bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of Partially Saturated Non-cohesive Soils
Authors: Świdziński Waldemar , Mierczyński Jacek , Mikos Agata
Published: April 2018

This paper analyses and discusses experimental results of undrained triaxial tests. The tests were performed on non-cohesive partially saturated soil samples subjected to monotonic and cyclic loading. The tests were aimed at determining the influence of saturation degree on soil’s undrained response (shear strength, excess pore pressure generation). The saturation of samples was monitored by checking Skempton’s parameter B. Additionally, seismic P-wave velocity measurements were carried out on samples characterized by various degrees of saturation. The tests clearly showed that liquefaction may also take place in non-cohesive soils that are not fully saturated and that the liquefaction potential of such soils strongly depends on the B parameter.
Influence of hygrothermal condition on dynamic viscoelasticity of Chinese fir (Cunninghamia lanceolata). Part 1: moisture adsorption
Authors: Zhan Tianyi , Jiang Jiali , Lu Jianxiong , Zhang Yaoli , Chang Jianmin
Published: April 2018

The dynamic viscoelasticity of Chinese fir was investigated by dynamic mechanical analysis (DMA), while the influence of the moisture adsorption (MAds) was the focus of the study. The specimens were climatized at 30, 40, 50, 60, 70 and 80°C under two relative humidity (RH) modes. The RHramp mode included 0, 30, 60 and 90% RH with varied ramping rates (0.5, 1.0 and 2.0% RH min−1), while the RHisohume method worked with constant RHs of 30, 60 and 90%, respectively, for 60, 120 or 240 min. During the MAds process, a decrease in stiffness and an increase in damping of the wood were seen and were attributed to the combination of the plasticization, mechano-sorptive (MS) effects and heating. High temperatures accelerate the MAds pace and intensify the plasticization and MS effects. In RHramp experiments, the glass transition RH (RHg) of xylan was visible, as determined by the maximum of damping. The values of RHg varied from 60 to 90% at 50°C or above. In the RHisohume mode, the thermal softening of hemicelluloses and lignin occurred for shorter time periods under more severe hygrothermal (HT) levels between 40–60°C and 70–80°C, respectively. During MAds, the MS effect diminished as the wood approached a new equilibrium moisture content (EMC). The MAds times to new EMCs became shorter at the expense of intensifying the unstable arrangement of the wood cell wall. Severe HT levels led to great residual instabilities in the wood cell wall, which could be evaluated by the relationship between the extent of the MS effect and the difference between the MC and EMC.
A Japanese patient with congenital central hypothyroidism caused by a novel IGSF1 mutation
Authors: Yamaguchi Takeshi , Hothubo Tomoyuki , Morikawa Shuntaro , Nakamura Akie , Mori Toshihiko , Tajima Toshihiro
Published: April 2018

Background:

IGSF1 abnormality causes diverse symptoms, including congenital central hypothyroidism (CCH), prolactin hyposecretion, testicular enlargement and delayed puberty.

Case presentation:

Here, we report a case of a male patient who visited our hospital with a chief complaint of abdominal pain and short stature, in whom we identified a novel IGSF1 mutation. He was closely examined because of chronic constipation since infancy, persistent abdominal pain at 14 years of age and marked short stature (−4.7 standard deviation [SD] for normal Japanese boys). He was diagnosed with CCH. Decreased prolactin (PRL) secretion was also observed. IGSF1 analysis revealed a novel mutation at the splicing donor site (c.2065+1G>A) in intron 11. In silico analysis predicted this mutation to be a non-functional splice donor site. After thyroid hormone replacement, his thyroid function, constipation and growth rate improved.

