bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective Cell Immunoablation in Undisrupted Developing Avian Embryos
Authors: López-Díaz Maríacruz , Buján-Varela Julia , Cadórniga-Valiño Carlos
Published: December 2016

In birds the construction of germline chimeras by grafting exogenous primordial germ cells (PGCs) during embryonic development is feasible since they migrate to the gonads through the blood. Up to date, the efficiencies are highly variable, in part dependent on the destruction of endogenous PGCs in the recipient embryo. We show an almost complete ablation of the endogenous PGCs in stage X embryos using a baby rabbit serum (BRS), with previous cellular signaling by specific antibodies (SSEA1). The application of the treatments, either on epiblast or subgerminaly, produced the reduction of the PGCs in the embryos in a dose dependent manner. No malformations or damages were detected in the treated embryos. However, subgerminal injection of this cocktail produced a massive cellular destruction in all embryos. Therefore, sequential application is a selective and effective method to produce receptor embryos. Nevertheless, it can also be highly destructive if the mixture is applied locally, this could be useful in the treatment of malignancies.

SUMMARY STATEMENT

An immunosurgery procedure is described that yields an almost complete ablation of primordial germ cells in early developing chick embryos, thus increasing the expected rates of chimerism when foreign PGCs are grafted onto these embryos
Analyses of the core eukaryotic protein subunit of telomerase support extensive adaptation to different evolutionary and life histories in the Metazoa
Authors: Lai Alvina G. , Pouchkina-Stantcheva Natalia , Di Donfrancesco Alessia , Kildisiute Gerda , Sahu Sounak , Aboobaker A. Aziz
Published: December 2016

Most animals employ telomerase, which consists of a catalytic subunit known as the telomerase reverse transcriptase (TERT) and an RNA template, to maintain telomere ends. Given the importance of TERT and the apparent importance of telomere biology in core metazoan life history traits like ageing and the control of somatic cell proliferation, we hypothesised that TERT would have patterns of sequence and regulatory evolution reflecting adaptations to diverse evolutionary and life histories across the Animal Kingdom. To test this, we performed a complete investigation of the evolutionary history of TERT across animals. We show that although TERT is almost ubiquitous across Metazoa, it has undergone substantial sequence evolution in canonical motifs. Beyond the known canonical motifs, we also identify and compare regions that are highly variable between lineages, but for which conservation exists within phyla. Recent data have highlighted the importance of alternate splice forms of TERT in non-canonical functions in some animals. Although animals may share some conserved introns, we find that the selection of exons for alternative splicing appears to be highly variable, and regulation by alternative splicing appears to be a very dynamic feature of TERT evolution. We show that even within a closely related group of triclad flatworms, where alternative splicing of TERT was previously correlated with reproductive strategy, we observe highly diverse alternative splicing patterns. Our work establishes that the evolutionary history and structural evolution of TERT involves previously unappreciated levels of change, supporting the view that this core eukaryotic protein has adapted to the requirements of diverse animal life histories.
Multi-scale approaches for high-speed imaging and analysis of large neural populations
Authors: Friedrich Johannes , Yang Weijian , Soudry Daniel , Mu Yu , Ahrens Misha B. , Yuste Rafael , Peterka Darcy S. , Paninski Liam
Published: December 2016

Progress in modern neuroscience critically depends on our ability to observe the activity of large neuronal populations with cellular spatial and high temporal resolution. However, two bottlenecks constrain efforts towards fast imaging of large populations. First, the resulting large video data is challenging to analyze. Second, there is an explicit tradeoff between imaging speed, signal-to-noise, and field of view: with current recording technology we cannot image very large neuronal populations with simultaneously high spatial and temporal resolution.

Here we describe multi-scale approaches for alleviating both of these bottlenecks. First, we show that spatial and temporal decimation techniques provide order-of-magnitude speedups in spatiotemporally demixing calcium video data into estimates of single-cell neural activity. Second, once the shapes of individual neurons have been identified (e.g., after an initial phase of conventional imaging with standard temporal and spatial resolution), we find that the spatial/temporal resolution tradeoff shifts dramatically: after demixing we can accurately recover neural activity from data that has been spatially decimated by an order of magnitude. This offers a cheap method for compressing this large video data, and also implies that it is possible to either speed up imaging significantly, or to “zoom out” by a corresponding factor to image order-of-magnitude larger neuronal populations with minimal loss in accuracy or temporal resolution.

Author Summary

The voxel rate of imaging systems ultimately sets the limit on the speed of data acquisition. These limits often mean that only a small fraction of the activity of large neuronal populations can be observed at high spatio-temporal resolution. For imaging of very large populations with single cell resolution, temporal resolution is typically sacrificed. Here we propose a multi-scale approach to achieve single cell precision using fast imaging at reduced spatial resolution. In the first phase the spatial location and shape of each neuron is obtained at standard spatial resolution; in the second phase imaging is performed at much lower spatial resolution. We show that we can apply a demixing algorithm to accurately recover each neuron’s activity from the low-resolution data by exploiting the high-resolution cellular maps estimated in the first imaging phase. Thus by decreasing the spatial resolution in the second phase, we can compress the video data significantly, and potentially acquire images over an order-of-magnitude larger area, or image at significantly higher temporal resolution, with minimal loss in accuracy of the recovered neuronal activity. We evaluate this approach on real data from light-sheet and 2-photon calcium imaging.
Senescence gives insights into the morphogenetic evolution of anamniotes
Authors: Villiard Éric , Denis Jean-François , Hashemi Faranak Sadat , Igelmann Sebastian , Ferbeyre Gerardo , Roy Stéphane
Published: December 2016

Summary statement

We report the presence of senescent cells in several transient structures in developing amphibian and teleost fish, suggesting novel mechanisms of morphogenesis that appeared early in vertebrate evolution.

