bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulations are needed to protect freshwater ecosystems from salinization
Authors: Schuler Matthew S. , Cañedo-Argüelles Miguel , Hintz William D. , Dyack Brenda , Birk Sebastian , Relyea Rick A.
Published: December 2018

Anthropogenic activities such as mining, agriculture and industrial wastes have increased the rate of salinization of freshwater ecosystems around the world. Despite the known and probable consequences of freshwater salinization, few consequential regulatory standards and management procedures exist. Current regulations are generally inadequate because they are regionally inconsistent, lack legal consequences and have few ion-specific standards. The lack of ion-specific standards is problematic, because each anthropogenic source of freshwater salinization is associated with a distinct set of ions that can present unique social and economic costs. Additionally, the environmental and toxicological consequences of freshwater salinization are often dependent on the occurrence, concentration and ratios of specific ions. Therefore, to protect fresh waters from continued salinization, discrete, ion-specific management and regulatory strategies should be considered for each source of freshwater salinization, using data from standardized, ion-specific monitoring practices. To develop comprehensive monitoring, regulatory, and management guidelines, we recommend the use of co-adaptive, multi-stakeholder approaches that balance environmental, social, and economic costs and benefits associated with freshwater salinization.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Why are mayflies (Ephemeroptera) lost following small increases in salinity? Three conceptual osmophysiological hypotheses
Authors: Kefford Ben J.
Published: December 2018

The salinity of many freshwaters is increasing globally as a result of human activities. Associated with this increase in salinity are losses of Ephemeroptera (mayfly) abundance and richness. The salinity concentrations at which Ephemeroptera decline in nature are lower than their internal salinity or haemolymph osmolality. Many species also suffer substantial mortality in single species laboratory toxicity tests at salinities lower than their internal salinity. These findings are problematic as conventional osmoregulation theory suggests that freshwater animals should not experience stress where external osmolality is greater than haemolymph osmolality. Here I explore three hypotheses to explain salt sensitivity in Ephemeroptera. These conceptual hypotheses are based on the observations that as the external sodium ion (Na+) concentration increases so does the Na+turnover rate (both uptake and elimination rates increase). Sulphate () uptake in mayflies also increases with increasing externalalthough, unlike Na+, its rate of increase decreases with increasing external. The first hypothesis is premised on ion turnover being energetically costly. The first hypothesis proposes that individuals must devote a greater proportion of their energy to ion homeostasis at the expense of other uses including growth and development. Lethal levels of salinity presumably result from individuals not being able to devote enough energy to maintain ion homeostasis without critical loss of other vital functions. The second hypothesis is premised on the uptake of Na+exchanged for (an outgoing) H+, leading to (localized) loss of pH regulation. The third hypothesis is premised on localized Na+toxicity or poisoning with increased Na turnover as salinity increases. None of the proposed hypotheses is without potential problems, yet all are testable, and research effort should be focused at attempting to falsify them.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Drivers of spatio-temporal patterns of salinity in Spanish rivers: a nationwide assessment
Authors: Estévez Edurne , Rodríguez-Castillo Tamara , González-Ferreras Alexia María , Cañedo-Argüelles Miguel , Barquín José
Published: December 2018

The salinization of freshwaters is a global water quality problem that leads to the biological degradation of aquatic ecosystems. However, little is known about the spatial extent of freshwater salinization and the relative contribution of each human activity (e.g. agriculture, urbanization, mining or shale-gas extraction). Here, we investigated environmental factors that explain spatio-temporal patterns of water salinity and examined the causes, the extent and the degree of salinization of Spanish rivers. Results showed a strong variation in water salinity among river typologies and between river reaches in good and poor ecological status according to the Water Framework Directive. The variation in water salinity was largely explained by a combination of natural (i.e. climate and geology) and anthropogenic (i.e. land use) factors. By contrast, land use factors as urbanization and agriculture were the main drivers of salinization, which affected more than one quarter of the rivers and streams in Spain, especially those in the most arid regions (central and southern regions) and in the main courses of the largest rivers such as the Ebro, Douro and Tajo rivers. The information provided here can be relevant to set priority regions and actions to ameliorate freshwater salinization.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Multiple riparian–stream connections are predicted to change in response to salinization
Authors: Entrekin Sally A. , Clay Natalie A. , Mogilevski Anastasia , Howard-Parker Brooke , Evans-White Michelle A.
Published: December 2018

