bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance analysis of an orbital angular momentum multiplexed amplify-and-forward radio relay chain with inter-modal crosstalk
Authors: Allen B. , Simmons D. , Drysdale T. D. , Coon J.
Published: January 2019

The end-to-end spectral efficiency and bit error rate (BER) of an amplify-and-forward (AF) radio relay chain employing orbital angular momentum (OAM) multiplexing is presented. The inherent divergence of a beam carrying OAM is overcome by means of a lens. Modelled and measured inter-modal crosstalk levels are incorporated into the analysis. The results show that an end-to-end spectral efficiency of up to 8 bits s
−1
Hz
−1
is achievable using four OAM modes to multiplex four parallel data streams over 20 hops, provided that the detrimental effects of inter-modal crosstalk are mitigated. The spectral efficiency is expected to scale further by using more OAM modes. The BER profile along the relay chain is analysed for each of the four OAM modes.
General isochronous rhythm in echolocation calls and social vocalizations of the batSaccopteryx bilineata
Authors: Burchardt Lara S. , Norton Philipp , Behr Oliver , Scharff Constance , Knörnschild Mirjam
Published: January 2019

Rhythm is an essential component of human speech and music but very little is known about its evolutionary origin and its distribution in animal vocalizations. We found a regular rhythm in three multisyllabic vocalization types (echolocation call sequences, male territorial songs and pup isolation calls) of the neotropical batSaccopteryx bilineata. The intervals between element onsets were used to fit the rhythm for each individual. For echolocation call sequences, we expected rhythm frequencies around 6–24 Hz, corresponding to the wingbeat inS. bilineatawhich is strongly coupled to echolocation calls during flight. Surprisingly, we found rhythm frequencies between 6 and 24 Hz not only for echolocation sequences but also for social vocalizations, e.g. male territorial songs and pup isolation calls, which were emitted while bats were stationary. Fourier analysis of element onsets confirmed an isochronous rhythm across individuals and vocalization types. We speculate that attentional tuning to the rhythms of echolocation calls on the receivers' side might make the production of equally steady rhythmic social vocalizations beneficial.
A red fluorescent BODIPY probe for iridium (III) ion and its application in living cells
Authors: Qu Xingyu , Bian Yongjun , Li Jianqing , Pan Yufeng , Bai Yang
Published: January 2019

A new red fluorescent probe
1
based on BODIPY skeleton has been successfully synthesized through introduction of 2-(thiophen-2-yl) quinoline moiety at
meso
- and 3-position, which exhibits excellent optical performance, including high fluorescence quantum yield, large pseudo Stokes' shift as well as high selectivity and sensitivity towards iridium (III) ion in aqueous solution and in living cells.
On discovering functions in actin filament automata
Authors: Adamatzky Andrew
Published: January 2019

We simulate an actin filament as an automaton network. Every atom takes two or three states and updates its state, in discrete time, depending on a ratio of its neighbours in some selected state. All atoms/automata simultaneously update their states by the same rule. Two state transition rules are considered. In semi-totalistic Game of Life like actin filament automaton atoms take binary states ‘0’ and ‘1’ and update their states depending on a ratio of neighbours in the state ‘1’. In excitable actin filament automaton atoms take three states: resting, excited and refractory. A resting atom excites if a ratio of its excited neighbours belong to some specified interval; transitions from excited state to refractory state and from refractory state to resting state are unconditional. In computational experiments, we implement mappings of an 8-bit input string to an 8-bit output string via dynamics of perturbation/excitation on actin filament automata. We assign eight domains in an actin filament as I/O ports. To write True to a port, we perturb/excite a certain percentage of the nodes in the domain corresponding to the port. We read outputs at the ports after some time interval. A port is considered to be in a state True if a number of excited nodes in the port's domain exceed a certain threshold. A range of eight-argument Boolean functions is uncovered in a series of computational trials when all possible configurations of eight-elements binary strings were mapped onto excitation outputs of the I/O domains.
Theoretical investigation of the structural and spectroscopic properties of expanded metalloporphyrin complexes
Authors: Jiang Jie , Guo Shengwei , Wang Xiaorong , Xu Liyan , Li Qiang , Zhang Xiaoxin
Published: January 2019

The frontier molecular orbitals, UV–Vis absorption spectra, charge transfer (CT) and triplet excited states of 12 expanded D–A porphyrin/benzoporphyrin complexes were investigated using the density functional theory (DFT) method and time-dependent DFT in this work. The results showed that thiophene was an effective fragment for absorption of ‘long wavelength’, while the benzoporphyrin worked on the ‘short wavelength’, which was derived from its saddle-shaped structure; this expanded D–A conjugated system had a mild CT process with anthraquinone/isoindigo as acceptors and a strong CT process with naphtoquinone as acceptor. In addition, based on the simulation of the triplet state, the theoretical phosphorescence wavelength range of this series of derivatives was between 1000 and 1200 nm. This study is expected to assist the design of conjugated porphyrin for the field of porphyrin chemistry.
Identification of reactive intermediate formation and bioactivation pathways in Abemaciclib metabolism by LC–MS/MS:
in vitro
metabolic investigation
Authors: Kadi Adnan A. , Darwish Hany W. , Abuelizz Hatem A. , Alsubi Thamer A. , Attwa Mohamed W.
Published: January 2019

