Do intelligent leaders differentiate exchange relationships intelligently? A functional leadership approach to leader-member exchange differentiation.

The burgeoning literature on leader-member exchange (LMX) differentiation indicates that differentiating LMX relationships within groups has both benefits and costs when it comes to group effectiveness. Although some clarity is emerging surrounding the null total effect of LMX differentiation on group performance, we still know little about how leaders themselves shape the differentiation process. In this article, we extend theory to suggest that some leaders may differentiate more effectively than others. Drawing from functional leadership theory, we first identify a potential approach available to leaders likely to enhance their functional effectiveness-strategically investing in and developing stronger social exchange relationships with subordinates who can best help them fulfill the task functions (via task performance-based differentiation) and group maintenance functions (via contextual performance-based differentiation) specified within functional leadership theory. Embedding this potential approach within the ability-motivation-opportunity framework, we then develop a theory for which leaders are best positioned to recognize and pursue strategic relationship development this way. Specifically, we posit that leaders with stronger cognitive abilities (g) are more likely to recognize the value of such an approach, and those high in core self-evaluation are more likely to believe in their capabilities to successfully process, execute on, and persist with the approach. The results from two studies-a multisource study of leaders and team members in newly formed teams as well as a preregistered online vignette study using a sample of current and former supervisors-largely supported our predictions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation.

Transcription is regulated by a multitude of activators and repressors, which bind to the RNA polymerase II (Pol II) machinery and modulate its progression. Death-inducer obliterator 3 (DIDO3) and PHD finger protein 3 (PHF3) are paralogue proteins that regulate transcription elongation by docking onto phosphorylated serine-2 in the C-terminal domain (CTD) of Pol II through their SPOC domains. Here, we show that DIDO3 and PHF3 form a complex that bridges the Pol II elongation machinery with chromatin and RNA processing factors and tethers Pol II in a phase-separated microenvironment. Their SPOC domains and C-terminal intrinsically disordered regions are critical for transcription regulation. PHF3 and DIDO exert cooperative and antagonistic effects on the expression of neuronal genes and are both essential for neuronal differentiation. In the absence of PHF3, DIDO3 is upregulated as a compensatory mechanism. In addition to shared gene targets, DIDO specifically regulates genes required for lipid metabolism. Collectively, our work reveals multiple layers of gene expression regulation by the DIDO3 and PHF3 paralogues, which have specific, co-regulatory and redundant functions in transcription.

The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action.

The molecular events governing skeletal muscle glucose uptake have pharmacological potential for managing insulin resistance in conditions such as obesity, diabetes, and cancer. With no current pharmacological treatments to target skeletal muscle insulin sensitivity, there is an unmet need to identify the molecular mechanisms that control insulin sensitivity in skeletal muscle. Here, the Rho guanine dissociation inhibitor α (RhoGDIα) is identified as a point of control in the regulation of insulin sensitivity. In skeletal muscle cells, RhoGDIα interacted with, and thereby inhibited, the Rho GTPase Rac1. In response to insulin, RhoGDIα was phosphorylated at S101 and Rac1 dissociated from RhoGDIα to facilitate skeletal muscle GLUT4 translocation. Accordingly, siRNA-mediated RhoGDIα depletion increased Rac1 activity and elevated GLUT4 translocation. Consistent with RhoGDIα's inhibitory effect, rAAV-mediated RhoGDIα overexpression in mouse muscle decreased insulin-stimulated glucose uptake and was detrimental to whole-body glucose tolerance. Aligning with RhoGDIα's negative role in insulin sensitivity, RhoGDIα protein content was elevated in skeletal muscle from insulin-resistant patients with type 2 diabetes. These data identify RhoGDIα as a clinically relevant controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis, mechanistically by modulating Rac1 activity.

Disruption of mitochondrial dynamics triggers muscle inflammation through interorganellar contacts and mitochondrial DNA mislocation.

Some forms of mitochondrial dysfunction induce sterile inflammation through mitochondrial DNA recognition by intracellular DNA sensors. However, the involvement of mitochondrial dynamics in mitigating such processes and their impact on muscle fitness remain unaddressed. Here we report that opposite mitochondrial morphologies induce distinct inflammatory signatures, caused by differential activation of DNA sensors TLR9 or cGAS. In the context of mitochondrial fragmentation, we demonstrate that mitochondria-endosome contacts mediated by the endosomal protein Rab5C are required in TLR9 activation in cells. Skeletal muscle mitochondrial fragmentation promotes TLR9-dependent inflammation, muscle atrophy, reduced physical performance and enhanced IL6 response to exercise, which improved upon chronic anti-inflammatory treatment. Taken together, our data demonstrate that mitochondrial dynamics is key in preventing sterile inflammatory responses, which precede the development of muscle atrophy and impaired physical performance. Thus, we propose the targeting of mitochondrial dynamics as an approach to treating disorders characterized by chronic inflammation and mitochondrial dysfunction.

Predictors of intraoperative pain during cesarean delivery under regional anesthesia.