Senescence represents a mechanism to avoid undesired cell proliferation that plays a role in tumor suppression, wound healing and embryonic development. In order to gain insight on the evolution of senescence, we looked at its presence in developing axolotls (urodele amphibians) and in zebrafish (teleost fish), which are both anamniotes. Our data indicate that cellular senescence is present in various developing structures in axolotls (pronephros, olfactory nerve fascicles, lateral organs, gums) and in zebrafish (epithelium of the yolk sac and in the lower part of the gut). Senescence was particularly associated with transient structures (pronephros in axolotls & yolk sac in zebrafish) suggesting that it plays a role in the elimination of these tissues. Our data supports the notion that cellular senescence evolved early in vertebrate evolution to influence embryonic development.
Resonance modulation, annihilation and generation of antiresonance and antiphasonance in 3D neuronal systems: interplay of resonant and amplifying currents with slow dynamics
Authors: Rotstein Horacio G.
Published: December 2016

Subthreshold (membrane potential) resonance and phasonance (preferred amplitude and zero-phase responses to oscillatory inputs) in single neurons arise from the interaction between positive and negative feedback effects provided by relatively fast amplifying currents and slower resonant currents. In 2D neuronal systems, amplifying currents are required to be slaved to voltage (instantaneously fast) for these phenomena to occur. In higher dimensional systems, additional currents operating at various effective time scales may modulate and annihilate existing resonances and generate antiresonance (minimum amplitude response) and antiphasonance (zero-phase response with phase monotonic properties opposite to phasonance). We use mathematical modeling, numerical simulations and dynamical systems tools to investigate the mechanisms underlying these phenomena in 3D linear models, which are obtained as the linearization of biophysical (conductance-based) models. We characterize the parameter regimes for which the system exhibits the various types of behavior mentioned above in the rather general case in which the underlying 2D system exhibits resonance. We consider two cases: (i) the interplay of two resonant gating variables, and (ii) the interplay of one resonant and one amplifying gating variables. Increasing levels of an amplifying current cause (i) a response amplification if the amplifying current is faster than the resonant current, (ii) resonance and phasonance attenuation and annihilation if the amplifying and resonant currents have identical dynamics, and (iii) antiresonance and antiphasonance if the amplifying current is slower than the resonant current. We investigate the underlying mechanisms by extending the envelope-plane diagram approach developed in previous work (for 2D systems) to three dimensions to include the additional gating variable, and constructing the corresponding envelope curves in these envelope-space diagrams. We find that antiresonance and antiphasonance emerge as the result of an asymptotic boundary layer problem in the frequency domain created by the different balances between the intrinsic time constants of the cell and the input frequencyfas it changes. For large enough values offthe envelope curves are quasi-2D and the impedance profile decrease with the input frequency. In contrast, forf≪ 1 the dynamics is quasi-1D and the impedance profile increases above the limiting value in the other regime. Antiresonance is created because the continuity of the solution requires the impedance profile to connect the portions belonging to the two regimes. If in doing so the phase profile crosses the zero value, then antiphasonance is also generated.
Mechanism of ribosome rescue by ArfA and RF2
Authors: Demo Gabriel , Svidritskiy Egor , Madireddy Rohini , Diaz-Avalos Ruben , Grant Timothy , Grigorieff Nikolaus , Sousa Duncan , Korostelev Andrei A.
Published: December 2016

ArfA rescues ribosomes stalled on truncated mRNAs by recruiting the release factor RF2, which normally binds stop codons to catalyze peptide release. We report two 3.2-Å resolution cryo-EM structures – determined from a single sample – of the 70S ribosome with ArfA∙RF2 in the A site. In both states, the ArfA C-terminus occupies the mRNA tunnel downstream of the A site. One state contains a compact inactive RF2 conformation, hitherto unobserved in 70S termination complexes. Ordering of the ArfA N-terminus in the second state rearranges RF2 into an extended conformation that docks the catalytic GGQ motif into the peptidyl-transferase center. Our work thus reveals the structural dynamics of ribosome rescue. The structures demonstrate how ArfA “senses” the vacant mRNA tunnel and activates RF2 to mediate peptide release without a stop codon, allowing stalled ribosomes to be recycled.
Pathways analyses of schizophrenia GWAS focusing on known and novel drug targets
Authors: Gaspar H.A. , Breen G.
Published: December 2016

