bluuebunny/crossref_metadata_2025 huggingface dataset:
Gain of the triceps surae stretch reflex in decerebrate and spinal cats during postural and locomotor activities.
Authors: Bennett D J , De Serres S J , Stein R B
Published: December 2014

1. The triceps surae (TS) stretch reflex was measured in decerebrate cats during crossed extensor stimulation and after spinalization during rhythmic locomotor activity induced by clonidine and manual perineal stimulation. The TS force in response to sinusoidal stretch was measured at a given contraction level before and after deafferentation, and the ‘reflex force’ was computed by subtracting these two responses. Reflex ‘gain’ was computed as the ratio of the reflex and deafferented force responses (a unitless estimate of the open loop feedback gain). 2. Prior to locomotion the spontaneous muscle activity was low (less than 15% of maximum), but the reflex gain was relatively high (close to 1.0 with a 5 Hz stretch). When locomotion commenced the reflex gain was markedly lowered when measured at the same contraction level as before locomotion (25% of the gain prior to locomotion). At higher contraction levels the reflex gain was not significantly increased. The reflex force and EMG responses to stretch increased with the contraction level, but their effect on the total reflex gain was cancelled by an associated increase in the intrinsic muscle stiffness. 3. In the decerebrate cat, during weak tonic contractions (spontaneous), the reflex gain was high and comparable with the gain in the resting spinal cat. However, with increased tonic contractions produced by crossed extensor stimulation the reflex gain dropped. At higher contraction levels the gain was not significantly different from the gain during spinal locomotion. 4. When the frequency of stretch was increased from 3 to 20 Hz, EMG responses to stretch increased, but the reflex force decreased, since a more fused contraction developed with the more frequent reflex activations. Overall, the reflex gain decreased with frequency in both spinal and decerebrate cats. The phase lag of the reflex force, relative to the intrinsic muscle force, increased with increasing frequency, due to reflex delays, with a 180 deg lag occurring between 12 and 18 Hz (tremor frequencies). The mean gain was significantly lower and the phase lag was significantly greater during locomotion than during tonic crossed extensor contractions, suggesting different reflex mechanisms. 5. In conclusion, during locomotion in spinal cats afferent feedback from low frequency ankle movements, similar to those occurring during the normal step cycle, reflexly produces a small but significant fraction of the extensor force (about a quarter of the stretch‐related force modulation). This fraction is remarkably constant at the different contraction levels of the step cycle. Afferent feedback during higher frequency movement is less effective, minimizing the chance of instability and tremor. In contrast during tonic contractions afferent feedback produces half of the total muscle force during perturbations, clearly contributing to the maintenance of posture.
Interaction between intracortical inhibition and facilitation in human motor cortex.
Authors: Ziemann U , Rothwell J C , Ridding M C
Published: December 2014

1. In seven normal subjects, subthreshold transcranial magnetic conditioning stimuli (using a figure‐of‐eight coil) were applied over the motor cortex in order to evoke activity in intracortical neuronal circuits. The net effect on cortical excitability was evaluated by measuring the effect on the size of EMG responses elicited in the abductor digiti minimi (ADM) muscle by a subsequent suprathreshold test stimulus. 2. A single conditioning stimulus suppressed the size of the test response at interstimulus intervals (ISIs) of 1‐4 ms whereas the response was facilitated at ISIs of 6‐20 ms. The facilitation could be augmented if pairs of conditioning stimuli were given. 3. Inhibition and facilitation appeared to have separate mechanisms. The threshold for inhibition (0.7 active motor threshold) was slightly lower than that for facilitation (0.8 active threshold). Similarly, the inhibitory effect was independent of the direction of current flow induced in the cortex by the conditioning shock, whereas facilitation was maximal with posterior‐anterior currents and minimal with lateromedial current. 4. Direct corticospinal effects were probably not responsible for the results since facilitation of cortical test responses could be produced by conditioning stimuli which had no effect on the amplitude of H reflexes elicited in active ADM muscle. 5. Inhibition and facilitation appeared to interact in a roughly linear manner, consistent with separate inputs to a common neurone. 6. We suggest that subthreshold transcranial magnetic stimulation is capable of activating separate populations of excitatory and inhibitory interneurones in the motor cortex.
Co‐ordinated modulation of Ca2+ and K+ currents during ascidian muscle development.
Authors: Greaves A A , Davis A K , Dallman J E , Moody W J
Published: December 2014

1. The development of Ca2+ and K+ currents was studied in ascidian muscle cells at twelve embryonic stages from gastrulation to the mature cell, a period of 24 h. A high degree of co‐ordination occurs between the development of the inwardly rectifying K+ current (IK(IR)), which sets the resting potential, and Ca2+ and outward K+ currents, which determine action potential waveform. 2. At neurulation IK(IR), which had been present since fertilization, begins to decrease, reaching 12% of its previous density in 6 h. IK(IR) then immediately begins to increase again, reaching its previous density in another 6 h. 3. When IK(IR) begins to decrease, a high‐threshold inactivating Ca2+ current and a slowly activating voltage‐gated K+ current appear. 4. When IK(IR) returns to its previous density, two new currents appear: a sustained Ca2+ current with the same voltage dependence, but different conotoxin sensitivity than the inactivating Ca2+ current; and a Ca(2+)‐dependent K+ current, which activates 8‐10 times faster and at potentials 20‐30 mV more negative than the voltage‐dependent K+ current. 5. The transient downregulation of IK(IR) destabilizes the resting potential and causes spontaneous action potentials to occur. Because IK(IR) is absent when only a slowly activating high‐threshold outward K+ current is present, these action potentials are long in duration. 6. The return of IK(IR) and the appearance of the rapidly activating Ca(2+)‐dependent K+ current eventually terminate this activity. The action potentials of the mature cell occur only on stimulation, and are 10 times shorter in duration than those in the immature cell.
Hypoxia increases persistent sodium current in rat ventricular myocytes.
Authors: Ju Y K , Saint D A , Gage P W
Published: December 2014

