Miracle-dz/UniFAR-FTUs huggingface dataset:
CB1 receptors down‐regulate a cAMP/Epac2/PLC pathway to silence the nerve terminals of cerebellar granule cells

Cannabinoid receptors mediate short‐term retrograde inhibition of neurotransmitter release, as well as long‐term depression of synaptic transmission at excitatory synapses. The responses of individual nerve terminals in VGLUT1‐pHluorin transfected cerebellar granule cells to cannabinoids have shown that prolonged activation of cannabinoid type 1 receptors (CB1Rs) silences a subpopulation of previously active synaptic boutons. Adopting a combined pharmacological and genetic approach to study the molecular mechanisms of CB1R‐induced silencing, we found that adenylyl cyclase inhibition decreases cAMP levels while it increases the number of silent synaptic boutons and occludes the induction of further silencing by the cannabinoid agonist HU‐210. Guanine nucleotide exchange proteins directly activated by cAMP (Epac proteins) mediate some of the presynaptic effects of cAMP in the potentiation of synaptic transmission. ESI05, a selective Epac2 inhibitor, and U‐73122, the specific inhibitor of phospholipase C (PLC), both augment the number of silent synaptic boutons. Moreover, they abolish the capacity of the Epac activator, 8‐(4‐chlorophenylthio)‐2′‐O‐methyladenosine 3′,5′‐cyclic monophosphate monosodium hydrate, to prevent HU‐210‐induced silencing consistent with PLC signaling lying downstream of Epac2 proteins. Furthermore, Rab3‐interacting molecule (RIM)1α KO cells have many more basally silent synaptic boutons (12.9 ± 3.5%) than wild‐type cells (1.1 ± 0.5%). HU‐210 induced further silencing in these mutant cells, although 8‐(4‐chlorophenylthio)‐2′‐O‐methyladenosine 3′,5′‐cyclic monophosphate monosodium hydrate only awoke the HU‐210‐induced silence and not the basally silent synaptic boutons. This behavior can be rescued by expressing RIM1α in RIM1α KO cells, these cells behaving very much like wild‐type cells. These findings support the hypothesis that a cAMP/Epac/PLC signaling pathway targeting the release machinery appears to mediate cannabinoid‐induced presynaptic silencing.
Kinetic modeling of [18F]VAT, a novel radioligand for positron emission tomography imaging vesicular acetylcholine transporter in non‐human primate brain

Molecular imaging of vesicular acetylcholine transporter (VAChT) in the brain provides an important cholinergic biomarker for the pathophysiology and treatment of dementias including Alzheimer's disease. In this study, kinetics modeling methods were applied and compared for quantifying regional brain uptake of the VAChT‐specific positron emission tomography radiotracer, ((−)‐(1‐(‐8‐(2‐fluoroethoxy)‐3‐hydroxy‐1,2,3,4‐tetrahydronaphthalen‐2‐yl)piperidin‐4‐yl)(4‐fluorophenyl)‐methanone) ([18F]VAT) in macaques. Total volume distribution (VT) estimates were compared for one‐tissue compartment model (1TCM), two‐tissue compartment model (2TCM), Logan graphic analysis (LoganAIF) and multiple linear analysis (MA1) with arterial blood input function using data from three macaques. Using the cerebellum‐hemispheres as the reference region with data from seven macaques, three additional models were compared: reference tissue model (RTM), simplified RTM (SRTM), and Logan graphic analysis (LoganREF). Model selection criterion indicated that a) 2TCM and SRTM were the most appropriate kinetics models for [18F]VAT; and b) SRTM was strongly correlated with 2TCM (Pearson's coefficients r > 0.93, p < 0.05). Test–retest studies demonstrated that [18F]VAT has good reproducibility and reliability (TRV < 10%, ICC > 0.72). These studies demonstrate [18F]VAT is a promising VAChT positron emission tomography tracer for quantitative assessment of VAChT levels in the brain of living subjects.
Size Control of Gold Nanoparticles Synthesized by Laser Ablation in Liquid Media

