bluuebunny/crossref_metadata_2025 huggingface dataset:
Allele-specific single-cell RNA sequencing reveals different architectures of intrinsic and extrinsic gene expression noises
Authors: Sun Mengyi , Zhang Jianzhi
Published: November 2019

Gene expression noise refers to the variation of the expression level of a gene among isogenic cells in the same environment, and has two sources: extrinsic noise arising from the disparity of the cell state and intrinsic noise arising from the stochastic process of gene expression in the same cell state. Due to the low throughput of the existing method for measuring the two noise components, the architectures of intrinsic and extrinsic expression noises remain elusive. Using allele-specific single-cell RNA sequencing, we here estimate the two noise components of 3975 genes in mouse fibroblast cells. Our analyses verify predicted influences of several factors such as the TATA-box and microRNA targeting on intrinsic or extrinsic noises and reveal gene function-associated noise trends implicating the action of natural selection. These findings unravel differential regulations, optimizations, and biological consequences of intrinsic and extrinsic noises and can aid the construction of desired synthetic circuits.
Accelerated FDPS: Algorithms to use accelerators with FDPS
Authors: Iwasawa Masaki , Namekata Daisuke , Nitadori Keigo , Nomura Kentaro , Wang Long , Tsubouchi Miyuki , Makino Junichiro
Published: November 2019

We describe algorithms implemented in FDPS (Framework for Developing Particle Simulators) to make efficient use of accelerator hardware such as GPGPUs (general-purpose computing on graphics processing units). We have developed FDPS to make it possible for researchers to develop their own high-performance parallel particle-based simulation programs without spending large amounts of time on parallelization and performance tuning. FDPS provides a high-performance implementation of parallel algorithms for particle-based simulations in a “generic” form, so that researchers can define their own particle data structure and interparticle interaction functions. FDPS compiled with user-supplied data types and interaction functions provides all the necessary functions for parallelization, and researchers can thus write their programs as though they are writing simple non-parallel code. It has previously been possible to use accelerators with FDPS by writing an interaction function that uses the accelerator. However, the efficiency was limited by the latency and bandwidth of communication between the CPU and the accelerator, and also by the mismatch between the available degree of parallelism of the interaction function and that of the hardware parallelism. We have modified the interface of the user-provided interaction functions so that accelerators are more efficiently used. We also implemented new techniques which reduce the amount of work on the CPU side and the amount of communication between CPU and accelerators. We have measured the performance of N-body simulations on a system with an NVIDIA Volta GPGPU using FDPS and the achieved performance is around 27% of the theoretical peak limit. We have constructed a detailed performance model, and found that the current implementation can achieve good performance on systems with much smaller memory and communication bandwidth. Thus, our implementation will be applicable to future generations of accelerator system.
Taxa–area and distance–decay relationships of unicellular eukaryotes along an elevation gradient of mountainous freshwater ecosystems
Authors: Macingo Sofia C , Kormas Konstantinos A , Oikonomou Andreas , Karayanni Hera
Published: November 2019

Unicellular eukaryotes have pivotal ecological roles in aquatic ecosystems by participating in biogeochemical processes and structuring microbial food webs. However, revealing their biogeographical patterns remains challenging, as it is reflected in the rather limited available knowledge. In this study, two central patterns, the taxa–area and the distance–decay relationships, were tested for freshwater unicellular eukaryotes. Sampling was performed in 31 mountainous freshwater ecosystems in Thessaly (Greece). Sampling sites had different geohydromorphological characteristics (altitude, 124–704 m; depth, 0.3–1 m; surface area, 188–123 000 m2; geographical distances, 0.03–48.4 km). Unicellular eukaryote diversity was assessed by 18S rRNA gene diversity with high-throughput sequencing. Five supergroups (Stramenopiles, Alveolata, Rhizaria, Archaeplastida and Opisthokonta) were found with the most abundant taxa being Stramenopiles and Alveolata. Aquatic unicellular eukaryotes showed statistically significant but weak DDR and TAR. This can be attributed to the large proportion of specialists (91.9% of operational taxonomic units according to Levin’s index). These results indicate that although mountainous pools and ponds can host high diversity of unicellular eukaryotes, the shaping of their communities is mainly regulated by niche-specific processes and environmental filtering and to a lesser extent by species dispersion processes.
Unmet needs of women with GDM: a health needs assessment in Sandwell, West Midlands
Authors: Plant Nicola , Šumilo Dana , Chapman Rachel , Webber Jonathan , Saravanan Ponnusamy , Nirantharakumar Krishnarajah
Published: November 2019

Background

Gestational diabetes mellitus (GDM) affects over 4% of pregnancies in England. We investigated GDM epidemiology within ethnically diverse population and the current offer of services to women with previous GDM to reduce their type 2 diabetes mellitus (T2DM) risk.

