bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Response and Symptomatic Remission in Children Treated With Lisdexamfetamine Dimesylate for Attention-Deficit/Hyperactivity Disorder
Authors: Findling Robert L. , Adeyi Ben , Chen Gary , Dirks Bryan , Babcock Thomas , Scheckner Brian , Lasser Robert , Pucci Michael L. , Abdullah Huda I. , McGough James J.
Published: February 2017

Objective: To examine clinical response and symptomatic remission in two studies of lisdexamfetamine dimesylate (LDX) in children with attention-deficit/hyperactivity disorder (ADHD).

Methods: In a 4-week, placebo-controlled, double-blind trial, children 6–12 years of age with ADHD received LDX (30–70 mg/day) or placebo. In an open-label trial, children from previous studies were titrated to optimal dose over 4 weeks and maintained up to 1 year. Primary and secondary efficacy assessments were the ADHD Rating Scale IV (ADHD-RS-IV) and Clinical Global Impressions-Improvement (CGI-I) scale, respectively. Clinical response was defined as ≥30% reduction in ADHD-RS-IV total score with a CGI-I rating of 1 or 2; symptomatic remission was defined by ADHD-RS-IV total score ≤18.

Results: In the 4-week study (N=285), at any postdose assessment, 79.3% achieved response (median 13 days) and 67.1% achieved remission (median 22 days) with LDX versus 29.2% and 23.6% with placebo. In the long-term study (N=251), at any postdose assessment, 96.0% responded and 62.7% maintained response; 88.8% achieved remission and 46.4% maintained remission.

Conclusion: Most children treated with LDX achieved clinical response and symptomatic remission at one time point; once achieved, almost half maintained remission.
Altered Regional Cerebral Glucose Metabolism in Internet Game Overusers: A 18F-fluorodeoxyglucose Positron Emission Tomography Study
Authors: Park Hyun Soo , Kim Sang Hee , Bang Seong Ae , Yoon Eun Jin , Cho Sang Soo , Kim Sang Eun
Published: February 2017

Introduction: Internet game overuse is an emerging disorder and features diminished impulse control and poor reward-processing. In an attempt to understand the neurobiological bases of Internet game overuse, we investigated the differences in regional cerebral glucose metabolism at resting state between young individuals with Internet game overuse and those with normal use using 18F-fluorodeoxyglucose positron emission tomography study.

Methods: Twenty right-handed male participants (9 normal users: 24.7±2.4 years of age, 11 overusers: 23.5±2.9 years of age) participated. A trait measure of impulsivity was also completed after scanning.

Results: Internet game overusers showed greater impulsiveness than the normal users and there was a positive correlation between the severity of Internet game overuse and impulsiveness. Imaging data showed that the overusers had increased glucose metabolism in the right middle orbitofrontal gyrus, left caudate nucleus, and right insula, and decreased metabolism in the bilateral postcentral gyrus, left precentrai gyrus, and bilateral occipital regions compared to normal users.

Conclusion: Internet game overuse may be associated with abnormal neurobiological mechanisms in the orbitofrontal cortex, striatum, and sensory regions, which are implicated in impulse control, reward processing, and somatic representation of previous experiences. Our results support the idea that Internet game overuse shares psychological and neural mechanisms with other types of impulse control disorders and substance/non-substance-related addiction.
L-Methylfolate, Methylcobalamin, andN-Acetylcysteine in the Treatment of Alzheimer's Disease-Related Cognitive Decline
Authors: McCaddon Andrew , Hudson Peter R.
Published: February 2017

Almost 36 million people will have dementia in 2010—an alarming figure set to double every 20 years with the “greying” of the world population. Alzheimer's disease (AD) and dementia have enormous financial and social impacts on society. Prevention or illness delay of even a small percentage of cases would provide significant cost benefits for health-care systems. This review considers the rationale for a combined B-vitamin and antioxidant supplement (Cerefolin NAC) in treating and slowing AD-related cognitive decline.

Vitamin B12and folate deficiencies are associated with various cognitive disorders, including dementia. In the 1980s, plasma total homocysteine (tHcy) assays were introduced to assist in diagnosing these deficiencies. Hey is derived from dietary methionine. Cells re-methylate Hey to methionine using B12-dependent methionine synthase; 5-methyltetrahydrofolate (5-MTHF) acts as a methyl donor (Figure 1A). Alternatively, Hey is converted to cystathionine, and ultimately cysteine, by B6-dependent cystathionine β-synthase. Blood Hey levels rise in B6, B6, and folate deficiencies.Higher levels are also associated with aging, smoking, male gender, renal impairment, and drugs including methotrexate, metformin, and levodopa.

Using tHcy as a marker, B vitamin deficiencies were found to be highly prevalent in the elderly. This led to speculation that elevated blood Hey, hyperhomocysteinemia, might occur commonly in dementias, including AD. Hyperhomocysteinemia implies impaired meth-ylation reactions (hypomethylation), with predictable adverse effects for neurotransmitter synthesis and AD neuropathology. Hey is also associated with vascular disease, itself a risk factor for dementia.

