bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strength-frequency curve for micromagnetic neurostimulation through EPSPs on rat hippocampal neurons and numerical modeling of magnetic microcoil (μcoil)
Authors: Saha Renata , Faramarzi Sadegh , Bloom Robert P. , Benally Onri J. , Wu Kai , di Girolamo Arturo , Tonini Denis , Keirstead Susan A. , Low Walter C. , Netoff Theoden I. , Wang Jian-Ping 
Published: December 2021

AbstractObjectiveThe objective of this study was to measure the effect of micromagnetic stimulation (μMS) on hippocampal neurons, by using single microcoil (μcoil) prototype,MagneticPen(MagPen). MagPen will be used to stimulate the CA3 region magnetically and excitatory post synaptic potential (EPSP) response measurements will be made from the CA1 region. The threshold for micromagnetic neurostimulation as a function of stimulation frequency of the current driving the μcoil will be demonstrated. Finally, the optimal stimulation frequency of the current driving the μcoil to minimize power will be estimated.ApproachA biocompatible, watertight, non-corrosive prototype, MagPen was built, and customized such that it is easy to adjust the orientation of the μcoil and its distance over the hippocampal tissue in anin vitrorecording setting. Finite element modeling (FEM) of the μcoil design was performed to estimate the spatial profiles of the magnetic flux density (in T) and the induced electric fields (in V/m). The induced electric field profiles generated at different values of current applied to the μcoil can elicit a neuron response, which was validated by numerical modeling. The modeling settings for the μcoil were replicated in experiments on rat hippocampal neurons.Main resultsThe preferred orientation of MagPen over the Schaffer Collateral fibers was demonstrated such that they elicit a neuron response. The recorded EPSPs from CA1 region due to μMS at CA3 region were validated by applying tetrodotoxin (TTX). Application of TTX to the hippocampal slice blocked the EPSPs from μMS while after prolonged TTX washout, a partial recovery of the EPSP from μMS was observed. Finally, it was interpreted through numerical analysis that increasing frequency of the current driving the μcoil, led to a decrease in the current amplitude threshold for micromagnetic neurostimulation.SignificanceThis work reports that micromagnetic neurostimulation can be used to evoke population EPSP responses in the CA1 region of the hippocampus. It demonstrates the strengthfrequency curve for μMS and its unique features related to orientation dependence of the μcoils, spatial selectivity and stimulation threshold related to distance dependence. Finally, the challenges related to μMS experiments were studied including ways to overcome them.
TWISTED DWARF1 regulates Arabidopsis stamen development by differential activation of ABCB-mediated auxin transport
Authors: Liu Jie , Ghelli Roberta , Cardarelli Maura , Geisler Markus 
Published: December 2021

AbstractDespite clear evidence that a local accumulation of auxin is likewise critical for male fertility, much less is known about the components that regulate auxin-controlled stamen development.In this study, we analyzed physiological and morphological parameters in mutants of key players of ABCB-mediated auxin transport and spatially and temporally dissected their expression on the protein level as well as auxin fluxes in the Arabidopsis stamens. Our analyses revealed that the FKBP42, TWISTED DWARF1 (TWD1), promotes stamen elongation and, to a lesser extent, anther dehiscence, as well as pollen maturation and thus is required for seed development. Most of the described developmental defects in twd1 are shared with the abcb1 abcb19 mutant, which can be attributed to the fact that TWD1 - as a described ABCB chaperon - is a positive regulator of ABCB1 and ABCB19-mediated auxin transport. However, reduced stamen number was dependent on TWD1 but not on investigated ABCBs, suggesting additional actors down-stream of TWD1. We predict an overall housekeeping function for ABCB1 during earlier stages, while ABCB19 seems to be responsible for the key event of rapid elongation at later stages of stamen development. Our data indicate that TWD1 controls stamen development by differential activation of ABCB-mediated auxin transport in the stamen.HighlightBy using a mix of phenotypical and imaging analyses, we here identify and functionally characterize a new master regulator of flower development.
Time-sensitive prefrontal involvement in associating confidence with task performance illustrates metacognitive introspection in monkeys
Authors: Cai Yudian , Jin Zhiyong , Zhai Chenxi , Wang Huimin , Wang Jijun , Tang Yingying , Kwok Sze Chai 
Published: December 2021