Using successful genome-wide association results in psychiatry for drug repurposing is an ongoing challenge. Databases collecting drug targets and gene annotations are growing and can be harnessed to shed a new light on psychiatric disorders. We used GWAS summary statistics from the Psychiatric Genetics Consortium (PGC) Schizophrenia working group and a repositioning model for schizophrenia by testing the enrichment of antipsychotics. As sample size increases, schizophrenia GWAS results show increasing enrichment for known antipsychotic drugs, selective calcium channel blockers, and antiepileptics. Each of these therapeutical classes targets different gene subnetworks. We identify 162 Bonferroni-significant druggable genes, and 128 FDR-significant biological pathways related to neurons, synapses, genic intolerance, membrane transport, epilepsy, and mental disorders. These results suggest that, in schizophrenia, current well-powered GWAS results can reliably detect known schizophrenia drugs and thus may hold considerable potential for the identification of new therapeutic leads. Moreover, antiepileptics and calcium channel blockers may provide repurposing opportunities. This study also reveals significant pathways in schizophrenia that were not identified previously, and provides a workflow for pathway analysis and drug repurposing using GWAS results.
Negative regulation of uPAR activity by a GPI-specific phospholipase C
Authors: van Veen Michiel , Matas-Rico Elisa , van de Wetering Koen , Leyton-Puig Daniela , Kedziora Katarzyna M. , Sidenius Nicolai , Jalink Kees , Perrakis Anastassis , Moolenaar Wouter H.
Published: December 2016

The urokinase receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein that promotes tissue remodeling, tumor cell adhesion, migration and invasion. uPAR mediates degradation of the extracellular matrix through protease recruitment and enhances cell adhesion, migration and signaling through vitronectin binding and interactions with integrins and other receptors. Full-length uPAR is released from the cell surface, but the mechanism and functional significance of uPAR release remain obscure. Here we show that transmembrane glycerophosphodiesterase GDE3 is a GPI-specific phospholipase C that cleaves and releases uPAR with consequent loss of the proteolytic and non-proteolytic activities of uPAR. In breast cancer cells, high GDE3 expression depletes endogenous uPAR resulting in a less transformed phenotype, correlating with higher survival probability in patients. Our results establish GDE3 as a negative regulator of the uPAR signaling network and, more generally, highlight GPI-anchor hydrolysis as a cell-intrinsic mechanism to alter cell behavior.
CharacterizingXenopus tropicalisendurance capacities with multilevel transcriptomics
Authors: Richards Adam J. , Herrel Anthony , Videlier Mathieu , Paszkiewicz Konrad , Pollet Nicolas , Bonneaud Camille
Published: December 2016

Vertebrate endurance capacity is a phenotype with considerable genetic heterogeneity. RNA-Seq technologies are an ideal tool to investigate the involved genes and processes, but several challenges exist when the phenotype of interest has a complex genetic background. Difficulties manifest at the level of results interpretation because commonly used statistical methods are designed to identify strongly associated genes. If an observed phenotype can be achieved though multiple distinct genetic mechanisms then typical gene-centric methods come with the attached risk that signal may be lost or misconstrued.

Gene set analysis (GSA) methods are now widely accepted as a means to address some of the shortcomings of gene-by-gene analysis methods. We carry out both gene level and gene set level analyses onXenopus tropicalisto identify the genetic factors that contribute to endurance heterogeneity. A typical workflow might consider gene level and pathway level analyses, but in this work we propose an additional focus at the intermediate level of functional modules. We generate functional modules for GSA testing in order to be explicit in how ontology information is used with respect to the functional genomics ofXenopus. Additionally, we make use of multiple assemblies to corroborate implicated genes and processes.

We identified 42 core genes, 10 functional modules, and 14 pathways based on gene expression differences between endurant and non-endurant frogs. The majority of the genes and processes are readily associated with muscle contraction or catabolism. A substantial number of these genes are involved in lipid metabolic processes, suggesting an important role in frog endurance heterogeneity. Unsurprisingly, many of the gene expression differences between endurant and non-endurant frogs can be distilled down to the capacity to utilize substrate for energy, but at the individual level frogs appear to make use of diverse machinery to achieve these differences.
Compositional Inductive Biases in Function Learning
Authors: Schulz Eric , Tenenbaum Joshua B. , Duvenaud David , Speekenbrink Maarten , Gershman Samuel J.
Published: December 2016

How do people recognize and learn about complex functional structure? Taking inspiration from other areas of cognitive science, we propose that this is achieved by harnessing compositionality: complex structure is decomposed into simpler building blocks. We formalize this idea within the framework of Bayesian regression using a grammar over Gaussian process kernels, and compare this approach with other structure learning approaches. Participants consistently chose compositional (over non-compositional) extrapolations and interpolations of functions. Experiments designed to elicit priors over functional patterns revealed an inductive bias for compositional structure. Compositional functions were perceived as subjectively more predictable than non-compositional functions, and exhibited other signatures of predictability, such as enhanced memorability and reduced numerosity. Taken together, these results support the view that the human intuitive theory of functions is inherently compositional.
Resource Competition Shapes the Response of Genetic Circuits
Authors: Qian Yili , Huang Hsin-Ho , Jimenéz José I. , Del Vecchio Domitilla
Published: December 2016