Evidence for the “homocysteine hypothesis of dementia” came with reports of hyperhomocysteinemia in patients with clinically and pathologically confirmed AD. Raised blood levels were also observed in mild cognitive impairment (MCI) and vascular dementia. Although elevated Hey could be a consequence of, or coincidental with, dementia hyperhomocysteinemia, it is now recognised to be associated with an increased risk for both cognitive decline and incident dementia.
First-Episode Schizophrenia
Authors: Robinson Delbert
Published: February 2017

Clinicians treating patients with first-episode (FE) schizophrenia can draw upon the vast literature on the treatment of patients with multiple-episode schizophrenia. Studies with multi-episode patients, however, may not fully generalize to the treatment of FE patients. Studies with multi-episode patients typically recruit from hospitals or other acute care units, settings where patients usually have been either non-responsive or non-adherent to previous treatment, or mixtures of both. Studies of multi-episode patients therefore tend to include patients who are not fully responsive
to treatment. Without the filter of prior treatment history, FE compared with multi-episode patients may show a broader range of treatment patterns, ranging from extremely good to very poor. Further, studies of FE patients may be very instructive about side effects, as the confounding effect of prior medication use is particularly important with side effects. Finally, data suggest that much of the deterioration (eg, more severe negative symptoms) associated with schizophrenia may occur during the 5 years following illness onset. Providing patients with better treatment at illness onset offers the hope of improving their long-term outcome.

FE studies do have limitations. Relatively few new cases of schizophrenia occur each year. The typically chronic course of schizophrenia results in a large number of patients with multi-episode schizophrenia for every FE patient at any one time. Recruitment for studies of FE schizophrenia compared with those of multi-episode schizophrenia is often more difficult given the smaller number of available patients. We systematically know less about the treatment of FE patients than we do about the treatment of multi-episode patients.
Differential Diagnosis of Bipolar Disorder
Authors: Goldberg Joseph F.
Published: February 2017

Before reviewing the differential diagnosis of bipolar disorder, it is important to understand the epidemiology, incident, and prevalence of the disorder as well as to divide it by type: type I, type II, or the phenomenon of not otherwise specified, which is defined as subthreshold mania or hypomania. Subthreshold mania or hypomania entails fewer than the requisite number of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition symptoms of mania or hypomania, or an insufficient duration of time with which to make a diagnosis of a syndrome of mania or hypomania. Currently, the most reliable epidemiology of prevalence rates were reported in a replication study of 9,282 respondents to the National Comorbidity Survey conducted by Merikangas and colleagues.

Those data show there is a lifetime prevalence rate of bipolar I disorder of 1 % and bipolar II disorder of 1.1%. In this study, not otherwise specified was labeled subthreshold bipolar disorder as the illness duration was not long enough or the number of symptoms was not extensive enough to constitute syndromal mania or hypomania. This type had a prevalence rate of 2.4%, for a total lifetime prevalence of ~4.4%. This rate is somewhat higher than has been described in the past, but included the subdivision that researchers believe comprises the bipolar spectrum.

There has been much underdiagnosis or lack of diagnostic accuracy of bipolar disorder, with relative overdiagnosis of major depressive disorder, which historically has been well documented. However, in the last 10 years, there has been a substantial increase in the making of diagnoses of bipolar disorder in various clinical settings. One dataset examined ambulatory medical care survey data and found that among adults over an ~10-year period, there was approximately a doubling in the incidence of diagnosing bipolar disorder of any type (Slide 1).
The Quick Inventory of Depressive Symptomatology (Clinician and
Self-Report Versions) in Patients With Bipolar Disorder
Authors: Bernstein Ira H. , Rush A. John , Suppes Trisha , Kyotoku Yakasushi , Warden Diane
Published: February 2017

Introduction: The clinical and self-report
versions of the Quick Inventory of Depressive Symptomatology
(QIDS-C16 and QIDS-SR16) have
been well studied in patients with major depressive disorder and in one
recent study using patients with bipolar disorder. This article examines
these measures in a second sample of 141 outpatients with bipolar disorder
in different phases of the illness.

Methods: At baseline, 61 patients were depressed
and 30 were euthymic; at exit, 50 were depressed and 52 were euthymic. The
remaining patients (at baseline or exit) were in either a manic or mixed
phase and were pooled for statistical reasons.

Results: Similar results were found for the
QIDS-C16 and QIDS-SR16. Scores
were reasonably reliable to the extent that variability within groups
permitted. As expected, euthymic patients showed less depressive
symptomatology than depressed patients. Sad mood and general interest were
tne most discriminating symptoms between depressed and euthymic phases.
Changes in illness phase (baseline to exit) were associated with substantial
changes in scores. The relation of individual depressive symptoms to the
overall level of depression was consistent across phases.

