A temperate labrid fish demonstrates compensatory mechanisms to feed at torpor‐inducing temperatures

In the anatomy of a normal spine, due to the curvatures in various regions, the C7 plumb line (C7PL) passes through the sacrum so that the head is centered over the pelvic-ball and socket hip and ankle joints. A failure to recognize malalignment in the sagittal plane can affect the patient's activity as well as social interaction due to deficient forward gaze. The sagittal balance configuration leads to the body undertaking the least muscular activities as possible necessary to maintain spinal balance. Global sagittal imbalance is energy consuming and often results in painful compensatory mechanisms that in turn negatively influence the patient's quality of life, self-image, and social interaction due to inability to maintain a horizontal gaze. Deformity, scoliosis, kyphosis, trauma, and/or surgery are some ways that this optimal configuration can be disturbed, thus requiring higher muscular activity to maintain posture and balance. Several parameters such as the thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), and hip and leg positions influence the sagittal balance and thus the optimal configuration of spinal alignment. This review examines the clinical and biomechanical aspects of spinal imbalance, and the biomechanics of spinal balance as dictated by deformities—ankylosing spondylitis (AS), scoliosis and kyphosis; surgical corrections—pedicle subtraction osteotomies (PSO), long segment stabilizations, and consequent postural complications like proximal and distal junctional kyphosis. The study of the biomechanics involved in spinal imbalance is relatively new and thus the literature is rather sparse. This review suggests several potential research topics in the area of spinal biomechanics.

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Compensatory mechanisms in resistant Anopheles gambiae AcerKis and KdrKis neurons modulate insecticide-based mosquito control

Communications Biology ◽

10.1038/s42003-021-02192-0 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Stéphane Perrier ◽

Eléonore Moreau ◽

Caroline Deshayes ◽

Marine El-Adouzi ◽

Delphine Goven ◽

...

Keyword(s):

Sodium Channel ◽

Anopheles Gambiae ◽

Calcium Concentration ◽

Mosquito Control ◽

Point Mutations ◽

Resting Membrane Potential ◽

Compensatory Mechanisms ◽

Pyrethroid Insecticides

AbstractIn the malaria vector Anopheles gambiae, two point mutations in the acetylcholinesterase (ace-1R) and the sodium channel (kdrR) genes confer resistance to organophosphate/carbamate and pyrethroid insecticides, respectively. The mechanisms of compensation that recover the functional alterations associated with these mutations and their role in the modulation of insecticide efficacy are unknown. Using multidisciplinary approaches adapted to neurons isolated from resistant Anopheles gambiae AcerKis and KdrKis strains together with larval bioassays, we demonstrate that nAChRs, and the intracellular calcium concentration represent the key components of an adaptation strategy ensuring neuronal functions maintenance. In AcerKis neurons, the increased effect of acetylcholine related to the reduced acetylcholinesterase activity is compensated by expressing higher density of nAChRs permeable to calcium. In KdrKis neurons, changes in the biophysical properties of the L1014F mutant sodium channel, leading to enhance overlap between activation and inactivation relationships, diminish the resting membrane potential and reduce the fraction of calcium channels available involved in acetylcholine release. Together with the lower intracellular basal calcium concentration observed, these factors increase nAChRs sensitivity to maintain the effect of low concentration of acetylcholine. These results explain the opposite effects of the insecticide clothianidin observed in AcerKis and KdrKis neurons in vitro and in vivo.

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Sex-Dependent End-of-Life Mental and Vascular Scenarios for Compensatory Mechanisms in Mice with Normal and AD-Neurodegenerative Aging

Biomedicines ◽

10.3390/biomedicines9020111 ◽

2021 ◽

Vol 9 (2) ◽

pp. 111

Author(s):

Aida Muntsant ◽

Francesc Jiménez-Altayó ◽

Lidia Puertas-Umbert ◽

Elena Jiménez-Xarrie ◽

Elisabet Vila ◽

...

