bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of drought tolerance in Arabidopsis involves PLATZ4-mediated transcriptional suppression of PIP2;8
Authors: Liu Miao , Wang Chunyan , Ji Zhen , Zhang Lei , Li Chunlong , Huang Jinguang , Yang Guodong , Yan Kang , Zhang Shizhong , Zheng Chengchao , Wu Changai 
Published: October 2021

AbstractPLATZ transcription factors play important roles in plant growth, development, and biotic and abiotic stress responses. However, how PLATZ regulates plant drought tolerance and ABA sensitivity remains largely unknown. Here, we show that PLATZ4 increases drought tolerance and ABA sensitivity in Arabidopsis thaliana by suppressing the expression of PIP2;8, DEG3, At1g33840 and At3g01345, while upregulating the expression of PR1, ABI3, ABI4 and ABI5. Moreover, PLATZ4 directly binds A/T-rich sequences within the PIP2;8 promoter but not ABI3, ABI4 and ABI5 promoters. Consistent with this, PIP2;8 acts epistatically to PLATZ4. Furthermore, the aquaporin activity of PIP2;8 was confirmed in Xenopus laevis oocytes and yeast cells in response to osmotic stress. Analysis of water loss of seedlings overexpressing PIP2;8 or lacking PIP2;8 function indicated that PIP2;8-mediated water flow is particularly active in response to drought stress in planta. Accordingly, stomatal closure was enhanced in pip2;8 mutants but reduced in PIP2;8-overexpressing plants. In platz4 mutant and PLATZ4-overexpressing plants, water loss and stomatal closure changed oppositely to those in pip2;8 mutants and PIP2;8-overexpressing plants, respectively. In addition, the interaction between PLATZ4 and AITR6 was confirmed by several assays, and the binding of PIP2;8 promoter by PLATZ4 was strengthened by an interaction with AITR6. Collectively, our findings reveal that PLATZ4 interacts with AITR6 to increase ABA sensitivity and drought tolerance in Arabidopsis by upregulating expression of PR1, ABI3, ABI4 and ABI5 while inhibiting the expression of PIP2;8 and associated genes.One sentence summaryPLATZ4 interacted with AITR6 to increase drought tolerance and ABA sensitivity in Arabidopsis thaliana by directly bind A/T-rich sequences within the plasma membrane aquaporin (PIP)2;8 promoter.
Tuning the sensitivity of genetically encoded fluorescent potassium indicators through structure-guided and genome mining strategies
Authors: Torres Cabán Cristina C. , Yang Minghan , Lai Cuixin , Yang Lina , Subach Fedor , Smith Brian O. , Piatkevich Kiryl D. , Boyden Edward S. 
Published: October 2021

AbstractGenetically encoded potassium indicators lack optimal binding affinity for monitoring intracellular dynamics in mammalian cells. Through structure-guided design and genome mining of potassium binding proteins, we developed green fluorescent potassium indicators with a broad range of binding affinities. KRaION1, based on the insertion of a potassium binding protein (Ec-Kbp) into the fluorescent protein mNeonGreen, exhibits an isotonically measured Kdof 69±10 (mM; mean ± standard deviation used throughout). We identified Ec-Kbp’s binding site using NMR spectroscopy to detect protein-thallium scalar couplings and refined the structure of Ec-Kbp in its potassium-bound state. Guided by this structure, we modified KRaION1, yielding KRaION2, which exhibits an isotonically measured Kdof 96±9 (mM). We identified four Ec-Kbp homologs as potassium binding proteins, which yielded indicators with isotonically measured binding affinities in the 39-112 (mM) range. KRaIONs expressed and functioned in HeLa cells, but exhibited lower Kdvalues, which were mirrored by lower Kdvalues measured in vitro when holding sodium constant. Thus, potassium indicator Kdmay need to be evaluated in the context of a given experimental goal.
Processive translocation of cohesive and non-cohesive cohesin in vivo
Authors: Borrie Melinda S. , Gartenberg Marc R. 
Published: October 2021

