Output Cycles Research Articles

Temporal control of responses to chemically induced oxidative stress in the gill mucosa of Atlantic salmon (Salmo salar)

Molecular clocks are known to mediate cellular responses during oxidative stress. This important interplay is less understood in fish, particularly at mucosal surfaces. Here we report the coordinated modulation of the molecular clocks and antioxidant defence following chemically induced oxidative stress in the gill mucosa of Atlantic salmon (Salmo salar). A short-term gill explant (GE) culture was used as a model in a series of experiments aiming to demonstrate how photoperiod during culture, levels of environmental reactive oxygen species (ROS), time of oxidative stress induction, and the daily light-dark cycle affect the expression of molecular clocks and antioxidant genes in the gills. Photoperiod (either 12 light:12 dark cycle, LD or 0 light:24 dark cycle, DD) during explant culture affected the transcription of two clock genes, circadian locomotor output cycles kaput (clk) and period 1 (per1), as well as one antioxidant gene, glutathione peroxidase (gpx). When the GEs were exposed to two ROS-generating oxidants (i.e., peracetic acid, PAA and hydrogen peroxide, H2O2), photoperiod condition was demonstrated to have a significant impact on the transcription of the core genes. PAA significantly downregulated the expression of reverb alpha (reverbα) under LD, while per1 and per2 expression were significantly upregulated under DD. Nevertheless, there was no distinct pattern in the oxidant-induced expression of clock genes. On the other hand, photoperiod was shown to influence the antioxidant defence under increased ROS level, where significant transcriptional upregulation was a hallmark response under LD. Interestingly, no changes were identified under DD. Induction of oxidative stress either at ZT2 (2 h after lights on) or at ZT14 (2 h after lights off) revealed striking differences that highlighted the temporal sensitivity of the oxidative defence repertoire. Per1 was significantly modulated following time-dependent induction of oxidative stress among the clock genes. Inducing oxidative stress at ZT2 resulted in a significant upregulation of antioxidant genes; but when the same stimuli were given at ZT14, all antioxidant genes exhibited downregulation. It was further revealed that neither of the genes demonstrated daily rhythmicity in their expression in the GE cultures. Collectively, the study revealed the coordinated expression of the core elements in the molecular clock and antioxidant systems in the gill mucosa following oxidative stress. Furthermore, the results reveal that the time of day plays a crucial influence on how defences are mobilised during oxidative stress, adding new insights into the rhythms of oxidative stress response in mucosal tissues in fish.

Effect of a single bout of exercise on clock gene expression in human leukocyte.

Mammals have circadian clocks, which consist of the central clock in the suprachiasmatic nucleus and the peripheral clocks in the peripheral tissues. The effect of exercise on phase of peripheral clocks have been reported in rodents but not in humans. Continuous sampling is necessary to assess the phase of the circadian rhythm of peripheral clock gene expressions. It has been assumed that the expression of the genes in leukocyte may be "an accessible window to the multiorgan transcriptome." The present study aimed to examine whether exercise affects the level and phase of clock gene expression in human leukocytes. Eleven young men participated in three trials, in which they performed a single bout of exercise at 60% V̇o2max for 1 h beginning either at 0700 (morning exercise) or 1600 (afternoon exercise) or no exercise (control). Blood samples were collected at 0600, 0900, 1200, 1500, 1800, 2100, and 2300 and at 0600 the next morning, to assess diurnal changes of clock gene expression in leukocytes. Brain and muscle ARNT-like protein 1 (Bmal1) expression level increased after morning and afternoon exercise, and Cryptochrome 1 (Cry1) expression level increased after morning exercise. Compared with control trial, acrophase of Bmal1 expression tended to be earlier in morning exercise trial and later in afternoon exercise trial. Acrophase of Cry1 expression was earlier in morning exercise trial but not affected by afternoon exercise. Circadian locomotor output cycles kaput (Clock), Period 1-3 (Per1-3), and Cry2 expression levels and those acrophases were not affected by exercise. The present results suggest a potential role of a single bout of exercise to modify peripheral clocks in humans.NEW & NOTEWORTHY The present study showed that a single bout of exercise affected peripheral clock gene expression in human leukocytes and the effect of exercise depended on when it was performed. Brain and muscle ARNT-like protein 1 (Bmal1) expression was increased after exercises performed in the morning and afternoon. Cryptochrome 1 (Cry1) expression was also increased after the morning exercise. The effect of exercise on acrophase of Bmal1 depended on the time of the exercise: advanced after morning exercise and delayed after afternoon exercise.