We investigate the influence of salt, acidic, and basic solutions (citrate, NaOH, and HCl) on the size of gold nanoparticles (AuNPs) synthesized by laser ablation in aqueous media. We found that NP size increases from 3 nm to 13 nm when Zeta potential varies from −100 mV to −10 mV whatever the concentration and the nature of chemical solution are namely, citrate, NaOH, and HCl. These results demonstrated that the final size of gold NPs produced by laser ablation in liquid media is mainly governed by the charge-dependent growth mechanism.
Peripheral Adrenoceptors: The Impetus Behind Glucose Dysregulation and Insulin Resistance

It is now accepted that several pharmacological drug treatments trigger clinical manifestations of glucose dysregulation, such as hyperglycaemia, glucose intolerance and insulin resistance, in part through poorly understood mechanisms. Persistent sympathoadrenal activation is linked to glucose dysregulation and insulin resistance, both of which significantly increase the risk of emergent endocrinological disorders, including metabolic syndrome and type 2 diabetes mellitus. Through the use of targeted mutagenesis and pharmacological methods, preclinical and clinical research has confirmed physiological glucoregulatory roles for several peripheral α‐ and β‐adrenoceptor subtypes. Adrenoceptor isoforms in the pancreas (α2A and β2), skeletal muscle (α1A and β2), liver (α1A & B and β2) and adipose tissue (α1A and β1 & 3) are convincing aetiological targets that account for both immediate and long‐lasting alterations in blood glucose homeostasis. Because significant overlap exists between the therapeutic applications of numerous classes of drugs and their associated adverse side‐effects, a better understanding of peripheral adrenoceptor‐mediated glucose metabolism is thus warranted. Therefore, at the same time as providing a brief review of glucose homeostasis in the periphery, the present review addresses both functional and pathophysiological roles of the mammalian α1, α2, and β‐adrenoceptor isoforms in whole‐body glucose turnover. We highlight evidence relating to the clinical use of common adrenergic drugs and their impacts on glucose metabolism.
Immunohistochemical Evidence for the Presence of Various Kisspeptin Isoforms in the Mammalian Brain

Kisspeptins are small peptides encoded by the Kiss1 gene that have been the focus of intense neuroendocrine research during the last decade. Kisspeptin is now considered to have important roles in the regulation of puberty onset and adult oestrogen‐dependent feedback mechanisms on gonadotrophin‐releasing hormone secretion. Several kisspeptin antibodies have been generated that have enabled an overall view of kisspeptin peptide distribution in the brain of many mammalian species. However, it remains that the distribution of the different kisspeptin isoforms is unclear in the mammalian brain. In the present study, we report on two new N‐terminal‐directed kisspeptin antibodies, one against the mouse kisspeptin‐52 sequence (AC053) and one against the rat kisspeptin‐52 sequence (AC067), and use them to specifically map these long isoforms in the brains of mouse and rat, respectively. Kisspeptin‐52 immunoreactivity was detected in the two main kisspeptin neuronal populations of the rostral periventricular area and arcuate nucleus but not in the dorsomedial hypothahamus. A large number of fibres throughout the ventral forebrain were also labelled with these two antibodies. Finally, a comparison with the most commonly used C‐terminal‐directed kisspeptin antibodies further suggests the presence of shorter kisspeptin fragments in the brain with specific inter‐ and intracellular expression patterns.
Performance evaluation of a high-resolution brain PET scanner using four-layer MPPC DOI detectors

