bluuebunny/crossref_metadata_2025 huggingface dataset:
Examination of signatures of recent positive selection on genes involved in human sialic acid biology
Authors: Moon Jiyun M. , Aronoff David M. , Capra John A. , Abbot Patrick , Rokas Antonis
Published: May 2017

Abstract

Sialic acids are nine carbon sugars ubiquitously found on the surfaces of vertebrate cells and are involved in various immune response-related processes. In humans, at least 58 genes spanning diverse functions, from biosynthesis and activation to recycling and degradation, are involved in sialic acid biology. Because of their role in immunity, sialic acid biology genes have been hypothesized to exhibit elevated rates of evolutionary change. Consistent with this hypothesis, several genes involved in sialic acid biology have experienced higher rates of non-synonymous substitutions in the human lineage than their counterparts in other great apes, perhaps in response to ancient pathogens that infected hominins millions of years ago (paleopathogens). To test whether sialic acid biology genes have also experienced more recent positive selection during the evolution of the modern human lineage, reflecting adaptation to contemporary cosmopolitan or geographically-restricted pathogens, we examined whether their protein-coding regions showed evidence of recent hard and soft selective sweeps. This examination involved the calculation of four measures that quantify changes in allele frequency spectra, extent of population differentiation, and haplotype homozygosity caused by recent hard and soft selective sweeps for 55 sialic acid biology genes using publicly available whole genome sequencing data from 1,668 humans from three ethnic groups. To disentangle evidence for selection from confounding demographic effects, we compared the observed patterns in sialic acid biology genes to simulated sequences of the same length under a model of neutral evolution that takes into account human demographic history. We found that the patterns of genetic variation of most sialic acid biology genes did not significantly deviate from neutral expectations and were not significantly different among genes belonging to different functional categories. Those few sialic acid biology genes that significantly deviated from neutrality either experienced soft sweeps or population-specific hard sweeps. Interestingly, while most hard sweeps occurred on genes involved in sialic acid recognition, most soft sweeps involved genes associated with recycling, degradation and activation, transport, and transfer functions. We propose that the lack of signatures of recent positive selection for the majority of the sialic acid biology genes is consistent with the view that these genes regulate immune responses against ancient rather than contemporary cosmopolitan or geographically restricted pathogens.
Systematic genetic dissection of chitin degradation and uptake inVibrio cholerae
Authors: Hayes Chelsea A. , Dalia Triana N. , Dalia Ankur B.
Published: May 2017

Vibrio choleraeis a natural resident of the aquatic environment, where a common nutrient is the chitinous exoskeletons of microscopic crustaceans. Chitin utilization requires chitinases, which degrade this insoluble polymer into soluble chitin oligosaccharides. These oligosaccharides also serve as an inducing cue for natural transformation inVibriospecies. There are 7 predicted endochitinase-like genes in theV. choleraegenome. Here, we systematically dissect the contribution of each gene to growth on chitin as well as induction of natural transformation. Specifically, we created a strain that lacks all 7 putative chitinases and from this strain, generated a panel of strains where each expresses a single chitinase. We also generated expression plasmids to ectopically express all 7 chitinases in our chitinase deficient strain. Through this analysis, we found that low levels of chitinase activity are sufficient for natural transformation, while growth on insoluble chitin as a sole carbon source requires more robust and concerted chitinase activity. We also assessed the role that the three uptake systems for the chitin degradation products GlcNAc, (GlcNAc)2, and (GlcN)2, play in chitin utilization and competence induction. Cumulatively, this study provides mechanistic details for how this pathogen utilizes chitin to thrive and evolve in its environmental reservoir.

ORIGINALITY-SIGNIFICANCE STATEMENT

Vibrio cholerae, the causative agent of the diarrheal disease cholera, interacts with the chitinous shells of crustacean zooplankton in the aquatic environment, which serves as an environmental reservoir for this pathogen. It degrades and utilizes chitin-derived products as a source of carbon and nitrogen. Also, chitin serves as an inducing cue for natural transformation – an important mechanism of horizontal gene transfer in this species. Here, we systematically dissect the genes required for chitin degradation and uptake, and characterize the role of these genes for growth on chitin as a nutrient and during chitininduced natural transformation. Thus, this study provides mechanistic details for how this pathogen utilizes chitin to thrive and evolve in its environmental reservoir.
Improved Split Fluorescent Proteins for Endogenous Protein Labeling
Authors: Feng Siyu , Sekine Sayaka , Pessino Veronica , Li Han , Leonetti Manuel D. , Huang Bo
Published: May 2017

Self-complementing split fluorescent proteins (FPs) have been widely used for protein labeling, visualization of subcellular protein localization, and detection of cell-cell contact. To expand this toolset, we have developed a screening strategy for the direct engineering of self-complementing split FPs. Via this strategy, we have generated a yellow-green split-mNeonGreen21-10/11that improves the ratio of complemented signal to the background of FP1-10-expressing cells compared to the commonly used split-GFP1-10/11,as well as a 10-fold brighter red-colored split-sfCherry21-10/11. Based on split-sfCherry2, we have engineered a photoactivatable variant that enables single-molecule localization-based super-resolution microscopy. We have demonstrated dual-color endogenous protein tagging with sfCherry211and GFP11, revealing that endoplasmic reticulum translocon complex Sec61B has reduced abundance in certain peripheral tubules. These new split FPs not only offer multiple colors for imaging interaction networks of endogenous proteins, but also hold the potential to provide orthogonal handles for biochemical isolation of native protein complexes.
A single checkpoint pathway eliminates mouse oocytes with dna damage or chromosome synapsis failure
Authors: Rinaldi Vera D. , Bolcun-Filas Ewelina , Kogo Hiroshi , Kurahashi Hiroki , Schimenti John C.
Published: May 2017

