bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to feed patients with gastrointestinal mucositis
Authors: Arends Jann 
Published: April 2018

Purpose of review
Gastrointestinal mucositis is a frequent side effect of systemic anticancer treatment and radiotherapy. The occurrence endangers body resources by decreasing food intake and absorption. This review highlights new developments in treatment and prevention.

Recent findings
Recent clinical practice guidelines recommend supplying adequate amounts of energy and nutrients to cancer patients undergoing anticancer treatments. This requires repeated screening for risk of malnutrition and in at-risk patients, assessment of food intake and nutritional status, followed by nutritional interventions targeted at individual deficiencies and tolerance to oral, enteral or parenteral feeding. Recent preclinical data report beneficial effects of stimulating the sensor for cell damage signals TRPA1, blocking histamine H2 receptors or supplying probiotics. In a recent clinical trial, amifostine reduced gastrointestinal symptoms and was well tolerated. Probiotics are studied in ongoing clinical trials and glucagon-like peptide 2 analogues are considered for future trials. Due to limited options available today, it has been suggested to also consider several plant-based complementary therapies.

Summary
Although options for prevention and treatment of chemotherapy or radiotherapy-induced gastrointestinal mucositis today are still limited, inadequate energy and nutrient intake should trigger nutritional interventions, including counselling, oral nutritional supplements, tube feeding and parenteral nutrition. To prevent gastrointestinal mucositis, several new agents have shown promising results in preclinical trials.
Climate and development: enhancing impact through stronger linkages in the implementation of the Paris Agreement and the Sustainable Development Goals (SDGs)
Authors: Gomez-Echeverri Luis 
Published: April 2018

One of the greatest achievements in the global negotiations of 2015 that delivered the 2030 Agenda for Sustainable Development or Sustainable Development Goals (SDGs) and the Paris Agreement on climate change is that, for the first time, the linkages between climate and development were enshrined in each of the documents. This was done in recognition that climate change and development need to be addressed together in order not only to avoid harmful trade-offs and high costs, particularly for poorer countries, but also to exploit the benefits that come from strengthening these linkages. This review presents some of the latest data that argue for stronger linkages as well as the challenges of implementation which are not only politically and economically related but also include issues such as knowledge gaps, finance and governance. Finally, the review also presents a glimpse at the pathways that will be required to reach the ambitious global temperature targets of the Paris Agreement of less than 2°C above pre-industrial levels with efforts to limit temperature rise even further to 1.5°C. This provides the context for some conclusions and recommendations for policy-makers, including on methodologies for assessing linkages and leveraging them for greater benefit.
This article is part of the theme issue ‘The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels’.
Phrank measures phenotype sets similarity to greatly improve Mendelian diagnostic disease prioritization
Authors: Jagadeesh Karthik A. , Birgmeier Johannes , Guturu Harendra , Deisseroth Cole A. , Wenger Aaron M. , Bernstein Jonathan A. , Bejerano Gill 
Published: April 2018

AbstractPurposeExome sequencing and diagnosis is beginning to spread across the medical establishment. The most time-consuming part of genome based diagnosis is the manual step of matching the potentially long list of patient candidate genes to patient phenotypes to identify the causative disease.MethodsWe introduce Phrank (for phenotype ranking), an information-theory inspired method that utilizes a Bayesian Network to prioritize candidate diseases or genes, as a stand-alone module that can be run with any underlying knowledgebase and any variant filtering scheme.ResultsPhrank outperforms existing methods at ranking the causative disease or gene when applied to 169 real patient exomes with Mendelian diagnoses. Phrank’s greatest improvement is in disease space, where across all 169 patients it ranks only 3 diseases on average ahead of the true diagnosis, whereas Phenomizer ranks 32 diseases ahead of the causal one.ConclusionUsing Phrank to rank all patient candidate genes or diseases, as they start working through a new case, will save the busy clinician much time in deriving a genetic diagnosis.
Constant conflict betweenGypsyLTR retrotransposons and CHH methylation within a stress-adapted mangrove genome
Authors: Wang Yushuai , Liang Weiqi , Tang Tian 
Published: April 2018

