bluuebunny/crossref_metadata_2025 huggingface dataset:
Grassland irrigation and fertilisation alter vegetation height and vegetation within temperature and negatively affect orthopteran populations
Authors: Humbert Jean-Yves , Delley Sarah , Arlettaz Raphaël
Published: January 2020

European mountain meadows are hosting an exceptionally rich biodiversity. While they have long been exposed to land abandonment, they are nowadays additionally threatened by agriculture intensification through aerial irrigation and slurry application. The consequences of this intensification on arthropods are not well documented and studies are needed to fulfil this knowledge gap. Six experimental management treatments combining a full factorial design and a gradual level of fertilisation and irrigation were implemented in 2010 in twelve different montane and subalpine Swiss meadows. In 2013, orthopterans were sampled to assess the influence of the management practices on their population. In addition changes in vegetation height and temperature induced by intensification were recorded in order to better appraise underlying mechanisms. Intensification had a negative impact on Caelifera (grasshoppers); with decreases of up to 70% in densities and 50% in species richness in the most intensively managed treatment plots. In parallel intensification induced an increase in mean vegetation height and a cooling of up to 4.2 °C (10 cm aboveground) within most intensively managed plots. These microhabitat and microclimate changes are likely to have affected Caelifera development, in particular thermophilous species. In contrast, Ensifera (bush crickets) densities and species richness did not respond to the management treatments. The use of irrigation (without fertilisation) had limited impacts on orthopterans and microclimate. In conclusion, orthopterans, in particular Caelifera, are relatively sensitive to grassland intensification and to conserve the full community, mountain agricultural systems need to maintain extensively managed meadows.
Supraphysiological protection from replication stress does not extend mammalian lifespan
Authors: Albers Eliene , Avram Alexandra , Sbroggio Mauro , Fernandez-Capetillo Oscar , Lopez-Contreras Andres J
Published: January 2020

Replication Stress (RS) is a type of DNA damage generated at the replication fork, characterized by single-stranded DNA (ssDNA) accumulation, and which can be caused by a variety of factors. Previous studies have reported elevated RS levels in aged cells. In addition, mouse models with a deficient RS response show accelerated aging. However, the relevance of endogenous or physiological RS, compared to other sources of genomic instability, for the normal onset of aging is unknown. We have performed long term survival studies of transgenic mice with extra copies of theChk1and/orRrm2genes, which we previously showed extend the lifespan of a progeroid ATR-hypomorphic model suffering from high levels of RS. In contrast to their effect in the context of progeria, the lifespan ofChk1, Rrm2andChk1/Rrm2transgenic mice was similar to WT littermates in physiological settings. Most mice studied died due to tumors -mainly lymphomas-irrespective of their genetic background. Interestingly, a slightly higher percentage of transgenic mice developed tumors compared to WT mice. Our results indicate that supraphysiological protection from RS does not extend lifespan, indicating that RS may not be a relevant source of genomic instability on the onset of “normal” aging.
ATX expression from GFAP+cells is essential for embryonic development
Authors: Sevastou Ioanna , Ninou Ioanna , Aidinis Vassilis
Published: January 2020

Autotaxin (ATX) is secreted by various type of cells in health and disease and catalyzes the extracellular production of lysophosphatidic acid (LPA). In turn, LPA is a bioactive lysophospholipid promoting a wide array of cellular functions through its multiple G-protein coupled receptors, differentially expressed in almost all cell types. ATX expression has been shown necessary for embryonic development and has been suggested to participate in the pathogenesis of different chronic inflammatory diseases and cancer. Deregulated ATX and LPA levels have been reported in multiple sclerosis (MS) and its experimental model, experimental autoimmune encephalomyelitis (EAE). ATX genetic deletion from macrophages and microglia (CD11b+cells) attenuated the severity of EAE, thus proposing a pathogenic role for the ATX/LPA axis in MS/EAE. In this report, increased ATX staining was localized to glial fibrillary acidic protein positive (GFAP+) cells, mostly astrocytes, in spinal cord sections from EAE mice at the peak of the disease. However, genetic deletion of ATX from GFAP+cells resulted in embryonic lethality, suggesting a major role for ΑΤΧ expression from GFAP+cells in embryonic development, that urges further dissection. Moreover, the re-expression of ATX from GFAP+ cells during the pathogenesis of EAE, reinforces the concept that ATX/LPA is a developmental program aberrantly reactivated upon chronic inflammation.
A computational model to unravel the function of amyloid-βpeptide in contact with a phospholipid membrane
Authors: Quoc Huy Pham Dinh , Krupa Pawel , Nguyen Hoang Linh , La Penna Giovanni , Li Mai Suan
Published: January 2020

The normal synapse activity involves the release of copper and other divalent cations in the synaptic region. These ions have a strong impact on the membrane properties, especially when the membrane has charged groups, like it is the case of synapse. In this work we use an atomistic computational model of dimyristoyl-phosphatidylcholine (DMPC) membrane bilayer. We perturb this model with a simple model of divalent cation (Mg2+), and with a single amyloid-β(Aβ) peptide of 42 residues, both with and without a single Cu2+ion bound to the N-terminus. In agreement with experimental results reported in the literature, the model confirms that divalent cations locally destabilize the DMPC membrane bilayer, and, for the first time, that the monomeric form of Aβhelps in avoiding the interactions between divalent cations and DMPC, preventing significant effects on the DMPC bilayer properties. These results are discussed in the frame of a protective role of diluted Aβpeptide floating in the synaptic region.