Risk prediction for severe acute kidney injury by integration of urine output, glomerular filtration, and urinary cell cycle arrest biomarkers

Frequent assessment of urine output (UO), serum creatinine (sCr) and urinary cell cycle arrest biomarkers (CCAB) may improve acute kidney injury (AKI) prediction. To study the performance of UO, short term sCr changes and urinary CCAB to predict severe AKI. We measured 6 hours of UO, 6-hourly sCr changes, and urinary CCABs in all critically ill patients with cardiovascular or respiratory failure or early signs of renal stress between February and October 2018. We studied the association of such measurements, and their combination, with the development of AKI Stage 2 or 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) definition at 12 hours. We evaluated predictive performance with logistic regression, area under the receiver operating characteristic (AUROC) curve, and net reclassification indices. We computed an optimal cut-off value for each biomarker. We assessed 622 patients and, as per the exclusion criteria, we enrolled 105 critically ill patients. After 12 hours of enrolment, AKI occurred in 32 patients (30%). UO, sCr change over 6 hours and CCABs were significantly associated with severe AKI at 12 hours, with all variables achieving an AUROC > 0.7 after adjustment. Combination of any of the two or three variables achieved an AUROC > 0.7 for subsequent severe AKI at 12 hours. The optimal predictive high specificity cut-off values were ≤ 0.4 mL/kg/h for UO, variation of +15 μmol/L over 6 hours in sCr, and ≥ 1.5 (ng/mL)2/1000 for CCABs. In this prospective study, an integrative approach using UO, short term sCr change and/or urinary CCABs showed a satisfactory performance for the prediction of severe AKI development at 12 hours.

A CLOCK-binding small molecule disrupts the interaction between CLOCK and BMAL1 and enhances circadian rhythm amplitude

Proper function of many physiological processes requires a robust circadian clock. Disruptions of the circadian clock can result in metabolic diseases, mood disorders, and accelerated aging. Therefore, identifying small molecules that specifically modulate regulatory core clock proteins may potentially enable better management of these disorders. In this study, we applied a structure-based molecular-docking approach to find small molecules that specifically bind to the core circadian regulator, the transcription factor circadian locomotor output cycles kaput (CLOCK). We identified 100 candidate molecules by virtual screening of ∼2 million small molecules for those predicted to bind closely to the interface in CLOCK that interacts with its transcriptional co-regulator, Brain and muscle Arnt-like protein-1 (BMAL1). Using a mammalian two-hybrid system, real-time monitoring of circadian rhythm in U2OS cells, and various biochemical assays, we tested these compounds experimentally and found one, named CLK8, that specifically bound to and interfered with CLOCK activity. We show that CLK8 disrupts the interaction between CLOCK and BMAL1 and interferes with nuclear translocation of CLOCK both in vivo and in vitro Results from further experiments indicated that CLK8 enhances the amplitude of the cellular circadian rhythm by stabilizing the negative arm of the transcription/translation feedback loop without affecting period length. Our results reveal CLK8 as a tool for further studies of CLOCK's role in circadian rhythm amplitude regulation and as a potential candidate for therapeutic development to manage disorders associated with dampened circadian rhythms.

