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Abstract Propagation of membrane tension mediates mechanical signal transduction along surfaces of live cells and sets the time scale of mechanical equilibration of cell membranes. Recent studies in several cell types and under different conditions revealed a strikingly wide variation range of the tension propagation speeds including extremely low ones. The latter suggests a possibility of long-living inhomogeneities of membrane tension crucially affecting mechano-sensitive membrane processes. Here, we propose, analyze theoretically, and support experimentally a mechanism of tension propagation in membranes crumpled by the contractile cortical cytoskeleton. The tension spreading is mediated by the membrane flow between the crumples. We predict the pace of the tension propagation to be controlled by the intra-cellular pressure and the degree of the membrane crumpling. We provide experimental support for the suggested mechanism by monitoring the rate of tension propagation in cells exposed to external media of different osmolarities.

This case report on recurrent urinary tract infections (UTIs) caused by multidrug-resistant (MDR) Klebsiella pneumoniae in a post-renal transplant patient underscores the significant clinical challenge of managing MDR infections in immunocompromised individuals, particularly in the context of renal transplantation. The patient was treated with an extended infusion of meropenem, which offers prolonged drug exposure and enhances bactericidal activity against MDR pathogens. This approach is critical in overcoming the resistance mechanisms inherent to Klebsiella pneumoniae, thereby improving the likelihood of therapeutic success. The findings presented here highlight the potential efficacy of extended meropenem infusion in treating MDR infections, providing a valuable therapeutic option for clinicians facing similar cases. This report contributes to the growing evidence supporting advanced antibiotic administration techniques in managing complicated urinary tract infections in transplant in resource limited countries.

The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear events. The host factor cleavage and polyadenylation specificity factor 6 (CPSF6) assists HIV-1 nuclear localization and post-entry integration targeting. Here, we used a CPSF6 truncation mutant lacking a functional nuclear localization signal (NLS), CPSF6-358, and appended heterologous NLSs to rescue nuclear localization. We show that some, but not all, NLSs drive CPSF6-358 into the nucleus. Interestingly, we found that some nuclear localized CPSF6-NLS chimeras supported inefficient HIV-1 infection. We found that HIV-1 still enters the nucleus in these cell lines but fails to traffic to speckle-associated domains (SPADs). Additionally, we show that HIV-1 fails to efficiently integrate in these cell lines. Collectively, our results demonstrate that the NLS of CPSF6 facilitates steps of HIV-1 infection subsequent to nuclear import and additionally identify the ability of canonical NLS sequences to influence cargo localization in the nucleus following nuclear import. Author summary: During HIV-1 infection, the viral capsid, which encloses the viral genome and essential proteins required for reverse transcription and integration, traffics towards the nucleus and enters through the nuclear pore complex (NPC). Following entry into the nucleus, reverse transcription is completed and viral capsid disassembles for integration of the viral DNA into a host chromosome. In this study, we investigated the role of the capsid-binding host factor CPSF6 in these events, specifically focusing on its nuclear localization signal (NLS) located at the protein's C-terminus. Swapping the NLS for heterologous NLSs from other proteins significantly impacted HIV-1's ability to infect cells. For NLSs that conveyed CPSF6 nuclear import, we further showed this defect in infection occurred at the level of viral DNA integration. This study highlights the importance of the NLS in CPSF6 to dictate nuclear import pathways that are congruent with functional HIV-1 infection. By extension, our study emphasizes that different NLSs can have comparatively dramatic post-nuclear effects on host cargo function. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the accuracy of tricuspid spectral Doppler (E/A) and tissue Doppler parameters (E/E') to diagnose right ventricular diastolic dysfunction (RVDD) in comparison to American Society of Echocardiography (ASE criteria) in pediatric tetralogy of Fallot (TOF) patients after surgical repair. Methods: This prospective, observational study was done at a tertiary care hospital involving 40 pediatric TOF patients aged less than 2 years who underwent complete intracardiac repair with cardiopulmonary bypass (CPB). Echocardiographic observations were made using a pediatric transesophageal echocardiography probe after surgical repair in the post-CPB period. The ASE-described parameters (late diastolic forward flow in the main pulmonary artery, right atrial dilatation, inferior vena cava dilatation, and hepatic venous flow reversal) were acquired to diagnose the RVDD. The tricuspid Doppler parameters (E/A and E/E') were measured, and its predictive ability to diagnose RVDD was analyzed and compared with the ASE criteria. Results: Based on the ASE criteria, 13 patients (32.5%) were diagnosed to have RVDD. We found that an E/E' ratio of ≥ 6.26 and an E/A ratio of >1.34 can be taken as the cutoff for diagnosing the RVDD. Based on the tricuspid Doppler parameters (E/A > 1.34 and E/E' >6.26), 17 patients (42.5%) were diagnosed to have RVDD, which was comparable to that of the diagnosis by ASE criteria (P > 0.05). Conclusion: The results suggested that the use of tricuspid Doppler parameters can be equally accurate and reproducible to the current ASE-described echocardiographic parameters for diagnosing RVDD after surgical repair of TOF. [ABSTRACT FROM AUTHOR]