bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arabidopsis MLO4 Functions as a Ca2+ Channel Essential for Mechanosensing in Root Tips
Authors: Zhang Zhengli , Sun Yujia , Lu Pengfei , Feng Changxin , Niu Qi , Lin Geng , Kong Dongdong , Liu Liangyu , Luan Sheng , Li Legong , Hou Congcong 
Published: June 2022

ABSTRACTMechanical stimuli guide root growth to avoid obstacles in the soil. Although mechanisms underlying root mechanosensing remain largely unknown, calcium signaling is proposed to be an early event that proceeds directional root growth. In response to mechanical perturbations, root cells produce transient spikes in the cytosolic free Ca2+ levels. Loss-of-function mutations of MLOs cause root curling upon contact with hard surface of obstacles, the mechanism for MLOs action in root thigmomorphogenesis has been enigmatic. WT and mlo4 seedlings were grown on MS media containing gradient agar concentrations mimicking different levels of soil hardness and compared their root growth into the agar gradient mlo4 had much less roots penetrated the harder agar barrier as compared to WT roots. The channel activity of MLO4 was examined in Xenopus oocytes using the two-electrode voltage clamp (TEVC) method. The TEVC recording showed that the oocytes injected with MLO cRNA displayed large inward currents in the presence of Ca2+. MLO4 rescued the cch1/mid1 from growth arrest by the pheromone, these results indicate that MLO4 constitutes a novel Ca2+-permeable channel. Ca2+ spike was hardly detectable in mlo4/GCaMP6s seedings in response to a hard surface during root elongation. In summary, MLO4 functions as a typical Ca2+ channel that links touch stimulation to Ca2+ elevation in root tip cells.
Chromosomal conservatism vs chromosomal megaevolution: enigma of karyotypic evolution in Lepidoptera
Authors: Pazhenkova Elena A. , Lukhtanov Vladimir A. 
Published: June 2022

AbstractIn the evolution of many organisms, periods of very slow genome reorganization (=chromosomal conservatism) are interrupted by bursts of numerous chromosomal changes (=chromosomal megaevolution). However, the patterns, mechanisms, and consequences of conservative and rapid chromosomal evolution are still poorly understood and widely discussed. Here we show that in blue butterflies (Lepidoptera: Lycaenidae), the periods of chromosome number conservatism are characterized by the real stability of most autosomes and the highly dynamic evolution of the sex chromosome Z, which, due to autosome-sex chromosome fusions and fissions, is carried out according to the cycle Z=>NeoZ1=>Z=>NeoZ2=>Z=>NeoZ3. These fusions and fissions result in a fluctuation of chromosomal number (±1) around the ancestral value, a phenomenon previously observed (but not explained) in numerous groups of Lepidoptera. In the phase of chromosomal megaevolution, the explosive increase in the chromosome number occurs mainly due to simple chromosomal fissions, in some cases complicated by autosomal translocations. Interestingly, these translocations are not random and found to occur only between fragmented chromosomes originated from the same primary linkage group. We also found that the Z chromosomes of two closely related Lysandra species are differentiated by a large inversion. We argue that the special role of sex chromosomes in speciation can be reinforced via sex chromosome – autosome fusion. The cycles of fusions and fissions of sex chromosomes with autosomes, such as those found in the blue butterflies, indicate that the species divergence driven by neo-Z chromosome formation is widely distributed in Lepidoptera.
Simultaneously cholinergic projection in Ascending and Descending Circuits from Midbrain
Authors: Zhao Peilin , Jiang Tao , Wang Huading , Jia Xueyan , Li Anan , Yuan Jing , Luo Qingming , Li Xiangning , Gong Hui 
Published: June 2022