Author summary

We modelled the behavior of a Mg2+divalent cation, with the size of Zn2+and Cu2+, in contact with a phosphatidyl lipid bilayer. We also modelled the monomeric amyloid-βpeptide 1-42, both free and Cu-loaded, the latter mimicking the final step of the binding between the peptide and the divalent cation. On the basis of the simulation results, we propose that the peptide hinders the strong interactions between the divalent cation and the membrane.
Zero-determinant strategies under observation errors in repeated games
Authors: Mamiya Azumi , Ichinose Genki
Published: January 2020

Zero-determinant (ZD) strategies are a novel class of strategies in the repeated prisoner’s dilemma (RPD) game discovered by Press and Dyson. This strategy set enforces a linear payoff relationship between a focal player and the opponent regardless of the opponent’s strategy. In the RPD game, games with discounting and observation errors represent an important generalization, because they are better able to capture real life interactions which are often noisy. However, they have not been considered in the original discovery of ZD strategies. In some preceding studies, each of them has been considered independently. Here, we analytically study the strategies that enforce linear payoff relationships in the RPD game considering both a discount factor and observation errors. As a result, we first reveal that the payoffs of two players can be represented by the form of determinants as shown by Press and Dyson even with the two factors. Then, we search for all possible strategies that enforce linear payoff relationships and find that both ZD strategies and unconditional strategies are the only strategy sets to satisfy the condition. We also show that neither Extortion nor Generous strategies, which are subsets of ZD strategies, exist when there are errors. Finally, we numerically derive the threshold values above which the subsets of ZD strategies exist. These results contribute to a deep understanding of ZD strategies in society.
Genome-wide co-expression distributions as a metric to prioritize genes of functional importance
Authors: Alexandre Pâmela A. , Hudson Nicholas J. , Lehnert Sigrid A. , Fortes Marina R.S. , Naval-Sánchez Marina , Nguyen Loan T. , Porto-Neto Laercio R. , Reverter Antonio
Published: January 2020

Genome-wide gene expression is routinely used as a tool to gain a systems-level understanding of complex, biological processes. Numerical approaches that have been used to highlight influential genes include abundance, differential expression, differential variation, network connectivity and differential connectivity. Network connectivity tends to be built on a small subset of extremely high co-expression signals that are deemed significant, but this overlooks the vast majority of pairwise signals. Here, we aimed to assess a complementary strategy, namely whether the entire shape of the distribution of genome-wide co-expression values contains a meaningful biological signal that has hitherto remained hidden from view. We have developed a computational pipeline to assign one of 8 distributions (including normal, skewed, bimodal, kurtotic, inverted) to every gene. We then used a hypergeometric enrichment process to determine if particular genes (regulators versus non-regulators) and properties (differentially expressed or not) tend to be associated with particular distributions greater than would be expected by chance. Examination of several distinct data sets spanning 4 species indicates that there is indeed an additional biological signal present in the genome-wide distribution of co-expression values which would be overlooked by currently adopted approaches.

Author summary

High-throughput technologies, such as RNA-Seq, enables access to a vast amount of data. Here, we describe a new approach to interrogate these data and extract further information to help researchers to understand complex phenotypes. Our method is based on gene-level co-expression distributions which were compared to eight possible template shapes to group genes with similar behaviours. The method was tested using five different datasets and the consistency of the results indicate it can be used as a complementary strategy to analyse transcriptomic data.
iterb-PPse: Identification of transcriptional terminators in bacterial by incorporating nucleotide properties into PseKNC
Authors: Fan Yongxian , Wang Wanru , Zhu Qingqi
Published: January 2020

Terminator is a DNA sequence that give the RNA polymerase the transcriptional termination signal. Identifying terminators correctly can optimize the genome annotation, more importantly, it has considerable application value in disease diagnosis and therapies. However, accurate prediction methods are deficient and in urgent need. Therefore, we proposed a prediction method “iterb-PPse” for terminators by incorporating 47 nucleotide properties into PseKNC-Iand PseKNC-IIand utilizing Extreme Gradient Boosting to predict terminators based onEscherichia coliandBacillus subtilis. Combing with the preceding methods, we employed three new feature extraction methods K-pwm, Base-content, Nucleotidepro to formulate raw samples. The two-step method was applied to select features. When identifying terminators based on optimized features, we compared five single models as well as 16 ensemble models. As a result, the accuracy of our method on benchmark dataset achieved 99.88%, higher than the existing state-of-the-art predictor iTerm-PseKNC in 100 times five-fold cross-validation test. It’s prediction accuracy for two independent datasets reached 94.24% and 99.45% respectively. For the convenience of users, a software was developed with the same name on the basis of “iterb-PPse”. The open software and source code of “iterb-PPse” are available athttps://github.com/Sarahyouzi/iterb-PPse.
Ribosome association primes the stringent factor Rel for recruitment of deacylated tRNA to ribosomal A-site
Authors: Takada Hiraku , Roghanian Mohammad , Caballero-Montes Julien , Van Nerom Katleen , Jimmy Steffi , Kudrin Pavel , Trebini Fabio , Murayama Rikinori , Akanuma Genki , Garcia-Pino Abel , Hauryliuk Vasili
Published: January 2020

