Miracle-dz/UniFAR-FTUs huggingface dataset:
A Membrane-Bound NAC Transcription Factor, ANAC017, Mediates Mitochondrial Retrograde Signaling in Arabidopsis[W][OPEN]

This work identifies a biological role for ANAC017 as an integral cellular component in mitochondrial retrograde signaling and a high-level transcriptional regulator that is necessary for H2O2-mediated primary stress responses in plants. Plants require daily coordinated regulation of energy metabolism for optimal growth and survival and therefore need to integrate cellular responses with both mitochondrial and plastid retrograde signaling. Using a forward genetic screen to characterize regulators of alternative oxidase1a (rao) mutants, we identified RAO2/Arabidopsis NAC domain-containing protein17 (ANAC017) as a direct positive regulator of AOX1a. RAO2/ANAC017 is targeted to connections and junctions in the endoplasmic reticulum (ER) and F-actin via a C-terminal transmembrane (TM) domain. A consensus rhomboid protease cleavage site is present in ANAC017 just prior to the predicted TM domain. Furthermore, addition of the rhomboid protease inhibitor N-p-Tosyl-l-Phe chloromethyl abolishes the induction of AOX1a upon antimycin A treatment. Simultaneous fluorescent tagging of ANAC017 with N-terminal red fluorescent protein (RFP) and C-terminal green fluorescent protein (GFP) revealed that the N-terminal RFP domain migrated into the nucleus, while the C-terminal GFP tag remained in the ER. Genome-wide analysis of the transcriptional network regulated by RAO2/ANAC017 under stress treatment revealed that RAO2/ANAC017 function was necessary for >85% of the changes observed as a primary response to cytosolic hydrogen peroxide (H2O2), but only ∼33% of transcriptional changes observed in response to antimycin A treatment. Plants with mutated rao2/anac017 were more stress sensitive, whereas a gain-of-function mutation resulted in plants that had lower cellular levels of H2O2 under untreated conditions.
Prosodic Structure and Focus Prosody of South Kyungsang Korean

This paper shows how focus prosody of South Kyungsang Korean interacts with the prosodic structure of the dialect. Based on the prosodic structure defined by intonation, it is claimed that the domain of lexical pitch accent assignment is a Prosodic Word, but the prosodic domain of focus, or the realization of focus prominence, is an Accentual Phrase. This model can explain the phenomenon of mismatch between the domain of semantic focus and the domain of accent/prosodic prominence.
A calcium-dependent transient outward current in Xenopus laevis oocytes

Membrane currents were investigated in Xenopus laevis oocytes under voltage clamp. Depolarizing pulses, given from a holding potential of about –100 mV, elicited a transient outward current when the membrane potential was made more positive than about –20 mV. As the potential was made increasingly positive the transient outward current first increased and then decreased. The amplitude of the transient current increased when the external Ca2+ concentration was raised; and the current was abolished by Mn2+. It appears that when the membrane is depolarized Ca2+ ions enter the oocyte and trigger an outward current, possibly by opening Cl– channels.
Signal Transduction in Matrix Contraction and the Migration of Vascular Smooth Muscle Cells in Three-Dimensional Matrix

The interaction of vascular smooth muscle cells (SMCs) and extracellular matrix plays important roles in vascular remodeling. We investigated the signaling pathways involved in SMC-induced matrix contraction and SMC migration in three-dimensional (3D) collagen matrix. Matrix contraction is inhibited by the disruption of actin filaments but not microtubules. Therefore, we investigated the roles of signaling pathways related to actin filaments in matrix contraction. SMC-induced matrix contraction was markedly blocked (–80%) by inhibiting the Rho-p160ROCK pathway and myosin light chain kinase, and was decreased to a lesser extent (30–40%) by a negative mutant of Rac and inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase) or p38 mitogen-activated protein kinase (MAPK), but it was not affected by the inhibition of Ras and Cdc42-Wiskott-Aldrich syndrome protein (WASP) pathways. Inhibition of extracellular-signal-regulated kinase (ERK) decreased SMC-induced matrix contraction by only 15%. The migration speed and persistence of SMCs in the 3D matrix were decreased by the inhibition of p160ROCK, PI 3-kinase, p38 MAPK or WASP to different extents, and p160ROCK inhibitor had the strongest inhibitory effect. Our results suggest that the SMC-induced matrix contraction and the migration of SMCs in 3D matrix share some signaling pathways leading to force generation at cell-matrix adhesions and that various signaling pathways have different relative importance in the regulations of these processes in SMCs.
Calcineurin inhibitors stimulate and mycophenolic acid inhibits replication of hepatitis E virus.