Development of a High‐Performance Handheld Triboelectric Nanogenerator with a Lightweight Power Transmission Unit

AbstractA triboelectric nanogenerator (TENG) is a promising energy harvester that exploits the combination of contact electrification between two different material surfaces and electrical induction. In this study, a handheld‐TENG (HH‐TENG) is developed to harvest biomechanical energy effectively, especially energy generated from finger motions, which is one of the most common body movements involving lots of energy. To enhance the electrical output performance of the device while minimizing the inconvenience caused by carrying it, a rationally designed lightweight power transmission unit is adopted. As a result, an extremely high number of output cycles with high specific peak power (greater than 10 µW g–1) can be achieved in a single operation of the HH‐TENG. Although the proposed HH‐TENG weighs less than 70 g, the developed HH‐TENG can be connected with commercially available electric circuits such as an AC‐DC converter to generate not only reliable and continuous DC voltage to power portable electronics, but also further boosted open‐circuit voltage greater than 2.5 kV, which is sufficient to generate microplasma in a room environment. Adoption of a lightweight power transmission unit with the TENG can be considered as an effective strategy to significantly enhance the specific power, which advances the TENG toward practical implementation.

Financial Stress Interacts With CLOCK Gene to Affect Migraine.

Previous studies suggested that both maladaptive stress response and circadian dysregulation might have a role in the background of migraine. However, effects of circadian genes on migraine have not been tested yet. In the present study, we investigated the main effect of rs10462028 of the circadian locomotor output cycles kaput (CLOCK) gene and its interaction with different stress factors on migraine. In our cross-sectional study 2,157 subjects recruited from Manchester and Budapest completed the ID-Migraine questionnaire to detect migraine type headaches (migraineID). Additional stress factors were assessed by a shortened version of the Childhood Trauma Questionnaire, the List of Threatening Experiences questionnaire, and a validated questionnaire to identify financial difficulties. Rs10462028 showed no main genetic effect on migraineID. However, chronic stress indexed by financial difficulties showed a significant interaction effect with rs10462028 (p = 0.006 in recessive model) on migraineID. This result remained significant after correction for lifetime bipolar and unipolar depression and was replicated in both subsamples, although only a trend effect was reached after Bonferroni-correction, which is the strictest correction not considering interdependences. Childhood adversity (CHA) and Recent negative life events (RLE) showed no significant gene × stress interaction with rs10462028. In addition, in silico analysis demonstrated that the genetic region tagged by rs10462028 alters the binding of several miRNAs. Our exploratory study suggests that variations in the CLOCK gene, with moderating effect on gene function through miRNA binding, in interaction with financial difficulties might influence the risk of migraine-type headaches. Thus, financial hardship as a chronic stress factor may affect migraine through altering circadian rhythms.

A Non-canonical Function of BMAL1 Metabolically Limits Obesity-Promoted Triple-Negative Breast Cancer.

SummaryThe epidemiological association between disrupted circadian rhythms and metabolic diseases is implicated in increased risk of human breast cancer and poor therapeutic outcomes. To define a metabolic phenotype and the underlying molecular mechanism, we applied chronic insulin treatment (CIT) to an in vitro model of triple-negative breast cancer to directly address how BMAL1, a key circadian transcription factor, regulates cancer cell respiration and governs tumor progression. At the cellular level, BMAL1 suppresses the flexibility of mitochondrial substrate usage and the pyruvate-dependent mitochondrial respiration induced by CIT. We established an animal model of diet-induced obesity/hyperinsulinemia and observed that BMAL1 functions as a tumor suppressor in obese, but not lean, mice. Downregulation of BMAL1 is associated with higher risk of metastasis in human breast tumors. In summary, loss of BMAL1 in tumors confers advantages to cancer cells in both intrinsic mitochondrial metabolism and extrinsic inflammatory tumor microenvironment during pre-diabetic obesity/hyperinsulinemia.

Effect of time-restricted feeding on metabolic risk and circadian rhythm associated with gut microbiome in healthy males.