In the Gram-positive Firmicute bacteriumBacillus subtilis, amino acid starvation induces synthesis of the alarmone (p)ppGpp by the multi-domain RelA/SpoT Homolog factor Rel. This bifunctional enzyme is capable of both synthesizing and hydrolysing (p)ppGpp. To detect amino acid deficiency, Rel monitors the aminoacylation status of the ribosomal A-site tRNA by directly inspecting the tRNA’s CCA end. Here we uncover the molecular mechanism of Rel-mediated stringent response. Off the ribosome, Rel assumes a ‘closed’ conformation which has predominantly (p)ppGpp hydrolysis activity. This state does not specifically inspect tRNA and the interaction is only moderately affected by tRNA aminoacylation. Once bound to the vacant ribosomal A-site, Rel assumes an ‘open’ conformation, which primes its TGS and Helical domains for specific recognition and recruitment of cognate deacylated tRNA to the ribosome. The tRNA locks Rel on the ribosome in a hyperactivated state that processively synthesises (p)ppGpp while the hydrolysis is suppressed. In stark contrast to non-specific tRNA interactions off the ribosome, tRNA-dependent Rel locking on the ribosome and activation of (p)ppGpp synthesis are highly specific and completely abrogated by tRNA aminoacylation. Binding pppGpp to a dedicated allosteric site located in the N-terminal catalytic domain region of the enzyme further enhances its synthetase activity.
Transcription factors involved in stem cell maintenance are downstream of Slug/Snail2 and repressed by TGF-β in bronchial basal stem/progenitor cells from COPD
Authors: de la Grange Pierre , Jolly Ariane , Courageux Charlotte , Brahim Chamseddine Ben , Leroy Pascale
Published: January 2020

Patients with COPD have many anomalies in their airway epithelium, and their basal stem/progenitor cells show a decrease in self-renewal and differentiation potential. The objective of this study was to identify deregulations in the genetic program of COPD bronchial basal stem/progenitor cells that could account for their exhaustion. TGF-β is found at higher levels in the lungs of COPD subjects. It has been shown to play a role in stem/progenitor cell fate and also to regulate the expression of the EMT-inducing transcription factor Slug/Snail2. In contrast to other transcription factors of the Snail family, Slug is highly expressed in basal progenitor cells, the adult stem/progenitors of human airway epithelium. We aimed at identifying genes downstream of Slug that respond to TGF-β, and whose expression is deregulated in COPD airway basal stem/progenitor cells, and could account for the decrease in count and functional ability of these cells observed in COPD. For this, we knocked down Slug in primary bronchial basal progenitor cells from COPD and normal subjects and, among the genes downstream of Slug, we selected those responding to TGF-β and differentiation. We identified 5 genes coding for transcription factors involved in stem cell maintenance that are repressed downstream of Slug and by TGF-β in COPD but not normal basal progenitor cells. Our results bring a molecular perspective to the exhaustion of airway basal stem/progenitor cells observed in COPD by revealing that stem cell maintenance genes are repressed in these cells, with TGF-β and Slug being involved in this deregulation.
The TMJ disc is a common ancestral feature in all mammals, as evidenced by the presence of a rudimentary disc during monotreme development
Authors: Anthwal Neal , Tucker Abigail S
Published: January 2020

The novel mammalian jaw joint, known in humans as the temporomandibular joint or TMJ, is cushioned by a fibrocartilage disc. This disc is secondarily absent in therian mammals that have lost their dentition, such as giant anteaters and some baleen whales. The disc is also absent in all monotremes. However, it is not known if the absence in monotremes is secondary to the loss of dentition, or if it is an ancestral absence. We use museum held platypus and echidna histological sections to demonstrate that the developing monotreme jaw joint forms a disc primordium that fails to mature and become separated from the mandibular condyle. We then show that monotreme developmental anatomy is similar to that observed in transgenic mouse mutants with reduced musculature. We therefore suggest that the absence of the disc on monotremes is a consequence of the changes in jaw musculature associated with the loss of adult teeth. Taken together, these data indicate that the ancestors of extant monotremes likely had a jaw joint disc, and that the disc evolved in the last common ancestor or all mammals.
Measuring social networks in primates: wearable sensors vs. direct observations
Authors: Gelardi Valeria , Godard Jeanne , Paleressompoulle Dany , Claidière Nicolas , Barrat Alain
Published: January 2020

