Physiological Mechanisms Regulating Lens Transport

The transparency and refractive properties of the lens are maintained by the cellular physiology provided by an internal microcirculation system that utilizes spatial differences in ion channels, transporters and gap junctions to establish standing electrochemical and hydrostatic pressure gradients that drive the transport of ions, water and nutrients through this avascular tissue. Aging has negative effects on lens transport, degrading ion and water homeostasis, and producing changes in lens water content. This alters the properties of the lens, causing changes in optical quality and accommodative amplitude that initially result in presbyopia in middle age and ultimately manifest as cataract in the elderly. Recent advances have highlighted that the lens hydrostatic pressure gradient responds to tension transmitted to the lens through the Zonules of Zinn through a mechanism utilizing mechanosensitive channels, multiple sodium transporters respond to changes in hydrostatic pressure to restore equilibrium, and that connexin hemichannels and diverse intracellular signaling cascades play a critical role in these responses. The mechanistic insight gained from these studies has advanced our understanding of lens transport and how it responds and adapts to different inputs both from within the lens, and from surrounding ocular structures.

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Differences between the Sexes in the Relationship between Chronic Pain, Fatigue, and QuickDASH among Community-Dwelling Elderly People in Japan

Healthcare ◽

10.3390/healthcare9060630 ◽

2021 ◽

Vol 9 (6) ◽

pp. 630

Author(s):

Satoshi Shimo ◽

Yuta Sakamoto ◽

Takashi Amari ◽

Masaaki Chino ◽

Rie Sakamoto ◽

...

Keyword(s):

Chronic Pain ◽

Elderly People ◽

Physical Disability ◽

The Elderly ◽

Daily Basis ◽

Community Dwelling ◽

Negative Effects ◽

The Relationship ◽

Elderly Healthcare ◽

Disability Research

Chronic pain and fatigue have negative effects on the health, ADL, work, and hobbies of the elderly. As the proportion of people 65 years of age and older in the population increases, chronic pain and disability research regarding this group is receiving more consideration. However, little empirical evidence of the association between chronic pain, fatigue, and physical disability between the sexes is available. This study investigated the association between chronic pain, fatigue, and instrumental activities of daily living among community-dwelling elderly people by sex in Japan. Concerning the presence of chronic pain, 61% of males and 78% of females reported chronic pain, indicating that many elderly people living in the community suffer from chronic pain and fatigue on a daily basis. The number of sites of chronic pain was higher in females than in males (p = 0.016), with more chronic pain in the knees (p < 0.001) and upper arms (p = 0.014). Regarding chronic pain, males showed a higher correlation with QuickDASH-DS (rs = 0.433, p = 0.017) and QuickDASH-SM (rs = 0.643, p = 0.018) than females. Furthermore, fatigue also showed a higher correlation with QuickDASH-W (rs = 0.531, p = 0.003) in males than in females. These results indicate that the association between chronic pain, fatigue, and QuickDASH differed between the sexes among community-dwelling elderly people in Japan. A better understanding of the risk factors for elderly chronic pain and fatigue among sexes will facilitate the development of elderly healthcare welfare and policies.

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d-Cystine di(m)ethyl ester reverses the deleterious effects of morphine on ventilation and arterial blood gas chemistry while promoting antinociception

Scientific Reports ◽

10.1038/s41598-021-89455-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Benjamin Gaston ◽

Santhosh M. Baby ◽

Walter J. May ◽

Alex P. Young ◽

Alan Grossfield ◽

...