Methods

(i) Analysis of routinely collected maternity data examining GDM incidence and risk factors; (ii) local authority self-assessment questionnaire on public health interventions targeting women with previous GDM and (iii) service development discussions regarding the current pathway and areas for improvement.

Results

Of 9390 births between 2014 and 2018, 6.8% had a record of GDM. High body mass index (BMI), maternal age, and ethnicity (South Asian and some mixed ethnic backgrounds) were independent predictors of GDM. There were no public health commissioned services specifically targeting women with previous GDM. Weaknesses in transition from secondary to primary care and areas for improvement when screening for GDM were identified.

Conclusions

GDM burden in this population was high. Awareness should be raised on the importance of regular glucose testing and lifestyle modification to delay or prevent progression to T2DM, particularly within high risk groups. The potential for health visitors to contribute to this should be explored. Commissioners should review evidence to develop a flexible lifestyle services model to meet the specific needs of these women.
Work productivity loss among rheumatoid arthritis patients in India: a qualitative study
Authors: Jain Avinash , Aggarwal Amita , Adams Jo , Jordan Rachel E , Sadhra Steven , Dubey Shirish , Allen Kerry , Kumar Kanta
Published: November 2019

Objective

The aim was to explore the extent to which RA impacts work productivity in patients living with RA in India.

Methods

Face-to-face semi-structured interviews took place with 13 male and seven female patients attending outpatient clinics at Sanjay Gandhi Postgraduate Institute of Medical Sciences, India, living with RA. Patients who were currently working were recruited. Data were audio recorded, transcribed by an independent translation company and analysed using the framework method of thematic analysis.

Results

Four themes that explained patients’ experiences of coping with work whilst having RA were identified. These were as follows: balancing act of work and RA, in which participants expressed their day-to-day struggle of living with RA and coping at work; workplace adaptation after RA, in which participants shared insights into communicating with employers and their efforts to adapt at the workplace; support from others and information to manage RA and work, in which participants considered seeking support from different sources that would help them cope at work and understand RA; and wanting a better support mechanism, in which participants made recommendations that could help them to cope at work.

Conclusion

This is the first study to explore the impact of RA on patients’ work productivity in India. Patients might have different support needs compared with previous studies in other countries. Patients seem to be adopting additional coping strategies not addressed by current interventions or country systems, which might not be sufficient to support patients in remaining employed. Patients made future recommendations.
How to protect the taxpayer against abuse in the use of exchanges of information by the French tax authorities?
Authors: Naudin Maryse
Published: November 2019

The contemporary global financial environment legitimates transparency of information worldwide. The question of this legitimacy is no longer a matter for debate, and it is now necessary to focus on finding ways to protect taxpayers against the misuse of information collected. The tax aspects are far from being the most important, as information can also be used against fundamental principles. In order to face the risks of the inappropriate use of exchange of information, the taxpayer’s advisors in all States should cooperate and unify their force and determination to improve the protection of the right of a defense.
Family-based treatment for children and adolescents with eating disorders: a mixed-methods evaluation of a blended evidence-based implementation approach
Authors: Couturier Jennifer , Kimber Melissa , Barwick Melanie , Woodford Tracy , Mcvey Gail , Findlay Sheri , Webb Cheryl , Niccols Alison , Lock James
Published: November 2019

In this study, we evaluated a blended implementation approach with teams learning to provide family-based treatment (FBT) to adolescents with eating disorders.

Four sites participated in a sequential mixed method pre–post study to evaluate the implementation of FBT in their clinical settings. The implementation approach included: (a) preparatory site visits; (b) the establishment of implementation teams; (c) a training workshop; (d) monthly clinical consultation; (e) monthly implementation consultation; and (f) fidelity assessment. Quantitative measures examining attitudes toward evidence-based practice, organizational learning environment and organizational readiness for change, as well as, individual readiness for change were delivered pre- and postimplementation. Correlational analyses were used to examine associations between baseline variables and therapist fidelity to FBT. Fundamental qualitative description guided the sampling and data collection for the qualitative interviews performed at the conclusion of the study. Seventeen individuals participated in this study (nine therapists, four medical practitioners, and four administrators). The predetermined threshold of implementation success of 80% fidelity in every FBT session was achieved by only one therapist. However, mean fidelity scores were similar to those reported in other studies. Participant attitudes, readiness, and self-efficacy were not associated with fidelity and did not change significantly from pre- to postimplementation. In qualitative interviews, all participants reported that the implementation intervention was helpful in adopting FBT. Our blended implementation approach was well received by participants. A larger trial is needed to determine which implementation factors predict FBT fidelity and impact patient outcomes.
Inoculum and Infection Dynamics of Polystigma amygdalinum in Almond Orchards in Spain
Authors: Zúñiga Erick , Romero Joaquín , Ollero-Lara Andrés , Lovera María , Arquero Octavio , Miarnau Xavier , Torguet Laura , Trapero Antonio , Luque Jordi
Published: November 2019