A high-resolution positron emission tomography (PET) scanner, dedicated to brain studies, was developed and its performance was evaluated. A four-layer depth of interaction detector was designed containing five detector units axially lined up per layer board. Each of the detector units consists of a finely segmented (1.2 mm) LYSO scintillator array and an 8 × 8 array of multi-pixel photon counters. Each detector layer has independent front-end and signal processing circuits, and the four detector layers are assembled as a detector module. The new scanner was designed to form a detector ring of 430 mm diameter with 32 detector modules and 168 detector rings with a 1.2 mm pitch. The total crystal number is 655 360. The transaxial and axial field of views (FOVs) are 330 mm in diameter and 201.6 mm, respectively, which are sufficient to measure a whole human brain. The single-event data generated at each detector module were transferred to the data acquisition servers through optical fiber cables. The single-event data from all detector modules were merged and processed to create coincidence event data in on-the-fly software in the data acquisition servers. For image reconstruction, the high-resolution mode (HR-mode) used a 1.2 mm2 crystal segment size and the high-speed mode (HS-mode) used a 4.8 mm2 size by collecting 16 crystal segments of 1.2 mm each to reduce the computational cost. The performance of the brain PET scanner was evaluated. For the intrinsic spatial resolution of the detector module, coincidence response functions of the detector module pair, which faced each other at various angles, were measured by scanning a 0.25 mm diameter 22Na point source. The intrinsic resolutions were obtained with 1.08 mm full width at half-maximum (FWHM) and 1.25 mm FWHM on average at 0 and 22.5 degrees in the first layer pair, respectively. The system spatial resolutions were less than 1.0 mm FWHM throughout the whole FOV, using a list-mode dynamic RAMLA (LM-DRAMA). The system sensitivity was 21.4 cps kBq−1 as measured using an 18F line source aligned with the center of the transaxial FOV. High count rate capability was evaluated using a cylindrical phantom (20 cm diameter × 70 cm length), resulting in 249 kcps in true and 27.9 kcps at 11.9 kBq ml−1 at the peak count in a noise equivalent count rate (NECR_2R). Single-event data acquisition and on-the-fly software coincidence detection performed well, exceeding 25 Mcps and 2.3 Mcps for single and coincidence count rates, respectively. Using phantom studies, we also demonstrated its imaging capabilities by means of a 3D Hoffman brain phantom and an ultra-micro hot-spot phantom. The images obtained were of acceptable quality for high-resolution determination. As clinical and pre-clinical studies, we imaged brains of a human and of small animals.
Long‐Term Effects of Early‐Life Exposure to Environmental Oestrogens on Ovarian Function: Role of Epigenetics

Oestrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is considered that developmental exposure to environmental oestrogens can disrupt neural and reproductive tract development, potentially resulting in long‐term alterations in neurobehaviour and reproductive function. Many chemicals have been shown to have oestrogenic activity, whereas others affect oestrogen production and turnover, resulting in the disruption of oestrogen signalling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on oestrogen‐sensitive target tissues. Hence, alternative mechanisms are assumed to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including oestrogenic chemicals. We suggest that toxicant‐induced changes in epigenetic signatures are important mechanisms underlying the disruption of ovarian follicular development. In addition, we discuss how exposure to environmental oestrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology.
Decreases in Mineralocorticoid but not Glucocorticoid Receptor mRNA Expression During the Short Arctic Breeding Season in Free‐Living Gambel's White‐Crowned Sparrow (Zonotrichia leucophrys gambelii)

The acute stress response in vertebrates is a highly adaptive suite of physiological and behavioural mechanisms that promote survival in the face of deleterious stimuli from the environment. Facultative changes of physiology and behaviour are mediated through changes in circulating levels of glucocorticoids (corticosterone, cortisol) and their subsequent binding to the high‐affinity mineralocorticoid receptor (MR) or the low‐affinity glucocorticoid receptor (GR). Free‐living male wild Gambel's white‐crowned sparrows (Zonotrichia leucophrys gambelii) display annual fluctuations in the stress response with marked attenuation during the transition from the pre‐parental to the parental stage. We investigated whether this rapid reduction in the stress response is mediated through changes in MR and GR mRNA expression in the brain using in situ hybridisation. MR mRNA expression was found to be significantly lower in the hippocampus as the male birds became parental. No changes were observed in GR mRNA expression in the paraventricular nucleus (PVN) or preoptic area (POA) at this time. No significant correlations were found between initial capture levels of corticosterone and GR or MR mRNA expression. No differences were found in basal levels of corticosterone between pre‐parental and parental in birds collected for in situ hybridisation. Stress response data revealed no difference at baseline but reductions in peak levels of corticosterone as birds became parental. These data suggest that changes in MR expression may be important for the regulation of the stress response or behavioural stress sensitivity with respect to promoting parental care and investment.
Investigating the generalisation of an atlas-based synthetic-CT algorithm to another centre and MR scanner for prostate MR-only radiotherapy