Keyword(s):

Gas Exchange ◽

Intracellular Signaling ◽

Dimethyl Ester ◽

Diethyl Ester ◽

Blood Gas ◽

Negative Effects ◽

Arterial Blood Gas ◽

Arterial Blood ◽

Gas Chemistry ◽

Ventilatory Drive

AbstractWe have identified thiolesters that reverse the negative effects of opioids on breathing without compromising antinociception. Here we report the effects of d-cystine diethyl ester (d-cystine diEE) or d-cystine dimethyl ester (d-cystine diME) on morphine-induced changes in ventilation, arterial-blood gas chemistry, A-a gradient (index of gas-exchange in the lungs) and antinociception in freely moving rats. Injection of morphine (10 mg/kg, IV) elicited negative effects on breathing (e.g., depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive). Subsequent injection of d-cystine diEE (500 μmol/kg, IV) elicited an immediate and sustained reversal of these effects of morphine. Injection of morphine (10 mg/kg, IV) also elicited pronounced decreases in arterial blood pH, pO2 and sO2 accompanied by pronounced increases in pCO2 (all indicative of a decrease in ventilatory drive) and A-a gradient (mismatch in ventilation-perfusion in the lungs). These effects of morphine were reversed in an immediate and sustained fashion by d-cystine diME (500 μmol/kg, IV). Finally, the duration of morphine (5 and 10 mg/kg, IV) antinociception was augmented by d-cystine diEE. d-cystine diEE and d-cystine diME may be clinically useful agents that can effectively reverse the negative effects of morphine on breathing and gas-exchange in the lungs while promoting antinociception. Our study suggests that the d-cystine thiolesters are able to differentially modulate the intracellular signaling cascades that mediate morphine-induced ventilatory depression as opposed to those that mediate morphine-induced antinociception and sedation.

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The Inflammatory Role of Pro-Resolving Mediators in Endometriosis: An Integrative Review

International Journal of Molecular Sciences ◽

10.3390/ijms22094370 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4370

Author(s):

Cássia de Fáveri ◽

Paula M. Poeta Fermino ◽

Anna P. Piovezan ◽

Lia K. Volpato

Keyword(s):

Intracellular Signaling ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Critical Role ◽

Integrative Review ◽

Inflammatory Factors ◽

Resolvin D1 ◽

Endogenous Factors

The pathogenesis of endometriosis is still controversial, although it is known that the inflammatory immune response plays a critical role in this process. The resolution of inflammation is an active process where the activation of endogenous factors allows the host tissue to maintain homeostasis. The mechanisms by which pro-resolving mediators (PRM) act in endometriosis are still little explored. Thus, this integrative review aims to synthesize the available content regarding the role of PRM in endometriosis. Experimental and in vitro studies with Lipoxin A4 demonstrate a potential inhibitory effect on endometrial lesions’ progression, attenuating pro-inflammatory and angiogenic signals, inhibiting proliferative and invasive action suppressing intracellular signaling induced by cytokines and estradiol, mainly through the FPR2/ALX. Investigations with Resolvin D1 demonstrated the inhibition of endometrial lesions and decreased pro-inflammatory factors. Annexin A1 is expressed in the endometrium and is specifically present in women with endometriosis, although the available studies are still inconsistent. Thus, we believe there is a gap in knowledge regarding the PRM pathways in patients with endometriosis. It is important to note that these substances’ therapeutic potential is evident since the immune and abnormal inflammatory responses play an essential role in endometriosis development and progression.

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Signaling through mitogen-activated protein kinase and Rac/Rho does not duplicate the effects of activated Ras on skeletal myogenesis.

Molecular and Cellular Biology ◽

10.1128/mcb.17.7.3547 ◽

1997 ◽

Vol 17 (7) ◽

pp. 3547-3555 ◽

Cited By ~ 59

Author(s):

M B Ramocki ◽

S E Johnson ◽

M A White ◽

C L Ashendel ◽

S F Konieczny ◽

...