1. A persistent inward current activated by depolarization was recorded using the whole‐cell, tight seal technique in rat isolated cardiac myocytes. The amplitude of the inward current increased when cells were exposed to a solution with low oxygen tension. 2. The persistent inward current had the characteristics of the persistent Na+ current described previously in rat ventricular myocytes: it was activated at negative potentials (‐70 mV), reversed close to the equilibrium potential for Na+ (ENa), was blocked by TTX and was resistant to inactivation. 3. Persistent single Na+ channel currents activated by long (200‐400 ms) depolarizations were recorded in cell‐attached patches on isolated ventricular myocytes. Hypoxia increased the frequency of opening of the persistent Na+ channels. 4. Persistent Na+ channels recorded during hypoxia had characteristics similar to those of persistent Na+ channels recorded at normal oxygen tensions. They had a null potential at ENa, their amplitude varied with [Na+], they were resistant to inactivation and their mean open time increased with increasing depolarization. 5. The persistent Na+ channels in cell‐attached patches were blocked by TTX (50 microM) in the patch pipette and by lidocaine (100 microM). 6. It was concluded that hypoxia increases the open probability of TTX‐sensitive, inactivation‐resistant Na+ channels. The voltage dependence of these channels, and their greatly increased activity during hypoxia, suggest that they may play an important role in the generation of arrhythmias during hypoxia.
Synaptic input from the retina to the suprachiasmatic nucleus changes with the light‐dark cycle in the Syrian hamster.
Authors: Cui L N , Dyball R E
Published: December 2014

1. Single cell extracellular recordings were made from the suprachiasmatic nucleus (SCN) in urethane‐anaesthetized Syrian hamsters at different times of the light‐dark cycle. Peristimulus time histograms (PSTHs) were created following stimulation of the optic nerve. 2. Both short‐latency (< 50 ms) and long‐latency (> 50 ms) excitatory responses were seen. Almost all inhibitory responses had a short latency. 3. A total of 288 SCN neurones were recorded. Taking all types of response together, 55 (36.9%) of the 149 neurones tested in the dark period responded to optic nerve stimulation while only 23 (16.6%) of the 139 neurones tested in the light period responded. The difference between the proportion of all responsive and non‐responsive neurones in the dark and light periods was highly significant (P < 0.01, Fisher's exact probability test). The difference in the proportion of excitatory responses was also significant (P < 0.01). 4. During the dark period, the mean spontaneous firing rate (5.00 +/‐ 0.88 spikes s‐1; mean +/‐ S.E.M., n = 55) of the responsive cells was significantly higher than that of the non‐responsive cells (2.65 +/‐ 0.33 spikes s‐1; mean +/‐ S.E.M., n = 74; P < 0.01; Student's unpaired t test). 5. Injection of APV (20 mM, 2 microliters, I.C.V.; n = 6), an antagonist for the NMDA receptor, or CNQX (10 mM, 2 microliters, I.C.V.; n = 5), an antagonist of the non‐NMDA receptor, significantly reduced the responses of all the neurones tested. 6. We conclude that there is daily variation in the firing of SCN neurones in vivo and the variation is restricted to those cells receiving optic nerve inputs. The change in the responsiveness of the SCN to optic nerve stimulation at different times of day suggests that there is a rapidly changing cycle of synaptic function in the SCN. The action of the antagonists suggests that the excitatory retinal projections to the SCN which show this variation are mediated by glutamate and that both NMDA and non‐NMDA receptors are involved.
Intestinal blood flow is controlled by both feed arteries and microcirculatory resistance vessels in freely moving rats.
Authors: Fenger-Gron J , Mulvany M J , Christensen K L
Published: December 2014

1. In freely moving rats, intestinal blood flow, aortic blood pressure and blood pressure at the base of mesenteric arcades were measured simultaneously so as to determine the role of feed arteries and of the microcirculation in the control of intestinal vascular resistance. Segmental resistances of feed arteries (Rfeed) and of microcirculatory vessels (Rmicro) were calculated. 2. At rest, Rfeed and Rmicro were 32 and 68%, respectively, of the total intestinal vascular resistance. 3. Injection of noradrenaline (2 micrograms i.v,) increased Rfeed by 151% and Rmicro by 243%. Angiotensin II (400 ng i.v.) did not increase Rfeed significantly, but increased Rmicro by 239%. Conversely, serotonin (15 micrograms i.v.) increased Rfeed by 414% but did not affect Rmicro significantly. 4. Spontaneous physical activity increased Rfeed by 29% and Rmicro by 39%, while sudden environmental stress increased Rfeed by 116% and Rmicro by 129%. Infused noradrenaline (1 microgram min‐1 i.v.) or adrenaline (0.8 microgram min‐1 i.v.) reduced intestinal flow by 21 and 16% respectively, while noradrenaline, but not adrenaline, increased intestinal resistances. 5. alpha 1‐Blockade with prazosin (0.1 mg i.v.) reduced Rfeed and Rmicro by 43 and 16%, respectively. Thereafter, environmental stress decreased Rfeed by 24% while Rmicro was unaffected. Intravenous noradrenaline and adrenaline responses were attenuated. 6. We conclude that in freely moving rats, mesenteric feed arteries, as well as microcirculatory vessels, are true resistance vessels, and that both participate in the control of intestinal blood flow.
4‐aminopyridine activates potassium currents by activation of a muscarinic receptor in feline atrial myocytes.
Authors: Navarro-Polanco R A , Sánchez-Chapula J A
Published: December 2014

