bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tea plant (Camellia sinensis) FLOWERING LOCUS C-like gene CsFLC1 is correlated with bud dormancy and triggers early flowering in Arabidopsis
Authors: Liu Ying , Dreni Ludovico , Zhang Haojie , Zhang Xinzhong , Li Nana , Zhang Kexin , Di Taimei , Wang Lu , Yang Yajun , Hao Xinyuan , Wang Xinchao 
Published: September 2022

AbstractFlowering and bud dormancy are crucial stages in the life cycle of perennial angiosperms in temperate climates. MADS-box family genes are involved in many plant growth and development processes. Here, we identified 3 MADS-box genes in tea plant belonging to the FLOWERING LOCUS C (CsFLC) family. We monitored CsFLC1 transcription throughout the year and found that CsFLC1 was expressed at a higher level during the winter bud dormancy and flowering phases. To clarify the function of CsFLC1, we developed transgenic Arabidopsis thaliana plants heterologously expressing 35S::CsFLC1. These lines bolted and bloomed earlier than the WT (Col-0), and the seed germination rate was inversely proportional to the increased CsFLC1 expression level. RNA-seq of 35S::CsFLC1 transgenic Arabidopsis showed that many genes responding to ageing, flower development and leaf senescence were affected, and phytohormone-related pathways were especially enriched. According to the results of hormone content detection and RNA transcript level analysis, CsFLC1 controls flowering time possibly by regulating SOC1, AGL42, SEP3 and AP3 and hormone signalling, accumulation and metabolism. Our results suggest that CsFLC1 might play dual roles in flowering and winter bud dormancy and provide new insight into the molecular mechanisms of FLC in tea plants as well as other plant species.HighlightThree FLOWERING LOCUS C-like genes were identified in tea plants, among them CsFLC1 played dual roles in flowering and winter bud dormancy.
Ecological corridors homogenize plant root endospheric mycobiota
Authors: Hu Jie , Vandenkoornhuyse Philippe , Khalfallah Fadwa , Causse-Védrines Romain , Mony Cendrine 
Published: September 2022

SummaryEcological corridors have been shown to promote species coexistence in fragmented habitats where dispersal limits species fluxes. The corridor concept was developed and investigated mainly by focusing on macroorganisms while microorganisms, the invisible majority of biodiversity, have been disregarded.Combining an experimental corridor-mesocosm design with high-throughput amplicon sequencing, we analyzed the effect of corridors on the dynamics of endospheric fungal assemblages associated with plant roots at metric scale over two years (i.e. at five time points).We show that the plant symbiotic compartment was sensitive to corridor effects when the corridors were set up at a small spatial scale. The endospheric mycobiota of connected plants displayed higher species richness, lower beta-diversity, and a more deterministic assembly than the mycobiota of isolated plants. These effects became more pronounced with the development of host plants.Biotic corridors composed of host plants may thus play a key role in the spatial dynamics of microbial community and may influence microbial diversity and related ecological functions.
Neural responses to movie naturalistic stimuli are related to listening demand in cochlear implant users
Authors: Xiu Bowen , Paul Brandon T. , Chen Joseph , Le Trung , Lin Vincent , Dimitrijevic Andrew 
Published: September 2022

AbstractThere is a weak relationship between clinical and self-reported speech perception outcomes in cochlear implant (CI) listeners. Such poor correspondence may be due to differences in clinical and “real-world” listening environments and stimuli. Speech sounds in the real world are often accompanied by visual cues, background environmental noise and is generally in the context of a connected conversation. The aims of this study were to determine if brain responses to naturalistic speech could index speech perception and listening demand in CI users. Accordingly, we recorded high density EEG while CI users listened/watched a naturalistic stimulus (i.e., the television show, “The Office”). We used continuous EEG to quantify “speech neural tracking” (i.e., TRFs, temporal response functions) to the television show audio track and additionally 8–12 Hz (alpha) brain rhythms commonly related to listening effort. Background noise at three different signal-to-noise ratios (SNRs), +5, +10, and +15 dB were presented to vary the difficulty of following the television show mimicking a natural noisy environment. The task included an additional condition of audio-only (no video). After each condition, participants subjectively rated listening demand and the degree of words and conversations they felt they could understand. Fifteen CI users reported progressively higher degrees of listening demand and less words and conversation with increasing background noise. Listening demand and conversation understanding in the audio-only condition was comparable to that of the highest noise condition (+5 dB). The addition of the background noise reduced the degree of speech neural tracking. Mixed effect modeling showed that listening demand and conversation understanding were correlated to cortical speech tracking such that high demand and low conversation understanding lower associated with lower amplitude TRFs. In the high noise condition, greater listening demand was negatively correlated to parietal alpha power such that higher demand was related to lower alpha power. No significant correlations were observed between TRF/alpha and clinical speech perception scores. These results are similar to previous findings showing little relationship between speech perception and quality of life in CI users. However, the physiological responses to complex natural speech may anticipate aspects of quality-of-life measures such as self-perceived listening demand.
Optimization and deoptimization of codons in SARS-CoV-2 and the implications for vaccine development
Authors: Wu Xinkai , Shan Kejia , Zan Fuwen , Tang Xiaolu , Qian Zhaohui , Lu Jian 
Published: September 2022

