bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental enrichment delays the development of stereotypic behavior and reduces variability in behavioral experiments using California mice (Peromyscus californicus)
Authors: Minie Vanessa , Ramos-Maciel Stephanie , Wright Emily , Petric Radmila , Trainor Brian , Duque-Wilckens Natalia
Published: January 2021

Domesticated mice and rats have shown to be powerful model systems for biomedical research, but there are cases in which the biology of species is a poor match for the hypotheses under study. The California mouse (Peromyscus californicus) has unique physiological and behavioral traits and has emerged as a powerful model for studying sex differences in the biology of psychiatric disease, which is particularly relevant considering the new NIH guidelines that require the inclusion of sex as a biological variable. Despite its growing role in preclinical research, there is a lack of studies assessing species-specific housing needs, which presents a challenge for research facilities seeking to ensure good welfare and obtaining high-quality experimental data. Indeed, captive California mice present a high prevalence of stereotypic backflipping behavior, a common consequence of suboptimal housing and a potential source of experimental outcome variability. Using three different cage systems, the present studies show that increasing housing space as well as social and environmental complexity can delay the development of stereotypic behavior in male and female California mice. Critically, this reduction in stereotypy is accompanied by increased effect sizes of stress in an established model for social anxiety. These results suggest that increased cage size and enrichment could enhance welfare in California mice while simultaneously increasing the quality of behavioral experiments.
The skin environment controls local dendritic cell differentiation and function through innate IL-13
Authors: Mayer Johannes U , Lamiable Olivier , Hilligan Kerry L , Chandler Jodie S , Old Samuel I , Eccles David A , Yang Jianping , Webb Greta R , Domingues Rita G , Munoz-Erazo Luis , Wakelin Kirsty A , Hyde Evelyn J , Tang Shiau-Choot , Chappell Sally C , Mackay Charles R , Brombacher Frank , Sher Alan , Tussiwand Roxane , Connor Lisa M , Jankovic Dragana , Hepworth Matthew R , Le Gros Graham , Ronchese Franca
Published: January 2021

The signals driving the adaptation of type-2 dendritic cells (DC2s) to diverse peripheral environments are not well understood. We show that the development of CD11blowmigratory DC2s, a DC2 population unique to the dermis, requires STAT6- and KLF4-dependent IL-13 signaling, whereas DC2s in lung and small intestine are STAT6-independent. Dermal IL-13 is mostly derived from innate lymphoid cells expressing a resting ICOS+ KLRG1-ST2-phenotype. Analysis of public datasets indicates that human skin DC2s also express an IL-4/IL-13 gene signature compared to blood or spleen, suggesting a similar developmental pathway in mice and humans. In the absence of IL-13 signaling, dermal DC2s are stable in number but remain CD11bhiand show defective activation in response to allergen with diminished ability to support IL-4+ GATA3+ Th development, whereas anti-fungal IL-17+ RORγt+ responses are increased. Thus, steady-state IL-13 fosters a non-inflammatory and pro-allergic environment in healthy skin via conditioning of local DC2s.
Physical theory of biological noise buffering by multi-component phase separation
Authors: Deviri Dan , Safran Samuel A.
Published: January 2021

Maintaining homeostasis is a fundamental characteristic of living systems. In cells, this is contributed to by assembly of biochemically-distinct organelles, many of whom are not membrane-bound, but form by the physical process of liquid-liquid phase separation (LLPS). By analogy with LLPS in binary solutions, cellular LLPS was hypothesized to contribute to homeostasis by facilitating “concentration buffering”, which renders the local protein concentration within the organelle robust to global variations in the average, cellular concentration (e.g. due to expression noise). Interestingly, concentration buffering was experimentally measured in vivo, in a simple organelle with a single solute, while it was observed not to be obeyed in one with several solutes. Here, we formulate theoretically and solve analytically a physical model of LLPS in a ternary solution of two solutes (A and B) that interact both homotypically (A-A attractions) and heterotypically (A-B attractions). Our physical theory predicts how the equilibrium concentrations in LLPS are related to expression noise and thus generalizes the concept of concentration buffering to multi-component systems. This allows us to reconcile the seemingly contradictory experimental observations. Furthermore, we predict that incremental changes of the homotypic and heterotypic interactions among the molecules that undergo LLPS, such as those that are caused by mutations in the genes encoding the proteins, may increase the efficiency of concentration buffering of a given system. Thus, we hypothesize that evolution may optimize concentration buffering as an efficient mechanism to maintain LLPS homeostasis, and suggest experimental approaches to test this in different systems.

