TAZ Suppresses NFAT5 Activity through Tyrosine Phosphorylation

Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney, and a deficiency of this protein results in multiple renal cysts and urinary concentration defects; however, the molecular functions of TAZ in renal cells remain largely unknown. In this study, we examined the effects of osmotic stress on TAZ expression and activity in renal cells. We found that hyperosmotic stress selectively increased protein phosphorylation at tyrosine 316 of TAZ and that this was enhanced by c-Abl activation in response to hyperosmotic stress. Interestingly, phosphorylated TAZ physically interacted with nuclear factor of activated T cells 5 (NFAT5), a major osmoregulatory transcription factor, and subsequently suppressed DNA binding and transcriptional activity of NFAT5. Furthermore, TAZ deficiency elicited an increase in NFAT5 activity in vitro and in vivo, which then reverted to basal levels following restoration of wild-type TAZ but not mutant TAZ (Y316F). Collectively, the data suggest that TAZ modulates cellular responses to hyperosmotic stress through fine-tuning of NFAT5 activity via tyrosine phosphorylation.open3

Principal factors that determine the extension of detection range in molecular beacon aptamer/conjugated polyelectrolyte bioassays.

A strategy to extend the detection range of weakly-binding targets is reported that takes advantage of fluorescence resonance energy transfer (FRET)-based bioassays based on molecular beacon aptamers (MBAs) and cationic conjugated polyelectrolytes (CPEs). In comparison to other aptamer-target pairs, the aptamer-based adenosine triphosphate (ATP) detection assays are limited by the relatively weak binding between the two partners. In response, a series of MBAs were designed that have different stem stabilities while keeping the constant ATP-specific aptamer sequence in the loop part. The MBAs are labeled with a fluorophore and a quencher at both termini. In the absence of ATP, the hairpin MBAs can be opened by CPEs via a combination of electrostatic and hydrophobic interactions, showing a FRET-sensitized fluorophore signal. In the presence of ATP, the aptamer forms a G-quadruplex and the FRET signal decreases due to tighter contact between the fluorophore and quencher in the ATP/MBA/CPE triplex structure. The FRET-sensitized signal is inversely proportional to [ATP]. The extension of the detection range is determined by the competition between opening of the ATP/MBA G-quadruplex by CPEs and the composite influence by ATP/aptamer binding and the stem interactions. With increasing stem stability, the weak binding of ATP and its aptamer is successfully compensated to show the resistance to disruption by CPEs, resulting in a substantially broadened detection range (from millimolar up to nanomolar concentrations) and a remarkably improved limit of detection. From a general perspective, this strategy has the potential to be extended to other chemical- and biological-assays with low target binding affinity

When Literature is Limited: Using Grant Language and Project Partner Notes to Conceptually Frame a Study

Abstract Expanding beyond traditional roles, some museums are now striving to serve as public learning and social catalyst institutions for their communities. Museums are increasingly engaging with communities to address social, environmental and other complex contemporary issues, sometimes partnering with other institutions and organizations to engage and serve community members. Because these roles and programs are often untested, assessment is critical for identifying potential outcomes, developing recommendations for program improvement, and justifying their existence in a world that increasingly demands accountability. However, literature relevant to museum programs addressing specific social issues is limited. This paper presents an alternative strategy for developing a conceptual framework for a future program assessment, using grant language and project notes as the foundation

Evaluating Impacts of a Museum-Based Program for Transitional Homeless Adults

Abstract One broad goal of museums is to benefit community members, within their respective museum missions. Some museums are expanding their audiences beyond traditional on-site visitors to broaden and diversify their impacts, including at-risk populations. Evaluation of newly developed museum-based programs is important for program staff, partners, and sponsors to understand effectiveness of, and to find ways to improve, their programs. This study assessed perceived impacts of a museum-based program, Your Story and Mine (YSM), which was developed for homeless adults in mid-Michigan. Semi-structured in-depth interviews were conducted with six program participants. Based on a three-tier “hierarchy of evidence” framework, developed specifically for evaluating the YSM program, responses were coded and categorized into three levels of impacts: i) knowledge/awareness gain; ii) attitude and behavior change; and iii) group development. An emerging fourth response category, “program features” valued by respondents, was added. Participants’ responses reflected their perceptions of program benefits

