the WTO Appellate Body (AB)'s ruling in US‒Countervailing Measures (China), the AB decision has not put in question the practice of imposing countervailing duties (CVDs). While the US has formally ‘lost’ the case, a change in the procedures and tests used to motivate the CVD will allow the US to continue using this policy tool on the specified products. From an economic point of view, this is not welcome news since CVDs have the standard distortionary effects of tariffs and could go against environmental goals. From a political-economy point of view, the CVDs in this case appear driven by pressure of domestic manufacturers of clean energy technology and products.
Unterrichtsbezogene Fehlerorientierung von Lehrkräften – Adaption und Validierung eines Fragebogens
Authors: Böhnke Anja , Thiel Felicitas
Published: March 2016

Zusammenfassung. Fehlerorientierung gilt als zentrale individuelle Bedingung des Lernens aus Fehlern. Beim Lernen aus Fehlern werden Lernprozesse durch die Reflexion dysfunktionaler Handlungsroutinen provoziert. Der vorliegende Beitrag eröffnet den Blick auf eine Nutzbarmachung des Konzepts der Fehlerorientierung für die Analyse des Handelns von Lehrkräften im Unterricht. Vorgestellt wird ein adaptiertes, domänenspezifisches Instrument zur Erfassung der unterrichtsbezogenen Fehlerorientierung von Lehrkräften, das durch Expertenbeurteilungen inhaltlich validiert wurde. 959 Lehrpersonen aus drei Substichproben unterschiedlicher Expertisestufen (Lehramtsstudierende, Referendare, Lehrkräfte) bearbeiteten das adaptierte Instrument. Konfirmatorische Mehrgruppen-Faktorenanalysen ergaben (1) eine konsistente sechsdimensionale Struktur für alle drei Stichproben, (2) überzeugende Modellkennwerte hinsichtlich vorliegender metrischer und partieller skalarer Messinvarianz und (3) theoriegerechte Zusammenhänge mit beruflicher Zielorientierung und Lehrerselbstwirksamkeit. Trotz einiger Limitationen der Studie gibt es erste Belege dafür, dass mit dem adaptierten Instrument eine valide und domänenspezifische Messung der unterrichtsbezogenen Fehlerorientierung von Lehrkräften möglich ist.
Das nephrotische Syndrom beim Erwachsenen – Ursachen und Komplikationen
Authors: Seeger Harald , Fehr Thomas
Published: March 2016

Zusammenfassung. Das nephrotische Syndrom (NS) beim Erwachsenen ist ein seltenes Krankheitsbild. Es ist gekennzeichnet durch die Kombination von Ödemen, Proteinurie, Hypoalbuminämie und Hypercholesterinämie. Neben intrinsischen glomerulären Erkrankungen können sekundäre Schädigungen des Glomerulums durch Systemerkrankungen, Infektionen oder Medikamente zugrundeliegen. Aufgabe des erstbehandelnden Arztes ist es, das NS von anderen Ödemerkrankungen abzugrenzen. Die Abklärung der Ätiologie sollte durch einen Nephrologen erfolgen. Das NS ist mit verschiedenen Komplikationen assoziiert. Neben Proteinurie, Dyslipidämie und Ödemen können eine Thrombophilie, eine vermehrte Infektneigung, ein akutes Nierenversagen sowie ein Vitamin-D-Mangel vorliegen. Als Folge einer Therapie der Grunderkrankung mit Immunsuppressiva können Spätschäden wie Urothelkarzinome oder Hauttumoren auftreten. Für das erfolgreiche Management des NS sind neben der Therapie der Grunderkrankung die Kenntnis der Komplikationen und deren Behandlung entscheidend.
«Warum sehe und höre ich immer schlechter?»
Authors: Dolliana Patrik , Nüesch Reto
Published: March 2016

Zusammenfassung. Wir präsentieren den Fall einer 66-jährigen Frau, die sich mit einem heterogenen Beschwerdebild, primär aber mit einer Seh- und Hörstörung präsentierte und schliesslich an einem Multiorganversagen starb. Ursächlich konnte präterminal eine Kobaltintoxikation aufgrund einer defekten Hüftprothese gezeigt werden. Therapeutisch vordergründig ist die Explantation der Prothese. Wichtig ist die Awareness über das heterogene Krankheitsbild bei breitem Einsatz derartiger Implantate in der Vergangenheit.
Shisa6 traps AMPA receptors at postsynaptic sites and prevents their desensitization during synaptic activity
Authors: Klaassen Remco V. , Stroeder Jasper , Coussen Françoise , Hafner Anne-Sophie , Petersen Jennifer D. , Renancio Cedric , Schmitz Leanne J. M. , Normand Elisabeth , Lodder Johannes C. , Rotaru Diana C. , Rao-Ruiz Priyanka , Spijker Sabine , Mansvelder Huibert D. , Choquet Daniel , Smit August B.
Published: March 2016