A common approach to design genetic circuits is to compose gene expression cassettes together. While appealing, this modular approach is challenged by the fact that expression of each gene depends on the availability of transcriptional/translational resources, which is in turn determined by the presence of other genes in the circuit. This raises the question of how competition for resources by different genes affects a circuit’s behavior. Here, we create a library of genetic activation cascades in bacteriaE. coli, where we explicitly tune the resource demand by each gene. We develop a general Hill-function-based model that incorporates resource competition effects through resource demand coefficients. These coefficients lead to non-regulatory interactions among genes that reshape circuit’s behavior. For the activation cascade, such interactions result in surprising biphasic or monotonically decreasing responses. Finally, we use resource demand coefficients to guide the choice of ribosome binding site (RBS) and DNA copy number to restore the cascade’s intended monotonically increasing response. Our results demonstrate how unintended circuit’s behavior arises from resource competition and provide a model-guided methodology to minimize the resulting effects.
Mindboggling morphometry of human brains
Authors: Klein Arno , Ghosh Satrajit S. , Bao Forrest S. , Giard Joachim , Häme Yrjö , Stavsky Eliezer , Lee Noah , Rossa Brian , Reuter Martin , Chaibub Neto Elias , Keshavan Anisha
Published: December 2016

Mindboggle (http://mindboggle.info) is an open source brain morphometry platform that takes in preprocessed T1-weighted MRI data and outputs volume, surface, and tabular data containing label, feature, and shape information for further analysis. In this article, we document the software and demonstrate its use in studies of shape variation in healthy and diseased humans. The number of different shape measures and the size of the populations make this the largest and most detailed shape analysis of human brains every conducted. Brain image morphometry shows great potential for providing much-needed biological markers for diagnosing, tracking, and predicting progression of mental health disorders. Very few software algorithms provide more than measures of volume and cortical thickness, and more subtle shape measures may provide more sensitive and specific biomarkers. Mindboggle computes a variety of (primarily surface-based) shapes: area, volume, thickness, curvature, depth, Laplace-Beltrami spectra, Zernike moments, etc. We evaluate Mindboggle’s algorithms using the largest set of manually labeled, publicly available brain images in the world and compare them against state-of-the-art algorithms where they exist. All data, code, and results of these evaluations are publicly available.

Author Summary

Brains vary in many ways, including their shape. Analysing differences in shape between brains or changes in brain shape over time has been used to characterize morphology of diseased brains, but these analyses conventionally rely on simple volumetric shape measures. We believe that access to a greater variety of shape measures could provide greater sensitivity and specificity to morphological disturbances, and could aid in diagnosis, tracking, and prediction of the progression of mental health disorders. Mindboggle is open source software that provides neuroscientists (and indeed, anyone interested in computing shapes) tools for computing a variety of shape measures, including area, volume, thickness, curvature, geodesic depth, travel depth, Laplace-Beltrami spectra, and Zernike moments. In addition to algorithmic contributions, we conducted evaluations and applied Mindboggle to conduct the most detailed shape analysis of human brains.
Exploring the mutational robustness of nucleic acids by searching genotype neighbourhoods in sequence space
Authors: Zhou Qingtong , Sun Xianbao , Xia Xiaole , Fan Zhou , Luo Zhaofeng , Zhao Suwen , Liang Haojun , Shakhnovich Eugene
Published: December 2016

To assess the mutational robustness of nucleic acids, many genome- and protein-level studies have been performed; in these investigations, nucleic acids are treated as genetic information carriers and transferrers. However, the molecular mechanism through which mutations alter the structural, dynamic and functional properties of nucleic acids is poorly understood. Here, we performed SELEX in silico study to investigate the fitness distribution of the nucleic acid genotype neighborhood in a sequence space for L-Arm binding aptamer. Although most mutants of the L-Arm-binding aptamer failed to retain their ligand-binding ability, two novel functional genotype neighborhoods were isolated by SELEX in silico and experimentally verified to have similar binding affinity (Kd= 69.3 μM and 110.7 μM) as the wild-type aptamer (Kd= 114.4 μM). Based on data from the current study and previous research, mutational robustness is strongly influenced by the local base environment and ligand-binding mode, whereas bases distant from the binding pocket provide potential evolutionary pathways to approach global fitness maximum. Our work provides an example of successful application of SELEX in silico to optimize an aptamer and demonstrates the strong sensitivity of mutational robustness to the site of genetic variation.
The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate browning of adipose tissue
Authors: Wada Shogo , Neinast Michael , Jang Cholsoon , Ibrahim Yasir H. , Lee Gina , Babu Apoorva , Li Jian , Hoshino Atsushi , Rowe Glenn C. , Rhee James , Martina José A. , Puertollano Rosa , Blenis John , Morley Michael , Baur Joseph A. , Seale Patrick , Arany Zoltan
Published: December 2016

