bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional support for a novel mechanism that enhances tissue oxygen extraction in a teleost fish
Authors: Harter T. S. , Zanuzzo F. S. , Supuran C. T. , Gamperl A. K. , Brauner C. J.
Published: May 2019

A successful spawning migration in salmon depends on their athletic ability, and thus on efficient cardiovascular oxygen (O2) transport. Most teleost fishes have highly pH-sensitive haemoglobins (Hb) that can release large amounts of O2when the blood is acidified at the tissues. We hypothesized that plasma-accessible carbonic anhydrase (paCA; the enzyme that catalyses proton production from CO2) is required to acidify the blood at the tissues and promote tissue O2extraction. Previous studies have reported an elevated tissue O2extraction in hypoxia-acclimated teleosts that may also be facilitated by paCA. Thus, to create experimental contrasts in tissue O2extraction, Atlantic salmon were acclimated to normoxia or hypoxia (40% air saturation for more than six weeks), and the role of paCA in enhancing tissue O2extraction was tested by inhibiting paCA at rest and during submaximal exercise. Our results show that: (i) in both acclimation groups, the inhibition of paCA increased cardiac output by one-third, indicating a role of paCA in promoting tissue O2extraction during exercise, recovery and at rest; (ii) the recruitment of paCA was plastic and increased following hypoxic acclimation; and (iii) maximal exercise performance in salmon, and thus a successful spawning migration, may not be possible without paCA.
Swimbladder morphology masks Southern Ocean mesopelagic fish biomass
Authors: Dornan Tracey , Fielding Sophie , Saunders Ryan A. , Genner Martin J.
Published: May 2019

Within the twilight of the oceanic mesopelagic realm, 200–1000 m below sea level, are potentially vast resources of fish. Collectively, these mesopelagic fishes are the most abundant vertebrates on Earth, and this global fish community plays a vital role in the function of oceanic ecosystems. The biomass of these fishes has recently been estimated using acoustic survey methods, which rely on echosounder-generated signals being reflected from gas-filled swimbladders and detected by transducers on vessels. Here, we use X-ray computed tomography scans to demonstrate that several of the most abundant species of mesopelagic fish in the Southern Ocean lack gas-filled swimbladders. We also show using catch data from survey trawls that the fish community switches from fish possessing gas-filled swimbladders to those lacking swimbladders as latitude increases towards the Antarctic continent. Thus, the acoustic surveys that repeatedly show a decrease in mesopelagic fish biomass towards polar environments systematically overlook a large proportion of fish species that dominate polar seas. Importantly, this includes lanternfish species that are key prey items for top predators in the region, including king penguins and elephant seals. This latitudinal community switch, from gas to non-gas dominance, has considerable implications for acoustic biomass estimation, ecosystem modelling and long-term monitoring of species at risk from climate change and potential exploitation.
Categorical colour perception occurs in both signalling and non-signalling colour ranges in a songbird
Authors: Zipple Matthew N. , Caves Eleanor M. , Green Patrick A. , Peters Susan , Johnsen Sönke , Nowicki Stephen
Published: May 2019

Although perception begins when a stimulus is transduced by a sensory neuron, numerous perceptual mechanisms can modify sensory information as it is processed by an animal's nervous system. One such mechanism is categorical perception, in which (1) continuously varying stimuli are labelled as belonging to a discrete number of categories and (2) there is enhanced discrimination between stimuli from different categories as compared with equally different stimuli from within the same category. We have shown previously that female zebra finches (Taeniopygia guttata) categorically perceive colours along an orange–red continuum that aligns with the carotenoid-based coloration of male beaks, a trait that serves as an assessment signal in female mate choice. Here, we demonstrate that categorical perception occurs along a blue–green continuum as well, suggesting that categorical colour perception may be a general feature of zebra finch vision. Although we identified two categories in both the blue–green and the orange–red ranges, we also found that individuals could better differentiate colours from within the same category in the blue–green as compared with the orange–red range, indicative of less clear categorization in the blue–green range. We discuss reasons why categorical perception may vary across the visible spectrum, including the possibility that such differences are linked to the behavioural or ecological function of different colour ranges.
Loser-effect duration evolves independently of fighting ability
Authors: Okada Kensuke , Okada Yasukazu , Dall Sasha R. X. , Hosken David J.
Published: May 2019

Winning or losing contests can impact subsequent competitive behaviour and the duration of these effects can be prolonged. While it is clear effects depend on social and developmental environments, the extent to which they are heritable, and hence evolvable, is less clear and remains untested. Furthermore, theory predicts that winner and loser effects should evolve independently of actual fighting ability, but again tests of this prediction are limited. Here we used artificial selection on replicated beetle populations to show that the duration of loser effects can evolve, with a realized heritability of about 17%. We also find that naive fighting ability does not co-evolve with reductions in the duration of the loser effect. We discuss the implications of these findings and how they corroborate theoretical predictions.
Lyme neuroborreliosis and bird populations in northern Europe
Authors: Mysterud Atle , Heylen Dieter J. A. , Matthysen Erik , Garcia Aïda Lopez , Jore Solveig , Viljugrein Hildegunn
Published: May 2019