Time-restricted feeding (TRF) confers protection against nutritional challenges that predispose obesity and metabolic risks through involvement of circadian locomotor output cycles protein kaput genes and gut microbiome, but the underlying mechanism is not clearly understood. Therefore, the present study examined the effects of TRF on metabolic markers and circadian rhythm associated with gut microbiota in healthy males. Two groups (TRF, n 56; non-TRF, n 24) of male adults were enrolled. The TRF group provided blood at pre-TRF and post-TRF, while non-TRF one time after 25 d of trial. Serum lipid and liver profiles were determined. Real time-PCR was applied for circadian and inflammatory gene expression. The 16S rRNA genes were sequenced on the Illumina Miseq v3 platform to comprehensively catalogue the composition and abundance of bacteria in stool. We showed that TRF ameliorated the serum lipid and liver profiles of the individuals. In the TRF group, gut microbial richness was significantly enhanced, with enrichment of Prevotellaceae and Bacteroideaceae. TRF enhanced circadian gene expression probably by activation of sirtuin-1, which is positively associated with gut microbiome richness. TRF could be a safe remedy for the prevention of metabolic diseases related to dyslipidaemia, as it regulates circadian rhythm associated with gut microbiome modulation.

Asymmetric Business Cycles in Segmented Labour Markets

We document the presence of asymmetric business cycles in both regular and contract labour markets in India and investigate the role of nominal wage rigidities and labour adjustment costs in accounting for these asymmetries. Using data from Annual Survey of Industries, we find that (i) the growth rate of output is negatively skewed, (ii) the growth of regular employment is negatively skewed while that of contract employment is positively skewed, (iii) the nominal wage growth of regular workers is positively skewed while that of contract workers is negatively skewed. We show that a standard business cycle model augmented with asymmetric wage adjustment cost for both regular and contract labour coupled with symmetric labour adjustment cost for regular workers does a good job of explaining the asymmetries in both output and employment cycles. We also find that the presence of contract labour relaxes the constraint of downward nominal wage rigidity, and hence decreases the optimal level of grease inflation required in the economy.

Circadian Clock Regulation on Lipid Metabolism and Metabolic Diseases.

The basic helix-loop-helix-PAS transcription factor (CLOCK, Circadian locomotor output cycles protein kaput) was discovered in 1994 as a circadian clock. Soon after its discovery, the circadian clock, Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL, also call BMAL1), was shown to regulate adiposity and body weight by controlling on the brain hypothalamic suprachiasmatic nucleus (SCN). Farther, circadian clock genes were determined to exert several of lipid metabolic and diabetes effects, overall indicating that CLOCK and BMAL1 act as a central master circadian clock. A master circadian clock acts through the neurons and hormones, with expression in the intestine, liver, kidney, lung, heart, SCN of brain, and other various cell types of the organization. Among circadian clock genes, numerous metabolic syndromes are the most important in the regulation of food intake (via regulation of circadian clock genes or clock-controlled genes in peripheral tissue), which lead to a variation in plasma phospholipids and tissue phospholipids. Circadian clock genes affect the regulation of transporters and proteins included in the regulation of phospholipid metabolism. These genes have recently received increasing recognition because a pharmacological target of circadian clock genes may be of therapeutic worth to make better resistance against insulin, diabetes, obesity, metabolism syndrome, atherosclerosis, and brain diseases. In this book chapter, we focus on the regulation of circadian clock and summarize its phospholipid effect as well as discuss the chemical, physiology, and molecular value of circadian clock pathway regulation for the treatment of plasma lipids and atherosclerosis.

PPARα mediates night neon light-induced weight gain: role of lipid homeostasis.

Rationale: Light pollution leads to high risk of obesity but the underlying mechanism is not known except for the influence of altered circadian rhythm. Peroxisome proliferator-activated receptor α (PPARα) regulates lipid metabolism, but its role in circadian-related obesity is not clear.Methods: Wild-type (WT) and Ppara-null (KO) mice on a high-fat diet (HFD) were treated with neon light at night for 6 weeks. Body weights were recorded and diet consumption measured. The hypothalamus, liver, adipose and serum were collected for mechanism experimentation.Results: WT mice on a HFD and exposed to night neon light gained about 19% body weight more than the WT control mice without light exposure and KO control mice on a HFD and exposed to night neon light. The increase in adipose tissue weight and adipocyte size led to the differences in body weights. Biochemical analysis suggested increased hepatic lipid accumulated and increased transport of lipid from the liver to peripheral tissues in the WT mice that gained weight under neon light exposure. Unlike KO mice, the expression of genes involved in lipid metabolism and the circadian factor circadian locomotor output cycles kaput (CLOCK) in both liver and adipose tissues were elevated in WT mice under neon light exposure.Conclusions: PPARα mediated weight gain of HFD-treated mice exposed to night neon light. More lipids were synthesized in the liver and transported to peripheral tissue leading to adaptive metabolism and lipid deposition in the adipose tissue. These data revealed an important mechanism of obesity induced by artificial light pollution where PPARα was implicated.