1. The effects of 4‐aminopyridine (4‐AP) on action potentials, macroscopic membrane currents and single‐channel recording from cardiac left atrial myocytes of the adult cat were studied using the whole‐cell and cell‐attached configurations of the patch‐clamp technique. 2. 4‐AP (1 mM) produced a hyperpolarization of the resting membrane potential and a shortening of action potential duration. Under voltage‐clamp conditions, we have found that 4‐AP increased a background current and a delayed rectifier outward current. These effects were antagonized by atropine. In addition, both effects seemed to be mediated through a pertussis toxin‐sensitive G protein. 3. The background current induced by 4‐AP displayed properties that are highly similar to those of the inwardly rectifying potassium current activated by acetylcholine (IK(ACh)). The time‐dependent potassium current activated by 4‐AP has kinetic and pharmacological properties different from those of the delayed rectifier potassium current previously identified in cardiac myocytes. 4. The activation of the delayed rectifier‐like potassium current could be explained by the activation of a novel muscarinic receptor subtype in which acetylcholine acts as the antagonist. Another possibility is that 4‐AP activates IK(ACh) in a time‐ and voltage‐dependent manner.
ATP‐gated cation channels (P2X purinoceptors) in trigeminal mesencephalic nucleus neurons of the rat.
Authors: Khakh B S , Humphrey P P , Henderson G
Published: December 2014

1. We have investigated whether receptors for ATP exist on neurones of the trigeminal mesencephalic nucleus (MNV) of the rat using whole‐cell and outside‐out patch‐clamp recording in coronal brainstem slices. 2. With whole‐cell recording, the batch application of ATP, adenosine 5'‐O‐[3‐thiotriphosphate] (ATP gamma S) and alpha,beta methylene adenosine triphosphate (alpha beta meATP) caused concentration‐dependent inward currents in all cells tested (holding potential, ‐62 mV), with EC50 values of 437, 15 and 254 microM, respectively. All three agonist‐evoked currents developed rapidly (rise time, approximately 10‐25 s), desensitized slowly (over approximately 20‐50 s), cross‐desensitized with each other, were associated with an increase in membrane conductance and were attenuated by the application of suramin (30 microM). 3. The inward current evoked by ATP decreased as the membrane potential was made less negative and had a zero current potential of +1.0 +/‐ 3.7 mV. The current‐voltage relationship showed marked inward rectification. 4. Brief flickery single‐channel openings could be resolved in response to ATP (3 microM) in outside‐out membrane patches. Unitary current at ‐82 mV was ‐1.81 +/‐ 0.2 pA, which corresponds to a unitary conductance of 22 pS. 5. We conclude that proprioceptive MNV neurones contain ATP‐gated cation channels. Such P2X purinoceptors may be involved in the processing of proprioceptive information, thus suggesting a potentially important physiological role of ATP.
Molecular determinants of NMDA receptor function in GABAergic neurones of rat forebrain.
Authors: Plant T , Schirra C , Garaschuk O , Rossier J , Konnerth A
Published: December 2014

1. The functional and molecular properties of NMDA receptors (NMDA‐Rs) were studied in single, visually identified GABAergic medial septal neurones of the rat forebrain using patch clamp, fluorometric Ca2+ measurements and the single‐cell reverse transcription‐polymerase chain reaction (RT‐PCR) technique. 2. Large neurones close to the mid‐line of the medial septal region were shown by the expression of mRNA for a form of glutamate decarboxylase (GAD65) to be almost exclusively GABAergic. A variety of NR2 subunit combinations were detected in the same population of neurones. When tested for NR2A‐C, all but one neurone were shown to express mRNA for NR2B. The NR2B subunit mRNA was usually detected together with NR2A or NR2C. mRNA for NR2D was detected in most neurones from a separate batch of cells tested only for this subunit. 3. Single channel measurements in outside‐out patches combined with RT‐PCR on the same cell showed that NMDA‐R channels from these neurones had main single channel conductance levels of 42 pS in 2 mM Ca2+ and 49 pS in 1 mM Ca2+. In addition, a number of other conductance levels were observed, with values in 2 mM Ca2+ of 51, 31, 19 and 13 pS. No clear difference was observed in the pattern of conductance levels displayed by neurones in which different subunit combinations were detected. 4. Whole‐cell agonist‐induced currents were strongly reduced by the NMDA‐R antagonist ifenprodil, at a concentration that mainly affects receptors containing NR2B in recombinant systems. Currents activated by NMDA had a high sensitivity to extracellular Mg2+. 5. The fraction of the total cation current through NMDA‐R that was carried by Ca2+, measured using a combination of patch clamp and fluorometry in neurones loaded with a high concentration of the Ca2+ indicator fura‐2, was found to be approximately 12%. 6. NMDA‐R‐mediated excitatory synaptic currents (EPSCs) had similar time courses to those in neurones in other brain regions. The decay kinetics were biexponential, with respective mean values for the fast (tau f) and slow (tau 8) time constants of 79 and 300 ms at ‐60 mV, and 66 and 284 ms at +40 mV. EPSCs were greatly reduced by ifenprodil (3 microM). 7. In conclusion, NMDA receptors in GABAergic medial septal neurones display a characteristic functional profile. The NR2 subunit mRNA detected and the single channel conductance levels observed suggest that, in addition to NR2B, which is present in nearly all cells, NR2A, NR2C and NR2D are also expressed. However, most of the functional properties of NMDA‐Rs in these neurones, including the strong inhibition by ifenprodil and Mg2+, the high fractional Ca2+ current, and the time course of the synaptic currents, are more consistent with those known for NR2B than for the other NR2 subunits. These results suggest that the NR2B subunit dominates over other NR2 subunits in determining the functional properties of NMDA‐Rs in these neurones.
Renal handling of guanidino compounds in rat and rabbit.
Authors: Levillain O , Marescau B , De Deyn P P
Published: December 2014