Many vector-borne diseases are transmitted through complex pathogen–vector–host networks, which makes it challenging to identify the role of specific host groups in disease emergence. Lyme borreliosis in humans is now the most common vector-borne zoonosis in the Northern Hemisphere. The disease is caused by multiple genospecies of
Borrelia burgdorferi sensu
lato
bacteria transmitted by ixodid (hard) ticks, and the major host groups transmit
Borrelia
genospecies with different pathogenicity, causing variable clinical symptoms in humans. The health impact of a given host group is a function of the number of ticks it infects as well as the pathogenicity of the genospecies it carries.
Borrelia afzelii
, with mainly small mammals as reservoirs, is the most common pathogen causing Lyme borreliosis, and it is often responsible for the largest proportion of infected host-seeking tick nymphs in Europe. The bird-borne
Borrelia garinii
, though less prevalent in nymphal ticks, is more likely to cause Lyme neuroborreliosis, but whether
B. garinii
causes disseminated disease more frequently has not been documented. Based on extensive data of annual disease incidence across Norway from 1995 to 2017, we show here that 69% of disseminated Lyme borreliosis cases were neuroborreliosis, which is three times higher than predicted from the infection prevalence of
B. garinii
in host-seeking ticks (21%). The population estimate of migratory birds, mainly of thrushes, explained part of the annual variation in cases of neuroborreliosis, with a one-year time lag. We highlight the important role of the genospecies' pathogenicity and the host associations for understanding the epidemiology of disseminated Lyme borreliosis.
Older paternal ages and grandpaternal ages at conception predict longer telomeres in human descendants
Authors: Eisenberg Dan T. A. , Lee Nanette R. , Rej Peter H. , Hayes M. Geoffrey , Kuzawa Christopher W.
Published: May 2019

Telomere length (TL) declines with age in most human tissues, and shorter TL appears to accelerate senescence. By contrast, men's sperm TL is positively correlated with age. Correspondingly, in humans, older paternal age at conception (PAC) predicts longer offspring TL. We have hypothesized that this PAC effect could persist across multiple generations, and thereby contribute to a transgenerational genetic plasticity that increases expenditures on somatic maintenance as the average age at reproduction is delayed within a lineage. Here, we examine TL data from 3282 humans together with PAC data across four generations. In this sample, the PAC effect is detectable in children and grandchildren. The PAC effect is transmitted through the matriline and patriline with similar strength and is characterized by a generational decay. PACs of more distant male ancestors were not significant predictors, although statistical power was limited in these analyses. Sensitivity analyses suggest that the PAC effect is linear, not moderated by offspring age, or maternal age, and is robust to controls for income, urbanicity and ancestry. These findings show that TL reflects the age at the reproduction of recent male matrilineal and patrilineal ancestors, with an effect that decays across generations.
Modulation of emotion perception and memory via sub-threshold amygdala stimulation in humans
Authors: Bujarski Krzysztof A. , Song Yinchen , Kolankiewicz Sophia I. , Wozniak Gabriella H. , Andrews Angeline S. , Guillory Sean A. , Roberts Dave W. , Aronson Joshua P. , Jobst Barbara C.
Published: May 2019

A common human experience is noticing that emotional life events are more vividly remembered than dull ones. Studies show that the amygdala plays a central role in such emotionally driven enhancement of memory. With this in mind, we investigated the effect of electrical brain stimulation of the left human amygdala on performance on an emotional perception and emotional memory task. We randomly applied sub-threshold 50 Hz stimulation to the left amygdala in 10 patients (5 female and 5 male) with intracranial electrodes during the encoding portion of an emotional valence perception and emotional memory task. We found that amygdala stimulation did not affect reported valence for neutral stimuli (non-stimulated group average valence 5.34, stimulated 5.38, p=0.68) but it did affect positively (non-stimulated group average valence 7.31, stimulated 6.70, p=0.004) and negatively (non-stimulated group average valence 2.79, stimulated 3.55, p=0.0002) valenced stimuli in effect reporting both valence categories as more neutral. Furthermore, we found that stimulation did not significantly disrupt memory for neutral stimuli (68% vs. 61% correctly remembered p=0.48) or positive stimuli (87% vs. 70% correct, trend towards significant difference p=0.09) but did for negative stimuli (83% vs. 67% correct, p=0.03). These results suggest that electrical brain stimulation by our parameters likely reversibly inhibits amygdala function disrupting neural networks responsible for emotional perception and memory. This effect may have clinical implications in treatment of certain neuropsychiatric disorders, such as emotional dysregulation and post-traumatic stress disorder.