SummaryEvolutionary dynamics of the conflict between transposable elements (TEs) and their host genome remain elusive. This conflict would be intense in stress-adapted plants as stress can often reactivate TEs. Mangroves reduce TE load convergently in their adaptation to intertidal environments and thus provide a unique opportunity to address the host-TE conflict and its interaction with stress adaptation.Using the mangroveRhizophora apiculataas a model, we investigated methylation and short interfering RNA (siRNA) targeting patterns in relation to the abundance and age of long terminal repeat (LTR) retrotransposons. We also examined LTR retrotransposons’ distance to genes, impact on neighboring gene expression, and population frequencies.We found differential accumulation among classes of LTR retrotransposons despite high overall methylation levels. This can be attributed to 24-nt siRNA-mediated CHH methylation preferentially targetingGypsyelements, particularly in their LTR regions. OldGypsyelements possess unusually abundant siRNAs which show cross-mapping to young copies.Gypsyelements appear to be closer to genes and under stronger purifying selection than other classes.Our results suggest a continuous host-TE battle masked by the TE load reduction inR. apiculata. This conflict may enable mangroves likeR. apiculatato maintain genetic diversity and thus evolutionary potential during stress adaptation.
Plant odour and sex pheromone are integral elements of specific mate recognition in an insect herbivore
Authors: Borrero-Echeverry Felipe , Bengtsson Marie , Witzgall Peter 
Published: April 2018

SummarySpecific mate recognition strongly relies on the chemical senses in many animals, and especially in nocturnal insects. Two signal types lend to premating olfactory communication in terrestrial habitats: sex signals blend into an atmosphere of habitat odorants, where plant volatiles prevail. We show for the first time that males of the African cotton leafwormSpodoptera littoralisperceive female sex pheromone and volatiles of its plant host cotton as a unit, rather than as independent messages. In clean air,S.littoralismales are attracted to flawed pheromone signals, such as single synthetic pheromone components or even the pheromone of a sibling species, Oriental leafwormS.litura. Presence of host plant volatiles, however, strongly reduces the male response to deficient or heterospecific pheromone signals. That plant cues enhance discrimination of sex pheromone quality confirms the idea that specific mate recognition in noctuid moths has evolved in concert with host plant adaptation. A participation of host plant odour in sexual communication suggests that mate recognition is under natural and sexual selection. Moreover, shifts in either female host preference or sex pheromone biosynthesis give rise to new communication channels that have the potential to initiate or contribute to reproductive isolation.
A conserved Lkb1 signaling axis modulates TORC2 signaling in budding yeast
Authors: Alcaide-Gavilán Maria , Lucena Rafael , Schubert Katherine , Artiles Karen , Zapata Jessica , Kellogg Douglas R. 
Published: April 2018

ABSTRACTNutrient availability, growth rate and cell size are closely linked. For example, in budding yeast, the rate of cell growth is proportional to nutrient availability, cell size is proportional to growth rate, and growth rate is proportional to cell size. Thus, cells grow slowly in poor nutrients and are nearly half the size of cells growing in rich nutrients. Moreover, large cells grow faster than small cells. A signaling network that surrounds Tor kinase complex 2 (TORC2) plays an important role in enforcing these proportional relationships. Cells that lack components of the TORC2 network fail to modulate their growth rate or size in response to changes in nutrient availability. Here, we show that budding yeast homologs of the Lkb1 tumor suppressor kinase are required for normal modulation of TORC2 signaling and in response to changes in carbon source. Lkb1 kinases activate Snf1/AMPK to initiate transcription of genes required for utilization of poor carbon sources. However, Lkb1 influences TORC2 signaling via a novel pathway that is independent of Snf1/AMPK. Of the three Lkb1 homologs in budding yeast, Elm1 plays the most important role in modulating TORC2. Elm1 activates a pair of related kinases called Gin4 and Hsl1. Previous work found that loss of Gin4 and Hsl1 causes cells to undergo unrestrained growth during a prolonged mitotic arrest, which suggests that play a role in linking cell cycle progression to cell growth. We found that Gin4 and Hsl1 also control the TORC2 network. In addition, Gin4 and Hsl1 are themselves influenced by signals from the TORC2 network, consistent with previous work showing that the TORC2 network constitutes a feedback loop. Together, the data suggest a model in which the TORC2 network sets growth rate in response to carbon source, while also relaying signals via Gin4 and Hsl1 that set the critical amount of growth required for cell cycle progression. This kind of close linkage between control of cell growth and size would suggest a simple mechanistic explanation for the proportional relationship between cell size and growth rate.
Many rice genes are differentially spliced between roots and shoots but cytokinin has minimal effect on splicing
Authors: Freese Nowlan H. , Estrada April R. , Blakley Ivory C. , Duan Jinjie , Loraine Ann E. 
Published: April 2018