Noncanonical mechanistic target of rapamycin (mTOR) pathways remain poorly understood. Mutations in the tumor suppressor folliculin (FLCN) cause Birt-Hogg-Dubé syndrome, a hamartomatous disease marked by mitochondria-rich kidney tumors. FLCN functionally interacts with mTOR and is expressed in most tissues, but its role in fat has not been explored. We show here that FLCN regulates adipose tissue browning via mTOR and the transcription factor TFE3. Adipose-specific deletion of FLCN relieves mTOR-dependent cytoplasmic retention of TFE3, leading to direct induction of the PGC-1 transcriptional coactivators, drivers of mitochondrial biogenesis and the browning program. Cytoplasmic retention of TFE3 by mTOR is sensitive to ambient amino acids, is independent of growth factor and tuberous sclerosis complex (TSC) signaling, is driven by RagC/D, and is separable from canonical mTOR signaling to S6K. Codeletion of TFE3 in adipose-specific FLCN knockout animals rescues adipose tissue browning, as does codeletion of PGC-1β. Conversely, inducible expression of PGC-1β in white adipose tissue is sufficient to induce beige fat gene expression in vivo. These data thus unveil a novel FLCN–mTOR–TFE3–PGC-1β pathway—separate from the canonical TSC–mTOR–S6K pathway—that regulates browning of adipose tissue.
Diagnostic usefulness of dermoscopy in differentiating lichen aureus from nummular eczema
Authors: Suh Kee Suck , Park Jong Bin , Yang Myeong Hyeon , Choi Soo Young , Hwangbo Hyun , Jang Min Soo
Published: December 2016

Lichen aureus (LA) is a variant of pigmented purpuric dermatosis that is characterized clinically by rust macules, papules or plaques, mainly on the legs. In some cases, LA can be difficult to be distinguished from nummular eczema (NE) with the naked eye. Dermoscopy can be applied to skin lesions, revealing additional features that can be highly valuable for correct diagnosis. This study was conducted to investigate characteristic dermoscopic findings of LA and to identify distinctive features that can differentiate it from NE. Fourteen LA patients and 14 NE patients diagnosed by skin biopsy were enrolled. Skin lesions were evaluated via polarized dermoscopy. On dermoscopy, “coppery orange diffuse coloration of background”, “round to oval red globules”, “gray dots”, and “networks of brownish to gray interconnected lines” were more commonly seen in LA (100%, 92.9%, 42.9% and 64.3%, respectively) compared with NE. “Scales”, “shiny yellow clods” and “irregularly distributed brownish‐red globules” were more commonly seen in NE (100%, 85.7% and 57.1%, respectively) compared with LA. Dermoscopy provides valuable information for diagnosis of LA and aids in differentiating it from NE.
Non‐paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans
Authors: Orime Mari , Tomiyama Katsuhiro , Hashidate Hideki , Yoshida Satoru , Hokari Satoshi , Tsuda Akiko , Yokoyama Hisashi , Narita Jun‐ichi , Uchida Youhei , Kanekura Takuro , Abe Riichiro , Ishii Norito , Hashimoto Takashi , Kawai Kazuhiro
Published: December 2016

Bronchiolitis obliterans is a small‐airway obstructive lung disease for which immunologically mediated pathogenesis is supposed. Frequent association of bronchiolitis obliterans with paraneoplastic pemphigus is well known, but its association with other autoimmune bullous diseases has not been reported except for a case of anti‐laminin‐332‐type mucous membrane pemphigoid in a patient with chronic graft‐versus‐host disease. We report a case of non‐paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans in a patient without transplantation. Although the patient's serum contained immunoglobulin (Ig)A antibodies to the 180‐kDa bullous pemphigoid antigen/type XVII collagen and IgG antibodies to laminin‐332, diagnosis of either linear IgA bullous dermatosis or mucous membrane pemphigoid could not be made because of the failure to detect linear IgA deposition at the basement membrane zone by direct immunofluorescence and the lack of mucous membrane lesions. Physicians should be aware that autoimmune bullous diseases other than paraneoplastic pemphigus can also associate with this rare but potentially fatal lung disease.
Successful treatment of multiple in‐transit melanomas on the leg with intensity‐modulated radiotherapy and immune checkpoint inhibitors: Report of two cases
Authors: Fujimura Taku , Kambayashi Yumi , Furudate Sadanori , Hidaka Takanori , Sato Yota , Tanita Kayo , Tono Hisayuki , Tsukada Akira , Hashimoto Akira , Aiba Setsuya
Published: December 2016

Because the efficacy rates of monotherapy with immune checkpoint inhibitors such as nivolumab or ipilimumab are not sufficient, to enhance the antitumor effects of these reagents is of great interest among dermato‐oncologists. In this report, we describe two cases of multiple in‐transit metastatic melanomas on the leg successfully treated with intensity‐modulated radiotherapy (IMRT) using a CyberKnife in combination with ipilimumab or nivolumab. Our cases suggested that IMRT could enhance the antitumor effects of immune checkpoint inhibitors in patients with multiple in‐transit melanomas.
Evaluation of a retrospective diary for peri‐conceptual and mid‐pregnancy drinking in Scotland: a cross‐sectional study
Authors: Symon Andrew , Rankin Jean , Butcher Geraldine , Smith Lesley , Cochrane Lynda
Published: December 2016

Introduction

Heavy episodic (“binge”) drinking among women in Scotland is commonplace; prepregnancy drinking is associated with continued antenatal drinking. Evidence for effectiveness of standardized antenatal alcohol assessment is lacking. Alcohol‐exposed pregnancies may be missed. We assessed peri‐conceptual and mid‐pregnancy consumption using a week‐long retrospective diary and standard alcohol questionnaires, and evaluated the agreement between these instruments.