Pairing and synapsis of homologous chromosomes during meiosis is crucial for producing genetically normal gametes, and is dependent upon repair of SPO11-induced double stranded breaks (DSBs) by homologous recombination. To prevent transmission of genetic defects, diverse organisms have evolved mechanisms to eliminate meiocytes containing unrepaired DSBs or unsynapsed chromosomes. Here, we show that the CHK2 (CHEK2)-dependent DNA damage checkpoint culls not only recombination-defective mouse oocytes, but also SPO11-deficient oocytes that are severely defective in homolog synapsis. The checkpoint is triggered by spontaneous DSBs that arise in late prophase I, accumulating above the checkpoint activation threshold (∼10 DSBs) because presence of HORMAD1/2 on unsynapsed chromosome axes prevents their repair. Furthermore,Hormad2deletion rescued fertility and meiotic DSB repair of oocytes containing a synapsis-proficient, non-crossover recombination defective mutation in a gene (Trip13) required for removal of HORMADs from synapsed chromosomes, indicating that a substantial fraction of meiotic DSBs are normally repaired by intersister recombination in mice.
Learning and attention reveal a general relationship between neuronal variability and perception
Authors: Ni Amy M. , Ruff Douglas A. , Alberts Joshua J. , Symmonds Jen , Cohen Marlene R.
Published: May 2017

The trial-to-trial response variability that is shared between pairs of neurons (termed spike count correlations1orrSC) has been the subject of many recent studies largely because it might limit the amount of information that can be encoded by neuronal populations. Spike count correlations are flexible and change depending on task demands2-7. However, the relationship between correlated variability and information coding is a matter of current debate2-14. This debate has been difficult to resolve because testing the theoretical predictions would require simultaneous recordings from an experimentally unfeasible number of neurons. We hypothesized that if correlated variability limits population coding, then spike count correlations in visual cortex should a) covary with subjects’ performance on visually guided tasks and b) lie along the dimensions in neuronal population space that contain information that is used to guide behavior. We focused on two processes that are known to improve visual performance: visual attention, which allows observers to focus on important parts of a visual scene15-17, and perceptual learning, which slowly improves observers’ ability to discriminate specific, well-practiced stimuli18-20. Both attention and learning improve performance on visually guided tasks, but the two processes operate on very different timescales and are typically studied using different perceptual tasks. Here, by manipulating attention and learning in the same task, subjects, trials, and neuronal populations, we show that there is a single, robust relationship between correlated variability in populations of visual neurons and performance on a change-detection task. We also propose an explanation for the mystery of how correlated variability might affect performance: it is oriented along the dimensions of population space used by the animal to make perceptual decisions. Our results suggest that attention and learning affect the same aspects of the neuronal population activity in visual cortex, which may be responsible for learning- and attention-related improvements in behavioral performance. More generally, our study provides a framework for leveraging the activity of simultaneously recorded populations of neurons, cognitive factors, and perceptual decisions to understand the neuronal underpinnings of behavior.
LTR_retriever: a highly accurate and sensitive program for identification of LTR retrotransposons
Authors: Ou Shujun , Jiang Ning
Published: May 2017

Long terminal-repeat retrotransposons (LTR-RTs) are prevalent in plant genomes. Identification of LTR-RTs is critical for achieving high-quality gene annotation. Based on the well-conserved structure, multiple programs were developed forde novoidentification of LTR-RTs; however, these programs are associated with low specificity and high false discovery rate (FDR). Here we report LTR_retriever, a multithreading empowered Perl program that identifies LTR-RTs and generates high-quality LTR libraries from genomic sequences. LTR_retriever demonstrated significant improvements by achieving high levels of sensitivity (91.8%), specificity (94.7%), accuracy (94.3%), and precision (90.6%) in model plants. LTR_retriever is also compatible with long sequencing reads. With 40k self-corrected PacBio reads equivalent to 4.5X genome coverage in Arabidopsis, the constructed LTR library showed excellent sensitivity and specificity. In addition to canonical LTR-RTs with 5'-TG..CA-3' termini, LTR_retriever also identifies non-canonical LTR-RTs (non-TGCA), which have been largely ignored in genome-wide studies. We identified seven types of non-canonical LTRs from 42 out of 50 plant genomes. The majority of non-canonical LTRs areCopiaelements, with which the LTR is four times shorter than that of otherCopiaelements, which may be a result of their target specificity. Strikingly, non-TGCACopiaelements are often located in genic regions and preferentially insert nearby or within genes, indicating their impact on the evolution of genes and potential as mutagenesis tools.
Amortized Hypothesis Generation
Authors: Dasgupta Ishita , Schulz Eric , Goodman Noah D. , Gershman Samuel J.
Published: May 2017