Conclusions:

This is the first report of a patient in whom constipation and short stature led to a diagnosis of CCH with a novel IGSF1 mutation.
The safety of Lipistart, a medium-chain triglyceride based formula, in the dietary treatment of long-chain fatty acid disorders: a phase I study
Authors: MacDonald Anita , Webster Rachel , Whitlock Matthew , Gerrard Adam , Daly Anne , Preece Mary Anne , Evans Sharon , Ashmore Catherine , Chakrapani Anupam , Vijay Suresh , Santra Saikat
Published: April 2018

Background:

Children with long-chain fatty acid β-oxidation disorders (LCFAOD) presenting with clinical symptoms are treated with a specialist infant formula, with medium chain triglyceride (MCT) mainly replacing long chain triglyceride (LCT). It is essential that the safety and efficacy of any new specialist formula designed for LCFAOD be tested in infants and children.

Methods:

In an open-label, 21-day, phase I trial, we studied the safety of a new MCT-based formula (feed 1) in six well-controlled children (three male), aged 7–13 years (median 9 years) with LCFAOD (very long chain acyl CoA dehydrogenase deficiency [VLCADD], n=2; long chain 3-hydroxyacyl CoA dehydrogenase deficiency [LCHADD], n=2; carnitine acyl carnitine translocase deficiency [CACTD], n=2). Feed 1 (Lipistart; Vitaflo) contained 30% energy from MCT, 7.5% LCT and 3% linoleic acid and it was compared with a conventional MCT feed (Monogen; Nutricia) (feed 2) containing 17% energy from MCT, 3% LCT and 1.1% linoleic acid. Subjects consumed feed 2 for 7 days then feed 1 for 7 days and finally resumed feed 2 for 7 days. Vital signs, blood biochemistry, ECG, weight, height, food/feed intake and symptoms were monitored.

Results:

Five subjects completed the study. Their median daily volume of both feeds was 720 mL (range 500–1900 mL/day). Feed 1 was associated with minimal changes in tolerance, free fatty acids (FFA), acylcarnitines, 3-hydroxybutyrate (3-HB), creatine kinase (CK), blood glucose, liver enzymes and no change in an electrocardiogram (ECG). No child complained of muscle pain or symptoms associated with LCFAOD on either feed.

Conclusions:

This is the first safety trial reported of an MCT formula specifically designed for infants and children with LCFAOD. In this short-term study, it appeared safe and well tolerated in this challenging group.
Crystal structure of N-(3-chlorophenyl)(propan-2-yloxy)carbothioamide, C10H12ClNOS
Authors: Yeo Chien Ing , Tiekink Edward R.T.
Published: April 2018

C10H12ClNOS, monoclinic, P21/n (no. 14), a = 13.2003(12) Å, b = 6.0448(6) Å, c = 13.9403(13) Å, β = 101.9180(10)°, V = 1088.36(18) Å3, Z = 4, R
gt(F) = 0.0291, wR
ref(F
2) = 0.0807, T = 100(2) K.
Acute Effect of Foam Rolling and Dynamic Stretching on Flexibility and Jump Height
Authors: Smith Jason C. , Pridgeon Brooke , Hall MacGregor C.
Published: April 2018

Smith, JC, Pridgeon, B, and Hall, MC. Acute effect of foam rolling and dynamic stretching on flexibility and jump height. J Strength Cond Res 32(8): 2209–2215, 2018—Dynamic stretching (DS) can acutely improve vertical jump (VJ) performance but its effect lasts no more than 5 minutes. Foam rolling (FR), a form of self-myofascial release, can acutely increase range of motion (ROM) with this effect lasting less than 10 minutes. Therefore, the purpose of this study was to evaluate the time course of these effects, separately and combined, on VJ height and ROM. Twenty-nine university students completed 4 different sessions (control, FR, DS, and combo) in a randomized order. After a warm-up and baseline assessments of VJ height and sit-and-reach, participants rested (control) and performed FR, DS, and the combination of FR and DS (combo). Vertical jump height and ROM were assessed every 5 minutes for 20 minutes after treatment. Mean scores at each time point were expressed as a percent change from baseline scores. Immediately after FR, sit-and-reach was significantly greater than control (p = 0.003). Vertical jump height immediately after treatment for DS and combo was significantly greater than the control and FR counterparts (p ≤ 0.002). Vertical jump height for DS and combo was also significantly greater than the control counterpart at 5 minutes after treatment (p < 0.001). At 15 minutes after treatment, the percent change in VJ height for the combo was significantly greater than the control counterpart (p = 0.002). Although FR has no effect on VJ performance, it can acutely increase ROM, but its effect was quickly dissipated. Foam rolling does not seem to enhance VJ height either alone or in combination with DS.
Allometric Grip Strength Norms for American Children
Authors: Kocher Morgan H. , Oba Yukiya , Kimura Iris F. , Stickley Christopher D. , Morgan Charles F. , Hetzler Ronald K.
Published: April 2018