Red leaf blotch (RLB) disease of almond, caused by Polystigma amygdalinum, is an important foliar disease in most production regions of the Mediterranean basin and the Middle East because severe infections may cause a premature defoliation of the tree. Some key aspects on the epidemiology of P. amygdalinum were studied in multiyear trials in two almond-growing regions in Spain, which included the seasonal development of perithecia and production and germination of ascospores along with the disease incubation and plant infectivity periods. Our results showed that primary inoculum was available in extended periods (January to August). Significant differences in ascospore amounts among regions, higher in the southern Andalusia and lower in the northern Catalonia, and years of study were detected. The factors geographical location, sampling period, and evaluation year were found significant on the development of P. amygdalinum perithecia. Variable ascospore germination rates were observed from April to July: >15% but rarely exceeding 30%. The RLB infectivity period in Catalonia extended from March to mid-June, whereas in Andalusia it was from March to May. The incubation period was mainly in a range of 5 to 10 weeks in Catalonia. The environmental conditions of October to January influence the available ascospore amounts in the next season. RLB infection occurs in spring to summer when mean temperatures are in the range 10 to 20°C. These results represent the first step in developing a prediction model of the disease that might serve as a tool for the control of RLB.
Ginsenoside Rg3 suppresses the NLRP3 inflammasome activation through inhibition of its assembly
Authors: Shi Yuhua , Wang Huanan , Zheng Mengjie , Xu Wei , Yang Yang , Shi Fushan
Published: November 2019

Ginsenoside Rg3 is one of the main constituents of Panax ginseng. Compelling evidence has demonstrated that ginsenoside Rg3 is capable of inhibiting inflammation. However, the mechanism mediating its anti‐inflammatory effects remain unclear. Here we show that ginsenoside Rg3 blocks IL‐1β secretion and caspase‐1 activation through inhibiting LPS priming and the NLRP3 inflammasome activation in human and mouse macrophages. Rg3 specifically inhibits activation of NLRP3 but not the NLRC4 or AIM2 inflammasomes. In addition, Rg3 has no effect on upstream regulation of NLRP3 inflammasome, such as K+ efflux, ROS production, or mitochondrial membrane potential. Mechanistically, Rg3 abrogates NEK7‐NLRP3 interaction, and subsequently inhibits NLRP3‐ASC interaction, ASC oligomerization, and speckle formation. More importantly, Rg3 can reduce IL‐1β secretion induced by LPS in mice and protect mice from lethal endotoxic shock. Thus, our findings reveal an anti‐inflammatory mechanism for Rg3 and suggest its potential use in NLRP3‐driven diseases.
Eco-evolutionary feedbacks link prey adaptation to predator performance
Authors: Fryxell David C. , Wood Zachary T. , Robinson Rebecca , Kinnison Michael T. , Palkovacs Eric P.
Published: November 2019

Eco-evolutionary feedbacks may determine the outcome of predator–prey interactions in nature, but little work has been done to quantify the feedback effect of short-term prey adaptation on predator performance. We tested the effects of prey availability and recent (less than 100 years) prey adaptation on the feeding and growth rate of largemouth bass (
Micropterus salmoides
), foraging on western mosquitofish (
Gambusia affinis
). Field surveys showed higher densities and larger average body sizes of mosquitofish in recently introduced populations without bass. Over a six-week mesocosm experiment, bass were presented with either a high or low availability of mosquitofish prey from recently established populations either naive or experienced with bass. Naive mosquitofish were larger, less cryptic and more vulnerable to bass predation compared to their experienced counterparts. Bass consumed more naive prey, grew more quickly with naive prey, and grew more quickly per unit biomass of naive prey consumed. The effect of mosquitofish history with the bass on bass growth was similar in magnitude to the effect of mosquitofish availability. In showing that recently derived predation-related prey phenotypes strongly affect predator performance, this study supports the presence of reciprocal predator–prey trait feedbacks in nature.
Late Cretaceous domatia reveal the antiquity of plant–mite mutualisms in flowering plants
Authors: Maccracken S. Augusta , Miller Ian M. , Labandeira Conrad C.
Published: November 2019

Mite houses, or acarodomatia, are found on the leaves of over 2000 living species of flowering plants today. These structures facilitate tri-trophic interactions between the host plant, its fungi or herbivore adversaries, and fungivorous or predaceous mites by providing shelter for the mite consumers. Previously, the oldest acarodomatia were described on a Cenozoic Era fossil leaf dating to 49 Myr in age. Here, we report the first occurrence of Mesozoic Era acarodomatia in the fossil record from leaves discovered in the Upper Cretaceous Kaiparowits Formation (76.6–74.5 Ma) in southern UT, USA. This discovery extends the origin of acarodomatia by greater than 25 Myr, and the antiquity of this plant–mite mutualism provides important constraints for the evolutionary history of acarodomatia on angiosperms.
Chinese and UK participants' preferences for physical attractiveness and social status in potential mates
Authors: Zhang Lingshan , Wang Hongyi , Lee Anthony J. , DeBruine Lisa M. , Jones Benedict C.
Published: November 2019