Keyword(s):

Map Kinase ◽

Signaling Pathways ◽

Transcriptional Activation ◽

Intracellular Signaling ◽

Mitogen Activated Protein Kinase ◽

Ras Signaling ◽

Negative Effects ◽

Intracellular Signaling Pathway ◽

Helix Loop Helix ◽

Mitogen Activated Protein

The ability of basic helix-loop-helix muscle regulatory factors (MRFs), such as MyoD, to convert nonmuscle cells to a myogenic lineage is regulated by numerous growth factor and oncoprotein signaling pathways. Previous studies have shown that H-Ras 12V inhibits differentiation to a skeletal muscle lineage by disrupting MRF function via a mechanism that is independent of the dimerization, DNA binding, and inherent transcriptional activation properties of the proteins. To investigate the intracellular signaling pathway(s) that mediates the inhibition of MRF-induced myogenesis by oncogenic Ras, we tested two transformation-defective H-Ras 12V effector domain variants for their ability to alter terminal differentiation. H-Ras 12V,35S retains the ability to activate the Raf/MEK/mitogen-activated protein (MAP) kinase cascade, whereas H-Ras 12V,40C is unable to interact directly with Raf-1 yet still influences other signaling intermediates, including Rac and Rho. Expression of each H-Ras 12V variant in C3H10T1/2 cells abrogates MyoD-induced activation of the complete myogenic program, suggesting that MAP kinase-dependent and -independent Ras signaling pathways individually block myogenesis in this model system. However, additional studies with constitutively activated Rac1 and RhoA proteins revealed no negative effects on MyoD-induced myogenesis. Similarly, treatment of Ras-inhibited myoblasts with the MEK1 inhibitor PD98059 revealed that elevated MAP kinase activity is not a significant contributor to the H-Ras 12V effect. These data suggest that an additional Ras pathway, distinct from the well-characterized MAP kinase and Rac/Rho pathways known to be important for the transforming function of activated Ras, is primarily responsible for the inhibition of myogenesis by H-Ras 12V.

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Identifying Human-Induced Spatial Differences of Soil Erosion Change in a Hilly Red Soil Region of Southern China

Sustainability ◽

10.3390/su11113103 ◽

2019 ◽

Vol 11 (11) ◽

pp. 3103

Author(s):

Dong Huang ◽

Xiaohuan Yang ◽

Hongyan Cai ◽

Zuolin Xiao ◽

Dongrui Han

Keyword(s):

Soil Erosion ◽

Human Impact ◽

Human Impacts ◽

Southern China ◽

Red Soil ◽

Jiangxi Province ◽

Negative Effects ◽

Gravity Center ◽

Local Conditions ◽

Spatial Differences

Soil erosion (SE) processes are closely related to natural conditions and human activities, posing a threat to environment and society. Identifying the human impact on regional SE changes is increasingly essential for pertinent SE management. Jiangxi province is studied here as a representative area of hilly-red-soil regions within southern China. The main objectives of this study were to investigate the changing trend of SE within Jiangxi and identify human impacts on regional SE change from the perspective of spatial differences, through a new approach based on a gravity-center model. Our results showed that SE status presented an overall amelioration from 1990 to 2015, while the average soil erosion modulus (SEM) declined from 864 to 281 Mg/(km2·a). Compared to the situation under human and natural impacts, human-induced spatial differences of SE change demonstrated that the western and northwest regions showed stronger negative effects; the southern region shifted towards negative effects; the northeast region presented a much weaker negative effect. Our results indicated that 4 cities with strong negative effects need more attention in further SE management suited to their local conditions and development, and also suggested that the approach based on a gravity-center has potential for identifying the human impact on regional SE change from the perspective of spatial patterns.

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The role of tourism awareness in developing accessible tourism

ARID International Journal of Social Sciences and Humanities ◽

10.36772/arid.aijssh.2020.s.2120 ◽

2020 ◽

pp. 437-463

Author(s):

طه مهدي محمود ◽

حسين محمد علي أسد

Keyword(s):