ABSTRACTThe spread of Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 coronavirus, has progressed into a global pandemic. To date, thousands of genetic variants have been identified across SARS-CoV-2 isolates from patients. Sequence analysis reveals that the codon usage of viral sequences decreased over time but fluctuated from time to time. In this study, through evolution modeling, we found that this phenomenon might result from the virus’ preference for mutations during transmission. Using dual luciferase assays, we further discovered that the deoptimization of codons on viruses might weaken protein expression during the virus evolution, indicating that the choice of codon usage might play important role in virus fitness. Finally, given the importance of codon usage in protein expression and particularly for mRNA vaccine, we designed several omicron BA.2.12.1 and BA.4/5 spike mRNA vaccine candidates based on codon optimization, and experimentally validated their high levels of expression. Our study highlights the importance of codon usage in virus evolution and mRNA vaccine development.
Tracking canopy gap dynamics across four sites in the Brazilian Amazon
Authors: Gorgens Eric Bastos , Keller Michael , Jackson Toby D , Marra Daniel Magnabosco , Reis Cristiano Rodrigues , de Almeida Danilo Roberti Alves , Coomes David A. , Ometto Jean Pierre 
Published: September 2022

AbstractBackground information to give context to the studyCanopy gaps are the most evident manifestation of how disturbances disrupt forest landscapes. The size distribution and return frequency of gaps, and subsequent recovery processes, determine whether the old-growth state can be reached.The aim or research questionWe used remote sensing metrics to compare the disturbance regime of four Amazon regions based on the size distribution of gaps, their dynamics and geometric characteristics.A brief summary of the methodology usedWe assessed gap dynamics at four sites in the central, central eastern, southeastern, and northeastern regions of the Brazilian Amazon using repeated airborne laser scanning surveys. We developed a novel analysis to quantify four possible stages of gap dynamics: formation, expansion, persisting and recovering. For that, we overlapped layers of gap locations from two consecutive airborne laser scanning surveys.Key results with some significance measuresThe gap fraction in our study sites varied between 1.26% to 7.84%. All the sites have similar proportion of gaps among size classes. What notably changed between sites was not the gap size-distribution, but the relative importance of stages of gap dynamics. Growing and persisting rates were greatest in the site with the stronger seasonal variation in climate, lower annual precipitation, higher mean wind speed and higher solar radiation.The conclusions, which address the main aimsThe concept of stability reflects the tendency of a system to quickly return to a position of equilibrium when disturbed. We showed that gap dynamics varied among sites, with one example of low recovery rate contrasted to three other sites with faster recovery. Our results support that such as assessing the size distribution of gaps, investigating their return frequency and severity is crucial for understanding forest dynamics at the landscape and regional scales.
Combined blockade of VEGF, Angiopoietin-2, and PD1 reprograms glioblastoma endothelial cells into quasi-antigen-presenting cells
Authors: Amoozgar Zohreh , Ren Jun , Wang Nancy , Andersson Patrik , Ferraro Gino B. , Krishnan Shanmugarajan , Lei Pin-Ji , Subudhi Sonu , Kawaguchi Kosuke , Tay Rong En , Gomes-Santos Igor L. , Huang Peigen , Kim Hye-Jung , Fukumura Dai , Jain Rakesh K. 
Published: September 2022