Men are hypothesized to show stronger preferences for physical attractiveness in potential mates than women are, particularly when assessing the attractiveness of potential mates for short-term relationships. By contrast, women are thought to show stronger preferences for social status in potential mates than men are, particularly when assessing the attractiveness of potential mates for long-term relationships. These mate-preference sex differences are often claimed to be ‘universal' (i.e. stable across cultures). Consequently, we used an established ‘budget-allocation' task to investigate Chinese and UK participants' preferences for physical attractiveness and social status in potential mates. Confirmatory analyses replicated these sex differences in both samples, consistent with the suggestion that they occur in diverse cultures. However, confirmatory analyses also showed that Chinese women had stronger preferences for social status than UK women did, suggesting cultural differences in the magnitude of mate-preference sex differences can also occur.
Territorial landscapes: incorporating density-dependence into wolf habitat selection studies
Authors: O'Neil Shawn T. , Beyer Dean E. , Bump Joseph K.
Published: November 2019

Habitat selection is a process that spans space, time and individual life histories. Ecological analyses of animal distributions and preferences are most accurate when they account for inherent dynamics of the habitat selection process. Strong territoriality can constrain perception of habitat availability by individual animals or groups attempting to colonize or establish new territory. Because habitat selection is a function of habitat availability, broad-scale changes in habitat availability or occupancy can drive density-dependent habitat functional responses. We investigated density-dependent habitat selection over a 19-year period of grey wolf (
Canis lupus
) recovery in Michigan, USA, using a generalized linear mixed model framework to develop a resource selection probability function (RSPF) with habitat coefficients conditioned on random effects for wolf packs and random year intercepts. In addition, we allowed habitat coefficients to vary as interactions with increasing wolf density over space and time. Results indicated that pack presence was driven by factors representing topography, human development, winter prey availability, forest structure, roads, streams and snow. Importantly, responses to many of these predictors were density-dependent. Spatio-temporal dynamics and population changes can cause considerable variation in wildlife–habitat relationships, possibly confounding interpretation of conventional habitat selection models. By incorporating territoriality into an RSPF analysis, we determined that wolves' habitat use in Michigan shifted over time, for example, exhibiting declining responses to winter prey indices and switching from positive to negative responses with respect to stream densities. We consider this an important example of a habitat functional response in wolves, driven by colonization, density-dependence and changes in occupancy during a time period of range expansion and population increase.
Perspective-taking across cultures: shared biases in Taiwanese and British adults
Authors: Wang J. Jessica , Tseng Philip , Juan Chi-Hung , Frisson Steven , Apperly Ian A.
Published: November 2019

The influential hypothesis by Markus & Kitayama (Markus, Kitayama 1991.
Psychol. Rev.
98
, 224) postulates that individuals from interdependent cultures place others above self in interpersonal contexts. This led to the prediction and finding that individuals from interdependent cultures are less egocentric than those from independent cultures (Wu, Barr, Gann, Keysar 2013.
Front. Hum. Neurosci.
7
, 1–7; Wu, Keysar. 2007
Psychol. Sci.
18
, 600–606). However, variation in egocentrism can only provide indirect evidence for the Markus and Kitayama hypothesis. The current study sought direct evidence by giving British (independent) and Taiwanese (interdependent) participants two perspective-taking tasks on which an other-focused ‘altercentric’ processing bias might be observed. One task assessed the calculation of simple perspectives; the other assessed the use of others' perspectives in communication. Sixty-two Taiwanese and British adults were tested in their native languages at their home institutions of study. Results revealed similar degrees of both altercentric and egocentric interference between the two cultural groups. This is the first evidence that listeners account for a speaker's limited perspective at the cost of their own performance. Furthermore, the shared biases point towards similarities rather than differences in perspective-taking across cultures.
Overwintering tropical herbivores accelerate detritus production on temperate reefs
Authors: Zarco-Perello Salvador , Langlois Tim J. , Holmes Thomas , Vanderklift Mathew A. , Wernberg Thomas
Published: November 2019

The tropicalization of temperate marine ecosystems can lead to increased herbivory rates, reducing the standing stock of seaweeds and potentially causing increases in detritus production. However, long-term studies analysing these processes associated with the persistence of tropical herbivores in temperate reefs are lacking. We assessed the seasonal variation in abundances, macrophyte consumption, feeding modes and defecation rates of the range-extending tropical rabbitfishSiganus fuscescensand the temperate silver drummerKyphosus sydneyanusand herring caleOlisthops cyanomelason tropicalized reefs of Western Australia. Rabbitfish overwintered in temperate reefs, consumed more kelp and other macrophytes in all feeding modes, and defecated more during both summer and winter than the temperate herbivores. Herbivory and defecation increased with rabbitfish abundance, but this was dependent on temperature, with higher rates attained by big schools during summer and lower rates in winter. Still, rabbitfish surpassed temperate herbivores, leading to a fivefold acceleration in the transformation of macrophyte standing stock to detritus, a function usually attributed to sea urchins in kelp forests. Our results suggest that further warming and tropicalization will not only increase primary consumption and affect the habitat structure of temperate reefs but also increase detritus production, with the potential to modify energy pathways.
Polarization of foliar reflectance: novel host plant cue for insect herbivores
Authors: Blake Adam J. , Go Matthew C. , Hahn Gina S. , Grey Hayley , Couture Samuel , Gries Gerhard
Published: November 2019