Network analysis represents a valuable and flexible framework to understand the structure of individual interactions at the population level in animal societies. The versatility of network representations is moreover suited to different types of datasets describing these interactions. However, depending on the data collection method, different pictures of the social bonds between individuals could a priori emerge. Understanding how the data collection method influences the description of the social structure of a group is thus essential to assess the reliability of social studies based on different types of data. This is however rarely feasible, especially for animal groups, where data collection is often challenging. Here, we address this issue by comparing datasets of interactions between primates collected through two different methods: behavioral observations and wearable proximity sensors. We show that, although many directly observed interactions are not detected by the sensors, the global pictures obtained when aggregating the data to build interaction networks turn out to be remarkably similar. Sensors data yield moreover a reliable social network already over short timescales and can be used for long term campaigns, showing their important potential for detailed studies of the evolution of animal social groups.
The npBAF to nBAF Chromatin Switch Regulates Cell Cycle Exit in the Developing Mammalian Cortex
Authors: Braun Simon MG , Petrova Ralitsa , Tang Jiong , Krokhotin Andrey , Miller Erik L , Tang Yitai , Panagiotakos Georgia , Crabtree Gerald R
Published: January 2020

Nervous system development is orchestrated by tightly-regulated progenitor cell divisions, followed by differentiation at precise but varying times across different regions. As progenitors exit the cell cycle, they initiate a subunit switch of the mSWI/SNF or npBAF complex to generate neuron-specific nBAF complexes. These chromatin regulatory complexes play dosage-sensitive roles in neural development and are frequently mutated in neurodevelopmental disorders. Here we manipulated the timing of BAF subunit exchange in the developing mouse brain and find that deletion of the npBAF subunit BAF53a blocks progenitor proliferation, leading to impaired neurogenesis. We show that npBAF complexes regulate cell cycle progression by antagonizing Polycomb complexes to promote chromatin accessibility at cell cycle and NPC identity genes. Replacement of the actin-related protein, Actl6a (BAF53a) by the neuron-specific actin-related protein, Actl6b (BAF53b), but not other regulators of proliferation, rescues progenitors by promoting neuronal differentiation. We propose that the function of the npBAF to nBAF chromatin switch is to control progenitor cell cycle exit and promote synchronous neural differentiation.
Classification of emotions based on functional connectivity patterns of the human brain
Authors: Saarimäki Heini , Glerean Enrico , Smirnov Dmitry , Mynttinen Henri , Jääskeläinen Iiro P. , Sams Mikko , Nummenmaa Lauri
Published: January 2020

Neurophysiological and psychological models posit that emotions depend on connections across wide-spread corticolimbic circuits. While previous studies using pattern recognition on neuroimaging data have shown differences between various discrete emotions in brain activity patterns, less is known about the differences in functional connectivity. Thus, we employed multivariate pattern analysis on functional magnetic resonance imaging data (i) to develop a pipeline for applying pattern recognition in functional connectivity data, and (ii) to test whether connectivity signatures differ across emotions. Six emotions (anger, fear, disgust, happiness, sadness, and surprise) and a neutral state were induced in 16 participants using one-minute-long emotional narratives with natural prosody while brain activity was measured with functional magnetic resonance imaging (fMRI). We computed emotion-wise connectivity matrices both for whole-brain connections and for 10 previously defined functionally connected brain subnetworks, and trained an across-participant classifier to categorize the emotional states based on whole-brain data and for each subnetwork separately. The whole-brain classifier performed above chance level with all emotions except sadness, suggesting that different emotions are characterized by differences in large-scale connectivity patterns. When focusing on the connectivity within the 10 subnetworks, classification was successful within the default mode system and for all emotions. We conclude that functional connectivity patterns consistently differ across different emotions particularly within the default mode system.
Network Insights into Improving Drug Target Inference Algorithms
Authors: Wang Muying , Noh Heeju , Mochan Ericka , Shoemaker Jason E.
Published: January 2020

To improve the efficacy of drug research and development (R&D), a better understanding of drug mechanisms of action (MoA) is needed to improve drug discovery. Computational algorithms, such as ProTINA, that integrate protein-protein interactions (PPIs), protein-gene interactions (PGIs) and gene expression data have shown promising performance on drug target inference. In this work, we evaluated how network and gene expression data affect ProTINA’s accuracy. Network data predominantly determines the accuracy of ProTINA instead of gene expression, while the size of an interaction network or selecting cell/tissue-specific networks have limited effects on the accuracy. However, we found that protein network betweenness values showed high accuracy in predicting drug targets. Therefore, we suggested a new algorithm, TREAP (https://github.com/ImmuSystems-Lab/TREAP), that combines betweenness values and adjustedp-values for target inference. This algorithm has resulted in higher accuracy than ProTINA using the same datasets.
Harmonic-Balance Circuit Analysis for Electro-Neural Interfaces
Authors: Chen Zhijie Charles , Wang Bingyi , Palanker Daniel
Published: January 2020

Objective

Avoidance of the adverse electrochemical reactions at the electrode-electrolyte interface defines the voltage safety window and limits the charge injection capacity (CIC) of an electrode material. For an electrode that is not ideally capacitive, the CIC depends on the waveform of the stimulus. We study the modeling of the charge injection dynamics to optimize the waveforms for efficient neural stimulation within the electrochemical safety limits.

