USP10 inhibits aberrant cytoplasmic aggregation of TDP-43 by promoting stress granule clearance

TDP-43 is a causative factor of amyotrophic lateral sclerosis (ALS). Cytoplasmic TDP-43 aggregates in neurons are a hallmark pathology of ALS. Under various stress conditions, TDP-43 localizes sequentially to two cytoplasmic protein aggregates: stress granules (SGs) first, and then aggresomes. Accumulating evidence suggests that delayed clearance of TDP-43-positive SGs is associated with pathological TDP-43 aggregates in ALS. We found that USP10 promotes the clearance of TDP-43-positive SGs in cells treated with proteasome inhibitor, thereby promoting the formation of TDP-43-positive aggresomes, and the depletion of USP10 increases the amount of insoluble TDP-35, a cleaved product of TDP-43, in the cytoplasm. TDP-35 interacted with USP10 in an RNA-binding dependent manner; however, impaired RNA-binding of TDP-35 reduced the localization in SGs and aggresomes and induced USP10-negative TDP-35 aggregates. Immunohistochemistry showed that most of the cytoplasmic TDP-43/TDP-35-aggregates in the neurons of ALS patients were USP10-negative. Our findings suggest that USP10 inhibits aberrant aggregation of TDP-43/TDP-35 in the cytoplasm of neuronal cells by promoting the clearance of TDP-43/TDP-35-positive SGs and facilitating the formation of TDP-43/TDP-35-positive aggresomes.

Vitreomacular Interface Abnormalities in Myopic Foveoschisis: Correlation With Morphological Features and Outcome of Vitrectomy

Purpose: To compare the morphologic characteristics and response to surgery of myopic foveoschisis (MF) with different patterns of vitreomacular interface abnormalities (VMIAs).Methods: In this observational case series, 158 eyes of 121 MF patients with epiretinal membrane (ERM) or vitreomacular traction (VMT) based on optical coherence tomography (OCT) were enrolled. All the eyes were divided into two groups by the pattern of VMIAs: ERM and VMT group. Sixty-one eyes underwent pars plana vitrectomy (PPV) and were followed up for at least 6 months. The morphologic characteristics based on OCT and the surgical outcome were evaluated.Outcome: ERM and VMT were found in 47.47 and 52.53% of the cases, respectively. A higher rate of foveal detachment (61.4 vs. 26.7%; p < 0.001) and a higher rate of outer lamellar macular hole (45.8 vs. 21.3%; p = 0.001) were detected in the eyes with VMT compared with those with ERM. In contrast, a lower rate of inner lamellar macular hole (28.9 vs. 60.0%; p = 0.001) was detected in the eyes with VMT compared with those with ERM. The disruption of the external limiting membrane (ELM) was more common in the eyes with VMT than in those with ERM (45.8 vs. 21.3%; p = 0.001). PPV was performed in 61 eyes with a mean follow-up time of 23.55 ± 19.92 months. After surgery, anatomical resolution was achieved in 51 eyes (83.6%). At the final visit, the mean central foveal thickness (CFT) decreased significantly from 547.83 to 118.74 μm, and the mean LogMAR BCVA improved significantly from 0.92 to 0.57. The VMT group was associated with a higher proportion of eyes with visual acuity improvement postoperatively (p = 0.02) and had more a decrease of CFT (P = 0.007) compared with the ERM group.Conclusion: In the eyes with MF, outer retinal lesions occurred more frequently in the eyes with VMT, whereas inner retinal lesions occurred more frequently in the eyes with ERM. Tangential force generated by ERM may act as a causative factor for the inner retinal lesions in MF, and inward-directed force resulting from VMT may act as a causative factor for outer retinal lesions in MF.

The Impact of Oxidative Stress in Male Infertility

At present infertility is affecting about 15% of couples and male factor is responsible for almost 50% of infertility cases. Oxidative stress, due to enhanced Reactive Oxygen Species (ROS) production and/or decreased antioxidants, has been repeatedly suggested as a new emerging causative factor of this condition. However, the central roles exerted by ROS in sperm physiology cannot be neglected. On these bases, the present review is focused on illustrating both the role of ROS in male infertility and their main sources of production. Oxidative stress assessment, the clinical use of redox biomarkers and the treatment of oxidative stress-related male infertility are also discussed.