Bayesian models of cognition posit that people compute probability distributions over hypotheses, possibly by constructing a sample-based approximation. Since people encounter many closely related distributions, a computationally efficient strategy is to selectively reuse computations – either the samples themselves or some summary statistic. We refer to these reuse strategies asamortized inference. In two experiments, we present evidence consistent with amortization. When sequentially answering two related queries about natural scenes, we show that answers to the second query vary systematically depending on the structure of the first query. Using a cognitive load manipulation, we find evidence that people cache summary statistics rather than raw sample sets. These results enrich our notions of how the brain approximates probabilistic inference.
DNA damage checkpoint dynamics drive cell cycle phase transitions
Authors: Chao Hui Xiao , Poovey Cere E. , Privette Ashley A. , Grant Gavin D. , Chao Hui Yan , Cook Jeanette G. , Purvis Jeremy E.
Published: May 2017

DNA damage checkpoints are cellular mechanisms that protect the integrity of the genome during cell cycle progression. In response to genotoxic stress, these checkpoints halt cell cycle progression until the damage is repaired, allowing cells enough time to recover from damage before resuming normal proliferation. Here, we investigate the temporal dynamics of DNA damage checkpoints in individual proliferating cells by observing cell cycle phase transitions following acute DNA damage. We find that in gap phases (G1 and G2), DNA damage triggers an abrupt halt to cell cycle progression in which the duration of arrest correlates with the severity of damage. However, cells that have already progressed beyond a proposed “commitment point” within a given cell cycle phase readily transition to the next phase, revealing a relaxation of checkpoint stringency during later stages of certain cell cycle phases. In contrast to G1 and G2, cell cycle progression in S phase is significantly less sensitive to DNA damage. Instead of exhibiting a complete halt, we find that increasing DNA damage doses leads to decreased rates of S-phase progression followed by arrest in the subsequent G2. Moreover, these phase-specific differences in DNA damage checkpoint dynamics are associated with corresponding differences in the proportions of irreversibly arrested cells. Thus, the precise timing of DNA damage determines the sensitivity, rate of cell cycle progression, and functional outcomes for damaged cells. These findings should inform our understanding of cell fate decisions after treatment with common cancer therapeutics such as genotoxins or spindle poisons, which often target cells in a specific cell cycle phase.
Quadratization: From conductance-based models to caricature models with parabolic nonlinearities
Authors: Turnquist Axel G. R. , Rotstein Horacio G.
Published: May 2017

Definition

Quadratizationof biophysical (conductance-based) models having a parabolic-like voltage nullcline in the subthreshold voltage regime refers to the process by which these models are substituted by “caricature” models having a strictly parabolic voltage nullcline and a linear nullcline for the recovery variable. We refer to the latter as quadratic or parabolic models. The parabolic-like and strictly parabolic voltage nullclines coincide at their extrema (minima or maxima) and are well approximated by each other in vicinities of these extrema whose size depend on the model parameters. Quadratic models are simplified by a change of variables that translates these extrema into the origin of the phase-plane diagram. A further simplification (parameter reduction) can be achieved by nondimensionalizing the quadratic models. This procedure can be extended to three-dimensional models having a parabolic-cylinder-like shaped voltage nullsurface and to models having time-dependent inputs and synaptic currents.
Estimation of universal and taxon-specific parameters of prokaryotic genome evolution
Authors: Sela Itamar , Wolf Yuri I. , Koonin Eugene V.
Published: May 2017

Our recent study on mathematical modeling of microbial genome evolution indicated that, on average, genomes of bacteria and archaea evolve in the regime of mutation-selection balance defined by positive selection coefficients associated with gene acquisition that is counter-acted by the intrinsic deletion bias. This analysis was based on the strong assumption that parameters of genome evolution are universal across the diversity of bacteria and archaea, and yielded extremely low values of the selection coefficient. Here we further refine the modeling approach by taking into account evolutionary factors specific for individual groups of microbes using two independent fitting strategies, an ad hoc hard fitting scheme and an hierarchical Bayesian model. The resulting estimate of the mean selection coefficient ofs∼10-10associated with the gain of one gene implies that, on average, acquisition of a gene is beneficial, and that microbial genomes typically evolve under a weak selection regime that might transition to strong selection in highly abundant organisms with large effective population sizes. The apparent selective pressure towards larger genomes is balanced by the deletion bias, which is estimated to be consistently greater than unity for all analyzed groups of microbes. The estimated values ofsare more realistic than the lower values obtained previously, indicating that global and group-specific evolutionary factors synergistically affect microbial genome evolution that seems to be driven primarily by adaptation to existence in diverse niches.
The opposite effects of nitric oxide donor, S‐nitrosoglutathione, on myocardial ischaemia/reperfusion injury in diabetic and non‐diabetic mice
Authors: Liu Yi , Xia Chenhai , Wang Rutao , Zhang Jinglong , Yin Tao , Ma Yanzuo , Tao Ling
Published: May 2017