Significance

The stochastic nature of transcription/translation implies that the concentrations of cellular proteins are “noisy” and not constant in time or across cell populations. Liquid-liquid phase separation (LLPS), can reduce or “buffer” this noise by maintaining well-defined concentrations, even in the presence of concentration distributions. However, this idea was recently challenged experimentally in multicomponent systems. Our physical theory of LLPS in ternary systems (solutes A and B in a solvent), predicts their LLPS properties as a function of the A-A (homotypic) and A-B (heterotypic) interaction strengths. We show how buffering can be effective if the noise distribution aligns with the tie-lines of the phase diagram and suggest that evolution may optimize concentration buffering by selecting mutations that lead to this.
Monod law is insufficient to explain biomass growth in nitrogen-limited yeast fermentation
Authors: Henriques David , Balsa-Canto Eva
Published: January 2021

The yeastSaccharomyces cerevisiaeis an essential microorganism in food biotechnology; particularly, in wine and beer making. During wine fermentation, yeasts transform sugars present in the grape juice into ethanol and carbon dioxide. The process occurs in batch conditions and is, for the most part, an anaerobic process. Previous studies linked limited-nitrogen conditions with problematic fermentations, with negative consequences for the performance of the process and the quality of the final product. It is, therefore, of the highest interest to anticipate such problems through mathematical models. Here we propose a model to explain problematic fermentations under nitrogen-limited anaerobic conditions. We separated the biomass formation into two phases: growth and carbohydrate accumulation. Growth was modelled using the well-known Monod law while carbohydrate accumulation was modelled by an empirical function, analogous to a proportional controller activated by the limitation of available nitrogen. We also proposed to formulate the fermentation rate as a function of the total protein content when relevant data are available. The final model was used to successfully explain a series of experiments taken from the literature, performed under normal and nitrogen-limited conditions. Our results revealed that Monod law is insufficient to explain biomass formation kinetics in nitrogen-limited fermentations ofS. cerevisiae. The goodness-of-fit of the herewith proposed model is superior to that of previously published models, offering the means to predict, and thus control, problematic fermentations.

IMPORTANCE

Problematic fermentations still occur in the winemaking industrial practise. Problems include sluggish rates of fermentation, which have been linked to insufficient levels of assimilable nitrogen. Data and relevant models can help anticipate poor fermentation performance. In this work, we proposed a model to predict biomass growth and fermentation rate under nitrogen-limited conditions and tested its performance with previously published experimental data. Our results show that the well-known Monod law does not suffice to explain biomass formation. A second term accounting for carbohydrate accumulation is required to predict successfully, and thus control, problematic fermentations.
Antiviral activity of bacterial TIR domains via signaling molecules that trigger cell death
Authors: Ofir Gal , Herbst Ehud , Baroz Maya , Cohen Daniel , Millman Adi , Doron Shany , Tal Nitzan , Malheiro Daniel B. A. , Malitsky Sergey , Amitai Gil , Sorek Rotem
Published: January 2021

The Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule which is a variant of cyclic ADP-ribose (v-cADPR). This molecule is hypothesized to activate plant cell death via a yet unresolved pathway. TIR domains were recently also shown to be involved in a bacterial anti-phage defense system called Thoeris, but the mechanism of Thoeris defense remained unknown. In this study we report that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We further show that similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe a new antiviral signaling pathway in bacteria, and suggest that generation of intracellular signaling molecules is an ancient immunological function of TIR domains conserved in both plant and bacterial immunity.
West Nile virus detection in horses in three Brazilian states
Authors: Costa Erica Azevedo , Giovanetti Marta , Catenacci Lilian Silva , Fonseca Vagner , Aburjaile Flavia , Iani Felipe Melo Campos , da Cunha e Silva Vieira Marcelo Adriano , Henriques Danielle Freitas , de Almeida Daniele Barbosa , Coelho Guedes Maria Isabel Maldonado , da Silva Ramos Beatriz Senra Álvares , Silva Aila Solimar Gonçalves , de Oliveira Tulio , Jardim Cavalcante Karina Ribeiro Leite , de Moura Noely Fabiana Oliveira , Romano Alessandro Pecego Martins , de Albuquerque Carlos F. Campelo , Feitosa Lauro César Soares , Bayeux José Joffre Martins , Teixeira Raffaella Bertoni Cavalcanti , Lobato Osmaikon Lisboa , da Costa Silva Silvokleio , Lourenço José , Alcantara Luiz Carlos Junior
Published: January 2021

We report genetic evidence of WNV circulation from southern and northeastern Brazilian states isolated from equine red blood cells. In the northeastern state the tenth human case was also detected, presenting neuroinvasive disease compatible with WNV infection. Our analyses demonstrate that much is still unknown on the virus’ local epidemiology. We advocate for a shift to active surveillance, to ensure adequate control for future epidemics with spill-over potential to humans.
Tetherin antagonism by SARS-CoV-2 enhances virus release: multiple mechanisms including ORF3a-mediated defective retrograde traffic
Authors: Stewart Hazel , Palmulli Roberta , Johansen Kristoffer H. , McGovern Naomi , Shehata Ola M. , Carnell George W. , Jackson Hannah K. , Lee Jin S. , Brown Jonathan C. , Burgoyne Thomas , Heeney Jonathan L. , Okkenhaug Klaus , Firth Andrew E. , Peden Andrew A. , Edgar James R.
Published: January 2021

The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including theCoronaviridae. Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrated that SARS-CoV-2 infection causes tetherin downregulation, and that tetherin depletion from cells enhances SARS-CoV-2 viral titres. We investigated the potential viral proteins involved in abrogating tetherin function and found that SARS- CoV-2 ORF3a reduces tetherin localisation within biosynthetic organelles via reduced retrograde recycling and increases tetherin localisation to late endocytic organelles. By removing tetherin from the Coronavirus budding compartments, ORF3a enhances virus release. We also found expression of Spike protein caused a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS-CoV-2 and highlight the multiple distinct mechanisms by which SARS-CoV-2 subverts tetherin function.

