Functional Evidence of the Involvement of the Dynein Light Chain DYNLRB2 in Murine Leukemia Virus Infection.

How murine leukemia virus (MLV) travels from the cell membrane to the nucleus and the mechanism for nuclear entry of MLV DNA in dividing cells still remain unclear. It seems likely that the MLV preintegration complex (PIC) interacts with cellular proteins to perform these tasks. We recently published that the microtubule motor cytoplasmic dynein complex and its regulator proteins interact with the MLV PIC at early times of infection, suggesting a functional interaction between the incoming viral particles, the dynein complex, and dynein regulators. To better understand the role of the dynein complex in MLV infection, we performed short hairpin RNA (shRNA) screening of the dynein light chains on MLV infection. We found that silencing of a specific light chain of the cytoplasmic dynein complex, DYNLRB2, reduced the efficiency of infection by MLV reporter viruses without affecting HIV-1 infection. Furthermore, the overexpression of DYNLRB2 increased infection by MLV. We conclude that the DYNLRB2 light chain of the cytoplasmic dynein complex is an important and specific piece of the host machinery needed for MLV infection.IMPORTANCE Retroviruses must reach the chromatin of their host to integrate their viral DNA, but first they must get into the nucleus. The cytoplasm is a crowded environment in which simple diffusion is slow, and thus viruses utilize retrograde transport along the microtubule network, mediated by the dynein complex. Different viruses use different components of this multisubunit complex. We have found that murine leukemia virus (MLV) associates functionally and specifically with the dynein light chain DYNLRB2, which is required for infection. Our study provides more insight into the molecular requirements for retrograde transport of the MLV preintegration complex and demonstrates, for the first time, a role for DYNLRB2 in viral infection.

Fecal cortisol levels predict breeding but not survival of females in the short-lived rodent, Octodon degus.

The cort-adaptation hypothesis indicates that an association between glucocorticoid (cort) levels and fitness may vary with the extent to which reproduction or breeding effort is a major determinant of cort levels. Support for a context dependent association between cort and fitness comes mostly from relatively long-lived, bird species. We tested the hypothesis that there are gender and context (life-history) specific cort-fitness relationships in degus, a short-lived and generally semelparous social rodent. In particular, we used demographical records on a natural population to estimate adult survival through seasons and years and linked that to records of baseline cort (based on fecal cortisol metabolites). We found no evidence for a direct relationship between baseline cort and adult survival across seasons, and this lack of association was recorded irrespective of sex and life history stage. Yet, cort levels during early lactation predicted the probability that females produce a second litter during the same breeding season, supporting a connection between baseline cort levels and breeding effort. Overall, the differential effects of cort on survival and breeding supported that the extent of cort-fitness relationships depends on the fitness component examined.

Impact of interorganelle coordination between the conventional early secretory pathway and autophagy in cellular homeostasis and stress response.

The conventional early secretory pathway and autophagy are two essential interconnected cellular processes that are crucial for maintaining cellular homeostasis. The conventional secretory pathway is an anabolic cellular process synthesizing and delivering proteins to distinct locations, including different organelles, the plasma membrane, and the extracellular media. On the other hand, autophagy is a catabolic cellular process that engulfs damaged organelles and aberrant cytosolic constituents into the double autophagosome membrane. After fusion with the lysosome and autolysosome formation, this process triggers digestion and recycling. A growing list of evidence indicates that these anabolic and catabolic processes are mutually regulated. While knowledge about the molecular actors involved in the coordination and functional cooperation between these two processes has increased over time, the mechanisms are still poorly understood. This review article summarized and discussed the most relevant evidence about the key molecular players implicated in the interorganelle crosstalk between the early secretory pathway and autophagy under normal and stressful conditions.

Efficacy of Platelet-Rich Plasma in Reduction of Post-Operative Split-Thickness Skin Graft Loss and Hematoma Formation: A Meta-Analysis.

Split-thickness skin grafting is a very popular technique of wound closure, especially for large wounds. The success rate of a split-thickness skin graft (STSG) has consistently been in the range of 70-90%. Multiple techniques have been introduced to further improve graft survival, for example, the use of autologous platelet-rich plasma (PRP), thrombin gel, platelet-rich fibrin matrix, and negative pressure wound therapy. We evaluated the impact of PRP use on the survival of STSG through a meta-analysis. We conducted the analysis in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol and performed a literature search using the following databases: PubMed, Cochrane, and ClinicalTrials.gov. A total of 126 articles were yielded by the search, out of which four randomized controlled trials (RCTs) were included according to our eligibility criteria and irrelevant articles were excluded. The intervention group received PRP application to the wound bed before applying the graft while the control group received treatment with conventional fixation procedures (sutures and staples). We estimated the pooled odds ratio with a 95% confidence interval (CI). The total number of participants in the analysis was 460. The participants had wounds of varying etiology. Post-operative graft loss and hematoma formation were taken to be the primary and secondary outcome measures, respectively. Thirty-four participants suffered graft loss of differing extent in the control group while three participants suffered graft loss in the intervention group. The pooled odds ratio for graft loss was 0.15 (95% CI: 0.05-0.49; I2=38%; p=0.184) signifying that PRP use decreased the odds of graft loss by 85%. For our secondary outcome measure, 440 participants were studied. Forty-four participants suffered hematoma formation in the control group versus 11 in the intervention group. The pooled odds ratio for hematoma formation was calculated as 0.21 (95% CI: 0.09-0.50; I2=0%; p=0.869) signifying that PRP use decreased the odds of hematoma formation by 79%. PRP appears to significantly impact graft survival, and further studies are needed to strengthen the evidence base for its use in split-thickness skin grafting.

