Miracle-dz/UniFAR-FTUs huggingface dataset:
Characteristics and physiological role of hyperpolarization activated currents in mouse cold thermoreceptors

Hyperpolarization‐activated currents (Ih) are mediated by the expression of combinations of hyperpolarization‐activated, cyclic nucleotide‐gated (HCN) channel subunits (HCN1–4). These cation currents are key regulators of cellular excitability in the heart and many neurons in the nervous system. Subunit composition determines the gating properties and cAMP sensitivity of native Ih currents. We investigated the functional properties of Ih in adult mouse cold thermoreceptor neurons from the trigeminal ganglion, identified by their high sensitivity to moderate cooling and responsiveness to menthol. All cultured cold‐sensitive (CS) neurons expressed a fast activating Ih, which was fully blocked by extracellular Cs+ or ZD7288 and had biophysical properties consistent with those of heteromeric HCN1–HCN2 channels. In CS neurons from HCN1(−/−) animals, Ih was greatly reduced but not abolished. We find that Ih activity is not essential for the transduction of cold stimuli in CS neurons. Nevertheless, Ih has the potential to shape the excitability of CS neurons. First, Ih blockade caused a membrane hyperpolarization in CS neurons of about 5 mV. Furthermore, impedance power analysis showed that all CS neurons had a prominent subthreshold membrane resonance in the 5–7 Hz range, completely abolished upon blockade of Ih and absent in HCN1 null mice. This frequency range matches the spontaneous firing frequency of cold thermoreceptor terminals in vivo. Behavioural responses to cooling were reduced in HCN1 null mice and after peripheral pharmacological blockade of Ih with ZD7288, suggesting that Ih plays an important role in peripheral sensitivity to cold.
Randomized controlled pilot study of mindfulness‐based stress reduction for persistently fatigued cancer survivors

Cancer‐related fatigue (CRF) is one of the most common, persistent, and disabling symptoms associated with cancer and its treatment. Evidence‐based treatments that are acceptable to patients are critically needed. This study examined the efficacy of mindfulness‐based stress reduction (MBSR) for CRF and related symptoms.
Citrobacter rodentium colitis evokes post‐infectious hyperexcitability of mouse nociceptive colonic dorsal root ganglion neurons

To investigate the possible contribution of peripheral sensory mechanisms to abdominal pain following infectious colitis, we examined whether the Citrobacter rodentium mouse model of human E. coli infection caused hyperexcitability of nociceptive colonic dorsal root ganglion (DRG) neurons and whether these changes persisted following recovery from infection. Mice were gavaged with C. rodentium or distilled water. Perforated patch clamp recordings were obtained from acutely dissociated Fast Blue labelled colonic DRG neurons and afferent nerve recordings were obtained from colonic afferents during ramp colonic distensions. Recordings were obtained on day 10 (acute infection) and day 30 (infection resolved). Following gavage, colonic weights, myeloperoxidase (MPO) activity, stool cultures, and histological scoring established that infection caused colitis at day 10 which resolved by day 30 in most tissues. Electrophysiological recordings at day 10 demonstrated hyperexcitability of colonic DRG neurons (40% mean decrease in rheobase, P= 0.02; 50% mean increase in action potential discharge at twice rheobase, P= 0.02). At day 30, the increase in action potential discharge persisted (∼150% increase versus control; P= 0.04). In voltage clamp studies, transient outward (IA) and delayed rectifier (IK) currents were suppressed at day 10 and IA currents remained suppressed at day 30. Colonic afferent nerve recordings during colonic distension demonstrated enhanced firing at day 30 in infected animals. These studies demonstrate that acute infectious colitis evokes hyperexcitability of colonic DRG neurons which persists following resolution of the infection and that suppression of IA currents may play a role. Together, these findings suggest that peripheral pain mechanisms could contribute to post‐infectious symptoms in conditions such as post‐infectious irritable bowel syndrome.
Calcium diffusion enhanced after cleavage of negatively charged components of brain extracellular matrix by chondroitinase ABC