Abemaciclib (Verzenio
®
) is approved as a tyrosine kinase inhibitor (TKI) for breast cancer treatment. In this study,
in vitro
phase I metabolic profiling of Abemaciclib (ABC) was done using rat liver microsomes (RLMs). We checked the formation of reactive intermediates in ABC metabolism using RLMs in the presence of potassium cyanide (KCN) that was used as a capturing agent for iminium reactive intermediates forming a stable complex that can be characterized by LC–MS/MS. Nine
in vitro
phase I metabolites and three cyano adducts were identified. The metabolic reactions involved in the formation of these metabolites and adducts are reduction, oxidation, hydroxylation and cyanide addition. The bioactivation pathway was also proposed. Knowing the electrodeficient bioactive centre in ABC structure helped in making targeted modifications to improve its safety and retain its efficacy. Blocking or isosteric replacement of α-carbon to the tertiary nitrogen atoms of piperazine ring can aid in reducing toxic side effects of ABC. No previous articles were found about
in vitro
metabolic profiling for ABC or structural identification of the formed reactive metabolites for ABC.
Graphene quantum dots as nanoprobes for fluorescent detection of propofol in emulsions
Authors: Diao Juanjuan , Wang Tingting , Li Li
Published: January 2019

We report a new fluorescent detection method for propofol based on graphene quantum dots (GQDs). Citric acid (CA) was selected as the carbon precursor, and fluorescent GQDs were prepared by carbonizing CA. The product, which efficiently quenched the fluorescence of GQDs, could be obtained through the oxidation of propofol in the presence of horseradish peroxidase and hydrogen peroxide. The fluorescence intensity ratio of GQDs (
F
/
F
0
) was positively correlated with the concentration of propofol, which ranged within 5.34–89.07 mg l
−1
, the limit of detection was 0.5 mg l
−1
and the limit of quantity was 5.34 mg l
−1
. The developed fluorescence method reported in the present study is simple, sensitive, reproducible, and can serve in determining propofol contents in emulsions.
Efficacy of environmental DNA to detect and quantify stream tadpoles of
Odorrana splendida
Authors: Iwai Noriko , Yasumiba Kiyomi , Takahara Teruhiko
Published: January 2019

Environmental DNA (eDNA) can be used to detect and estimate the density of rare or secretive species, especially in aquatic systems. However, the efficacy of eDNA method has not been validated in lotic systems. We examined the efficacy of the eDNA method to detect and estimate abundance and biomass of a stream-dwelling frog species,
Odorrana splendida
. We conducted eight field surveys over 2 years and obtained 53 water samples from 10 streams with known distribution of
O. splendida
tadpoles. The eDNA method accurately detected the presence of
O. splendida
in 79.2% of survey samples. The amount of
O. splendida
eDNA (copies s
−1
) in the water samples fluctuated seasonally and each site showed different peaks during different seasons. The relationship between the abundance or biomass of tadpoles and the amount of eDNA was significantly positive, but was not strong, probably because of a large difference in the relationship patterns among streams. In lotic systems, water flow might prevent even distribution of eDNA and thus make it difficult to obtain eDNA reflecting its total amount in the water. Sampling a larger amount of water or higher number of subsamples might more accurately reflect the presence and absolute amount of eDNA in water.
New crystal forms and amorphous phase of sophoricoside: X-ray structures and characterization
Authors: Xing Cheng , Zhang Guo shun , Gong Ning bo , hua Du Guan , Lu Yang
Published: January 2019

Sophoricoside, which is an isoflavone glycoside found in many plant species, has recently attracted attention because of its anti-fertility activity. One solvent-free form, two solvatomorphs and an amorphous phase of sophoricoside are reported for the first time. X-ray diffractometry, differential scanning calorimetry, thermal gravimetric analysis and Fourier-transform infrared spectroscopy were used to characterize the different forms. The results show that factors such as crystal symmetry, intermolecular arrangement, conformational flexibility, hydrogen-bonding interactions and solvent incorporation lead to different solid-state forms. An investigation of the transformations of the four forms showed that they can interconvert with each other under certain conditions. Amorphous phase and solvatomorphism were unstable but can improve the solubility of sophoricoside in water.
Beyond buying time: the role of plasticity in phenotypic adaptation to rapid environmental change
Authors: Fox Rebecca J. , Donelson Jennifer M. , Schunter Celia , Ravasi Timothy , Gaitán-Espitia Juan D.
Published: January 2019

How populations and species respond to modified environmental conditions is critical to their persistence both now and into the future, particularly given the increasing pace of environmental change. The process of adaptation to novel environmental conditions can occur via two mechanisms: (1) the expression of phenotypic plasticity (the ability of one genotype to express varying phenotypes when exposed to different environmental conditions), and (2) evolution via selection for particular phenotypes, resulting in the modification of genetic variation in the population. Plasticity, because it acts at the level of the individual, is often hailed as a rapid-response mechanism that will enable organisms to adapt and survive in our rapidly changing world. But plasticity can also retard adaptation by shifting the distribution of phenotypes in the population, shielding it from natural selection. In addition to which, not all plastic responses are adaptive—now well-documented in cases of ecological traps. In this theme issue, we aim to present a considered view of plasticity and the role it could play in facilitating or hindering adaption to environmental change. This introduction provides a re-examination of our current understanding of the role of phenotypic plasticity in adaptation and sets the theme issue's contributions in their broader context. Four key themes emerge: the need to measure plasticity across both space and time; the importance of the past in predicting the future; the importance of the link between plasticity and sexual selection; and the need to understand more about the nature of selection on plasticity itself. We conclude by advocating the need for cross-disciplinary collaborations to settle the question of whether plasticity will promote or retard species' rates of adaptation to ever-more stressful environmental conditions.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Adaptation to climate change through genetic accommodation and assimilation of plastic phenotypes
Authors: Kelly Morgan
Published: January 2019