Trafficking and biophysical properties of AMPA receptors (AMPARs) in the brain depend on interactions with associated proteins. We identify Shisa6, a single transmembrane protein, as a stable and directly interacting bona fide AMPAR auxiliary subunit. Shisa6 is enriched at hippocampal postsynaptic membranes and co-localizes with AMPARs. The Shisa6 C-terminus harbours a PDZ domain ligand that binds to PSD-95, constraining mobility of AMPARs in the plasma membrane and confining them to postsynaptic densities. Shisa6 expressed in HEK293 cells alters GluA1- and GluA2-mediated currents by prolonging decay times and decreasing the extent of AMPAR desensitization, while slowing the rate of recovery from desensitization. Using gene deletion, we show that Shisa6 increases rise and decay times of hippocampal CA1 miniature excitatory postsynaptic currents (mEPSCs). Shisa6-containing AMPARs show prominent sustained currents, indicating protection from full desensitization. Accordingly, Shisa6 prevents synaptically trapped AMPARs from depression at high-frequency synaptic transmission.
mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex
Authors: Pema Monika , Drusian Luca , Chiaravalli Marco , Castelli Maddalena , Yao Qin , Ricciardi Sara , Somlo Stefan , Qian Feng , Biffo Stefano , Boletta Alessandra
Published: March 2016

Previous studies report a cross-talk between the polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC) genes. mTOR signalling is upregulated in PKD and rapamycin slows cyst expansion, whereas renal inactivation of the Tsc genes causes cysts. Here we identify a new interplay between the PKD and TSC genes, with important implications for the pathophysiology of both diseases. Kidney-specific inactivation of either Pkd1 or Tsc1 using an identical Cre (KspCre) results in aggressive or very mild PKD, respectively. Unexpectedly, we find that mTORC1 negatively regulates the biogenesis of polycystin-1 (PC-1) and trafficking of the PC-1/2 complex to cilia. Genetic interaction studies reveal an important role for PC-1 downregulation by mTORC1 in the cystogenesis of Tsc1 mutants. Our data potentially explain the severe renal manifestations of the TSC/PKD contiguous gene syndrome and open new perspectives for the use of mTOR inhibitors in autosomal dominant PKD caused by hypomorphic or missense PKD1 mutations.
Observation of magnon-mediated current drag in Pt/yttrium iron garnet/Pt(Ta) trilayers
Authors: Li Junxue , Xu Yadong , Aldosary Mohammed , Tang Chi , Lin Zhisheng , Zhang Shufeng , Lake Roger , Shi Jing
Published: March 2016

Pure spin current, a flow of spin angular momentum without flow of any accompanying net charge, is generated in two common ways. One makes use of the spin Hall effect in normal metals (NM) with strong spin–orbit coupling, such as Pt or Ta. The other utilizes the collective motion of magnetic moments or spin waves with the quasi-particle excitations called magnons. A popular material for the latter is yttrium iron garnet, a magnetic insulator (MI). Here we demonstrate in NM/MI/NM trilayers that these two types of spin currents are interconvertible across the interfaces, predicated as the magnon-mediated current drag phenomenon. The transmitted signal scales linearly with the driving current without a threshold and follows the power-law Tn with n ranging from 1.5 to 2.5. Our results indicate that the NM/MI/NM trilayer structure can serve as a scalable pure spin current valve device which is an essential ingredient in spintronics.
Myocardial pathology induced by aldosterone is dependent on non-canonical activities of G protein-coupled receptor kinases
Authors: Cannavo Alessandro , Liccardo Daniela , Eguchi Akito , Elliott Katherine J. , Traynham Christopher J. , Ibetti Jessica , Eguchi Satoru , Leosco Dario , Ferrara Nicola , Rengo Giuseppe , Koch Walter J.
Published: March 2016