The concentration of extracellular calcium plays a critical role in synaptic transmission and neuronal excitability as well as other physiological processes. The time course and extent of local fluctuations in the concentration of this ion largely depend on its effective diffusion coefficient (D*) and it has been speculated that fixed negative charges on chondroitin sulphate proteoglycans (CSPGs) and other components of the extracellular matrix may influence calcium diffusion because it is a divalent cation. In this study we used ion‐selective microelectrodes combined with pressure ejection or iontophoresis of ions from a micropipette to quantify diffusion characteristics of neocortex and hippocampus in rat brain slices. We show that D* for calcium is less than the value predicted from the behaviour of the monovalent cation tetramethylammonium (TMA), a commonly used diffusion probe, but D* for calcium increases in both brain regions after the slices are treated with chondroitinase ABC, an enzyme that predominantly cleaves chondroitin sulphate glycans. These results suggest that CSPGs do play a role in determining the local diffusion properties of calcium in brain tissue, most likely through electrostatic interactions mediating rapid equilibrium binding. In contrast, chondroitinase ABC does not affect either the TMA diffusion or the extracellular volume fraction, indicating that the enzyme does not alter the structure of the extracellular space and that the diffusion of small monovalent cations is not affected by CSPGs in the normal brain ionic milieu. Both calcium and CSPGs are known to have many distinct roles in brain physiology, including brain repair, and our study suggests they may be functionally coupled through calcium diffusion properties.
Uteroplacental insufficiency causes a nephron deficit, modest renal insufficiency but no hypertension with ageing in female rats

In rats, uteroplacental insufficiency induced by uterine vessel ligation restricts fetal growth and impairs mammary development compromising postnatal growth. In male offspring, this results in a nephron deficit and hypertension which can be reversed by improving lactation and postnatal growth. Here, growth, blood pressure and nephron endowment in female offspring from mothers which underwent bilateral uterine vessel ligation (Restricted) on day 18 of pregnancy were examined. Sham surgery (Control) and a reduced litter group (Reduced at birth to 5, equivalent to Restricted group) were used as controls. Offspring (Control, Reduced, Restricted) were cross‐fostered on postnatal day 1 onto a Control (normal lactation) or Restricted (impaired lactation) mother. Restricted‐on‐Restricted offspring were born small but were of similar weight to Control‐on‐Control by postnatal day 35. Blood pressure was not different between groups at 8, 12 or 20 weeks of age. Glomerular number was reduced in Restricted‐on‐Restricted offspring at 6 months without glomerular hypertrophy. Cross‐fostering a Restricted pup onto a Control dam resulted in a glomerular number intermediate between Control‐on‐Control and Restricted‐on‐Restricted. Blood pressure, along with renal function, morphology and mRNA expression, was examined in Control‐on‐Control and Restricted‐on‐Restricted females at 18 months. Restricted‐on‐Restricted offspring did not become hypertensive but developed glomerular hypertrophy by 18 months. They had elevated plasma creatinine and alterations in renal mRNA expression of transforming growth factor‐β1, collagen IV (α1) and matrix matelloproteinase‐9. This suggests that perinatally growth restricted female offspring may be susceptible to onset of renal injury and renal insufficiency with ageing in the absence of concomitant hypertension.
Comparison of the Tastes of L-Alanine and Monosodium Glutamate in C57BL/6J Wild Type and T1r3 Knockout Mice

Previous research showed that L-alanine and monosodium L-glutamate elicit similar taste sensations in rats. This study reports the results of behavioral experiments designed to compare the taste capacity of C57BL/6J wild type and T1r3- mice for these 2 amino acids. In conditioned taste aversion (CTA) experiments, wild-type mice exhibited greater sensitivity than knockout mice for both L-amino acids, although knockout mice were clearly able to detect both amino acids at 50 mM and higher concentrations. Generalization of CTA between L-alanine and L-glutamate was bidirectionally equivalent for both mouse genotypes, indicating that both substances elicited similar tastes in both genotypes. This was verified by the discrimination experiments in which both mouse genotypes performed at or near chance levels at 75 and 150 mM. Above 150 mM, discrimination performance improved, suggesting the taste qualities of the 2 L-amino acids are not identical. No differences between knockout and wild-type mice in discrimination ability were detected. These results indicate that while the T1r3 receptor is important for tasting L-alanine and L-glutamate, other receptors are also important for tasting these amino acids.
New roles of calsequestrin and triadin in cardiac muscle