Approach

The charge injection dynamics at the electrode-electrolyte interface is typically characterized by the electrochemical impedance spectrum, and is often approximated by discrete-element circuit models. We compare the modeling of the complete circuit, including a non-linear driver such as a photodiode, based on the harmonic-balance (HB) analysis with the analysis based on various discrete element approximations. To validate the modeling results, we performed experiments with iridium-oxide electrodes driven by a current source with diodes in parallel, which mimics a photovoltaic circuit.

Main results

Application of HB analysis based on a full impedance spectrum in frequency domain eliminates the complication of finding the discrete-element circuit model in traditional approaches. HB-based results agree with the experimental data better than the discrete-element circuit analysis. HB technique can be applied not only to demonstrate the circuit response to periodic stimulation, but also to describe the initial transient behavior when a burst waveform is applied.

Significance

HB-based circuit analysis accurately describes the dynamics of electrode-electrolyte interfaces and driving circuits for all pulsing schemes. This allows optimizing the stimulus waveform to maximize the CIC, based on the impedance spectrum alone.
Multimodal magnetic resonance imaging predicts regional amyloid- β burden in the brain
Authors: Rangarajan Anusha , Wu Minjie , Joseph Naomi , Karim Helmet T. , Laymon Charles , Tudorascu Dana , Cohen Annie , Klunk William , Aizenstein Howard J.
Published: January 2020

Alzheimer’s disease (AD) is the most common cause of dementia and identifying early markers of this disease is important for prevention and treatment strategies. Amyloid -βprotein deposition is one of the earliest detectable pathological changes in AD. But in-vivo detection of amyloid -βusing positron emission tomography (PET) is hampered by high cost and limited geographical accessibility. These factors can become limiting when PET is used to screen large numbers of subjects into prevention trials when only a minority are expected to be amyloid- β - positive. Structural MRI is advantageous; as it is relatively inexpensive and more accessible. Thus it could be widely used in large studies, even when frequent or repetitive imaging is necessary. We used a machine learning, pattern recognition, approach using intensity-based features from individual and combination of MR modalities (T1 weighted, T2 weighted, T2 fluid attenuated inversion recovery [FLAIR], susceptibility weighted imaging) to predict voxel-level amyloid- β in the brain. The MR- amyloidβrelation was learned within each subject and generalized across subjects using subject–specific features (demographic, clinical, and summary MR features). When compared to other modalities, combination of T1-weighted, T2-weighted FLAIR, and SWI performed best in predicting the amyloid- β status as positive or negative. T2- weighted performed the best in predicting change in amyloid- β over two timepoints. Overall, our results show feasibility of amyloid- β prediction by MRI.
Individual deviations from normative models of brain structure in a large cross-sectional schizophrenia cohort
Authors: Lv Jinglei , Di Biase Maria , Cash Robin F. H. , Cocchi Luca , Cropley Vanessa , Klauser Paul , Tian Ye , Bayer Johanna , Schmaal Lianne , Cetin-Karayumak Suheyla , Rathi Yogesh , Pasternak Ofer , Bousman Chad , Pantelis Christos , Calamante Fernando , Zalesky Andrew
Published: January 2020

Background

The heterogeneity of schizophrenia has defied efforts to derive reproducible and definitive anatomical maps of structural brain changes associated with the disorder. We aimed to map deviations from normative ranges of brain structure for individual patients and evaluate whether the loci of individual deviations recapitulated group-average brain maps of schizophrenia pathology.

Methods

For each of 48 white matter tracts and 68 cortical regions, normative percentiles of variation in fractional anisotropy (FA) and cortical thickness (CT) were established using diffusion-weighted and structural MRI from healthy adults (n=195). Individuals with schizophrenia (n=322) were classified as either within the normative range for healthy individuals of the same age and sex (5-95% percentiles), infra-normal (<5% percentile) or supra-normal (>95% percentile). Repeating this classification for each tract and region yielded a deviation map for each individual.

Results

Compared to the healthy comparison group, the schizophrenia group showed widespread reductions in FA and CT, involving virtually all white matter tracts and cortical regions. Paradoxically, however, no more than 15-20% of patients deviated from the normative range for any single tract or region, whereas 79% of patients showed infra-normal deviations for at least one locus (healthy individuals: 59±2%, p<0.001). Higher polygenic risk for schizophrenia associated with a greater number of regions with infra-normal deviations in CT (r=-0.17, p=0.006).

Conclusions

Anatomical loci of schizophrenia-related changes are highly heterogeneous across individuals to the extent that group-consensus pathological maps are not representative of most individual patients. Normative modeling can aid in parsing schizophrenia heterogeneity and guiding personalized interventions.
The relationship between eDNA particle concentration and organism abundance in nature is strengthened by allometric scaling
Authors: Yates M.C , Glaser D. , Post J. , Cristescu M.E. , Fraser D.J. , Derry A.M.
Published: January 2020