Theory suggests that evolutionary changes in phenotypic plasticity could either hinder or facilitate evolutionary rescue in a changing climate. Nevertheless, the actual role of evolving plasticity in the responses of natural populations to climate change remains unresolved. Direct observations of evolutionary change in nature are rare, making it difficult to assess the relative contributions of changes in trait means versus changes in plasticity to climate change responses. To address this gap, this review explores several proxies that can be used to understand evolving plasticity in the context of climate change, including space for time substitutions, experimental evolution and tests for genomic divergence at environmentally responsive loci. Comparisons among populations indicate a prominent role for divergence in environmentally responsive traits in local adaptation to climatic gradients. Moreover, genomic comparisons among such populations have identified pervasive divergence in the regulatory regions of environmentally responsive loci. Taken together, these lines of evidence suggest that divergence in plasticity plays a prominent role in adaptation to climatic gradients over space, indicating that evolving plasticity is also likely to play a key role in adaptive responses to climate change through time. This suggests that genetic variation in plastic responses to the environment (G × E) might be an important predictor of species' vulnerabilities to climate-driven decline or extinction.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Trait variation in extreme thermal environments under constant and fluctuating temperatures
Authors: Salinas Santiago , Irvine Shannon E. , Schertzing Claire L. , Golden Shelby Q. , Munch Stephan B.
Published: January 2019

Climate change is increasingly exposing populations to rare and novel environmental conditions. Theory suggests that extreme conditions will expose cryptic phenotypes, with a concomitant increase in trait variation. Although some empirical support for this exists, it is also well established that physiological mechanisms (e.g. heat shock protein expression) change when organisms are exposed to constant versus fluctuating temperatures. To determine the effect of common, rare and novel temperatures on the release of hidden variation, we exposed fathead minnows,Pimephales promelas, to five fluctuating and four constant temperature regimes (constant treatments: 23.5, 25, 28.5 and 31°C; all fluctuating treatments shared a minimum temperature of 22°C at 00.00 and a maximum of 25, 28, 31, 34 or 37°C at 12.00). We measured each individual's length weekly over 60 days, critical thermal maximum (CTmax), five morphometric traits (eye anterior–posterior distance, pelvic fin length, pectoral fin length, pelvic fin ray count and pectoral fin ray count) and fluctuating asymmetry (FA, absolute difference between left and right morphometric measurements; FA is typically associated with stress). Length-at-age in both constant and fluctuating conditions decreased with temperature, and this trait's variance decreased with temperature under fluctuating conditions but increased and then decreased in constant temperatures. CTmaxin both treatments increased with increasing water temperature, while its variance decreased in warmer waters. No consistent pattern in mean or variance was found across morphometric traits or FA. Our results suggest that, for fathead minnows, variance can decrease in important traits (e.g. length-at-age and CTmax) as the environment becomes more stressful, so it may be difficult to establish comprehensive rules for the effects of rarer or stressful environments on trait variation.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Phenotypic plasticity in response to climate change: the importance of cue variation
Authors: Bonamour Suzanne , Chevin Luis-Miguel , Charmantier Anne , Teplitsky Céline
Published: January 2019

Phenotypic plasticity is a major mechanism of response to global change. However, current plastic responses will only remain adaptive under future conditions if informative environmental cues are still available. We briefly summarize current knowledge of the evolutionary origin and mechanistic underpinnings of environmental cues for phenotypic plasticity, before highlighting the potentially complex effects of global change on cue availability and reliability. We then illustrate some of these aspects with a case study, comparing plasticity of blue tit breeding phenology in two contrasted habitats: evergreen and deciduous forests. Using long-term datasets, we investigate the climatic factors linked to the breeding phenology of the birds and their main food source. Blue tits occupying different habitats differ extensively in the cues affecting laying date plasticity, as well as in the reliability of these cues as predictors of the putative driver of selective pressure, the date of caterpillar peak. The temporal trend for earlier laying date, detected only in the evergreen populations, is explained by increased temperature during their cue windows. Our results highlight the importance of integrating ecological mechanisms shaping variation in plasticity if we are to understand how global change will affect plasticity and its consequences for population biology.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Ecological and evolutionary consequences of metabolic rate plasticity in response to environmental change
Authors: Norin Tommy , Metcalfe Neil B.
Published: January 2019

