The first step of the base excision repair (BER) pathway responsible for removing oxidative DNA damage utilizes DNA glycosylases to find and remove the damaged DNA base. How glycosylases find the ...damaged base amidst a sea of undamaged bases has long been a question in the BER field. Single molecule total internal reflection fluorescence microscopy (SM TIRFM) experiments have allowed for an exciting look into this search mechanism and have found that DNA glycosylases scan along the DNA backbone in a bidirectional and random fashion. By comparing the search behavior of bacterial glycosylases from different structural families and with varying substrate specificities, it was found that glycosylases search for damage by periodically inserting a wedge residue into the DNA stack as they redundantly search tracks of DNA that are 450–600bp in length. These studies open up a wealth of possibilities for further study in real time of the interactions of DNA glycosylases and other BER enzymes with various DNA substrates.
Display omitted
•DNA glycosylases bidirectionally, randomly and rotationally diffuse along DNA.•DNA glycosylases insert a wedge amino acid into the DNA duplex to locate damages.•DNA glycosylases stop upon encountering their substrate damage.•TIRF microscopy has provided insights into the DNA damage search by DNA glycosylases.
Epidemiology of Parkinson Disease Lee, Andrea; Gilbert, Rebecca M
Neurologic clinics,
11/2016, Letnik:
34, Številka:
4
Journal Article
Recenzirano
Parkinson disease (PD) is a common progressive neurodegenerative condition, causing both motor and non motor symptoms. Motor symptoms include stiffness, slowness, rest tremor and poor postural ...reflexes, whereas nonmotor symptoms include abnormalities of mood, cognition, sleep and autonomic function. Affected patients show cell loss in the substantia nigra pars compacta, and accumulation of aggregated alpha-synuclein into intracellular structures called Lewy bodies, within specific brain regions. The main known non modifiable risk factor is age. The neuroepidemiology of PD is complex with susceptibility genes and a number of modifiable risk factors that can increase and others that can mitigate risk and outcome.
Sex Differences in Atrial Fibrillation Andrade, Jason G.; Deyell, Marc W.; Lee, Andrea Y.K. ...
Canadian journal of cardiology,
April 2018, 2018-04-00, 20180401, Letnik:
34, Številka:
4
Journal Article
Recenzirano
Atrial fibrillation (AF) is a chronic progressive disease characterized by exacerbations and remissions. It remains the most common sustained arrhythmia seen in clinical practice, and represents a ...major burden to health care systems. Similar to other cardiovascular conditions, significant sex-specific differences have been observed in the epidemiology (lower rate of prevalence in women, women present at a later age), pathophysiology (sex-related differences in AF triggers and substrate), clinical presentation (women are more likely symptomatic, with relatively more severe symptoms), and natural history. Moreover, similar to other cardiovascular conditions there are substantial sex-specific differences in the management of AF, with women being significantly less likely to receive therapeutic anticoagulation, attempts at rhythm control, or undergo invasive cardiovascular procedures. The purpose of this review is to explore these sex-specific differences.
La fibrillation auriculaire (FA) est une maladie chronique évolutive qui est caractérisée par des périodes d’exacerbation et de rémission. Elle demeure l’arythmie soutenue la plus fréquemment observée dans la pratique clinique et constitue un fardeau considérable pour les systèmes de soins de santé. Au même titre que les autres maladies cardiovasculaires, on a observé des différences importantes entre les sexes en ce qui concerne l’épidémiologie (taux de prévalence plus faibles chez les femmes, et à un âge plus avancé), la physiopathologie (différences entre les sexes pour ce qui est des facteurs déclenchants et du substrat de la FA), le tableau clinique (les femmes sont plus susceptibles de présenter des symptômes, voire des symptômes plus graves) et l’évolution naturelle de la maladie. En outre, comme dans les autres maladies cardiovasculaires, les femmes montrent des différences substantielles dans la prise en charge de la FA, puisqu’elles sont beaucoup moins susceptibles de recevoir une anticoagulation thérapeutique, de tenter un traitement régulateur du rythme ou de subir des interventions invasives de chirurgie cardiovasculaire. L’objectif de cette revue est d’examiner ces différences entre les sexes.
Rodent tendons are widely used to study human pathologies such as tendinopathy and repair, and to address fundamental physiological questions about development, growth, and remodeling. However, how ...the gross morphology and multi‐scale hierarchical structure of rat tendons, such as the tail, plantaris, and Achilles tendons, compare with that of human tendons are unknown. In addition, there remains disagreement about terminology and definitions. Specifically, the definitions of fascicle and fiber are often dependent on diameter sizes, not their characteristic features, and these definitions impair the ability to compare hierarchical structure across species, where the sizes of the fiber and fascicle may change with animal size and tendon function. Thus, the objective of the study was to select a single species that is commonly used for tendon research (rat) and tendons with varying mechanical functions (tail, plantaris, Achilles) to evaluate the hierarchical structure at multiple length scales using histology, SEM, and confocal imaging. With the exception of the specialized rat tail tendon, we confirmed that in rat tendons there are no fascicles and the fiber is the largest subunit. In addition, we provided a structurally based definition of a fiber as a bundle of collagen fibrils that is surrounded by elongated cells, and this definition was supported by both histologically processed and unprocessed samples. In all rat tendons studied, the fiber diameters were consistently between 10 and 50 μm, and this diameter range appears to be conserved across larger species. Specific recommendations were made highlighting the strengths and limitations of each rat tendon as a research model. Understanding the hierarchical structure of tendon can advance the design and interpretation of experiments and development of tissue‐engineered constructs.