AbstractThe midbrain participates in complex neural information processing in the ascending and descending circuits, but their organization remains unclear due to the lack of comprehensive dissection of the characterization of individual neurons. Combining fluorescent micro-optical sectional tomography with sparse labeling, we acquired the whole-brain dataset with high resolution and reconstructed the detailed morphology of the pontine-tegmental cholinergic neurons (PTCNs). As the main cholinergic system of the midbrain, the individual PTCNs own abundant axons with length up to 60 cm and 5000 terminal branches and innervate multiple brain regions from the spinal cord to cortex in both hemispheres. According to various targeting regions in the ascending and descending circuits, individual PTCNs could be grouped into four types and the axonal fibers of cholinergic neurons in the pedunculopontine nucleus present more divergent while neurons in the laterodorsal tegmental nucleus contain richer axonal fibers and dendrites. In the axonal targeting nuclei, such as in the thalamus or cortex, the individual neurons innervate multiple sub-regions with separate pathways. These results provide the detailed organization characterization of the cholinergic neurons to understand the connection logic of the midbrain.
Statistical Methods for Detecting Circadian Rhythmicity and Differential Circadian Patterns with Repeated Measurement in Transcriptomic Applications
Authors: Ding Haocheng , Meng Lingsong , Xing Chengguo , Esser Karyn A. , Huo Zhiguang 
Published: June 2022

AbstractCircadian analysis via transcriptomic data has been successful in revealing the clock output changes underlying many diseases and physiological processes. Repeated measurement design in a circadian study is prevalent, in which the same subject is repeatedly measured over time. Several methods are currently available to perform circadian analysis, however, none of them take advantage of the repeated measurement design. And ignoring the within-subject correlation from the repeated measurement could result in lower statistical power. To address this issue, we developed linear mixed model based methods to detect (i) circadian rhythmicity (i.e., Rpt_rhythmicity) and (ii) differential circadian patterns comparing two experimental conditions (i.e., Rpt_diff). Our model includes a subject-specific random effect, which will account for the within-subject correlation. Via simulations, we showed our method not only could control the type I error rate around the nominal level, but also achieve higher statistical power compared to other methods that cannot model repeated measurement. The superior performance of Rpt_rhythmicity and Rpt_diff were also demonstrated in two real data applications, including a human restricted feeding data and a human sleep restriction data. An R package for our methods is publicly available on GitHub to promote the application of our methods.
Pathobionts from chemically disrupted gut microbiota induce insulin-dependent diabetes in mice
Authors: Yang Xin , Wang Zhiyi , Niu Junling , Zhai Rui , Xue Xinhe , Wu Guojun , Meng Guangxun , Yuan Huijuan , Zhao Liping , Zhang Chenhong 
Published: June 2022

ABSTRACTBackgroundDysbiotic gut microbiome, genetically predisposed or chemically disrupted, has been linked with insulin-dependent diabetes (IDD) including autoimmune type 1 diabetes (T1D) in both humans and animal models. However, specific IDD-inducing gut bacteria remain to be identified and their casual role in disease development demonstrated via experiments that can fulfill Koch’s postulates.ResultsHere, we show that novel gut pathobionts in the Muribaculaceae family, enriched by a low-dose dextran sulfate sodium (DSS) treatment, translocated to the pancreas and caused local inflammation, beta cell destruction and IDD in C57BL/6 mice. Antibiotic removal and transplantation of gut microbiota showed that this low DSS disrupted gut microbiota was both necessary and sufficient to induce IDD. Reduced butyrate content in the gut and decreased gene expression levels of an antimicrobial peptide in the pancreas allowed for the enrichment of members in the Muribaculaceae family in the gut and their translocation to the pancreas. Pure isolate of one such members induced IDD in wildtype germ-free mice on normal diet either alone or in combination with normal gut microbiome after gavaged into stomach and translocated to pancreas.ConclusionThe pathobionts that are chemically enriched in dysbiotic gut microbiota are sufficient to induce insulin-dependent diabetes after translocation to the pancreas. This indicates that IDD can be mainly a microbiome-dependent disease, inspiring the need to search for novel pathobionts for IDD development in humans.
The magnocellular division of the human medial geniculate nucleus preferentially responds to auditory transients
Authors: Meng Qianli , Schneider Keith A. 
Published: June 2022