Basal or standard metabolic rate reflects the minimum amount of energy required to maintain body processes, while the maximum metabolic rate sets the ceiling for aerobic work. There is typically up to three-fold intraspecific variation in both minimal and maximal rates of metabolism, even after controlling for size, sex and age; these differences are consistent over time within a given context, but both minimal and maximal metabolic rates are plastic and can vary in response to changing environments. Here we explore the causes of intraspecific and phenotypic variation at the organ, tissue and mitochondrial levels. We highlight the growing evidence that individuals differ predictably in the flexibility of their metabolic rates and in the extent to which they can suppress minimal metabolism when food is limiting but increase the capacity for aerobic metabolism when a high work rate is beneficial. It is unclear why this intraspecific variation in metabolic flexibility persists—possibly because of trade-offs with the flexibility of other traits—but it has consequences for the ability of populations to respond to a changing world. It is clear that metabolic rates are targets of selection, but more research is needed on the fitness consequences of rates of metabolism and their plasticity at different life stages, especially in natural conditions.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Transgenerational effects of parental light environment on progeny competitive performance and lifetime fitness
Authors: Baker Brennan H. , Sultan Sonia E. , Lopez-Ichikawa Maya , Waterman Robin
Published: January 2019

Plant and animal parents may respond to environmental conditions such as resource stress by altering traits of their offspring via heritable non-genetic effects. While such transgenerational plasticity can result in progeny phenotypes that are functionally pre-adapted to the inducing environment, it is unclear whether such parental effects measurably enhance the adult competitive success and lifetime reproductive output of progeny, and whether they may also adversely affect fitness if offspring encounter contrasting conditions. In glasshouse experiments with inbred genotypes of the annual plantPolygonum persicaria, we tested the effects of parental shade versus sun on (a) competitive performance of progeny in shade, and (b) lifetime reproductive fitness of progeny in three contrasting treatments. Shaded parents produced offspring with increased fitness in shade despite competition, as well as greater competitive impact on plant neighbours. Inherited effects of parental light conditions also significantly altered lifetime fitness: parental shade increased reproductive output for progeny in neighbour and understorey shade, but decreased fitness for progeny in sunny, dry conditions. Along with these substantial adaptive and maladaptive transgenerational effects, results show complex interactions between genotypes, parent environment and progeny conditions that underscore the role of environmental variability and change in shaping future adaptive potential.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Within-generation and transgenerational plasticity of mate choice in oceanic stickleback under climate change
Authors: Fuxjäger Lukas , Wanzenböck Sylvia , Ringler Eva , Wegner K. Mathias , Ahnelt Harald , Shama Lisa N. S.
Published: January 2019

Plasticity, both within and across generations, can shape sexual traits involved in mate choice and reproductive success, and thus direct measures of fitness. Especially, transgenerational plasticity (TGP), where parental environment influences offspring plasticity in future environments, could compensate for otherwise negative effects of environmental change on offspring sexual traits. We conducted a mate choice experiment using stickleback (Gasterosteus aculeatus) with different thermal histories (ambient 17°C or elevated 21°C) within and across generations under simulated ocean warming using outdoor mesocosms. Parentage analysis of egg clutches revealed that maternal developmental temperature and reproductive (mesocosm) environment affected egg size, with females that developed at 17°C laying smaller eggs in 21°C mesocosms, likely owing to metabolic costs at elevated temperature. Paternal developmental temperature interacted with the reproductive environment to influence mating success, particularly under simulated ocean warming, with males that developed at 21°C showing lower overall mating success compared with 17°C males, but higher mating success in 21°C mesocosms. Furthermore, mating success of males was influenced by the interaction between F1 developmental temperature and F0 parent acclimation temperature, demonstrating the potential role of both TGP and within-generation plasticity in shaping traits involved in sexual selection and mate choice, potentially facilitating rapid responses to environmental change.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Understanding interactions between plasticity, adaptation and range shifts in response to marine environmental change
Authors: Donelson Jennifer M. , Sunday Jennifer M. , Figueira Will F. , Gaitán-Espitia Juan Diego , Hobday Alistair J. , Johnson Craig R. , Leis Jeffrey M. , Ling Scott D. , Marshall Dustin , Pandolfi John M. , Pecl Gretta , Rodgers Giverny G. , Booth David J. , Munday Philip L.
Published: January 2019

Climate change is leading to shifts in species geographical distributions, but populations are also probably adapting to environmental change at different rates across their range. Owing to a lack of natural and empirical data on the influence of phenotypic adaptation on range shifts of marine species, we provide a general conceptual model for understanding population responses to climate change that incorporates plasticity and adaptation to environmental change in marine ecosystems. We use this conceptual model to help inform where within the geographical range each mechanism will probably operate most strongly and explore the supporting evidence in species. We then expand the discussion from a single-species perspective to community-level responses and use the conceptual model to visualize and guide research into the important yet poorly understood processes of plasticity and adaptation.

This article is part of the theme issue ‘The role of plasticity in phenotypic adaptation to rapid environmental change’.
Neuroticism as a predictor of frailty in old age: a genetically informative approach
Authors: Danielsdottir Hilda Bjork , Jylhävä Juulia , Hägg Sara , Lu Yi , Colodro-Conde Lucía , Martin Nicholas G. , Pedersen Nancy L. , Mosing Miriam A. , Lehto Kelli
Published: January 2019

Objective

Neuroticism is associated with poor health outcomes, but its contribution to the accumulation of health deficits in old age, i.e. frailty, is largely unknown. We aimed to explore associations between neuroticism and frailty cross-sectionally and over up to 29 years, and to investigate the contribution of shared genetic influences.