The current study examined the association of COVID-19 contraction worry for self and for family members with COVID-19 peritraumatic distress and loneliness in Chinese residents in North America. A ...sample of 943 Chinese residents (immigrants, citizens, visitors, and international students) in North America completed a cross-sectional online survey during the second wave of the COVID-19 pandemic (between January and February 2021). Univariate analysis of variance (ANOVA) models identified possible sociodemographic variables that were included in the subsequent hierarchical regression models. According to the hierarchical regression models, self-contraction worry was significantly associated with both COVID-19 peritraumatic distress (B = −4.340, p < 0.001) and loneliness (B = −0.771, p = 0.006) after controlling for related sociodemographic covariates; however, family-contraction worry was not significantly associated with the outcome variables. Additionally, poorer health status and experienced discrimination significantly predicted higher COVID-19 peritraumatic distress, whereas poorer health status and perceived discrimination significantly predicted increased loneliness. The results highlighted the detrimental impacts of self-contraction worry on peritraumatic distress and loneliness during the COVID-19 pandemic in Chinese residents in North America.
It is common in biomechanics to use previously frozen tissues, where it is assumed that the freeze–thaw process does not cause consequential mechanical or structural changes. We have recently ...quantified multiscale tendon mechanics and damage mechanisms using previously frozen tissue, where damage was defined as an irreversible change in the microstructure that alters the macroscopic mechanical parameters. Because freezing has been shown to alter tendon microstructures, the objective of this study was to determine if freezing alters tendon multiscale mechanics and damage mechanisms. Multiscale testing using a protocol that was designed to evaluate tendon damage (tensile stress–relaxation followed by unloaded recovery) was performed on fresh and previously frozen rat tail tendon fascicles. At both the fascicle and fibril levels, there was no difference between the fresh and frozen groups for any of the parameters, suggesting that there is no effect of freezing on tendon mechanics. After unloading, the microscale fibril strain fully recovered, and interfibrillar sliding only partially recovered, suggesting that the tendon damage is localized to the interfibrillar structures and that mechanisms of damage are the same in both fresh and previously frozen tendons.
The human fetal immune system begins to develop early during gestation; however, factors responsible for fetal immune-priming remain elusive. We explored potential exposure to microbial agents in ...utero and their contribution toward activation of memory T cells in fetal tissues. We profiled microbes across fetal organs using 16S rRNA gene sequencing and detected low but consistent microbial signal in fetal gut, skin, placenta, and lungs in the 2nd trimester of gestation. We identified several live bacterial strains including Staphylococcus and Lactobacillus in fetal tissues, which induced in vitro activation of memory T cells in fetal mesenteric lymph node, supporting the role of microbial exposure in fetal immune-priming. Finally, using SEM and RNA-ISH, we visualized discrete localization of bacteria-like structures and eubacterial-RNA within 14th weeks fetal gut lumen. These findings indicate selective presence of live microbes in fetal organs during the 2nd trimester of gestation and have broader implications toward the establishment of immune competency and priming before birth.
Display omitted
•Human fetuses in 2nd trimester show T cell diversity with effector-memory phenotype•Fetal organs show diverse bacterial genera that can be cultured and propagated•Bacterial structures with mucin-like threads are visualized in 14-weeks EGA fetal gut•Fetal bacteria induce syngeneic memory T cell activation in fetal mLN T cells
Analysis of human fetal tissues and the placenta in the 2nd trimester of gestation identifies live bacterial strains that are able to induce the activation of memory T cells in the fetal mesenteric lymph node, thus providing insights into early life immunity.
PURPOSE OF REVIEWThere has been a resurgent interest in frequent premature ventricular contractions (PVCs) led by the novel concept that they may be a potential cause of, or at least contribute to, ...cardiomyopathy. This review evaluates recent advances in our understanding of PVC-induced cardiomyopathy.
RECENT FINDINGSRecent studies have focused on identifying the predictors of PVC-induced cardiomyopathy, with the most consistent predictors being PVC burden and PVC QRS duration. Multiple studies have investigated the effect of catheter ablation on PVC burden and resultant left ventricular function, with the efficacy of catheter ablation and the overall PVC response rates varying between 60 and 88%. After successful ablation, the rates of improvement in left ventricular ejection fraction have varied between 47 and 100%. A recent study raises the question that perhaps even a lower PVC burden could result in PVC cardiomyopathy and adverse outcomes.
SUMMARYThere is an increasing body of literature supporting a causal role of frequent PVCs in the development of left ventricular dysfunction. Effective therapy for PVCs exists; however, the optimal indications for therapy have yet to be determined.
As a result of the COVID-19 pandemic, many educators had to transition from face to face to online classes. Zoom has become a popular platform for live, online classes in different educational ...contexts including English language learning. This phenomenological study sought to gain insight into South Korean students’ satisfaction with Zoom breakout rooms in English communication classes. Participants included 25 undergraduate students attending English communication classes at a university in central South Korea. Data collection comprised an open-ended survey, a focus group, and individual interviews. Data analysis centered on examining significant statements and developing themes. The results of this study indicate that most students were satisfied with using Zoom breakout rooms for EFL classes. Further, students expanded on various benefits of using Zoom breakout rooms and provided recommendations for improvement. This paper concludes with practical implications and suggestions for future research pertaining to the use of Zoom breakout rooms in EFL classes. KCI Citation Count: 5
PDF