Author Summary

Since it was identified in 2019, SARS-CoV-2 has displayed voracious transmissibility which has resulted in rapid spread of the virus and a global pandemic. SARS-CoV-2 is a member of theCoronaviridaefamily whose members are encapsulated by a host-derived protective membrane shell. Whilst the viral envelope may provide protection for the virus, it also provides an opportunity for the host cell to restrict the virus and stop it spreading. The anti-viral restriction factor, tetherin, acts to crosslink viruses to the surface of infected cells and prevent their spread to uninfected cells. Here, we demonstrate that SARS-CoV-2 undergoes viral restriction by tetherin, and that SARS-CoV-2 moves tetherin away from the site of Coronavirus budding to enhance its ability to escape and infect naïve cells. Tetherin depletion from cells enhanced SARS-CoV-2 viral release and increased propagation of the virus. We found that the SARS-CoV-2 protein, ORF3a, redirects tetherin away from the biosynthetic organelles where tetherin would become incorporated to newly forming SARS-CoV-2 virions – and instead relocalises tetherin to late endocytic organelles. We also found that SARS-CoV-2 Spike downregulates tetherin. These two mechanisms, in addition to the well described antagonism of interferon and subsequent ISGs highlight the multiple mechanisms by which SARS-CoV-2 abrogates tetherin function. Our study provides new insights into how SARS-CoV-2 subverts human antiviral responses and escapes from infected cells.
Maintenance of Complex I and respiratory super-complexes by NDUF-11 is essential for respiratory function, mitochondrial structure and health inC. elegans
Authors: Knapp-Wilson Amber , Pereira Gonçalo C. , Buzzard Emma , Richardson Andrew , Corey Robin A. , Neal Chris , Verkade Paul , Halestrap Andrew P. , Gold Vicki A.M. , Kuwabara Patricia , Collinson Ian
Published: January 2021

Mitochondrial super-complexes form around a conserved core of monomeric complex I and dimeric complex III; wherein subunit NDUFA11, of the former, is conspicuously situated at the interface. We identifiedB0491.5(NDUF-11) as theC. eleganshomologue, of which animals homozygous for a CRISPR-Cas9 generated knockout allele arrested at the L2 development stage. Reducing expression by RNAi allowed development to the adult stage, enabling characterisation of the consequences: destabilisation of complex I and its super-complexes, and perturbation of respiratory function. The loss of NADH-dehydrogenase activity is compensated by enhanced complex II activity, resulting in excessive detrimental ROS production. Meanwhile, electron cryo-tomography highlight aberrant cristae morphology and widening of the inter-membrane space and cristae junctions. The requirement of NDUF-11 for balanced respiration, mitochondrial morphology and development highlights the importance of complex I/ super-complex maintenance. Their perturbation by this, or other means, is likely to be the cause of metabolic stress and disease.
Recognition of a Tandem Lesion by DNA Glycosylases Explored Combining Molecular Dynamics and Machine Learning
Authors: Bignon Emmanuelle , Gillet Natacha , Chan Chen-Hui , Jiang Tao , Monari Antonio , Dumont Elise
Published: January 2021

The combination of several closely spaced DNA lesions, which can be induced by a single radical hit, constitutes a hallmark in the DNA damage landscape and radiation chemistry. The occurrence of such tandem base lesions give rise to a strong coupling with the double helix degrees of freedom and induce important structural deformations, in contrast to DNA strands containing a single oxidized nucleobase. Although such complex lesions are known to be refractory to repair by DNA glycosylases, there is still a lack of structural evidence to rationalize these phenomena. In this contribution, we explore, by numerical modeling and molecular simulations, the behavior of the bacterial glycosylase responsible for base excision repair (MutM), specialized in excising oxidatively-damaged defects such as 7,8-dihydro-8-oxoguanine (8-oxoG). The difference in lesion recognition between a simple damage and a tandem lesions featuring an additional abasic site is assessed at atomistic resolution owing to microsecond molecular dynamics simulation and machine learning postprocessing, allowing to extensively pinpoint crucial differences in the interaction patterns of the damaged bases. This work advocates for the use of such high throughput numerical simulations for exploring the complex combinatorial chemistry of tandem DNA lesions repair and more generally multiple damaged sites of the utmost significance in radiation chemistry.
Are we missing the forest for the trees? Conspecific negative density dependence in a temperate deciduous forest
Authors: Barry Kathryn E. , Schnitzer Stefan A.
Published: January 2021