AbstractMetacognition refers to the ability to be aware of one’s own cognition. Ample evidence indicates that metacognition in the human primate is highly dissociable from cognition, specialized across domains, and subserved by distinct neural substrates. However, these aspects remain relatively understudied in macaque monkeys. In the present study, we investigated the functionality of macaque metacognition by combining a confidence proxy, hierarchical Bayesian meta-d′ computational modelling, and a single-pulse transcranial magnetic stimulation technique. We found that Brodmann area 46d (BA46d) played a critical role in supporting metacognition independent of task performance; we also found that the critical role of this region in meta-calculation was time-sensitive. Additionally, we report that macaque metacognition is highly domain-specific with respect to memory and perception decisions. These findings carry implications for our understanding of metacognitive introspection within the primate lineage.
Cataract Surgery Outcomes and Postoperative Patient Compliance in Limited English Proficiency Patients at a County Hospital
Authors: Yard Colleen C. , Walter Kayla R. , Zhao Ning O. , Chuang Alice Z. , Mankiewicz Kimberly A. , Crowell Eric L. 
Published: December 2021

ABSTRACTBackground/AimsInvestigate the role of language barriers in cataract surgery outcomes at a county hospital.MethodsRetrospective chart review of patients who underwent cataract surgery March 2018-February 2019 at Lyndon B. Johnson Hospital. Patients who underwent cataract surgery combined with another procedure or had severe glaucoma or proliferative diabetic retinopathy were excluded. Patients were classified into limited English proficient (LEP) or English proficient (non-LEP) groups based on language preferences. Demographics, baseline ocular characteristics, intraoperative complications, postoperative BCVA (best-corrected visual acuity), complications, and compliance were recorded. The primary outcome was incidence of poor visual outcomes (BCVA<20/40) at the postoperative 1-month visit.Results354 patients (199 [56%] LEP and 155 [44%] non-LEP) with 125 (35%) males and a mean age 66.1 (±10.9) years were included. LEP patients were about 5 years older than non-LEP patients (P<0.001) and were mostly Hispanic (172 [86%] LEP vs. 36 [26%] non-LEP, P<0.001). The baseline ocular characteristics were similar (P >0.05), except severity of cataract (125 [63%] NSC grade >2+ for LEP vs 70 [51%] for non-LEP, P =0.03). No significant differences in intraoperative complications (P =0.18), incidence of poor vision (P =0.59), postoperative cystoid macular edema (P =0.32), and compliance with the postoperative drop regimen (P =0.11) were noted.ConclusionThere were no statistically significant differences in incidence of poor vision, complications, or compliance. However, there was a trend toward significance, showing that language barriers may lead to more advanced disease and compliance issues with postoperative medications.SYNOPSISLanguage barriers may lead to compliance issues with postoperative medication regimens, as shown by the difference in postoperative care adherence rates between limited English proficient and English proficient patients.
Distributed processing for action control by prelimbic circuits targeting anterior-posterior dorsal striatal subregions
Authors: Choi Kyuhyun , Piasini Eugenio , Cifuentes-Vargas Luigim , Díaz-Hernández Edgar , Henderson Nathan T. , Subramaniyan Manivannan , Gerfen Charles R. , Fuccillo Marc V. 
Published: December 2021

