Epididymitis with Pasteurella multocida isolated from two male Japanese Black beef calves.

Two male Japanese Black calves developed an enlarged scrotum and testis. Orchiectomy was performed and pus was collected during surgery. After removal of the testis, bacteriological and histopathological examinations were conducted to investigate the cause and confirm the diagnosis. Based on the results obtained, both cases were diagnosed with epididymitis caused by an infection with Pasteurella multocida. This is the first study to show that P. multocida causes epididymitis in male calves. Further studies are required to clarify the details underlying the infection of calves with P. multocida.

Changes in Retinal Hemodynamics in the Optic Nerve Head of Healthy Participants Measured Using Laser Speckle Flowgraphy after a Cold Pressor Test.

PURPOSE: Autoregulation of retinal vessels is stronger than that of choroidal vessels. This study aimed to use laser speckle flowgraphy to determine the time course of changes in retinal hemodynamics of healthy eyes after a cold pressor test. METHODS: This prospective study included 44 right eyes of 44 healthy volunteers (age, 21.7 ± 5.0 years). The mean blur rate, which is a quantitative index of the relative blood flow velocity in the retina, was measured using laser speckle flowgraphy. The vessel average of mean blur rate at the optic nerve head, intraocular pressure, systolic blood pressure, diastolic blood pressure, mean blood pressure, heart rate, and ocular perfusion pressure were evaluated at baseline, immediately after the cold pressor test, and 10, 20, and 30 minutes after the test. RESULTS: Immediately after the test (0 minutes), systolic blood pressure, diastolic blood pressure, mean blood pressure, and ocular perfusion pressure were significantly increased compared with those at baseline; however, no changes were observed at 10, 20, and 30 minutes after the test. In contrast, intraocular pressure, heart rate, and the vascular mean blur rate values at the optic nerve head did not change throughout the course of the study. CONCLUSIONS: Sympathetic hyperactivity induced by the cold pressor test increased systemic circulatory dynamics, but not retinal circulatory hemodynamics, suggesting the involvement of vascular autoregulation.

Surgical treatment of bovine nasal granuloma and an allergological exploration.

Nasal granuloma in cattle results from inflammation within, and attendant proliferation of, the nasal mucosa possibly in response to an allergic response. However, the relationship between nasal granuloma and allergies remains unclear. Furthermore, severe cases have a poor prognosis because there is currently no effective treatment. Herein, we report three cases of nasal granuloma with severe stertorous breathing that were treated surgically. We also conducted an allergological exploration. Following surgical removal clinical signs did not recur in two of the three cases; however, stertorous breathing persisted in one case, and the cow was sacrificed 4 months later. A histopathological examination revealed that all nasal granulomas featured varying infiltrations of macrophages eosinophils, mast cells, and lymphocytes. The number of mast cells and the proportion of these cells that had degranulated were significantly higher in the granulomas than in normal nasal mucosae. In addition, serum histamine levels were higher in nasal granuloma cases than in normal cows, although serum immunoglobulin E levels were similar, and lymphocyte infiltration in the submucosal layer suggested type I and type IV allergies. Collectively, the results indicate the efficacy of complete surgical curettage for the treatment of allergic nasal granuloma in cattle. Further studies are required to identify the causes and risk factors of allergic nasal granuloma in cows.

Cardiac tumor comprising a malignant peripheral nerve sheath tumor and spontaneous atrial osseous metaplasia in a sheep.

Primary cardiac tumors in animals are very rare. The purpose of this report was to describe the first case of a cardiac tumor comprising a malignant peripheral nerve sheath tumor and spontaneous atrial osseous metaplasia in a Corriedale sheep. Histologically, the tumor in the bilateral atrial pericardium consisted of dense cellular components comprising tumor cells and a sparse cellular area, and non-neoplastic mature bone tissue. The tumor cells were spindle-shaped, round, or polygonal, and proliferating, with fascicular, storiform, palisading, and sheet patterns. Immunohistochemically, the tumor cells were positive for vimentin, S-100, occasionally positive for myeline basic protein, glial fibrillary acidic protein, neurofilament, neuron specific enolase, and neuron growth factor receptor suggesting that they originated from the nervous system. On the basis of these findings, the final diagnosis was a malignant peripheral nerve sheath tumor and spontaneous atrial osseous metaplasia.