One of the central goals of ecology is to determine the mechanisms that enable coexistence among species. Evidence is accruing that conspecific negative density dependence (CNDD), the process by which plant seedlings are unable to survive in the area surrounding adults of their same species, is a major contributor to tree species coexistence. However, for CNDD to maintain diversity, three conditions must be met. First, CNDD must maintain diversity for the majority of the woody plant community (rather than merely specific groups). Second, the pattern of repelled recruitment must increase in with plant size. Third, CNDD must occurs across life history strategies and not be restricted to a single life history strategy. These three conditions are rarely tested simultaneously. In this study, we simultaneously test all three conditions in a woody plant community in a North American temperate forest. We examined whether the different woody plant growth forms (shrubs, understory trees, mid-story trees, canopy trees, and lianas) at different ontogenetic stages (seedling, sapling, and adult) were overdispersed – a spatial pattern indicative of CNDD – using spatial point pattern analysis across life history stages and strategies. We found that there was a strong signal of overdispersal at the community level. However, this pattern was driven by adult canopy trees. By contrast, understory plants, which can constitute up to 80% of temperate forest plant diversity, were not overdispersed as adults. The lack of overdispersal suggests that CNDD is unlikely to be a major mechanism maintaining understory plant diversity. The focus on trees for the vast majority of CNDD studies may have biased the perception of the prevalence of CNDD as a dominant mechanism that maintains community-level diversity when, according to our data, CNDD may be restricted largely to trees.
Incidence and Characteristics of Co-infection and Secondary Infection in Patients with COVID-19
Authors: Guo Yingyi , Qu Jiuxin , Cheng Lingling , Li Xiaohe , Liu Ningjing , Li Tungngai , Jiang Ying , Wan Qiao , Zhuo Chuyue , Xiao Shunian , Liu Baomo , Chen Yan , Fu lin , Chen Zhixu , Ma Mingcong , zhuo Chao , Zhong Nanshan
Published: January 2021

Objective

The etiology and epidemiology of co-infection and secondary infection in COVID-19 patients remain unknown. The study aims to investigate the occurrence and characteristics of co-infection and secondary infection in COVID-19 patients, mainly focusing on Streptococcus pneumoniae co-infections.

Methods

This study was a prospective, observational cohort study of the inpatients diagnosed with COVID-19 in two designated hospitals in south China enrolled between Jan 11 and Feb 22, 2020. The urine specimen was collected on admission and applied for pneumococcal urinary antigen tests (PUATs). Demographic, clinical and microbiological data of patients were recorded simultaneously.

Result

A total of 146 patients with a confirm diagnosis of COVID-19 at the median age of 50.0 years (IQR 36.0-61.0) were enrolled, in which, 16 (11.0%) were classified as severe cases and 130 (89.0%) as non-severe cases. Of the enrolled patients, only 3 (2.1%) were considered to present the co-infection, in which 1 was co-infected with S.pneumoniae, 1 with B. Ovatus infection and the other one with Influenza A virus infection. Secondary infection occurred in 16 patients, with S. maltophilia as the most commonly isolated pathogen (43.8%), followed by P. aeruginosa (25.0%), E. aerogenes (25.0%), C. parapsilosis (25.0%) and A. fumigates (18.8%).

Conclusion

Patients with confirmed COVID-19 were rarely co-infected with Streptococcus pneumoniae or other pathogens, indicating that the application of antibiotics against CAP on admission may not be necessary in the treatment of COVID-19 cases.
Evolution to alternative levels of stable diversity leaves areas of niche space unexplored
Authors: Rubin Ilan N. , Ispolatov Iaroslav , Doebeli Michael
Published: January 2021

One of the oldest and most persistent questions in ecology and evolution is whether natural communities tend to evolve toward saturation and maximal diversity. Robert MacArthur’s classical theory of niche packing and the theory of adaptive radiations both imply that populations will diversify and fully partition any available niche space. However, the saturation of natural populations is still very much an open area of debate and investigation. Additionally, recent evolutionary theory suggests the existence of alternative evolutionary stable states (ESSs), which implies that some stable communities may not be fully saturated. Using models with classical Lokta-Volterra ecological dynamics and three formulations of evolutionary dynamics (a model using adaptive dynamics, an individual-based model, and a partial differential equation model), we show that following an adaptive radiation, communities can often get stuck in low diversity states when limited by mutations of small phenotypic effect. These low diversity metastable states can also be maintained by limited resources and finite population sizes. When small mutations and finite populations are considered together, it is clear that despite the presence of higher-diversity stable states, natural populations are likely not fully saturating their environment and leaving potential niche space unfilled. Additionally, within-species variation can further reduce community diversity from levels predicted by models that assume species-level homogeneity.