Statement of significance

The current study builds and expands on extensive prior research into the function of the human amygdala. It provides the first systematic description in humans of a cognitive change brought about by direct electrical stimulation of the amygdala on perception of emotional valence and emotional memory. The results provide further evidence on the importance of the amygdala in human cognition. Likewise, out method utilized to study the function of the amygdala can be extended to study the function of other brain regions in humans, such as the cingulate. While these results are preliminary and need to be duplicated, we aim to further study the effects of amygdala stimulation on emotional processing including possible therapeutic application for diverse group of neuropsychiatric conditions.
An Inordinate Fondness for Species with Intermediate Dispersal Abilities
Authors: Ashby Ben , Shaw Allison K. , Kokko Hanna
Published: May 2019

Abstract

JBS Haldane is widely quoted to have quipped that the Creator, if one exists, has an inordinate fondness for beetles. Although Coleoptera may not be the most speciose order once Hymenopteran diversity is fully accounted for, as a whole the very clear differences in species diversity among taxa require an explanation. Here we show both analytically and through stochastic simulations that dispersal has eco-evolutionary effects that predict taxa to become particularly species-rich when dispersal is neither too low nor too high. Our models combine recent advances in understanding coexistence in niche space with previously verbally expressed ideas, where too low dispersal imposes biogeographic constraints that prevent a lineage from finding new areas to colonize (reducing opportunities for speciation), while too high dispersal impedes population divergence, leading to few but widely distributed species. We show that this logic holds for species richness and is robust to a variety of model assumptions, but peak diversification rate is instead predicted to increase with dispersal. Our work unifies findings of increasing and decreasing effects of dispersal rate on speciation, and explains why organisms with moderate dispersal abilities have the best prospects for high global species richness.
Sleep, regional grey matter volumes, and psychological functioning in adolescents
Authors: Lapidaire Winok , Urrila Anna S. , Artiges Eric , Miranda Ruben , Vulser Hélène , Bézivin-Frere Pauline , Lemaître Hervé , Penttilä Jani , Banaschewski Tobias , Bokde Arun L.W. , Bromberg Uli , Büchel Christian , Conrod Patricia J. , Desrivières Sylvane , Frouin Vincent , Gallinat Jürgen , Garavan Hugh , Gowland Penny , Heinz Andreas , Ittermann Bernd , Papadopoulos-Orfanos Dimitri , Paus Tomáš , Smolka Michael N. , Schumann Gunter , Paillère Martinot Marie-Laure , Martinot Jean-Luc
Published: May 2019

Changing sleep rhythms in adolescents often lead to sleep deficits and increased variability in sleep schedules. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n=101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationship between regional grey matter volumes with psychological functioning. Sleep was assessed with self-reports and psychological functioning with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and both externalising and internalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development.
PP2ACdc55dephosphorylates Pds1 to inhibit spindle elongation
Authors: Khondker Shoily , Kajjo Sam , Chandler-Brown Devon , Skotheim Jan , Rudner Adam , Ikui Amy
Published: May 2019

DNA replication stress stalls replication forks leading to chromosome breakage and Intra-S checkpoint activation. InS. cerevisiae, this checkpoint arrests the cell cycle by stabilizing securin (Pds1) and inhibiting the cyclin dependent kinase (CDK) through multiple pathways. Pds1 inhibits separase (Esp1) which cleaves the cohesin subunit Scc1 and also functions in spindle elongation. However, the role of Pds1-Esp1 in spindle elongation during replication stress response is unknown. Here, we show that Pds1 phosphorylation plays a positive role in spindle elongation through the Pds1-Esp1 interaction in unperturbed and replication stress conditions. PP2ACdc55directly dephosphorylates Pds1 bothin vivoandin vitro. Pds1 hyperphosphorylation in acdc55Δmutant enhanced the Pds1-Esp1 interaction, which accelerated spindle elongation. This PP2ACdc55-dependent Pds1 dephosphorylation plays a role during replication stress and acts independently of the known Mec1, Swe1 or Spindle Assembly Checkpoint (SAC) checkpoint pathways. We propose a model where PP2ACdc55dephosphorylates Pds1 to disrupt the Pds1-Esp1 interaction that inhibits spindle elongation during replication stress.
Anin silicosurvey ofClostridioides difficileextrachromosomal elements
Authors: Hornung Bastian , Kuijper Ed J. , Smits Wiep Klaas
Published: May 2019

The gram-positive enteropathogenClostridioides difficileis the major cause of healthcare associated diarrhoea and is also an important cause of community-acquired infectious diarrhoea. Considering the burden of the disease, many studies have employed whole genome sequencing to identify factors that contribute to virulence and pathogenesis. Though extrachromosomal elements such as plasmids are important for these processes in other bacteria, the few characterized plasmids ofC. difficilehave no relevant functions assigned and no systematic identification of plasmids has been carried out to date. Here, we perform anin silicoanalysis of publicly available sequence data, to show that ∼13% of allC. difficilestrains contain extrachromosomal elements, with 1-6 elements per strain. Our approach identifies known plasmids (e.g. pCD6, pCD630 and cloning plasmids) and 6 novel putative plasmid families. Our study shows that plasmids are abundant and may encode functions that are relevant forC. difficilephysiology. The newly identified plasmids may also form the basis for the construction of novel cloning plasmids forC. difficilethat are compatible with existing tools.