Young Children ◽

Pregnant Women ◽

Special Needs ◽

The Elderly ◽

Tourism Industry ◽

Negative Effects ◽

High Quality ◽

Tourism Sector ◽

Effective Contribution

Tourism awareness is one of the most important pillars that contribute to the development of the tourism industry in general, and the development of various tourism patterns in particular, and among those patterns are accessible tourism, because of its great importance in reducing the negative effects that may accompany the tourism industry by building educated tourism employees And be aware, knowledgeable and aware of the importance of the accomplishments and successes achieved by the tourism sector and the opportunities that this sector offers and economic opportunities that ultimately reflect on the members of society and the country. Perhaps the sensitivity of dealing with the categories of accessible tourism (those with special needs, the elderly, pregnant women, mothers for young children) need special type employees who possess a set of special skills and experiences in dealing with those groups to make the details of the tourist trip for the concerned individuals, the most important of which is accommodation (the hotel). And to achieve the best possibility to enjoy the tourist activity in general. This research aims to highlight on the role of tourism awareness for a sample of employees of the holy Karbala hotels and their effective contribution to achieve the development of soft tourism by providing high-quality services that reassure the targeted tourists and thus contribute to attract the largest number of them, which is greatly reflected in the development of tourism and making years Coming golden years for this tourist pattern, which is considered an ethical and human duty to care about and develop.

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Mechanisms and Dynamics in the Interplay of Trust and Distrust: Insights from Project-based Collaboration

Organization Studies ◽

10.1177/01708406211040215 ◽

2021 ◽

pp. 017084062110402

Author(s):

Angelos Kostis ◽

Maria Bengtsson ◽

Malin Harryson Näsholm

Keyword(s):

Critical Role ◽

Negative Effects ◽

Interorganizational Trust ◽

Complex Products ◽

Conceptual Distinction ◽

Interorganizational Projects ◽

Complex Solutions ◽

Behavioral Mechanisms ◽

Organizing Principles

Trust and distrust are two distinct organizing principles that play a critical role in interorganizational projects where highly interdependent organizations collaborate to build tailor-made and technologically-complex solutions. Whereas an emerging body of research has debated the conceptual distinction between trust and distrust, this paper emphasizes the processual nature of trusting and distrusting and the interplay between them. Drawing upon insights from project-based collaboration in a complex products and systems (CoPS) industry, we explore the distinct cognitive and behavioral mechanisms through which trust and distrust work, and orient firms towards optimism and watchfulness in the interaction. Our findings show that trust and distrust can act both as substitutes and complements through three interconnected dynamics—undermining, enabling and compensating. These dynamics develop and recursively interrelate through interfirm interactions within single projects and in the broader network. We conclude by presenting our contributions to interorganizational trust literature and by proposing that the interplay of trust and distrust can have both positive and negative effects on the pursuit of project-based relationships.

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Impacts of Emission Reduction Technological Changes on China’s City-Level PM2.5 Concentration Based on Sustainable Development

Mathematical Problems in Engineering ◽

10.1155/2021/4358661 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Jiandong Chen ◽

Yu Wei ◽

Ming Gao ◽

Shuo Huang

Keyword(s):

Emission Reduction ◽

Critical Role ◽

Technological Changes ◽

Index Method ◽

Econometric Methods ◽

Energy Technologies ◽

Spatial Differences ◽

Level Scale ◽

The Impact ◽

Pm2.5 Concentration

As an important field for human activities, cities play a critical role in PM2.5 reductions. Among the determinants for PM2.5 concentration, technological progress is considered to exhibit significant inhibitory effects. Although most extant research has focused on energy technologies or total factor productivity, due to limitations in data and methods, few scholars have focused on emission reduction technological changes at a city-level scale. Therefore, based on the combination of k-means clustering and the log-mean Divisia index method, this study estimates and explores the impact of PM2.5 emission reduction technology (PME) on the temporal changes and spatial differences of 262 Chinese cities’ PM2.5 concentration during 2003–2017. The findings show the following: (1) although the results based on econometric methods indicate that emission reduction technological changes decreased China’s city-level PM2.5 concentration, there were turning points in the yearly impacts, indicating that the improvements to emission reduction efficiency were not stable; (2) compared with PME, energy intensity played a more stable role in PM2.5 emissions reductions, implying that the improvement of energy efficiency was still very important in controlling PM2.5 concentrations; (3) based on the classified groups after clustering, most cities’ PME contributed to negative differences, but the PME of a small number of cities was very weak to largely lower the average level of their group; and (4) distributions of the spatial decomposition of the three classified groups were stable in the period of 2003–2017, implying that the catch-up and transcendence effects of PME within the group were limited. Thus, policymakers should focus on the impact of different policies on PME differences between cities.