Material and methods

Cross‐sectional study in two Scottish health board areas involving 510 women attending mid‐pregnancy ultrasound scan clinics. Face‐to‐face administration of alcohol retrospective diary and AUDIT or AUDIT‐C assessed weekly and daily alcohol consumption levels and patterns. Depression‐Anxiety‐Stress Scale (DASS‐21) assessed maternal wellbeing. A sub‐sample (n = 30) provided hair for alcohol metabolite analysis. Pearson's correlation coefficient investigated associations between questionnaires and alcohol metabolite data.

Results

The response rate was 73.8%. The retrospective diary correlated moderately with AUDIT‐C and AUDIT but elicited reports of significantly higher peri‐conceptual consumption, (median unit consumption on “drinking days” 6.8; range 0.4–63.8). Additional “special occasions” consumption ranged from 1 to 125 units per week. Correlations between DASS‐21 and retrospective diary were weak. Biomarker analysis identified three instances of hazardous peri‐conceptual drinking.

Conclusions

Women reported higher consumption levels when completing the retrospective diary, especially regarding peri‐conceptual “binge” drinking. Routine clinical practice methods may not capture potentially harmful or irregular drinking patterns. Given the association between prepregnancy and antenatal drinking, and alcohol's known teratogenic effects, particularly in the first trimester, the retrospective diary may be a useful low‐tech tool to gather information on alcohol intake patterns and levels.
Endoresection with adjuvant ruthenium brachytherapy for selected uveal melanoma patients – the Tuebingen experience
Authors: Süsskind Daniela , Dürr Carina , Paulsen Frank , Kaulich Theodor , Bartz‐Schmidt Karl U.
Published: December 2016

Purpose

To evaluate the treatment of selected patients with uveal melanoma with endoresection and adjuvant ruthenium brachytherapy.

Methods

Thirty‐five patients with uveal melanoma not suitable for ruthenium plaque monotherapy were treated with endoresection and adjuvant ruthenium brachytherapy between January 2001 and October 2013. Recurrence‐free survival, globe retention, course of visual acuity (VA), occurrence of therapy‐related complications and metastasis‐free and overall survival were analysed retrospectively.

Results

Eight patients (22.9%) had a tumour recurrence after a median follow‐up of 49.5 months (range: 21–134 months). Enucleation was necessary in eight patients. Thirty‐two patients (91%) had a loss of VA with a median loss of nine lines (range: 0 to −39 lines); VA was stable in three patients and no patients had a gain in VA. Four patients (11.4%) developed radiation retinopathy. Metastases were detected in seven patients (20.0%) during follow‐up. The occurrence of metastasis was significantly associated with monosomy 3 (p < 0.0001). Twenty‐four patients (68.6%) were alive at the end of follow‐up. Five patients (14.3%) died because of uveal melanoma (UM) metastasis.

Conclusions

Endoresection with adjuvant ruthenium brachytherapy is an option for selected patients with UM who cannot be treated with brachytherapy as monotherapy. About two‐thirds of eyes can be retained long term without recurrences. Visual acuity cannot be maintained in most cases, and may even decrease considerably. Radiation complications are comparatively rare and not a significant problem.
So It Is, So It Shall Be: Group Regularities License Children's Prescriptive Judgments
Authors: Roberts Steven O. , Gelman Susan A. , Ho Arnold K.
Published: December 2016

When do descriptive regularities (what characteristics individuals have) become prescriptive norms (what characteristics individuals should have)? We examined children's (4–13 years) and adults' use of group regularities to make prescriptive judgments, employing novel groups (Hibbles and Glerks) that engaged in morally neutral behaviors (e.g., eating different kinds of berries). Participants were introduced to conforming or non‐conforming individuals (e.g., a Hibble who ate berries more typical of a Glerk). Children negatively evaluated non‐conformity, with negative evaluations declining with age (Study 1). These effects were replicable across competitive and cooperative intergroup contexts (Study 2) and stemmed from reasoning about group regularities rather than reasoning about individual regularities (Study 3). These data provide new insights into children's group concepts and have important implications for understanding the development of stereotyping and norm enforcement.
Prophylactic rectal indomethacin may be ineffective for preventing post‐endoscopic retrograde cholangiopancreatography pancreatitis in general patients: A meta‐analysis
Authors: Feng Yunlu , Navaneethan Udayakumar , Zhu Xiang , Varadarajulu Shyam , Schwartz Ingrid , Hawes Robert , Hasan Muhammad , Yang Aiming
Published: December 2016

Background and Aim

Efficacy of prophylactic indomethacin for prevention of post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in general patients remains controversial. To address this, we conducted a meta‐analysis of clinical trials specifically on rectal indomethacin in prevention of PEP in consecutive patients undergoing ERCP.

Methods

We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases to identify randomized, double‐blind, controlled clinical trials on rectal indomethacin in the prevention of PEP in consecutive patients undergoing ERCP. Primary outcome was the overall rate of PEP. Secondary outcomes were the overall rates of moderate to severe PEP and mild PEP.