Nitric oxide is a potent anti‐apoptotic and cardioprotective molecule in healthy animals. However, recent study demonstrates that overexpression of eNOS exacerbates the liver injury in diabetic animals. whether diabetes may also alter NO's biologic activity in ischaemic/reperfused heart remains unknown. The present experiment was designed to determine whether the nitric oxide donor, S‐nitrosoglutathione, may exert different effects on diabetic and non‐diabetic myocardial ischaemia/reperfusion (MI/R) injury. Diabetic state was induced in mice by multiple intraperitoneal injections of low‐dose streptozotocin (STZ). The control or diabetic mice were subjected to 30 minutes ischaemia and 3 or 24 hours reperfusion. At 10 minutes before reperfusion, diabetic and non‐diabetic mice were received an intraperitoneal injection of S‐nitrosoglutathione (GSNO, a nitric oxide donor, 1 μmol/kg). GSNO attenuated MI/R injury in non‐diabetic mice, as measured by improved cardiac function, reduced infarct size and decreased cardiomyocyte apoptosis. In contrast, GSNO failed to attenuate but, rather, aggravated the MI/R injury in diabetic mice. Mechanically, the diabetic heart exhibited an increased nitrative/oxidative stress level, as measured by peroxynitrite formation, compared with non‐diabetic mice. Co‐administration of GSNO with EUK134 (a peroxynitrite scavenger) or MnTE‐2‐PyP5 (a superoxide dismutase mimetic) or Apocynin (a NADPH oxidase inhibitor) 10 minutes before reperfusion significantly decreased the MI/R‐induced peroxynitrite formation and the MI/R injury. Collectively, the present study for the first time demonstrated that diabetes may cause superoxide overproduction, increase NO inactivation and peroxynitrite formation, and thus convert GSNO from a cardioprotective molecule to a cardiotoxic molecule.
Hot water immersion of Allium hookeri roots for the control of the plant parasitic nematodes Meloidogyne javanica and Pratylenchus coffeae
Authors: Cho Dong‐Hun , Park Bok‐Ri , Chun Jae‐Yong , Noh Young‐Ho , Kim Yang‐Ho , Park Min‐Gu , Kim Dongwoo , Lee Kyeong‐Yeoll
Published: May 2017

Nematodes are important quarantine pests of bulbous plants such as hooker chives. Although control methods such as fumigation, chemical immersion, and heat are often applied, it has proved difficult to disinfect nematodes from plant roots in quarantine. As heat treatment has been successfully useful for the control of nematodes in other agricultural products in quarantine, we investigated the susceptibility and mortality rates of Meloidogyne javanica and Pratylenchus coffeae, which infest hooker chive roots, using a hot water immersion method. Heat damage to the hooker chive roots was noticeable at temperatures over 50°C. Temperatures for the effective time to kill 99% at 1 min (ET99) for M. javanica and P. coffeae juveniles were 49.3°C and 49.1°C, respectively. However, the time to kill 99% of M. javanica eggs at 48°C and 49°C were 27.0 min and 8.3 min, respectively. Using a thermal equilibrium formula, the optimum commercial scale condition, in a 1400‐L chamber, for nematode control without associated plant damage was water immersion at 48.2°C for 30 min or at 49.2°C for 13 min with a filling ratio less than 12%. This result can be applicable for the nematode disinfestation of hooker chive roots in plant quarantine.
Don't Label Me: A Qualitative Study of Patients’ Perceptions and Experiences of Sedation During Behavioral Emergencies in the Emergency Department
Authors: Yap Celene Y. L. , Knott Jonathan C. , Kong David C. M. , Gerdtz Marie , Stewart Kay , Taylor David M.
Published: May 2017

Objectives

Behavioral emergencies are commonly seen in emergency departments (EDs). Acutely agitated patients can be difficult to manage and sedation may be required to decrease dangerous behavior and to ensure the safety of both the patient and the staff. While the experience of staff caring for this population has been reported, patients’ experiences with their overall management remains unknown. We aimed to describe the perceptions and experiences of patients regarding the use of sedation during acute behavioral emergencies.

Methods

Face‐to‐face semistructured interviews were conducted with adults aged 18 years or older, who had received parenteral sedative medication for the management of a behavioral emergency and were deemed capable to participate. The participants were asked about their experiences of receiving care in the ED during the episode and their perceptions of sedation. All interviews were transcribed verbatim and analyzed thematically.

Results

Data saturation was reached after 13 interviews. Two broad themes emerged: trusting relationships and needs or wants following sedation. A trusting relationship is built through 1) confidence in care, 2) sedation as an appropriate treatment, 3) insight into own behavior, and 4) humane treatment. Four subthemes of needs or wants were identified: 1) empathy, 2) debrief, 3) addressing concerns, and 4) follow‐up.

Conclusions

A trusting relationship was identified as crucial to minimize the negative impact of coercive measures used to manage behavioral emergencies. Participants expressed similar needs to patients presenting with medical problems. This study illustrates their needs for compassionate communication, adequate information about the treatment provided, and follow‐up care.
A 0‐Hour/1‐Hour Protocol for Safe, Early Discharge of Chest Pain Patients
Authors: Mokhtari Arash , Lindahl Bertil , Schiopu Alexandru , Yndigegn Troels , Khoshnood Ardavan , Gilje Patrik , Ekelund Ulf
Published: May 2017

Objectives

Guidelines recommend a 0‐hour/1‐hour high‐sensitivity cardiac troponin T (hs‐cTnT) diagnostic strategy in acute chest pain patients. There are, however, little data on the performance of this strategy when combined with clinical risk stratification. We aimed to evaluate the diagnostic accuracy of an accelerated diagnostic protocol (ADP) using the 0‐hour/1‐hour hs‐cTnT strategy together with an adapted Thrombolysis In Myocardial Infarction (TIMI) score and electrocardiogram (ECG) for ruling out major adverse cardiac events (MACE) within 30 days.

Methods

This prospective observational study enrolled consecutive emergency department (ED) chest pain patients. TIMI score variables, ED physicians’ assessments of the ECG, and 0‐ and 1‐hour hs‐cTnT were collected. Thirty‐day MACE was defined as acute myocardial infarction (AMI), unstable angina (UA), cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of cardiac or unknown cause.