Metabolic elasticity: A new measure of age.

Promoting healthy aging is contingent on understanding the underlying mechanisms for the age-associated decline in metabolic physiology. Through developing a novel concept of "metabolic elasticity" to evaluate metabolic adaptability in response to cyclical changes in energy balance, Zhou et al. present an impactful gauge of metabolic health that is particularly relevant to aging.

A simulation study of in-beam visualization system for proton therapy by monitoring scattered protons.

Recently, in-beam positron emission tomography (PET) has been actively researched for reducing biological washout effects and dose monitoring during irradiation. However, the positron distribution does not precisely reflect the dose distribution since positron production and ionization are completely different physical processes. Thus, a novel in-beam system was proposed to determine proton dose range by measuring scattered protons with dozens of scintillation detectors surrounding the body surface. While previous studies conducted a preliminary experiment with a simple phantom, we simulated more complex situations in this paper. Especially, we conducted three stepwise simulation studies to demonstrate the feasibility of the proposed method. First, a simple rectangular phantom was reproduced on simulation and irradiated with protons for obtaining current values and Monte Carlo (MC) dose. Next, we trained a deep learning model to estimate 2-dimensional-dose range (2D-DL dose) from measured current values for simulation (A). We simulated plastic scintillators as detectors to measure the scattered protons. Second, a rectangular phantom with an air layer was used, and 3D-DL dose was estimated in simulation (B). Finally, a cylindrical phantom that mimics the human body was used for confirming the estimation quality of the simulation (C). Consequently, the position of the Bragg peak was estimated with an error of 1.0 mm in simulation (A). In addition, the position of the air layer, as well as the verifying peak position with an error of 2.1 mm, was successfully estimated in simulation (B). Although the estimation error of the peak position was 12.6 mm in simulation (C), the quality was successfully further improved to 9.3 mm by incorporating the mass density distribution obtained from the computed tomography (CT). These simulation results demonstrated the potential of the as-proposed verification system. Additionally, the effectiveness of CT utilization for estimating the DL dose was also indicated.

The circadian clock CRY1 regulates pluripotent stem cell identity and somatic cell reprogramming.

Distinct metabolic conditions rewire circadian-clock-controlled signaling pathways leading to the de novo construction of signal transduction networks. However, it remains unclear whether metabolic hallmarks unique to pluripotent stem cells (PSCs) are connected to clock functions. Reprogramming somatic cells to a pluripotent state, here we highlighted non-canonical functions of the circadian repressor CRY1 specific to PSCs. Metabolic reprogramming, including AMPK inactivation and SREBP1 activation, was coupled with the accumulation of CRY1 in PSCs. Functional assays verified that CRY1 is required for the maintenance of self-renewal capacity, colony organization, and metabolic signatures. Genome-wide occupancy of CRY1 identified CRY1-regulatory genes enriched in development and differentiation in PSCs, albeit not somatic cells. Last, cells lacking CRY1 exhibit differential gene expression profiles during induced PSC (iPSC) reprogramming, resulting in impaired iPSC reprogramming efficiency. Collectively, these results suggest the functional implication of CRY1 in pluripotent reprogramming and ontogenesis, thereby dictating PSC identity.

Circadian Regulation of Metabolism: Commitment to Health and Diseases.