Conclusion: Both the
QIDS-SR16 and QIDS-C16 are
suitable measures of depressive symptoms in patients with bipolar
disorder.
The Spectrum of Adjustment Disorders: Too Broad to be Clinically
Helpful
Authors: Semprini Federica , Fava Giovanni Andrea , Sonino Nicoletta
Published: February 2017

The clinical value of the current Diagnostic and
Statistical Manual of Mental Disorders diagnosis of
adjustment disorder is controversial. The aim of this article is to review
the literature on adjustment disorder and to present suggestions for the
improvement of this diagnostic category in future classification systems.
The literature utilized for this review was retrieved by MEDLINE (1967 until
May 2009) and was supplemented by a manual search of the literature. The
analysis of the literature indicates that the diagnosis of adjustment
disorder is not characterized by consistent clinical description and
prognosis, adequate differentiation from other disorders, or specific
psychometric and neurobiologic features. The spectrum of affective
disturbances entailed by the diagnosis of adjustment disorder appears to be
too broad. A major problem seems to lie in the fact that it is an exclusion
diagnosis that overlaps with subthreshold manifestations of mood and anxiety
disorders. More precise characterizations of stress-related disturbances are
available.
Rooted in Poverty?: The Political Economy of Terrorism in Xinjiang
Authors: YIN WEIWEN
Published: February 2017

It has been one of the most debated puzzles in the study of political economy of terrorism whether economic development can curb terrorism. In Xinjiang, a multi-ethnic region in West China, it is widely believed that higher income levels can decrease the likelihood of terrorism conducted by Uyghur separatists or Islamic extremists. However, the county-level data for the year of 2013 show that better economic performance may not work as is expected. Instead, empirical evidence indicates that income is positively associated with the probability of terrorist attacks, and the effect is statistically significant. Projects that are aimed at boosting local economic growth result in a flood of migrants, and the local Uyghurs are disadvantaged in the employment market. Consequently, economic grievances will be generated. Some, but not all, Uyghurs have a shared motivation to resist, but tight social control in the region constrains the form of resistance, in the sense that neither mass protests nor armed rebellion are feasible. Terrorist attacks that come at a lower cost become a preferable choice. In addition to economic grievances and tight control, external factors also help to boost terrorist activities in Xinjiang, but more empirical and field research is needed before we could clarify how external factors, such as the international jihadist movement, interact with local conditions and result in terrorism in the region.
Partisan Divergence and Public Support for the Courts of Taiwan
Authors: WU CHUNG-LI
Published: February 2017

The role of the court system in national policymaking has long been a central issue in democratic theory. Two contending theories, the traditional view and the realist one, have been offered to explain the influence of the judiciary compared to other political institutions. Looking at the subject from Dahl's realist perspective, it is hypothesized that supporters of the ruling majority generally have a favorable attitude toward the courts,ceteris paribus. This study sheds some light on the issue of public support by examining the public's evaluation of the judicial system in Taiwan. It evaluates the impact of political factors (especially party identification) on public support for the judiciary, based on the results of a national survey carried out in 2014 to assess public attitudes toward the courts and other political institutions. The findings reveal that, compared with other institutions, the courts enjoy a relatively high degree of popular confidence. The results also confirm the realist view that supporters of the policymaking majority generally hold favorable attitudes toward the judiciary, whereas opponents of the ruling coalition tend to express lower levels of diffuse support for the courts.
Interseeding berseem clover in winter wheat
Authors: Anderson Randy L.
Published: February 2017

Interseeding annual clovers in cereal grains may help organic producers reduce use of tillage following cereal harvest. Using clovers that winterkill would minimize need for tillage in the spring also. The objective of this study was to evaluate seedling emergence and survival of berseem clover (Trifolium alexandrinum L.) in winter wheat (Triticum aestivum L.). Berseem clover (hereafter, referred to as berseem) was planted 0, 2 and 4 weeks after initiation of winter wheat growth in the spring. Berseem density was highest when planted on April 12, 2 weeks after winter wheat broke dormancy. Establishment density was 40–80% less with the other planting dates. A dry interval during the 5 weeks preceding winter wheat harvest reduced seedling survival of berseem, killing more than 80% of seedlings. Winter wheat yield was reduced at the last planting date of berseem, which was attributed to mechanical injury to winter wheat by the drill when planting berseem. Berseem may not be viable for interseeding at this location or in drier regions. Clover species that are more drought tolerant will be needed.
Leukocyte and Skeletal Muscle Telomere Length and Body Composition in Monozygotic Twin Pairs Discordant for Long-term Hormone Replacement Therapy
Authors: Sillanpää Elina , Niskala Paula , Laakkonen Eija K. , Ponsot Elodie , Alén Markku , Kaprio Jaakko , Kadi Fawzi , Kovanen Vuokko , Sipilä Sarianna
Published: February 2017

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r= 0.69,p= .020) and in mean (r= 0.74,p= .014) and minimum SMTL (r= 0.88,p= .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r2= 0.30,p= .030), percentage total body (r2= 0.43,p= .014), and thigh (r2= 0.55,p= .004) fat, while minimum SMTL was associated with fat-free mass (r2= 0.27,p= .020) and thigh muscle area (r2= 0.42,p= .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.
Honoring Earth and Space Scientists
Authors:   AGU
Published: February 2017

AGU members and others in the news.
Cultivation and characterization of Candidatus Nitrosocosmicus exaquare, an ammonia-oxidizing archaeon from a municipal wastewater treatment system
Authors: Sauder Laura A , Albertsen Mads , Engel Katja , Schwarz Jasmin , Nielsen Per H , Wagner Michael , Neufeld Josh D
Published: February 2017

