Long-read isoform sequencing reveals tissue-specific isoform expression between active and hibernating brown bears (Ursus arctos)

Understanding hibernation in brown bears (Ursus arctos) can provide insight into some human diseases. During hibernation, brown bears experience periods of insulin resistance, physical inactivity, extreme bradycardia, obesity, and the absence of urine production. These states closely mimic aspects of human diseases such as type 2 diabetes, muscle atrophy, as well as renal and heart failure. The reversibility of these states from hibernation to active season enables the identification of mediators with possible therapeutic value for humans. Recent studies have identified genes and pathways that are differentially expressed between active and hibernation seasons. However, little is known about the role of differential expression of gene isoforms on hibernation physiology. To identify both distinct and novel mRNA isoforms, full-length RNA-sequencing (Iso-Seq) was performed on adipose, skeletal muscle, and liver from three individuals sampled during both active and hibernation seasons. The existing reference annotation was improved by combining it with the Iso-Seq data. Short-read RNA-sequencing data from six individuals was mapped to the new reference annotation to quantify differential isoform usage between tissues and seasons. We identified differentially expressed isoforms in all three tissues, to varying degrees. Adipose had a high level of differential isoform usage with isoform switching, regardless of whether the genes were differentially expressed. Our analyses revealed that differential isoform usage, even in the absence of differential gene expression, is an important mechanism for modulating genes during hibernation. These findings demonstrate the value of isoform expression studies and will serve as the basis for deeper exploration into hibernation biology.

Impact of Alternative Routes and Timing of Dopamine and Mannitol Administrations to Reduce Negative Properties of Extended Cardiopulmonary Bypass on Renal Function in Coronary Artery Operations

Objectives: To analyze impact of alternative routes and timing of dopamine and mannitol administrations to reduce negative properties of extended cardiopulmonary bypass on renal function in coronary artery operations. Methods: Set I (n: 26 individual): Mannitol (1 g/kg) has been introduced to the CPB priming solution. Set II (n: 25 patients): Even during interval among anesthetic induction and operation, 3 g/kg/min of IV dopamine was delivered. Group III (n = 25 patients): 2 g/kg/min IV dopamine was provided among anesthesia initiation and operation conclusion, and 1 g/kg mannitol were added to priming solution for CPB. Furosemide was administered to Group IV (n = 26 cases) when urine production was poor. Results: There would be a substantial rise in the post-operative urine microalbumin/creatinine ratios over all classes (p 0.06), as well as a rise in cystatin-c in Set 1, 2, and 3 (p 0.02). Conclusions: Researchers suggest that combining dopamine infusion (1 g/kg/min) and mannitol (2 g/kg) throughout CPB seems to be the more actual method for preventing detrimental possessions of CPB on renal functioning.

Living donor kidney transplant following nephrectomy for renal artery stenosis with arterial reconstruction and viability assessment using ex vivo normothermic perfusion

Ex vivo normothermic perfusion (EVNP) is increasingly recognised as a viability tool to increase organ utilisation in deceased donor transplantation. We report the use of EVNP to assess graft perfusion quality following indication nephrectomy and back-bench arterial reconstruction in a case of renal artery stenosis, unamenable to endovascular treatment. Once explanted, it was not possible to effectively cold perfuse the graft through the main renal artery or collaterals. An arterial reconstruction was performed with patch angioplasty using the largest collateral creating a single common stem. EVNP was used to assess organ perfusion and, therefore, viability. Excellent global perfusion was evident alongside urine production, demonstrating that the arterial reconstruction was satisfactory. A patient with end-stage renal disease was consented with particular attention to the uncertainty of the underlying donor disease process and long-term outcome of the reconstruction. Primary function was achieved and recipient estimated glomerular filtration rate (eGFR) remains stable at 58 mL/min/1.73 m² at 6 months.