Repositories

The assembled circular type plasmids have been deposited at the European Nucleotide Archive (ENA) under accession numbers ERZ940801 and ERZ940803-ERZ940808.
Designing Distributed Cell Classifier Circuits using a Genetic Algorithm
Authors: Nowicka Melania , Siebert Heike
Published: May 2019

Cell classifiers are decision-making synthetic circuits that allow in vivo cell-type classification. Their design is based on finding a relationship between differential expression of miRNAs and the cell condition. Such biological devices have shown potential to become a valuable tool in cancer treatment as a new type-specific cell targeting approach. So far, only single-circuit classifiers were designed in this context. However, reliable designs come with high complexity, making them difficult to assemble in the lab. Here, we apply so-called Distributed Classifiers (DC) consisting of simple single circuits, that decide collectively according to a threshold function. Such architecture potentially simplifies the assembly process and provides design flexibility. Here, we present a genetic algorithm that allows the design and optimization of DCs. Breast cancer case studies show that DCs perform with high accuracy on real-world data. Optimized classifiers capture biologically relevant miRNAs that are cancer-type specific. The comparison to a single-circuit classifier design approach shows that DCs perform with significantly higher accuracy than individual circuits. The algorithm is implemented as an open source tool.
Low handgrip strength is closely associated with anemia among adults: A cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES)
Authors: Gi Yu-mi , Jung Boyoung , Kim Koh-Woon , Cho Jae-Heung , Ha In-Hyuk
Published: May 2019

Background

Anemia occurs because of insufficient hemoglobin, which provides oxygen to the body. Because of its close relationship with various illnesses, it must always be investigated clinically. Previous studies have demonstrated an association between hemoglobin concentration and handgrip strength. Thus, we aimed to analyze the association between handgrip strength and anemia in Korean adults to determine whether the handgrip strength test can be used as a tool to identify anemia.

Methods

The research subjects’ data were extracted from the 6thand 7thKorean National Health and Nutrition Examination Survey, between January 2013 and December 2017. Overall, data of 16,637 adults (weighted n= 9,734,598) were analyzed. Differences in sociodemographic factors (sex, age, education, income, and employment), lifestyle factors (alcohol consumption, smoking, and physical activity), and illness and health factors (body mass index, vitamin intake, iron intake, comorbid illnesses, and handgrip strength) by existence of anemia were analyzed using a chi square test. Binary logistic regression was performed to identify factors of anemia. Subgroup analysis, stratified by sex and age, was performed.

Results

Among Korean adults aged ≥ 19 years, 745,296 (7.7%) had anemia. Higher odds ratio (OR) of anemia occurred in the weak handgrip strength group compared to the strong handgrip strength group (OR=1.92, 95% CI: 1.58-2.33). The subgroup analysis showed a higher OR for anemia in the weak handgrip strength group than in the strong handgrip strength group, regardless of sex or age. However, the results showed that this association was greater for males (OR=2.13, 95% CI: 1.35-3.34) and for those aged ≥65 years (OR=1.92, 95% CI: 1.42-2.58).

Conclusion

This study showed a strong association between handgrip strength and anemia, which was particularly strong for males and those aged ≥65 years. Therefore, it is anticipated that handgrip strength can be used in anemia screening tests as a useful tool.
A systems biology-based molecular model of the protein kinase C life cycle
Authors: Aslam Naveed , Alvi Farah
Published: May 2019

Protein kinase C (PKC) enzymes are a family of kinases that mediate signal transduction originating at the cell surface. Most cell membranes can contain functional PKC enzymes. Aberrations in the PKC life cycle may result cellular damage and dysfunction. For example, some cancerous cells exhibit alterations in PKC activity. Here, we use a systems biology approach to describe a molecular model of the PKC life cycle. Understanding the PKC life cycle is necessary to identify new anticancer drug targets. The PKC life cycle is composed of three key regulatory processes: maturation, activation and termination. These processes precisely control PKC enzyme levels. This model describes the fate of PKC duringde novosynthesis and PKC’s lipid-mediated activation cycle. We utilize a systems biology approach to show the PKC life cycle is controlled by multiple phosphorylation and dephosphorylation events. PKC processing events can be divided into two types: maturation via processing of newly synthesized enzyme and secondary messenger-dependent activation of dormant, but catalytically-competent enzyme. Newly synthesized PKC enzyme is constitutively processed through three ordered phosphorylations and stored in the cytosol as a stable, signaling-competent inactive and autoinhibited molecule. Upon extracellular stimulation, diacylglycerol (DAG) and calcium ion (Ca+2) generated at the membrane bind PKC. PKC then undergoes cytosol-to-membrane translocation and subsequent activation. Our model shows that, once activated, PKC is prone to dephosphorylation and subsequent degradation. This model also describes the role of HSP70 in stabilization and re-phosphorylation of dephosphorylated PKC, replenishing the PKC pool. Our model shows how the PKC pool responds to different intensities of extracellular stimuli? We show that blocking PHLPP dephosphorylation replenishes the PKC pool in a dose-dependent manner. This model provides a comprehensive understanding of PKC life cycle regulation.
Protein lysine methylation is involved in modulating the response of sensitive and tolerant Arabidopsis species to cadmium stress
Authors: Serre Nelson B.C. , Sarthou Manon , Gigarel Océane , Figuet Sylvie , Corso Massimiliano , Choulet Justine , Rofidal Valérie , Alban Claude , Santoni Véronique , Bourguignon Jacques , Verbruggen Nathalie , Ravanel Stéphane
Published: May 2019