Results

A total of 1,020 patients were included in the final analysis. The combination of an adapted TIMI score ≤1, a nonischemic ECG, and either a 0‐hour hs‐cTnT < 5 ng/L or a 0‐hour hs‐cTnT < 12 ng/L combined with a 1‐hour increase < 3 ng/L identified 432 (42.4%) patients as very low risk with a negative predictive value of 99.5% (95% confidence interval [CI] = 98.3%–99.9%) and a negative likelihood ratio of 0.04 (95% CI = 0.01–0.14) for 30‐day MACE. The ADP missed only two patients with UA and no patients with AMI or other forms of MACE.

Conclusion

An ADP using the guideline recommended 0‐hour/1‐hour hs‐cTnT strategy rapidly identified patients with a very low risk of 30‐day MACE including UA where no further cardiac testing would be needed. This could potentially allow safe early discharge of about 40% of ED chest pain patients.
Assessment of the effects of transgenic Bt cotton Bollgard II on the abundance of nontarget arthropods in Burkina Faso
Authors: Héma Omer S. A. , Ouédraogo Issoufou , Traoré Oumar , Zagré Blaise K. , Ouattara Delphine
Published: May 2017

The effect of transgenic cotton Bollgard II on the abundance of nontarget arthropods was assessed under field conditions in three areas in Burkina Faso for four successive years (2010–2013).

The experiment was carried out on two 0.5‐ha plots of which one was seeded with the Bollgard II and one with the non‐Bacillus thuringiensis Berliner (Bt) isogenic cultivar.

Over four collection methods [plastic bagging (28 collections), water trap (28 collections), beat cloth (six collections) and pitfall traps (six collections)] and 4 years, no statistically significant differences were detected between Bollgard II and the conventional control for 45 out of 48 comparisons.

Differences detected were rather random and not consistently detected across collection methods, sites and/or years. Thus, these differences were not indicative of a consistent response associated with the trait and are not considered biologically meaningful in terms of an adverse environmental impact (nontarget arthropod abundance) of Bollgard II compared to conventional cotton receiving six insecticide sprays.
Temporal trends in thyroid‐stimulating hormone (TSH) and thyroid peroxidase antibody (ATPO) testing across two phases of iodine fortification in Tasmania (1995‐2013)
Authors: Hong A. , Stokes B. , Otahal P. , Owens D. , Burgess J.R.
Published: May 2017

Context

Tasmania is an island state of the Australian Commonwealth with a well‐documented history of mild iodine deficiency. Between 2001 and 2009, Tasmania experienced two incremental phases of iodine fortification.

Objective

To examine trends in thyroid‐stimulating hormone (TSH) and thyroid peroxidase antibody (ATPO) testing and their relationship to different phases of iodine nutrition in the Tasmanian population between 1995 and 2013.

Design

Retrospective longitudinal study.

Setting and participants

The major primary care and largest public hospital pathology providers in Tasmania submitted data for all TSH and ATPO tests performed between 1995 and 2013. Data linkage methodology was used to determine trends in TSH and ATPO testing.

Results

A total of 1.66 million TSH assessments, involving 389,910 individual patients, were performed in Tasmania between 1995 and 2013. There was approximately a fourfold increase in the overall rate of TSH testing during this period with the rate of incident TSH assessment remaining relatively stable over the study period. The incidence of overt suppression and elevation of TSH (TSH≤0.1 mIU/L and ≥10 mIU/L) declined 62.3% and 59.7%, respectively, with a trend for increased incidence of borderline TSH elevation ≥4.0 mIU/L. The incidence of thyroid autoimmunity as determined by the proportion of abnormal ATPO results remained stable, with the absolute number of positive test results increasing during the study period.

Conclusion

Iodine supplementation of this mildly iodine‐deficient population was not associated with an obvious increase in incidence of overt thyroid dysfunction or autoimmunity. Whilst the volume of TSH testing increased over the study period, the increase was driven by patients undergoing follow‐up TSH assessments.
Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids
Authors: Rasmussen Jon Jarløv , Schou Morten , Selmer Christian , Johansen Marie Louise , Gustafsson Finn , Frystyk Jan , Dela Flemming , Faber Jens , Kistorp Caroline
Published: May 2017

Objective

Abuse of anabolic androgenic steroids (AAS) is prevalent among young men, but information regarding effects on insulin sensitivity and fat distribution is limited. The objective was to investigate insulin sensitivity in relation to fat distribution and adipocytokines among current and former AAS abusers compared with controls.

Design

Cross‐sectional study among men involved in recreational strength training. Current and former AAS abusers (n=37 and n=33) and controls (n=30) volunteered from the community.

Methods

We assessed insulin sensitivity by Matsuda index (oral glucose tolerance test). Using overnight fasting blood samples, adiponectin and leptin were measured. Body composition and fat distribution, including visceral adipose tissue (VAT), were assessed by dual energy X‐ray absorptiometry.

Results

Current and former AAS abusers displayed lower Matsuda index than controls (%‐difference (95%CI) from controls, −26% (−45; −1) and −39% (−55; −18)). Testosterone was markedly higher among current AAS abusers and subnormal among former AAS abusers compared with controls. Current AAS abusers displayed higher mean VAT than controls (388 (17) vs 293 (12) cm3, P<.001) whereas body fat %, adiponectin and leptin concentrations were lower. In contrast, former AAS abusers showed highest leptin concentrations and body fat %. Multivariate linear regressions identified VAT as independent predictor of lower Matsuda index among current AAS abusers compared with controls; while body fat % independently predicted lower Matsuda index among former AAS abusers.