ABSTRACTAlternatively spliced genes produce multiple spliced isoforms, called transcript variants. In differential alternative splicing, transcript variant abundance differs across sample types. Differential alternative splicing is common in animal systems and influences cellular development in many processes, but its extent and significance is not as well known in plants. To investigate alternative splicing in plants, we examined RNA-Seq data from rice seedlings. The data included three biological replicates per sample type, approximately 30 million sequence alignments per replicate, and four sample types: roots and shoots treated with exogenous cytokinin delivered hydroponically or a mock treatment. Cytokinin treatment triggered expression changes in thousands of genes but had negligible effect on splicing patterns. However, many genes were alternatively spliced between mock-treated roots and shoots, indicating that our methods were sufficiently sensitive to detect differential splicing in a data set. Quantitative fragment analysis of reverse transcriptase-PCR products made from newly prepared rice samples confirmed nine of ten differential splicing events between rice roots and shoots. Differential alternative splicing typically changed the relative abundance of splice variants that co-occurred in a data set. Analysis of a similar (but less deeply sequenced) RNA-Seq data set from Arabidopsis showed the same pattern. In both the Arabidopsis and rice RNA-Seq data sets, most genes annotated as alternatively spliced had small minor variant frequencies. Of splicing choices with abundant support for minor forms, most alternative splicing events were located within the protein-coding sequence and maintained the annotated reading frame. A tool for visualizing protein annotations in the context of genomic sequence (ProtAnnot) together with a genome browser (Integrated Genome Browser) were used to visualize and assess effects of differential splicing on gene function. In general, differentially spliced regions coincided with conserved regions in the encoded proteins, indicating that differential alternative splicing is likely to affect protein function between root and shoot tissue in rice.
Wnt/β-catenin regulates an ancient signaling network during zebrafish scale development
Authors: Aman Andrew J. , Fulbright Alexis N. , Parichy David M. 
Published: April 2018

ABSTRACTUnderstanding how patterning influences cell behaviors to generate three dimensional morphologies is a central goal of developmental biology. Additionally, comparing these regulatory mechanisms among morphologically diverse tissues allows for rigorous testing of evolutionary hypotheses. Zebrafish skin is endowed with a coat of precisely patterned bony scales. We use in-toto live imaging during scale development and manipulations of cell signaling activity to elucidate core features of scale patterning and morphogenesis. These analyses show that scale development requires the concerted activity of Wnt/β-catenin, Ectodysplasin (Eda) and Fibroblast growth factor (Fgf) signaling. This regulatory module coordinates Hedgehog (HH) dependent collective cell migration during epidermal invagination, a cell behavior not previously implicated in skin appendage morphogenesis. Our analyses demonstrate the utility of zebrafish scale development as a tractable system in which to elucidate mechanisms of developmental patterning and morphogenesis, and suggest a single, ancient origin of skin appendage patterning mechanisms in vertebrates.
A transgenic pig model expressing a ZsGreen1 reporter across an extensive array of tissues
Authors: Desaulniers Amy T. , Cederberg Rebecca A. , Carreiro Elizabeth P. , Gurumurthy Channabasavaiah B. , White Brett R. 
Published: April 2018