The mechanisms underlying the response and adaptation of plants to excess of trace elements are not fully described. Here, we analyzed the importance of protein lysine methylation for plants to cope with cadmium. We analyzed the effect of cadmium on lysine-methylated proteins and protein lysine methyltransferases (KMTs) in two cadmium-sensitive species,Arabidopsis thalianaandA. lyrata, and in three populations ofA. halleriwith contrasting cadmium accumulation and tolerance traits. We showed that some proteins are differentially methylated at lysine residues in response to Cd and that a few genes coding KMTs is regulated by cadmium. Also, we showed that nine out of 23A. thalianamutants interrupted inKMTgenes have a tolerance to cadmium that is significantly different from that of wild-type seedlings. We further characterized two of these mutants, one was knocked-out in the calmodulin lysine methyltransferase gene and displayed increased tolerance to cadmium, the other was interrupted in aKMTgene of unknown function and showed a decreased capacity to cope with cadmium. Together, our results showed that lysine methylation of non-histone proteins is impacted by cadmium and that several methylation events are important for modulating the response of Arabidopsis plants to cadmium stress.
The dynamics of motor learning through the formation of internal models
Authors: Pierella Camilla , Casadio Maura , Solla Sara A. , Mussa-Ivaldi Ferinando A.
Published: May 2019

A medical student learning to perform a laparoscopic procedure as well as a recently paralyzed user of a powered wheelchair must learn to operate machinery via interfaces that translate their actions into commands for the external device. Mathematically, we describe this type of learning as a deterministic dynamical process, whose state is the evolving forward and inverse internal models of the interface. The forward model predicts the outcomes of actions while the inverse model generates actions designed to attain desired outcomes. Both the mathematical analysis of learning dynamics and the performance observed in a group of subjects demonstrate first-order exponential convergence of the learning process toward a particular state that depends only on the initial inverse and forward models and on the supplied sequence of targets. Noise is not only present but necessary for the convergence of learning through the minimization of the difference between actual and predicted outcomes.

Author summary

Several studies have suggested that as we learn a new skill our brain forms representations, or “internal models”, of the skill and of the environment in which we operate. Theories of motor learning postulate that the brain builds forward models that predict the sensory consequences of motor commands, and inverse models that generate successful commands from planned movements. We test this hypothesis taking advantage of a special interface that generates a novel relation between the subject’s actions and the position of a cursor on a computer monitor, thus allowing subjects to control an external device by movements of their body. We recorded the motions of the body and of the cursor, and obtained estimates of both forward and inverse models. We followed how these estimates evolved in time as subjects practiced and acquired a new skill. We found that the description of learning as a simple deterministic process driven by the sequence of targets is sufficient to capture the observed convergence to a single solution of the inverse model among an infinite variety of alternative possibilities. This work is relevant to the study of fundamental learning mechanisms as well as to the design of intelligent interfaces for people with paralysis.
Strain-level diversity impacts cheese rind microbiome assembly and function
Authors: Niccum Brittany A. , Kastman Erik K. , Kfoury Nicole , Robbat Albert , Wolfe Benjamin E.
Published: May 2019

Taxa that are consistently found across microbial communities are often considered members of a core microbiome. One common assumption is that taxonomically identical core microbiomes will have similar dynamics and functions across communities. However, strain-level genomic and phenotypic variation of core taxa could lead to differences in how core microbiomes assemble and function. Using cheese rinds, we tested whether taxonomically identical core microbiomes isolated from distinct locations have similar assembly dynamics and functional outputs. We first isolated the same three bacterial species (Staphylococcus equorum, Brevibacterium auranticum, andBrachybacterium alimentarium) from nine cheeses produced in different regions of the United States and Europe. Comparative genomics identified distinct phylogenetic clusters and significant variation in genome content across the nine core microbiomes. When we assembled each core microbiome with initially identical compositions, community structure diverged over time resulting in communities with different dominant taxa. The core microbiomes had variable responses to abiotic (high salt) and biotic (the fungusPenicillium) perturbations, with some communities showing no response and others substantially shifting in composition. Functional differences were also observed across the nine core communities, with considerable variation in pigment production (light yellow to orange) and composition of volatile organic compound profiles emitted from the rinds (nutty to sulfury). Our work demonstrates that core microbiomes isolated from independent communities may not function in the same manner due to strain-level variation of core taxa. Strain-level diversity across core cheese rind microbiomes may contribute to variability in the aesthetics and quality of surface-ripened cheeses.
Estimation of the Hemoglobin Glycation Rate Constant
Authors: Kameyama Masashi , Okumiya Toshika , Tokuhiro Shinji , Matsumura Yoshihisa , Matsui Hirotaka , Ono Yasuhiro , Iwasaka Tsuyoshi , Hiratani Kazuyuki , Koga Masafumi
Published: May 2019