AbstractGlioblastoma (GBM) remains a highly aggressive and uniformly fatal primary tumor, which resists cytotoxic, targeted, antiangiogenic, and immune therapies, even when used in combination. Here we report that tumor endothelial cell dysfunction confers resistance to immunotherapy in preclinical GBM models. Anti-VEGF-therapy-induced vascular normalization is insufficient to fully restore the endothelial cell function. Strikingly, concomitant blockade of Ang2, VEGF, and PD1 reprograms dysfunctional endothelial cells to quasi-antigen presenting cells and upregulates receptors required for cytotoxic T lymphocyte entry into the tumor. Blocking VEGF, Ang2, and PD1 induces durable anti-tumor T cell responses. Upregulation of the transcription factor T-bet is both necessary and sufficient for generating resident memory T cells elicited by this combination therapy. In summary, our study reveals the role of Ang2 in resistance to PD1-blockade and provides a compelling rationale for clinical evaluation of blocking Ang2 along with VEGF and PD1 in GBM patients.Statement of SignificanceOur study is the first to demonstrate Ang2 as a resistance pathway for both αVEGF and αPD1 in GBM. Concomitant blockade of Ang2 reprograms endothelial cells to recruit, activate and retain CD8 T cells, overcomes resistance to αVEGF and αPD1, and imparts T cell memory formation via T-bet in GBM.
Structures and membrane interactions of native serotonin transporter in complexes with psychostimulants
Authors: Yang Dongxue , Zhao Zhiyu , Tajkhorshid Emad , Gouaux Eric 
Published: September 2022

AbstractThe serotonin transporter (SERT) is a member of the SLC6 neurotransmitter transporter family that mediates serotonin reuptake at presynaptic nerve terminals. SERT is the target of both therapeutic antidepressant drugs and illicit psychostimulant substances such as cocaine and methamphetamines, which are small molecules that perturb normal serotonergic transmission by interfering with serotonin transport. Despite decades of studies, important functional aspects of SERT such as the oligomerization state of native SERT and its interactions with potential proteins remain unresolved. Here we develop methods to isolate SERT from porcine brain (pSERT) using a mild, non-ionic detergent, utilize fluorescence- detection size-exclusion chromatography to investigate its oligomerization state and interactions with other proteins, and employ single-particle cryo-electron microscopy to elucidate the structures of pSERT in complexes with methamphetamine or cocaine, providing structural insights into psychostimulant recognition and accompanying pSERT conformations. Methamphetamine and cocaine both bind to SERT central site, stabilizing the transporter in an outward open conformation. We also identify densities attributable to multiple cholesterol or cholesteryl hemisuccinate (CHS) molecules, as well as to a detergent molecule bound to SERT allosteric site. Under our conditions of isolation, we find that pSERT is best described as a monomeric entity, isolated without interacting proteins, and is ensconced by multiple cholesterol or CHS molecules.SignificanceThe serotonin transporter (SERT) is the target of antidepressants and illicit psychostimulants. Despite its importance in the nervous, cardiovascular and gastrointestinal systems, there is no direct knowledge of SERT’s oligomerization state(s) and interactions with other proteins. Here, we develop methods to isolate porcine SERT (pSERT) from native brain tissue in the presence of a mild, non-ionic detergent, and investigated its properties by biochemical, structural and computational methods. We show how cocaine and methamphetamine exert their pharmacological effect on SERT, binding to a site halfway across the membrane-spanning region of the transporter, stabilizing pSERT in an outward open conformation. pSERT is best described as a monomeric entity, requiring neither oligomerization or additional proteins for its structure or function.
Combined Molnupiravir and Nirmatrelvir Treatment Improves the Inhibitory Effect on SARS-CoV-2 in Rhesus Macaques
Authors: Rosenke Kyle , Lewis Matt C. , Feldmann Friederike , Bohrnsen Eric , Schwarz Benjamin , Okumura Atsushi , Bohler W. Forrest , Callison Julie , Shaia Carl , Bosio Catharine M. , Lovaglio Jamie , Saturday Greg , Jarvis Michael A. , Feldmann Heinz 
Published: September 2022