AbstractCohesin is a central architectural element of chromosomes that regulates numerous DNA-based events. The complex holds sister chromatids together until anaphase onset and organizes individual chromosomal DNAs into loops. Purified cohesin translocates along DNA in a diffusive fashion that can be propelled by transcribing RNA polymerase. The complex also extrudes DNA loops in a process that consumes ATP. In this study we examine processive genomic translocation of cohesin in vivo. To this end, obstacles of increasing size were tethered to DNA to act as roadblocks to complexes mobilized by transcription in yeast. The obstacles were built from a GFP-lacI core fused to one or more mCherries. A chimera with four mCherries blocked cohesin passage in late G1. During M phase, the threshold barrier depended on the state of cohesion: non-cohesive complexes were also blocked by four mCherries whereas cohesive complexes were blocked by as few as three mCherries. Furthermore, cohesive complexes that were stalled at obstacles, in turn, blocked the passage of non-cohesive complexes. That synthetic barriers alter cohesin redistribution demonstrates that the complex translocates processively on chromatin in vivo. The approach provides a relative measure of the maximum size of the DNA binding chamber(s) of cohesin. Together, this study reveals unexplored limitations to cohesin movement on chromosomes.Significance StatementCohesin is an architectural protein that brings distant chromosomal DNA sites together. The complex links sister chromatids cohesion but it also binds to single pieces of DNA in ways that do not generate cohesion. One class of non-cohesive complexes organizes chromosomal DNA into loops. All cohesin complexes move on DNA but the constraints on such movement are not fully explored. Here, we use size-calibrated obstacles in yeast to interrogate cohesin and the properties of its movement on DNA. We show that both cohesive and non-cohesive complexes translocate processively on chromosomes. In addition, we show that cohesive and non-cohesive complexes are blocked by obstacles of different size. Lastly, we show that stalled cohesive complexes block passage of non-cohesive complexes.
Genomic and metabolic adaptations of biofilms to ecological windows of opportunities in glacier-fed streams
Authors: Busi Susheel Bhanu , Bourquin Massimo , Fodelianakis Stilianos , Michoud Grégoire , Kohler Tyler J. , Peter Hannes , Pramateftaki Paraskevi , Styllas Michail , Tolosano Matteo , De Staercke Vincent , Schön Martina , de Nies Laura , Marasco Ramona , Daffonchio Daniele , Ezzat Leïla , Wilmes Paul , Battin Tom J. 
Published: October 2021

AbstractMicroorganisms dominate life in cryospheric ecosystems. In glacier-fed streams (GFSs), ecological windows of opportunities allow complex microbial biofilms to develop and transiently form the basis of the food web, thereby controlling key ecosystem processes. Here, using high-resolution metagenomics, we unravel strategies that allow biofilms to seize this opportunity in an ecosystem otherwise characterized by harsh environmental conditions. We found a diverse microbiome spanning the entire tree of life and including a rich virome. Various and co-existing energy acquisition pathways point to diverse niches and the simultaneous exploitation of available resources, likely fostering the establishment of complex biofilms in GFSs during windows of opportunity. The wide occurrence of rhodopsins across metagenome-assembled genomes (MAGs), besides chlorophyll, highlights the role of solar energy capture in these biofilms. Concomitantly, internal carbon and nutrient cycling between photoautotrophs and heterotrophs may help overcome constraints imposed by the high oligotrophy in GFSs. MAGs also revealed mechanisms potentially protecting bacteria against low temperatures and high UV-radiation. The selective pressure of the GFS environment is further highlighted by the phylogenomic analysis, differentiating the representatives of the genusPolaromonas, an important component of the GFS microbiome, from those found in other ecosystems. Our findings reveal key genomic underpinnings of adaptive traits that contribute to the success of complex biofilms to exploit environmental opportunities in GFSs, now rapidly changing owing to global warming.
The Relative Binding Position of Nck and Grb2 Adaptors Dramatically Impacts Actin-Based Motility of Vaccinia Virus
Authors: Basant Angika , Way Michael 
Published: October 2021

ABSTRACTPhosphotyrosine (pTyr) motifs in unstructured polypeptides orchestrate important cellular processes by engaging SH2-containing adaptors to nucleate complex signalling networks. The concept of phase separation has recently changed our appreciation of such multivalent networks, however, the role of pTyr motif positioning in their function remains to be explored. We have now explored this parameter in the assembly and operation of the signalling cascade driving actin-based motility and spread of Vaccinia virus. This network involves two pTyr motifs in the viral protein A36 that recruit the adaptors Nck and Grb2 upstream of N-WASP and Arp2/3-mediated actin polymerization. We generated synthetic networks on Vaccinia by manipulating pTyr motifs in A36 and the unrelated p14 from Orthoreovirus. In contrast to predictions, we find that only specific spatial arrangements of Grb2 and Nck binding sites result in robust N-WASP recruitment, Arp2/3 driven actin polymerization and viral spread. Our results suggest that the relative position of pTyr adaptor binding sites is optimised for signal output. This finding may explain why the relative positions of pTyr motifs are usually conserved in proteins from widely different species. It also has important implications for regulation of physiological networks, including those that undergo phase transitions.
Angiotensin converting enzyme 2 (ACE2) is expressed in murine cutaneous under single-cell transcriptome resolution
Authors: Chu Chenyu , Hu Chen , Liu Li , Wang Yuanjing , Qu Yili , Man Yi 
Published: October 2021