Aim

In a previous study, a method of obtaining mean erythrocyte age (MRBC) from HbA1c and average plasma glucose (AG) was proposed. However, the true value of the hemoglobin glycation constant (kgdL/mg/day), required for this model has yet to be well characterized. Another study also proposed a method of derivingMRBCfrom erythrocyte creatine (EC). Utilizing these formulae, this study aimed to determine a more accurate estimate ofkg.

Methods

107 subjects including 31 patients with hemolytic anemia and 76 subjects without anemia were included in this study. EC and HbA1c data were analyzed, andMRBCusing HbA1c, AG and the newly-derived constant,kgwere compared toMRBCusing traditional51Cr in three patients whose data were taken from previous case studies.

Result

A value of 7.0 × 10−6dL/mg/day was determined forkg.MRBCusing HbA1c, AG andkgwere found to no be significantly different (pairedt-test,p= 0.45) toMRBCusing traditional51Cr.

Conclusions

kgenables the estimation ofMRBCfrom HbA1c and AG.
The Deubiquitinating Enzyme USP37 Stabilizes CHK1 to Promote the Cellular Response to Replication Stress
Authors: Singh Mayank , Burrows Amy C. , Torres Adrian E. , Pal Debjani , Stromberg Benjamin , Insinna Christine , Dickson Andrew , Westlake Christopher J. , Summers Matthew K.
Published: May 2019

The deubiquitinating enzyme USP37 is known to contribute to timely S-phase onset. However, it is not clear if USP37 is essential beyond S-phase entry despite expression and activity of USP37 peaking within S-phase. Here, we determine that USP37-depleted cells exhibited altered S-phase kinetics and harbored increased levels of the replication stress and DNA damage markers γH2AX and 53BP1 in response to perturbed replication. Depletion of USP37 also reduced cellular proliferation and led to increased sensitivity to agents that induce replication stress. Underlying the increased sensitivity, we found that the checkpoint kinase CHK1 is destabilized in the absence of USP37, attenuating its function. We further demonstrated that USP37 deubquitinates and stabilizes CHK1. Our data contribute to an evolving understanding of UPS37 as a multifaceted regulator of genome regulation.
N-terminal ubiquitination of amyloidogenic proteins triggers removal of their oligomers by the proteasome holoenzyme
Authors: Ye Yu , Klenerman David , Finley Daniel
Published: May 2019

Aggregation of amyloidogenic proteins is an abnormal biological process implicated in neurodegenerative disorders. While the aggregation process of amyloid-forming proteins has been studied extensively, the mechanism of aggregate removal is poorly understood. We recently demonstrated that proteasomes could fragment filamentous aggregates into smaller entities, restricting aggregate size[1]. Here, we show in vitro that UBE2W can modify the N-terminus of both αS and tauK18 with a single ubiquitin moiety. We demonstrate that an engineered N-terminal Ub modification changes the aggregation process of both proteins, resulting in the formation of structurally distinct aggregates. Single-molecule approaches further reveal that the proteasome can target soluble oligomers assembled from Ub-modified proteins independent of its peptidase activity, consistent with our recently reported fibril-fragmenting activity. Based on these results, we propose that proteasomes are able to target oligomers assembled from N-terminally ubiquitinated proteins. Our data suggest a possible disassembly mechanism by which N-terminal ubiquitination and the proteasome may together impede aggregate formation.
MemSTATS: A Benchmark Set of Membrane Protein Symmetries and Pseudo-Symmetries
Authors: Aleksandrova Antoniya A. , Sarti Edoardo , Forrest Lucy R.
Published: May 2019

In membrane proteins, symmetry and pseudo-symmetry often have functional or evolutionary implications. However, available symmetry detection methods have not been tested systematically on this class of proteins due to the lack of an appropriate benchmark set. Here we present MemSTATS, a publicly-available benchmark set of both quaternary and internal symmetries in membrane protein structures described in terms of order, repeated elements, and orientation of the axis with respect to the membrane plane. Moreover, using MemSTATS, we compare the performance of four widely-used symmetry detection algorithms and highlight specific challenges and areas for improvement in the future.
The methyl cycle is a conserved regulator of biological clocks
Authors: Fustin Jean-Michel , Ye Shiqi , Rakers Christin , Versteven Marijke , Cargill Samantha J. , Tamai T. Katherine , Xu Yao , Jabbur Maria Luísa , Kojima Rika , Lamberti Melisa L. , Yoshioka-Kobayashi Kumiko , Whitmore David , Kageyama Ryoichiro , Matsuo Takuya , Stanewsky Ralf , Golombek Diego A. , Johnson Carl Hirschie , van Ooijen Gerben , Okamura Hitoshi
Published: May 2019