AbstractThe periodic emergence of SARS-CoV-2 variants of concern (VOCs) with unpredictable clinical severity and ability to escape preexisting immunity emphasizes the continued need for antiviral interventions. Two small molecule inhibitors, molnupiravir (MK-4482), a nucleoside analog, and nirmatrelvir (PF-07321332), a 3C-like protease inhibitor, have each recently been approved as monotherapy for use in high risk COVID-19 patients. As preclinical data are only available for rodent and ferret models, we originally assessed the efficacy of MK-4482 and PF-07321332 alone and then in combination Against infection with the SARS-CoV-2 Delta VOC in the rhesus macaque COVID-19 model. Notably, use of MK-4482 and PF-07321332 in combination improved the individual inhibitory effect of both drugs. Combined treatment resulted in milder disease progression, stronger reduction of virus shedding from mucosal tissues of the upper respiratory tract, stronger reduction of viral replication in the lower respiratory tract, and reduced lung pathology. Our data strongly indicate superiority of combined MK-4482 and PF-07321332 treatment of SARS-CoV-2 infections as demonstrated here in the closest COVID-19 surrogate model.One Sentence SummaryThe combination of molnupiravir and nirmatrelvir inhibits SARS-CoV-2 replication and shedding more effectively than individual treatments in the rhesus macaque model.
Roles of the distinct N-terminal amino acid between H3 and H3.3 in Drosophila male germline stem cell lineage
Authors: Chandrasekhara Chinmayi , Ranjan Rajesh , Urban Jennifer A. , Ku Wai Lim , Snedeker Jonathan , Zhao Keji , Chen Xin 
Published: September 2022

AbstractAdult stem cells undergo asymmetric cell divisions to produce two daughter cells with distinct cell fates: one capable of self-renewal and the other committed for differentiation. Mis-regulation of this delicate balance can lead to cancer and tissue degeneration. During asymmetric division of Drosophila male germline stem cells (GSCs), preexisting (old) and newly synthesized histone H3 are differentially segregated whereas old and new histone variant H3.3 are more equally inherited. However, what underlies these distinct inheritance patterns remains unknown. Here, we report that the N-terminal tails of H3 and H3.3 are critical for their inheritance patterns, as well as GSC maintenance and proper differentiation. H3 and H3.3 differ at the 31st position in their N-termini with Alanine for H3 and Serine for H3.3. By swapping these two amino acids, we generated two mutant histones (i.e., H3A31S and H3.3S31A). Upon expressing them in the early-stage germline, we identified opposing phenotypes: over-population of early-stage germ cells in the H3A31S-expressing testes and significant germ cell loss in testes expressing the H3.3S31A. Asymmetric H3 inheritance is disrupted in the H3A31S-expressing GSCs, due to mis-incorporation of old histones between sister chromatids during DNA replication. Furthermore, H3.3S31A mutation accelerates old histone turn-over in the GSCs. Finally, using a modified Chromatin Immunocleavage assay on early-stage germ cells, we found that H3A31S has an enhanced occupancy at the promoters and transcription starting sites than H3, while H3.3S31A is more enriched at transcriptionally silent intergenic regions compared to H3.3. Overall, these results suggest that the 31st amino acids for both H3 and H3.3 are critical for their proper genomic occupancy and function. Together, our findings indicate a critical role for the different amino acid composition of the N-terminal tails between H3 and H3.3 in an endogenous stem cell lineage, and provide insights into the importance of proper histone inheritance in specifying cell fates and regulating cellular differentiation.
Comparing Inference under the MSC versus the MSC-with-Recombination
Authors: Yan Zhi , Ogilvie Huw A. , Nakhleh Luay 
Published: September 2022

AbstractAccurate inference of population parameters plays a pivotal role in unravelling the evolutionary histories. While recombination has been universally accepted as a fundamental process in the evolution of sexually reproducing organisms, it remains challenging to model it exactly. Thus, existing coalescent-based approaches make different assumptions or approximations to facilitate phylogenetic inference, which can potentially bring about biases in estimates of evolutionary parameters when recombination is present. In this article, we evaluate the performance of population parameters estimation using three classes of methods: StarBEAST2, SNAPP, and diCal2. We performed whole-genome simulations in which recombination rates, mutation rates, and levels of ILS were varied. We show that StarBEAST2 using short or medium-sized loci is robust to realistic rates of recombination, which is in agreement with previous studies. SNAPP, as expected, is generally unaffected by recombination events. Most surprisingly, diCal2, a method that is designed to explicitly account for recombination, performs considerably worse than other methods under comparison.
XerC is required for the repair of antibiotic- and immune-mediated DNA damage inStaphylococcus aureus
Authors: Ledger Elizabeth V. K. , Lau Katie , Tate Edward W. , Edwards Andrew M. 
Published: September 2022