Author summary

Understanding if and when communities evolve to saturate their local environments is imperative to our understanding of natural populations. Using computer simulations of classical evolutionary models, we study whether adaptive radiations tend to lead toward saturated communities, in which no new species can invade or remain trapped in alternative, lower diversity stable states. We show that with asymmetric competition and small effect mutations, evolutionary Red Queen dynamics can trap communities in low diversity metastable states. Moreover, limited resources not only reduces community population sizes, but also reduces community diversity, denying the formation of saturated communities and stabilizing low diversity, non-stationary evolutionary dynamics. Our results are directly relevant to the longstanding questions important to both ecological empiricists and theoreticians on the species packing and saturation of natural environments. Also, by showing the ease evolution can trap communities in low diversity metastable states, we demonstrate the potential harm in relying solely on ESSs to answer questions of biodiversity.
Predictors of virus prevalence and diversity across a wild bumblebee community
Authors: Pascall David J. , Tinsley Matthew C. , Clark Bethany L. , Obbard Darren J. , Wilfert Lena
Published: January 2021

Viruses are key regulators of natural populations. Despite this, we have limited knowledge of the diversity and ecology of viruses that lack obvious fitness effects on their host. This is even the case in wild host populations that provide ecosystem services, where small fitness effects may have major ecological and financial impacts in aggregate. One such group of hosts are the bumblebees, which have a major role in the pollination of food crops and have suffered population declines and range contractions in recent decades. In this study, we used a multivariate generalised linear mixed model to investigate the ecological factors that determine the prevalence of four recently discovered bumblebee viruses (Mayfield virus 1, Mayfield virus 2, River Liunaeg virus and Loch Morlich virus), and two previously known viruses that infect both wild bumblebees and managed honeybees (Acute bee paralysis virus and Slow bee paralysis virus). We show that the recently discovered bumblebee viruses were more genetically diverse than the viruses shared with honeybees, potentially due to spillover dynamics of shared viruses. We found evidence for ecological drivers of prevalence in our samples, with relatively weak evidence for a positive effect of precipitation on the prevalence of River Luinaeg virus. Coinfection is potentially important in shaping prevalence: we found a strong positive association between River Liunaeg virus and Loch Morlich virus presence after controlling for host species, location and other relevant ecological variables. This study represents a first step in the description of predictors of bumblebee infection in the wild not driven by spillover from honeybees.
Combining single-molecule super-resolved localization microscopy with fluorescence polarization imaging to study cellular processes
Authors: Shepherd Jack W , Payne-Dwyer Alex L , Lee Ji-Eun , Syeda Aisha , Leake Mark C
Published: January 2021

Super-resolution microscopy has catalyzed valuable insights into the sub-cellular, mechanistic details of many different biological processes across a wide range of cell types. Fluorescence polarization spectroscopy tools have also enabled important insights into cellular processes through identifying orientational changes of biological molecules typically at an ensemble level. Here, we combine these two biophysical methodologies in a single home-made instrument to enable the simultaneous detection of orthogonal fluorescence polarization signals from single fluorescent protein molecules used as common reporters on the localization of proteins in cellular processes. These enable measurement of spatial location to a super-resolved precision better than the diffraction-limited optical resolution, as well as estimation of molecular stoichiometry based on the brightness of individual fluorophores. In this innovation we have adapted a millisecond timescale microscope used for single-molecule detection to enable splitting of fluorescence polarization emissions into two separate imaging channels for s- and p-polarization signals, which are imaged onto separate halves of the same high sensitivity back-illuminated CMOS camera detector. We applied this fluorescence polarization super-resolved imaging modality to a range of test fluorescent samples relevant to the study of biological processes, including purified monomeric green fluorescent protein, single combed DNA molecules, and protein assemblies and complexes from live Escherichia coli and Saccharomyces cerevisiae cells. Our findings are qualitative but demonstrate promise in showing how fluorescence polarization and super-resolved localization microscopy can be combined on the same sample to enable simultaneous measurements of polarization and stoichiometry of tracked molecular complexes, as well as the translational diffusion coefficient.
The H3K36me2 writer-reader dependency in H3K27M-DIPG
Authors: Yu Jia-Ray , LeRoy Gary , Bready Devin , Frenster Joshua D. , Saldaña-Meyer Ricardo , Jin Ying , Descostes Nicolas , Stafford James M. , Placantonakis Dimitris G. , Reinberg Danny
Published: January 2021

The lysine-to-methionine mutation at residue 27 of histone H3 (H3K27M) is a driving mutation in Diffuse Intrinsic Pontine Glioma (DIPG), a highly aggressive form of pediatric brain tumor with no effective treatment and little chance of survival. H3K27M reshapes the epigenome through a global inhibition of PRC2 catalytic activity, the placement of methylation at lysine 27 of histone H3 (H3K27me2/3), promoting oncogenesis of DIPG. As a consequence, a histone modification H3K36me2, antagonistic to H3K27me2/3, is aberrantly elevated. Here, we investigate the role of H3K36me2 in H3K27M-DIPG by tackling its upstream catalyzing enzymes (writers) and downstream binding factors (readers). We determine that NSD1 and NSD2 are the key writers for H3K36me2. Loss of NSD1/2 in H3K27M-DIPG impedes cellular proliferation in vitro and tumorigenesis in vivo, and disrupts tumor-promoting gene expression programs. Further, we demonstrate that LEDGF and HDGF2 are the main readers that mediate the pro-tumorigenic effects downstream of NSD1/2-H3K36me2. Treatment with a chemically modified peptide mimicking endogenous H3K36me2 dislodges LEDGF/HDGF2 from chromatin and specifically inhibits the proliferation of H3K27M-DIPG. Together, our results indicate a functional pathway of NSD1/2-H3K36me2-LEDGF/HDGF2 as an acquired dependency in H3K27M-DIPG and suggest a possibility to target this pathway for therapeutic interventions.
Domain-general conflict monitoring predicts neural and behavioral indices of linguistic error processing during reading comprehension
Authors: Brothers Trevor , Zeitlin Margarita , Perrachione Arim Choi , Choi Connie , Kuperberg Gina
Published: January 2021