Organism abundance is a critical parameter in ecology, but its estimation is often challenging. Approaches utilizing eDNA to indirectly estimate abundance have recently generated substantial interest. However, preliminary correlations observed between eDNA concentration and abundance in nature are typically moderate in strength with significant unexplained variation. Here we apply a novel approach to integrate allometric scaling coefficients into models of eDNA concentration and organism abundance. We hypothesize that eDNA particle production scales non-linearly with mass, with scaling coefficients < 1. Wild populations often exhibit substantial variation in individual body size distributions; we therefore predict that the distribution of mass across individuals within a population will influence population-level eDNA production rates. To test our hypothesis, we collected standardized body size distribution and mark-recapture abundance data using whole-lake experiments involving nine populations of brook trout. We correlated eDNA concentration with three metrics of abundance: density (individuals/ha), biomass (kg/ha), and allometrically scaled mass (ASM) (∑(individual mass0.73)/ha). Density and biomass were both significantly positively correlated with eDNA concentration (adj. R2= 0.59 and 0.63, respectively), but ASM exhibited improved model fit (adj. R2= 0.78). We also demonstrate how estimates of ASM derived from eDNA samples in ‘unknown’ systems can be converted to biomass or density estimates with additional size structure data. Future experiments should empirically validate allometric scaling coefficients for eDNA production, particularly where substantial intraspecific size distribution variation exists. Incorporating allometric scaling may improve predictive models to the extent that eDNA concentration may become a reliable indicator of abundance in nature.
Life trajectories towards suicide: developmental role and specificities of adolescence
Authors: Notredame Charles-Edouard , Chawky Nadia , Beauchamp Guy , Vaiva Guillaume , Séguin Monique
Published: January 2020

Objective

Considering that adolescence is a crucial period of allostatic maturation, we aimed at testing whether it represents a breakpoint in adversity trajectories to suicide and, relatedly, whether life trajectories of adolescents who died by suicide differ from those of adult counterparts.

Method

In 303 individuals who died by suicide, a panel of experts derived longitudinal burden of adversity ratings from extensive clinical interviews conducted with informants. Piecewise Joint Latent Class Models allowed to identify patterns of adversity trajectories and test the introduction of breakpoints in life-paths. The classes inferred from the optimal model were compared in terms of socio-demographics, psychopathology and nature of experienced events.

Results

The most accurate model derived 2 trajectory patterns with a breakpoint in early adolescence. In the first class (n = 43 individuals), the burden of adversity increased steadily from birth to death, which occurred on average at 23 (SE = 1.29). In the second class (n = 259), where individuals died on average at 43 years (SE = 0.96), the burden of adversity followed a similar trajectory during infancy but stabilized between ages 10 and 14 years and rebounded at about 25. The classes differed in terms of childhood family stability, occurrence of dependent events, distal exposure to suicide and intra-family sexual victimization.

Conclusion

Although subject to inherent limitations of the retrospective designs, our results encourage clinicians and researchers to pay greater attention to the diathetic maturation processes occurring during adolescence when considering suicidal behaviors in young people.
Competitive exclusion of uropathogenicE. colibiofilm bySalmonellathrough matrix inhibition
Authors: Miryala Sandeep , Chandramohan S , Srinandan C. S.
Published: January 2020

Biofilm is a predominant lifestyle of bacteria in host and non-host environments with cell collectives and extracellular matrix as the defining principles of biofilm. Several factors trigger biofilm formation including response to competition. Urinary tract infections (UTI) are highly prevalent worldwide and mainly caused by uropathogenicE. coli(UPEC), which progresses into chronic form due to the biofilm formation by the pathogen. In this study, we hypothesized that competition for territorial space could occur between species by intervening in the biofilm matrix production, particularly of UPEC, thereby reducing its colonizing ability. UPEC colony displays different morphology in congo red media based on matrix production, which we exploited for screening bacterial isolates capable of inhibiting the matrix. This was validated by using the cell-free supernatants of the isolates to impair UPEC biofilm. Isolates that inhibited matrix production belonged to species of Shigella, Escherichia, Enterobacter, and Salmonella from Enterobacteriaceae family. Competition experiments between the isolates and UPEC revealed spiteful interactions particularly during biofilm formation, indicating fierce competition for territorial space colonization. The isolateSalmonella entericaB1 could competitively exclude UPEC in the biofilm. Altogether, we show that interference competition by matrix inhibition occurs as a strategy by bacteria to colonize territorial space.
A HOTAIR regulatory element modulates glioma cell sensitivity to temozolomide through long-range regulation of multiple target genes
Authors: Zhang Lei , He Anshun , Chen Bohan , Bi Jinfang , Chen Jun , Guo Dianhao , Qian Yuyang , Wang Wenbin , Shi Tengfei , Zhao Zhongfang , Shi Jiandang , An Woojin , Attenello Frank , Lu Wange
Published: January 2020

Temozolomide (TMZ) is a frequently used chemotherapy for glioma; however, chemoresistance is a major problem limiting its effectiveness. Thus, knowledge of mechanisms underlying this outcome could improve patient prognosis. Here, we report that deletion of a regulatory element in the HOTAIR locus increases glioma cell sensitivity to TMZ and alters transcription of multiple genes. Analysis of a combination of RNA-seq, Capture Hi-C, and patient survival data suggests that CALCOCO1 and ZC3H10 are target genes repressed by the HOTAIR regulatory element and that both function in regulating glioma cell sensitivity to TMZ. Rescue experiments and 3C data confirmed this hypothesis. We propose a new regulatory mechanism governing glioma cell TMZ sensitivity.
Risk of herpes zoster in the Japanese population with immunocompromising and chronic disease conditions: Results from a claims database cohort study, from 2005 to 2014
Authors: Imafuku Shinichi , Dormal Giulia , Goto Yasushi , Jégou Céline , Rosillon Dominique , Matsuki Taizo
Published: January 2020