Hyper-aldosteronism is associated with myocardial dysfunction including induction of cardiac fibrosis and maladaptive hypertrophy. Mechanisms of these cardiotoxicities are not fully understood. Here we show that mineralocorticoid receptor (MR) activation by aldosterone leads to pathological myocardial signalling mediated by mitochondrial G protein-coupled receptor kinase 2 (GRK2) pro-death activity and GRK5 pro-hypertrophic action. Moreover, these MR-dependent GRK2 and GRK5 non-canonical activities appear to involve cross-talk with the angiotensin II type-1 receptor (AT1R). Most importantly, we show that ventricular dysfunction caused by chronic hyper-aldosteronism in vivo is completely prevented in cardiac Grk2 knockout mice (KO) and to a lesser extent in Grk5 KO mice. However, aldosterone-induced cardiac hypertrophy is totally prevented in Grk5 KO mice. We also show human data consistent with MR activation status in heart failure influencing GRK2 levels. Therefore, our study uncovers GRKs as targets for ameliorating pathological cardiac effects associated with high-aldosterone levels.
Spin generation via bulk spin current in three-dimensional topological insulators
Authors: Peng Xingyue , Yang Yiming , Singh Rajiv R.P. , Savrasov Sergey Y. , Yu Dong
Published: March 2016

To date, spin generation in three-dimensional topological insulators is primarily modelled as a single-surface phenomenon, attributed to the momentum-spin locking on each individual surface. In this article, we propose a mechanism of spin generation where the role of the insulating yet topologically non-trivial bulk becomes explicit: an external electric field creates a transverse pure spin current through the bulk of a three-dimensional topological insulator, which transports spins between the top and bottom surfaces. Under sufficiently high surface disorder, the spin relaxation time can be extended via the Dyakonov–Perel mechanism. Consequently, both the spin generation efficiency and surface conductivity are largely enhanced. Numerical simulation confirms that this spin generation mechanism originates from the unique topological connection of the top and bottom surfaces and is absent in other two-dimensional systems such as graphene, even though they possess a similar Dirac cone-type dispersion.
A de novo 2.78-Mb duplication on chromosome 21q22.11 implicates candidate genes in the partial trisomy 21 phenotype
Authors: Weisfeld-Adams James D , Tkachuk Amanda K , Maclean Kenneth N , Meeks Naomi L , Scott Stuart A
Published: March 2016

Down syndrome (DS) is the most common genetic cause of intellectual disability (ID) and in the majority of cases is the result of complete trisomy 21. The hypothesis that the characteristic DS clinical features are due to a single DS critical region (DSCR) at distal chromosome 21q has been refuted by recently reported segmental trisomy 21 cases characterised by microarray-based comparative genomic hybridisation (aCGH). These rare cases have implicated multiple regions on chromosome 21 in the aetiology of distinct features of DS; however, the map of chromosome 21 copy-number aberrations and their associated phenotypes remains incompletely defined. We report a child with ID who was deemed very high risk for DS on antenatal screening (1 in 13) and has partial, but distinct, dysmorphologic features of DS without congenital heart disease (CHD). Oligonucleotide aCGH testing of the proband detected a previously unreported de novo 2.78-Mb duplication on chromosome 21q22.11 that includes 16 genes; however, this aberration does not harbour any of the historical DSCR genes (APP, DSCR1, DYRK1A and DSCAM). This informative case implicates previously under-recognised candidate genes (SOD1, SYNJ1 and ITSN1) in the pathogenesis of specific DS clinical features and supports a critical region for CHD located more distal on chromosome 21q. In addition, this unique case illustrates how the increasing resolution of microarray and high-throughput sequencing technologies can continue to reveal new biology and enhance understanding of widely studied genetic diseases that were originally described over 50 years ago.
Periscope: quantitative prediction of soluble protein expression in the periplasm of Escherichia coli
Authors: Chang Catherine Ching Han , Li Chen , Webb Geoffrey I. , Tey BengTi , Song Jiangning , Ramanan Ramakrishnan Nagasundara
Published: March 2016