Insect herbivores exploit plant cues to discern host and non-host plants. Studies of visual plant cues have focused on colour despite the inherent polarization sensitivity of insect photoreceptors and the information carried by polarization of foliar reflectance, most notably the degree of linear polarization (DoLP; 0–100%). TheDoLPof foliar reflection was hypothesized to be a host plant cue for insects but was never experimentally tested. Here, we show that cabbage white butterflies,Pieris rapae(Pieridae), exploit theDoLPof foliar reflections to discriminate among plants. In experiments with paired digital plant images,P. rapaefemales preferred images of the host plant cabbage with a lowDoLP(31%) characteristic of cabbage foliage over images of a non-host potato plant with a higherDoLP(50%). By reversing theDoLPof these images, we were able to shift the butterflies' preference for the cabbage host plant image to the potato non-host plant image, indicating that theDoLPhad a greater effect on foraging decisions than the differential colour, intensity, or shape of the two plant images. Although previously not recognized, theDoLPof foliar reflection is an essential plant cue that may commonly be exploited by foraging insect herbivores.
Sexual conflict mediated by ecological sex differences can generate diverse patterns of transgenerational plasticity
Authors: Burke Nathan William , Nakagawa Shinichi , Bonduriansky Russell
Published: November 2019

Transgenerational plasticity (TGP) occurs when the environment experienced by parents induces changes in traits of offspring and/or subsequent generations. Such effects can be adaptive or non-adaptive and are increasingly recognised as key determinants of health, cognition, development and performance across a wide range of taxa, including humans. While the conditions that favour maternal TGP are well understood, rapidly accumulating evidence indicates that TGP can be maternal or paternal, and offspring responses can be sex-specific. However, the evolutionary mechanisms that drive this diversity are unknown. We used an individual-based model to investigate the evolution of TGP when the sexes experience different ecologies. We find that adaptive TGP rarely evolves when alleles at loci that determine offspring responses to environmental information originating from the mother and father are subject to sexually antagonistic selection. By contrast, duplication and sex-limitation of such loci can allow for the evolution of a variety of sex-specific responses, including non-adaptive sex-specific TGP when sexual selection is strong. Sexual conflict could therefore help to explain why adaptive TGP evolves in some species but not others, why sons and daughters respond to parental signals in different ways, and why complex patterns of sex-specific TGP may often be non-adaptive.
Novel methodology for assessing total recovery time in response to unexpected perturbations while walking
Authors: Rosenblum Uri , Kribus-Shmiel Lotem , Zeilig Gabi , Bahat Yotam , Kimel-Naor Shani , Melzer Itshak , Plotnik Meir
Published: November 2019

Walking stability is achieved by adjusting the medio-lateral and anterior-posterior dimensions of the base of support (step length and step width, respectively) to contain an extrapolated center of mass. We aimed to calculate total recovery time after different types of perturbations during walking, and use it to compare young and older adults following different types of perturbations. Walking trials were performed in 12 young (age 26.92 ± 3.40 years) and 12 older (age 66.83 ± 1.60 years) adults. Perturbations were introduced at different phases of the gait cycle, on both legs and in anterior-posterior or medio-lateral directions, in random order. A novel algorithm was developed to determine total recovery time values for regaining stable step length and step width parameters following the different perturbations and compared between the two participant groups under low and high cognitive load conditions, using principal component analysis (PCA). We analyzed 829 perturbations each for step length and step width. The algorithm successfully estimated total recovery time in 91.07% of the runs. PCA and statistical comparisons showed significant differences in step length and step width recovery times between anterior-posterior and medio-lateral perturbations, but no age-related differences. Initial analyses demonstrated the feasibility of comparisons based on total recovery time calculated using our algorithm.
The neuroanatomical ultrastructure and function of a biological ring attractor
Authors: Turner-Evans Daniel B. , Jensen Kristopher T. , Ali Saba , Paterson Tyler , Sheridan Arlo , Ray Robert P. , Wolff Tanya , Lauritzen Scott , Rubin Gerald M. , Bock Davi , Jayaraman Vivek
Published: November 2019