ABSTRACTBackgroundThe advent of genetically engineered pig production has revealed a wide array of opportunities to enhance both biomedical and agricultural industries. One powerful method to develop these models is transgenesis; however, selection of a suitable promoter to drive transgene expression is critical. The cytomegalovirus (CMV) promoter is the most commonly used viral promoter as it robustly drives transgene expression in a ubiquitous nature. However, recent reports suggest that the level of CMV promoter activity is tissue-dependent in the pig. Therefore, the objective of this study was to quantify the activity of the CMV promoter in a wide range of porcine tissues. Swine harboring a CMV-ZsGreen1 transgene with a single integration site were utilized for this study. Thirty five tissue samples were collected from neonatal hemizygous (n = 3) and homozygous (n = 3) transgenic piglets and analyzed for ZsGreen1 abundance via immunoblot.ResultsZsGreen1 was detected in all tissues examined; however, quantification revealed that ZsGreen1 protein levels were tissue-specific. Within organs of the digestive system, for example, ZsGreen1 was most abundant in the salivary gland, moderately produced in the esophagus and levels were lowest in the stomach. Interestingly, abundance of ZsGreen1 also differed within organ. For instance, levels were highest in the right ventricle compared with other chambers of the heart. There was no effect of transgene dose as ZsGreen1 expression patterns were similar between homozygous and hemizygous piglets.ConclusionsUltimately, these results elucidate the tissue-specific activity of the CMV promoter in the neonatal pig. Moreover, this model can serve as a useful tool for research applications requiring reporter gene activity in mammalian organs.
On the deformability of an empirical fitness landscape by microbial evolution
Authors: Bajić Djordje , Vila Jean C.C. , Blount Zachary D. , Sánchez Alvaro 
Published: April 2018

AbstractA fitness landscape is a map between the genotype and its reproductive success in a given environment. The topography of fitness landscapes largely governs adaptive dynamics, constraining evolutionary trajectories and the predictability of evolution. Theory suggests that this topography can be “deformed” by mutations that produce substantial changes to the environment. In spite of its importance, the deformability of fitness landscapes has not been systematically studied beyond abstract models, and little is known about its reach and consequences in empirical systems. Here we have systematically characterized the deformability of the genome-wide metabolic fitness landscape of the bacteriumE. coli. Deformability is quantified by the non-commutativity of epistatic interactions, which we experimentally demonstrate in mutant strains on the path to an evolutionary innovation. Our analysis shows that the deformation of fitness landscapes by metabolic mutations rarely affects evolutionary trajectories in the short-range. However, mutations with large environmental effects leave these as a “legacy”, producing long-range landscape deformations in distant regions of the genotype space that affect the fitness of later descendants. Our methods and results provide the basis for an integration between adaptive and eco-evolutionary dynamics with complex genetics and genomics.
Phylogenetic evidence for independent origins of GDF1 and GDF3 genes in amphibians and mammals
Authors: Opazo Juan C. , Zavala Kattina 
Published: April 2018

AbstractGrowth differentiation factors 1 (GDF1) and 3 (GDF3) are members of the transforming growth factor superfamily (TGF-β) that is involved in fundamental early-developmental processes that are conserved across vertebrates. The evolutionary history of these genes is still under debate due to ambiguous definitions of homologous relationships among vertebrates. Thus, the goal of this study was to unravel the evolution of the GDF1 and GDF3 genes of vertebrates, emphasizing the understanding of homologous relationships and their evolutionary origin. Surprisingly, our results revealed that the GDF1 and GDF3 genes found in amphibians and mammals are the products of independent duplication events of an ancestral gene in the ancestor of each of these lineages. The main implication of this result is that the GDF1 and GDF3 genes of amphibians and mammals are not 1:1 orthologs. In other words, genes that participate in fundamental processes during early development have been reinvented two independent times during the evolutionary history of tetrapods.
CD95 receptor activation by ligand-induced trimerization is independent of its partial pre-ligand assembly
Authors: Liesche C. , Berndt J. , Fricke F. , Aschenbrenner S. , Heilemann M. , Eils R. , Beaudouin J. 
Published: April 2018