Older adults, women and patients with immunocompromised (IC) or chronic medical conditions have a higher incidence of herpes zoster (HZ) and are at higher risk of developing HZ‐associated complications such as postherpetic neuralgia. The incidence rates of HZ in various IC and chronic conditions have been previously reported in a retrospective cohort study using claims data from Japanese adults. Here, we report further analyses from this cohort using univariate and multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) associated with different IC and chronic conditions. After adjusting for multiple covariates (age, sex and other coexisting medical conditions), the risk of HZ was higher in women (HR, 1.14 [95% CI, 1.11–1.17]), irrespective of age and increased with increasing age, being substantially higher in patients aged 65 years or older (HR, 3.28 [95% CI, 3.07–3.49]) when compared with those aged 18–29 years. The highest HRs were observed for the following specific IC conditions; hematopoietic stem cell transplant recipients (HR, 9.85 [95% CI, 6.80–14.28]), hematological malignancy (HR, 3.22 [95% CI, 2.54–4.09]), systemic lupus erythematosus (HR, 2.46 [95% CI, 1.45–4.15]) and inflammatory bowel disease (HR, 1.59 [95% CI, 1.14–2.21]). For most other IC and chronic medical conditions, a higher risk was also apparent though of a smaller magnitude (HRs ranging from 1.2 to <1.5). These results corroborate our previous findings and demonstrate an increased risk of HZ associated with different IC and chronic conditions.
Improved melanoma outcomes and survival in patients monitored by total body photography: A natural experiment
Authors: Strunck Jennifer L. , Smart Tristan C. , Boucher Kenneth M. , Secrest Aaron M. , Grossman Douglas
Published: January 2020

Total body photography (TBP) facilitates early melanoma detection, but long‐term outcomes have not been well studied. Our objectives were to examine melanoma diagnoses, role of TBP‐associated follow‐up visits, and survival in patients monitored by TBP. A total of 1955 patients meeting inclusion criteria received TBP from 2004–2013 at a single academic center. We compared the melanoma diagnoses and overall survival of 1253 patients with any follow‐up visits (median, three visits; range, 1–18) and 702 patients with no follow‐up visits. Use of TBP photographs influenced decision to biopsy 66 of 121 (54.5%) melanomas diagnosed after TBP. Lower invasive melanoma Breslow depth was significantly associated with having one or more follow‐up visit (median, 0.83 vs 0.33 mm; P = .002) and photographic review (median, 0.31 vs 0.48 mm; P = 0.02). In multivariable analyses, greater overall survival was significantly associated with having one or more follow‐up visit after TBP (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.14–0.91; P < 0.032) and having more than 100 nevi (HR, 0.37; 95% CI, 0.22–0.64; P = 0.004). Worse overall survival was significantly associated with increasing age (HR per year, 1.06; 95% CI, 1.04–1.08; P < 0.001) and male sex (HR, 2.65; 95% CI, 1.48–4.73; P = 0.001). Thus, monitoring by TBP was associated with subsequent melanoma diagnoses of lower stage and depth and greater overall survival.
Body mass index in psoriatic patients with or without familial psoriasis
Authors: Bayaraa Bolortuya , Arima Hisatomi , Imafuku Shinichi
Published: January 2020

Psoriasis is a chronic inflammatory disease caused by both genetic and environmental factors. The occurrence of psoriasis in family members indicates a genetic predisposition, while obesity is also a major contributor to psoriasis. We examined whether patients with versus without familial psoriasis were obese at the onset of psoriasis. Clinical information, including age at onset, age at first visit and body mass index (BMI) at first visit, was extracted from the Fukuoka University Psoriasis Registry. To compare BMI, patients aged 10 years or older who visited the clinic within 3 years of onset were selected. Familial psoriasis was observed in 27 patients (15 male, 12 female) out of 428 individuals (264 male, 164 female) with psoriasis, accounting for 6.3% of cases. Age at onset was younger for both men and women with familial psoriasis (34 ± 17 and 40 ± 15 years, respectively) relative to those with non‐familial psoriasis (48 ± 19 and 53 ± 19 years, respectively). We examined age‐ and sex‐adjusted average values of BMI at initial presentation after onset of psoriasis, finding that patients with familial psoriasis had lower BMI (22.0 kg/m2 [95% confidence interval, 21.8–22.4]) than those with non‐familial psoriasis (23.2 [23.1–23.3], P < 0.001). Individuals with a family history of psoriasis should be considered to be at risk for developing the disease even if obesity is not present.
Impact of rainfall seasonality on intraspecific trait variation in a shrub from a Mediterranean climate
Authors: Moore Timothy E. , Jones Cynthia S. , Chong Caroline , Schlichting Carl D.
Published: January 2020

Selection pressures along climate gradients give rise to predictable variation in plant functional traits of individual species suggestive of local adaptation. Species whose ranges include winter rainfall, Mediterranean climates, or other strongly seasonal climates, may be exposed to divergent selection pressures at different ends of seasonality gradients.