1. Guanidino compounds (GCs) have been quantified in different mammalian tissues such as brain, liver, muscle and kidney. The high anatomical heterogeneity of the kidney suggests that GCs could be unevenly distributed along the corticopapillary axis of the kidney in different species. 2. This study was designed to quantify twelve GCs in the different zones of rat and rabbit kidney. The kidneys were sliced and pieces of seven definite zones were weighed and homogenized for further GC extraction. GCs were determined by liquid chromatography. 3. The results indicate that: (1) GCs were unevenly distributed along rat and rabbit kidney; (2) qualitative and quantitative studies proved that each GC shows a particular distribution pattern along the corticopapillary axis for a given species; (3) in rats, alpha‐keto‐delta‐guanidinovaleric acid, guanidinosuccinic acid, creatinine (CTN), methylguanidine and to a lesser extent gamma‐guanidinobutyric acid increased steeply along the inner medulla in parallel to urea, whereas in rabbits, most of the GCs reached a plateau in the inner medulla and remained constant at this level; (4) gamma‐guanidinobutyric acid was specifically found in the rat kidney; (5) argininic acid was higher in rabbit compared with rat kidney; (6) significantly higher levels of homoarginine were found in all zones of the rat kidney compared with the rabbit kidney. 4. The results suggest that: (1) GCs are mostly localized within the nephron segments; (2) an accumulation of GCs in the inner medulla might be explained either by a recycling process or by an intracellular storage as has been reported for urea, amino acids and organic osmolytes; (3) some GCs might be synthesized in nephron segments as reported for arginine (Arg) and guanidinoacetic acid (GAA); (4) several metabolic pathways of the GCs seemed to differ between rat and rabbit; (5) except for creatine, CTN, Arg and GAA, it seems unlikely that GCs might significantly increase the intracellular osmolality.
Modulation of hybrid bass retinal gap junctional channel gating by nitric oxide.
Authors: Lu C , McMahon D G
Published: December 2014

1. To elucidate the role of the nitric oxide (NO) transmitter system in the regulation of gap junctional channel gating, we have examined the effects of the NO donor sodium nitroprusside (SNP) on the electrical synapses of hybrid bass H2‐type horizontal cells. 2. SNP reversibly reduced the macroscopic junctional conductance without significantly changing voltage sensitivity. 3. Kinetic analyses showed that SNP made the voltage‐dependent decay of junctional currents more rapid. 4. Single‐channel data showed that SNP reduced channel open probability by reducing channel open frequency. 5. The action of SNP can be prevented or largely reduced by the NO scavenger, haemoglobin. NO release by SNP solutions was detected directly by a NO sensor. 6. NO appears to modulate the gap junctional conductance by activating the cGMP‐cGMP‐dependent protein kinase G (PKG) pathway. A membrane‐permeable cGMP analogue, 8‐Br‐cGMP, mimics the action of SNP. A soluble guanylate cyclase inhibitor (LY‐83583) and a highly specific cGMP‐dependent protein kinase inhibitor (RKRARKE) blocked the action of NO. 3‐Isobutyl‐1‐methylxanthine (IBMX), a non‐specific phosphodiesterase inhibitor, potentiated the effect of SNP. 7. [Ca2+]i image studies showed that NO donors did not change [Ca2+]i in horizontal cells, suggesting that the regulation of junctional channels by NO is [Ca2+]i independent.
Scrapie infection alters the membrane and synaptic properties of mouse hippocampal CA1 pyramidal neurones.
Authors: Johnston A R , Black C , Fraser J , MacLeod N
Published: December 2014

1. Electrophysiological recordings using conventional intracellular and extracellular techniques were made from the CA1 region of the hippocampus of ME7 scrapie‐infected mice in a brain slice preparation at specific stages during the incubation period of the disease and compared with data obtained from age‐matched control animals. 2. Extracellular field EPSP recordings in the stratum radiatum showed a gradual increase in the effective stimulus threshold and a reduction in amplitude of the response 5 months after inoculation with scrapie. Terminal animals showed a complete loss of the field EPSP. 3. Intracellular recordings from CA1 pyramidal cells of scrapie‐infected animals after 5 months showed that the Schaffer collateral‐evoked EPSP was attenuated, the effective stimulus threshold was increased and the rise time was slower in slices from scrapie‐infected mice than in age‐matched control mice. Inhibitory potentials evoked by the same stimulus also appeared weaker in scrapie‐infected mice at this time. 4. To determine if the mechanisms of transmitter release during low‐frequency stimulation of the Schaffer collaterals were altered in scrapie‐infected mice, paired‐pulse experiments were performed, but failed to show any differences between cells from scrapie‐infected and control animals. 5. Pyramidal cells from scrapie‐infected mice showed depolarized resting potentials and an increased membrane resistance compared with age‐matched control cells. 6. The majority of scrapie‐infected cells were spontaneously active, showing both single spike and bursting activity. The observed bursting activity was abolished and the spontaneous discharge rate of infected cells was markedly reduced by removing the CA3 area from the slice. 7. The action potential of cells from scrapie‐infected mice showed a faster falling phase and larger amplitude fast and medium after‐hyperpolarizations (AHPs) than age‐matched control cells. In response to depolarizing current pulses cells from infected tissue showed a loss of early spike frequency adaptation. 8. Morphological observations of biocytin‐labelled neurones confirmed our recordings were from pyramidal cells and showed that CA1 cells from scrapie‐infected mice after 5 months showed a marked loss of dendritic spines and an abnormal dendritic morphology that included the appearance of vacuolar swellings. 9. The data show that membrane and synaptic abnormalities of the CA1 pyramidal neurones develop around 5 months after intracerebral infection of the mouse hippocampus with ME7 scrapie.
Direct observations of sympathetic cholinergic vasodilatation of skeletal muscle small arteries in the cat.
Authors: Matsukawa K , Shindo T , Shirai M , Ninomiya I
Published: December 2014