Conclusions

Both current and former AAS abusers displayed lower insulin sensitivity which could be mediated by higher VAT and total body fat %, respectively.
A Review of Social Dilemmas and Social‐Ecological Traps in Conservation and Natural Resource Management
Authors: Cumming Graeme S.
Published: May 2017

Successful conservation depends as much on people working together as it does on sound science and good governance. Research on cooperation in businesses, economics, psychology, and natural resource management has identified shared social and social‐ecological dynamics, reviewed and categorized in this article that can create unwanted surprises and problems for conservation efforts. Cooperation may fail when: (1) individual and group benefits are in conflict (social dilemmas) or (2) social‐ecological systems become caught in problem‐causing and problem‐enhancing feedbacks (SES traps). Knowing about and recognizing these dynamics can help decision makers to understand and change key elements of problems and learn from the experiences of others. Social dilemmas have winners and losers, and involve give‐some or take‐some choices; SES traps are lose‐lose situations. Solutions to problems of cooperation in conservation contexts involve identifying the conservation objective and context, diagnosing systemic social dilemmas and SES traps, and developing practical solutions that work with group processes and individuals toward shared and positively reinforcing goals, goal structures, and expectations. Research on cooperation in conservation has largely ignored problems of scale, scaling, and group heterogeneity. The field would benefit from a shift from a probabilistic, empirical approach to a stronger theory‐driven, mechanistic, and more diagnostic approach.
‘Real’ wages? Contractors, workers, and pay in London building trades, 1650–1800
Authors: Stephenson Judy Z.
Published: May 2017

Existing series suggest wages in London were higher than in other European cities from 1650 to 1800. This article presents new evidence from the construction sites that supplied the underlying wage data, and uncovers the contractual and organizational context in which they were recorded. Institutional records of wages were profoundly affected by structural changes in the seventeenth century, particularly the emergence of large‐scale building contractors. The actual wages paid to London building workers were substantially below current estimates.
Analysis of serum markers of cellular immune activation in patients with bullous pemphigoid
Authors: Bieber Katja , Ernst Anna Lara , Tukaj Stefan , Holtsche Maike M. , Schmidt Enno , Zillikens Detlef , Ludwig Ralf J. , Kasperkiewicz Michael
Published: May 2017

Experimental models of bullous pemphigoid (BP), the most frequent subepidermal autoimmune bullous disease, revealed that the immune response leading to blister formation represents an incompletely understood complex process involving different inflammatory cells. In contrast to previous reports commonly focusing on limited molecular and cellular phenotypes of the disease, the aim of this study was to investigate a broad spectrum of markers of cellular immune activation in patients with BP. We found that serum levels of soluble CD4, myeloperoxidase, S100A12, eosinophil cationic protein and soluble P‐selectin were significantly elevated in patients with active BP compared with normal controls. Mast cell tryptase and neopterin serum levels significantly decreased at the time of clinical remission of the patients. Additionally, serum concentrations of soluble IL‐2 receptor, mast cell tryptase and soluble P‐selectin were significantly associated with levels of circulating anti‐BP180 autoantibodies. Our findings confirm and extend previous reports suggesting some concomitant involvement of a panel of molecules representative for a wide spectrum of cellular players (T cells, mast cells, neutrophils, eosinophils, macrophages and platelets) orchestrating the inflammatory reaction in BP. These data may favour the employment of broad‐spectrum or combined immunosuppressants, potentially together with an anticoagulant treatment, over cell‐ or molecule‐specific targeted therapy in patients with this disorder.
Red tattoos, ultraviolet radiation and skin cancer in mice
Authors: Lerche Catharina M. , Heerfordt Ida M. , Serup Jørgen , Poulsen Thomas , Wulf Hans Christian
Published: May 2017

Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and red tattoos may be associated with increased risk of skin cancer due to potential carcinogens in tattoo inks. This combination has not been studied previously. Immunocompetent C3.Cg/TifBomTac hairless mice (n=99) were tattooed on their back with a popular red tattoo ink. This often used ink is banned for use on humans because of high content of the potential carcinogen 2‐anisidine. Half of the mice were irradiated with three standard erythema doses UVR thrice weekly. Time to induction of first, second and third squamous cell carcinoma (SCC) was measured. All UV‐irradiated mice developed SCCs. The time to the onset of the first and second tumor was identical in the red‐tattooed group compared with the control group (182 vs 186 days and 196 vs 203 days, P=ns). Statistically, the third tumor appeared slightly faster in the red‐tattooed group than in the controls (214 vs 224 days, P=.043). For the second and third tumor, the growth rate was faster in the red‐tattooed group compared with the control (31 vs 49 days, P=.009 and 30 vs 38 days, P=.036). In conclusion, no spontaneous cancers were observed in skin tattooed with a red ink containing 2‐anisidine. However, red tattoos exposed to UVR showed faster tumor onset regarding the third tumor, and faster growth rate of the second and third tumor indicating red ink acts as a cocarcinogen with UVR. The cocarcinogenic effect was weak and may not be clinically relevant.
Integrating the genomic architecture of human nucleolar organizer regions with the biophysical properties of nucleoli
Authors: Mangan Hazel , Gailín Michael Ó , McStay Brian
Published: May 2017