Excess consumption of Lavana Rasa (Salty taste) – A cause of Amlapitta (Hyperacidity)

Amlapitta (Hyperacidity) is one of the ever growing diseases observed in society. Intake of salt in excess can lead into Amlapitta due to its Vidahi and Agneya property. Foods like cheese, chips, sauces, buttermilk, etc. contains variety of salts including common salt. The disease Amlapitta/ Amlika can be interpreted as Hyperacidity; is not separately described in Samhita, but mentioned as Lakshana (symptom) of Atiyoga (excessive intake) of Lavana Rasa. Hence an observational study was designed. Aim: To examine whether Atiyoga of Lavana Rasa (common salt) can be a Hetu (causative factor) of Amlapitta. Methodology: Study included 100 identified patients of Amlapitta; both males and females from the age group of 20-60 years suffering from Amlodgar (sour blenching) as the predominant symptom. A structured, pilot tested 6 item questionnaire was used to collect data. Statistical Analysis: Descriptive data was analyzed using number and percentage. Results: Maximum patients were from 20-29 years age group; with Kapha-Pittaja Prakruti (77.78 %) and Pitta-Kaphaja Prakruti (68.75%) who used to consume Lavana rasa in variety of type and in excess quantity. Family history of the disease Amlapitta showed maximum % in female patients as 31.03% whereas only 4.76% males suffered from the disease. Liking towards Lavana, Katu and Amla rasa in population was found to be 36%, 28%, 16% respectively. In causative factors of Amlapitta, Lavana Rasadhikya was noted in 62 patients whereas Vidahi Anna followed by spicy food and oily food was found in 60, 58, 56 number of patients respectively. Conclusion: From the study, it is observed that there is proneness of Amlapitta mostly in age group 20-29 years having liking towards salty, spicy and Katu Rasa. Maximum (58) female patients, with 31.03% who had family history of Amlapitta and 77.78% patients found to have Kapha-Pitta dominent Prakruti which indicate towards importance of Prakriti and family history of an individual in disease manifestation.

Analisa Strategi E-Marketing Dinas Koperasi UKM Kota Medan terhadap UKM Binaan di Tengah Pandemi Covid-19 Tahun 2020

The objectives of this study are to: 1) Analyze and explain the effectiveness of internet-based online marketing strategies for SME products, 2) Analyze and explain the implementation of internet-based online marketing strategies for SME products, 3) Analyze and describe the supporting factors for the success of internet-based online marketing strategies for SME products, and 4) Analyze and describe the factors inhibiting the success of the internet-based online marketing strategy for SME products. The results showed that the effectiveness of the internet-based online marketing strategy of the SME products assisted by the Medan City Cooperative Office was still not optimal. The causative factor for this is due to the limited promotional budget owned by the Medan City UKM Cooperative Office in 2020 as well as the refocusing policy. The implementation of an internet-based online marketing strategy for SME products guided by the Medan City UKM Cooperative Office in 2020 in the midst of the Covid-19 pandemic was implemented and complied with the principles of coordination, the idea of cooperation through BRI banks to open easy access to credit, cooperation with online businesses to build digital market place with Grabfood, providing a market place at Bukalapak. Barriers to training distance and high interest in participating in training were seen to be quite dominant.

ROLE OF RASA DHATU IN THE MAINTENANCE OF BODY

Ayurveda emphasizes on maintenance of health in a healthy individual and treating the diseased ones. The human body comprises Tridosha, Saptadhatu, Trimala (structural and functional entities of the body). Sharira (body) is a mula for health as well as disease. Srotas (body channels) are those channels that transport and transform the sub- stances to respective tissues, cells of the human body required for life sustenance. As the Dhatu’s are classified as Sthayi and Asthayi dhatu, based on the Aahara (food) consumed the respective Dosha Utpatti (biotransformation) takes place leading to Saara Kitta Vibhajana (formation of metabolic nutrients and waste). Rasa dhatu is an Asthayi Dhatu which is predominant of Jala Mahabhuta. From the Aahara Rasa, Rasa Dhatu is formed which is the prime Dhatu resulting in the development of subsequent dhatus of the sharira. Rasa Saara Purusha is en- dowed with Aayushmanta (longer life span) and Aarogya (health). As Rasadhatu Dusti Janya Vikaras are abun- dant in our clinics, understanding of Rasavaha Srotodusti Nidana (causative factor) and Lakshana (signs and symptoms) in a patient with a relevant examination by means of Trividha Pariksha and prescribing appropriate Chikitsa (treatment) by understanding Guna -Karma principle is the need of the hour. Keywords: Rasavaha Srotas (lymph channels), Pariksha (examination), Chikitsa (treatment)