The circadian clock is a biological timekeeping system to govern temporal rhythms of the endocrine system and metabolism. The master pacemaker of biological rhythms is housed in the hypothalamic suprachiasmatic nucleus (SCN) where approximately 20,000 neurons exist and receive light stimulus as a predominant timed external cue (zeitgeber). The central SCN clock orchestrates molecular clock rhythms in peripheral tissues and coordinates circadian metabolic homeostasis at a systemic level. Accumulated evidence underscores an intertwined relationship between the circadian clock system and metabolism: the circadian clock provides daily dynamics of metabolic activity whereas the circadian clock activity is modulated by metabolic and epigenetic mechanisms. Disruption of circadian rhythms due to shift work and jet lag confounds the daily metabolic cycle, thereby increasing risks of various metabolic diseases, such as obesity and type 2 diabetes. Food intake serves as a powerful zeitgeber to entrain molecular clocks and circadian clock regulation of metabolic pathways, independently of light exposure to the SCN. Thus, the daily timing of food intake rather than the diet quantity and quality contributes to promoting health and preventing disease development through restoring circadian control of metabolic pathways. In this review, we discuss how the circadian clock dominates metabolic homeostasis and how chrononutritional strategies benefit metabolic health, summarizing the latest evidence from basic and translational studies.

Arnold Chiari malformation classified as Chiari 1.5 malformation in a Japanese black calf.

A 2-day-old male black calf presented with neurological symptoms, including opisthotonus. It was unable to stand due to hindquarter paresis. At 5 days old, the calf was able to stand, but exhibited a crossed forelimb gait. Computed tomography and magnetic resonance imaging revealed the expansion of the sutures between the squamous-lateral part of the occipital bone and between the occipital-temporal bone, cerebellar tonsillar herniation, posterior displacement of the brainstem, and cervical syringomyelia at 12 days old. This is the first case report of a live calf diagnosed with Arnold Chiari malformation classified as Chiari type 1.5 malformation in humans.

Enhancing the metabolic benefits of exercise: Is timing the key?

Physical activity represents a potent, non-pharmacological intervention delaying the onset of over 40 chronic metabolic and cardiovascular diseases, including type 2 diabetes, coronary heart disease, and reducing all-cause mortality. Acute exercise improves glucose homeostasis, with regular participation in physical activity promoting long-term improvements in insulin sensitivity spanning healthy and disease population groups. At the skeletal muscle level, exercise promotes significant cellular reprogramming of metabolic pathways through the activation of mechano- and metabolic sensors, which coordinate downstream activation of transcription factors, augmenting target gene transcription associated with substrate metabolism and mitochondrial biogenesis. It is well established that frequency, intensity, duration, and modality of exercise play a critical role in the type and magnitude of adaptation; albeit, exercise is increasingly considered a vital lifestyle factor with a critical role in the entrainment of the biological clock. Recent research efforts revealed the time-of-day-dependent impact of exercise on metabolism, adaptation, performance, and subsequent health outcomes. The synchrony between external environmental and behavioural cues with internal molecular circadian clock activity is a crucial regulator of circadian homeostasis in physiology and metabolism, defining distinct metabolic and physiological responses to exercise unique to the time of day. Optimising exercise outcomes following when to exercise would be essential to establishing personalised exercise medicine depending on exercise objectives linked to disease states. We aim to provide an overview of the bimodal impact of exercise timing, i.e. the role of exercise as a time-giver (zeitgeber) to improve circadian clock alignment and the underpinning clock control of metabolism and the temporal impact of exercise timing on the metabolic and functional outcomes associated with exercise. We will propose research opportunities that may further our understanding of the metabolic rewiring induced by specific exercise timing.

Accidental laceration of the vaginal wall by an intravaginal thermometer as a calving detection device in a Japanese black cow.

An intravaginal thermometer was inserted into a 59-month-old Japanese black cow to predict calving. After calving, the thermometer penetrated the vaginal wall and could not be removed by farm staff. Surgery to remove the thermometer was successful. The cow left the animal hospital without hospitalization. In the follow-up, the cow remained healthy on the farm for more than one year and is now pregnant. No symptoms related to damage to the vagina or infection developed. This is the first case report of a vaginal laceration caused by an intravaginal thermometer in a Japanese black cow. Insertional vaginal devices may cause vaginal lacerations in cattle.