Nucleoli are the sites of ribosome biogenesis and the largest membraneless subnuclear structures. They are intimately linked with growth and proliferation control and function as sensors of cellular stress. Nucleoli form around arrays of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs). In humans, NORs are located on the short arms of all five human acrocentric chromosomes. Multiple NORs contribute to the formation of large heterochromatin‐surrounded nucleoli observed in most human cells. Here we will review recent findings about their genomic architecture. The dynamic nature of nucleoli began to be appreciated with the advent of photodynamic experiments using fluorescent protein fusions. We review more recent data on nucleoli in Xenopus germinal vesicles (GVs) which has revealed a liquid droplet‐like behavior that facilitates nucleolar fusion. Further analysis in both XenopusGVs and Drosophila embryos indicates that the internal organization of nucleoli is generated by a combination of liquid–liquid phase separation and active processes involving rDNA. We will attempt to integrate these recent findings with the genomic architecture of human NORs to advance our understanding of how nucleoli form and respond to stress in human cells.
The future distribution of river fish: The complex interplay of climate and land use changes, species dispersal and movement barriers
Authors: Radinger Johannes , Essl Franz , Hölker Franz , Horký Pavel , Slavík Ondřej , Wolter Christian
Published: May 2017

The future distribution of river fishes will be jointly affected by climate and land use changes forcing species to move in space. However, little is known whether fish species will be able to keep pace with predicted climate and land use‐driven habitat shifts, in particular in fragmented river networks. In this study, we coupled species distribution models (stepwise boosted regression trees) of 17 fish species with species‐specific models of their dispersal (fish dispersal model FIDIMO) in the European River Elbe catchment. We quantified (i) the extent and direction (up‐ vs. downstream) of predicted habitat shifts under coupled “moderate” and “severe” climate and land use change scenarios for 2050, and (ii) the dispersal abilities of fishes to track predicted habitat shifts while explicitly considering movement barriers (e.g., weirs, dams). Our results revealed median net losses of suitable habitats of 24 and 94 river kilometers per species for the moderate and severe future scenarios, respectively. Predicted habitat gains and losses and the direction of habitat shifts were highly variable among species. Habitat gains were negatively related to fish body size, i.e., suitable habitats were projected to expand for smaller‐bodied fishes and to contract for larger‐bodied fishes. Moreover, habitats of lowland fish species were predicted to shift downstream, whereas those of headwater species showed upstream shifts. The dispersal model indicated that suitable habitats are likely to shift faster than species might disperse. In particular, smaller‐bodied fish (<200 mm) seem most vulnerable and least able to track future environmental change as their habitat shifted most and they are typically weaker dispersers. Furthermore, fishes and particularly larger‐bodied species might substantially be restricted by movement barriers to respond to predicted climate and land use changes, while smaller‐bodied species are rather restricted by their specific dispersal ability.
Factors predicting overall response and overall survival in hepatocellular carcinoma patients undergoing balloon‐occluded transcatheter arterial chemoembolization: A retrospective cohort study
Authors: Hatanaka Takeshi , Arai Hirotaka , Shibasaki Mitsuhiko , Tojima Hiroki , Takizawa Daichi , Toyoda Mitsuo , Takayama Hisashi , Abe Takehiko , Sato Ken , Kakizaki Satoru , Yamada Masanobu
Published: May 2017

Aim

This study aimed to investigate the factors predicting overall response and overall survival in hepatocellular carcinoma patients undergoing balloon‐occluded transcatheter arterial chemoembolization (B‐TACE).

Methods

Sixty‐six patients treated with B‐TACE at a Japanese tertiary referral hospital between January 2011 and August 2015 were included in this retrospective cohort study.

Results

The overall response was classified as complete response, partial response, stable disease, and progressive disease in 35 (53.0%), 7 (10.6%), 13 (19.7%), and 11 (16.7%) patients, respectively. The response rate was 63.6%, and the disease control rate was 83.3%. The number of tumors (hazard ratio [HR], 4.44; 95% confidence interval [CI], 1.26–15.7; P = 0.021) and α‐fetoprotein level (HR, 11.40; 95% CI, 2.75–46.9; P < 0.001) were significantly associated with the tumor response in a multivariate analysis. The 1‐, 2‐, and 3‐year survival rates were 76.8% (95% CI, 64.5–85.3%), 57.3% (95% CI, 42.3–69.7%), and 46.7% (95% CI, 30.7–61.2%), respectively. The median survival time was 902 days. Albumin (≥3.4 g/dL) (HR, 0.28; 95% CI, 0.12–0.63; P = 0.002) and overall response (complete response and partial response) (HR, 0.33; 95% CI, 0.16–0.71; P = 0.004) were factors significantly associated with overall survival in a multivariate analysis. No mortalities were observed, but biloma requiring percutaneous transhepatic biliary drainage occurred in one patient (1.5%).

Conclusion

Balloon‐occluded transcatheter arterial chemoembolization may exert a good antitumor effect and result in good overall survival in select hepatocellular carcinoma patients.
Three phases of changes in carabid assemblages during secondary succession in a pine forest disturbed by windthrow – results from the first 10 years of observations
Authors: Skłodowski Jarosław J.
Published: May 2017

A windthrow disturbance alters the functioning and structure of a forest ecosystem and causes substantial economic losses.