AbstractThe medial geniculate nucleus (MGN), the auditory relay in the thalamus, is composed of three anatomical subdivisions: the ventral, dorsal and medial or magnocellular division. The functional differences among these nuclei have not been studied in humans, and in particular, the function of the magnocellular division is poorly understood in mammals in general. We anatomically segmented the MGN using proton-density-weighted magnetic resonance images (MRI) and measured the functional responses of the MGN to sustained and transient sounds, using functional MRI (fMRI). We observed that voxels in the ventromedial portion of the MGN, corresponding to the magnocellular division, exhibited a strong preference to transient sounds, whereas the remainder of the MGN showed no preference between sustained and transient sounds. We concluded that the magnocellular neurons in the MGN parallel the magnocellular neurons in its visual counterpart, the lateral geniculate nucleus (LGN), and constitute an information stream specialized for encoding stimuli dynamics.Significance statementThe medial geniculate nucleus is the auditory relay in the thalamus. It is composed of three anatomical divisions, of which the function of the magnocellular division is poorly understood. We show, using functional magnetic resonance imaging (fMRI) in humans, that the magnocellular neurons are strongly activated by transient auditory stimuli, similar to the magnocellular neurons in the lateral geniculate nucleus, the visual thalamic relay, which are rapidly adapting and specialized to encode visual transients. These results confirm that the auditory system represents stimuli using parallel information streams, employing similar encoding strategies as in other sensory modalities.
Widespread epistasis among beneficial genetic variants revealed by high-throughput genome editing
Authors: Ang Roy Moh Lik , Chen Shi-An Anderson , Kern Alexander F. , Xie Yihua , Fraser Hunter B. 
Published: June 2022

AbstractGenetic interactions occur when a variant’s phenotypic effect is altered by variation at other genomic loci. Also known as epistasis, these interactions shape the genetic architecture of complex traits and modify phenotypes across genetic backgrounds. However, the factors associated with their occurrence remain poorly understood. To investigate this, we employed high-throughput genome editing to measure the fitness effects of 1,826 naturally polymorphic variants in four genetically diverse strains of Saccharomyces cerevisiae. About 31% of variants affect fitness in a common laboratory environment, of which 24% have strain-specific fitness effects indicative of epistasis. We found that beneficial variants are more likely to exhibit genetic interactions, and that genetic interactions are depleted among variants at higher allele frequencies. In addition, we demonstrate that these epistatic interactions for fitness can be mediated by specific traits such as flocculation ability. This work suggests that adaptive evolution from standing variation will often involve trade-offs where a variant is only beneficial in some genetic backgrounds, potentially explaining why many beneficial variants remain polymorphic. In sum, we provide a framework to understand the factors influencing epistasis in natural genetic variants with single-nucleotide resolution, revealing widespread epistasis among beneficial variants.
Effectiveness of BNT162b2 booster doses in England: an observational study in OpenSAFELY-TPP
Authors: Hulme William J , Williamson Elizabeth J , Horne Elsie , Green Amelia , Nab Linda , Keogh Ruth , Parker Edward PK , Walker Venexia , Palmer Tom , Curtis Helen , Wiedemann Milan , Cunningham Christine , Walker Alex J , Fisher Louis , MacKenna Brian , Rentsch Christopher T , Schultze Anna , Bhaskaran Krishnan , Tazare John , Tomlinson Laurie , McDonald Helen I , Morton Caroline E , Croker Richard , Andrews Colm , Parks Robin , Hopcroft Lisa , Massey Jon , Morley Jessica , Mehrkar Amir , Bacon Seb , Evans Dave , Inglesby Peter , Hickman George , Davy Simon , Dillingham Iain , Ward Tom , Mahalingasivam Viyasaan , Zheng Bang , Douglas Ian J , Evans Stephen JW , Bates Chris , Sterne Jonathan AC , Hernán Miguel A , Goldacre Ben 
Published: June 2022