Mitochondrial Oxidative Stress—A Causative Factor and Therapeutic Target in Many Diseases

The excessive formation of reactive oxygen species (ROS) and impairment of defensive antioxidant systems leads to a condition known as oxidative stress. The main source of free radicals responsible for oxidative stress is mitochondrial respiration. The deleterious effects of ROS on cellular biomolecules, including DNA, is a well-known phenomenon that can disrupt mitochondrial function and contribute to cellular damage and death, and the subsequent development of various disease processes. In this review, we summarize the most important findings that implicated mitochondrial oxidative stress in a wide variety of pathologies from Alzheimer disease (AD) to autoimmune type 1 diabetes. This review also discusses attempts to affect oxidative stress as a therapeutic avenue.

The Analysis of Code Mixing Among Luwuk Socities’ Conversation in the Mids of Covid-19 Pandemic

The aim of this research is focused on the code-mixing used in the mids of covid-19 pandemic by luwuk societies’ conversation. The purposes of this research were investigated the kinds of code-mixing, the dominant kind of code-mixing, and the factors of code-mixing. This research used descriptive qualitative approach as the research method. Observation and interview were chosen as the collecting data technique. This research result showed that there were three kinds of code-mixing namely intra-sentential code-mixing, intra-lexical code-mixing and involving change pronunciation. The dominant kind is intra-sentential code-mixing. Moreover, there were attitudinal factors and linguistic factors as the causative factor. Attitudinal factors which is included of new culture introduction and social value. Linguistic factors included of popular term, code limited, speaker personal, conversation topic, conversation purpose, humor sense, and listener. The implication of this research was researchers’ and language observers’ contribution about the development of language variety among the societies of Luwuk City, Banggai Regency.

Geochemistry of Groundwater in the Uva Province, Sri Lanka—Implications for Chronic Kidney Disease of Uncertain Origin

The prevalence of chronic kidney disease of uncertain etiology (CKDu) in the Uva Province (UP) of Sri Lanka has received much attention over the past two decades. Many scientists assumed that prolonged consumption of drinking water with high levels of contaminants may be the causative factor. Thus, the prime objective of this study is to develop a binary logistic regression model based on water quality parameters and the prevalence of CKDu to find out the geochemical risk factors that affect the CKDu. For this, 260 groundwater samples were collected following a stratified random sampling method and analyzed for its major cations, anions, and selected trace element contents. In the model, the dichotomous dependent variable defines the availability of CKDu patients, and explanatory variables define groundwater quality parameters. According to the best-fit model, F− and PO43- levels of the groundwater were found to be the geochemical risk factors that were significantly associated with the progression of CKDu in the study area. Furthermore, it was shown that geochemical processes such as dissolution of bedrocks are the causative phenomenon of the enhancement of F− levels in the groundwater sources. It has also been observed that the PO43- concentrations of the groundwater possibly increase because of the intensive application of agrochemicals in addition to geogenic sources. The results of this study can be used by the government authorities in groundwater management and the management of the prevalence of CKDu disease in the study area. Furthermore, the findings of this study will contribute to the policy-makers in Sri Lanka for providing safe drinking water to meet the sustainable development goals (SDGs).

Mitochondrial Dysfunction as a Causative Factor in Alzheimer’s Disease-Spectrum Disorders: Lymphocytes as a Window to the Brain

: Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. Today, AD affects millions of people worldwide and the number of AD cases will further increase with longer life expectancy. The AD brain is marked by severe neurodegeneration, such as the loss of synapses and neurons, atrophy and depletion of neurotransmitter systems, especially in the hip- pocampus and cerebral cortex. Recent findings highlight the important role of mitochondrial dys- function and increased oxidative stress in the pathophysiology of late-onset Alzheimer’s disease (LOAD). These alterations are not only observed in the brain of AD patients but also in the periph- ery. In this review, we discuss the potential role of elevated apoptosis, increased oxidative stress and mitochondrial dysfunction as peripheral markers for the detection of AD in blood cells e.g. lymphocytes. We evaluate recent findings regarding impaired mitochondrial function comprising mitochondrial respiration, reduced complex activities of the respiratory chain and altered Mitochon- drial Membrane Potential (MMP) in lymphocytes as well as in neurons. Finally, we will question whether these mitochondrial parameters might be suitable as an early peripheral marker for the de- tection of LOAD but also for the transitional stage between normal aging and Dementia, “Mild Cognitive Impairment” (MCI).