Thaumarchaeota have been detected in several industrial and municipal wastewater treatment plants (WWTPs), despite the fact that ammonia-oxidizing archaea (AOA) are thought to be adapted to low ammonia environments. However, the activity, physiology and metabolism of WWTP-associated AOA remain poorly understood. We report the cultivation and complete genome sequence of Candidatus Nitrosocosmicus exaquare, a novel AOA representative from a municipal WWTP in Guelph, Ontario (Canada). In enrichment culture, Ca. N. exaquare oxidizes ammonia to nitrite stoichiometrically, is mesophilic, and tolerates at least 15 mm of ammonium chloride or sodium nitrite. Microautoradiography (MAR) for enrichment cultures demonstrates that Ca. N. exaquare assimilates bicarbonate in association with ammonia oxidation. However, despite using inorganic carbon, the ammonia-oxidizing activity of Ca. N. exaquare is greatly stimulated in enrichment culture by the addition of organic compounds, especially malate and succinate. Ca. N. exaquare cells are coccoid with a diameter of ~1–2 μm. Phylogenetically, Ca. N. exaquare belongs to the Nitrososphaera sister cluster within the Group I.1b Thaumarchaeota, a lineage which includes most other reported AOA sequences from municipal and industrial WWTPs. The 2.99 Mbp genome of Ca. N. exaquare encodes pathways for ammonia oxidation, bicarbonate fixation, and urea transport and breakdown. In addition, this genome encodes several key genes for dealing with oxidative stress, including peroxidase and catalase. Incubations of WWTP biofilm demonstrate partial inhibition of ammonia-oxidizing activity by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), suggesting that Ca. N. exaquare-like AOA may contribute to nitrification in situ. However, CARD-FISH-MAR showed no incorporation of bicarbonate by detected Thaumarchaeaota, suggesting that detected AOA may incorporate non-bicarbonate carbon sources or rely on an alternative and yet unknown metabolism.
Towards human exploration of space: the THESEUS review series on muscle and bone research priorities
Authors: Lang Thomas , Van Loon Jack J.W.A. , Bloomfield Susan , Vico Laurence , Chopard Angele , Rittweger Joern , Kyparos Antonios , Blottner Dieter , Vuori Ilkka , Gerzer Rupert , Cavanagh Peter R.
Published: February 2017

Without effective countermeasures, the musculoskeletal system is altered by the microgravity environment of long-duration spaceflight, resulting in atrophy of bone and muscle tissue, as well as in deficits in the function of cartilage, tendons, and vertebral disks. While inflight countermeasures implemented on the International Space Station have evidenced reduction of bone and muscle loss on low-Earth orbit missions of several months in length, important knowledge gaps must be addressed in order to develop effective strategies for managing human musculoskeletal health on exploration class missions well beyond Earth orbit. Analog environments, such as bed rest and/or isolation environments, may be employed in conjunction with large sample sizes to understand sex differences in countermeasure effectiveness, as well as interaction of exercise with pharmacologic, nutritional, immune system, sleep and psychological countermeasures. Studies of musculoskeletal biomechanics, involving both human subject and computer simulation studies, are essential to developing strategies to avoid bone fractures or other injuries to connective tissue during exercise and extravehicular activities. Animal models may be employed to understand effects of the space environment that cannot be modeled using human analog studies. These include studies of radiation effects on bone and muscle, unraveling the effects of genetics on bone and muscle loss, and characterizing the process of fracture healing in the mechanically unloaded and immuno-compromised spaceflight environment. In addition to setting the stage for evidence-based management of musculoskeletal health in long-duration space missions, the body of knowledge acquired in the process of addressing this array of scientific problems will lend insight into the understanding of terrestrial health conditions such as age-related osteoporosis and sarcopenia.
In situ study of nucleation and aggregation phases for nanoparticles grown by laser-driven methods
Authors: Barberio M. , Antici P.
Published: February 2017

In the last decades, nanomaterials and nanotechnologies have become fundamental and irreplaceable in many fields of science and technology. When used in applications, their properties depend on many factors such as size, shape, internal structure and composition. For this, exact knowledge of their structural features is essential when developing fabrication technologies and searching for new types of nanostructures or nanoparticles with specific properties. For the latter, the knowledge of the precise temporal evolution of the growth processes is fundamental when it comes to industrial production and applications. Here we present a method to control, with very high precision, the starting of the aggregation phase during the Laser Ablation in solution growth process. This is obtained by monitoring the optical absorption of the colloidal solution. We apply this control method on the most popular metallic nanoparticle materials (Ag, Al, Co, and Ti) and verify the technique using morphological analysis conducted by AFM and SEM microscopy. The experimental results are explained in terms of Mie extinction theory and Thermal Model for Laser Ablation.
Concomitant underexpression of TGFBR2 and overexpression of hTERT are associated with poor prognosis in cervical cancer
Authors: Yang Hui , Zhang Hongyan , Zhong Yahua , Wang Qiaoli , Yang Lei , Kang Hong , Gao Xiaojia , Yu Haijun , Xie Conghua , Zhou Fuxiang , Zhou Yunfeng
Published: February 2017