1. The aim of this study was to examine the actual changes of the internal diameter (i.d.) of arterial vessels of skeletal muscle evoked by activation of sympathetic cholinergic nerve fibres during stimulation of the hypothalamic defence area in anaesthetized cats. 2. For this purpose, we have used our novel X‐ray TV system for visualizing small arteries (100‐500 microm i.d.) of the triceps surae muscle and larger extramuscular arteries (500‐1400 microm i.d.) of the hindlimb (the femoral (FA), popliteal (PA) and distal caudal femoral (DCFA) arteries). The passage of a contrast medium from the large extramuscular arteries to the smaller intramuscular arteries was serially measured before and during hypothalamic stimulation. 3. Hypothalamic stimulation increased mean arterial blood pressure, heart rate and femoral vascular conductance. The i.d. of FA, PA, and DCFA did not change during the hypothalamic stimulation, whereas the i.d. of small arteries in the triceps surae muscle increased by 48 +/‐ 2% (mean +/‐ S.E.M.) and the cross‐sectional area increased concomitantly by 118%. The maximum increase in i.d. of 78 +/‐ 6%, was observed in arteries of 100‐200 microm. These increases in diameter were markedly reduced by intra‐arterial injection of atropine or by cutting the sciatic nerve, but not by phentolamine and propranolol given together. 4. The vasodilatation evoked by hypothalamic stimulation was seen in almost all the sections of the small arteries observed under control conditions and was distributed along the entire length of the vessel. In addition, the number of arterial vessels that could be detected increased by 42% during hypothalamic stimulation. The newly detected arterial branches, which ranged from 100 to 300 microm in diameter, mostly arose from the branching points. 5. It is concluded that stimulation of sympathetic cholinergic nerve fibres dilates the small arteries of skeletal muscle ranging from 100 to 500 microm, but not the larger extramuscular arteries.
Differential control of the hyperpolarization‐activated current (i(f)) by cAMP gating and phosphatase inhibition in rabbit sino‐atrial node myocytes.
Authors: Accili E A , Redaelli G , DiFrancesco D
Published: December 2014

1. The actions of the phosphatase inhibitor calyculin A on the hyperpolarization‐activated cardiac ‘pacemaker’ current (i(f)) were determined in single cells isolated from the sino‐atrial (SA) node of the rabbit. 2. Cells were incubated for 8 min in Tyrode solution containing calyculin A (0.5 microM) and then superfused with normal Tyrode solution. The mean normalized i(f) measured in eight cells at mid‐activation voltages during and after exposure to calyculin A increased maximally by 47% with a time constant of 466 s, a time much longer than that required for cAMP‐mediated i(f) stimulation (about 8 s). 3. In two‐pulse protocols, calyculin A treatment increased i(f) at full as well as at mid‐activation voltages, indicating a higher i(f) conductance. 4. Measurement of the conductance‐voltage (gf(V)) relation by voltage ramp protocols confirmed a conductance increase by calyculin A, with no significant change in the position of the activation curve on the voltage axis. Data pooled together from ramp and two‐pulse protocols yielded a calyculin A‐induced increase in fully activated i(f) conductance of 39.6 +/‐ 6.4% (n = 16 cells). 5. The positive and negative shift of i(f) voltage dependence in response to beta‐adrenergic (1 microM isoprenaline) and muscarinic stimulation (1 microM acetylcholine), respectively, was preserved after the calyculin A‐induced increase in conductance. The shift of the i(f) activation curve induced by 1 microM isoprenaline was significantly larger in calyculin A‐treated cells (8.8 vs. 5.8 mV). 6. These data indicate that phosphatase inhibition increases i(f) in a manner distinct from the direct cAMP pathway and potentiates the beta‐adrenergic‐mediated i(f) modulation.
Nutritional Epidemiology—There's Life in the Old Dog Yet!
Authors: Potter John D.
Published: December 2014

Consideration is given to the idea that the nutritional epidemiology of cancer is dead, as some in the media have claimed. The basis for the claim does not lie in science nor has anyone with relevant knowledge made such a statement—although that, too, has been claimed. Evidence is adduced for the importance of past achievements of nutritional epidemiology. Attention is similarly drawn to recent contributions. In particular, I note the state of play of cancer and plant foods, fat and breast cancer, meat and cancer, vegetarians, intervention studies, migrant studies, and westernization of diet and lifestyle. Some next steps and some currently important questions are outlined. Cancer Epidemiol Biomarkers Prev; 24(2); 323–30. ©2014 AACR.
Checkpoint Blockade Immunotherapy Relies on T-bet but Not Eomes to Induce Effector Function in Tumor-Infiltrating CD8+ T Cells
Authors: Berrien-Elliott Melissa M. , Yuan Jinyun , Swier Lauryn E. , Jackson Stephanie R. , Chen Collin L. , Donlin Maureen J. , Teague Ryan M.
Published: December 2014