Periplasmic expression of soluble proteins inEscherichia colinot only offers a much-simplified downstream purification process, but also enhances the probability of obtaining correctly folded and biologically active proteins. Different combinations of signal peptides and target proteins lead to different soluble protein expression levels, ranging from negligible to several grams per litre. Accurate algorithms for rational selection of promising candidates can serve as a powerful tool to complement with current trial-and-error approaches. Accordingly, proteomics studies can be conducted with greater efficiency and cost-effectiveness. Here, we developed a predictor with a two-stage architecture, to predict the real-valued expression level of target protein in the periplasm. The output of the first-stage support vector machine (SVM) classifier determines which second-stage support vector regression (SVR) classifier to be used. When tested on an independent test dataset, the predictor achieved an overall prediction accuracy of 78% and a Pearson’s correlation coefficient (PCC) of 0.77. We further illustrate the relative importance of various features with respect to different models. The results indicate that the occurrence of dipeptide glutamine and aspartic acid is the most important feature for the classification model. Finally, we provide access to the implemented predictor through the Periscope webserver, freely accessible athttp://lightning.med.monash.edu/periscope/.
Genetic and pharmacological inhibition of vanin-1 activity in animal models of type 2 diabetes
Authors: van Diepen Janna A. , Jansen Patrick A. , Ballak Dov B. , Hijmans Anneke , Rutjes Floris P.J.T. , Tack Cees J. , Netea Mihai G. , Schalkwijk Joost , Stienstra Rinke
Published: March 2016

Vanins are enzymes that convert pantetheine to pantothenic acid (vitamin B5). Insights into the function of vanins have evolved lately, indicating vanin-1 to play a role in inflammation, oxidative stress and cell migration. Moreover, vanin-1 has recently gained attention as a novel modulator of hepatic glucose and lipid metabolism. In the present study, we investigated the role of vanin-1 in the development of hepatic steatosis and insulin resistance in animal models of obesity and diabetes. In addition, we evaluated the potency of RR6, a novel pharmacological vanin-1 inhibitor, as an anti-diabetic drug. Increased vanin activity was observed in plasma and liver of high fat diet (HFD)-induced obese mice, as well as ZDF-diabetic rats. Ablation of vanin-1 (Vnn1−/− mice) mildly improved glucose tolerance and insulin sensitivity in HFD-fed mice, but had no effects on body weight, hepatic steatosis or circulating lipid levels. Oral administration of RR6 for 8 days completely inhibited plasma vanin activity, but did not affect hepatic glucose production, insulin sensitivity or hepatic steatosis in ZDF-diabetes rats. In conclusion, absence of vanin-1 activity improves insulin sensitivity in HFD-fed animals, yet short-term inhibition of vanin activity may have limited value as an anti-diabetic strategy.
Titanium trisulfide (TiS3): a 2D semiconductor with quasi-1D optical and electronic properties
Authors: Island Joshua O. , Biele Robert , Barawi Mariam , Clamagirand José M. , Ares José R. , Sánchez Carlos , van der Zant Herre S. J. , Ferrer Isabel J. , D’Agosta Roberto , Castellanos-Gomez Andres
Published: March 2016

We present characterizations of few-layer titanium trisulfide (TiS3) flakes which, due to their reduced in-plane structural symmetry, display strong anisotropy in their electrical and optical properties. Exfoliated few-layer flakes show marked anisotropy of their in-plane mobilities reaching ratios as high as 7.6 at low temperatures. Based on the preferential growth axis of TiS3 nanoribbons, we develop a simple method to identify the in-plane crystalline axes of exfoliated few-layer flakes through angle resolved polarization Raman spectroscopy. Optical transmission measurements show that TiS3 flakes display strong linear dichroism with a magnitude (transmission ratios up to 30) much greater than that observed for other anisotropic two-dimensional (2D) materials. Finally, we calculate the absorption and transmittance spectra of TiS3 in the random-phase-approximation (RPA) and find that the calculations are in qualitative agreement with the observed experimental optical transmittance.
The fetal ovary exhibits temporal sensitivity to a ‘real-life’ mixture of environmental chemicals
Authors: Lea Richard G. , Amezaga Maria R. , Loup Benoit , Mandon-Pépin Béatrice , Stefansdottir Agnes , Filis Panagiotis , Kyle Carol , Zhang Zulin , Allen Ceri , Purdie Laura , Jouneau Luc , Cotinot Corinne , Rhind Stewart M. , Sinclair Kevin D. , Fowler Paul A.
Published: March 2016