Method

Data were derived from the UK Biobank (UKB, n=502,631), the Australian Over 50’s Study (AO50, n=3,011) and the Swedish Twin Registry (SALT n=23,744, SATSA n=1,637). Associations between neuroticism and the Frailty Index were investigated using regression analysis cross-sectionally in UKB, AO50 and SATSA, and longitudinally in SALT (25-29y follow-up) and SATSA (6 and 23y follow-up). The co-twin control method was applied to explore the contribution of underlying shared familial factors (SALT, SATSA, AO50). Genome-wide polygenic risk scores for neuroticism in all samples were used to further assess whether common genetic variants associated with neuroticism predict frailty.

Results

High neuroticism was consistently associated with greater frailty cross-sectionally (adjusted β, 95% confidence intervals in UKB= 0.32, 0.32-0.33; AO50= 0.35, 0.31-0.39; SATSA= 0.33, 0.27-0.39) and longitudinally up to 29 years (SALT= 0.24; 0.22-0.25; SATSA 6y= 0.31, 0.24-0.38; SATSA 23y= 0.16, 0.07-0.25). When controlling for underlying shared genetic and environmental factors the neuroticism-frailty association remained significant, although decreased. Polygenic risk scores for neuroticism significantly predicted frailty in the two larger samples (meta-analyzed total β= 0.06, 0.05-0.06).

Conclusion

High neuroticism is associated with the development and course of frailty. Both environmental and genetic influences, including neuroticism-associated genetic variants, contribute to this relationship.
The two chemotaxis inCaulobacter crescentusoperons play different roles in chemotaxis and biofilm regulation
Authors: Berne Cécile , Brun Yves V.
Published: January 2019

The holdfast polysaccharide adhesin is crucial for irreversible cell adhesion and biofilm formation inCaulobacter crescentus. Holdfast production is tightly controlled via developmental regulators, and environmental and physical signals. Here we identified a novel mechanism of holdfast production regulation that involves chemotaxis proteins. We characterized the two identified chemotaxis operons ofC. crescentusand showed that only the previously characterized, major operon is involved in chemotactic response towards different carbon sources. However, both chemotaxis operons encoded in theC. crescentusgenome play a role in biofilm formation and holdfast production, by regulating the expression ofhfiA, the gene encoding the holdfast inhibitor HfiA. We show that CheA and CheB proteins act in an antagonistic manner: while the two CheA proteins negatively regulatehfiAexpression, the CheB proteins are positive regulators, thus providing a modulation of holdfast synthesis and surface attachment.

IMPORTANCE

Chemosensory pathways are major signal transduction mechanisms in bacteria. These systems are involved in chemotaxis and other cell responses to environment conditions, such as production of adhesins that enable irreversible adhesion to a surface and surface colonization. TheC. crescentusgenome encodes two complete chemotaxis operons. Here we characterized the second, novel chemotaxis-like operon. While only the major chemotaxis operon is involved in chemotaxis, both chemotaxis systems modulateC. crescentusadhesion by controlling expression of the holdfast synthesis inhibitor, HfiA. Thus, we identified a new level in holdfast regulation, providing new insights into the control of adhesin production that leads to the formation of biofilms.
Deep learning enables accurate clustering and batch effect removal in single-cell RNA-seq analysis
Authors: Li Xiangjie , Lyu Yafei , Park Jihwan , Zhang Jingxiao , Stambolian Dwight , Susztak Katalin , Hu Gang , Li Mingyao
Published: January 2019

Single-cell RNA sequencing (scRNA-seq) can characterize cell types and states through unsupervised clustering, but the ever increasing number of cells imposes computational challenges. We present an unsupervised deep embedding algorithm for single-cell clustering (DESC) that iteratively learns cluster-specific gene expression signatures and cluster assignment. DESC significantly improves clustering accuracy across various datasets and is capable of removing complex batch effects while maintaining true biological variations.
A stochastic model of adult neurogenesis coupling cell cycle progression and differentiation
Authors: Stopka Anna , Boareto Marcelo
Published: January 2019

Long-term tissue homeostasis requires a precise balance between stem cell self-renewal and the generation of differentiated progeny. Recently, it has been shown that in the adult murine brain, neural stem cells (NSCs) divide mostly symmetrically. This finding suggests that the required balance for tissue homeostasis is accomplished at the population level. However, it remains unclear how this balance is enabled. Furthermore, there is experimental evidence that proneural differentiation factors not only promote differentiation, but also cell cycle progression, suggesting a link between the two processes in NSCs. To study the effect of such a link on NSC dynamics, we developed a stochastic model in which stem cells have an intrinsic probability to progress through cell cycle and to differentiate. Our results show that increasing heterogeneity in differentiation probabilities leads to a decreased probability of long-term tissue homeostasis, and that this effect can be compensated when cell cycle progression and differentiation are positively coupled. Using single-cell RNA-Seq profiling of adult NSCs, we found a positive correlation in the expression levels of cell cycle and differentiation markers. Our findings suggest that a coupling between cell cycle progression and differentiation on the cellular level is part of the process that maintains tissue homeostasis in the adult brain.
Mechanistic insights into Zika virus NS3 helicase inhibition by Epigallocatechin-3-gallate
Authors: Kumar Deepak , Sharma Nitin , Aarthy Murali , Singh Sanjeev Kumar , Giri Rajanish
Published: January 2019