A 10‐year pitfall study of carabid assemblages (Coleoptera, Carabidae) was carried out in pine stands disturbed by windthrow (Pisz Forest, North Poland) in the first year after the disturbance, with different classes of severity: severely disturbed stands (canopy cover up to 30%), moderately disturbed stands (canopy cover of 40–60%) and least disturbed stands (canopy cover of 70–90%).

Based on the number of carabid species and their ecological traits, I confirmed the hypothesis that the amplitude of changes in carabid assemblages inhabiting severely and moderately disturbed stands would be greater than in the least disturbed stands. Variation in carabid assemblages was also linked to soil pH and to carbon and nitrogen content in the soil.

The study confirmed my hypothesis regarding the delayed replacement of late successional carabid fauna by early successional fauna, which was linked to the broken pines lying on the soil, allowing late successional fauna to survive in the first few years after the windthrow.

The principal response curve analysis identified three phases of post‐disturbance succession in carabid assemblages: (i) slight changes in the number of species and their ecological traits, lasting for 4 years; (ii) ‘rapid’ changes, lasting for 3 years, involving an increase in the number of species and rapid replacement of late successional carabid fauna by early successional fauna; and (iii) the slow recovery of late carabid successional fauna.
Microencapsulated Lactobacillus reuteri combined with modified atmosphere as a way to improve tuna burger shelf life
Authors: Angiolillo Luisa , Conte Amalia , Del Nobile Matteo A.
Published: May 2017

In this study, tuna burgers were subjected to a bio‐preservation treatment combined with modified atmosphere packaging (MAP) in order to prolong the shelf life. After L. reuteri production of reuterin, the antimicrobial compound was microencapsulated and then added to tuna burger formulation. Reuterin content was analysed before and after the spray drying treatment, thus assessing its final concentration. Then, the effects of spray‐dried reuterin on tuna burgers quality were investigated with success on samples packaged under both ordinary and MAP conditions. The efficacy of bio‐control was evident in all the samples. For burgers stored in air, a shelf life of about 7.63 days was recorded for the active samples with respect to the 5.78 days of the reuterin‐free samples. Under MAP, a similar reuterin effectiveness was recorded but a general shelf life improvement was reached, accounting for about 13 days in the active samples and 12 days in the reuterin‐free samples.
A comparative study using thrombin generation and three different INR methods in patients on Vitamin K antagonist treatment
Authors: Riva N. , Vella K. , Meli S. , Hickey K. , Zammit D. , Calamatta C. , Makris M. , Kitchen S. , Ageno W. , Gatt A.
Published: May 2017

Introduction

Vitamin K antagonist (VKA) treatment requires routine monitoring using the international normalized ratio (INR). However, different INR assays may vary in their results. The aim of this study was to assess the agreement of three different INR methods, compared with thrombin generation, in patients on VKA treatment.

Methods

Sixty patients attending the Anticoagulation Clinic at Mater Dei Hospital (Msida, Malta) for VKA monitoring between August and September 2015 were enrolled. The INR was tested using a point‐of‐care (POC) device (CoaguChek XS Plus, Roche Diagnostics) for both capillary and venous blood samples, a photo‐optical (Sysmex CS‐2100i/CA‐1500, Siemens) and a mechanical clot detection system (Thrombolyzer XRC, Behnk Elektronik). All assays used human recombinant thromboplastin as reagent. Thrombin generation was performed using the calibrated automated thrombogram.

Results

There was a negative curvilinear correlation between the endogenous thrombin potential and different INR assays (r≤−.75) and a strong positive linear correlation between the CoaguChek XS Plus on capillary samples and the other INR methodologies (r≥.96).

Conclusion

All different INR assays showed good correlation with the thrombin generation potential. The POC INR showed one of the highest correlation coefficients with thrombin generation, confirming the POC devices as an accurate, valid alternative to laboratory INR in VKA patients.
Spectral management and energy‐transfer mechanism of Eu3+‐doped β‐NaGdF4:Yb3+,Er3+ microcrystals
Authors: Yao Lu , Xu Dekang , Lin Hao , Li Anming , Yang Shenghong , Zhang Yueli
Published: May 2017

β‐NaGdF4:Yb3+,Er3+ upconversion (UC) microcrystals were prepared by a facile hydrothermal process with the assistance of ethylene diamine tertraacetic acid (EDTA). The β‐NaGdF4 UC microcrystal morphology was controlled by changing the doses of EDTA and NaF. Uniform hexagonal structure can be obtained at the 2 mmol EDTA and 9‐10 mmol NaF. The UC emissions of β‐NaGdF4:Yb3+,Er3+ microcrystals were tuned by the variation of Eu3+ doping level (0%‐5%), where the red/green intensity ratio decreased with the Eu3+ concentration increase. It was found on the base of rate equations that with the Eu3+ doping, the energy back transfer process 2H11/2/4S3/2 (Er3+) → 4I13/2 (Er3+) decreased. In addition, an energy‐transfer process from 4F7/2 (Er3+) to 5D1 (Eu3+) and a cross relaxation process of 7H9/2 (Er3+) + 5D0 (Eu3+) → 4F7/2 (Er3+) + 5D2 (Eu3+) were proposed and verified by rate equations, which dominated the energy‐transfer mechanism between Er3+ and Eu3+, resulted in the spectra tuning of β‐NaGdF4:Yb3+,Er3+. The results suggested that the color tuning of β‐NaGdF4:Yb3+,Er3+,Eu3+ UC microcrystals would have potential applications in such fields as flat‐panel displays, solid‐state lasers, and photovoltaics.