The methyl cycle is a universally conserved metabolic pathway operating in prokaryotes and eukaryotes. In this pathway, the amino acid methionine is used to synthesize S-adenosylmethionine, the methyl donor co-substrate in the methylation of nucleic acids, histone and non-histone proteins and many other molecules within the cell. The methylation of nucleic acids and proteins is the foundation of epigenetic and epitranscriptomic regulations of gene expression, but whether the methyl cycle centrally regulates gene expression and function by controlling the availability of methyl moieties is poorly understood.

From cyanobacteria to humans, a circadian clock that involves an exquisitely regulated transcription-translation-feedback loop driving oscillations in gene expression and orchestrating physiology and behavior has been described. We reported previously that inhibition of the methyl cycle in mammalian cells caused the lengthening of the period of these oscillations, suggesting the methyl cycle may indeed act as a central regulator of gene expression, at least in mammals. Here, we investigated whether the methyl cycle, given its universal presence among living beings, regulates the circadian clock in species across the phylogenetic tree of life.

We reveal a remarkable evolutionary conservation of the link between the methyl cycle and the circadian clock. Moreover, we show that the methyl cycle also regulates the somite segmentation clock, another transcription-translation negative feedback loop-based timing mechanism that orchestrate embryonic development in vertebrates, highlighting the methyl cycle as a master regulator of biological clocks.

SIGNIFICANCE STATEMENT

Here we reveal that the methyl cycle, a universal metabolic pathway leading to the synthesis of S-adenosylmethionine, the methyl donor co-substrate in virtually all transmethylation reactions within the cell, is a conserved regulator of biological clocks. These discoveries highlight the methyl cycle as a metabolic hub that regulates gene expression via the availability of methyl moieties for the methylation of nucleic acids, proteins and many other molecules with the cell.
Monogenic and polygenic inheritance become instruments for clonal selection
Authors: Loh Po-Ru , Genovese Giulio , McCarroll Steven A
Published: May 2019

Clonally expanded blood cells with somatic mutations (clonal hematopoiesis, CH) are commonly acquired with age and increase risk of later blood cancer. To identify genes and mutations that give selective advantage to mutant clones, we identified among 482,789 UK Biobank participants some 19,632 autosomal mosaic chromosomal alterations (mCAs), including deletions, duplications, and copy number-neutral loss of heterozygosity (CNN-LOH). Analysis of these acquired mutations, along with inherited genetic variation, revealed 52 inherited, rare, large-effect coding or splice variants (in seven genes) that greatly (odds ratios of 11 to 758) increased vulnerability to CH with specific acquired CNN-LOH mutations. Acquired mutations systematically replaced the inherited risk alleles (at MPL) or duplicated them to the homologous chromosome (at FH, NBN, MRE11, ATM, SH2B3, and TM2D3). Three of the seven genes (MRE11, NBN, and ATM) encode components of the MRN-ATM pathway, which limits cell division after DNA damage and telomere attrition; another two (MPL, SH2B3) encode proteins that regulate stem cell self-renewal. In addition to these monogenic inherited forms of CH, we found a common and surprisingly polygenic form: CNN-LOH mutations across the genome tended to cause chromosomal segments with alleles that promote hematopoietic cell proliferation to replace their homologous (allelic) counter-parts, increasing polygenic drive for blood-cell proliferation traits. This dynamic reveals a challenge for lifelong cytopoiesis in any genetically diverse species: individuals inherit unequal proliferative genetic potentials on paternally and maternally derived chromosomepairs, and readily-acquired mutations that replace chromosomal segments with their homologous counterparts give selective advantage to mutant cells.
ASA3P: An automatic and scalable pipeline for the assembly, annotation and higher level analysis of closely related bacterial isolates
Authors: Schwengers Oliver , Hoek Andreas , Fritzenwanker Moritz , Falgenhauer Linda , Hain Torsten , Chakraborty Trinad , Goesmann Alexander
Published: May 2019