BACKGROUND & AIMS Many recipients of organ transplants develop chronic hepatitis, due to infection with the hepatitis E virus (HEV). Although chronic HEV infection is generally associated with immunosuppressive therapies, little is known about how different immunosuppressants affect HEV infection. METHODS A subgenomic HEV replication model, in which expression of a luciferase reporter gene is measured, and a full-length infection model were used. We studied the effects of different immunosuppressants, including steroids, calcineurin inhibitors (tacrolimus [FK506] and cyclosporin A), and mycophenolic acid (MPA, an inhibitor of inosine monophosphate dehydrogenase) on HEV replication in human hepatoma cell line Huh7. Expression of cyclophilins A and B (the targets of cyclosporin A) were knocked down using small hairpin RNAs. RESULTS Steroids had no significant effect on HEV replication. Cyclosporin A promoted replication of HEV in the subgenomic and infectious models. Knockdown of cyclophilin A and B increased levels of HEV genomic RNA by 4.0- ± 0.6-fold and 7.2- ± 1.9-fold, respectively (n = 6; P < .05). A high dose of FK506 promoted infection of liver cells with HEV. In contrast, MPA inhibited HEV replication. Incubation of cells with guanosine blocked the antiviral activity of MPA, indicating that the antiviral effects of this drug involve nucleotide depletion. The combination of MPA and ribavirin had a greater ability to inhibit HEV replication than MPA or ribavirin alone. CONCLUSIONS Cyclophilins A and B inhibit replication of HEV; this might explain the ability of cyclosporin A to promote HEV infection. On the other hand, the immunosuppressant MPA inhibits HEV replication. These findings should be considered when physicians select immunosuppressive therapies for recipients of organ transplants who are infected with HEV.
Transcriptional and epigenetic networks of helper T and innate lymphoid cells

The discovery of the specification of CD4+ helper T cells to discrete effector ‘lineages’ represented a watershed event in conceptualizing mechanisms of host defense and immunoregulation. However, our appreciation for the actual complexity of helper T‐cell subsets continues unabated. Just as the Sami language of Scandinavia has 1000 different words for reindeer, immunologists recognize the range of fates available for a CD4+ T cell is numerous and may be underestimated. Added to the crowded scene for helper T‐cell subsets is the continuously growing family of innate lymphoid cells (ILCs), endowed with common effector responses and the previously defined ‘master regulators’ for CD4+ helper T‐cell subsets are also shared by ILC subsets. Within the context of this extraordinary complexity are concomitant advances in the understanding of transcriptomes and epigenomes. So what do terms like ‘lineage commitment’ and helper T‐cell ‘specification’ mean in the early 21st century? How do we put all of this together in a coherent conceptual framework? It would be arrogant to assume that we have a sophisticated enough understanding to seriously answer these questions. Instead, we review the current status of the flexibility of helper T‐cell responses in relation to their genetic regulatory networks and epigenetic landscapes. Recent data have provided major surprises as to what master regulators can or cannot do, how they interact with other transcription factors and impact global genome‐wide changes, and how all these factors come together to influence helper cell function.
Telomeres, A Busy Platform for Cell Signaling

Telomeres are the terminal structures at the ends of linear chromosomes that represent a solution to the end replication problem. Specific binding of the six-protein subunit complex shelterin to telomeric, repetitive TTAGGG DNA sequences contributes to the stable architecture and maintenance of telomeres. Proteins involved in the DNA damage response are also localized at telomeres, and play a role in the surveillance and maintenance of telomere integrity. The enzyme responsible for telomere extension is telomerase, a ribonucleoprotein with reverse transcriptase activity. In the absence of telomerase, telomeres shorten to a length threshold that triggers the DNA damage response and replicative senescence. Here, we will summarize the latest findings concerning vertebrate telomere structure and epigenetics, and we present data regarding the impact of short telomeres upon cell signaling. In particular, in murine embryonic stem cells lacking telomerase, we found that distribution of cytosolic/nuclear β-catenin, a key component of the Wnt signaling pathway, changes when telomeres become critically short. We discuss implications and future perspectives of the effect of epigenetic modifications and/or conformational changes of telomeres on cell metabolism and signaling networks. Such an analysis may unveil potential therapeutic targets for pathologies like cancer, where the integrity of telomeres is altered.
Unified Constraint-Based Task Specification for Complex Sensor-Based Robot Systems