Tryptophan metabolism is a physiological integrator regulating circadian rhythms.

OBJECTIVE: The circadian clock aligns physiology with the 24-hour rotation of Earth. Light and food are the main environmental cues (zeitgebers) regulating circadian rhythms in mammals. Yet, little is known about the interaction between specific dietary components and light in coordinating circadian homeostasis. Herein, we focused on the role of essential amino acids. METHODS: Mice were fed diets depleted of specific essential amino acids and their behavioral rhythms were monitored and tryptophan was selected for downstream analyses. The role of tryptophan metabolism in modulating circadian homeostasis was studied using isotope tracing as well as transcriptomic- and metabolomic- analyses. RESULTS: Dietary tryptophan depletion alters behavioral rhythms in mice. Furthermore, tryptophan metabolism was shown to be regulated in a time- and light- dependent manner. A multi-omics approach and combinatory diet/light interventions demonstrated that tryptophan metabolism modulates temporal regulation of metabolism and transcription programs by buffering photic cues. Specifically, tryptophan metabolites regulate central circadian functions of the suprachiasmatic nucleus and the core clock machinery in the liver. CONCLUSIONS: Tryptophan metabolism is a modulator of circadian homeostasis by integrating environmental cues. Our findings propose tryptophan metabolism as a potential point for pharmacologic intervention to modulate phenotypes associated with disrupted circadian rhythms.

Exercise timing influences multi-tissue metabolome and skeletal muscle proteome profiles in type 2 diabetic patients - A randomized crossover trial.

AIMS/HYPOTHESIS: Metabolic effects of exercise may partly depend on the time-of-day when exercise is performed. We tested the hypothesis that exercise timing affects the adaptations in multi-tissue metabolome and skeletal muscle proteome profiles in men with type 2 diabetes. METHODS: Men fitting the inclusion (type 2 diabetes, age 45-68 years and body mass index 23-33 kg/m2) and exclusion criteria (insulin treatment, smoking, concurrent systemic disease, and regular exercise training) were included in a randomized crossover trial (n = 15). Participants included in this metabolomics and proteomics analysis fully completed all exercise sessions (n = 8). The trial consisted of two weeks of high-intensity interval training (HIT) (three sessions/week) either in the morning (08:00, n = 5) or afternoon (16:45, n = 3), a two-week wash-out period, and an additional two weeks of HIT at the opposing time. Participants and researchers were not blinded to group allocation. Blood, skeletal muscle and subcutaneous adipose tissue were obtained before the first, and after each training period. Broad-spectrum, untargeted proteomic analysis was performed on skeletal muscle, and metabolomic analysis was performed on all biosamples. Differential content was assessed by linear regression and pathway set enrichment analyses were performed. Coordinated metabolic changes across tissues were identified by Spearman correlation analysis. RESULTS: Metabolic and proteomic profiles remained stable after two weeks of HIT, and individual metabolites and proteins were not altered, irrespective of the time of day at which the training was performed. However, coordinated changes in relevant metabolic pathways and protein categories were identified. Morning and afternoon HIT similarly increased plasma diacylglycerols, skeletal muscle acyl-carnitines, and subcutaneous adipose tissue sphingomyelins and lysophospholipids. Acyl-carnitines were central to training-induced metabolic cross-talk across tissues. Plasma carbohydrates, via the penthose phosphate pathway, were increased and skeletal muscle lipids were decreased after morning compared to afternoon HIT. Skeletal muscle lipoproteins were higher, and mitochondrial complex III abundance was lower after morning compared to afternoon HIT. CONCLUSIONS/INTERPRETATION: We provide a comprehensive analysis of a multi-tissue metabolomic and skeletal muscle proteomic responses to training at different times of the day in men with type 2 diabetes. Increased circulating lipids and changes in adipose tissue lipid composition were common between morning and afternoon HIT. However, afternoon HIT increased skeletal muscle lipids and mitochondrial content to a greater degree than morning training. Thus, there is a diurnal component in the metabolomic and proteomic response to exercise in men with type 2 diabetes. The clinical relevance of this response warrants further investigation.

