Serving the cause when my organization does not: a self‐affirmation model of employees’ compensatory responses to ideological contract breach

Transactional and relational contract breach occur when organizations fail to deliver on promised personal benefits for employees and are associated with negative behaviors reciprocating such mistreatment. However, recent research suggests that ideological contract breach, a unique form of contract breach, may yield constructive behaviors because it is not organizations’ direct personal mistreatment of employees, but organizations’ abandonment of a valued cause to benefit a third party. Such an interesting prediction goes beyond the dominant social-exchange framework, which mainly forecasts destructive responses to breach. In this research, we develop a novel self-affirmation model to explain how ideological contract breach results in counterintuitive positive outcomes. In a hospital field study among medical professionals (N = 362) and their supervisors (N = 129), we found that ideological contract breach induces employees’ rumination about the breach, which in turn prompts them to self-affirm core values at work. This self-affirmation eventually spurs proactive serving behavior and self-improvement behavior to compensate for the breached ideology. Professional identification enhances this self-affirmation process

In vivo anticancer activity of a rhodium metalloinsertor in the HCT116 xenograft tumor model

Mismatch repair (MMR) deficiencies are a hallmark of various cancers causing accumulation of DNA mutations and mismatches, which often results in chemotherapy resistance. Metalloinsertor complexes, including [Rh(chrysi)(phen)(PPO)]Cl₂ (Rh-PPO), specifically target DNA mismatches and selectively induce cytotoxicity within MMR-deficient cells. Here, we present an in vivo analysis of Rh-PPO, our most potent metalloinsertor. Studies with HCT116 xenograft tumors revealed a 25% reduction in tumor volume and 12% increase in survival with metalloinsertor treatment (1 mg/kg; nine intraperitoneal doses over 20 d). When compared to oxaliplatin, Rh-PPO displays ninefold higher potency at tumor sites. Pharmacokinetic studies revealed rapid absorption of Rh-PPO in plasma with notable accumulation in the liver compared to tumors. Additionally, intratumoral metalloinsertor administration resulted in enhanced anticancer effects, pointing to a need for more selective delivery methods. Overall, these data show that Rh-PPO inhibits xenograft tumor growth, supporting the strategy of using Rh-PPO as a chemotherapeutic targeted to MMR-deficient cancers

In vivo anticancer activity of a rhodium metalloinsertor in the HCT116 xenograft tumor model

Mismatch repair (MMR) deficiencies are a hallmark of various cancers causing accumulation of DNA mutations and mismatches, which often results in chemotherapy resistance. Metalloinsertor complexes, including [Rh(chrysi)(phen)(PPO)]Cl₂ (Rh-PPO), specifically target DNA mismatches and selectively induce cytotoxicity within MMR-deficient cells. Here, we present an in vivo analysis of Rh-PPO, our most potent metalloinsertor. Studies with HCT116 xenograft tumors revealed a 25% reduction in tumor volume and 12% increase in survival with metalloinsertor treatment (1 mg/kg; nine intraperitoneal doses over 20 d). When compared to oxaliplatin, Rh-PPO displays ninefold higher potency at tumor sites. Pharmacokinetic studies revealed rapid absorption of Rh-PPO in plasma with notable accumulation in the liver compared to tumors. Additionally, intratumoral metalloinsertor administration resulted in enhanced anticancer effects, pointing to a need for more selective delivery methods. Overall, these data show that Rh-PPO inhibits xenograft tumor growth, supporting the strategy of using Rh-PPO as a chemotherapeutic targeted to MMR-deficient cancers

Greater Pre-Stimulus Effective Connectivity from the Left Inferior Frontal Area to other Areas is Associated with Better Phonological Decoding in Dyslexic Readers