This paper presents a unified task specification formalism and a unified control scheme for the lowest control level of sensor-based robot tasks. The formalism is based on: (i) the integration of any sensor that provides (direct or indirect) distance (and time derivatives) and force information; (ii) the possibility to use multiple "Tool Centre Points", e.g. defined relative to the robot end effector, other links or the environment; (iii) the integration of optimization functions for underconstrained as well as overconstrained specifications with linear constraints; (iv) the integration of on-line estimators; and (v) compatibility with all major low level control approaches. The unified formalism applies to the whole range from industrial manipulators over cooperating robots to humanoid robots, and from pure position control tasks over industrial processes to interaction between a humanoid robot and its environment.
Genome-Wide Identification of Bcl11b Gene Targets Reveals Role in Brain-Derived Neurotrophic Factor Signaling

B-cell leukemia/lymphoma 11B (Bcl11b) is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.
Long-term Subjective Benefit With a Bone Conduction Implant Sound Processor in 44 Patients With Single-Sided Deafness

Introduction Studies that investigate the subjective benefit from a bone conduction implant (BCI) sound processor in patients with single-sided sensorineural deafness (SSD) have been limited to examining short- and mid-term benefit. In the current study, we performed a survey among 44 SSD BCI users with a median follow-up time of 50 months. Materials and Methods Forty-four experienced SSD BCI users participated in the survey, which consisted of the Abbreviated Profile of Hearing Aid Benefit, the Single-Sided Deafness Questionnaire, the Short Hearing Handicap Inventory for Adults, and a self-made user questionnaire. For patients with tinnitus, the Tinnitus Questionnaire was also completed. The results of the survey were correlated with contralateral hearing loss, age at implantation, duration of the hearing loss at the time of implantation, duration of BCI use, and the presence and burden of tinnitus. Results In total, 86% of the patients still used their sound processor. The Abbreviated Profile of Hearing Aid Benefit and the Short Hearing Handicap Inventory for Adults show a statistically significant overall improvement with the BCI. The Single-Sided Deafness Questionnaire and the user questionnaire showed that almost 40% of the patients reported daily use of the sound processor. However, the survey of daily use reveals benefit only in certain circumstances. Speech understanding in noisy situations is rated rather low, and 58% of all patients reported that their BCI benefit was less than expected. Conclusion The majority of the patients reported an overall improvement from using their BCI. However, the number of users decreases during a longer follow-up time and patients get less enthusiastic about the device after an extended period of use, especially in noisy situations. However, diminished satisfaction because of time-related reductions in processor function could not be ruled out.
STAR REDUCIBLE COXETER GROUPS

We define “star reducible” Coxeter groups to be those Coxeter groups for which every fully commutative element (in the sense of Stembridge) is equivalent to a product of commuting generators by a sequence of length-decreasing star operations (in the sense of Lusztig). We show that the Kazhdan–Lusztig bases of these groups have a nice projection property to the Temperley–Lieb type quotient, and furthermore that the images of the basis elements $C'_w$ (for fully commutative $w$) in the quotient have structure constants in ${\mathbb Z}^{\geq 0}[v, v^{-1}]$. We also classify the star reducible Coxeter groups and show that they form nine infinite families with two exceptional cases.
Childhood abuse, parental warmth, and adult multisystem biological risk in the Coronary Artery Risk Development in Young Adults study

Significance Adverse social relations in early life are thought to negatively influence health throughout the lifespan. The present findings provide a biological link regarding why negative early life experiences affect health and further suggest that a loving parental figure may provide protection. It is well recognized that providing children in adverse circumstances with a nurturing relationship is beneficial for their overall wellbeing. Our findings suggest that a loving relationship may also prevent the rise in biomarkers indicative of disease risk across numerous physiological systems, impacting adverse health outcomes decades later. The results contribute in a meaningful way to several biological literatures and to the social sciences and, as such, will have a substantial impact. Childhood abuse increases adult risk for morbidity and mortality. Less clear is how this “toxic” stress becomes embedded to influence health decades later, and whether protective factors guard against these effects. Early biological embedding is hypothesized to occur through programming of the neural circuitry that influences physiological response patterns to subsequent stress, causing wear and tear across multiple regulatory systems. To examine this hypothesis, we related reports of childhood abuse to a comprehensive 18-biomarker measure of multisystem risk and also examined whether presence of a loving parental figure buffers against the impact of childhood abuse on adult risk. A total of 756 subjects (45.8% white, 42.7% male) participated in this ancillary substudy of the Coronary Artery Risk Development in Young Adults Study. Childhood stress was determined by using the Risky Families Questionnaire, a well-validated retrospective self-report scale. Linear regression models adjusting for age, sex, race, parental education, and oral contraceptive use found a significant positive relationship between reports of childhood abuse and multisystem health risks [B (SE) = 0.68 (0.16); P < 0.001]. Inversely, higher amounts of reported parental warmth and affection during childhood was associated with lower multisystem health risks [B (SE) = −0.40 (0.14); P < 0.005]. A significant interaction of abuse and warmth (P < 0.05) was found, such that individuals reporting low levels of love and affection and high levels of abuse in childhood had the highest multisystem risk in adulthood.
Special Theme of Research in Information Systems Analysis and Design-IV Evaluation Criteria for Information Systems Development Methodologies