Secondary freshwater salinization, a common anthropogenic alteration, has detrimental, lethal and sub-lethal effects on aquatic biota. Ions from secondary salinization can become toxic to terrestrial and aquatic organisms when exposed to salinized runoff that causes periodic high-concentration pulses. Gradual, low-level (less than 1000 ppm salinity) increases in salt concentrations are also commonly documented in regions with urbanization, agriculture, drilling and mining. Despite widespread low-level salt increases, little is known about the biological and ecological consequences in coupled riparian–stream systems. Recent research indicates lethal and even sub-lethal levels of ions can subsidize or stress microbial decomposer and macroinvertebrate detritivores that could lead to alterations of three riparian–stream pathways: (i) salinized runoff that changes microbial decomposer and macroinvertebrate detritivore and algae performance leading to changes in composition and processing of detrital pools; (ii) riparian plant salt uptake and altered litter chemistry, and litterfall for riparian and aquatic detritivores and their subsequent enrichment, stimulating decomposition rates and production of dissolved and fine organic matter; and (iii) salt consumption in salinized soils could increase riparian detritivore growth, decomposition and dissolved organic matter production. Subsidy–stress and reciprocal flows in coupled riparian–stream connections provide frameworks to identify the extent and magnitude of changes in detrital processing from salinization.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Salinization effects on coastal ecosystems: a terrestrial model ecosystem approach
Authors: Pereira C. S. , Lopes I. , Abrantes I. , Sousa J. P. , Chelinho S.
Published: December 2018

In coastal areas, intrusion/irrigation with seawater can threaten biodiversity along with crop yields, and the leaching of salts from areas affected by these processes can increase the salinity of water bodies nearby. The aims of this study were to evaluate the effects of salinization on coastal soil ecosystems due to saline intrusion/irrigation. Terrestrial model ecosystems were used to simulate two soil salinization scenarios: (i) seawater intrusion and irrigation with distilled water and (ii) seawater intrusion and irrigation with saline water. Three sampling periods were established: T0—after acclimation period; T1—salinization effects; and T2—populations' recovery. In each sampling period, the abundance of nematodes, enchytraeids, springtails, mites and earthworms, and plant biomass were measured. Immediate negative effects on enchytraeid abundance were detected, especially at the higher level of saltwater via intrusion+irrigation. Eight weeks after the cessation of saline irrigation, the abundance of enchytraeids fully recovered, and some delayed effects were observed in earthworm abundance and plant biomass, especially at the higher soil conductivity level. The observed low capacity of soil to retain salts suggests that, particularly at high soil conductivities, nearby freshwater bodies can also be endangered. Under saline conditions similar to the ones assayed, survival of some soil communities can be threatened, leading to the loss of biodiversity.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Sensitivity of freshwater species under single and multigenerational exposure to seawater intrusion
Authors: Venâncio C. , Castro B. B. , Ribeiro R. , Antunes S. C. , Abrantes N. , Soares A. M. V. M. , Lopes I.
Published: December 2018

Salinization of coastal freshwater ecosystems is already occurring in some regions of the world. This phenomenon raises serious concerns on the protection of coastal freshwater ecosystems, since many of them support and shelter a large number of species and are considered hotspots of biodiversity. This work intended to assess the adverse effects that salinization, caused by the intrusion of seawater (SW), may pose to freshwater organisms. In this study, three specific goals were addressed: (i) to assess if sodium chloride (NaCl) may be used as a surrogate of natural SW at early-stages of risk assessment; (ii) to identify the most sensitive freshwater species to salinity NaCl; and (iii) to determine if increased tolerance to salinity may be acquired after multigenerational exposure to low levels of salinization (induced with NaCl). A total of 12 standard monospecific bioassays were carried out by exposing organisms from different taxonomic groups (Cyanobacteria: one species, Tracheophyta: two species, Rotifera: one species, Arthropoda: two species and Mollusca: one species) to a series of concentrations of NaCl (ranging from 0.95 to 22.8 mS cm
–1
) or dilutions of SW (ranging from 1.70 to 52.3 mS cm
−1
). In general, NaCl exerted similar or higher toxicity than SW, both at lethal and sublethal levels, suggesting that it may be proposed as a protective surrogate of SW for first tiers of salinization risk assessment. Among all tested species, the cyanobacterium
Cylindrospermopsis raciborskii
, the daphnid
Daphnia longispina
and the rotifer
Brachionus plicatilis
were the most sensitive taxa to salinization (EC
50
≤ 4.38 mS cm
−1
). Given their position at the basis of the food web, it is suggested that small increments of salinity may be enough to induce structural changes in freshwater communities or induce changes in trophic relations. No clear evidences of increased tolerance after multigenerational exposure to low levels of salinity were found.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Challenges and future prospects for developing Ca and Mg water quality guidelines: a meta-analysis
Authors: Bogart Sarah J. , Azizishirazi Ali , Pyle Greg G.
Published: December 2018

Anthropogenic activities have the potential to increase water hardness (Ca + Mg) in receiving waters to toxic concentrations, and thus, water quality guidelines (WQG) for Ca and Mg are warranted. However, Ca can modify Mg toxicity in Ca-poor water and additional interactions with other major ions (Na+, K+, HCO3−/CO32−, SO42−and Cl−) may occur, potentially obscuring the water hardness–effect relationship. In a meta-analysis of toxicological studies, we: (i) evaluate the performance of three WQG derivation methods, and (ii) determine the influence of several variables (acute/chronic data, anions, Ca:Mg ratios, non-geographically relevant species) on the models. We find that the most sensitive species- or species sensitivity distribution (SSD)-based WQG derivation methods greatly overestimate water hardness toxicity, particularly if non-resident species are included. Broad-scale implementation of most sensitive species- or SSD-based WQG is impractical because water hardness varies beyond and within the regional scale. Anion type does not affect water hardness toxicity across species, but the Ca : Mg ratio is toxicologically relevant, underscoring the importance of considering ion ratios when developing major ion WQG. Although data supporting formal water hardness WQG are unavailable, we suggest using a two-component background condition approach that supports simultaneous management of water hardness and Ca : Mg ratio, and WQG that are applicable beyond the regional scale.