The human telomerase reverse transcriptase (hTERT) is highly expressed in a variety of tumors. The transforming growth factor beta receptor type II (TGFBR2) is a downstream protein of transforming growth factor beta (TGF-β) which suppresses telomerase activity. However, the relevance of survival to the expression of TGFBR2, hTERT or TGFBR2/hTERT has not been previously investigated in cervical cancer tissues. Our study showed that patients with low level of TGFBR2 were associated with poor prognosis (HR = 1.704, P = 0.021), but no significant relevance between hTERT expression and survival (HR = 1.390, P = 0.181). However, a combination of low level of TGFBR2 and high level of hTERT was associated with a worse survival (HR = 1.892, P = 0.020), which had higher impact of hazard ratio (HR) on the overall survival (OS) than the low TGFBR2 expression alone. Knockdown of TGFBR2 expression by shRNA in Hela cells increased cell proliferation, cell invasion, G1/S transition and telomere homeostasis but decreased cell apoptosis. Overexpressing TGFBR2 and inhibiting hTERT suppressed Hela cell growth. These results would lead us to further explore whether a phenotype of TGFBR2low/hTERThigh could be considered as a predictor of poor prognosis, and whether simultaneous use of TGFBR2 agonist and hTERT inhibitor could be developed as a therapeutic strategy.
Molecular dietary analysis of two sympatric felids in the Mountains of Southwest China biodiversity hotspot and conservation implications
Authors: Xiong Mengyin , Wang Dajun , Bu Hongliang , Shao Xinning , Zhang Dan , Li Sheng , Wang Rongjiang , Yao Meng
Published: February 2017

Dietary information is lacking in most of small to mid-sized carnivores due to their elusive predatory behaviour and versatile feeding habits. The leopard cat (LPC;Prionailurus bengalensis) and the Asiatic golden cat (AGC;Catopuma temminckii) are two important yet increasingly endangered carnivore species in the temperate mountain forest ecosystem in Southwest China, a global biodiversity hotspot and a significant reservoir of China’s endemic species. We investigated the vertebrate prey of the two sympatric felids using faecal DNA and a next-generation sequencing (NGS)/metabarcoding approach. Forty vertebrate prey taxa were identified from 93 LPC and 10 AGC faecal samples; 37 taxa were found in the LPC diet, and 20 were detected in the AGC diet. Prey included 27 mammalian taxa, 11 birds, one lizard and one fish, with 73% (29/40) of the taxa assigned to the species level. Rodents and pikas were the most dominant LPC prey categories, whereas rodents, pheasant, fowl and ungulates were the main AGC prey. We also analysed the seasonal and altitudinal variations in the LPC diet. Our results provide the most comprehensive dietary data for these felids and valuable information for their conservation planning.
ERBB4 Confers Risk for Polycystic Ovary Syndrome in Han Chinese
Authors: Peng Yingqian , Zhang Wei , Yang Ping , Tian Ye , Su Shizhen , Zhang Changming , Chen Zi-Jiang , Zhao Han
Published: February 2017

A recent genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in European cohorts has identified six susceptibility loci mapping to 11q22.1 (YAP1), 2p21 (THADA), 11p14.1 (FSHB), 2q34 (ERBB4), 12q21.2 (KRR1), and 5q31.1 (RAD50). The loci of 11q22.1, 2p21 and 11p14.1 have been confirmed to be associated with PCOS in Chinese; whereas the other three new loci (2q34, 12q21.2, and 5q31.1) still need to be evaluated in Chinese. This study was aimed to determine if the three new loci identified in European PCOS also confer risks for PCOS in Han Chinese. We performed a case-control genetic association study comprising 1500 PCOS cases and 1220 age-matched control subjects. Marker SNPs rs1351592 (2q34, ERBB4), rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50) were genotyped using TaqMan-MGB probe assay. Genotyping analysis showed the allele frequency of rs1351592 in gene ERBB4 was significantly different (P = 1.05E-03) between PCOS cases and control group, and remained significant even after BMI adjustment (Padjusted = 2.09E-04). However, the allele frequencies of the other two risk variants, rs1275468 (12q21.2, KRR1) and rs13164856 (5q31.1, RAD50), were not significantly different in the replication cohort. Our results demonstrate that ERBB4, with the strongest association in European PCOS, also confers risk for PCOS in Han Chinese.
NG2 glial cells regulate neuroimmunological responses to maintain neuronal function and survival
Authors: Nakano Masayuki , Tamura Yasuhisa , Yamato Masanori , Kume Satoshi , Eguchi Asami , Takata Kumi , Watanabe Yasuyoshi , Kataoka Yosky
Published: February 2017