ABSTRACTFronto-striatal circuits have been extensively implicated in the cognitive control of behavioral output for both social and appetitive rewards. The functional diversity of prefrontal cortical populations is strongly dependent on their synaptic targets, with control of motor output strongly mediated by connectivity to the dorsal striatum. Despite evidence for functional diversity along the anterior-posterior axis of the dorsomedial striatum (DMS), it is unclear how distinct fronto- striatal sub-circuits support neural computations essential for action selection. Here we identify prefrontal populations targeting distinct DMS subregions and characterize their functional roles. We first performed neural circuit tracing to reveal segregated prefrontal populations defined by anterior/posterior dorsomedial striatal target. We then probed the functional relevance of these parallel circuits via in vivo calcium imaging and temporally precise causal manipulations during a feedback-based 2-alternative choice task. Single-photon imaging revealed circuit-specific representations of task-relevant information with prelimbic neurons targeting anterior DMS (PL::A- DMS) uniquely encoded choices and responses to negative outcomes, while prelimbic neurons targeting posterior DMS (PL::P-DMS) encoded internal representations of value and positive outcomes contingent on prior choice. Consistent with this distributed coding, optogenetic inhibition of PL::A-DMS circuits strongly impacted choice monitoring and behavioral control in response to negative outcomes while perturbation of PL::P-DMS signals impaired task engagement and strategies following positive outcomes. Di-synaptic retrograde tracing uncovered differences in afferent connectivity that may underlie these pathways functional divergence. Together our data uncover novel PL populations engaged in distributed processing for action control.SUMMARYPrelimbic cortex engages A- and P-DMS via distinct circuitsPL::A-DMS and PL::P-DMS pathways encode divergent aspects of a simple goal-directed taskPL::A-DMS pathways shape responding to negative outcomes via multiple mechanismsPL::P-DMS pathways guide engagement and choices in response to positive outcomesAfferent connectomes of PL neurons defined by A-P DMS target are distinct
Tertiary lymphoid structures induced by CXCL13-producing CD4+ T cells increase tumor infiltrating CD8+ T cells and B cells in ovarian cancer
Authors: Ukita Masayo , Hamanishi Junzo , Yoshitomi Hiroyuki , Yamanoi Koji , Takamatsu Shiro , Ueda Akihiko , Suzuki Haruka , Hosoe Yuko , Furutake Yoko , Taki Mana , Abiko Kaoru , Yamaguchi Ken , Nakai Hidekatsu , Baba Tsukasa , Matsumura Noriomi , Yoshizawa Akihiko , Ueno Hideki , Mandai Masaki 
Published: December 2021

AbstractBackgroundTertiary lymphoid structures (TLSs) are transient ectopic lymphoid aggregates whose formation might be caused by chronic inflammation states, such as cancer. The presence of TLS is associated with a favorable prognosis in most solid malignancies. The recognition of the relevance of TLS to cancer has led to a growing interest in TLS as an immunomodulatory target to enhance tumor immunity, although how TLSs are induced in the tumor microenvironment (TME) and how they affect patient survival are not well understood.MethodsTLS distribution in relation to tumor infiltrating lymphocytes (TILs) and related gene expression were investigated in high grade serous ovarian cancer (HGSC) specimens. CXCL13 expression, which is strongly associated with TLS, and its localization in immune cells, were examined. We explored the tumor microenvironment for CXCL13 secretion by adding various inflammatory cytokines in vitro. The induction of TLS by CXCL13 was examined in a mouse model of ovarian cancer.ResultsCXCL13 gene expression correlated with TLS formation and the infiltration of T cells and B cells, and was a favorable prognostic factor for HGSC patients. The coexistence of CD8+ T cells and B-cell lineages in the TME was associated with a better prognosis of HGSC and was closely related to the presence of TLSs. CXCL13 expression was predominantly coincident with CD4+ T cells in TLSs and CD8+ T cells in TILs, and shifted from CD4+ T cells to CD21+ follicular dendritic cells as the TLS matured. Although TGF-β was reported to stimulate CXCL13 production, our in vitro results revealed that CXCL13 secretion was promoted in CD4+ T cells under TGF-β + IL-2-restricted conditions and in CD8+ T cells under TGF-β + IL-12-rich conditions. In a mouse model of ovarian cancer, recombinant CXCL13 induced TLSs and enhanced survival by the infiltration of CD8+ T cells.ConclusionsTLS formation was promoted by CXCL13-producing CD4+ T cells and TLSs facilitated the coordinated antitumor responses of cellular and humoral immunity in ovarian cancer.
ANXA2 enhances virus replication through negatively regulating cGAS-STING and RLRs-mediated signal pathway
Authors: Xue Mengdi , Liu Hongyang , Zhang Zhaoxia , Feng Chunying , Zhang Kunli , Liu Xiaohong , Ye Guangqiang , Zhou Qiongqiong , Li Changyao , Weng Changjiang , Huang Li 
Published: December 2021