This article is part of the theme issue ‘Salt in freshwaters: causes, ecological consequences and future prospects’.
Landscape-scale forest loss as a catalyst of population and biodiversity change
Authors: Daskalova Gergana N. , Myers-Smith Isla H. , Bjorkman Anne D. , Blowes Shane A. , Supp Sarah R. , Magurran Anne , Dornelas Maria
Published: December 2018

Global assessments have highlighted land-use change as a key driver of biodiversity change. However, we lack real-world global-scale estimates of how habitat transformations such as forest loss and gain are reshaping biodiversity over time. Here, we quantify the influence of 150 years of forest cover change on populations and ecological assemblages worldwide and across taxa by analyzing change in 6,667 time series. We found that forest loss simultaneously intensified ongoing increases and decreases in abundance, species richness and temporal species replacement (turnover) by up to 48%. Temporal lags in these responses extended up to 50 years and increased with species’ generation time. Our findings demonstrate that land-use change precipitates divergent population and biodiversity change, highlighting the complex biotic consequences of deforestation and afforestation.

One Sentence Summary

Declines in forest cover amplify both gains and losses in population abundance and biodiversity over time.
MAU2 and NIPBL variants in Cornelia de Lange syndrome reveal MAU2-independent loading of cohesin and uncover a protective mechanism against early truncating mutations in NIPBL
Authors: Parenti Ilaria , Diab Farah , Gil Sara Ruiz , Mulugeta Eskeatnaf , Casa Valentina , Berutti Riccardo , Brouwer Rutger W.W. , Dupé Valerie , Eckhold Juliane , Graf Elisabeth , Puisac Beatriz , Ramos Feliciano , Schwarzmayr Thomas , van Staveren Thomas , van IJcken Wilfred F. J. , Strom Tim M. , Pié Juan , Watrin Erwan , Kaiser Frank J. , Wendt Kerstin S.
Published: December 2018

Cornelia de Lange syndrome (CdLS) is a rare developmental disorder caused by mutations in genes related to the cohesin complex. For its association with chromatin, cohesin depends on a heterodimer formed by NIPBL and MAU2, which interact via their respective N-termini. Variants in NIPBL are the main cause of CdLS and result in NIPBL haploinsufficiency.

Using CRISPR, we generated cells homozygous for an out-of-frame duplication in NIPBL. Remarkably, alternative translation initiation rescued NIPBL expression in these cells and produced an N-terminally truncated NIPBL that lacks MAU2-interaction domain, causing a dramatic reduction of MAU2 protein levels. Strikingly, this protective mechanism allows nearly normal amounts of cohesin to be loaded onto chromatin in a manner that is independent of functional NIPBL/MAU2 complexes and therefore in contrast to previous findings.

We also report the first pathogenic variant in MAU2, a deletion of seven amino acids important for wrapping the N-terminus of NIPBL within MAU2. The mutation causes dramatic reduction of MAU2 heterodimerization with NIPBL, hence undermining the stability of both proteins.

Our data confirm NIPBL haploinsufficiency as the major pathogenic mechanism of CdLS and give new insights into the molecular mechanisms responsible for this neurodevelopmental disorder. Our work also unveils an alternative translation-based mechanism that protects cells from out-of-frame variants of NIPBL and that may be of relevance in other genetic conditions.
Stress, novel sex genes and epigenetic reprogramming orchestrate socially-controlled sex change
Authors: Todd Erica V , Ortega-Recalde Oscar , Liu Hui , Lamm Melissa S , Rutherford Kim M , Cross Hugh , Black Michael A , Kardailsky Olga , Marshall Graves Jennifer A , Hore Timothy A , Godwin John R , Gemmell Neil J
Published: December 2018

Bluehead wrasses undergo dramatic, socially-cued female to male sex change. We apply transcriptomic and methylome approaches in this wild coral reef fish to identify the primary trigger and subsequent molecular cascade of gonadal metamorphosis. Our data suggest that the environmental stimulus is exerted via the stress axis, that repression of the aromatase gene (encoding the enzyme converting androgens to estrogens) triggers a cascaded collapse of feminizing gene expression, and identifies notable sex-specific gene neofunctionalization. Furthermore, sex change involves distinct epigenetic reprogramming and an intermediate state with altered epigenetic machinery expression akin to the early developmental cells of mammals. These findings reveal at a molecular level how a normally committed developmental process remains plastic and is reversed to completely alter organ structures.