Inhibition of CRY2 by STAT3/miRNA-7-5p Promotes Osteoblast Differentiation through Upregulation of CLOCK/BMAL1/P300 Expression

Accumulating evidence indicates that cryptochrome circadian regulatory (CRY) proteins have emerged as crucial regulators of osteogenic differentiation. However, the associated mechanisms are quite elusive. In this study, we show that knockdown of CRY2 downregulated the expression of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN) to facilitate osteoblast differentiation. Further study identified that CRY2 was directly targeted by microRNA (miR)-7-5p, which was highly induced during osteoblast differentiation. The expression of Runx2, ALP, collagen type I alpha 1 (Col1a1), and OCN was upregulated by overexpression of miR-7-5p and induction of osteoblast differentiation. Moreover, signal transducer and activator of transcription 3 (STAT3) transcriptionally activated miR-7-5p to significantly enhance the expression of above osteogenic marker genes and mineral formation. However, overexpression of CRY2 abolished the osteogenic differentiation induced by miR-7-5p overexpression. Silencing of CRY2 unraveled the binding of CRY2 with the circadian locomotor output cycles kaput (CLOCK)/brain and muscle ARNT-like 1 (BMAL1) complex to release CLOCK/BMAL1, which facilitated the binding of CLOCK/BMAL1 to the promoter region of the P300 E-box to stimulate the transcription of P300. P300 subsequently promoted the acetylation of histone 3 and the formation of a transcriptional complex with Runx2 to enhance osteogenesis. Taken together, our study revealed that CRY2 is repressed by STAT3/miR-7-5p to promote osteogenic differentiation through CLOCK/BMAL1/P300 signaling. The involved molecules may be potentially targeted for treatment of osteoporosis.

Impact of circadian rhythms on female reproduction and infertility treatment success.

In recent years, new studies have investigated the role and influence of sleep on female fertility and early pregnancy outcomes, providing a growing body of knowledge demonstrating how regulation by sleep of hormones are important to reproduction, and how disruptions in sleep, circadian rhythms, and genes regulating circadian rhythmicity can negatively impact fertility and early pregnancy outcomes. This review aims to summarize the most recent research on the relationship among circadian rhythms, fertility, and early pregnancy outcomes in women, and to explore possible fertility interventions. Recent studies have found altered levels of FSH, LH, and prolactin with sleep disturbance or circadian dysrhythmia. Disruption of circadian rhythms in the form of shift work, jet lag, and daylight savings time changes have been associated with poorer fertility and early pregnancy outcomes. Alterations in the expression of circadian rhythm-regulating circadian locomotor output cycles kaput (CLOCK) genes have been associated with decreased fertility and increased rates of miscarriage. Overall, undisrupted sleep and circadian rhythmicity appear to optimize fertility and early pregnancy outcomes and may play an important role in the success of fertility treatment.

Serotonin Prevents Differentiation of Brown Adipocytes by Interfering with Their Clock.