Macrophage Meets the Circadian Clock: Implication of the Circadian Clock in the Role of Macrophages in Acute Lower Respiratory Tract Infection.

The circadian rhythm is a biological system that creates daily variations of physiology and behavior with a 24-h cycle, which is precisely controlled by the molecular circadian clock. The circadian clock dominates temporal activity of physiological homeostasis at the molecular level, including endocrine secretion, metabolic, immune response, coupled with extrinsic environmental cues (e.g., light/dark cycles) and behavioral cues (e.g., sleep/wake cycles and feeding/fasting cycles). The other side of the clock is that the misaligned circadian rhythm contributes to the onset of a variety of diseases, such as cancer, metabolic diseases, and cardiovascular diseases, the acceleration of aging, and the development of systemic inflammation. The role played by macrophages is a key mediator between circadian disruption and systemic inflammation. At the molecular level, macrophage functions are under the direct control of the circadian clock, and thus the circadian misalignment remodels the phenotype of macrophages toward a 'killer' mode. Remarkably, the inflammatory macrophages induce systemic and chronic inflammation, leading to the development of inflammatory diseases and the dampened immune defensive machinery against infectious diseases such as COVID-19. Here, we discuss how the circadian clock regulates macrophage immune functions and provide the potential risk of misaligned circadian rhythms against inflammatory and infectious diseases.

Atlas of exercise metabolism reveals time-dependent signatures of metabolic homeostasis.

Tissue sensitivity and response to exercise vary according to the time of day and alignment of circadian clocks, but the optimal exercise time to elicit a desired metabolic outcome is not fully defined. To understand how tissues independently and collectively respond to timed exercise, we applied a systems biology approach. We mapped and compared global metabolite responses of seven different mouse tissues and serum after an acute exercise bout performed at different times of the day. Comparative analyses of intra- and inter-tissue metabolite dynamics, including temporal profiling and blood sampling across liver and hindlimb muscles, uncovered an unbiased view of local and systemic metabolic responses to exercise unique to time of day. This comprehensive atlas of exercise metabolism provides clarity and physiological context regarding the production and distribution of canonical and novel time-dependent exerkine metabolites, such as 2-hydroxybutyrate (2-HB), and reveals insight into the health-promoting benefits of exercise on metabolism.

Rapid-acting antidepressants and the circadian clock.

A growing number of epidemiological and experimental studies has established that circadian disruption is strongly associated with psychiatric disorders, including major depressive disorder (MDD). This association is becoming increasingly relevant considering that modern lifestyles, social zeitgebers (time cues) and genetic variants contribute to disrupting circadian rhythms that may lead to psychiatric disorders. Circadian abnormalities associated with MDD include dysregulated rhythms of sleep, temperature, hormonal secretions, and mood which are modulated by the molecular clock. Rapid-acting antidepressants such as subanesthetic ketamine and sleep deprivation therapy can improve symptoms within 24 h in a subset of depressed patients, in striking contrast to conventional treatments, which generally require weeks for a full clinical response. Importantly, animal data show that sleep deprivation and ketamine have overlapping effects on clock gene expression. Furthermore, emerging data implicate the circadian system as a critical component involved in rapid antidepressant responses via several intracellular signaling pathways such as GSK3ß, mTOR, MAPK, and NOTCH to initiate synaptic plasticity. Future research on the relationship between depression and the circadian clock may contribute to the development of novel therapeutic strategies for depression-like symptoms. In this review we summarize recent evidence describing: (1) how the circadian clock is implicated in depression, (2) how clock genes may contribute to fast-acting antidepressants, and (3) the mechanistic links between the clock genes driving circadian rhythms and neuroplasticity.