Since 2007, repeated outbreaks of Zika virus (ZIKV) has affected millions of people worldwide and created global health concern with major complications like microcephaly and Guillain Barre’s syndrome. Generally, ZIKV transmits through mosquitoes (Aedes aegypti) like other flaviviruses, but reports show blood transfusion and sexual mode of ZIKV transmission which further makes the situation alarming. Till date, there is not a single Zika specific licensed drug or vaccine present in the market. However, in recent months, several antiviral molecules have been screened against viral and host proteins. Among those, (−)-Epigallocatechin-3-gallate (EGCG), a green tea polyphenol has shown great virucidal potential against flaviviruses including ZIKV. However, the mechanistic understanding of EGCG targeting viral proteins is not yet entirely deciphered except little is known about its interaction with viral envelope protein and viral protease. Since literature has shown significant inhibitory interactions of EGCG against various kinases and bacterial DNA gyrases; we designed our study to find inhibitory actions of EGCG against ZIKV NS3 helicase. NS3 helicase is playing a significant role in viral replication by unwinding RNA after hydrolyzing NTP. We employed molecular docking and simulation approach and found significant interactions at ATPase site and also at RNA binding site. Further, the enzymatic assay has shown significant inhibition of NTPase activity with an IC50 value of 295.7 nM and Ki of 0.387 ± 0.034 µM. Our study suggests the possibility that EGCG could be considered as prime backbone molecule for further broad-spectrum and multitargeted inhibitor development against ZIKV and other flaviviruses.
Asthma and affective traits in adults: a genetically informative study
Authors: Lehto Kelli , Pedersen Nancy L. , Almqvist Catarina , Lu Yi , Brew Bronwyn K
Published: January 2019

Depression, anxiety and high neuroticism (affective traits) are often comorbid with asthma. A causal direction between the affective traits and asthma is difficult to determine, however, it may be that there is a common underlying pathway attributable to shared genetic factors. Our aim was to determine whether a common genetic susceptibility exists for asthma and each of the affective traits.

An adult twin cohort from the Swedish Twin Register underwent questionnaire-based health assessments (n=23 693) and genotyping (n=15 908). Firstly, questionnaire-based associations between asthma and affective traits were explored. This was followed by genetic analyses: a) polygenic risk scores (PRS) for affective traits were used as predictors of asthma, and b) linkage-disequilibrium score regression based on genome-wide association results from UK Biobank was used to quantify genetic correlations.

Analyses found that the questionnaire-based associations between asthma and each affective trait were associated (OR 1.7, 95%CI 1.5-1.9 major depression, OR 1.5, 95%CI 1.3-1.6 anxiety, and OR 1.6, 95% 1.4-1.8 high neuroticism). Genetic susceptibility for neuroticism explained the variance in asthma with a dose response effect; that is, those in the highest neuroticism PRS quartile were more likely to have asthma than those in the lowest quartile (OR 1.4, 95%CI 1.2-1.6). Genetic correlations were found between depression and asthma (rg= 0.17), but not for anxiety or neuroticism score.

We conclude that the observed comorbidity between asthma and the affective traits may in part be due to shared genetic influences between asthma and depression and neuroticism, but not anxiety.
Mucoromycotina fine root endophyte fungi form nutritional mutualisms with vascular plants
Authors: Hoysted Grace A. , Jacob Alison S. , Kowal Jill , Giesemann Philipp , Bidartondo Martin I. , Duckett Jeffrey G. , Gebauer Gerhard , Rimington William R. , Schornack Sebastian , Pressel Silvia , Field Katie J.
Published: January 2019

Fungi and plants have engaged in intimate symbioses that are globally widespread and have driven terrestrial biogeochemical processes since plant terrestrialisation >500 Mya. Recently, hitherto unknown nutritional mutualisms involving ancient lineages of fungi and non-vascular plants have been discovered. However, their extent and functional significance in vascular plants remains uncertain. Here, we provide first evidence of abundant carbon-for-nitrogen exchange between an early-diverging vascular plant (Lycopodiaceae) and Mucoromycotina (Endogonales) fine root endophyte regardless of changes in atmospheric CO2 concentration. Furthermore, we provide evidence that the same fungi also colonize neighbouring non-vascular and flowering plants. These findings fundamentally change our understanding of the evolution, physiology, interrelationships and ecology of underground plant-fungal symbioses in terrestrial ecosystems by revealing an unprecedented nutritional role of Mucoromycotina fungal symbionts in vascular plants.
Defining reprogramming checkpoints from single-cell analysis of induced pluripotency
Authors: Tran Khoa A , Pietrzak Stefan J , Zaidan Nur Zafirah , Siahpirani Alireza , McCalla Sunnie Grace , Iyer Gopal , Roy Sushmita , Sridharan Rupa
Published: January 2019