Serotonin was shown to interfere with the differentiation of brown adipocytes. In addition, clock components inhibit brown adipogenesis through direct transcriptional control of key components of the transforming growth factor β pathway. The aim of this study was to investigate whether serotonin abrogates brown adipogenesis by affecting clock functionality. Nondifferentiated and differentiated HIB1B brown adipocytes were treated with serotonin, and their clock expression and functionality and differentiation state were examined. Nondifferentiated HIB1B brown adipocytes treated with serotonin showed increased brown adipocyte markers alongside increased brain-muscleArnt-like protein1 (Bmal1) andRAR related orphan receptor A (Rora) but decreasednuclear receptor Rev-erbα mRNA levels. BMAL1 overexpression together with serotonin led to significantly lower brown adipocyte markers. Serotonin in the differentiation cocktail led to reduced brown adipocyte markers as well as clock gene expression. After differentiation, serotonin treatment significantly decreased brown adipocyte markers and reduced BMAL1 and RORα but increased REV-ERBα protein levels. Addition of serotonin to the differentiation medium or addition after differentiation reduced activity of calcium/calmodulin-dependent protein kinasetype IIsubunit gamma, which interferes with circadian locomoter output cycles protein kaput (CLOCK):BMAL1 dimerization and transactivation. Clock expression is required at the early stages of differentiation to brown adipocytes, and serotonin interferes with this process by modulating clock functionality. Serotonin interferes with clock functionality by reducing the levels of the active form of calcium/calmodulin-dependent protein kinase typeIIsubunit gamma.

Research on key technologies of bearing preload of spindle based on piezoelectric actuators

This study analysed the influence of bearing preload on the stiffness of spindle bearings. MATLAB/Simulink is used to calculate the vibration of simplified spindle system. The vibration of the simplified spindle system decreases with the increase of bearing preload. A kind of force output characteristics of piezoelectric actuators test device was designed. Experimental analysis of the maximum force output characteristic, hysteresis characteristic, creep characteristic and stability characteristic of PSt 150/4/7 VS9-type piezoelectric actuators under different initial loads, voltage frequencies, cycles working and voltage travel. The evaluating indexes are the maximum output force, average hysteresis, maximum deviation, drift amount and cycle delay. In conclusion that the piezoelectric actuator has better repeatability and stability under the initial load is around 150 N and low-voltage frequency. It is not suitable for multiple cycles working. The increment of output force is proportional to starting voltage at same voltage travel. MATLAB/Simulink is used to calculate the feasibility of variable bearing preload strategy based on a piezoelectric actuator. It provided scientific references for the research of high performance and intelligent spindle.

Periodic Oxaliplatin Administration in Synergy with PER2-Mediated PCNA Transcription Repression Promotes Chronochemotherapeutic Efficacy of OSCC.

Developing chemotherapeutic resistance affects clinical outcomes of oxaliplatin treatment on various types of cancer. Thus, it is imperative to explore alternative therapeutic strategies to improve the efficacy of oxaliplatin. Here, it is shown that circadian regulator period 2 (PER2) can potentiate the cytotoxicity of oxaliplatin and boost cell apoptosis by inhibiting DNA adducts repair in human oral squamous cell carcinoma (OSCC) cells. The circadian timing system is closely involved in controling the activity of DNA adducts repair and gives it a 24 h rhythm. The mechanistic dissection clarifies that PER2 can periodically suppress proliferating cell nuclear antigen (PCNA) transcription by pulling down circadian locomotor output cycles kaput–brain and muscle arnt‐like 1 heterodimer from PCNA promoter in a CRY1/2‐dependent manner, which subsequently impedes oxaliplatin‐induced DNA adducts repair. Similarly, PER2 is capable of improving the efficacy of classical DNA‐damaging chemotherapeutic agents. The tumor‐bearing mouse model displays PER2 can be deployed as an oxaliplatin administration timing biomarker. In summary, it is believed that the chronochemotherapeutic strategy matching PER2 expression rhythm can efficiently improve the oxaliplatin efficacy of OSCC.