Coinhibitory receptor blockade is a promising strategy to boost T-cell immunity against a variety of human cancers. However, many patients still do not benefit from this treatment, and responders often experience immune-related toxicities. These issues highlight the need for advanced mechanistic understanding to improve patient outcomes and uncover clinically relevant biomarkers of treatment efficacy. However, the T-cell–intrinsic signaling pathways engaged during checkpoint blockade treatment are not well defined, particularly for combination approaches. Using a murine model to study how effector CD8+ T-cell responses to tumors may be enhanced in a tolerizing environment, we identified a critical role for the T-box transcription factor T-bet. Combination blockade of CTLA-4, PD-1, and LAG-3 induced T-bet expression in responding tumor/self-reactive CD8+ T cells. Eradication of established leukemia using this immunotherapy regimen depended on T-bet induction, which was required for IFNγ production and cytotoxicity by tumor-infiltrating T cells, and for efficient trafficking to disseminated tumor sites. These data provide new insight into the success of checkpoint blockade for cancer immunotherapy, revealing T-bet as a key transcriptional regulator of tumor-reactive CD8+ T-cell effector differentiation under otherwise tolerizing conditions. Cancer Immunol Res; 3(2); 116–24. ©2014 AACR.
Effects of MCP-1 Inhibition by Bindarit Therapy in a Rat Model of Polycystic Kidney Disease
Authors: Zoja Carlamaria , Corna Daniela , Locatelli Monica , Rottoli Daniela , Pezzotta Anna , Morigi Marina , Zanchi Cristina , Buelli Simona , Guglielmotti Angelo , Perico Norberto , Remuzzi Andrea , Remuzzi Giuseppe
Published: December 2014

Background/Aims: Experimental and clinical evidence suggested that monocyte chemoattractant protein-1 (MCP-1/CCL2) has a role in the development of interstitial inflammation and renal failure in polycystic kidney disease (PKD). We investigated whether bindarit, an inhibitor of MCP-1/CCL2 synthesis, could influence the evolution of PKD in PCK rats. Methods: PCK rats were treated from 5 to 15 weeks of age with vehicle or bindarit. Sprague-Dawley rats served as control. For in vitro studies, murine podocytes were exposed to albumin with or without bindarit. Results: MCP-1 mRNA was upregulated in the kidney of PCK rats and reduced by bindarit. Treatment limited overexpression of MCP-1 protein by epithelial cells of dilated tubules and cysts, and interstitial inflammatory cells. Excessive renal accumulation of monocytes/macrophages was lowered by bindarit by 41%. Serum creatinine slightly increased in PCK rats on vehicle and was similar to controls after bindarit. Kidney and liver cysts were not affected by treatment. Bindarit significantly reduced progressive proteinuria of PCK rats. The antiproteinuric effect was associated with the restoration of the defective nephrin expression in podocytes of PCK rats. Bindarit limited podocyte foot process effacement and ameliorated slit diaphragm frequency. In cultured podocytes, bindarit reduced MCP-1 production in response to albumin and inhibited albumin-induced cytoskeletal remodeling and cell migration. Conclusion: This study showed that although bindarit did not prevent renal cyst growth, it limited interstitial inflammation and renal dysfunction and reduced proteinuria in PKD. Thus, bindarit could be considered a therapeutic intervention complementary to therapies specifically acting to block renal cyst growth.
Provisional revision of American snapping shrimp allied to Alpheus floridanus Kingsley, 1878 (Crustacea: Decapoda: Alpheidae) with notes on A. floridanus africanus
Authors: BRACKEN-GRISSOM HEATHER D. , FELDER DARRYL L.
Published: December 2014

Alpheus floridanus Kingsley, 1878 has been previously treated as a single, morphologically diverse species with a broad distribution in the eastern and western Atlantic Ocean and eastern Pacific Ocean. However, variations in morphology and color patterns, in addition to genetic evidence, have prompted futher investigation. Morphological characters, including curvature and length of the scaphocerite, number teeth on the incisor process of the mandible, number of pereopodal spines, proportions of the major chela, as well as color patterns, support recognition of several species in the Alpheus floridanus complex. Alpheus floridanus sensu stricto (s.s.) is redescribed based upon a lectotype selected from the former syntypic pair. The mutilated second specimen of the syntypic pair is identified as A. platycheirus Boone, 1927, which is fully redescribed. Three species are described as new: A. hephaestus sp. nov. from the eastern Pacific, and A. roblesi sp. nov. and A. ulalae sp. nov. from the western Atlantic. Morphological comparisions to the eastern Atlantic A. floridanus africanus Balss, 1916 are discussed, however a formal treatment of this subspecies is not the objective of this study. Our proposed taxonomic revisions of the A. floridanus complex are supported in a companion molecular genetic analysis (following paper, this volume).
A FORMAÇÃO CONTINUADA NA REDE MUNICIPAL DE ENSINO DE CORUMBÁ/MS: LIMITES E PERSPECTIVAS
Authors: Sambugari Márcia Regina do Nascimento , Arruda Márcia Ramires de
Published: December 2014