Neural representations of head direction have been discovered in many species. A large body of theoretical work has proposed that the dynamics associated with these representations is generated, maintained, and updated by recurrent network structures called ring attractors. We performed electron microscopy-based circuit reconstruction and RNA profiling of identified cell types in the heading direction system ofDrosophila melanogasterto directly determine the underlying neural network. We identified network motifs that have been hypothesized to maintain the heading representation in darkness, update it when the animal turns, and tether it to visual cues. Functional studies provided additional support for the proposed roles of individual circuit elements. We also discovered recurrent connections between neuronal arbors with mixed pre- and post-synaptic specializations. Overall, our results confirm that theDrosophilaheading direction network contains the core components of a ring attractor while also revealing unpredicted structural features that might enhance the network’s computational power.
Cortico-thalamic dysconnectivity links with aberrant striatal dopamine in schizophreniaA simultaneous18F-DOPA-PET/resting-state fMRI study
Authors: Avram Mihai , Brandl Felix , Knolle Franziska , Cabello Jorge , Leucht Claudia , Scherr Martin , Mustafa Mona , Koutsouleris Nikolaos , Leucht Stefan , Ziegler Sibylle , Sorg Christian
Published: November 2019

In schizophrenia, among the most consistent brain changes are both aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei; however, it is unknown whether these changes are pathophysiologically related. Such a relationship is expected because cortico-thalamic-connectivity is modulated by striatal dopamine within topographically distinct, parallel but interacting cortico-basal-ganglia-thalamic circuits. We hypothesized: (1) Within-circuits, aberrant striatal dopamine contributes to aberrant cortico-thalamic-iFC, specifically, associative-striatum dopamine contributes to salience-network-thalamic-iFC, and sensorimotor-striatum dopamine to auditory-sensorimotor-network-thalamic-iFC. (2) Due to between-circuits interactions following an anterior-to-posterior gradient, salience-network-centered-system changes contribute to auditory-sensorimotor-network-centered-system changes. To test these hypotheses, 19 patients with schizophrenia during symptomatic remission of positive symptoms and 19 age- and sex-comparable controls underwent simultaneous fluorodihydroxyphenyl-L-alanine positron emission tomography (18F-DOPA-PET) and resting-state functional magnetic resonance imaging (rs-fMRI). The influx constant kicerbased on18F-DOPA-PET was used to measure dopamine synthesis capacity (DSC), indicating striatal dopamine function; correlation coefficients between rs-fMRI time-series of cortical networks and thalamic regions-of-interest were used to measure iFC. In the salience-network(SAL)-centered-system, patients had reduced associative-striatum-DSC, which correlated positively with SAL-mediodorsal-thalamus-iFC and mediated the reduction of SAL-thalamic-iFC in patients. In the auditory-sensorimotor-network(ASM)-centered-system, patients had reduced sensorimotor-striatum-DSC, which correlated positively with ASM-ventrolateral-thalamus-iFC, but did not mediate increased ASM-thalamic-iFC in patients. Finally, aberrant DSC and iFC of the SAL-centered-system mediated corresponding changes in the ASM-centered-system. Results demonstrate that cortico-thalamic-dysconnectivity links with aberrant striatal dopamine in schizophrenia - in a topographically distinct way, with an anterior-to-posterior gradient, and primary changes in the SAL-centered system.
Co-designed land-use scenarios and their implications for storm runoff and streamflow in New England
Authors: Guswa Andrew J. , Hall Brian , Cheng Chingwen , Thompson Jonathan R.
Published: November 2019

Future changes in both landscape and climate have the potential to create or exacerbate problems with stormwater management, high flows, and flooding. In New England, four plausible land-use scenarios were co-developed with stakeholders to give insight to the effects on ecosystem services of different trajectories of socio-economic connectedness and natural resource innovation. To assess the effects of these land-use scenarios on water-related ecosystem services, we applied the Soil and Water Assessment Tool to two watersheds under two climates. Differences in land use had minimal effects on the overall water balance but did affect high flows and the relative contribution of storm runoff to streamflow. For most of the scenarios, the effect was small and less than the effect due to climate change. For one scenario – envisioned to have global socio-economic connectedness and low levels of natural-resource innovation – the effects of land-use changes were comparable to the effects due to climate. For that scenario, changes to the landscape increased the annual maximum daily flow by 10%, similar to the 5-15% increase attributable to climate change. These results, which were consistent across both watersheds, can help inform planning and policies regarding land use, development, and maintenance of hydrologic ecosystem services.