AbstractTo survive in the host environment, pathogenic bacteria need to be able repair DNA damage caused by both antibiotics and the immune system. The SOS response is a key bacterial pathway to repair DNA double strand breaks and may therefore be a good target for novel therapeutics to sensitise bacteria to antibiotics and the immune response. However, the genes required for the SOS response inStaphylococcus aureushave not been fully established. Therefore, we carried out a screen of mutants involved in various DNA repair pathways to understand which were required for induction of the SOS response. This led to the identification of 16 genes that may play a role in SOS response induction, and of these, 3 that affected susceptibility ofS. aureusto ciprofloxacin. Further characterisation revealed that, in addition to ciprofloxacin, loss of the tyrosine recombinase XerC increased the susceptibility ofS. aureusto various classes of antibiotics, as well as to host immune defences. Therefore, the inhibition of XerC may be a viable therapeutic approach to sensitiseS. aureusto both antibiotics and the immune response.
Rgs1 is a regulator of effector gene expression during plant infection by the rice blast fungus Magnaporthe oryzae
Authors: Tang Bozeng , Yan Xia , Ryder Lauren S. , Cruz-Mireles Neftaly , Soanes Darren M. , Molinari Camilla , Foster Andrew J. , Talbot Nicholas J. 
Published: September 2022

AbstractTo cause rice blast disease the filamentous fungus Magnaporthe oryzae secretes a battery of effector proteins into host plant tissue to facilitate infection. Effector-encoding genes are expressed only during plant infection and show very low expression during other developmental stages. How effector gene expression is regulated in such a precise manner during invasive growth by M. oryzae is not known. Here, we report a forward-genetic screen to identify regulators of effector gene expression, based on selection of mutants that show constitutive effector gene expression. Using this simple screen, we identify Rgs1, a regulator of G-protein signalling (RGS) protein that is necessary for appressorium development, as a novel transcriptional regulator of effector gene expression, which acts prior to plant infection. We show that an N-terminal domain of Rgs1, possessing transactivation activity, is required for effector gene regulation and acts in an RGS-independent manner. Rgs1 controls expression of at least 60 temporally co-regulated effector genes, preventing their transcription during the pre-penetration stage of development prior to plant infection. A regulator of appressorium morphogenesis is therefore also required for orchestration of pathogen gene expression required for invasive growth by M. oryzae during plant infection.
A common cis-regulatory variant impacts normal-range and disease-associated human facial shape through regulation of PKDCC during chondrogenesis
Authors: Mohammed Jaaved , Arora Neha , Matthews Harold S. , Hansen Karissa , Bader Maram , Shaffer John R. , Weinberg Seth M. , Swigut Tomek , Claes Peter , Selleri Licia , Wysocka Joanna 
Published: September 2022

AbstractGenome-wide association studies (GWAS) identified thousands of genetic variants linked to phenotypic traits and disease risk. However, mechanistic understanding of how GWAS variants influence complex morphological traits and can, in certain cases, simultaneously confer normal-range phenotypic variation and disease predisposition, is still largely lacking. Here, we focus on rs6740960, a single nucleotide polymorphism (SNP) at the 2p21 locus, which in GWAS studies has been associated both with normal-range variation in jaw shape and with an increased risk of non-syndromic orofacial clefting. Using in vitro derived embryonic cell types relevant for human facial morphogenesis, we show that this SNP resides in an enhancer that regulates chondrocytic expression of PKDCC - a gene encoding a tyrosine kinase involved in chondrogenesis and skeletal development. In agreement, rs6740960 SNP is sufficient to confer a large difference in acetylation of its cognate enhancer preferentially in chondrocytes. By deploying dense landmark morphometric analysis of skull elements in mice, we show that changes in Pkdcc dosage are associated with quantitative changes in maxilla, mandible, and palatine bone shape that are concordant with the facial phenotypes and disease predisposition seen in humans. We further demonstrate that the frequency of the rs6740960 variant strongly deviated among different human populations, and that the activity of its cognate enhancer diverged in hominids. Our study provides a mechanistic explanation of how a common SNP can mediate normal-range and disease-associated morphological variation, with implications for the evolution of human facial features.