AbstractHost nucleic acid receptors can recognize the viral DNA or RNA upon virus infection, which further triggers multiple signal pathways to promote the translocation of the interferon regulatory factor 3 (IRF3) into nucleus and produce type I interferon (IFN), leading to the host antiviral response. Here, we report a novel negative regulator Annexin A2 (ANXA2) that regulates type I IFN production through multiple mechanisms. Ectopic expression of ANXA2 inhibited the production of type I IFN induced by DNA- and RNA viruses and enhanced virus replication, while knockout of ANXA2 expression enhanced the production of type I IFN and inhibited virus replication. Mechanistically, ANXA2 not only disrupted MDA5 recruiting MAVS, but also inhibited the interaction between MAVS and TRAF3 upon RNA virus infection. In addition, ANXA2 impacted the translocation of STING from endoplasmic reticulum to Golgi apparatus upon DNA virus infection. Interestingly, ANXA2 also inhibited IRF3 phosphorylation and nuclear translocation through competing with TANK-binds kinase 1 (TBK1) and inhibitor-κB kinase ε (IKKε) for binding to IRF3. Anxa2 deficiency in vivo increased the production of type I IFN, which resulted in suppression of encephalomyocarditis virus (EMCV) replication. Our findings reveal that ANXA2, as a negative regulator of type I IFN production, plays an important role in regulating the host antiviral responses.Author summaryAnnexin is a family of evolutionarily conserved multi-gene proteins, which are widely distributed in various tissues and cells of plants and animals. These proteins can reversibly bind to phospholipid membranes and to calcium ions (Ca2+). To date, several studies have confirmed that some members of the Annexin family regulate the antiviral innate immune response. Until now, regulation of the production of type I IFN by ANXA2 is not reported. In this study, ANXA2 were found to strongly inhibit the production of type I IFN, leading to increased virus replication while knockout of ANXA2 expression inhibited virus replication by increasing the amount of IFN. Compared with wild-type littermates, ANXA2 deficiency mice produced more type I IFN to inhibit virus replication. Our results provide methanistic insights into the novel role of ANXA2 in the antiviral innate immune responses.
Rice leaves undergo a rapid metabolic reconfiguration during a specific stage of primordium development
Authors: Cox Naomi , Walker Heather J. , Pitman James K. , Quick W. Paul , Smith Lisa M. , Fleming Andrew J. 
Published: December 2021

AbstractLeaf development is crucial to establish the photosynthetic competency of plants. It is a process that requires coordinated changes in cell number and differentiation, transcriptomes, metabolomes and physiology. However, despite the importance of leaf formation for our major crops, early developmental processes for rice have not been comprehensively described. Here we detail the temporal developmental trajectory of early rice leaf development and connect morphological changes to metabolism. In particular, a developmental index based on the patterning of epidermal differentiation visualised by electron microscopy enabled high resolution staging of early growth for single primordium metabolite profiling. These data demonstrate that a switch in the constellation of tricarboxylic acid (TCA) cycle metabolites defines a narrow window towards the end of the P3 stage of leaf development. Taken in the context of other data in the literature, our results substantiate that this phase of rice leaf growth, equivalent to a change of primordium length from around 5 to 7.5 mm, defines a major shift in rice leaf determination towards a photosynthetically defined structure. We speculate that efforts to engineer rice leaf structure should focus on the developmental window prior to these determining events.HighlightRice leaves undergo a shift in fundamental metabolism during a very early and narrow developmental window which co-incides with them acquiring the ability to capture light for photosynthesis
On eco-evolutionary dynamics of phenologies in competitive communities and their robustness to climate change
Authors: Cortier Thomas , Loeuille Nicolas 
Published: December 2021