Synaptic Mitochondria: An Early Target of Amyloid-ß and Tau in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by cognitive impairment and the presence of neurofibrillary tangles and senile plaques in the brain. Neurofibrillary tangles are composed of hyperphosphorylated tau, while senile plaques are formed by amyloid-ß (Aß) peptide. The amyloid hypothesis proposes that Aß accumulation is primarily responsible for the neurotoxicity in AD. Multiple Aß-mediated toxicity mechanisms have been proposed including mitochondrial dysfunction. However, it is unclear if it precedes Aß accumulation or if is a consequence of it. Aß promotes mitochondrial failure. However, amyloid ß precursor protein (AßPP) could be cleaved in the mitochondria producing Aß peptide. Mitochondrial-produced Aß could interact with newly formed ones or with Aß that enter the mitochondria, which may induce its oligomerization and contribute to further mitochondrial alterations, resulting in a vicious cycle. Another explanation for AD is the tau hypothesis, in which modified tau trigger toxic effects in neurons. Tau induces mitochondrial dysfunction by indirect and apparently by direct mechanisms. In neurons mitochondria are classified as non-synaptic or synaptic according to their localization, where synaptic mitochondrial function is fundamental supporting neurotransmission and hippocampal memory formation. Here, we focus on synaptic mitochondria as a primary target for Aß toxicity and/or formation, generating toxicity at the synapse and contributing to synaptic and memory impairment in AD. We also hypothesize that phospho-tau accumulates in mitochondria and triggers dysfunction. Finally, we discuss that synaptic mitochondrial dysfunction occur in aging and correlates with age-related memory loss. Therefore, synaptic mitochondrial dysfunction could be a predisposing factor for AD or an early marker of its onset.

Inexpensive and green electrochemical sensor for the determination of Cd(II) and Pb(II) by square wave anodic stripping voltammetry in bivalve mollusks.

An inexpensive and environmental friendly electrochemical sensor based on a glassy carbon electrode (GC) modified with graphene quantum dots (GQDs) and Nafion (NF) has been developed for the determination of Cd(II) and Pb(II) in bivalve mollusks using square wave anodic stripping voltammetry (SWASV). GQDs were characterized by UV-Vis spectroscopy, fluorescence and transmission electronic microscopy (TEM). The modified electrode was evaluated by cyclic voltammetry, scanning electronic microscopy (SEM) and electrochemical impedance spectroscopy (EIS). A linearity of 20-200 µg L-1 was found, with a limit of detection (LOD) of 11.30 µg L-1 for Cd(II) and 8.49 µg L-1 for Pb(II). The proposed methodology was validated with a certified reference material TMDA-64.2. The reproducibility of GC/GQDs-NF for both species had an RSD of less than 10%. The results were compared with ICP-OES. The method was applied in the determination of Cd(II) and Pb(II) in bivalve mollusks samples with excellent results.

KDEL receptor regulates secretion by lysosome relocation- and autophagy-dependent modulation of lipid-droplet turnover.

Inter-organelle signalling has essential roles in cell physiology encompassing cell metabolism, aging and temporal adaptation to external and internal perturbations. How such signalling coordinates different organelle functions within adaptive responses remains unknown. Membrane traffic is a fundamental process in which membrane fluxes need to be sensed for the adjustment of cellular requirements and homeostasis. Studying endoplasmic reticulum-to-Golgi trafficking, we found that Golgi-based, KDEL receptor-dependent signalling promotes lysosome repositioning to the perinuclear area, involving a complex process intertwined to autophagy, lipid-droplet turnover and Golgi-mediated secretion that engages the microtubule motor protein dynein-LRB1 and the autophagy cargo receptor p62/SQSTM1. This process, here named 'traffic-induced degradation response for secretion' (TIDeRS) discloses a cellular mechanism by which nutrient and membrane sensing machineries cooperate to sustain Golgi-dependent protein secretion.