One Sentence Summary

Ovary to testis transformation in a sex-changing fish involves transcriptomic and epigenomic reprogramming.
GRIBCG: A software for selection of sgRNAs in the design of balancer chromosomes
Authors: Merritt Brian B. , Cheung Lily S.
Published: December 2018

Background

Balancer chromosomes are tools used by fruit fly geneticists to prevent meiotic recombination. Recently, CRISPR/Cas9 genome editing has been shown capable of generating inversions similar to the chromosomal rearrangements present in balancer chromosomes. Extending the benefits of balancer chromosomes to other multicellular organisms could significantly accelerate biomedical and plant genetics research.

Results

Here, we present GRIBCG (Guide RNA Identifier for Balancer Chromosome Generation), a tool for the rational design of balancer chromosomes. GRIBCG identifies single guide RNAs (sgRNAs) for use withStreptococcus pyogenesCas9 (SpCas9). These sgRNAs would efficiently cut a chromosome multiple times while minimizing off-target cutting in the rest of the genome. We describe the performance of this tool on six model organisms and compare our results to two routinely used fruit fly balancer chromosomes.

Conclusion

GRIBCG is the first of its kind tool for the design of balancer chromosomes using CRISPR/Cas9. GRIBCG can accelerate genetics research by providing a fast, systematic and simple to use framework to induce chromosomal rearrangements.
Estimating statistical significance of local protein profile-profile alignments
Authors: Margelevičius Mindaugas
Published: December 2018

Alignment of sequence families described by profiles provides a sensitive means for establishing homology between proteins and is important in protein evolutionary, structural, and functional studies. In the context of a steadily growing amount of sequence data, estimating the statistical significance of alignments, including profile-profile alignments, plays a key role in alignment-based homology search algorithms. Still, it is an open question as to what and whether one type of distribution governs profile-profile alignment score, especially when profile-profile substitution scores involve such terms as secondary structure predictions. This study presents a methodology for estimating the statistical significance of this type of alignments. The methodology rests on a new algorithm developed for generating random profiles such that their alignment scores are distributed similarly to those obtained for real unrelated profiles. We show that improvements in statistical accuracy and sensitivity and high-quality alignment rate result from statistically characterizing alignments by establishing the dependence of statistical parameters on various measures associated with both individual and pairwise profile characteristics. Implemented in the COMER software, the proposed methodology yielded an increase of up to 34.2% in the number of true positives and up to 61.8% in the number of high-quality alignments with respect to the previous version of the COMER method. A new version (v1.5.1) of the COMER software is available at https://sourceforge.net/projects/comer. The COMER software is also available on Github at https://github.com/minmarg/comer and as a Docker image (https://hub.docker.com/r/minmar/comer).
Discovery of Novel Glycerolated Quinazolinones from Streptomyces sp. MBT27
Authors: Machushynets Nataliia , Wu Changsheng , Elsayed Somayah S. , Hankemeier Thomas , van Wezel Gilles P.
Published: December 2018

Actinobacteria are a major source of novel bioactive natural products. A challenge in the screening of these microorganisms lies in finding the favorable growth conditions for secondary metabolite production and dereplication of known molecules. Here, we report that Streptomyces sp. MBT27 produces 4-quinazolinone alkaloids in response to elevated levels of glycerol, whereby quinazolinones A (1) and B (2) form a new sub-class of this interesting family of natural products. Global Natural Product Social molecular networking (GNPS) resulted in a quinazolinone-related network that included anthranilic acid (3), anthranilamide (4), 4(3H)-quinazolinone (5) and 2,2-dimethyl-1,2-dihydroquinazolin-4(3H)-one (6). Actinomycins D (7) and X2 (8) were also identified in the extracts of Streptomyces sp. MBT27. The induction of quinazolinone production by glycerol combined with biosynthetic insights provide evidence that glycerol is integrated into the chemical scaffold. The unprecedented 1,4-dioxepane ring that is spiro-fused into the quinazolinone backbone, is most likely formed by intermolecular etherification of two units of glycerol. Our work underlines the importance of varying the growth conditions for the discovery of novel natural products and for understanding their biosynthesis.
Directionality and community-level selection
Authors: Bunin Guy
Published: December 2018

Many ecological community dynamics display some degree of directionality, known as succession patterns. But complex interaction networks frequently tend to non-directional dynamics such as chaos, unless additional structures or mechanisms impose some form of, often fragile or shot-lived, directionality. We exhibit here a novel property of emergent long-lasting directionality in competitive communities, which relies on very minimal assumptions. We model communities where each species has a few strong competitive interactions, and many weak ones. We find that, at high enough diversity, the dynamics become directional, meaning that the community state can be characterized by a function that increases in time, which we call "maturity". In the presence of noise, the community composition changes toward increasingly stable and productive states. This scenario occupies a middle ground between deterministic succession and purely random species associations: there are many overlapping stable states, with stochastic transitions, that are nevertheless biased in a particular direction. When a spatial dimension is added in the form of a meta-community, higher-maturity community states are able to expand in space, replacing others by (exact or approximate) copies of themselves. This leads to community-level selection, with the same maturity function acting as fitness. Classic concepts from evolutionary dynamics provide a powerful analogy to understand this strictly ecological, community-level phenomenon of emergent directionality.
Population dynamics of Cymodocea nodosa under future ocean scenarios.
Authors: Mishra Amrit K
Published: December 2018