NG2-expressing neural progenitor cells (i.e., NG2 glial cells) maintain their proliferative and migratory activities even in the adult mammalian central nervous system (CNS) and produce myelinating oligodendrocytes and astrocytes. Although NG2 glial cells have been observed in close proximity to neuronal cell bodies in order to receive synaptic inputs, substantive non-proliferative roles of NG2 glial cells in the adult CNS remain unclear. In the present study, we generated NG2-HSVtk transgenic rats and selectively ablated NG2 glial cells in the adult CNS. Ablation of NG2 glial cells produced defects in hippocampal neurons due to excessive neuroinflammation via activation of the interleukin-1 beta (IL-1β) pro-inflammatory pathway, resulting in hippocampal atrophy. Furthermore, we revealed that the loss of NG2 glial cell-derived hepatocyte growth factor (HGF) exacerbated these abnormalities. Our findings suggest that NG2 glial cells maintain neuronal function and survival via the control of neuroimmunological function.
Sensory augmentation: integration of an auditory compass signal into human perception of space
Authors: Schumann Frank , O’Regan J. Kevin
Published: February 2017

Bio-mimetic approaches to restoring sensory function show great promise in that they rapidly produce perceptual experience, but have the disadvantage of being invasive. In contrast, sensory substitution approaches are non-invasive, but may lead to cognitive rather than perceptual experience. Here we introduce a new non-invasive approach that leads to fast and truly perceptual experience like bio-mimetic techniques. Instead of building on existing circuits at the neural level as done in bio-mimetics, we piggy-back on sensorimotor contingencies at the stimulus level. We convey head orientation to geomagnetic North, a reliable spatial relation not normally sensed by humans, by mimicking sensorimotor contingencies of distal sounds via head-related transfer functions. We demonstrate rapid and long-lasting integration into the perception of self-rotation. Short training with amplified or reduced rotation gain in the magnetic signal can expand or compress the perceived extent of vestibular self-rotation, even with the magnetic signal absent in the test. We argue that it is the reliability of the magnetic signal that allows vestibular spatial recalibration, and the coding scheme mimicking sensorimotor contingencies of distal sounds that permits fast integration. Hence we propose that contingency-mimetic feedback has great potential for creating sensory augmentation devices that achieve fast and genuinely perceptual experiences.
Relationships between motor patterns and intraluminal pressure in the 3-taeniated proximal colon of the rabbit
Authors: Quan Xiaojing , Yang Zixian , Xue Mai , Chen Ji-Hong , Huizinga Jan D.
Published: February 2017

Manometry is used worldwide to assess motor function of the gastrointestinal tract, and the measured intraluminal pressure patterns are usually equated with contraction patterns. In the colon, simultaneous pressure increases throughout the entire colon are most often called simultaneous contractions, although this inference has never been verified. To evaluate the relationship between pressure and contraction in the colon we performed high-resolution manometry and measured diameter changes reflecting circular muscle contractions in the rabbit colon. We show that within a certain range of contraction amplitudes and frequencies, the intraluminal pressure pattern faithfully resembles the contraction pattern. However, when the frequency is very high (as in fast propagating contractions in a cluster) the consequent intraluminal pressures merge. When the contraction speed of propagation is very fast (above ~5 cm/s), the resulting pressure occurs simultaneous throughout the colon; hence simultaneous pressure is measured as are caused by fast propagating contractions. The very slow propagating, low amplitude haustral boundary contractions show a very characteristic pattern in spatiotemporal contraction maps that is not faithfully reproduced in the pressure maps. Correct interpretation of pressure events in high-resolution manometry is essential to make it a reliable tool for diagnosis and management of patients with colon motor dysfunction.
Polymodal Responses in C. elegans Phasmid Neurons Rely on Multiple Intracellular and Intercellular Signaling Pathways
Authors: Zou Wenjuan , Cheng Hankui , Li Shitian , Yue Xiaomin , Xue Yadan , Chen Sixi , Kang Lijun
Published: February 2017

Animals utilize specialized sensory neurons enabling the detection of a wide range of environmental stimuli from the presence of toxic chemicals to that of touch. However, how these neurons discriminate between different kinds of stimuli remains poorly understood. By combiningin vivocalcium imaging and molecular genetic manipulation, here we investigate the response patterns and the underlying mechanisms of theC. elegansphasmid neurons PHA/PHB to a variety of sensory stimuli. Our observations demonstrate that PHA/PHB neurons are polymodal sensory neurons which sense harmful chemicals, hyperosmotic solutions and mechanical stimulation. A repulsive concentration of IAA induces calcium elevations in PHA/PHB and both OSM-9 and TAX-4 are essential for IAA-sensing in PHA/PHB. Nevertheless, the PHA/PHB neurons are inhibited by copper and post-synaptically activated by copper removal. Neuropeptide is likely involved in copper removal-induced calcium elevations in PHA/PHB. Furthermore, mechanical stimulation activates PHA/PHB in an OSM-9-dependent manner. Our work demonstrates how PHA/PHB neurons respond to multiple environmental stimuli and lays a foundation for the further understanding of the mechanisms of polymodal signaling, such as nociception, in more complex organisms.
Strong plasmonic enhancement of biexciton emission: controlled coupling of a single quantum dot to a gold nanocone antenna
Authors: Matsuzaki Korenobu , Vassant Simon , Liu Hsuan-Wei , Dutschke Anke , Hoffmann Björn , Chen Xuewen , Christiansen Silke , Buck Matthew R. , Hollingsworth Jennifer A. , Götzinger Stephan , Sandoghdar Vahid
Published: February 2017