The ability to detect and respond to linguistic errors is critical for successful reading comprehension, but these skills can vary considerably across readers. In the current study, healthy adults (age 18-35) read short discourse scenarios for comprehension while monitoring for the presence of semantic anomalies. Using a factor analytic approach, we examined if performance in non-linguistic conflict monitoring tasks (Stroop, AX-CPT) would predict individual differences in neural and behavioral measures of linguistic error processing. Consistent with this hypothesis, domain-general conflict monitoring predicted both readers’ end-of-trial acceptability judgments and the amplitude of a late neural response (the P600) evoked by linguistic anomalies. Interestingly, the influence on the P600 was non-linear, suggesting that online neural responses to linguistic errors are influenced by both the effectiveness and efficiency of domain-general conflict monitoring. These relationships were also highly specific and remained after controlling for variability in working memory capacity and verbal knowledge. Finally, we found that domain-general conflict monitoring also predicted individual variability in measures of reading comprehension, and that this relationship was partially mediated by behavioral measures of linguistic error detection. These findings inform our understanding of the role of domain-general executive functions in reading comprehension, with potential implications for the diagnosis and treatment of language impairments.
The telomere regulatory gene POT1 responds to stress and predicts performance in nature: implications for telomeres and life history evolution
Authors: Wolf Sarah E. , Sanders Tiana L. , Beltran Sol E. , Rosvall Kimberly A.
Published: January 2021

Long telomeres have become nearly synonymous with a variety of fitness-related traits and may be mediators of ecologically relevant variation in life history strategies. Growing evidence suggests that telomere dynamics are more predictive of performance than length itself, but very little work considers how telomere regulatory mechanisms respond to environmental challenges or influence performance in nature. Here, we combine observational and experimental datasets from free-living tree swallows (Tachycineta bicolor) to assess how performance is predicted by the telomere regulatory gene POT1, which encodes a shelterin protein that sterically blocks telomerase from repairing the telomere. First, we show that lower POT1 gene expression was associated with higher female quality, i.e. earlier breeding, and heavier body mass. We next challenged mothers with an immune stressor (lipopolysaccharide injection) that led to ‘sickness’ in mothers and 24h of food restriction in their offspring. While POT1 did not respond to maternal injection, females with lower constitutive gene expression were better able to maintain feeding rates following treatment. Maternal injection also generated a one-day stressor for chicks, who responded with decreased POT1 gene expression and elongated telomeres. Other putatively stress-responsive mechanisms (i.e. glucocorticoids, antioxidants) were not significantly different between control and stress-exposed chicks. Model comparisons indicated that POT1 mRNA abundance was a largely better predictor of performance than telomere dynamics, indicating that telomere regulators may be powerful modulators of variation in life history strategies.
Endosomal cAMP production broadly impacts the cellular phosphoproteome
Authors: Tsvetanova Nikoleta G. , Trester-Zedlitz Michelle , Newton Billy W. , Peng Grace E. , Johnson Jeffrey R. , Jimenez-Morales David , Kurland Andrew P. , Krogan Nevan J. , von Zastrow Mark
Published: January 2021

Endosomal signaling downstream of G protein-coupled receptors (GPCRs) has emerged as a novel paradigm with important pharmacological and physiological implications. Yet, our knowledge of the functional consequences of intracellular signaling is incomplete. To begin to address this gap, we combined an optogenetic approach for site-specific generation of the prototypical second messenger generated by active GPCRs, cyclic AMP (cAMP), with unbiased mass spectrometry-based analysis of phosphoproteomic effects. We identified 218 unique, highconfidence sites whose phosphorylation is either increased or decreased in response to cAMP production. We next determined that the same amount of cAMP produced from endosomes led to more robust changes in phosphorylation than the plasma membrane. Remarkably, this was true for the entire repertoire of identified targets, and irrespective of their annotated sub-cellular localization. Furthermore, we identified a particularly strong endosome bias for a subset of proteins that are dephosphorylated in response to cAMP. Through bioinformatics analysis, we established these targets as putative substrates for protein phosphatase 2A (PP2A), and we propose compartmentalized activation of PP2A-B56δ as the likely underlying mechanism. Altogether, our study extends the concept that endosomal signaling is a significant functional contributor to cellular responsiveness by establishing a unique role for localized cAMP production in defining categorically distinct phosphoresponses.
The Great Western Development policy: how it affected grain crop production, land use and rural poverty in western China
Authors: Li Pei , Tian Ye , Wu JunJie , Xu Wenchao
Published: January 2021

Purpose

The purpose of this paper evaluates the effects of the Great Western Development (GWD) policy on agricultural intensification, land use, agricultural production and rural poverty in western China.