Neste artigo são apresentados alguns dados referentes à pesquisa realizada sobre a formação continuada sob o ponto de vista de professores. Quais cursos são oferecidos aos professores da rede municipal de ensino de Corumbá? Qual a importância desses cursos na visão dos professores? Partindo dessas questões iniciais, o estudo teve como finalidade conhecer a visão de professores que atuam do 1º ao 5º ano do Ensino Fundamental sobre a contribuição dos cursos de formação continuada oferecidos pela Secretaria Executiva de Educação (SEED) de Corumbá, MS, no período de 2008 a 2010. A metodologia da pesquisa pautou-se na revisão de estudos sobre a temática e no levantamento de documentos sobre os cursos de formação continuada oferecidos no período, para a identificação dos cursos e dos professores participantes. Com base nessas informações, foram selecionadas seis professoras que responderam ao questionário elaborado com questões fechadas e abertas. Os dados foram organizados sob forma de quadros e analisados com base na discussão dos autores que abordam a temática investigada. A análise dos dados apontou um empobrecimento dos cursos de formação continuada, principalmente por conta da racionalidade técnica, com um formato que ignora o perfil e as necessidades formativas e culturais das professoras, bem como a realidade de cada escola, ao propor encontros polarizados. Com a pesquisa, buscou-se contribuir para a discussão sobre formação continuada de professores centrada em ações contextualizadas, dinâmicas, críticas e coletivas.http://dx.doi.org/10.14572/nuances.v19i20.984
Translation-Based Chronicles, Twelfth to Thirteenth Centuries. New Sources for the Arabo-Latin Translation Movement in the Iberian Peninsula
Authors: Tischler Matthias M.
Published: December 2014

Within the well-known panorama of the Arabo-Latin translation movement in the Iberian Peninsula from the twelfth century onwards, the transfer of Arabic biographical and historiographical texts into Latin writing is clearly understudied. Earlier research has focussed on the Arabo-Latin transfer of philosophical, scientific and religious texts without taking into account the role of biohistorical material within the history of cultural exchange and entanglements between Muslims and Christians. And even more recent research on Latin historiographical writing has still not been fully aware of these processes of Arabo-Latin transfer and transformation that also exist. The article analyzes three outstanding Arabo-Latin chronicles from the twelfth and thirteenth centuries, the Chronica gothorum Pseudo-Isidoriana, the Chronica latina regum Castellae and Rodrigo Jiménez de Rada’s Historia Arabum, thus examining different types of written and oral transfer of Arabo-Latin historical knowledge and finally introducing the notion of ‘frontier historiography’ to describe these translation-based chronicles.
"Por que aprender isso, professora? " Sentido pessoal e atividade de estudo na psicologia histórico-cultural
Authors: Asbahr Flávia da Silva Ferreira , Souza Marilene Proença Rebello de
Published: December 2014

Esta pesquisa investigou o processo de atribuição de sentido pessoal à atividade de estudo de estudantes do Ensino Fundamental. A referência teórica é a Psicologia Histórico-Cultural. Foi realizada com estudantes de 4ª série de uma escola pública. Os procedimentos metodológicos foram: observação do cotidiano de uma turma; situações orientadas de aprendizagem; grupos focais; entrevistas. Como resultado, buscou-se delimitar a unidade de análise: a relação entre os motivos da atividade de estudo e os fins das ações de estudo. Defende-se a tese de que, para que a aprendizagem escolar ocorra, as ações de estudo dos estudantes devem ter um sentido pessoal correspondente aos motivos e aos significados sociais da atividade de estudo, no sentido da promoção do desenvolvimento humano.
Relações entre significado do trabalho e percepção de suporte para pessoas com deficiência em organizações brasileiras
Authors: Tette Raissa Pedrosa Gomes , Carvalho-Freitas Maria Nivalda de , Oliveira Marcos Santos de
Published: December 2014

Mediante a obrigatoriedade de contratação de pessoas com deficiência advinda com a Lei de Cotas, o processo de inclusão de pessoas com deficiência (PcD) nas organizações brasileiras tem sido permeado por desafios, tanto para as empresas quanto para as próprias PcD. Este trabalho foi desenvolvido com o propósito de verificar a influência da percepção de suporte social e de suporte organizacional no significado do trabalho para PcD. As investigações foram realizadas com uma amostra de 169 pessoas com deficiência que trabalham em organizações de diversos segmentos nas diferentes regiões do Brasil. Concluiu-se que as categorias que melhor descrevem o significado do trabalho concreto das pessoas com deficiência estão associadas à garantia de condições econômicas de sobrevivência e de sustento pessoal e familiar, da estabilidade no emprego, do salário e do progresso social. As percepções de 'Suporte Social no Trabalho' e de 'Suporte Organizacional' são variáveis preditivas do Significado do Trabalho.
Immunohistochemical detection and gene expression of tyrosine hydroxylase and vesicular monoamine transporter type 2 in intrinsic cardiac ganglia of socially isolated rats
Authors: Jovanovic Predrag , Puskas Nela , Stefanovic Bojana , Spasojevic Natasa , Dronjak Sladjana
Published: December 2014

Social isolation induced a significant increase in resting heart rate and
reduction in heart rate variability. Dysfunction of the intrinsic cardiac
nervous system is implicated in the genesis of cardiovascular diseases.
Previous evidence suggests that cardiac ganglia contain noradrenergic
neurons. Thus, immunohistochemical expression of catecholaminesynthesizing
enzyme tyrosine hydroxylase (TH) and vesicular monoamine transporter 2
(VMAT2) were analyzed, as well as the effects of social isolation stress on
mRNA and protein levels of this enzyme and transporter in the intrinsic
cardiac nervous system of adult rats. Our results indicate that cardiac
ganglion neurons express TH and VMAT2 immunoreactivity. Chronic isolated
stress of rats caused a decrease in TH mRNA and VMAT2 mRNA in the neurons of
intrinsic cardiac ganglia. No significant alterations in the protein levels
of TH and VMAT2 were observed in these neurons. These data indicate that the
neurons of intrinsic cardiac ganglia express TH as well as VMAT2 but that
social isolation stress does not change their protein levels.
Effects of pedunculate oak tree vitality on gypsy moth preference and performance
Authors: Milanovic Slobodan , Mihajlovic Ljubodrag , Karadzic Dragan , Jankovsky Libor , Aleksic Predrag , Jankovic-Tomanic Milena , Lazarevic Jelica
Published: December 2014