Renal cell markers: lighthouses for managing renal diseases

Kidneys, one of the vital organs in our body, are responsible for maintaining whole-body homeostasis. The complexity of renal function (e.g., filtration, reabsorption, fluid and electrolyte regulation, urine production) demands diversity not only at the level of cell types but also in their overall distribution and structural framework within the kidney. To gain an in-depth molecular-level understanding of the renal system, it is imperative to discern the components of kidney and the types of cells residing in each of the sub-regions. Recent developments in labeling, tracing, and imaging techniques enabled us to mark, monitor and identify these cells in vivo with high efficiency in a minimally invasive manner. In this review, we have summarized different cell types, specific markers that are uniquely associated with those cell types, and their distribution in kidney, which altogether make kidneys so special and different. Cellular sorting based on the presence of certain proteins on the cell surface allowed for assignment of multiple markers for each cell type. However, different studies using different techniques have found contradictions in the cell-type specific markers. Thus, the term "cell marker" might be imprecise and sub-optimal, leading to uncertainty when interpreting the data. Therefore, we strongly believe that there is an unmet need to define the best cell markers for a cell type. Although, the compendium of renal-selective marker proteins presented in this review is a resource that may be useful to the researchers, we acknowledge that the list may not be necessarily exhaustive.

The Candidate Schizophrenia Risk Gene Tmem108 Regulates Glucose Metabolism Homeostasis

BackgroundSchizophrenia (SCZ) is a severe psychiatric disease affected by genetic factors and environmental contributors, and premorbid abnormality of glucose metabolism is one of the SCZ characteristics supposed to contribute to the disease’s pathological process. Transmembrane protein 108 (Tmem108) is a susceptible gene associated with multiple psychiatric diseases, including SCZ. Moreover, Tmem108 mutant mice exhibit SCZ-like behaviors in the measurement of sensorimotor gating. However, it is unknown whether Tmem108 regulates glucose metabolism homeostasis while it involves SCZ pathophysiological process.ResultsIn this research, we found that Tmem108 mutant mice exhibited glucose intolerance, insulin resistance, and disturbed metabolic homeostasis. Food and oxygen consumption decreased, and urine production increased, accompanied by weak fatigue resistance in the mutant mice. Simultaneously, the glucose metabolic pathway was enhanced, and lipid metabolism decreased in the mutant mice, consistent with the elevated respiratory exchange ratio (RER). Furthermore, metformin attenuated plasma glucose levels and improved sensorimotor gating in Tmem108 mutant mice.ConclusionsHyperglycemia occurs more often in SCZ patients than in control, implying that these two diseases share common biological mechanisms, here we demonstrate that the Tmem108 mutant may represent such a comorbid mechanism.

Characteristics of Obstructive Anuria Patients in a Tertiary Hospital in East Java, Indonesia

Obstructive uropathy is an obstruction of urinary passage which may lead to anuria, a condition where urine production is less than 50 to 100 ml in 24 hours. The varying etiologies and underlying pathophysiology among different cases based on different demographics can make it difficult for physicians to decide the proper management. Therefore, we aimed to evaluate the clinical profile and management of anuria patients in Dr. Soetomo General Academic Hospital over a four-year period. This was a descriptive study with a retrospective approach evaluating all patients with anuria admitted from January 2016 to December 2019. Patient data taken from the medical record were presented descriptively. A total of 176 patients were obtained. Only 161 patients were included. Most of the patients were female (n=100, 62.11%) aged 51 to 60 years old (n=63, 39.1%). Postrenal obstruction due to urinary stone was the most frequent etiology (n=86, 53.4%). Consequently, some patients developed hydronephrosis, which was mostly dominated by the bilateral (n=130, 80.8%) and severe types (n=75, 46.6%). A total of 129 patients (80.1%) underwent hemodialysis. Most of the patients were treated with definitive treatment (n=46, 38.7%). Normalization of renal function mostly occurred in patients who underwent percutaneous nephrostomy (PNS) before giving a definitive treatment.