Elucidating the mechanism of reprogramming is confounded by heterogeneity due to the low efficiency and differential kinetics of obtaining induced pluripotent stem cells (iPSCs) from somatic cells. Therefore, we increased the efficiency with a novel combination of epigenetic and signaling molecules and profiled the transcriptomes of individual reprogramming cells. Contrary to the established temporal order, somatic gene inactivation and upregulation of cell cycle, epithelial, and early pluripotency genes can be triggered independently such that any combination of these events can occur in single cells. Sustained co-expression of Epcam, Nanog, and Sox2 with other genes is required to progress towards iPSCs. Ehf, Phlda2, and translation initiation factor Eif4a1 play novel functional roles in robust iPSC generation. Using regulatory network analysis, we identify a critical role for signaling inhibition by 2i in repressing somatic expression and synergy between the epigenetic modifiers ascorbic acid and a Dot1L inhibitor for pluripotency gene activation.
A causal inference framework for estimating genetic variance and pleiotropy from GWAS summary data
Authors: Park Yongjin , He Liang , Kellis Manolis
Published: January 2019

Motivation

Much of research in genome-wide association studies has only searched for significantly associated signals without explicitly removing unwanted source of variation. Confounder correction is a necessary step to reveal causal effects, but often skipped in a summary-based analysis.

Results

We present a novel causal inference algorithm that controls unwanted sources in genetic variance and covariance estimation tasks. We demonstrate substantially improved statistical power and accuracy in extensive simulations. In real-world applications on the UK biobank summary statistics data, our method recapitulates well-known pleiotropic modules, suggesting new insights into biobank-scale GWAS analysis.

Contact

YP (ypp@mit.edu) and MK (manoli@mit.edu)
High prevalence of class 1 integrase and characterization of class 1 integron gene cassettes in multiresistant bacteria isolated from the gut microbiota of extended antibiotic treated Salmo salar fish farms
Authors: Vásquez-Ponce Felipe , Higuera-Llantén Sebastián , Cortés Jimena , Zimin-Veselkoff Natalia , Marshall Sergio H. , Mardones Fernando O. , Olivares-Pacheco Jorge
Published: January 2019

The use of antimicrobials in aquaculture is a common practice. Chile is second larger producer of salmon worldwide, but unfortunately is the first consumer of antibiotics. Tonnes of florfenicol and oxytetracycline yearly are used in the Chilean salmoniculture to control the pathogens that threaten the sustainability of the industry. This excessive use of antibiotics have selected populations of resistant bacteria from the sediments and the water column that sorround the fish farms. In a recent work, our lab described the high prevalence of multiresistant bacteria and Antibiotic Resistance Genes (ARGs) in the gut microbiota of Antlactic salmon (Salmo salar) treated with high doses of antibiotics. In this work, we revisited the analysis of the previously described gut multiresistant bacteria grouped in banks of florfenicol resistant isolates (FB) and oxytetracycline resistant isolates (OB) looking for the presence of integron-integrase elements. These elements have been described as an important players in the Antimicrobial Resistance (AMR) phenomenon and they are considered a good markers of the anthopogenic activities pollution. The results showed that the 100% of the multiresistant isolates present the class 1 intagrase. Despite this result, no isolate from FB showed the typical structure of class 1 integrons: the presence in 3’-CS of qacEΔ1/sul1 genes. While in OB, only 23% of the isolates showed this characteristic structure. Additionally, only four isolates of OB and none of FB showed recognisable gene cassettes and no genes of resistance to florfenicol and oxytetacycline appeared in them. Of these four isolates, three of them showed a single gene cassette containing the dfrA-14 gene, which confers resistance to trimethoprim. Whilst the other isolate showed the aac(6’)31-qacH-blaoxa2 genes, which confers resistance to aminoglycosides, quaternary ammonium compounds and beta-lactams, respectively. Finally, it was possible to demonstrate that the described integrons probably come from anthropogenic activities like clinical settings and/or industrial animal husbandry, since they show integrases proteins identical to those carried by human pathogens.
Rosiglitazone in the thawing medium improves mitochondrial function in stallion spermatozoa through Akt phosphorylation and reduction of caspase 3
Authors: Ortiz-Rodriguez JM , Balao da Silva C , Masot J , Redondo E , Gazquez A , Gil MC , Ortega Ferrusola C , Peña FJ
Published: January 2019

Background

The population of stallion spermatozoa surviving thawing, experience, among other changes, compromised mitochondrial functionality and accelerated senescence. It is known that the stallion spermatozoa show very active oxidative phosphorylation that may accelerate sperm senescence through increased production of reactive oxygen species. Rosiglitazone has proven to enhance the glycolytic capability of stallion spermatozoa maintained in refrigeration.

Objectives

Thus, we hypothesized that thawed sperm may also benefit from rosiglitazone supplementation.

Material and Methods

Thawed sperm doses were washed and re-suspended in Tyrodes media, split sampled and supplemented with 0 or 75 μM rosiglitazone. After 1 and two hours of incubation, mitochondrial functionality, Akt phosphorylation and caspase 3 activity were evaluated. Further samples were incubated in presence of the Akt1/2 inhibitor, compound C (AMPK inhibitor) and GW9662 (antagonist of the PPARγ receptor).

Results

Rosiglitazone maintained Akt phosphorylated and reduced caspase 3 activation (p<0.01) that was prevented by incubation in presence of the three inhibitors. Rosiglitazone also enhanced mitochondrial functionality (p<0.01).