Research highlights

Stakeholder-engaged scenarios provide meaningful and plausible futures for the New England landscape and assessment of effects of land-use change on storm runoff and streamflow

Effects of land use on the overall water balance are small across the landscape scenarios

Future land-use change has the potential to affect storm runoff and high flows to a degree that is comparable to the effects due to changes in climate in 2060

The degree of natural resource innovation affects storm runoff and high flows when population growth is large and has a negligible effect when population growth is low
BET inhibition disrupts transcription but retains enhancer-promoter contact
Authors: Crump Nicholas T. , Ballabio Erica , Godfrey Laura , Thorne Ross , Repapi Emmanouela , Kerry Jon , Tapia Marta , Hua Peng , Filippakopoulos Panagis , Davies James O. J. , Milne Thomas A.
Published: November 2019

In higher eukaryotes, enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. The formation of phase condensates is thought to be an essential component of enhancer function. Here, we show that pharmacological targeting of cells with inhibitors of BET (Bromodomain and Extra-Terminal domain) proteins can have a strong impact on transcription but very little impact on enhancer-promoter interactions. Treatment with 1,6-hexanediol, which dissolves phase condensate structures and reduces BET and Mediator protein binding at enhancers, can also have a strong effect on gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancer-promoter interactions are separable events. Our findings further suggest that enhancer-promoter interactions are not dependent on high levels of BRD4 (Bromodomain-containing protein 4) and Mediator, and are likely maintained by a complex set of factors including additional activator complexes and loop extrusion by CTCF/cohesin.
Effect of antenatal tetramethylpyrazine on lung development and YAP expression in a rat model of experimental congenital diaphragmatic hernia
Authors: Liao Junzuo , Liu Wenying , Zhang Libin , Li Qin , Hou Fang
Published: November 2019

Tetramethylpyrazine (TMP) is a chemical compound found in extracts derived from the Chinese medicinal plant. Due to its remarkable therapeutic effects, availability, and low cost and toxicity, TMP has been used to treat cardiovascular diseases and pulmonary hypertension in China. The aim of this study was to investigate the therapeutic effects and underlying mechanism of TMP on lung development using a rat model of nitrofen-induced congenital diaphragmatic hernia (CDH). Pregnant rats were divided into three groups: control, CDH, and CDH+TMP. Nitrofen was used to induce CDH. In the CDH and CDH+TMP, Fetuses only with left diaphragmatic hernias were chosen for analysis. Lung and body weight were recorded and lung histologic evaluations, image analysis, and western blot analysis of YAP, p-YAP and LATS1 were performed after lung processing. A marked abnormal structure was observed, as evidenced by pulmonary hypoplasia and vascular remodeling, in the CDH. These abnormalities were improved in the CDH+TMP. There were significant differences between the CDH and CDH+TMP in percentage of medial wall thickness, arteriole muscularization, radial alveolar counts, AA%, and alveolar septal thickness. YAP expression was markedly increased in the CDH compared to the control, which was not affected by antenatal TMP administration. However, prenatal TMP intervention significantly increased expression of LATS1 and phosphorylation of YAP in the CDH fetuses. Our results demonstrate thatantenatal TMP administration improved vascular remodeling and promoted lung development in a rat model of CDH, potentially through increasing expression of LATS1 and phosphorylation of YAP.
Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb and reverses HIV-1 latency
Authors: Stoszko Mateusz , Al-Hatmi Abdullah M.S. , Skriba Anton , Roling Michael , Ne Enrico , Mueller Yvonne M. , Najafzadeh Mohammad Javad , Crespo Raquel , Kang Joyce , Ptackova Renata , Biswas Pritha , Bertoldi Alessia , Kan Tsung Wai , de Crignis Elisa , Palstra Robert-Jan , Sulc Miroslav , Lebbink Joyce H.G. , Rokx Casper , Verbon Annelies , van Ijcken Wilfred , Katsikis Peter D. , Havlicek Vladimir , de Hoog Sybren , Mahmoudi Tokameh
Published: November 2019

A leading pharmacological strategy towards HIV cure requires “shock” or activation of HIV gene expression in latently infected cells with Latency Reversal Agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs we used fungal secondary metabolites (extrolites) as a source of bio-active molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the P-TEFb inhibitory 7SK snRNP complex to be significantly reduced upon GTX treatment of independent donor CD4+T cells. GTX disrupted 7SK snRNP, releasing active P-TEFb, which then phosphorylated RNA Pol II CTD, inducing HIV transcription. Our data highlight the power of combining a medium throughput bioassay, mycology and orthogonal mass spectrometry to identify novel potentially therapeutic compounds.
Spatial organization of cortical actin alignments for the ooplasmic segregation of ascidianCionaeggs
Authors: Ishii Hirokazu , Tani Tomomi
Published: November 2019

Spatial reorganization of cytoplasm in zygotic cells is critically important for establishing the body plans of many animal species. In ascidian zygotes, maternal determinants (mRNAs) are first transported to the vegetal pole a few minutes after the fertilization, and then to the future posterior side of the zygotes in later phase of the cytoplasmic reorganization, before the first cell division. Here, by using a novel fluorescence polarization microscope that reports the position and the orientation of fluorescently labeled proteins in living cells, we mapped the local alignments and the time-dependent changes of cortical actin networks inCionaeggs. The initial cytoplasmic reorganization started with the contraction of vegetal hemisphere ∼20s after the fertilization induced [Ca2+] increase. Timing of the vegetal contraction was consistent with the emergence of highly aligned actin filaments at the cell cortex of vegetal hemisphere which ran perpendicular to the animal-vegetal axis. We propose that the first ooplasmic segregation is initiated by the local contraction of laterally aligned cortical actomyosin in the vegetal hemisphere, which in turn generates the convectional flow of cytoplasm within whole eggs.