There is increasing interest in MR-only radiotherapy planning since it provides superb soft-tissue contrast without the registration uncertainties inherent in a CT–MR registration. However, MR images cannot readily provide the electron density information necessary for radiotherapy dose calculation. An algorithm which generates synthetic CTs for dose calculations from MR images of the prostate using an atlas of 3 T MR images has been previously reported by two of the authors. This paper aimed to evaluate this algorithm using MR data acquired at a different field strength and a different centre to the algorithm atlas. Twenty-one prostate patients received planning 1.5 T MR and CT scans with routine immobilisation devices on a flat-top couch set-up using external lasers. The MR receive coils were supported by a coil bridge. Synthetic CTs were generated from the planning MR images with (sCT1V) and without (sCT) a one voxel body contour expansion included in the algorithm. This was to test whether this expansion was required for 1.5 T images. Both synthetic CTs were rigidly registered to the planning CT (pCT). A 6 MV volumetric modulated arc therapy plan was created on the pCT and recalculated on the sCT and sCT1V. The synthetic CTs’ dose distributions were compared to the dose distribution calculated on the pCT. The percentage dose difference at isocentre without the body contour expansion (sCT–pCT) was ΔDsCT=(0.9±0.8)% and with (sCT1V–pCT) was ΔDsCT1V=(−0.7±0.7)% (mean ± one standard deviation). The sCT1V result was within one standard deviation of zero and agreed with the result reported previously using 3 T MR data. The sCT dose difference only agreed within two standard deviations. The mean ± one standard deviation gamma pass rate was ΓsCT=96.1±2.9% for the sCT and ΓsCT1V=98.8±0.5% for the sCT1V (with 2% global dose difference and 2 mm distance to agreement gamma criteria). The one voxel body contour expansion improves the synthetic CT accuracy for MR images acquired at 1.5 T but requires the MR voxel size to be similar to the atlas MR voxel size. This study suggests that the atlas-based algorithm can be generalised to MR data acquired using a different field strength at a different centre.
DUI histories in intoxicated injured bicyclists

INTRODUCTION It has been well documented that the use of alcohol correlates with injury risk, especially in DUI (driving under the influence) and DWI (driving while intoxicated). Consumption of alcohol in patients presenting with bicycle-related injuries is associated with greater injury severity, longer hospitalization, and higher health care costs. We hypothesized that intoxicated patients operating a bicycle with traumatic injuries have previous DUI or DWI convictions and had lost their privilege to drive a motor vehicle, resorted to bicycling, and had continued alcohol consumption despite negative previous consequences. METHODS We retrospectively collected data on injured bicyclists older than 18 years with positive blood alcohol content levels treated from the period January 2009 to June 2014 at a large Level 1 urban trauma center. We then matched each patient by name and date of birth and were able to obtain public criminal records through the Superior Court of California for the local of county. RESULTS A total of 149 injured bicyclists with positive blood alcohol levels were identified. Their average blood alcohol content was 236.0 mg/dL, and their average age was 41 years. Sixty-six (44.2%) of these patients had prior DUI/DWI convictions with suspension of driving privileges. Ninety-five patients in this group (63.8%) had no health insurance, and 51 patients (34.2%) tested positive for other drugs. Intoxicated bicyclists trended toward longer hospital length compared with nonintoxicated bicyclists (4.60 vs. 3.44 days; p = 0.07). Three (0.02%) of 149 patients were charged with bicycling while intoxicated. CONCLUSION Intoxicated bicyclists involved in trauma are more likely to have a previous DUI/DWI, have other drug use, tend to have longer hospital stays, and are less likely to have insurance. Bicycle safety education and behavior modification targeting DUI/DWI offenders are warranted. In order to promote injury prevention, resources to increase awareness of this underestimated public health issue should be promoted. LEVEL OF EVIDENCE Epidemiologic study, level III.
The Medial Prefrontal Cortex: Coordinator of Autonomic, Neuroendocrine and Behavioural Responses to Stress