AbstractBackgroundThe UK COVID-19 vaccination programme delivered its first “booster” doses in September 2021, initially in groups at high risk of severe disease then across the adult population. The BNT162b2 Pfizer-BioNTech vaccine was used initially, with Moderna mRNA-1273 subsequently also used.MethodsWe used the OpenSAFELY-TPP database, covering 40% of English primary care practices and linked to national coronavirus surveillance, hospital episodes, and death registry data, to estimate the effectiveness of boosting with BNT162b2 compared with no boosting in eligible adults who had received two primary course vaccine doses between 16 September and 16 December 2021 when the Delta variant of SARS-CoV-2 was dominant. Follow up was for up to 10 weeks. Each booster recipient was matched with an unboosted control on factors relating to booster priority status and prior immunisation. Additional factors were adjusted for in Cox models estimating hazard ratios (HRs). Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, COVID-19 death and non-COVID-9 death. Booster vaccine effectiveness was defined as 1−HR.ResultsAmong 4,352,417 BNT162b2 booster recipients matched with unboosted controls, estimated effectiveness of a booster dose compared with two doses only was 50.7% (95% CI 50.1-51.3) for positive SARS-CoV-2 test, 80.1% (78.3-81.8) for COVID-19 hospitalisation, 88.5% (85.0-91.1) for COVID-19 death, and 80.3% (79.0-81.5) for non-COVID-19 death.Estimated effectiveness was similar among those who had received a BNT162b2 or ChAdOx1-S two-dose primary vaccination course, but effectiveness against severe COVID-19 was slightly lower in those classified as clinically extremely vulnerable (76.3% (73.1-79.1) for COVID-19 hospitalisation, and 85.1% (79.6-89.1) for COVID-19 death). Estimated effectiveness against each outcome was lower in those aged 18-65 years than in those aged 65 and over.ConclusionOur findings are consistent with strong protection of BNT162b2 boosting against positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death.
Understanding COVID-19 admissions in the UK; Analysis of Freedom of Information Requests
Authors: Jefferson T. , Brassey J , Heneghan C 
Published: June 2022

AbstractBackgroundThe progression and severity of the COVID 19 pandemic have been measured based on the daily and total numbers of cases, hospitalisations and deaths. We focused on the nature of hospitalisations from 2020 to 2022.MethodsWe analysed the role played by SARS-CoV-2 in the pandemic in the UK; we lodged FOI requests to Public Health Wales (PHW), Scotland (PHS), and Northern Ireland (PHA NI), the UK Health Security Agency (UKHSA) and NHS England. We asked for all-cause hospital admission monthly numbers reported by days of positivity to SARS-CoV-2 since admission from March 2020. We grouped replies by respondents. We considered any positive tests acquired from day 8 post admission as evidence of in hospital transmission.ResultsPHW, PHS and PHA NI, provided data within two months. The proportion of people admitted who became positive after eight or more days was 33% in Northern Ireland, 24% in Scotland and 45% in Wales. There are seasonal fluctuations reflecting community admissions but no evidence that the proportion of those infected in hospitals reduced over time. No authorities had viral load or symptoms data relating to their datasets. Given the limitations in PCR reporting, it is impossible to know how many “positive” cases were active. UKHSA did not hold the data, and NHS England did not clarify the content of its website.ConclusionAggregate data of “cases of Covid” in hospitals should not be used to inform policy of decision-makers until coordination, and proper interpretation of the dataset are instigated.
Chronic activation of Toll-like receptor 2 induces an ichthyotic skin phenotype
Authors: Tagoe Hephzi , Hassan Sakinah , Youssef Gehad , Heywood Wendy , Mills Kevin , Harper John I. , O’Shaughnessy Ryan F.L. 
Published: June 2022

AbstractIchthyosis defines a group of chronic conditions that manifest phenotypically as a thick layer of fish-like scales in response to disorders of cornification and often affects the entire skin. While the gene mutations that lead to ichthyosis are well documented, the actual signalling mechanisms that lead to scaling are poorly characterised, however recent publications suggest that there are common mechanisms active in ichthyotic tissue, and in analogous models of ichthyosis. Combining gene expression analysis of gene-specific shRNA knockdowns of more severe autosomal recessive congenital ichthyoses (ARCI) and proteomic analysis of skin scale from ARCI patients, we identified a common activation of the Toll-like receptor (TLR) 2 pathway. Exogenous activation of TLR2 led to increased expression of important cornified envelope genes and in organotypic culture caused hyperkeratosis. Conversely blockade of TLR2 signalling in ichthyosis patient keratinocytes and our shRNA models reduced the expression of keratin 1, a structural protein overexpressed in ichthyosis scale. A time-course of Tlr2 activation in rat epidermal keratinocytes revealed that although there was rapid initial activation of innate immune pathways, this was rapidly superseded by widespread up-regulation of epidermal differentiation related proteins. Both NFκβ phosphorylation and the Gata3 up-regulation was associated with this switch and Gata3 overexpression was sufficient to increase Keratin 1 expression. Taken together, these data define a dual role for Tlr2 during epidermal barrier repair, that may be a useful therapeutic modality in treating diseases of epidermal barrier dysfunction.
Projecting the futures of plant traits across habitats in Central Europe
Authors: Golivets Marina , Knapp Sonja , Essl Franz , Lenzner Bernd , Latombe Guillaume , Leung Brian , Kühn Ingolf 
Published: June 2022