Results

Six studies, with a total of 2473 patients, were included. Overall rate of PEP was 7% (95% CI, 6–9%). No statistical difference was observed in overall rates of PEP (OR, 0.67; 95% CI, 0.46–1.00, P = 0.050) and, additionally, rates of moderate to severe (OR, 0.66; 95% CI, 0.28–1.56, P = 0.345) or mild (OR, 0.71; 95% CI, 0.45–1.10, P = 0.127) PEP between indomethacin and placebo.

Conclusion

In a contemporary meta‐analysis of available randomized controlled trials of consecutive patients undergoing ERCP, rectal indomethacin did not show significant prevention effect of post‐ERCP pancreatitis.
Measurements of Rare Earth Element and Other Element Mass Fractions in Environmental Reference Materials (NIST SRM 1646a, NIST SRM 1400, IAEA‐395 and IAEA‐450) by INAA, ICP‐AES and ICP‐MS
Authors: Cao Vu Dong , Sucgang Raymond , Tran Thien Quang , Ho Doanh Van , Shirai Naoki , Ebihara Mitsuru
Published: December 2016

INAA, ICP‐AES and ICP‐MS were used to elementally characterise four environmental reference materials – NIST SRM 1646a (Estuarine Sediment), NIST SRM 1400 (Bone Ash), IAEA‐395 (Urban Dust) and IAEA‐450 (Algae). An analytical scheme consisting of the three methods was first applied to NIST SRM 1646a to validate the methodology because it has been extensively analysed and has certified values for many elements. With repeated analyses of NIST SRM 1646a, the accuracy and measurement repeatability of the data obtained were evaluated based on two statistical calculations (zeta‐score and Horwitz ratio) and were observed to be good enough for the analytical scheme to be applied to similar sorts of environmental/geochemical samples. Applying the same approach to NIST SRM 1400, IAEA‐395 and IAEA‐450, enabled mass fractions of 29, 38 and 28 elements to be determined, respectively. Among these results, the data for rare earth elements are of particular interest, not only for IAEA‐450 but also for the other three reference samples. The data for Pr, Gd, Dy, Ho, Er and Tm in NIST SRM 1646a are newly reported in this study. By using small test portions (< 100 mg) for NIST SRM 1646a and IAEA‐395, and recommended minimum amounts for NIST SRM 1400 and IAEA‐450, sample homogeneity was evaluated.
Clinical characteristics of testicular germ cell tumors in patients aged 50 years and older: A large‐scale study from the Cancer Registration Committee of the Japanese Urological Association
Authors: Kawai Taketo , Tanaka Yoshinori ,   the Cancer Registration Committee of the Japanese Urological Association
Published: December 2016

Objectives

To determine the characteristics of testicular germ cell tumors in older patients.

Methods

A testicular cancer survey was carried out by the Japanese Urological Association in 2011 to register the testicular cancers diagnosed in 2005 and 2008. The survey included age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, treatment and clinical outcomes. These factors were compared between patients aged ≥50 years and those aged <50 years at diagnosis.

Results

Of the 1119 cases of primary testicular germ cell tumors, 123 (11.0%) were diagnosed at age ≥50 years. Compared with patients aged <50 years, germ cell tumors in older patients were more frequently seminomas (74.8% vs 61.4%, P = 0.004) and clinical stage I at diagnosis (79.5% vs 70.7%, P = 0.041). Metastatic germ cell tumors in patients aged ≥50 years were more frequently classified into the good prognosis group according to the International Germ Cell Consensus Classification compared with those in younger patients (84.0% vs 53.8%, P = 0.003). Nevertheless, cancer‐specific survival of patients aged ≥50 years was not superior to that of younger patients (4‐year survival rates; 93.7% vs 97.8%).

Conclusions

Testicular germ cell tumors in patients aged ≥50 years are more commonly seminomas, and tend to be diagnosed at earlier stages compared with younger patients; however, the prognosis of older patients is not favorable compared with that of younger patients.
Cryotherapy for localized juvenile spongiotic gingival hyperplasia: preliminary findings on two cases
Authors: Nogueira Vinícius Krieger Costa , Fernandes Darcy , Navarro Cláudia Maria , Giro Elisa Maria Aparecida , de Almeida Luciana Yamamoto , León Jorge Esquiche , Bufalino Andreia
Published: December 2016

Background

Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a distinct subtype of inflammatory gingival hyperplasia that shows lack of response to traditional periodontal treatment, and after surgical excision, recurrence rate of 6–16% has been reported.

Case Report

Two girls (11‐ and 9‐year‐old) with multifocal red patches along the maxillary and mandibular labial gingiva showed no regression of the lesions after basic periodontal treatment. Surgical excision of focal lesion in each case was performed, which showed typical features of LJSGH. In both cases, the lesions presented recurrence. Hence, cryotherapy sessions in all lesions were performed.