Whole genome sequencing of bacteria has become daily routine in many fields. Advances in DNA sequencing technologies and continuously dropping costs have resulted in a tremendous increase in the amounts of available sequence data. However, comprehensive in-depth analysis of the resulting data remains an arduous and time consuming task. In order to keep pace with these promising but challenging developments and to transform raw data into valuable information, standardized analyses and scalable software tools are needed. Here, we introduce ASA3P, a fully automatic, locally executable and scalable assembly, annotation and analysis pipeline for bacterial genomes. The pipeline automatically executes necessary data processing steps, i.e. quality clipping and assembly of raw sequencing reads, scaffolding of contigs and annotation of the resulting genome sequences. Furthermore, ASA3P conducts comprehensive genome characterizations and analyses, e.g. taxonomic classification, detection of antibiotic resistance genes and identification of virulence factors. All results are presented via an HTML5 user interface providing aggregated information, interactive visualizations and access to intermediate results in standard bioinformatics file formats. We distribute ASA3P in two versions: a locally executable Docker container for small-to-medium-scale projects and an OpenStack based cloud computing version able to automatically create and manage self-scaling compute clusters. Thus, automatic and standardized analysis of hundreds of bacterial genomes becomes feasible within hours. The software and further information is available at: http://asap.computational.bio.
Evidence of the Cost-Efficiency of Scale as seen in Polio Vaccination and Surveillance Costs
Authors: Hagedorn Brittany L. , Mercer Laina D. , Chabot-Couture Guillaume
Published: May 2019

This analysis examined how polio program costs vary with scale for vaccination and disease surveillance, based on historical budget data published by the Global Polio Eradication Initiative (GPEI) from 2005 to 2018. We applied a linear mixed effects regression model in order to understand the cost structure of the historical GPEI budgets, with the goal that lessons learned from polio may be extended to other global disease elimination programs. Our findings demonstrate that there are economies of scale for vaccine delivery operations and for disease surveillance, which means that larger programs can leverage fixed costs and achieve better cost-efficiency as they scale. This finding should enable decision makers to create more reliable budgets, which support fundraising and optimal resource allocation. They also provide insight into how cost effectiveness changes as programs scale up during progressive disease control and elimination, as well as what level of resources are needed to sustain a program that is scaling back post-eradication and through to certification.
Conservation of the structure and function of bacterial tryptophan synthases
Authors: Michalska Karolina , Gale Jennifer , Joachimiak Grazyna , Chang Changsoo , Hatzos-Skintges Catherine , Nocek Boguslaw , Johnston Stephen E. , Bigelow Lance , Bajrami Besnik , Jedrzejczak Robert P. , Wellington Samantha , Hung Deborah T. , Nag Partha P. , Fisher Stewart L. , Endres Michael , Joachimiak Andrzej
Published: May 2019

Tryptophan biosynthesis is one of the most characterized processes in bacteria, in which the enzymes fromSalmonella typhimuriumandEscherichia coliserve as model systems. Tryptophan synthase (TrpAB) catalyzes the final two steps of tryptophan biosynthesis in plants, fungi and bacteria. This pyridoxal 5′-phosphate (PLP)-dependent enzyme consists of two protein chains, α (TrpA) and β (TrpB), functioning as a linear αββα heterotetrameric complex containing two TrpAB units. The reaction has a complicated, multistep mechanism resulting in the β-replacement of the hydroxyl group of L-serine with an indole moiety. Recent studies have shown that functional TrpAB is required for the survival of pathogenic bacteria in macrophages and for evading host defense. Therefore, TrpAB is a promising target for drug discovery, as its orthologs include enzymes from the important human pathogensStreptococcus pneumoniae,Legionella pneumophilaandFrancisella tularensis, the causative agents of pneumonia, legionnaires' disease and tularemia, respectively. However, specific biochemical and structural properties of the TrpABs from these organisms have not been investigated. To fill the important phylogenetic gaps in the understanding of TrpABs and to uncover unique features of TrpAB orthologs to spearhead future drug-discovery efforts, the TrpABs fromL. pneumophila,F. tularensisandS. pneumoniaehave been characterized. In addition to kinetic properties and inhibitor-sensitivity data, structural information gathered using X-ray crystallography is presented. The enzymes show remarkable structural conservation, but at the same time display local differences in both their catalytic and allosteric sites that may be responsible for the observed differences in catalysis and inhibitor binding. This functional dissimilarity may be exploited in the design of species-specific enzyme inhibitors.
The acquisition of the Arabic construct state (CS) constructions by Arabic-speaking children with ASD
Authors: Altakhaineh Abdel Rahman Mitib , Alkhatib Razan N.
Published: May 2019

Purpose

The purpose of this paper is to investigate whether age plays a role in the acquisition of construct state (CS) constructions in Arabic by 14 children with autism spectrum disorder (ASD). It also examined the challenges faced by children with ASD in producing different types of CS constructions. Finally, the study analysed the sources of difficulties children with ASD encounter during the learning process of the CS.

Design/methodology/approach

For the purposes of this study, the participants were asked to orally complete short sentences with the help of illustrative pictures.

Findings

Results revealed that the age of the 14 children with ASD plays a role in the acquisition of CS constructions. Children of age 12–15 performed better than those of age 8 and 10. Results also showed that children with ASD performed better in producing phrases rather than compounds. Moreover, the participants performed better on endocentric compounds as opposed to exocentric ones. Finally, analysing the errors produced on the text revealed that the acquisition of head direction precedes definiteness.

Originality/value

The topic of the study has not been investigated yet and the study concluded with some important findings concerning teaching Arabic CS to children with ADS.