Multiexcitonic transitions and emission of several photons per excitation comprise a very attractive feature of semiconductor quantum dots for optoelectronics applications. However, these higher-order radiative processes are usually quenched in colloidal quantum dots by Auger and other nonradiative decay channels. To increase the multiexcitonic quantum efficiency, several groups have explored plasmonic enhancement, so far with moderate results. By controlled positioning of individual quantum dots in the near field of gold nanocone antennas, we enhance the radiative decay rates of monoexcitons and biexcitons by 109 and 100 folds at quantum efficiencies of 60 and 70%, respectively, in very good agreement with the outcome of numerical calculations. We discuss the implications of our work for future fundamental and applied research in nano-optics.
A Novel Application of Non-Destructive Readout Technology to Localisation Microscopy
Authors: Barnett Samuel F. H. , Snape Mary , Hunter C. Neil , Juárez Miguel A. , Cadby Ashley J.
Published: February 2017

The fitting precision in localisation microscopy is highly dependent on the signal to noise ratio. To increase the quality of the image it is therefore important to increase the signal to noise ratio of the measurements. We present an imaging system for localisation microscopy based on non-destructive readout camera technology that can increase the signal to noise ratio of localisation based microscopy. This approach allows for much higher frame rates through subsampling a traditional camera frame. By matching the effective exposure to both the start time and duration of a single molecule we diminish the effects of read noise and temporal noise. We demonstrate the application of this novel method to localisation microscopy and show both an increase in the attainable signal to noise ratio of data collection and an increase in the number of detected events.
Finding Stable Graphene Conformations from Pull and Release Experiments with Molecular Dynamics
Authors: Yamaletdinov Ruslan D. , Pershin Yuriy V.
Published: February 2017

Here, we demonstrate that stable conformations of graphene nanoribbons can be identified using pull and release experiments, when the stretching force applied to a single-layer graphene nanoribbon is suddenly removed. As it is follows from our numerical experiments performed by means of molecular dynamics simulations, in such experiments, favorable conditions for the creation of folded structures exist. Importantly, at finite temperatures, the process of folding is probabilistic. We have calculated the transition probabilities to folded conformations for a graphene nanoribbon of a selected size. Moreover, the ground state conformation has been identified and it is shown that its type is dependent on the nanoribbon length. We anticipate that the suggested pull and release approach to graphene folding may find applications in the theoretical studies and fabrication of emergent materials and their structures.
How Native and Alien Metal Cations Bind ATP: Implications for Lithium as a Therapeutic Agent
Authors: Dudev Todor , Grauffel Cédric , Lim Carmay
Published: February 2017

Adenosine triphosphate (ATP), the major energy currency of the cell, exists in solution mostly as ATP-Mg. Recent experiments suggest that Mg2+ interacts with the highly charged ATP triphosphate group and Li+ can co-bind with the native Mg2+ to form ATP-Mg-Li and modulate the neuronal purine receptor response. However, it is unclear how the negatively charged ATP triphosphate group binds Mg2+ and Li+ (i.e. which phosphate group(s) bind Mg2+/Li+) and how the ATP solution conformation depends on the type of metal cation and the metal-binding mode. Here, we reveal the preferred ATP-binding mode of Mg2+/Li+ alone and combined: Mg2+ prefers to bind ATP tridentately to each of the three phosphate groups, but Li+ prefers to bind bidentately to the terminal two phosphates. We show that the solution ATP conformation depends on the cation and its binding site/mode, but it does not change significantly when Li+ binds to Mg2+-loaded ATP. Hence, ATP-Mg-Li, like Mg2+-ATP, can fit in the ATP-binding site of the host enzyme/receptor, activating specific signaling pathways.
miR302 regulates SNAI1 expression to control mesangial cell plasticity
Authors: De Chiara Letizia , Andrews Darrell , Watson Ariane , Oliviero Giorgio , Cagney Gerard , Crean John
Published: February 2017

Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFβ type II receptor and facilitated plasticity in a manner distinct from pluripotency, characterized by increased expression of Snail. miR302 overexpressing mesangial cells also exhibited enhanced expression of EZH2 coincident with Snail upregulation. esiRNA silencing of each component suggest that Smad3 and EZH2 are part of a complex that regulates plasticity and that miR302 regulates EZH2 and Snail independently. Subsequent manipulation of miR302 overexpressing cells demonstrated the potential of using this approach for reprogramming as evidenced by de novo expression of the tight junction components ZO-1 and E-cadherin and the formation of ZO-1 containing tight junctions. Understanding the processes through which dynamic epigenetic silencing is controlled in adults cells will allow us to address the epigenetic state of acquired disease and whether original states, regenerative in nature, can be restored with therapy.
A multiply-add engine with monolithically integrated 3D memristor crossbar/CMOS hybrid circuit
Authors: Chakrabarti B. , Lastras-Montaño M. A. , Adam G. , Prezioso M. , Hoskins B. , Payvand M. , Madhavan A. , Ghofrani A. , Theogarajan L. , Cheng K.-T. , Strukov D. B.
Published: February 2017