It is unclear why some patients experience pain during cesarean delivery despite receiving appropriate regional anesthesia. Our primary aim was to determine what demographic and clinical variables predict intraoperative pain during cesarean delivery with neuraxial anesthesia. From July 2019 through March 2020, we administered a previously validated patient satisfaction survey to parturients who had a cesarean delivery under regional anesthesia for nonemergent obstetric indications. We performed a post hoc analysis restricted to subjects who had single injection spinal and combined spinal-epidural anesthesia. Parturients who did and did not report pain differed in height, intrathecal hyperbaric bupivacaine dose, and the time from incision to wound closure. We performed an ordinal logistic regression analysis on the 168 subjects with complete data using the aforementioned variables along with the time of day of cesarean delivery. Incision to wound closure time (P < 0.01) predicted intraoperative pain. The multivariate logistic regression model was statistically significant (P < 0.01) and had a receiver operator curve value of 0.74. The duration of time from incision to wound closure predicted intraoperative pain during cesarean delivery under regional anesthesia.

What does it cost you to get there? The effects of emotional journeys on daily outcomes.

Scholarly understanding of emotions and emotion regulation rests on two incompatible truths-that positive emotions are positively beneficial and should be pursued, and that changing emotions may come at a cost. With both perspectives in mind, to really conclude that pursuing higher positive affect (PA) is a worthy journey, we must take into account the cost of that journey itself. We build from the affect shift literature and draw on self-regulation theories to argue that, although end-states characterized by more positive (and fewer negative) emotions will be beneficial, the emotional changes required to "get there" will have consequences for employee regulatory resources and subsequent behavior. In Study 1, we use experience sampling methodology to track employee emotional journeys-changes in emotions in terms of directionality (e.g., toward pleasure and away from pain) and distance (i.e., magnitude of change in terms of intensity changes within-emotions as well as magnitude of change in activation/valence level between emotions)-that capture the amount of emotion regulation preceding emotion end-states. Teasing apart variance attributable to the end-state versus the journey, we demonstrate that steeper daily PA trajectories (steeper increases in intensity of positive, activated emotions) and valence trajectories (steeper movement away from more negative emotions toward more positive emotions) lead to psychological depletion, ultimately triggering interpersonal counterproductive work behaviors and harming citizenship and performance. In Study 2, we test our core propositions in a lab experiment, demonstrating that different emotional journeys "leading up" to the same affective end-state can change the meaning of that end-state. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effects of Percutaneous Endoscopic Gastrostomy in Patients With Huntington Disease.

OBJECTIVE: To determine the impact of percutaneous endoscopic gastrostomy (PEG) tubes in patients with advanced Huntington disease (HD). METHODS: A retrospective chart review of patients with HD was conducted to assess the rate of pneumonia and pressure ulcer, length of life, changes in weight, and serologic nutritional measures. Surviving and deceased patients with and without PEG tubes were compared using descriptive statistical analysis. RESULTS: One hundred forty-eight records were reviewed (39 patients with PEG tubes). The mean age of patients still alive and diagnosed with HD was 58.3 ± 12.7 years and age at death (n = 62) 57.7 ± 10.3 years. At the time of analysis, the mean duration of HD was 14.2 ± 7 years. Groups were similar in sex, age, and weight at admission. In those deceased, insertion of a PEG tube increased the length of life with HD by 3.6 years (16.2 ± 6.7 vs 13.2 ± 4.9 years). PEG tube placement significantly reduced cholesterol levels, increased the prevalence of skin ulcers and the rate of pneumonia. Insertion of a PEG tube did not significantly change weight or albumin levels. CONCLUSIONS: PEG tube placement in advanced HD provided benefit in the length of life, but weight, other nutritional measures, and the rate of pneumonia were either not impacted or worsened with the insertion of a PEG tube. Impact on quality of life needs further study, but providers, patients, and families should consider all options when discussing preferences for interventions. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with advanced HD, PEG tube placement increases the length of life but has no or negative impacts on nutritional measures.

Cycloaddition/Electrocyclic Ring Opening Sequence between Alkynyl Sulfides and Azodicarboxylates To Provide N,N-Dicarbamoyl 2-Iminothioimidates.

The α-oxidized thioimidates are useful bidentate ligands and are important motifs in pharmaceuticals, pesticides, and fungicides. Despite their broad utility, a direct route for their synthesis has been elusive. Herein, we describe a one-step synthesis of N,N-dicarbamoyl 2-iminothioimidates from easily accessible thioacetylenes and commercially available azodicarboxylates (20 examples, ≤99% yield). Additionally, the mechanism of the transformation was extensively explored by variable-temperature NMR, in situ IR, and quantum mechanical simulations. These experiments suggest that the reaction commences with a highly asynchronous [2 + 2] cycloaddition, which leads to a four-membered diazacyclobutene intermediate with a barrier consistent with the observed reaction rate. This intermediate was then isolated for subsequent kinetic measurements, which yielded an experimental barrier within 1 kcal/mol of the calculated barrier for a subsequent 4π electrocyclic ring opening leading to the observed iminothioimidate products. This method represents the first direct route to α-oxidized thioimidates from readily accessible starting materials.