On Monotonic Aggregation for Open-domain QA

Question answering (QA) is a critical task for speech-based retrieval from knowledge sources, by sifting only the answers without requiring to read supporting documents. Specifically, open-domain QA aims to answer user questions on unrestricted knowledge sources. Ideally, adding a source should not decrease the accuracy, but we find this property (denoted as "monotonicity") does not hold for current state-of-the-art methods. We identify the cause, and based on that we propose Judge-Specialist framework. Our framework consists of (1) specialist retrievers/readers to cover individual sources, and (2) judge, a dedicated language model to select the final answer. Our experiments show that our framework not only ensures monotonicity, but also outperforms state-of-the-art multi-source QA methods on Natural Questions. Additionally, we show that our models robustly preserve the monotonicity against noise from speech recognition. We publicly release our code and setting.Comment: INTERSPEECH 2023 Camera Read

‘Evidence of an auxin signal pathway, microRNA167-ARF8-GH3, and its response to exogenous auxin in cultured rice cells’

MicroRNA167 (miR167) was shown to cleave auxin responsive factor 8 (ARF8) mRNA in cultured rice cells. MiR167 level was found to be controlled by the presence of auxin in the growth medium. When cells grew in auxin-free medium, miR167 level decreased, resulting in an increase in the level of ARF8 mRNA. Cells growing in the normal growth medium containing auxin showed a reversed trend. It was also shown that expression of OsGH3-2, an rice IAA-conjugating enzyme, was positively regulated by ARF8. Delivery of synthesized miR167 into cells led to decrease of both ARF8 mRNA and OsGH3-2 mRNA. This study provides an evidence in which the exogeneous auxin signal is transduced to OsGH3-2 through miR167 and ARF8 in sequence. This proposed auxin signal transduction pathway, auxin-miR167-ARF8-OsGH3-2, could be, in conjunction with the other microRNA-mediated auxin signals, an important one for responding to exogeneous auxin and for determining the cellular free auxin level which guides appropriate auxin responses

Validation of the Dimensions of Anger Reactions Scale (the DAR-5) in non-clinical South Korean adults

Background Posttraumatic anger is a commonly reported emotion among people who have experienced traumatic events. The current study aimed to demonstrate the reliability and validity of the South Korean version of the DAR-5 (DAR-5-K). The DAR-5 is a single scale with 5 items which measures posttraumatic anger. The DAR-5 is composed of five items that measure anger frequency, intensity, duration, aggression, and its interference with social relations. Methods Data were collected from 814 South Korean adults who had experienced traumatic events and participated in the study and analyzed via the combination of exploratory factor analysis (n = 405) and confirmatory factor analysis (n = 409). Results Results supported the one-factor structure, as reported in previous validation studies. The scale demonstrated robust internal reliability and concurrent validity with measures of posttraumatic stress disorder (PTSD) symptoms, depression, anxiety, and self-esteem. The DAR-5 cut-off score of 12 that was established in the original validation study successfully differentiated high from low scorers with regard to PTSD symptoms, depression, anxiety, and self-esteem. Conclusion The results confirm that the DAR-5-K is a brief and psychometrically robust measure of anger that can be used to examine South Korean adults who have experienced traumatic events

Clear Cell Hidradenoma of the Axilla: a Case Report with Literature Review

Clear cell hidradenoma is an uncommon benign skin appendageal tumor that typically involves the dermal layer of the head, face, and extremities. The breast is a rare site for this lesion, with only two documented cases, which were determined based on mammogram and sonogram findings. We present a case of clear cell hidradenoma of the axillary tail with radiological findings and a literature review

Isolated Weakness of Middle, Ring, and Little Fingers due to a Small Cortical Infarction in the Medial Precentral Gyrus

Small cortical strokes can produce predominant isolated weakness in a particular group of fingers: radial or ulnar. The traditional views are of point-to-point representations of each finger to neurons located in the precentral gyrus of the motor cortex such that the neurons of the radial fingers are located laterally and those of the ulnar fingers are located medially. We present a case of isolated weakness of middle, ring, and little fingers due to a small cortical infarction in the medial precentral gyrus