Design/methodology/approach

The authors collect county-level data on land use, input application, grain crop production, income, poverty and geophysical characteristics for 1996–2005 and use a quasi-natural experimental design of difference-in-differences (DD) in the empirical analysis.

Findings

Results suggest that the GWD policy significantly increased the grain crop production in western China. This increase resulted from higher yield, with increased fertilizer use and agricultural electricity consumption per hectare, and more land allocated to grow grain crops. The policy also increased land-use concentration, reduced crop diversity and alleviated rural poverty in western China.

Originality/value

This paper makes three contributions. First, the authors add to the growing literature on the GWD policy by evaluating its effects on farm household decisions and exploring the mechanisms and broad socioeconomic impacts in western China. Second, the authors take advantage of a quasi-natural experimental design to improve the identification strategy where input use, land allocation, production and off-farm labor participation are all endogenous in a farm household. Third, the authors explore a long list of variables within one integrated dataset to present a comprehensive picture of the impact of the GWD policy.
Regional rural and structural transformations and farmer's income in the past four decades in China
Authors: Huang Jikun , Shi Pengfei
Published: January 2021

Purpose

The purposes of this paper are to analyze the path and speed of rural transformation (RT) and explore the relationship between farmer's income and RT as well as structural transformation (ST) and typology of RT in the past four decades in China.

Design/methodology/approach

Based on the major indicators of RT and ST, graphic illustration is used to analyze the relationships between these indicators and farmer's income using the time-series and cross-provincial data in 1978–2017.

Findings

While China has experienced significant RT and ST, the levels and speeds of these transformations differed largely among provinces. Higher and faster RT and ST are often positively associated with the higher and faster growth of rural income. Based on this study, a general typology of rural and structural transformations and rural income is developed. The likely impacts of institutions, policies and investments (IPIs) on RT are discussed.

Originality/value

The authors believe that the findings of this study provide the insights on regional RT and ST and policy implications to increase farmer's income through facilitating and speeding up RT and ST with appropriate IPIs during the rural transformation.
Should healthcare organisations offer ongoing rehabilitation services for patients undergoing haematopoietic cell transplant? A narrative review
Authors: Mohammed Jaleel , Kabir Russell , Bakhsh Hadeel R. , Greenfield Diana , Georgievna Volkova Alisa , Bulińska Aleksandra , Rai Jayanti , Gonzales Anne , Hashmi Shahrukh K.
Published: January 2021

Purpose

Hematopoietic stem cell transplant (HSCT) patients can suffer from long-term transplant-related complications that affect their quality of life and daily activities. This study, a narrative review, aims to report the impact of HCT complications, the benefits of rehabilitation intervention, the need for long-term care and highlights the research gap in clinical trials involving rehabilitation.

Design/methodology/approach

A comprehensive search strategy was performed on several databases to look for relevant articles published from 1998 to 2018. Articles published in English with the following terms were used: hematopoietic stem cell transplant, chronic graft-versus-host disease, rehabilitation, exercise, physical therapy, occupational therapy. A patient/population, intervention, comparison, and outcomes (PICO) framework was employed to ensure that the search strategies were structured and precise. Study year, design, outcome, intervention, sample demographics, setting and study results were extracted.

Findings

Of the 1,411 records identified, 51 studies underwent title/abstract screening for appropriateness, 30 were reviewed in full, and 19 studies were included in the review. The review found that, for the majority of patients who underwent HSCT and developed treatment-related complications, rehabilitation exercises had a positive impact on their overall quality of life. However, exercise prescription in this patient group has not always reflected the scientific approach; there is a lack of high-quality clinical trials in general. The review also highlights the need to educate healthcare policymakers and insurance companies responsible for rationing services to recognise the importance of offering long-term follow-up care for this patient group, including rehabilitation services.

Practical implications

A large number of HSCT patients require long-term follow-up from a multidisciplinary team, including rehabilitation specialists. It is important for healthcare policymakers and insurance companies to recognise this need and take the necessary steps to ensure that HSCT patients receive adequate long-term care. This paper also highlights the urgent need for high-quality rehabilitation trials to demonstrate the feasibility and importance of rehabilitation teams.

Originality/value

Healthcare policymakers and insurance companies need to recognise that transplant patients need ongoing physiotherapy for early identification of any functional impairments and appropriate timely intervention.
Verification of pattern unlock and gait behavioural authentication through a machine learning approach
Authors: Chaitanya Gogineni Krishna , Raja Sekhar Krovi
Published: January 2021

Purpose

The existing authentication procedures (pin, pattern, password) are not very secure. Therefore, the Gait pattern authentication scheme is introduced to verify the own user. The current research proposes a running Gaussian grey wolf boosting (RGGWB) model to recognize the owner.

Design/methodology/approach

The biometrics system plays an important role in smartphones in securing confidential data stored in them. Moreover, the authentication schemes such as passwords and patterns are widely used in smartphones.

Findings

To validate this research model, the unauthenticated user's Gait was trained and tested simultaneously with owner gaits. Furthermore, if the gait matches, the smartphone unlocks automatically; otherwise, it rejects it.