Here, we evaluate how rainfall seasonality in conjunction with other key climatic variables impacts patterns of trait variation in Pelargonium scabrum, a woody shrub from the Greater Cape Floristic Region of South Africa. This biodiversity hotspot encompasses a Mediterranean climate (wet winters and hot, dry summers) and displays steep gradients in temperature and water availability.

We used Bayesian regression models to evaluate leaf trait–trait and trait–climate relationships among 26 populations. Models included rainfall seasonality and its interaction with other climate variables (mean annual temperature, mean annual precipitation and potential evapotranspiration) as predictors to test for the impact of climate variation on three leaf traits: size, dissection and leaf mass per area (LMA). We evaluated model explanatory power by calculating Bayesian R2 values, and predictive power via leave‐one‐out cross‐validation.

Trait–trait associations were modulated by rainfall seasonality, including a reversal in the relationship between leaf size and dissection depending on the proportion of rain received in winter. Trait–climate models were improved by including rainfall seasonality as a predictor for both explanatory and predictive power. For leaf dissection and LMA, we detected significant interactions between rainfall seasonality and other environmental variables, leading to reversals in the relationships between these traits and the three environmental variables depending on the proportion of winter rainfall.

Differences in the timing of rainfall, coupled with strong differences in the covariation of climate variables, impose divergent selection pressures on P. scabrum populations resulting in divergence of trait values, trait integration and responses to climate gradients. These patterns are consistent with local adaptation of P. scabrum populations mediated by the interactions between temperature and the amount and timing of rainfall. Species arrayed along broad climate gradients represent an excellent opportunity for investigating patterns of trait variation and abundances and distributions of species in relation to future changes in climate.

A free Plain Language Summary can be found within the Supporting Information of this article.
To mate, or not to mate: The evolution of reproductive diapause facilitates insect radiation into African savannahs in the Late Miocene
Authors: Halali Sridhar , Brakefield Paul M. , Collins Steve C. , Brattström Oskar
Published: January 2020

Many tropical environments experience cyclical seasonal changes, frequently with pronounced wet and dry seasons, leading to a highly uneven temporal distribution of resources. Short‐lived animals inhabiting such environments often show season‐specific adaptations to cope with alternating selection pressures.

African Bicyclus butterflies show strong seasonal polyphenism in a suite of phenotypic and life‐history traits, and their adults are thought to undergo reproductive diapause associated with the lack of available larval host plants during the dry season.

Using 3 years of longitudinal field data for three species in Malawi, dissections demonstrated that one forest species reproduces continuously, whereas two savannah species undergo reproductive diapause in the dry season, either with or without pre‐diapause mating. Using additional data from field‐collected and museum samples, we then documented the same three mating strategies for a further 37 species.

Phylogenetic analyses indicated that the ancestral state was a non‐diapausing forest species, and that habitat preference and mating strategy evolved in a correlated fashion.

Bicyclus butterflies underwent rapid diversification during the Late Miocene, coinciding with expansions into more open savannah habitat. We conclude that the ability to undergo reproductive diapause was a key trait that facilitated colonization and eventual radiation into savannahs in the Late Miocene.
Long non‐coding RNA UCA1 promotes autophagy by targeting miR‐96‐5p in acute myeloid leukaemia
Authors: Li Jia Jia , Chen Xiao Feng , Wang Meng , Zhang Ping Ping , Zhang Feng , Zhang Jing Jing
Published: January 2020

Long non‐coding RNA (lncRNA) urothelial carcinoma‐associated 1 (UCA1) has been identified as an oncogene and is involved in acute myeloid leukaemia (AML). Autophagy contributes to tumourigenesis and cancer cell survival. The purpose of this study was to investigate the regulatory role and mechanism of UCA1 in AML cell viability by its effect on autophagy. The expression of UCA1, miR‐96‐5p, and ATG7 was determined by qRT‐PCR and western blot. Cell proliferation was examined by MTT assay. The autophagy level was assessed by green fluorescent protein (GFP)‐LC3 immunofluorescence and western blot. The interaction between UCA1 and miR‐96‐5p or ATG7 was analyzed by luciferase reporter activity. The results showed that UCA1 promoted AML cell proliferation by inducing autophagy. Mechanistically, UCA1 acted as a sponge of miR‐96‐5p by binding to miR‐96‐5p. ATG7 was a direct target of miR‐96‐5p and positively regulated by UCA1. Further results showed that the miR‐96‐5p mimic effectively counteracted the UCA1 overexpression‐mediated induction of the ATG7/autophagy pathway. Collectively, UCA1 functions as a sponge of miR‐96‐5p to upregulate its target ATG7, thereby resulting in autophagy induction. Our findings reveal a UCA1‐mediated molecular mechanism responsible for autophagy induction in AML and help to improve the understanding of the molecular mechanism of AML progression.