Cardiac calsequestrin (Casq2) and triadin are proteins located in specialized areas of the sarcoplasmic reticulum (SR) where the SR forms junctions with the sarcolemma (junctional SR). Casq2, triadin and junctin form a protein complex that is associated with cardiac ryanodine receptor 2 (RyR2) SR Ca2+ release channels. This review highlights new insights of the roles of triadin and Casq2 derived from gene‐targeted knock‐out and knock‐in mouse models that have recently become available. Characterization of the mouse models suggests that Casq2's contribution to SR Ca2+ storage and release during excitation–contraction coupling is largely dispensable. Casq2's primary role appears to be in protecting the heart against premature Ca2+ release and triggered arrhythmias. Furthermore, both cardiac Casq2 and triadin are important for the structural organization of the SR, which had previously not been recognized. In particular, ablation of triadin causes a 50% reduction in the extent of the junctional SR, which results in impaired excitation–contraction coupling at the level of the myocyte. While catecholamines could normalize contractile function by increasing ICa and SR Ca2+ content, it comes at the price of an increased risk for spontaneous Ca2+ releases in triadin knock‐out myocytes and catecholamine‐induced ventricular arrhythmias in triadin knock‐out mice.
Exchange protein activated by cAMP (Epac) mediates cAMP‐dependent but protein kinase A‐insensitive modulation of vascular ATP‐sensitive potassium channels

Exchange proteins directly activated by cyclic AMP (Epacs or cAMP‐GEF) represent a family of novel cAMP‐binding effector proteins. The identification of Epacs and the recent development of pharmacological tools that discriminate between cAMP‐mediated pathways have revealed previously unrecognized roles for cAMP that are independent of its traditional target cAMP‐dependent protein kinase (PKA). Here we show that Epac exists in a complex with vascular ATP‐sensitive potassium (KATP) channel subunits and that cAMP‐mediated activation of Epac modulates KATP channel activity via a Ca2+‐dependent mechanism involving the activation of Ca2+‐sensitive protein phosphatase 2B (PP‐2B, calcineurin). Application of the Epac‐specific cAMP analogue 8‐pCPT‐2′‐O‐Me‐cAMP, at concentrations that activate Epac but not PKA, caused a 41.6 ± 4.7% inhibition (mean ±s.e.m.; n= 7) of pinacidil‐evoked whole‐cell KATP currents recorded in isolated rat aortic smooth muscle cells. Importantly, similar results were obtained when cAMP was elevated by addition of the adenylyl cyclase activator forskolin in the presence of the structurally distinct PKA inhibitors, Rp‐cAMPS or KT5720. Activation of Epac by 8‐pCPT‐2′‐O‐Me‐cAMP caused a transient 171.0 ± 18.0 nm (n= 5) increase in intracellular Ca2+ in Fura‐2‐loaded aortic myocytes, which persisted in the absence of extracellular Ca2+. Inclusion of the Ca2+‐specific chelator BAPTA in the pipette‐filling solution or preincubation with the calcineurin inhibitors, cyclosporin A or ascomycin, significantly reduced the ability of 8‐pCPT‐2′‐O‐Me‐cAMP to inhibit whole‐cell KATP currents. These results highlight a previously undescribed cAMP‐dependent regulatory mechanism that may be essential for understanding the physiological and pathophysiological roles ascribed to arterial KATP channels in the control of vascular tone and blood flow.
Calcium‐activated chloride currents in olfactory sensory neurons from mice lacking bestrophin‐2

Olfactory sensory neurons use a chloride‐based signal amplification mechanism to detect odorants. The binding of odorants to receptors in the cilia of olfactory sensory neurons activates a transduction cascade that involves the opening of cyclic nucleotide‐gated channels and the entry of Ca2+ into the cilia. Ca2+ activates a Cl− current that produces an efflux of Cl− ions and amplifies the depolarization. The molecular identity of Ca2+‐activated Cl− channels is still elusive, although some bestrophins have been shown to function as Ca2+‐activated Cl− channels when expressed in heterologous systems. In the olfactory epithelium, bestrophin‐2 (Best2) has been indicated as a candidate for being a molecular component of the olfactory Ca2+‐activated Cl− channel. In this study, we have analysed mice lacking Best2. We compared the electrophysiological responses of the olfactory epithelium to odorant stimulation, as well as the properties of Ca2+‐activated Cl− currents in wild‐type (WT) and knockout (KO) mice for Best2. Our results confirm that Best2 is expressed in the cilia of olfactory sensory neurons, while odorant responses and Ca2+‐activated Cl− currents were not significantly different between WT and KO mice. Thus, Best2 does not appear to be the main molecular component of the olfactory channel. Further studies are required to determine the function of Best2 in the cilia of olfactory sensory neurons.
Patterns of Alcohol Use among Patients Who Visited Community Emergency Care Services in Southwestern Brazil