Responding to real or potential threats in the environment requires the coordination of autonomic, neuroendocrine and behavioural processes to promote adaptation and survival. These diverging systems necessitate input from the limbic forebrain to integrate and modulate functional output in accordance with contextual demand. In the present review, we discuss the potential role of the medial prefrontal cortex (mPFC) as a coordinator of behavioural and physiological stress responses across multiple temporal and contextual domains. Furthermore, we highlight converging evidence from rodent and human research indicating the necessity of the mPFC for modulating physiological energetic systems to mobilise or limit energetic resources as needed to ultimately promote behavioural adaptation in the face of stress. We review the literature indicating that glucocorticoids act as one of the primary messengers in the reallocation of energetic resources having profound effects locally within the mPFC, as well as shaping how the mPFC acts within a network of brain structures to modulate responses to stress. Finally, we discuss how both rodent and human studies point toward a critical role of the mPFC in the coordination of anticipatory responses to stress and why this distinction is an important one to make in stress neurobiology.
Multiple image x-radiography for functional lung imaging

Detection and visualization of lung tissue structures is impaired by predominance of air. However, by using synchrotron x-rays, refraction of x-rays at the interface of tissue and air can be utilized to generate contrast which may in turn enable quantification of lung optical properties. We utilized multiple image radiography, a variant of diffraction enhanced imaging, at the Canadian light source to quantify changes in unique x-ray optical properties of lungs, namely attenuation, refraction and ultra small-angle scatter (USAXS or width) contrast ratios as a function of lung orientation in free-breathing or respiratory-gated mice before and after intra-nasal bacterial endotoxin (lipopolysaccharide) instillation. The lung ultra small-angle scatter and attenuation contrast ratios were significantly higher 9 h post lipopolysaccharide instillation compared to saline treatment whereas the refraction contrast decreased in magnitude. In ventilated mice, end-expiratory pressures result in an increase in ultra small-angle scatter contrast ratio when compared to end-inspiratory pressures. There were no detectable changes in lung attenuation or refraction contrast ratio with change in lung pressure alone. In effect, multiple image radiography can be applied towards following optical properties of lung air-tissue barrier over time during pathologies such as acute lung injury.
A new affinity approach to isolate Escherichia coli 6S RNA with histidine‐chromatography

6S RNA is an abundant non‐coding RNA in Escherichia coli (E. coli), but its function has not been discovered until recently. The first advance on 6S RNA function was the demonstration of its ability to bind the σ70‐holoenzyme form of RNA polymerase, inhibiting its activity and consequently the transcription process. The growing interest in the investigation of non‐coding small RNAs (sRNA) calls for the development of new methods for isolation and purification of RNA. This work presents an optimized RNA extraction procedure and describes a new affinity chromatography method using a histidine support to specifically purify 6S RNA from other E. coli sRNA species. The RNA extraction procedure was optimized, and a high yield was obtained in the separation of sRNA and ribosomal RNA (rRNA) from total RNA (RNAt). This improved method takes advantage of its simplicity and significant cost reduction, since some complex operations have been eliminated. A purification strategy was also developed to separate 6S RNA from an sRNA mixture. Pure RNA can be advantageously obtained using the histidine‐affinity chromatography method, aiming at its application to structural or functional studies. Copyright © 2010 John Wiley & Sons, Ltd.
In‐Season Resistance Training for High School Football

■オフシーズンの準備 我々が用いているアメリカンフット ボールの年間プログラムにおいて最初 に多量のトレーニングを行う時期は、 一般的にオフシーズン中やプレシーズ ンの準備開始の時点である。 我々の高 校の場合、この期間は前期の間と夏休 み中になる。 ここでは、8~12RMを 3~5セット行う4日間の全身プログ ラムが用いられている。 RMは、各個 人が決められた反復回数(レップ数) を挙上できる最大重量として定義され る(表1)。 この期間の主な目的は、 筋量を増やし、結合組織を強化して、 選手にフットボールシーズンの要求に 対応できるよう準備させることである (11)。 選手のトレーニングの進度をチェッ クするために、1日に2回行う練習を 開始する直前に、筋力や筋持久力、柔 軟性、身体組成、無酸素性能力、ス ピード、アジリティ、パワーなど、関 係のあるフィットネスとパフォーマン スのすべての測定値を徹底的に評価す る(7)。 特異的なテストを表2に挙げる。