Silicon (Si) based complementary metal-oxide semiconductor (CMOS) technology has been the driving force of the information-technology revolution. However, scaling of CMOS technology as per Moore’s law has reached a serious bottleneck. Among the emerging technologies memristive devices can be promising for both memory as well as computing applications. Hybrid CMOS/memristor circuits with CMOL (CMOS + “Molecular”) architecture have been proposed to combine the extremely high density of the memristive devices with the robustness of CMOS technology, leading to terabit-scale memory and extremely efficient computing paradigm. In this work, we demonstrate a hybrid 3D CMOL circuit with 2 layers of memristive crossbars monolithically integrated on a pre-fabricated CMOS substrate. The integrated crossbars can be fully operated through the underlying CMOS circuitry. The memristive devices in both layers exhibit analog switching behavior with controlled tunability and stable multi-level operation. We perform dot-product operations with the 2D and 3D memristive crossbars to demonstrate the applicability of such 3D CMOL hybrid circuits as a multiply-add engine. To the best of our knowledge this is the first demonstration of a functional 3D CMOL hybrid circuit.
Targeted gene knock-in by CRISPR/Cas ribonucleoproteins in porcine zygotes
Authors: Park Ki-Eun , Powell Anne , Sandmaier Shelley E. S. , Kim Chan-Mi , Mileham Alan , Donovan David M. , Telugu Bhanu P.
Published: February 2017

The domestic pig is an important “dual purpose” animal model for agricultural and biomedical applications. There is an emerging consensus in the biomedical community for the use of large animal models such as pigs to either serve as an alternative, or complement investigations from the mouse. However, the use of pig has not proven popular due to technical difficulties and time required in generating models with desired genetic modifications. In this regard, the ability to directly modify the genome in the zygote and generate edited animals is highly desirable. This report demonstrates for the first time, the generation of gene targeted animals by direct injection of Cas9 ribonucleoprotein complex and short stretches of DNA sequences into porcine zygotes. The Cas9 protein from Streptococcus pyogenes was pre-complexed with a single guide RNA targeting downstream of the ubiquitously expressed COL1A gene, and co-injected with a single-stranded repair template into porcine zygotes. Using this approach a line of pigs that carry pseudo attP sites within the COL1A locus to enable phiC31 integrase mediated introduction of transgenes has been generated. This new route for genome engineering in pigs via zygote injection should greatly enhance applications in both agriculture and biomedicine.
Differentiation in drought tolerance mirrors the geographic distributions of alpine plants on the Qinghai-Tibet Plateau and adjacent highlands
Authors: Meng Li-Hua , Yang Jie , Guo Wen , Tian Bin , Chen Guang-Jie , Yang Yong-Ping , Duan Yuan-Wen
Published: February 2017

Climatic tolerance, especially drought tolerance, is one of the major factors shaping the geographic distributions of plant species. Thus, the general decline in rainfall from the Himalaya-Hengduan Mountains (HHM) to the inner Qinghai-Tibet Plateau (QTP) might account for the significant differences in species distributions and richness between the two regions. To test this hypothesis, we conducted a water stress experiment using four Anisodus species (A. tanguticus, A. luridus, A. carniolicoides and A. acutangulus), which were treated with different levels of water stress in a glasshouse, and examined their differences in physiological responses. The results suggest that A. tanguticus, which inhabits the inner QTP, generally has higher fitness under severe water stress than the other species based on its high root:shoot ratio, long-term water use efficiency and photosynthetic rate, indicating that it possesses a genetically based drought tolerance mechanism. Our results suggest that plant species inhabiting the inner QTP may be more drought tolerant than those inhabiting the HHM regions. This provides a new example supporting the hypothesis that climatic tolerance plays a major role in shaping plant distributions on the QTP and its adjacent highlands and presents new insights into the patterns of geographic distribution and diversity of the plants inhabiting these areas.
Spatial assessment of wolf-dog hybridization in a single breeding period
Authors: Pacheco C. , López-Bao J. V. , García E. J. , Lema F. J. , Llaneza L. , Palacios V. , Godinho R.
Published: February 2017

Understanding the dynamics of wolf-dog hybridization and delineating evidence-based conservation strategies requires information on the spatial extent of wolf-dog hybridization in real-time, which remains largely unknown. We collected 332 wolf-like scats over ca. 5,000km2in the NW Iberian Peninsula to evaluate wolf-dog hybridization at population level in a single breeding/pup-rearing season. Mitochondrial DNA (MtDNA) and 18 ancestry informative markers were used for species and individual identification, and to detect wolf-dog hybrids. Genetic relatedness was assessed between hybrids and wolves. We identified 130 genotypes, including 67 wolves and 7 hybrids. Three of the hybrids were backcrosses to dog whereas the others were backcrosses to wolf, the latter accounting for a 5.6% rate of introgression into the wolf population. Our results show a previously undocumented scenario of multiple and widespread wolf-dog hybridization events at the population level. However, there is a clear maintenance of wolf genetic identity, as evidenced by the sharp genetic identification of pure individuals, suggesting the resilience of wolf populations to a small amount of hybridization. We consider that real-time population level assessments of hybridization provide a new perspective into the debate on wolf conservation, with particular focus on current management guidelines applied in wolf-dog hybridization events.