The evaluation of information systems development methodologies is becoming increasingly important. Some researchers propose their own criteria for conceptual evaluations. But such criteria are often constrained by the limitation of the researcher’s view toward and experience with development methodologies. Furthermore, existing evaluation criteria are either not practical for direct measurement or not tested for validity and reliability. The lack of a generally acceptable, practically valid, and reliable set of criteria for evaluation hinders the development of knowledge in this area. Our study is a step toward developing a systematic process to evaluate information systems development methodologies. We captured the opinions of a group of twenty-eight researchers and practitioners who are experienced in information systems development methodologies. Through a systematic content analysis, the authors classified these criteria into three categories: (1) methodology design, (2) methodology use, and (3) methodology deliverables. The three categories of criteria are not totally separate in that they represent the means and goals of information systems development methodologies. Appropriate criteria should be applied depending on the stages when evaluation is performed.
Cross-Language Domain Adaptation for Classifying Crisis-Related Short Messages

Rapid crisis response requires real-time analysis of messages. After a disaster happens, volunteers attempt to classify tweets to determine needs, e.g., supplies, infrastructure damage, etc. Given labeled data, supervised machine learning can help classify these messages. Scarcity of labeled data causes poor performance in machine training. Can we reuse old tweets to train classifiers? How can we choose labeled tweets for training? Specifically, we study the usefulness of labeled data of past events. Do labeled tweets in different language help? We observe the performance of our classifiers trained using different combinations of training sets obtained from past disasters. We perform extensive experimentation on real crisis datasets and show that the past labels are useful when both source and target events are of the same type (e.g. both earthquakes). For similar languages (e.g., Italian and Spanish), cross-language domain adaptation was useful, however, when for different languages (e.g., Italian and English), the performance decreased.
How Big are the Tax Benefits of Debt

I integrate under firm-specific benefit functions to estimate that the capitalized tax benefit of debt equals 9.7 percent of firm value (or as low as 4.3 percent, net of personal taxes). The typical firm could double tax benefits by issuing debt until the marginal tax benefit begins to decline. I infer how aggressively a firm uses debt by observing the shape of its tax benefit function. Paradoxically, large, liquid, profitable firms with low expected distress costs use debt conservatively. Product market factors, growth options, low asset collateral, and planning for future expenditures lead to conservative debt usage. Conservative debt policy is persistent.
Surgical outcome and prognostic factors of cryptogenic neocortical epilepsy

Surgical treatment of cryptogenic neocortical epilepsy is challenging. The aim of this study was to evaluate surgical outcomes and to identify possible prognostic factors including the results of various diagnostic tools. Eighty‐nine patients with neocortical epilepsy with normal magnetic resonance imaging (35 patients with frontal lobe epilepsy, 31 with neocortical temporal lobe epilepsy, 11 with occipital lobe epilepsy, 11 with parietal lobe epilepsy, and 1 with multifocal epilepsy) underwent invasive study and focal surgical resection. Patients were observed for at least 2 years after surgery. The localizing values of interictal electroencephalogram (EEG), ictal scalp EEG, interictal 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET), and subtraction ictal single‐photon emission computed tomography were evaluated. Seventy‐one patients (80.0%) had a good surgical outcome (Engel class 1–3); 42 patients were seizure free. Diagnostic sensitivities of interictal EEG, ictal scalp EEG, FDG‐PET, and subtraction ictal single‐photon emission computed tomography were 37.1%, 70.8%, 44.3%, and 41.1%, respectively. Localization by FDG‐PET and interictal EEG was correlated with a seizure‐free outcome. The localizing value of FDG‐PET was greatest in neocortical temporal lobe epilepsy. The focalization of ictal onset and also ictal onset frequency in invasive studies were not related to surgical outcome. Concordance with two or more presurgical evaluations was significantly related to a seizure‐free outcome. Ann Neurol 2005