Alcohol is among the most frequently consumed drugs worldwide. However, identification and intervention measures for alcohol abuse have not yet been established. This article reports the results of applying the Alcohol Use Disorders Identification Test (AUDIT) in 463 patients from five centers for emergency care community in a large city in the interior of Sao Paulo. The relationship between the AUDIT risk-levels of alcohol use and the socio-demographic variables of individuals seeking treatment between August and November 2010 was also examined. The instrument was administered by seven nurses and six students nurses. Individuals with AUDIT scores ≥07 received brief counseling (BC). The main reasons for seeking emergency care were “headache”, “pain”, and “ill-being”. Among the individuals in the study, 95.9% lived in the municipality where the data was collected, 40.7% had an incomplete elementary school education, and the percentage of alcohol dependence was lower among employed individuals (11.9%). The sample was composed of 61.1%
Resistance exercise‐induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men

We aimed to determine whether exercise‐induced elevations in systemic concentration of testosterone, growth hormone (GH) and insulin‐like growth factor‐1 (IGF‐1) enhanced post‐exercise myofibrillar protein synthesis (MPS) and phosphorylation of signalling proteins important in regulating mRNA translation. Eight young men (20 ± 1.1 years, BMI = 26 ± 3.5 kg m−2) completed two exercise protocols designed to maintain basal hormone concentrations (low hormone, LH) or elicit increases in endogenous hormones (high hormone, HH). In the LH protocol, participants performed a bout of unilateral resistance exercise with the elbow flexors. The HH protocol consisted of the same elbow flexor exercise with the contralateral arm followed immediately by high‐volume leg resistance exercise. Participants consumed 25 g of protein after arm exercise to maximize MPS. Muscle biopsies and blood samples were taken as appropriate. There were no changes in serum testosterone, GH or IGF‐1 after the LH protocol, whereas there were marked elevations after HH (testosterone, P < 0.001; GH, P < 0.001; IGF‐1, P < 0.05). Exercise stimulated a rise in MPS in the biceps brachii (rest = 0.040 ± 0.007, LH = 0.071 ± 0.008, HH = 0.064 ± 0.014% h−1; P < 0.05) with no effect of elevated hormones (P= 0.72). Phosphorylation of the 70 kDa S6 protein kinase (p70S6K) also increased post‐exercise (P < 0.05) with no differences between conditions. We conclude that the transient increases in endogenous purportedly anabolic hormones do not enhance fed‐state anabolic signalling or MPS following resistance exercise. Local mechanisms are likely to be of predominant importance for the post‐exercise increase in MPS.
Testing Turing's five minutes, parallel-paired imitation game

– The purpose of this paper is to consider Turing's two tests for machine intelligence: the parallel‐paired, three‐participants game presented in his 1950 paper, and the “jury‐service” one‐to‐one measure described two years later in a radio broadcast. Both versions were instantiated in practical Turing tests during the 18th Loebner Prize for artificial intelligence hosted at the University of Reading, UK, in October 2008. This involved jury‐service tests in the preliminary phase and parallel‐paired in the final phase. , – Almost 100 test results from the final have been evaluated and this paper reports some intriguing nuances which arose as a result of the unique contest. , – In the 2008 competition, Turing's 30 per cent pass rate is not achieved by any machine in the parallel‐paired tests but Turing's modified prediction: “at least in a hundred years time” is remembered. , – The paper presents actual responses from “modern Elizas” to human interrogators during contest dialogues that show considerable improvement in artificial conversational entities (ACE). Unlike their ancestor – Weizenbaum's natural language understanding system – ACE are now able to recall, share information and disclose personal interests.
Noninvasive detection of intracerebral hemorrhage using near-infrared spectroscopy (NIRS)

Intracerebral Hemorrhage (IH) is an important cause of secondary brain injury in neurosurgical patients. Early identification and treatment improve neurologic outcome. We have tested Near Infrared Spectroscopy (NIRS) as an alternative noninvasive diagnostic tool compared to CT-Scans to detect IH. We prospectively studied 212 patients with neurologic symptoms associated with intracranial pathology before performing a CT-scan. NIRS signals indicated pathologies in 181 cases (sensitivity 0.96; specificity 0.29). In a subgroup of subdural hematomas NIRS detected 45 of 46 hematomas (sensitivity 0.96; specificity 0.79). Identification of intracerebral hemorrhage using NIRS has the potential to allow early treatment, thus possibly avoiding further injury.
Psychometric properties of the Parenting Concerns Questionnaire in cancer survivors with minor and young adult children