Linking Depression to Epigenetics: Role of the Circadian Clock.

The circadian clock governs multiple biological functions at the molecular level and plays an essential role in providing temporal diversity of behavior and physiology including neuronal activity. Studies spanning the past two decades have deciphered the molecular mechanisms of the circadian clock, which appears to operate as an essential interface in linking cellular metabolism to epigenetic control. Accumulating evidence illustrates that disruption of circadian rhythms through jet lag, shift work, and temporary irregular life-style could lead to depression-like symptoms. Remarkably, abnormal neuronal activity and depression-like behavior appear in animals lacking elements of the molecular clock. Recent studies demonstrate that neuronal and synaptic gene induction is under epigenetic control, and robust epigenetic remodeling is observed under depression and related psychiatric disorders. Thus, the intertwined links between the circadian clock and epigenetics may point to novel approaches for antidepressant treatments, epigenetic therapy, and chronotherapy. In this chapter we summarize how the circadian clock is involved in neuronal functions and depressive-like behavior and propose that potential strategies for antidepressant therapy by incorporating circadian genomic and epigenetic rewiring of neuronal signaling pathways.

Author Correction: Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression.

Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction. To elucidate mechanisms underpinning the effects of short-term TRF, we investigated skeletal muscle and serum metabolic and transcriptomic profiles from 11 men with overweight/obesity after TRF (8 h day-1) and extended feeding (EXF, 15 h day-1) in a randomised cross-over design (trial registration: ACTRN12617000165381). Here we show that muscle core clock gene expression was similar after both interventions. TRF increases the amplitude of oscillating muscle transcripts, but not muscle or serum metabolites. In muscle, TRF induces rhythmicity of several amino acid transporter genes and metabolites. In serum, lipids are the largest class of periodic metabolites, while the majority of phase-shifted metabolites are amino acid related. In conclusion, short-term TRF in overweight men affects the rhythmicity of serum and muscle metabolites and regulates the rhythmicity of genes controlling amino acid transport, without perturbing core clock gene expression.

Performance demonstration of a hybrid Compton camera with an active pinhole for wide-band X-ray and gamma-ray imaging.

X-ray and gamma-ray imaging are technologies with several applications in nuclear medicine, homeland security, and high-energy astrophysics. However, it is generally difficult to realize simultaneous wide-band imaging ranging from a few tens of keV to MeV because different interactions between photons and the detector material occur, depending on the photon energies. For instance, photoabsorption occurs below 100 keV, whereas Compton scattering dominates above a few hundreds of keV. Moreover, radioactive sources generally emit both X-ray and gamma-ray photons. In this study, we develop a "hybrid" Compton camera that can simultaneously achieve X-ray and gamma-ray imaging by combining features of "Compton" and "pinhole" cameras in a single detector system. Similar to conventional Compton cameras, the detector consists of two layers of scintillator arrays with the forward layer acting as a scatterer for high-energy photons (> 200 keV) and an active pinhole for low-energy photons (< 200 keV). The experimental results on the performance of the hybrid camera were consistent with those from the Geant4 simulation. We simultaneously imaged [Formula: see text]Am (60 keV) and [Formula: see text]Cs (662 keV) in the same field of view, achieving an angular resolution of 10[Formula: see text] (FWHM) for both sources. In addition, imaging of [Formula: see text]At was conducted for the application in future nuclear medicine, particularly radionuclide therapy. The initial demonstrative images of the [Formula: see text]At phantom were reconstructed using the pinhole mode (using 79 keV) and Compton mode (using 570 keV), exhibiting significant similarities in source-position localization. We also verified that a mouse injected with 1 MBq of [Formula: see text]At can be imaged via pinhole-mode measurement in an hour.