Rising carbon dioxide (CO2) concentrations in the atmosphere will increase the average pCO2 level in the world oceans, which will have a knock-on effect on the marine ecosystem. Coastal seagrass communities are predicted to benefit from the increase in CO2 levels, but long-term effects of elevated CO2 on seagrass communities are less understood. Population reconstruction techniques were used to investigate the population dynamics of Cymodocea nodosa meadows, exposed to long term elevated CO2 at volcanic seeps off Greece and Italy. Effect of elevated CO2 was noticed on the growth, morphometry, density, biomass and age structure at CO2 seeps than reference sites. Above to below ground biomass ratio of C. nodosa were higher at CO2 seeps. The shoot age and shoot longevity of plants were lower at seeps. The present recruitment (sampled year) of the seagrass were higher than long-term average recruitment of the communities near the seeps. Carbon to nitrogen ratios (%DW) and annual leaf production of C. nodosa were higher in leaves at seeps. This study suggests under long-term CO2 enrichment C. nodosa production increases, but the plant survival rate decreases because of other co-factors such as nutrient availability and trace metal toxicity. Therefore, along with high CO2 other factors must be taken into consideration while predicting effects of future CO2 concentrations.
New perspectives into the evolutionary pressures acting on the Human intrinsically disordered proteins
Authors: Forcelloni Sergio , Giansanti Andrea
Published: December 2018

The codon usage bias is the well-known phenomenon of an unequal use of synonymous codons in coding DNA. These patterns reflect the action of weak selection working at the molecular level and allows to quantify the effects of natural selection, which tend to increase the fitness of the organisms. The prevailing hypothesis to explain the origin of codons usage bias is the selection-mutation-drift theory, according to which it results from a balance between the natural selection favoring optimal codons and combined action of random mutations and genetic drift which allow the persistence of nonoptimal codons. The main focus of this study is to quantify the extent of evolutionary pressures shaping the human genome. We found distinct patterns of mutational bias and natural selection in the human genes, depending on the structural properties of the encoded proteins (e.g. well-structured proteins, proteins with a long disordered segment embedded in a folded structure, or mostly unfolded proteins). Intrinsically disordered proteins are generally thought to evolve more rapidly, largely attributed to relaxed purifying selection due to the lack of structural constraint. Interestingly we observed that mostly unstructured proteins are not only affected by a basic mutational bias as the structured ones but are under a specific selective pressure underlining the important role of these proteins during evolution being freer to accept mutations, both neutral and selective. Our results provide new insight into understanding general laws and unknown aspects of protein evolution and they could be very useful in protein search and design.
UNC-16/JIP3 negatively regulates actin dynamics dependent on DLK-1 and microtubule dynamics independent of DLK-1 in regenerating neurons
Authors: Kulkarni Sucheta S. , Sabharwal Vidur , Sheoran Seema , Basu Atrayee , Matsumoto Kunihiro , Hisamoto Naoki , Ghosh-Roy Anindya , Koushika Sandhya P.
Published: December 2018

Neuronal regeneration after injury depends on the intrinsic growth potential of neurons. UNC-16, aC. elegansJIP3 homologue, inhibits axonal regeneration by regulating regrowth initiation and rate of regrowth. UNC-16/JIP3 inhibits the regeneration promoting activity of DLK-1 long but acts additively to and independently of inhibitory DLK-1 short isoform. UNC-16/JIP3 promotes DLK-1 punctate localization in a concentration dependent manner limiting DLK-1 long availability at the cut site minutes after injury. UNC-16 negatively regulates actin dynamics dependent on DLK-1 and microtubule dynamics independent of DLK-1. The faster regeneration seen inunc-16does not lead to functional recovery. We propose a model where UNC-16/JIP3 plays its inhibitory role through tight temporal and spatial control of DLK-1 function. The dual inhibitory control by both UNC-16 and DLK-1 short calibrate the intrinsic growth promoting function of DLK-1 long in vivo.
Bayesian parameter estimation in non-stationary semiflexible polymers from ensembles of trajectories
Authors: Penfold Christopher A
Published: December 2018