Keyword(s):

Life Expectancy ◽

End Of Life ◽

Mortality Rates ◽

Disability Adjusted Life Years ◽

Pharmacological Interventions ◽

Compensatory Mechanisms ◽

Healthy Life ◽

Disability Adjusted Life ◽

Life Years ◽

Bidirectional Interactions

Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative disorders strongly contributing to the total disability-adjusted life years. Interestingly, the morbidity/mortality paradox points to females having a worse healthy life expectancy. Since bidirectional interactions between cardiovascular and Alzheimer’s diseases (AD) have been reported, the study of this emerging field is promising. In the present work, we further explored the cardiovascular–brain interactions in mice survivors of two cohorts of non-transgenic and 3xTg-AD mice, including both sexes, to investigate the frailty/survival through their life span. Survival, monitored from birth, showed exceptionally worse mortality rates in females than males, independently of the genotype. This mortality selection provided a “survivors” cohort that could unveil brain–cardiovascular interaction mechanisms relevant for normal and neurodegenerative aging processes restricted to long-lived animals. The results show sex-dependent distinct physical (worse in 3xTg-AD males), neuropsychiatric-like and cognitive phenotypes (worse in 3xTg-AD females), and hypothalamic–pituitary–adrenal (HPA) axis activation (higher in females), with higher cerebral blood flow and improved cardiovascular phenotype in 3xTg-AD female mice survivors. The present study provides an experimental scenario to study the suggested potential compensatory hemodynamic mechanisms in end-of-life dementia, which is sex-dependent and can be a target for pharmacological and non-pharmacological interventions.

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Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction

Scientific Reports ◽

10.1038/s41598-021-91416-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aaron J. Velasquez-Mao ◽

Mark A. Velasquez ◽

Zhengxiong Hui ◽

Denise Armas-Ayon ◽

Jingshen Wang ◽

...

Keyword(s):

Blood Flow Rate ◽

Mode Switching ◽

Platelet Dysfunction ◽

Compensatory Mechanisms ◽

Before And After ◽

Basal Plasma ◽

Stage Renal Disease ◽

End Stage ◽

Plasma Factors ◽

Esrd Patients

AbstractMulti-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets from ESRD patients before and after HD to examine HD-modulation of platelets beyond thrombotic activation. Basal plasma levels of proteolytic regulators and fibrotic factors were elevated in ESRD patients compared to healthy controls, with isoform-specific changes during HD. Platelet lysate (PL) RNA transcripts for growth and coagulative factors were elevated post-HD, with upregulation correlated to HD vintage. Platelet secretome correlations to plasma factors reveal acutely induced pro-fibrotic platelet phenotypes in ESRD patients during HD characterized by preferentially enhanced proteolytic enzyme translation and secretion, platelet contribution to inflammatory response, and increasing platelet dysfunction with blood flow rate (BFR) and Vintage. Compensatory mechanisms of increased platelet growth factor synthesis with acute plasma matrix metalloproteinase (MMP) and tissue inhibitor of MMPs (TIMP) increases show short-term mode-switching between dialysis sessions leading to long-term pro-fibrotic bias. Chronic pro-fibrotic adaptation of platelet synthesis were observed through changes in differential secretory kinetics of heterogenous granule subtypes. We conclude that chronic and acute platelet responses to HD contribute to a pro-fibrotic milieu in ESRD.

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Integrated multi-omics analysis of RB-loss identifies widespread cellular programming and synthetic weaknesses

Communications Biology ◽

10.1038/s42003-021-02495-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Swetha Rajasekaran ◽

Jalal Siddiqui ◽

Jessica Rakijas ◽

Brandon Nicolay ◽

Chenyu Lin ◽

...