AbstractAngiotensin converting enzyme 2 (Ace2) is widely distributed in human organs, which was identified as a functional receptor for severe acute respiratory syndrome (SARS) coronavirus in human beings. It was also confirmed that SARS-CoV-2 uses the same cell entry receptor, ACE2, as SARS-CoV. However, related research still not discover the expression data associated with murine skin under single cell RNA resolution. In this study, we performed single-cell RNA sequencing (scRNA-seq) on unsorted cells from mouse dorsal skin after 7 days post-wounding. 8312 sequenced cells from four skin samples met quality control metrics and were analyzed.
The archaeal division protein CdvB1 assembles into polymers that are depolymerized by CdvC
Authors: Jover Alberto Blanch , De Franceschi Nicola , Fenel Daphna , Weissenhorn Winfried , Dekker Cees 
Published: October 2021

AbstractThe Cdv proteins constitute the cell-division system of the Crenarchaea, in a protein machinery that is closely related to the ESCRT system of eukaryotes. The CdvB paralog CdvB1 is believed to play a major role in the constricting ring that is the central actor in cell division in the crenarchaea. Here, we present an in vitro study of purified CdvB1 from the crenarchaeon M. sedula with a combination of TEM imaging and biochemical assays. We show that CdvB1 self-assembles into filamentous polymers that are depolymerized by the action of the Vps4-homolog ATPase CdvC. Using liposome flotation assays, we show that CdvB1 binds to negatively charged lipid membranes and can be detached from the membrane by the action of CdvC. Interestingly, we find that the polymerization and the membrane binding are mutually exclusive properties of the protein. Our findings provide novel insight into one of the main components of the archaeal cell division machinery.
LysM receptors in Coffea arabica: identification, characterization, and gene expression in response to Hemileia vastatrix
Authors: de Lima Santos Mariana , de Resende Mário Lúcio Vilela , dos Santos Ciscon Bárbara Alves , Freitas Natália Chagas , de Brito Pereira Matheus Henrique , Reichel Tharyn , Mathioni Sandra Marisa 
Published: October 2021

AbstractPathogen-associated molecular patterns (PAMPs) are recognized by pattern recognition receptors (PRRs) localized on the host plant cell wall. These receptors activate a broad-spectrum and durable defense, which are desired characteristics for disease resistance in plant breeding programs. In this study, candidate sequences for PRRs with lysin motifs (LysM) were investigated in the Coffea arabica genome. For this, approaches based on the principle of sequence similarity, conservation of motifs and domains, phylogenetic analysis, and modulation of gene expression in response to Hemileia vastatrix were used. The candidate sequences for PRRs in C. arabica (Ca1-LYP, Ca2-LYP, Ca1-CERK1, Ca2-CERK1, Ca-LYK4, Ca1-LYK5 and Ca2-LYK5) showed high similarity with the reference PRRs used: Os-CEBiP, At-CERK1, At-LYK4 and At-LYK5. Moreover, the ectodomains of these sequences showed high identity or similarity with the reference sequences, indicating structural and functional conservation. The studied sequences are also phylogenetically related to the reference PRRs described in Arabidopsis, rice, and other plant species. All candidates for receptors had their expression induced after the inoculation with H. vastatrix, since the first time of sampling at 6 hours post-inoculation (hpi). At 24 hpi, there was a significant increase in expression, for most of the receptors evaluated, and at 48 hpi, a suppression. The results showed that the candidate sequences for PRRs in the C. arabica genome display high homology with fungal PRRs already described in the literature. Besides, they respond to pathogen inoculation and seem to be involved in the perception or signaling of fungal chitin, acting as receptors or coreceptors of this molecule. These findings represent an advance in the understanding of the basal immunity of this species.
A Diversity Outbred F1 mouse model identifies host-intrinsic genetic regulators of response to immune checkpoint inhibitors
Authors: Hackett Justin B. , Glassbrook James E. , Muñiz Maria C. , Bross Madeline , Fielder Abigail , Dyson Gregory , Movahhedin Nasrin , McCasland Jennifer , McCarthy-Leo Claire , Gibson Heather M. 
Published: October 2021