During the cell-cycle and meiosis, during development, or in response to stress, chromosomes undertake dramatic programs of reorganisation, which can result in major changes to genomic architecture, as well as local changes to chromatin structure via chromatin remodelling and epigenetic modification. The biophysical properties of the genome may therefore vary significantly over time, from region to region, and from cell to cell. Semifleixble polymer models are frequently used to decipher the spatial and temporal aspects of chromosome organisation. Such models allow for parameter estimation from experimental observations (Bystricky et al., 2004, Ding et al., 2006, Koszul et al., 2008, Arbona et al., 2017), and so provide a concise quantification of the state of the system in terms of meaningful biophysical parameters, such as the compaction factor and bending-modulus. Simulation studies using appropriately parameterised models may also provide novel insights, and allow for predictions without confounding pleiotropic effects (Penfold et al., 2012), thus guiding future studies. Most semifleixble polymer models do not explicitly consider the spatial non-stationarity of chromosomes and chromatin. Furthermore, recent advances in chromosome conformation capture (3C)-based allow chromosome organisation to be (indirectly) measured in single cells (Belton et al., 2012, Nagano et al., 2013, 2016). The increasing availability of ensembles of trajectories sampled from potentially heterogeneous populations of cells means it is of interest to develop polymer statistic models that can capture both the spatial nonstationarity of the biophysical parameters, and the statistical relationships that exist within the population. Here we outline a statistical framework for non-stationary semiflexible polymers, and demonstrate how inference can be performed using ensembles of trajectories. For cells belonging to a homogenous population where the biophysical parameters are approximately identical in all cells, a (transformed) Gaussian process prior is assigned to the bending-modulus, and Markov chain Monte Carlo (MCMC) used to infer the posterior distribution of free parameters. For heterogeneous populations of cells, a transformed hierarchical GP (HGP) prior is assigned to the biophysical parameters, which naturally captures the statistical dependency of the parameters that exist across the population. Simulation studies demonstrate the accuracy of the model for homogenous and heterogeneous populations, while applications to yeast chromosome data demonstrates an improved ability to recapitulate trajectories of held out loci compared to related stationary models.
Linking the Resistome and Plasmidome to the Microbiome
Authors: Stalder Thibault , Press Max , Sullivan Shawn , Liachko Ivan , Top Eva M.
Published: December 2018

The rapid spread of antibiotic resistance is a serious human health threat. A range of environments have been identified as reservoirs of the antibiotic resistance genes (ARGs) found in pathogens. However, we lack understanding of the origins of these ARGs and their spread from environment to clinic. This is partly due to our inability to identify the bacterial hosts of ARGs and the mobile genetic elements that mediate this spread, such as plasmids and integrons. Here we demonstrated that the in vivo proximity ligation method Hi-C can determine the in situ host range of ARGs, plasmids, and integrons in a wastewater sample by physically linking them to their host chromosomes. Hi-C detected both previously known and novel associations between ARGs, mobile elements and host genomes, mostly validating this method. A better identification of the natural carriers of ARGs will aid the development of strategies to limit resistance spread to pathogens.
Human cortical organoids expose a differential function of GSK3 on direct and indirect neurogenesis
Authors: López-Tobón Alejandro , Villa Carlo Emanuele , Cheroni Cristina , Trattaro Sebastiano , Caporale Nicolò , Conforti Paola , Iennaco Raffaele , Lachgar Maria , Rigoli Marco Tullio , de la Cruz Berta Marcó , Riso Pietro Lo , Tenderini Erika , Troglio Flavia , de Simone Marco , Liste-Noya Isabel , Piccolo Stefano , Macino Giuseppe , Pagani Massimiliano , Cattaneo Elena , Testa Giuseppe
Published: December 2018

The regulation of proliferation and polarity of neural progenitors is crucial for the development of the brain cortex, with modes and timings of cell division intimately related to the stereotypical acquisition of layer-specific neuronal identities. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator of both proliferation and polarity, yet the functional relevance of its signaling for the unique features of human corticogenesis remain to be elucidated. Here we harness human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Our results indicate that chronic GSK3 inhibition increases the proliferation of neural progenitors and causes massive derangement of cortical tissue architecture. Surprisingly, single cell transcriptome profiling revealed only a discrete impact on early neurogenesis and uncovered a pivotal role of GSK3 in the regulation of NEUROD1/2 lineages and outer radial glia (oRG) output, without compromising direct neurogenic trajectories. Through this first single cell-level dissection of the GSK3 regulatory network in human corticogenesis, our work underscores the robustness of transcriptional programs in determining neuronal identity independent of tissue architecture.
A field guide for the compositional analysis of any-omics data
Authors: Quinn Thomas P. , Erb Ionas , Gloor Greg , Notredame Cedric , Richardson Mark F. , Crowley Tamsyn M.
Published: December 2018