AbstractGlobal changes currently cause temporal shifts in the favourable conditions for different phases of species life cycles. Phenologies characterizing temporal presence, may adapt through heritable evolution in response to these changes. Given a community context, this evolution may cause a change in the phenology overlap and thus a change of interspecific interactions such as competition. Using a model in which phenologies compete and coevolve, we study the conditions under which diversity emerges, as well as their annual distribution. We find that the environment richness (food quantity, light, pollinators…) and competition constrain the diversity and spread of phenologies. A robust pattern of phenologies distribution emerges consistent with Swedish flowering observations. Once a stable community is reached, we apply a progressive change in environmental conditions. We found that adaptation eventually restored diversity, but that the simulated change often led to numerous extinctions due to increased competition. The percentage of diversity lost depends on the speed of change and on the initial diversity. Phenologies already pre-adapted to the new environmental conditions drive the restoration of diversity after the change. We finally study a spatial version of the model in which local communities are organized along an environmental gradient. Pre-change, allowing dispersal decreases the local adaptation of phenologies to their local fixed environmental conditions. Dispersal however largely enhances the maintenance of biodiversity in changing environments, though its benefits are not homogeneous in space. Evolution remains the only rescue mechanism for southern phenotypes.
Invertebrate-induced priority effects and secondary metabolites control fungal community composition in dead wood
Authors: Lunde Lisa Fagerli , Jacobsen Rannveig , Kauserud Håvard , Boddy Lynne , Nybakken Line , Sverdrup-Thygeson Anne , Birkemoe Tone 
Published: December 2021

AbstractDuring decomposition of organic matter, microbial communities may follow different successional trajectories depending on the initial environment and colonizers. The timing and order of the assembly history can lead to divergent communities through priority effects. We explored how assembly history and resource quality affected fungal dead wood communities and decomposition, 1.5 and 4.5 years after tree felling. Additionally, we investigated the effect of invertebrate exclusion during the first two summers. For aspen (Populus tremula) logs, we measured initial resource quality of bark and wood, and surveyed the fungal communities by DNA metabarcoding at different time points during succession. We found that a gradient in fungal community composition was related to resource quality and discuss how this may reflect tolerance-dominance trade-offs in fungal life history strategies. As with previous studies, the initial amount of bark tannins was negatively correlated with wood decomposition rate over 4.5 years. The initial fungal community explained variation in community composition after 1.5, but not 4.5 years, of succession. Although the assembly history of initial colonizers may cause alternate trajectories in successional communities, our results indicate that the communities may easily converge with the arrival of secondary colonizers. We also identified a strong invertebrate-induced priority effect of fungal communities, even after 4.5 years of succession, thereby adding crucial knowledge to the importance of invertebrates in affecting fungal community development. By measuring and manipulating aspects of assembly history and resource quality that have rarely been studied, we expand our understanding of the complexity of fungal community dynamics.
Structure ofMycobacterium tuberculosisCya, an evolutionary ancestor of the mammalian membrane adenylyl cyclases
Authors: Mehta Ved , Khanppnavar Basavraj , Schuster Dina , Kantarci Ilayda , Vercellino Irene , Kosturanova Angela , Iype Tarun , Stefanic Sasa , Picotti Paola , Korkhov Volodymyr M. 
Published: December 2021

AbstractMycobacterium tuberculosisadenylyl cyclase (AC) Rv1625c / Cya is an evolutionary ancestor of the mammalian membrane ACs and a model system for studies of their structure and function. Although the vital role of ACs in cellular signaling is well established, the function of their transmembrane (TM) regions remains unknown. Here we describe the cryo-EM structure of Cya bound to a stabilizing nanobody at 3.6 Å resolution. The TM helices 1-5 form a structurally conserved domain that facilitates the assembly of the helical and catalytic domains. The TM region contains discrete pockets accessible from the extracellular and cytosolic side of the membrane. Neutralization of the negatively charged extracellular pocket Ex1 destabilizes the cytosolic helical domain and reduces the catalytic activity of the enzyme. The TM domain acts as a functional component of Cya, guiding the assembly of the catalytic domain and providing the means for direct regulation of catalytic activity in response to extracellular ligands.One-Sentence SummaryStructure ofM. tuberculosismembrane adenylyl cyclase Cya