Although cancer patients with minor children have become more of a focus of psycho‐oncological research, little is known about specific parenting concerns. Instruments to assess the concerns and worries of parents with cancer are rare. The Parenting Concerns Questionnaire (PCQ) addresses this issue. We analyzed parenting concerns in cancer survivors and evaluated the German version of the PCQ.
Sun-protective Behavior Among High-School and Collegiate Athletes in Los Angeles, CA

ObjectivesTo evaluate the use, knowledge, and perceptions of sun-protective behavior (SPB), among young athletes in Southern California. DesignCross-sectional survey, assessing various measures of SPB, sun exposure, attitudes, and knowledge. Setting and ParticipantsA total of 1006 students from 2 public high schools and 1 public university in the Los Angeles area volunteered. Athlete volunteers were recruited during sports preparticipation examinations. Nonathlete controls were recruited from physical education classes (high school) and from an introductory lecture class (university). Main Outcome MeasuresUse of SPB during sports and nonsports activities, sun exposure, sun-protection knowledge, and attitudes. Results from athletes were compared with those from controls at each site. ResultsOverall rates of SPB were low. During nonsports activities, university athletes had higher rates of sunscreen (37.7% vs. 32.3%, P=0.03) and hat use (34.7% vs. 17%, P<0.001) than did controls. However, university athletes had lower rates of use of long shirts (27.9% vs. 39.8%, P<0.001), long pants (38.8% vs. 63%, P<0.002), and had higher total sun exposure (16.1 vs. 10.1 h/wk, P<0.001). Similar results were seen among the high-school subjects. Despite having good knowledge of the potential dangers of ultraviolet radiation exposure, approximately 1 in 5 subjects overall had experienced a blistering sunburn within the past year. ConclusionsYoung athletes in the Los Angeles area reported low rates of SPB, high levels of ultraviolet radiation exposure, and high rates of sunburns, despite knowing the risks of sun exposure. Specific educational and behavioral interventions should be directed toward improving SPB in this high-risk group.
Characterisation of bipolar cell synaptic transmission in goldfish retina using paired recordings

Direct recordings from the large axon terminals of goldfish retinal bipolar cells (BCs) have revealed detailed information about the properties and regulation of exocytosis at this ribbon‐type synapse. However, the relationship between BC exocytosis and evoked postsynaptic responses in amacrine and ganglion cells is not known. To address this, I have made paired recordings from BC terminals (BCTs) and neurons in the ganglion cell layer (GCL) in goldfish retinal slices. BCT depolarisation evoked short‐latency, AMPA/kainate receptor‐mediated EPSCs in connected GCL neurons. NMDA receptors contributed to the response at +40 mV but not at −60 mV. Evoked EPSCs contained multiple temporal components that differed in their relative amplitudes between pairs. Changing the duration or amplitude of the presynaptic stimulus affected the size and kinetics of the EPSC, with weaker stimuli slowing the EPSC activation rate. Paired‐pulse stimulation caused greater depression of fast than slow EPSC components. A linear relationship was found between the amount of BCT exocytosis, measured via changes in membrane capacitance, and the charge of evoked EPSCs, whether they were mediated by AMPA/kainate receptors alone or in combination with NMDA receptors. In addition, analysis of miniature EPSCs in GCL neurons provided estimates of the quantal content of evoked EPSCs. The results demonstrate the feasibility of using this paired recording system to study synaptic transfer at ribbon synapses, and indicate that both the rapid and sustained phases of BC exocytosis are encoded in the postsynaptic response.
Illness representations, coping, and illness outcomes in people with cancer: a systematic review and meta‐analysis

Cancer is associated with negative health and emotional outcomes in those affected by it, suggesting the need to better understand the psychosocial determinants of illness outcomes and coping. The common sense model is the leading psychological model of self‐regulation in the face of illness and assumes that subjective illness representations explain how people attempt to cope with illness. This systematic review and meta‐analysis examines the associations of the common sense model's illness representation dimensions with health and coping outcomes in people with cancer.