Gypsy moths and powdery mildew play a significant role in oak decline
processes. However, information is lacking on the effects on the gypsy moth
of impaired tree vitality caused by defoliation or parasite infection. We
assessed how pedunculate oak leaves collected from vigorous, declining, and
infected trees influenced gypsy moth preference and performance (growth and
nutritional indices). We found a negative effect of powdery mildew-infected
leaves on gypsy moth performance, while declining trees had positive effects
on gypsy moth performance and preference. All examined parameters of larvae
fed declining oak leaves were higher than those of larvae fed vigorous oak
leaves. Increased growth on declining oak leaves was caused by both higher
consumption and more efficient food utilization. The results of this research
could help us to better understand multitrophic interactions in complex
communities such as oak forests.
Time-related sex differences in cerebral hypoperfusion-induced brain injury
Authors: Stanojlovic Milos , Gusevac Ivana , Grkovic Ivana , Mitrovic Natasa , Horvat Anica , Drakulic Dunja
Published: December 2014

Although the model of cerebral hypoperfusion in rats has been a matter of
many investigations over the years, the exact intracellular and biochemical
mechanisms that lead to neuron loss and memory decline have not been clearly
identified. In the current study, we examined whether cerebral hypoperfusion
causes changes in hippocampal protein expression of apoptotic markers in the
synaptosomal fraction and neurodegeneration in a time-dependent and
sex-specific manner. Adult male and female Wistar rats were divided into two
main groups, controls that underwent sham operation, and animals subjected to
permanent bilateral occlusion of common carotid arteries. Both male and
female rats were killed 3, 7 or 90 days following the insult. The obtained
results indicate that the peak of processes that lead to apoptosis occured on
postoperative day 7 and that they were more prominent in males, indicating
that neuroprotective effects of certain substances (planned for future
experiments), should be tested at this time point.
Influence of compression speed and deformation percentage on mechanical properties of calcium alginate particles
Authors: Tomovic Natasa , Trifkovic Kata , Rakin Marko , Rakin Marica , Bugarski Branko
Published: December 2014

Hydrogel particles are often used as a carrier for immobilization of enzymes,
polyphenolic antioxidants, whole microbial, plant or mammalian cells. In many
processes, mechanical properties of alginate particles are essential due to
their exposure to mechanical forces in production process. Determination and
improvement of hydrogels mechanical properties is very important in
prevention of the undesirable side effects during the manufacturing process
and product application. The aim of this study was to define the mechanical
properties of single particles submerged in water and in dry conditions using
the compression method between two flat surfaces. The results indicated that
the formulation of alginate beads and water loss during compression have
significant influence on their mechanical behavior and stiffness.
Calcium-alginate particles were produced using an electrostatic droplet
extrusion technique, with an initial sodium alginate concentration of 1.5%w/v
and calcium chloride (2.0% w/v) as gelling solution. The research findings
were used to determine the influence of working conditions, sample
deformation (10-50%) and different compression speeds (1-50mm/min) on
mechanical strength of alginate beads. The Young?s modules and maximal forces
for investigated deformation percentage of the alginate particles were
determined from generated force-displacement and stress-strain curves during
compression.
Ocular manifestations of childhood acute leukemia in a tertiiary level eye centre of Kathmandu, Nepal
Authors: Khadka Deepak , Sharma Ananda , Shrestha Jeevan K , Shrestha Gauri S , Shrestha Pun N , Pant Suresh R , Pant Bidya P
Published: December 2014

Introduction: In some instances, the understanding of the ocular manifestations in childhood leukemia is not only important to establish the diagnosis but also reflects the disease state and prognosis. Objective: To study the ocular manifestations of childhood acute leukemia among the children attending a tertiary-level hospital in Nepal. Materials and methods: A cross-sectional, descriptive study was undertaken at the B.P. Koirala Lions Centre for Ophthalmic Studies (BPKLCOS) and Kanti Children Hospital (KCH), Kathmandu, over a period of one-and-a-half years. Children diagnosed with acute childhood leukemia referred to the BPKLCOS from the Oncology Unit of the KCH and the Emergency Department of the Tribhuvan University Teaching Hospital (TUTH) were included in the study, using a non-probability sampling method. Results:Of the 71 cases with childhood acute leukemia, 55 (77.5%; 95% CI = 66% - 85%) had acute lymphoblastic leukemia(ALL)whereas the other 16 (23%) had acute myeloblastic leukemia (AML). Ocular involvement were seen in 33 cases (46%) and were more frequent in cases of AML as compared to those with ALL (p=0.001, OR 5.0, 95% CI= 1.4 – 17.5). Direct ocular involvement and secondary ocular involvement were observed in 12 (16.9%) and 29 (40.8%) subjects, respectively. Ocular symptoms were present in only 11 cases (15.49%). Cerebro-spinal fluid (CSF) and bone marrow examination in cases with direct ocular involvement showed 10 cases (83.3%) positive for blast cells in the CSF and 6 cases (50%) positive for blast cells in bone marrow. The most common secondary manifestation was retinal haemorrhage, seen in 23 cases (32.4%). Conclusion: In view of the high asymptomatic ocular involvement and the significant visual morbidity, a routine ophthalmic examination is recommended as an integral part of the medical examination in all cases of childhood acute leukemia.DOI: http://dx.doi.org/10.3126/nepjoph.v6i2.11678Nepal J Ophthalmol 2014; 6(12):  pp. 197-204