Conclusion

Cryotherapy appears to be successfully in LJSGH and well received by paediatric patients.
Passionate Experiences in Adolescence: Situational Variability and Long‐Term Stability
Authors: Moeller Julia , Dietrich Julia , Eccles Jacquelynne S. , Schneider Barbara
Published: December 2016

This study investigates adolescents' situational passionate experiences, defined as states of strong commitment and intense affect. We examine the extent to which experiencing passion was specific to situations versus individual differences, and explore which activities are likely to elicit adolescents' passion. Using longitudinal experience sampling method (ESM) data from a representative sample of 996 adolescents (54.6% females) in three cohorts (6th, 8th, and 10th grade at baseline), we examine whether adolescents' frequency of passionate experiences remained stable across 2 years. Results of multilevel analyses revealed that situational determinants accounted for 80% of variance in passion, while 20% were due to characteristics of the person that remained stable across 1 week of ESM assessment. An adolescent's percentage of passionate experiences among all observed experiences remained stable across 2 years in rank order and mean level.
Effect of Cranberry Extract on the Frequency of Bacteriuria in Dogs with Acute Thoracolumbar Disk Herniation: A Randomized Controlled Clinical Trial
Authors: Olby N.J. , Vaden S.L. , Williams K. , Griffith E.H. , Harris T. , Mariani C.L. , Muñana K.R. , Early P.J. , Platt S.R. , Boozer L. , Giovanella C. , Longshore R.
Published: December 2016

Background

Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria.

Hypothesis

Cranberry extract reduces risk of bacteriuria in dogs after acute TL‐IVDH.

Animals

Client‐owned dogs with acute onset TL‐IVDH causing nonambulatory status.

Methods

Randomized, placebo‐controlled, blinded, prospective clinical trial. Dogs with acute TL‐IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi‐squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria.

Results

Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047).

Conclusions and Clinical Importance

This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.
Demographic history of the trace metal hyperaccumulator Noccaea caerulescens (J. Presl and C. Presl) F. K. Mey. in Western Europe
Authors: Gonneau Cédric , Noret Nausicaa , Godé Cécile , Frérot Hélène , Sirguey Catherine , Sterckeman Thibault , Pauwels Maxime
Published: December 2016

Noccaea caerulescens (Brassicaceae) is a major pseudometallophyte model for the investigation of the genetics and evolution of metal hyperaccumulation in plants. We studied the population genetics and demographic history of this species to advance the understanding of among‐population differences in metal hyperaccumulation and tolerance abilities. Sampling of seven to 30 plants was carried out in 62 sites in Western Europe. Genotyping was carried out using a combination of new chloroplast and nuclear neutral markers. A strong genetic structure was detected, allowing the definition of three genetic subunits. Subunits showed a good geographic coherence. Accordingly, distant metallicolous populations generally belonged to distinct subunits. Approximate Bayesian computation analysis of demographic scenarios among subunits further supported a primary isolation of populations from the southern Massif Central prior to last glacial maximum, whereas northern populations may have derived during postglacial recolonization events. Estimated divergence times among subunits were rather recent in comparison with the species history, but certainly before the establishment of anthropogenic metalliferous sites. Our results suggest that the large‐scale genetic structure of N. caerulescens populations pre‐existed to the local adaptation to metalliferous sites. The population structure of quantitative variation for metal‐related adaptive traits must have established independently in isolated gene pools. However, features of the most divergent genetic unit (e.g. extreme levels of Cd accumulation observed in previous studies) question the putative relationships between adaptive evolution of metal‐related traits and subunits isolation. Finally, admixture signals among distant metallicolous populations suggest a putative role of human activities in facilitating long‐distance genetic exchanges.
Multiple processes drive genetic structure of humpback whale (Megaptera novaeangliae) populations across spatial scales
Authors: Kershaw Francine , Carvalho Inês , Loo Jacqueline , Pomilla Cristina , Best Peter B. , Findlay Ken P. , Cerchio Salvatore , Collins Tim , Engel Marcia H. , Minton Gianna , Ersts Peter , Barendse Jaco , Kotze P. G. H. , Razafindrakoto Yvette , Ngouessono Solange , Meÿer Michael , Thornton Meredith , Rosenbaum Howard C.
Published: December 2016

Elucidating patterns of population structure for species with complex life histories, and disentangling the processes driving such patterns, remains a significant analytical challenge. Humpback whale (Megaptera novaeangliae) populations display complex genetic structures that have not been fully resolved at all spatial scales. We generated a data set of nuclear markers for 3575 samples spanning the seven breeding stocks and substocks found in the South Atlantic and western and northern Indian Oceans. For the total sample, and males and females separately, we assessed genetic diversity, tested for genetic differentiation between putative populations and isolation by distance, estimated the number of genetic clusters without a priori population information and estimated rates of gene flow using maximum‐likelihood and Bayesian approaches. At the ocean basin scale, structure is governed by geographical distance (IBD P < 0.05) and female fidelity to breeding areas, in line with current understanding of the drivers of broadscale population structure. Consistent with previous studies, the Arabian Sea breeding stock was highly genetically differentiated (FST 0.034–0.161; P < 0.01 for all comparisons). However, the breeding stock boundary between west South Africa and east Africa was more porous than expected based on genetic differentiation, cluster and geneflow analyses. Instances of male fidelity to breeding areas and relatively high rates of dispersal for females were also observed between the three substocks in the western Indian Ocean. The relationships between demographic units and current management boundaries may have ramifications for assessments of the status and continued protections of populations still in recovery from commercial whaling.