Functional neuroimaging studies suggest that neural networks that subserve reading are organized differently in dyslexic readers (DRs) and typical readers (TRs), yet the hierarchical structure of these networks has not been well studied. We used Granger causality to examine the effective connectivity of the preparatory network that occurs prior to viewing a non-word stimulus that requires phonological decoding in 7 DRs and 10 TRs who were young adults. The neuromagnetic activity that occurred 500 ms prior to each rhyme trial was analyzed from sensors overlying the left and right inferior frontal areas (IFA), temporoparietal areas, and ventral occipital–temporal areas within the low, medium, and high beta and gamma sub-bands. A mixed-model analysis determined whether connectivity to or from the left and right IFAs differed across connectivity direction (into vs. out of the IFAs), brain areas, reading group, and/or performance. Results indicated that greater connectivity in the low beta sub-band from the left IFA to other cortical areas was significantly related to better non-word rhyme discrimination in DRs but not TRs. This suggests that the left IFA is an important cortical area involved in compensating for poor phonological function in DRs. We suggest that the left IFA activates a wider-than usual network prior to each trial in the service of supporting otherwise effortful phonological decoding in DRs. The fact that the left IFA provides top-down activation to both posterior left hemispheres areas used by TRs for phonological decoding and homologous right hemisphere areas is discussed. In contrast, within the high gamma sub-band, better performance was associated with decreased connectivity between the left IFA and other brain areas, in both reading groups. Overly strong gamma connectivity during the pre-stimulus period may interfere with subsequent transient activation and deactivation of sub-networks once the non-word appears

Effect of aging on cellular mechanotransduction

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, respiratory systems and skin

Validation of a New NIRS Method for Measuring Muscle Oxygenation During Rhythmic Handgrip Exercise

Near infrared spectroscopy (NIRS) is commonly used to measure muscle oxygenation during exercise and recovery. Current NIRS algorithms do not account for variation in water content and optical pathlength during exercise. The current effort attempts to validate a newly developed NIRS algorithm during rhythmic handgrip exercise and recovery. Six female subjects, aver age 28 +/- 6 yrs, participated in the study. A venous catheter was placed in the retrograde direction in the antecubital space. A NIRS sensor with 30 mm source-detector separation was placed on the flexor digitorum profundus. Subjects performed two 5-min bouts of rhythmic handgrip exercise (2 s contraction/1 s relaxation) at 15% and 30% of maximal voluntary contraction. Venous blood was sampled before each bout, during the last minute of exercise, and after 5 minutes of recovery. Venous oxygen saturation (SvO2) was measured with a I-stat CG-4+ cartridge. Spectra were collected between 700-900 nm. A modified Beer's Law formula was used to calculate the absolute concentration of oxyhemoglobin (HbO2), deoxyhemoglobin (Hb) and water, as well as effective pathlength for each spectrum. Muscle oxygen saturation (SmO2) was calculated from the HbO2 and Hb results. The correlation between SvO2 and SmO2 was determined. Optical pathlength and water varied significantly during each exercise bout, with pathlength increasing approximately 20% and water increasing about 2%. R2 between blood and muscle SO2 was found to be 0.74, the figure shows the relationship over SvO2 values between 22% and 82%. The NIRS measurement was, on average, 6% lower than the blood measurement. It was concluded that pathlength changes during exercise because muscle contraction causes variation in optical scattering. Water concentration also changes, but only slightly. A new NIRS algorithm which accounts for exercise-induced variation in water and pathlength provided an accurate assessment of muscle oxygen saturation before, during and after exercise

CRISPR artificial splicing factors.

Alternative splicing allows expression of mRNA isoforms from a single gene, expanding the diversity of the proteome. Its prevalence in normal biological and disease processes warrant precise tools for modulation. Here we report the engineering of CRISPR Artificial Splicing Factors (CASFx) based on RNA-targeting CRISPR-Cas systems. We show that simultaneous exon inclusion and exclusion can be induced at distinct targets by differential positioning of CASFx. We also create inducible CASFx (iCASFx) using the FKBP-FRB chemical-inducible dimerization domain, allowing small molecule control of alternative splicing. Finally, we demonstrate the activation of SMN2 exon 7 splicing in spinal muscular atrophy (SMA) patient fibroblasts, suggesting a potential application of the CASFx system