The development of fetal ovarian follicles is a critical determinant of adult female reproductive competence. Prolonged exposure to environmental chemicals (ECs) can perturb this process with detrimental consequences for offspring. Here we report on the exposure of pregnant ewes to an environmental mixture of ECs derived from pastures fertilized with sewage sludge (biosolids): a common global agricultural practice. Exposure of pregnant ewes to ECs over 80 day periods during early, mid or late gestation reduced the proportion of healthy early stage fetal follicles comprising the ovarian reserve. Mid and late gestation EC exposures had the most marked effects, disturbing maternal and fetal liver chemical profiles, masculinising fetal anogenital distance and greatly increasing the number of altered fetal ovarian genes and proteins. In conclusion, differential temporal sensitivity of the fetus and its ovaries to EC mixtures has implications for adult ovarian function following adverse exposures during pregnancy.
Sequence evidence for common ancestry of eukaryotic endomembrane coatomers
Authors: Promponas Vasilis J. , Katsani Katerina R. , Blencowe Benjamin J. , Ouzounis Christos A.
Published: March 2016

Eukaryotic cells are defined by compartments through which the trafficking of macromolecules is mediated by large complexes, such as the nuclear pore, transport vesicles and intraflagellar transport. The assembly and maintenance of these complexes is facilitated by endomembrane coatomers, long suspected to be divergently related on the basis of structural and more recently phylogenomic analysis. By performing supervised walks in sequence space across coatomer superfamilies, we uncover subtle sequence patterns that have remained elusive to date, ultimately unifying eukaryotic coatomers by divergent evolution. The conserved residues shared by 3,502 endomembrane coatomer components are mapped onto the solenoid superhelix of nucleoporin and COPII protein structures, thus determining the invariant elements of coatomer architecture. This ancient structural motif can be considered as a universal signature connecting eukaryotic coatomers involved in multiple cellular processes across cell physiology and human disease.
Antiferromagnetic proximity effect in epitaxial CoO/NiO/MgO(001) systems
Authors: Li Q. , Liang J. H. , Luo Y. M. , Ding Z. , Gu T. , Hu Z. , Hua C. Y. , Lin H.-J. , Pi T. W. , Kang S. P. , Won C. , Wu Y. Z.
Published: March 2016

Magnetic proximity effect between two magnetic layers is an important focus of research for discovering new physical properties of magnetic systems. Antiferromagnets (AFMs) are fundamental systems with magnetic ordering and promising candidate materials in the emerging field of antiferromagnetic spintronics. However, the magnetic proximity effect between antiferromagnetic bilayers is rarely studied because detecting the spin orientation of AFMs is challenging. Using X-ray linear dichroism and magneto-optical Kerr effect measurements, we investigated antiferromagnetic proximity effects in epitaxial CoO/NiO/MgO(001) systems. We found the antiferromagnetic spin of the NiO underwent a spin reorientation transition from in-plane to out-of-plane with increasing NiO thickness, with the existence of vertical exchange spring spin alignment in thick NiO. More interestingly, the Néel temperature of the CoO layer was greatly enhanced by the adjacent NiO layer, with the extent of the enhancement closely dependent on the spin orientation of NiO layer. This phenomenon was attributed to different exchange coupling strengths at the AFM/AFM interface depending on the relative spin directions. Our results indicate a new route for modifying the spin configuration and ordering temperature of AFMs through the magnetic proximity effect near room temperature, which should further benefit the design of AFM spintronic devices.
Dual-Color Fluorescence Imaging of Magnetic Nanoparticles in Live Cancer Cells Using Conjugated Polymer Probes
Authors: Sun Minjie , Sun Bin , Liu Yun , Shen Qun-Dong , Jiang Shaojun
Published: March 2016

Rapid growth in biological applications of nanomaterials brings about pressing needs for exploring nanomaterial-cell interactions. Cationic blue-emissive and anionic green-emissive conjugated polymers are applied as dual-color fluorescence probes to the surface of negatively charged magnetic nanoparticles through sequentially electrostatic adsorption. These conjugated polymers have large extinction coefficients and high fluorescence quantum yield (82% for PFN and 62% for ThPFS). Thereby, one can visualize trace amount (2.7 μg/mL) of fluorescence-labeled nanoparticles within cancer cells by confocal laser scanning microscopy. Fluorescence labeling by the conjugated polymers is also validated for quantitative determination of the internalized nanoparticles in each individual cell by flow cytometry analysis. Extensive overlap of blue and green fluorescence signals in the cytoplasm indicates that both conjugated polymer probes tightly bind to the surface of the nanoparticles during cellular internalization. The highly charged and fluorescence-labeled nanoparticles non-specifically bind to the cell membranes, followed by cellular uptake through endocytosis. The nanoparticles form aggregates inside endosomes, which yields a punctuated staining pattern. Cellular internalization of the nanoparticles is dependent on the dosage and time. Uptake efficiency can be enhanced three-fold by application of an external magnetic field. The nanoparticles are low cytotoxicity and suitable for simultaneously noninvasive fluorescence and magnetic resonance imaging application.
Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis
Authors: Zhao Jiang , Dong Xingyou , Hu Xiaoyan , Long Zhou , Wang Liang , Liu Qian , Sun Bishao , Wang Qingqing , Wu Qingjian , Li Longkun
Published: March 2016