The Effect of The Cucumber Consumption To The Level of Sodium Potassium in Mus Muscullus’s Urine Production

Cucumber (Cucumis sativus L.). was known for lowering blood pressure agents. Some researches show that Cucumber had a similar mechanism with a loop diuretic (Furosemide), exceeding sodium and potassium excretion. However, a part of Cucumber that gives a better effect on managing water and sodium balance remains unknown. This study was to explain the differences potential diuretic among parts of Cucumber (Cucumis sativus L.). This study was using a post-test only control group designed in animals. There were 44 male Mus musculus tested in this study. All of the animal testings was divided into 9 different treatment groups and 2 control groups. All Mus musculus got 1 mL methanol extract of Cucumber (Cucumis sativus L.) according to their group. The animal testing was put on metabolic cage to measure urine volume for 24 hours. The flesh and rind part of Cucumber (Cucumis sativus L.) showed a similar result with furosemide as diuretics agents. However, whole part of the fruit of Cucumber (Cucumis sativus L.) (flesh, rind, and seed) showed as natriuretic dan kaliuretic, Cucumber (Cucumis sativus L.) has a similar potential diuretic with Furosemide. Even in low concentrations of Cucumber extract, it led to having a potential diuretic, with natriuretic and kaliuretic effects in the whole part of the fruit. This could be suggested to people with chronic kidney diseases to prevent hyperkalemia.

Psychological stress induced bladder overactivity in female mice is associated with enhanced afferent nerve activity

Psychological stress has been linked to the development and exacerbation of overactive bladder symptoms, as well as afferent sensitisation in other organ systems. Therefore, we aimed to investigate the effects of water avoidance stress on bladder afferent nerve activity in response to bladder filling and pharmaceutical stimulation with carbachol and ATP in mice. Adult female C57BL/6J mice were exposed to either water avoidance stress (WAS) for 1 h/day for 10 days or normal housing conditions. Voiding behaviour was measured before starting and 24-h after final stress exposure and then animals were euthanised to measure afferent nerve activity in association with bladder compliance, spontaneous phasic activity, contractile responses, as well as release of urothelial mediators. WAS caused increased urinary frequency without affecting urine production. The afferent nerve activity at low bladder pressures (4–7 mmHg), relevant to normal physiological filling, was significantly increased after stress. Both low and high threshold nerves demonstrated enhanced activity at physiological bladder pressures. Urothelial ATP and acetylcholine release and bladder compliance were unaffected by stress as was the detrusor response to ATP (1 mM) and carbachol (1 µM). WAS caused enhanced activity of individual afferent nerve fibres in response bladder distension. The enhanced activity was seen in both low and high threshold nerves suggesting that stressed animals may experience enhanced bladder filling sensations at lower bladder volumes as well as increased pain sensations, both potentially contributing to the increased urinary frequency seen after stress.

The Impact of Movement, Physical Activity and Position on Urine Production: A Pilot Study

Background: Many different internal factors have been proven to influence urine production such as age, weight, and quality of sleep. External factors such as consumption of caffeine and fluid consumption have been shown to have an impact on urine production. Aim: To investigate the impact of movement, physical activity, and position on urine production. Methods: This prospective observational study was executed at Ghent University Hospital, Belgium. Study participation was open for anyone visiting the hospital. Participants collected 1 basic and 2 extended 24-hour urine collections and filled in questionnaires concerning their general health and physical activity. Urinary levels of osmolality, sodium, and creatinine were determined. Data on movement, physical activity and position was described. Results: An increase in body movement leads to a significant increase in diuresis during daytime, night-time, and 24 hours (p=0,002, p= <0,001, and p=<0,001, respectively). An increase in body movement leads to a significant decrease in osmolality during night-time and 24 hours (p=0,009, and p=0,004, respectively). However, no significant influence of movement on osmolality was found during daytime (p=0,12). An increase in body movement leads to a significant decrease in creatinine during daytime, night-time, and 24 hours (p=0,001, <0,001, and p=<0,001, respectively). An increase in body movement leads to a significant increase in sodium during daytime (p=0,046) but this was statistically significant during night-time and 24 hours (p=0,32, and p=0,84 respectively). Conclusion: Our study demonstrates a statistically significant association of movement, physical activity, and position with urine production. It would therefore be interesting to explore this association further with the use of new technology to have more accurate data. Here lays a potential role for conservative measurements and lifestyle adaptations in the management of patients with bothersome LUTS and more precisely nocturia.