AbstractCD95 (Fas, APO-1, TNFRSF6) is a widely expressed single-pass transmembrane protein that is implicated in cell death, inflammatory response, proliferation and cell migration. CD95 ligand (CD95L, FasL, TNFSF6), is a potent apoptotic inducer in the membrane form but not when cleaved into soluble CD95L (sCD95L). Here, we aimed at understanding the relation between ligand-receptor multimerization and receptor activation by correlating the kinetics of ligand binding, receptor oligomerization, FADD (FAS-Associated via Death Domain) recruitment and caspase-8 activation inside living cells. Using single molecule localization microscopy and Förster resonance energy transfer imaging we show that the majority of CD95 receptors on the plasma membrane are monomeric at rest. This was confirmed functionally as the wild-type receptor is not blocked by a receptor mutant that cannot bind ligand. Moreover, using time-resolved fluorescence imaging approaches we demonstrated that receptor multimerization follows instantaneously ligand binding, whereas FADD recruitment is delayed. This process can explain the typical delay time seen with caspase-8 activity reporters. Finally, the low activity of sCD95L, which was caused by inefficient FADD recruitment, was not explained by the low avidity for the receptor but by a receptor clustering mechanism that was different from the one induced by the strong apoptosis inducer IZ-sCD95L. Our results reveal that receptor activation is modulated by the capacity of its ligand to trimerize it.HighlightsAt a density of less than 10 receptors per µm2CD95 exists as monomer (58%) and dimer (42%)Pre-formed dimers do not contribute to ligand-induced CD95 apoptotic signalingThe PLAD of CD95 attenuates overexpression-induced, ligand-independent cell deathsoluble CD95L can rapidly multimerize CD95 after binding but it is still a poor inducer of apoptosis through inefficient FADD recruitmentFADD recruitment kinetics but not ligand binding kinetics correlates with caspase-8 onset of activity
Gene inversion increases evolvability in bacteria
Authors: Merrikh Christopher , Merrikh Houra 
Published: April 2018

AbstractIn bacteria, most genes are encoded on the leading strand, co-orienting the movement of the replication machinery with RNA polymerases. This co-orientation bias reduces the frequency of highly detrimental head-on collisions between the two machineries. This and other work set up the expectation that over evolutionary time, head-on alleles are selected against, maximizing genome co-orientation. Our findings challenge this model. Using the well-established GC skew method, we reveal the evolutionary inversion record of all chromosomally encoded genes in multiple divergent bacterial pathogens. We find that a surprisingly large number of co-oriented genes have inverted to, and are retained in the head-on orientation. Furthermore, we find that these head-on genes, (including key antibiotic resistance and virulence genes) have higher rates of nonsynonymous mutations and are more frequently under positive selection (dN/dS>1). Based on these results, we propose that bacteria increase their evolvability through gene inversion and promotion of head-on replication-transcription collisions.
The quantification of protein-protein interaction interfaces using solvent-excluded surface-defined properties
Authors: Wang Lincong 
Published: April 2018

AbstractProtein-protein interaction (PPI) is the cornerstone of nearly every biological process. During last forty years PPI interfaces have been investigated extensively both in vitro and in silico in order to understand both the strength and specificity of PPI. At least three different models, the buried surface model, the O-ring model and the rim- and-core model, have been proposed for PPI interface. However none of them provide much detail about PPI and a single model that reconciles them remains elusive. To identify common physical and geometrical features shared by various PPI interfaces we have analyzed several solvent-excluded surface (SES)-defined properties for a set of well-studied protein-protein complexes with crystal structures. Our analysis shows that the SES-defined properties for the interface atoms of a PPI partner are in general different from those for the surface atoms of a water-soluble protein. Most significantly we find that the partially-buried atoms of a PPI partner have unique SES-defined properties that set them well apart from either the buried atoms or the accessible atoms. Based on distinct SES-defined properties for the accessible, buried and partially-buried atoms shared by various PPI interfaces we propose a new model specified by a list of SES-defined properties shared by various PPI interfaces. Our model is quantitative in nature and should be useful for PPI site identification, protein-protein docking and structure-based design of chemicals targeting PPI.