Next-generation sequencing (NGS) has made it possible to determine the sequence and relative abundance of all nucleotides in a biological or environmental sample. Today, NGS is routinely used to understand many important topics in biology from human disease to microorganism diversity. A cornerstone of NGS is the quantification of RNA or DNA presence as counts. However, these counts are not counts per se: the magnitude of the counts are determined arbitrarily by the sequencing depth, not by the input material. Consequently, counts must undergo normalization prior to use. Conventional normalization methods require a set of assumptions: they assume that the majority of features are unchanged, and that all environments under study have the same carrying capacity for nucleotide synthesis. These assumptions are often untestable and may not hold when comparing heterogeneous samples (e.g., samples collected across distinct cancers or tissues). Instead, methods developed within the field of compositional data analysis offer a general solution that is assumption-free and valid for all data. In this manuscript, we synthesize the extant literature to provide a concise guide on how to apply compositional data analysis to NGS count data. In doing so, we review zero replacement, differential abundance analysis, and within-group and between-group coordination analysis. We then discuss how this pipeline can accommodate complex study design, facilitate the analysis of vertically and horizontally integrated data, including multiomics data, and further extend to single-cell sequencing data. In highlighting the limitations of total library size, effective library size, and spike-in normalizations, we propose the log-ratio transformation as a general solution to answer the question, “Relative to some important activity of the cell, what is changing?”. Taken together, this manuscript establishes the first fully comprehensive analysis protocol that is suitable for any and all -omics data.
Role of Physicochemical Properties of Protein in Modulating the Nanoparticle-Bio interface
Authors: Dhar Sunandan , Sood Vishesh , Lohiya Garima , Devenderan Harini , Katti Dhirendra S.
Published: December 2018

Nanoparticles, on exposure to the biological milieu, tend to interact with macromolecules to form a biomolecular corona. The biomolecular corona confers a unique biological identity to nanoparticles, and its protein composition plays a deterministic role in the biological fate of nanoparticles. The physiological behavior of proteins stems from their physicochemical aspects including surface charge, hydrophobicity, and structural stability. However, there is insufficient understanding about the role of physicochemical properties of proteins in biomolecular corona formation. We hypothesized that the physicochemical properties of proteins would influence their interaction with nanoparticles and have a deterministic effect on nanoparticle-cell interactions. To test our hypothesis, we used model proteins from different structural classes to understand the effect of secondary structure elements of proteins on the nanoparticle-protein interface. Further, we modified the surface of proteins to study the role of protein surface characteristics in governing the nanoparticle-protein interface. For this study, we used mesoporous silica nanoparticles as a model nanoparticle system. We observed that the surface charge of proteins governs the nature of the primary interaction as well as the extent of subsequent secondary interactions causing structural rearrangements of the protein. We also observed that the secondary structural contents of proteins significantly affected both the extent of secondary interactions at the nanoparticle-protein interface and the dispersion state of the nanoparticle-protein complex. Further, we also studied the interactions of different protein-coated nanoparticles with different types of cell (fibroblast, carcinoma, and macrophage). We observed that different cells internalized nanoparticle-protein complex as a function of secondary structural components of the protein. The type of model protein had a significant effect on their internalization by macrophages. Overall, we observed that the physicochemical characteristics of proteins had a significant role in modulating the nanoparticle-bio-interface at the level of both biomolecular corona formation and nanoparticle internalization by cells.
Social spread of positive facial signals: affiliative zygomatic synchrony in co-present individuals
Authors: Golland Yulia , Mevorah Dana , Levit-Binnun Nava
Published: December 2018

In social contexts individuals frequently act as social chameleons, synchronizing their responses with those of others. Such synchrony is believed to play an important role, promoting mutual emotional and social states. However, synchrony in facial signals, which serve as the main communicative channel between people, has not been systematically studied. To address this gap, we investigated the social spread of smiling dynamics in a naturalistic social setting and assessed its affiliative function. We also studied whether smiling synchrony between people is linked with convergence in their autonomic and emotional responses. To that aim we measured moment-by-moment changes in zygomatic electromyography and cardiovascular activity in dyads of previously unacquainted participants, who co-viewed emotional movies together. We found a robust, dyad-specific, zygomatic synchrony in co-viewing participants, after controlling for movie-driven effects. During the positive movie, zygomatic synchrony co-varied with cardiovascular synchrony and with convergence in positive feelings. No such links were found for the negative movie. Centrally, zygomatic synchrony in both emotional contexts predicted subsequently reported affiliative feelings of dyad members. These results demonstrate that a naturally unfolding smiling behavior is highly contagious. They further suggest that zygomatic synchrony functions as a social facilitator, eliciting affiliation towards previously unknown others.
The genome of the fungal pathogen Verticillium dahliae reveals extensive bacterial to fungal gene transfer
Authors: Shi Xiaoqian , van Koosten Mathijs , Depotter Jasper , Thomma Bart , Seidl Michael
Published: December 2018

Horizontal gene transfer (HGT) involves the transmission of genetic material between distinct evolutionary lineages and can be an important source of biological innovation. Reports of inter-kingdom HGT to eukaryotic microbial pathogens have accumulated over recent years. Verticillium dahliae is a notorious plant pathogen that causes vascular wilt disease on hundreds of plant species, resulting in high economic losses every year. Previously, the effector gene Ave1 and a glucosyltransferase-encoding gene were identified as virulence factor-encoding genes that were proposed to be horizontally acquired from a plant and a bacterial donor, respectively. However, to what extent HGT contributed to the overall genome composition of V. dahliae remained elusive. Here, we systematically searched for evidence of inter-kingdom HGT events in the genome of V. dahliae and provide evidence for extensive horizontal gene acquisition from bacterial origin.
SARM1 deficiency, which prevents Wallerian degeneration, upregulates XAF1 and accelerates prion disease
Authors: Zhu Caihong , Li Bei , Frontzek Karl , Liu Yingjun , Aguzzi Adriano
Published: December 2018