Zinc is an essential trace mineral for the normal functioning of the male reproductive system. Current studies have investigated the relationship between seminal plasma zinc and male infertility but have shown inconsistent results. Hence, we systematically searched PubMed, EMBASE, Science Direct/Elsevier, CNKI and the Cochrane Library for studies that examined the relationship between seminal plasma zinc and male infertility, as well as the effects of zinc supplementation on sperm parameters. Twenty studies were identified, including 2,600 cases and 867 controls. Our meta-analysis results indicated that the seminal plasma zinc concentrations from infertile males were significantly lower than those from normal controls (SMD (standard mean differences) [95% CI] −0.64 [−1.01, −0.28]). Zinc supplementation was found to significantly increase the semen volume, sperm motility and the percentage of normal sperm morphology (SMD [95% CI]: −0.99 [−1.60, −0.38], −1.82 [−2.63, −1.01], and −0.75 [−1.37, −0.14], respectively). The present study showed that the zinc level in the seminal plasma of infertile males was significantly lower than that of normal males. Zinc supplementation could significantly increase the sperm quality of infertile males. However, further studies are needed to better elucidate the correlation between seminal plasma zinc and male infertility.
A new approach to chemotherapy: drug-induced differentiation kills African trypanosomes
Authors: Wenzler Tanja , Schumann Burkard Gabriela , Schmidt Remo S. , Mäser Pascal , Bergner Andreas , Roditi Isabel , Brun Reto
Published: March 2016

Human African trypanosomiasis (sleeping sickness) is a neglected tropical disease caused by Trypanosoma brucei spp. The parasites are transmitted by tsetse flies and adapt to their different hosts and environments by undergoing a series of developmental changes. During differentiation, the trypanosome alters its protein coat. Bloodstream form trypanosomes in humans have a coat of variant surface glycoprotein (VSG) that shields them from the immune system. The procyclic form, the first life-cycle stage to develop in the tsetse fly, replaces the VSG coat by procyclins; these proteins do not protect the parasite from lysis by serum components. Our study exploits the parasite-specific process of differentiation from bloodstream to procyclic forms to screen for potential drug candidates. Using transgenic trypanosomes with a reporter gene in a procyclin locus, we established a whole-cell assay for differentiation in a medium-throughput format. We screened 7,495 drug-like compounds and identified 28 hits that induced expression of the reporter and loss of VSG at concentrations in the low micromolar range. Small molecules that induce differentiation to procyclic forms could facilitate studies on the regulation of differentiation as well as serving as scaffolds for medicinal chemistry for new treatments for sleeping sickness.
The Solar Spectrum in the Atacama Desert
Authors: Cordero R. R. , Damiani A. , Seckmeyer G. , Jorquera J. , Caballero M. , Rowe P. , Ferrer J. , Mubarak R. , Carrasco J. , Rondanelli R. , Matus M. , Laroze D.
Published: March 2016

The Atacama Desert has been pointed out as one of the places on earth where the highest surface irradiance may occur. This area is characterized by its high altitude, prevalent cloudless conditions and relatively low columns of ozone and water vapor. Aimed at the characterization of the solar spectrum in the Atacama Desert, we carried out in February-March 2015 ground-based measurements of the spectral irradiance (from the ultraviolet to the near infrared) at seven locations that ranged from the city of Antofagasta (on the southern pacific coastline) to the Chajnantor Plateau (5,100 m altitude). Our spectral measurements allowed us to retrieve the total ozone column, the precipitable water, and the aerosol properties at each location. We found that changes in these parameters, as well as the shorter optical path length at high-altitude locations, lead to significant increases in the surface irradiance with the altitude. Our measurements show that, in the range 0–5100 m altitude, surface irradiance increases with the altitude by about 27% in the infrared range, 6% in the visible range, and 20% in the ultraviolet range. Spectral measurements carried out at the Izaña Observatory (Tenerife, Spain), in Hannover (Germany) and in Santiago (Chile), were used for further comparisons.
Quantitatively probing the magnetic behavior of individual nanoparticles by an AC field-modulated magnetic force microscopy
Authors: Li Xiang , Lu Wei , Song Yiming , Wang Yuxin , Chen Aiying , Yan Biao , Yoshimura Satoru , Saito Hitoshi
Published: March 2016