Originality/value

Finally, the effectiveness of the proposed model is proved by attaining better accuracy and less error rate.
Management control systems and performance in strategic supply relationships
Authors: Beuren Ilse Maria , Dal Vesco Delci Grapégia
Published: January 2021

Purpose

This study analyzes the relationship between two elements of the management control systems (MCSs) (performance measurement systems (PMSs) and socialization processes) and four dimensions of the theory of cooperation (information sharing, problem-solving, adaptability to changes and restraint from the use of power) and how this translates into performance in contracts of strategic supply relationships (SSRs).

Design/methodology/approach

A survey was carried out to investigate the theoretical model of Mahama (2006) in the empirical field. The population investigated is composed of service stations dealers affiliated with a union of southern Brazil, and the sample consists of 75 questionnaires.

Findings

The structural equation show that the two elements of the management control systems (PMS and socialization processes) do not influence performance when their direct effects are evaluated. However, when evaluated together with the cooperation, the results indicate that information sharing and problem-solving reflect into improved performance in contracts of SSRs.

Research limitations/implications

The results are partially similar to Mahama's study (2006). In this study, direct association between socialization processes and cooperation dimensions, related to adaptability to changes and restraints from the use of power, was not identified. Furthermore, the use of PMSs is not associated with the improvement of performance in SSRs.

Originality/value

The distinction of this and Mahama's (2006) study focuses on the types of contracts, to identify whether the dimensions of cooperation imply in the contractual relationship.
Disclosure Prominence and the Quality of Non‐GAAP Earnings
Authors: CHEN JASON V. , GEE KURT H. , NEILSON JED J.
Published: January 2021

The SEC prohibits the presentation of non‐GAAP measures before corresponding GAAP measures; however, a large proportion of non‐GAAP reporters present non‐GAAP EPS before GAAP EPS in their earnings announcements. This noncompliance raises questions about whether firms use prominence to highlight higher or lower quality non‐GAAP information. For firms reporting non‐GAAP EPS between 2003 and 2016, prominent non‐GAAP EPS is associated with higher quality non‐GAAP reporting. Further tests reveal that nonregulatory incentives, rather than regulatory costs, explain this relation. Specifically, prominence is associated with higher quality non‐GAAP reporting in settings where prominence is not regulated, investors ignore prominence when non‐GAAP reporting quality is lower, and the minority of firms using prominence to mislead exhibit characteristics associated with weaker investor monitoring. Overall, we provide evidence that regulatory noncompliance can reflect an intent to inform, and that most firms use prominence to highlight higher quality non‐GAAP information despite prohibitive regulation.
Factors associated with hepcidin‐25 levels in maintenance hemodialysis patients
Authors: Savković Miljan , Simić‐Ogrizović Sanja , Dopsaj Violeta
Published: January 2021

This study aimed to investigate the factors that are independently associated with hepcidin‐25 and its relationship with doses of erythropoiesis‐stimulating agents (ESAs) and intravenous iron in stable maintenance hemodialysis patients (smHD) stratified by ESAs administration. In 103 adult smHD (ESAs therapy (N = 64) and ESAs‐free (N = 39)), median values of biologically active hepcidin‐25 (chemiluminescent direct ELISA assay) and ferritin levels were significantly higher whereas red blood cell count, hemoglobin, and hematocrit values were lower in ESAs therapy compared to ESAs‐free group (P < .001, for all). Our results suggest that ESAs‐independent smHD exhibit supposedly normal hepcidin‐25 levels and preserved iron homeostasis, with a lower degree of anemia. The results of our multivariable model indicate that hepcidin‐25 levels are independently and positively associated with iron stores and inflammation, and inversely with active erythropoiesis, regardless of ESAs administration. Maintenance ESAs and the intravenous iron dose were not related to hepcidin‐25 levels.
Phosphobacteria as key actors to overcome phosphorus deficiency in plants
Authors: Castagno Luis N. , Sannazzaro Analía I. , Gonzalez María E. , Pieckenstain Fernando L. , Estrella María J.
Published: January 2021

Phosphorus (P), an essential macronutrient for all living organisms, is required in large amounts for the growth and development of plants. Although total soil P level is high, P bioavailability to plants is suboptimal in most soils because of high fixation rates into inorganic and organic insoluble complexes. Hence, plants are highly dependent on mechanisms that allow them to adapt to low‐phosphate stress and/or achieve suitable levels of soluble P on the root surface. In this regard, the rhizospheric microbiota plays a key role in facilitating P nutrition and has long been recognised for their potential use as an environmental‐friendly alternative to chemical P fertilisation. Herein, we outline the advances in the identification of phosphate solubilising bacteria and phosphate mineralising bacteria, collectively known as phosphobacteria, and their role in rendering P accessible to plants. We review and discuss research progress related to the introduction of phosphobacteria and/or P‐mineralising enzymes into soil, as well as plant transformation with bacterial genes that encode such enzymes, as strategies to improve plant growth and P nutrition. We also provide an overview of studies about the impact of variations in soil P levels on the structure of soil and rhizospheric microbial communities and the potential consequences of such perturbations on plant growth. Finally, we discuss possible directions for future research to optimise the efficiency of biofertilisation strategies based on the use of phosphobacteria.