Conclusion

We provide, for the first time, evidences that the functionality of frozen stallion spermatozoa can be potentially improved after thawing through the activation pro survival pathways, opening new clues to improve current sperm biotechnologies.
Diagnosed and undiagnosed Diabetes mellitus among urban adults: a population based cross-sectional study
Authors: Ayele Behailu Hawulte , Shore Hirbo , Shunu Addisu , Mengesha Melkamu Merid
Published: January 2019

Background

Globally, diabetes mellitus (DM) accounts for 8.8% (424.9 million) morbidity and 4 million deaths. In 2017, more than 79% of people with diabetes live in low- and middle- income countries. To this end, locally available evidence can identify target groups for intervention. However, in resource-poor settings, population-based evidence on diabetes prevalence and on its risk factors is lacking. This study, therefore, assessed prevalence of Diabetes mellitus and associated factors among adults living in Dire Dawa town, Eastern Ethiopia.

Methods

A total of 782 data points were analyzed from a random sample of the adult population aged 25-64 years who lived in Dire Dawa. World health organization STEPwise approach to non-communicable disease risk factors surveillance (WHO NCD STEPS) instrument was used to collect data. We estimated undiagnosed DM, uncontrolled DM among existing cases and the overall prevalence of DM. Hierarchical logistic regression models were run to identify correlates of diabetes mellitus, and STATA v 14.2 was used for data management and analysis. All statistical tests were declared significant at p-value<0.05.

Results

The prevalence of DM among adults aged 25-64 was 8.95% (95% confidence interval (CI): 7.1, 11.2) and the magnitude of undiagnosed DM was 3.3% (95% CI: 2.3, 4.8). The magnitude of uncontrolled DM among those taking DM medications during the survey was 1.4% (95% CI: 0.8, 2.5). The prevalence of DM was 2.3 times more likely among the age group of 55-64 years (Adjusted Odds Ratio (AOR) 95% CI: 1.1, 5.0). Similarly, consuming two or less serving of vegetables/week increased the risk of DM, (AOR=2.1, 95% CI: 1.1, 2.9). Maintaining normal body mass index level was negatively correlated with the risk of DM, (AOR=0.6, 95% CI: 0.3, 0.8).

Conclusion

The overall prevalence of diabetes mellitus was relatively high, and the magnitude of undiagnosed DM was a great concern. Therefore, creating community awareness, regular blood sugar checking, appropriate weight control and, increased consumption of vegetables would be helpful in preventing incident cases of DM.
Autophagy modulates lipid metabolism to maintain metabolic flexibility for Lkb1-deficient Kras-driven lung tumorigenesis
Authors: Bhatt Vrushank , Khayati Khoosheh , Hu Zhixian Sherrie , Lee Amy , Kamran Wali , Su Xiaoyang , Guo Jessie Yanxiang
Published: January 2019

Loss of tumor suppressor liver kinase B1 (LKB1) promotes cancer cell proliferation but also leads to decreased metabolic plasticity in dealing with energy crises. Autophagy is a protective process involving self-cannibalization to maintain cellular energy homeostasis during nutrient deprivation. We developed a mouse model for Lkb1-deficient lung cancer with conditional deletion of essential autophagy gene Atg7 to test whether autophagy compensates for LKB1 loss for tumor cells to survive energy crises. We found that autophagy ablation was synthetically lethal during Lkb1-deficient lung tumorigenesis in both tumor initiation and tumor growth. We further found that autophagy deficiency causes defective intracellular recycling, which limits amino acids to support mitochondrial energy production in starved cancer cells and causes autophagy-deficient cells to be more dependent on fatty acid oxidation (FAO) for energy production, leading to reduced lipid reserve and energy crisis. Our findings strongly suggest that autophagy inhibition could be a strategy for treating LKB1-deficient lung tumors.
A conserved CAF40-binding motif in metazoan NOT4 mediates association with the CCR4–NOT complex
Authors: Keskeny Csilla , Raisch Tobias , Sgromo Annamaria , Igreja Cátia , Bhandari Dipankar , Weichenrieder Oliver , Izaurralde Elisa
Published: January 2019

The multisubunit CCR4–NOT mRNA deadenylase complex plays important roles in the posttranscriptional regulation of gene expression. The NOT4 E3 ubiquitin ligase is a stable component of the CCR4–NOT complex in yeast but does not copurify with the human or Drosophila melanogaster complex. Here we show that the C-terminal regions of human and D. melanogaster NOT4 contain a conserved sequence motif that directly binds the CAF40 subunit of the CCR4–NOT complex (CAF40-binding motif [CBM]). In addition, nonconserved sequences flanking the CBM also contact other subunits of the complex. Crystal structures of the CBM–CAF40 complex reveal a mutually exclusive binding surface for NOT4 and Roquin or Bag of marbles mRNA regulatory proteins. Furthermore, CAF40 depletion or structure-guided mutagenesis to disrupt the NOT4–CAF40 interaction impairs the ability of NOT4 to elicit decay of tethered reporter mRNAs in cells. Together with additional sequence analyses, our results reveal the molecular basis for the association of metazoan NOT4 with the CCR4–NOT complex and show that it deviates substantially from yeast. They mark the NOT4 ubiquitin ligase as an ancient but nonconstitutive cofactor of the CCR4–NOT deadenylase with potential recruitment and/or effector functions.