THE U.S. LABOR INCOME SHARE AND AUTOMATION SHOCKS

The causes and consequences of the 1964–2016 swings in the U.S. labor income share/labor share (LS) are parsed through the lens of a structural model estimated on aggregate and LS series jointly. Where conventional models fall short, the present model yields a counter‐cyclical LS unconditionally and in response to demand and monetary policy shocks, as well as a small wage pro‐cyclicality, via moderate wage indexation. Shifts in automation, workers' market power, investment efficiency, and the relative price of investment account for 54%, 24%, 6%, and 4% of LS fluctuations, respectively. Automation shocks explain the lion's share of the post‐2007 cyclical LS tumble and 11% of output cycles, and generate a distinctive counter‐cyclical labor response. (JEL E32, E25, E52)

Searching for solar-like interannual to bidecadal effects on temperature and precipitation over a Southern Hemisphere location

Precipitation and temperature over Tucuman (26.8°S, 65.2°W), a province located in the Northwestern region of Argentina, is analyzed for the interval 1889–2018 in search of any plausible statistical associations with impacts and responses from solar variability. The aim of the study was to contribute data to the controversial issue of climate variations in response to both anthropogenic and natural forcings. The long-term behavior of Tucuman climatic series involves overall warming and augmented precipitation tendencies, possibly linked to the increasing greenhouse gases concentration or even other local man-made factors like increasing urbanization. In addition, we identified sporadic ~4 and ~8-year periodicities, and a ~20-year oscillation after the 1950–1960's. Based on the physical hint that bidecadal periodicities detected in climate parameters are probably not linked to the solar 11-year-like irradiance cycles, we expand our scope of investigations to include another effect which has been recently considered in the dynamics of large rivers as “the planetary hypothesis of the solar cycles”. This new hypothesis supposes that the barycentric dynamics of the Sun could be involved in modulations of the intrinsic solar magnetic and radiative output cycles and therefore Earth-bound climatic responses. Thus, we present a wide-ranging statistical analysis of correlation, cross spectrum, and coherence between Tucuman's climatic series and solar orbital parameters, including also the analysis of hemispheric mean temperatures. Our results show significant coherence at the ~20-year cycle, which is clearly present in the Sun's barycentric dynamic that could in turn be linked to some features of the quasi-decadal solar activity variations.

The circadian rhythm of bladder clock genes in the spontaneously hypersensitive rat.

Circadian expression rhythms of clock gene products in the bladder are reportedly hindered by clock gene abnormalities. However, the role of clock gene products in various pathological lower urinary tract conditions is unknown. The present study examined the relationship between clock genes and voiding dysfunction in spontaneous hypertensive rats (SHR). The voluntary voiding behavior study using metabolic cages was performed in 18-weeks old male Wistar rats (control group, n = 36) and SHR (SHR group, n = 36) under 12-h light/12-h dark conditions. Bladders were harvested every 4 h at six time points (n = 6 for each time point for each group), and we analyzed the messenger RNA (mRNA) expression of several clock genes: period 2 (Per2), cryptochrome 2 (Cry2), brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), nuclear receptor subfamily 1, group D, member 1 (Rev-erbα), mechanosensors: transient receptor potential vanilloid channel 1 (TRPV1), TRPV4, Piezo1, and vesicular nucleotide transporter (VNUT) using real-time polymerase chain reaction. Though 24-h urination frequency for both light and dark periods was significantly higher in the SHR group, urine volume per voiding was significantly lower versus control. In controls, urine volume per voiding was significantly lower during the dark period (active phase) than the light period (rest phase); this parameter did not significantly differ between active and rest phases for SHR. SHR bladders showed significantly higher expression of Cry2 and Clock during the active phase compared to controls. In the SHR group, TRPV1, TRPV4, Piezo1, and VNUT mRNA levels were significantly higher during the active phase compared to the control group. We speculate that Cry2 and Clock may be contributing factors in the decrease of bladder capacity during the active phase in SHR through increase of TRPV1, TRPV4, Piezo1, and VNUT expression, but further research will be necessary to elucidate the precise mechanisms.

Business Cycle in Nigeria, What Explanation Fits?: An Investigation Using Wavelet Analysis

Various empirical evidences have attempted to provide explanations on the major factors responsible for output dynamics for different economies in the world and Nigeria in particular. In a quest to provide definite answer, this research was conducted in order to find new framework for understanding business cycle and its characteristics in Nigeria. To achieve the objective, three sets of explanations to business cycle were explored using time-frequency domain analysis. The evidence shows that output cycles are as a result of supply, demand and political factors. Hence the real and political business cycle explanations fit the Nigerian context.