AbstractImmune checkpoint inhibitors (ICI) have improved outcomes for a variety of malignancies; however, many patients fail to benefit. While tumor-intrinsic mechanisms are likely involved in therapy resistance, it is unclear to what extent host genetic background influences response. To investigate this, we utilized the Diversity Outbred (DO) and Collaborative Cross (CC) mouse models. DO mice are an outbred stock generated by crossbreeding 8 inbred founder strains, and CC mice are recombinant inbred mice generated from the same 8 founders. We generated 207 DOB6F1 mice representing 48 DO dams and demonstrated that these mice reliably accept the C57BL/6-syngeneic B16F0 tumor and that host genetic background influences response to ICI. Genetic linkage analysis from 142 mice identified multiple regions including one within chromosome 13 that associated with therapeutic response. We utilized 6 CC strains bearing the positive (NZO) or negative (C57BL/6) driver genotype in this locus. We found that 2/3 of predicted responder CCB6F1 crosses show reproducible ICI response. The chromosome 13 locus contains the murine prolactin family, which is a known immunomodulating cytokine associated with various autoimmune disorders. To directly test whether prolactin influences ICI response rates, we implanted inbred C57BL/6 mice with subcutaneous slow-release prolactin pellets to induce mild hyperprolactinemia. Prolactin augmented ICI response against B16F0, with increased CD8 infiltration and 5/8 mice exhibiting slowed tumor growth relative to controls. This study highlights the role of host genetics in ICI response and supports the use of F1 crosses in the DO and CC mouse populations as powerful cancer immunotherapy models.One Sentence SummaryUsing germline genetic analysis in Diversity Outbred and Collaborative Cross models, we identify prolactin as a host-intrinsic regulator of response to combined immune checkpoint inhibitors.
The DNAPKcs long-range C-NHEJ complex is required for blunt DNA end joining when XLF is weakened
Authors: Cisneros-Aguirre Metztli , Lopezcolorado Felicia Wednesday , Tsai Linda Jillianne , Bhargava Ragini , Stark Jeremy M. 
Published: October 2021

ABSTRACTCanonical non-homologous end joining (C-NHEJ) factors can assemble into a long-range (LR) complex with DNA ends relatively far apart that contains DNAPKcs, XLF, XRCC4, LIG4, and the KU heterodimer and a short-range (SR) complex lacking DNAPKcs that has the ends positioned for ligation. Since the SR complex can form de novo, the role of the LR complex (i.e., DNAPKcs) for chromosomal EJ is unclear. We have examined EJ of chromosomal blunt DNA double-strand breaks (DSBs), and found that DNAPKcs is significantly less important than XLF and XRCC4 for such EJ. However, weakening XLF via disrupting interaction interfaces (e.g., disrupting the XLF homodimer interface) causes a marked requirement for DNAPKcs, its kinase activity, and its ABCDE-cluster autophosphorylation sites for blunt DSB EJ. In contrast, other aspects of genome maintenance are sensitive to DNAPKcs kinase inhibition in a manner that is not further enhanced by XLF loss (i.e., suppression of homology-directed repair and structural variants, and IR-resistance). We suggest that DNAPKcs is required to position a weakened XLF in an LR complex that can transition into a functional SR complex for blunt DSB EJ, but also has distinct functions for other aspects of genome maintenance.
Dysfunction of cAMP-PKA-calcium signaling axis in striatal medium spiny neurons: a role in schizophrenia and Huntington’s disease pathogenesis
Authors: Fjodorova Marija , Noakes Zoe , De La Fuente Daniel C. , Errington Adam C. , Li Meng 
Published: October 2021