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Recognizing Physical Activity of hospitalized Older People from Wearable Sensors Data using IoT

International Journal of Organizational and Collective Intelligence ◽

10.4018/ijoci.2022010104 ◽

2022 ◽

Vol 12 (1) ◽

pp. 0-0

Keyword(s):

Technical Assistance ◽

Performance Metrics ◽

Wearable Sensors ◽

Critical Role ◽

Elderly Person ◽

The Elderly ◽

Classification Algorithms ◽

Complex Task ◽

Almost All ◽

Different Sources

The IoT is a new concept that provides a world where smart, connected, embedded systems operate, giving rise to the amount of data from different sources that are considered to have highly useful and valuable information. Data mining would play a critical role in creating smarter IoT. Traditional care of an elderly person is a difficult and complex task. The need to have a caregiver with the elderly person almost all the time drains the human and financial resources of the health care system. The emergence of Artificial intelligence has allowed the conception of technical assistance where it helps and reduces the time spent by the caregiver with the elderly person. This work aims to focus on analyzing techniques that are used for prediction purposes of falls in the elderly. We examine the applicability of three classification algorithms for IoT data. These algorithms are analyzed and a comparative study is undertaken to find the classifier that performs the best analysis on the dataset using a set of predefined performance metrics to compare the results of each classifier.

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Abstract 17319: Distinct Effects of Human Calmodulinopathy on the Function of Small Conductance Ca 2+ -Activated K + (SK) Channels

Circulation ◽

10.1161/circ.138.suppl_1.17319 ◽

2018 ◽

Vol 138 (Suppl_1) ◽

Author(s):

Hannah A Ledford ◽

Seojin Park ◽

Duncan Muir ◽

Wen Smith ◽

Ryan L Woltz ◽

...

Keyword(s):

Ion Channels ◽

Intracellular Signaling ◽

Critical Role ◽

Dominant Negative ◽

Polymorphic Ventricular Tachycardia ◽

Dominant Negative Effect ◽

Sk Channels ◽

Channel Function ◽

Sk Channel ◽

Small Conductance

Background: Calmodulin (CaM) plays a critical role in intracellular signaling and regulation of Ca 2+ -dependent ion channels. Mutations in CALM1, CALM2, and CALM3 have recently been linked to cardiac arrhythmias, such as Long QT Syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and familial idiopathic ventricular fibrillation (IVF). Small-conductance Ca 2+ - activated K + channels (SK) are voltage-independent channels that are regulated solely from beat-to-beat changes in intracellular calcium. CaM regulates the function of multiple ion channels, including SK channels, although the effect of CaM mutations on these channels is not yet understood. We hypothesize that human CaM mutations linked to sudden cardiac death disrupt SK channel function by distinct mechanisms. Methods and Results: We tested the effects of LQTS (CaM D96V , CaM D130G ), CPVT (CaM N54I , CaM N98S ), and IVF (CaM F90L ) CaM mutants compared to CaM WT on SK channel function. Using whole-cell voltage-clamp recordings, we found that CaM D96V and CaM D130G mutants significantly inhibited apamin-sensitive currents. Similarly, action potential studies in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) also revealed significant knockdown of apamin-sensitive currents. Immunofluorescent confocal microscopy confirmed that this effect was not due to changes in SK channel trafficking. Rather, co-immunoprecipitation studies showed a significant decrease in the association of these CaM mutants with the SK channel. Rosetta molecular modeling was used to identify a conformational change in CaM F90L structure compared to that of CaM WT . Conclusions: We found that CaM D96V and CaM D130G mutants significantly reduced apamin-sensitive currents, through a dominant negative effect on SK channel function. Consistent with our hypothesis, CaM F90L resulted in the least inhibitory effects. The data suggests that specific mutations with phenylalanine to leucine (CaM F90L ) may disrupt the interaction between apo-CaM with CaMBD on the SK2 channel.

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