SARM1 (sterile α and HEAT/armadillo motifs containing protein) is a member of the MyD88 (myeloid differentiation primary response gene 88) family which mediates innate immune responses. Because inactivation of SARM1 prevents various forms of axonal degeneration, we tested whether it might protect against prion-induced neurotoxicity. Instead, we found that SARM1 deficiency exacerbates the progression of prion pathogenesis. This deleterious effect was not due to SARM1-dependent modulation of prion-induced neuroinflammation, since microglial activation, astrogliosis and brain cytokine profiles were not altered by SARM1 deficiency. Whole-transcriptome analyses indicated that SARM1 deficiency led to strong, selective overexpression of the pro-apoptotic gene XAF1 (X-linked inhibitor of apoptosis-associated factor 1). Consequently, the activity of proapoptotic caspases and neuronal death were enhanced in prion-infected SARM1−/− mice. These results point to an unexpected function of SARM1 as a regulator of prion-induced neurodegeneration, and suggest that XAF1 might constitute a therapeutic target in prion disease.
DNA segment of African Swine Fever Virus first detected in hard ticks from sheep and bovine
Authors: Chen Ze , Xu Xiaofeng , Yang Xiaojun , Dou Weihao , Jin Xiufeng , Ji Haishuo , Liu Guangyuan , Luo Jianxun , Yin Hong , Shan Gao
Published: December 2018

In this study, we aimed to detect viruses in hard ticks using the small RNA sequencing based method. A 235-bp DNA segment was detected in Dermacentor nuttalli (hard ticks) and D. silvarum (hard ticks) from sheep and bovine, respectively. The detected 235-bp segment had an identity of 99% to a 235-bp DNA segment of African Swine Fever Virus (ASFV) and contained three single nucleotide mutations (C38T, C76T and A108C). C38T, resulting in an single amino acid mutation G66D, suggests the existence of a new ASFV strain, which is different from all reported ASFV strains in NCBI GenBank database. These results also suggest that ASFV could have a wide range of hosts or vectors, beyond the well known Suidae family and soft ticks. Our findings pave the way toward further studies of ASFV transmission and development of prevention and control measures.
Temporal identity establishes columnar neuron morphology, connectivity, and function in a Drosophila navigation circuit
Authors: Sullivan Luis F. , Warren Timothy L. , Doe Chris Q.
Published: December 2018

The insect central complex (CX) is a conserved brain region containing 60+ neuronal subtypes, several of which contribute to navigation. It is not known how CX neuronal diversity is generated or how developmental origin of subtypes relates to function. We mapped the developmental origin of four key CX subtypes and found that neurons with similar origin have matching axon/dendrite targeting. Moreover, we found that the temporal transcription factor (TTF) Eyeless/Pax6 regulates the development of two recurrently-connected CX subtypes: Eyeless loss simultaneously produces ectopic P-EN neurons with normal axon/dendrite projections, and reduces the number of E-PG neurons. Furthermore, the transient loss of Eyeless during development impairs adult flies’ capacity to perform celestial navigation. We conclude that neurons with similar developmental origin have similar connectivity, that Eyeless maintains equal E-PG and P-EN neuron number, and that Eyeless is required for the development of circuits that control adult navigation.
Beneficial effects of Spirogyra Neglecta Extract on antioxidant and anti-inflammatory factors in streptozotocin-induced diabetic rats
Authors: Mesbahzadeh Behzad , Rajaei Seyed Ali , Tarahomi Parnia , Seyedinia Seyed Ali , Rahmani Mehrnoush , Rezamohamadi Fatemeh , Kakar Muhammad Azam , Moradi-kor Nasroallah
Published: December 2018

Objectives: This study was conducted to evaluate the effects of oral supplementation of Spirogyra algae on oxidative damages and inflammatory responses in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced by administration of 55 mg/kg of streptozotocin. A total of sixty-four rats were divided into eight groups of eight rats each as follows:1) non-diabetic control; 2, 3, and 4) non-diabetic rats treated with 15, 30, and 45 mg of Spirogyra algae/kg/d; 5) control diabetic; and 6, 7, and 8) diabetic rats treated with 15, 30, and 45 mg of Spirogyra algae extract. At the end of the trial, the serum concentrations of glucose, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), C-reactive protein (CRP), insulin, triglycerides, and cholesterol were examined by specified procedures. Results: Our findings indicated that the administration of STZ significantly increased the serum concentrations of glucose, triglycerides, cholesterol, CRP, IL-6, TNF-alpha), and MDA and decreased the serum levels of GSH and TAS (P<0.05) in diabetic rats. Oral administration of Spirogyra alleviated adverse effects of diabetes on oxidative stress and inflammatory factors in diabetic rats (P<0.05). Conclusion: It can be stated that Spirogyra algae extract can be used for treatment of diabetes likely due to prevention of oxidative stress and alleviation of inflammation in the rat model.