SummaryBackgroundStriatal medium spiny neurons (MSNs) are preferentially lost in Huntington’s disease. Genomic studies also implicate a direct role for MSNs in schizophrenia, a psychiatric disorder known to involve cortical neuron dysfunction. It remains unknown whether the two diseases share similar MSN pathogenesis or if neuronal deficits can be attributed to cell type-dependent biological pathways. Transcription factor BCL11B, which is expressed by all MSNs and deep layer cortical neurons, was recently proposed to drive selective neurodegeneration in Huntington’s disease and identified as a candidate risk gene in schizophrenia.MethodsUsing human stem cell-derived neurons lacking BCL11B as a model, we investigated cellular pathology in MSNs and cortical neurons in the context of these disorders. Integrative analyses between differentially expressed transcripts and published GWAS datasets identified cell type-specific disease-related phenotypes.ResultsWe uncover a role for BCL11B in calcium homeostasis in both neuronal types, while deficits in mitochondrial function and protein kinase A (PKA)-dependent calcium transients are detected only in MSNs. Moreover, BCL11B-deficient MSNs display abnormal responses to glutamate and fail to integrate dopaminergic and glutamatergic stimulation, a key feature of striatal neurons in vivo. Gene enrichment analysis reveals overrepresentation of disorder risk genes among BCL11B-regulated pathways, primarily relating to cAMP-PKA-calcium signaling axis and synaptic signaling.ConclusionsOur study indicates that Huntington’s disease and schizophrenia are likely to share neuronal pathogenesis where dysregulation of intracellular calcium levels is found in both striatal and cortical neurons. In contrast, reduction in PKA signaling and abnormal dopamine/glutamate receptor signaling is largely specific to MSNs.
Towards enhancing creativity in university settings: does hope of academic knowledge workers matter?
Authors: Namono Rehema , Kemboi Ambrose Kiplimo , Chepkwony Joel 
Published: October 2021

PurposeAlthough a burgeoning body of literature has established the influence of hope and employee creativity, the debate on the relative importance of hope and its components of pathway and agency on its outcomes has not been clarified. Literature has it that hope and its individual components of pathway and agency have a varying magnitude of influence on its outcomes. Some scholars argue that agency and pathway components better predict its outcomes than overall hope. The current study establishes the relative importance of hope and its components on creativity using evidence from Makerere University, Uganda.Design/methodology/approachThe study adopted a cross-sectional quantitative survey design to collect data from the academic staff of Makerere University. The study used usefulness analysis to establish the relative importance of the predictor variables on the dependent variable.FindingsThe study findings revealed that agency and hope components of hope significantly predicted creativity. Overall, hope also significantly predicted creativity. Regarding relative importance, hope turned out to be the most “useful” predictor of creativity, followed by its components of agency and pathway.Research limitations/implicationsThe study was conducted in a public university setting located in urban areas. The findings may not be generalizable to private settings due to variations in the teacher's creative behaviour with variation in the creative environment. The study was also cross-sectional, which may not yield results of changing employee creativity over time. Further studies should establish the link between hope and creativity using a longitudinal survey to compare employee creativity using data collected at different intervals.Originality/valueThe value of the current study is both theoretical and empirical. Theoretically, the study findings enrich the hope theory by revealing the relative importance of hope on its outcomes over and above its components. The study also confirms the assertions of the dual pathway to creativity model by revealing that employees who are rich in hope components of agency and pathway have the cognitive flexibility to pursue creative goals and, when faced with failure, can generate alternative solutions to solve work problems.
Household acceptance of central bank digital currency: the role of institutional trust
Authors: Solberg Söilen Klaus , Benhayoun Lamiae 
Published: October 2021

PurposeThe authors investigate household acceptance of central bank digital currencies (CBDCs) by drawing on the unified theory of acceptance and use of technology and institutional trust theory.Design/methodology/approachThe authors build a research model including six hypotheses and quantitatively analyze it using partial least squares structural equation modeling (PLS-SEM) and importance–performance map analysis (IPMA) based on 282 answers to a survey questionnaire.FindingsThe continuous adoption of CBDCs by households is highly probable and is fostered by its expected high performance, the social recommendations and the existence of facilitating conditions. Nevertheless, institutions' efforts to propose a flexible and understandable currency can benefit its adoption only if these institutions also strive to build households' trust in the currency's system.Originality/valueThe authors provide a full review of the emerging literature on CBDCs and suggest that digital currency offerings can be divided into centralized, semi-centralized and de-centralized control in a meaningful taxonomy. The authors also complement extant studies on CBDCs that mostly apprehend its operational challenges by focusing on the customer side and provide implications to the launching of CBDCs by uncovering the customer-specific determinants of their adoption.