Despite decades of advances in magnetic imaging, obtaining direct, quantitative information with nanometer scale spatial resolution remains an outstanding challenge. Current approaches, for example, Hall micromagnetometer and nitrogen-vacancy magnetometer, are limited by highly complex experimental apparatus and a dedicated sample preparation process. Here we present a new AC field-modulated magnetic force microscopy (MFM) and report the local and quantitative measurements of the magnetic information of individual magnetic nanoparticles (MNPs), which is one of the most iconic objects of nanomagnetism. This technique provides simultaneously a direct visualization of the magnetization process of the individual MNPs, with spatial resolution and magnetic sensitivity of about 4.8 nm and 1.85 × 10−20 A m2, respectively, enabling us to separately estimate the distributions of the dipolar fields and the local switching fields of individual MNPs. Moreover, we demonstrate that quantitative magnetization moment of individual MNPs can be routinely obtained using MFM signals. Therefore, it underscores the power of the AC field-modulated MFM for biological and biomedical applications of MNPs and opens up the possibility for directly and quantitatively probing the weak magnetic stray fields from nanoscale magnetic systems with superior spatial resolution.
Experimental constraints on light elements in the Earth’s outer core
Authors: Zhang Youjun , Sekine Toshimori , He Hongliang , Yu Yin , Liu Fusheng , Zhang Mingjian
Published: March 2016

Earth’s outer core is liquid and dominantly composed of iron and nickel (~5–10 wt%). Its density, however, is ~8% lower than that of liquid iron, and requires the presence of a significant amount of light element(s). A good way to specify the light element(s) is a direct comparison of density and sound velocity measurements between seismological data and those of possible candidate compositions at the core conditions. We report the sound velocity measurements of a model core composition in the Fe-Ni-Si system at the outer core conditions by shock-wave experiments. Combining with the previous studies, we found that the best estimate for the outer core’s light elements is ~6 wt% Si, ~2 wt% S, and possible ~1–2.5 wt% O. This composition satisfies the requirements imposed by seismology, geochemistry, and some models of the early core formation. This finding may help us to further constrain the thermal structure of the Earth and the models of Earth’s core formation.
Involvement of splenic iron accumulation in the development of nonalcoholic steatohepatitis in Tsumura Suzuki Obese Diabetes mice
Authors: Murotomi Kazutoshi , Arai Shigeyuki , Uchida Satoko , Endo Shin , Mitsuzumi Hitoshi , Tabei Yosuke , Yoshida Yasukazu , Nakajima Yoshihiro
Published: March 2016

Nonalcoholic steatohepatitis (NASH) is a common hepatic manifestation of metabolic syndrome and can lead to hepatic cirrhosis and cancer. It is considered that NASH is caused by multiple parallel events, including abnormal lipid metabolism, gut-derived-endotoxin-induced inflammation and adipocytokines derived from adipose tissue, suggesting that other tissues are involved in NASH development. Previous studies demonstrated that spleen enlargement is observed during the course of NASH pathogenesis. However, the involvement of splenic status in the progression of NASH remains unclear. In this study, we examined hepatic and splenic histopathological findings in the early stage of NASH using the Tsumura Suzuki Obese Diabetes (TSOD) mouse model established for assessing NASH. We found that 12-week-old TSOD mice clearly exhibited the histopathological features of NASH in the early stage. At this age, the spleen of TSOD mice showed markedly higher iron level than that of control Tsumura Suzuki Non Obesity (TSNO) mice. The level of accumulated iron was significantly decreased by feeding a diet with glucosyl hesperidin, a bioactive flavonoid, accompanied with alleviation of hepatic lesions. Furthermore, we found that splenic iron level was positively correlated with the severity of NASH manifestations, suggesting that abnormalities in the spleen are involved in the development of NASH.