ABSTRACTMany plant traits covary with environmental gradients, reflecting shifts in adaptive strategies under changing conditions and thus providing information about potential consequences of future environmental change for vegetation and ecosystem functioning. Despite extensive efforts to map trait–environment relationships, the evidence remains heterogeneous and often conflicting, partially because of insufficient consideration of distinct trait syndromes for certain growth forms and habitats. Moreover, it is unclear whether traits of non-native and native plant taxa respond similarly to environmental gradients, limiting our ability to assess the consequences of future plant invasions. Here, using comprehensive data for Germany and the Czech Republic and a Bayesian multilevel modeling framework, we assessed relationships between three major plant traits (maximum height,Hmax; specific leaf area,SLA; and seed mass,SM) and environmental factors (7 climate variables and percentage of urban land cover) for native and non-native woody and herbaceous plant assemblages across six broad habitat types. We projected the trait change in these assemblages under future environmental change scenarios until 2081–2100 and quantified the change in trait difference between native and non-native plants. Our models depicted multiple trait–environment relationships, with several important differences attributed to biogeographical status and woodiness within and across habitat types. The overall magnitude of trait change is projected to be greater for non-native than native taxa and to increase under more extreme scenarios. Native woody plant assemblages may generally experience an increase across all three traits, whereas woody non-natives may decline inHmaxand increase inSLAandSM. HerbaceousHmaxis expected to increase andSLAto decrease in most habitats. The obtained trait projections highlight the conditions under which non-native plants may prevail over natives and vice versa and can serve as a starting point for projecting future changes in ecosystem functions and services.
Is the production of reactive oxygen and nitrogen species by macrophages associated with better infectious control in the experimental disseminated and pulmonary mucormycosis?
Authors: dos Santos Amanda Ribeiro , Fraga-Silva Thais Fernanda , Almeida Donanzam Débora de Fátima , Finatto Angela Carolina , Marchetti Camila , Andrade Maria Izilda , de Arruda Olavo Speranza , de Arruda Maria Sueli Parreira , Venturini James 
Published: June 2022

AbstractDifferent levels of resistance againstRhizopus oryzaeinfection have been observed between inbred (BALB/c) and outbred (Swiss) mice, with is associated with the genetic background of each mouse strain. Considering that macrophages play an important role in host resistance toRhizopusspecies, we use the different infectious outcomes observed in experimental mucormycosis to identify the most efficient macrophages responses pattern againstR. oryzae in vitroandin vivo. For this, we compared BALB/c and Swiss macrophage activity pre-and-post intravenous or intratrachealR. oryzaeinfections. Production of hydrogen peroxide (H2O2) and nitric oxide (NO) was determined in cultures of peritoneal (PMΦ) or alveolar macrophages (AMΦ) challenged, or not, with heat-killed spores ofR. oryzae. Levels of TNF-α and IL-10 were also measured to enhance our findings. Naïve PMΦ from BALB/c increased the production of H2O2, TNF-α, and IL-10 in the presence of heat-killed spores ofR. oryzae, while naïve PMΦ from Swiss mice was less responsive. Naïve AMΦ from two strains of mice were less reactive to heat-killed spores ofR. oryzaethan PMΦ. On 30 days ofR. oryzaeintravenous infection, lower fungal load in BALB/c strain of mice was accompanied by higher production of H2O2by PMΦ when compared with Swiss mice. Differently, AMΦ from BALB/c mice showed higher production of NO, TNF-α, and IL-10 after 7 days of intratracheal infection and after 30 days, lower fungal load, when compared with Swiss mice. According to the set of experiments performed, our findings reveal that independently of mice strain, PMΦ is more reactive againstR. oryzaein the first contact than AMΦ. In addition, increased PMΦ production of H2O2at the end of disseminated infection is related to efficient fungal clearance observed in resistant (BALB/c). Our findings provide new evidence to understand the parasite-hosts relationship in mucormycosis.