SUMMARY STATEMENT

Locally distinct, transient emergence of cortical F-actin alignments were observed in live ascidianCionaeggs during the first ooplasmic segregation by using fluorescence polarization microscopy.
RAF conformational autoinhibition and 14-3-3 proteins promote paradoxical activation
Authors: Mendiratta Gaurav , Abbott Kodye , Li Yao-Cheng , Yu Jingting , Huang Jianfeng , Shokhirev Maxim N. , McFall Thomas , Wahl Geoffrey M. , Stites Edward C.
Published: November 2019

RAF kinase inhibitors can, in some conditions, increase RAF kinase signaling. This process, which is commonly referred to as “paradoxical activation” (PA), is incompletely understood. RAF kinases are regulated by autoinhibitory conformational changes, and the role of these conformational changes in PA is unclear. Our mathematical investigations reveal that a dynamic equilibrium between autoinhibited and non-autoinhibited forms of RAF, along with the RAF inhibitor stabilization of the non-autoinhibited form, can be sufficient to create PA. Using both computational and experimental methods we demonstrate that 14-3-3 proteins, which stabilize both RAF autoinhibition and RAF dimerization, potentiate PA. Our model led us to hypothesize that increased 14-3-3 expression would amplify PA for the third generation RAF inhibitors that normally display minimal to no PA. Our subsequent experiments find that 14-3-3 overexpression increases PA, increases RAF dimerization, and promotes resistance to these inhibitors, effectively “breaking” these “paradox breaker” and pan-RAF inhibitors. Overall, this work reveals a robust mechanism for PA based solely on equilibrium dynamics of canonical interactions in RAF signaling and identifies conditions which allow PA to occur.
A latent profile analysis of work passion: structure, antecedent, and outcomes
Authors: Li Jingjing , Zhang Jian , Shao Bo , Chen Chunxiao
Published: November 2019

Purpose

Previous research draws on the dualistic model of passion (harmonious and obsessive passion) overlooks how the different two types of passion interact within individuals using a variable-centered approach. The purpose of this paper is to identify work passion profiles and their antecedent and consequences adopting a person-centered approach, and to explain inconsistences in previous studies.

Design/methodology/approach

This paper conducts three studies (n=2,749 in total) using a latent profile analysis. Study 1 identifies three work passion profiles, namely, dual passion, pro harmonious passion and pro obsessive passion; study 2 examines dialectical thinking as an antecedent to work passion profile membership; study 3 examines how each profile relates to work performance and well-being.

Findings

This paper finds that the participants with a dual passion profile showed higher task performance and subjective well-being than the participants with the other two profiles; the participants with a pro obsessive passion profile were higher in task performance, interpersonal performance and psychological well-being than the participants with a pro harmonious profile.

Originality/value

This paper is the first that uses a latent profile analysis approach to examining work passion configurations. It provides a unique perspective to investigate how different types of passion configure and interact within individuals; it explores an antecedent (i.e. dialectical thinking) and outcomes (i.e. performance and well-being) of the three work passion profiles.
HRM reforms and job-related well-being of academics
Authors: Xia Jie , Zhang Mingqiong Mike , Zhu Jiuhua Cherrie , Fan Di , Samaratunge Ramanie
Published: November 2019

Purpose

The purpose of this paper is to examine the influence of human resource management (HRM) reforms on job-related well-being of academics in Chinese universities. It also tests the mediating effect of work intensification (WI) and affective commitment (AC), and the moderating effect of perceived organizational justice (OJ) on the HRM‒well-being relationship to understand the influence mechanisms and boundary conditions.

Design/methodology/approach

A questionnaire survey was conducted in 25 Chinese universities, obtaining 638 usable questionnaires. Structural equation modeling (SEM) was used as the analytical technique to examine the model fit and test hypotheses.

Findings

The findings reveal that the relationship of HRM and well-being is neither direct nor unconditional, and a win‒win scenario for both management and employee well-being is possible when organizations pursue HRM innovations.

Research limitations/implications

The limitations of this study are that data were collected at once and at a defined time, with no time lag being involved. In addition, all variables were self-reported.

Practical implications

Commitment-oriented HRM practices can create a win‒win scenario; when control-oriented HRM practices are necessary, managers should ensure OJ to offset their negative influence on employees.

Originality/value

This study is among the first to examine the impact of HRM on employee well-being in the context of Chinese higher education, contributing to the limited studies on HRM in Chinese public sector and the on-going debate on the nature of HRM in China.