Keyword(s):

Metabolic Pathways ◽

Human Cells ◽

Cellular Reprogramming ◽

Hallmarks Of Cancer ◽

Compensatory Mechanisms ◽

Response Factors ◽

Cancer Data ◽

Cell Stress Response ◽

Metabolic Output

AbstractInactivation of RB is one of the hallmarks of cancer, however gaps remain in our understanding of how RB-loss changes human cells. Here we show that pRB-depletion results in cellular reprogramming, we quantitatively measured how RB-depletion altered the transcriptional, proteomic and metabolic output of non-tumorigenic RPE1 human cells. These profiles identified widespread changes in metabolic and cell stress response factors previously linked to E2F function. In addition, we find a number of additional pathways that are sensitive to RB-depletion that are not E2F-regulated that may represent compensatory mechanisms to support the growth of RB-depleted cells. To determine whether these molecular changes are also present in RB1−/− tumors, we compared these results to Retinoblastoma and Small Cell Lung Cancer data, and identified widespread conservation of alterations found in RPE1 cells. To define which of these changes contribute to the growth of cells with de-regulated E2F activity, we assayed how inhibiting or depleting these proteins affected the growth of RB1−/− cells and of Drosophila E2f1-RNAi models in vivo. From this analysis, we identify key metabolic pathways that are essential for the growth of pRB-deleted human cells.

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Pathogenic and Compensatory Mechanisms in Epidermis of Sphingomyelin Synthase 2-Deficient Mice

Skin Pharmacology and Physiology ◽

10.1159/000515608 ◽

2021 ◽

pp. 1-7

Author(s):

Shota Sakai ◽

Asami Makino ◽

Akihito Nishi ◽

Takeshi Ichikawa ◽

Tadashi Yamashita ◽

...

Keyword(s):

Plasma Membranes ◽

Lamellar Body ◽

Lipid Mediator ◽

Permeability Barrier ◽

Compensatory Mechanisms ◽

Terrestrial Environment ◽

Sphingomyelin Synthase ◽

Epidermal Permeability Barrier ◽

Deficient Mice

Sphingomyelin (SM) is a constituent of cellular membranes, while ceramides (Cer) produced from SM on plasma membranes serve as a lipid mediator that regulates cell proliferation, differentiation, and apoptosis. In the skin, SM also is a precursor of Cer, an important constituent of epidermal permeability barrier. We investigated the role of epidermal SM synthase (SMS)2, an isoform of SMS, which modulates SM and Cer levels on plasma membranes. Although SMS2-knockout (SMS2-KO) mice were not neonatal lethal, an ichthyotic phenotype with epidermal hyperplasia and hyperkeratosis was evident at birth, which persisted until 2 weeks of age. These mice showed abnormal lamellar body morphology and secretion, and abnormal extracellular lamellar membranes in the stratum corneum. These abnormalities were no longer evident by 4 weeks of age in SMS2-KO mice. Our study suggests that (1) exposure to a dry terrestrial environment initiates compensatory responses, thereby normalizing epidermal ichthyotic abnormalities and (2) that a nonlethal gene abnormality can cause an ichthyotic skin phenotype.

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Happy hypoxemia, or blunted ventilation?

Respiratory Research ◽

10.1186/s12931-020-01604-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Josuel Ora ◽

Paola Rogliani ◽

Mario Dauri ◽

Denis O’Donnell

Keyword(s):

Compensatory Mechanisms ◽

Early Stages ◽

Advanced Stages

AbstractHappy hypoxemia is an unspecified definition that is used in COVID-19 patients to define hypoxemia without dyspnoea. Dyspnoea is a very complex symptom, and although hypoxemia can cause breathlessness, dyspnoea is not related to hypoxemia, but is more closely related to inspiratory drive and mechanical alterations. The lack of dyspnoea in the early stages of the disease is likely related to the absence of increased inspiratory drive due to compensatory mechanisms of hypoxemia, while in the advanced stages there is no evidence of a lack of dyspnoea in COVID-19 patients.

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