Comparación en los niveles de ansiedad en pacientes previo a la realización de terapia endodóntica y periodontal / Comparison of anxiety levels in patients prior to performing endodontic and periodontal treatment

La ansiedad que generan los tratamientos odontológicos generalmente perturba el comportamiento de los pacientes constituyéndose en una problemática que dificulta, retarda y muchas veces impide la realización de los procedimientos dentales. Este estudio tiene por objetivo comparar los niveles de ansiedad rasgo (estado emocional de base) y de ansiedad estado (situación emocional transitoria) a 80 pacientes (40 hombres y 40 mujeres) que asistieron a las clínicas de pregrado de la Universidad Mayor. Antes de realizar el tratamiento propiamente dicho de patologías endodónticas y periodontales asintomáticas se aplicó la encuesta inventario STAI a toda la muestra, que fue dividida en 2 grupos. Grupo A: 40 pacientes (20 hombres y 20 mujeres) que iban a ser sometidos a terapias endodónticas. Grupo B: 40 pacientes (20 hombres y 20 mujeres) que iban a ser sometidos a terapias periodontales. Resultados Los pacientes manifestaron diferencias significativas en la ansiedad rasgo (p < 0,2473) y ansiedad estado (p < 0,0329) cuando enfrentaron tratamientos periodontales versus endodónticos. Al comparar en hombres y mujeres la ansiedad rasgo/estado, se encontraron diferencias significativas (p < 0,05). Conclusiones Los pacientes manifiestan mayor ansiedad cuando tienen que enfrentar tratamientos periodontales. Las mujeres enfrentan ambos tratamientos dentales con mayor ansiedad que los hombres.

Anxiety generated by dental treatment usually affects the behaviour of patients, and this is a problem that can impede patients from seeking treatment, or complicate or delay dental procedures. The objective of this study is to compare the state anxiety (normal state of anxiety on the day to day basis) and trait anxiety (arousal of anxiety due to a particular situation) levels in 80 patients (40 women and 40 men) who sought treatment at the undergraduate clinic at the Universidad Mayor. Before being treated for asymptomatic endodontic and periodontal diseases the State-Trait Anxiety Inventory questionnaire was completed in group A: 40 endodontic patients, and group B: 40 periodontal patients (men and women were evenly distributed between groups). Results Patients showed significant differences in trait anxiety (P = .2473) and state anxiety (P = .0329) before periodontal treatments versus endodontic treatments. Significant differences were found in the Trait/State Anxiety significant differences (P = .05) when comparing men and women. Conclusions (i) Patients feel more anxiety when faced with periodontal treatments than when faced with endodontic treatments, and (ii) women feel more anxiety than men when faced with either dental treatment.

Diagnóstico fractal de disfunción cardéaca severa: Dinámica fractal de la ramificación coronaria izquierda / Fractal diagnosis of severe cardiac dysfunction: Fractal dynamic of the left coronary branching

INTRODUCCIÓN Y OBJETIVOS: la geometría fractal evalúa la irregularidad de los objetos naturales, permitiendo caracterizar de forma imparcial la totalidad de la ramificación coronaria izquierda a diferencia de la metodología actual que evalúa únicamente partes de ésta. Con base en esta medida se generalizó una nueva metodología diagnóstica para detectar cualquier tipo de disfunción cardiaca severa. MÉTODOS: estudio de concordancia diagnóstica en el que se utilizó el método de box counting para medir dimensiones fractales de imágenes consecutivas entre sístole y diástole de la ramificación coronaria izquierda en proyección oblicua derecha anterior de angiografías de ocho pacientes con enfermedad arterial oclusiva leve. Así mismo, se evaluaron sus cambios por medio de los conceptos de variabilidad y diferencia neta y se compararon estos resultados con pacientes sin enfermedad arterial oclusiva, con enfermedad arterial oclusiva moderada y severa evaluados previamente de igual forma, para obtener una metodología matemática que evalúa el impacto de cualquier patología en la dinámica cardiaca. RESULTADOS: los casos que presentan diferencias netas de cero corresponden a pacientes con disfunciones cardiacas severas, independientemente del grado o ausencia de enfermedad arterial oclusiva diagnosticada. CONCLUSIONES: se generalizó una nueva metodología diagnóstica de aplicación clínica que detecta disfunciones cardiacas severas sub-diagnosticadas con las metodologías actuales, mediante la caracterización de la dinámica total de la ramificación coronaria izquierda.

INTRODUCTION AND OBJETIVES: fractal geometry evaluates the irregularity of natural objects, allowing impartially characterize the entire left coronary branching unlike the current methodology which evaluates only parts of it. Based on this measure, a new diagnostic method was generalized to detect any type of severe cardiac dysfunction. METHODS: Concordance study using the box counting method to measure fractal dimensions of consecutive images between systole and diastole of the left coronary branch in right anterior oblique projection in angiograms of eight patients with mild arterial occlusive disease. Likewise, we evaluated its changes through the concepts of variability and net difference and compared these results with patients without occlusive arterial disease, with moderate to severe arterial occlusive disease previously and similarly evaluated, to obtain a mathematical methodology to assess the impact of any pathology in cardiac dynamics. RESULTS: The cases with zero net differences occur in patients with severe cardiac dysfunction, regardless of the degree or absence of diagnosed occlusive arterial disease. Conclusions: a new diagnostic methodology of clinical application to detect sub-diagnosed severe heart dysfunction was generalized with current methodologies, through the characterization of the total dynamics of the left coronary branch.