Kocher, MH, Oba, Y, Kimura, IF, Stickley, CD, Morgan, CF, and Hetzler, RK. Allometric grip strength norms for American children. J Strength Cond Res 33(8): 2251–2261, 2019—To develop normative data from a large cohort of American school children (ages 6–18) for unscaled and allometrically scaled handgrip strength data that are uninfluenced by body size (body mass [BM] and stature [Ht]). Data (age, handgrip strength, BM, and Ht) were collected from the 2011–2012 and 2013–2014 National Health and Nutrition Examination Survey databases, resulting in 4,665 cases (2,384 boys and 2,281 girls). Multiple log-linear regressions were used to determine allometric exponents for BM and Ht separately for each age and sex to satisfy the common exponent and group difference principles described by Vanderburgh. Appropriateness of the allometric model was assessed through regression diagnostics, including normality and homoscedasticity of residuals. Allometrically scaled, ratio-scaled, and unscaled grip strength were then correlated with BM and Ht to examine the effectiveness of the procedure in controlling for body size. The data did not allow for development of a common exponent across age and sex that did not violate the common exponent and group difference principles. Correlations between allometrically scaled handgrip strength with BM and Ht were not significant (p ≤ 0.479) and approached zero, unlike correlations of unscaled handgrip strength with BM and Ht (p < 0.001 for all), indicating that allometric scaling was successful in removing the influence of body size. Allometric scaling handgrip strength by age and sex effectively controls for body size (Ht and BM) and perhaps maturation (Ht). The allometric exponents and normative values developed can be used to compare handgrip strength within age and sex while controlling for body size.
Role of Arm Mechanics During Sprint Running: A Review of the Literature and Practical Applications
Authors: Macadam Paul , Cronin John B. , Uthoff Aaron M. , Johnston Michael , Knicker Axel J.
Published: April 2018

THE IMPORTANCE OF ARM ACTION DURING SPRINT RUNNING HAS BEEN AN ONGOING DISCUSSION AMONG PRACTITIONERS. ALTHOUGH SOME COACHES BELIEVE THAT THE ARMS SERVE TO MERELY PROVIDE BALANCE TO THE ROTARY MOMENTUM OF THE LEGS, OTHERS BELIEVE THAT THE ARMS ARE VITAL TO SPRINT RUNNING PERFORMANCE AND CONTRIBUTE TO PROPULSIVE FORCES. ALTHOUGH A LARGE BODY OF RESEARCH HAS BEEN UNDERTAKEN INTO THE EFFECTS OF LEG KINEMATICS AND KINETICS ON SPRINT RUNNING PERFORMANCE, THE ROLE OF ARM ACTION REMAINS AMBIGUOUS AND UNDERINVESTIGATED. THEREFORE, THE PURPOSE OF THIS REVIEW IS TO IMPROVE UNDERSTANDING RELATED TO ARM MECHANICS DURING SPRINT RUNNING AND PROVIDE PRACTICAL CONTEXT GUIDELINES.
VLSI for a new generation of microelectronic coordinate-sensitive etectors with an extended field of analysis for use in mass spectrometry
Authors: Sidorenko V. P. , Radkevich O. I. , Prokofiev Yu. V. , Tayakin Yu. V. , Virozub T. M.
Published: April 2018

The authors have developed a custom VLSI chip for the new generation of MCSD devices — multichip detectors with an extended analysis field and higher technical characteristics, which can be used in elemental analysis devices to simultaneously determine the elements that make up the material with high sensitivity and accuracy in real time.
VLSI chip contains 384 channels with a spatial resolution of 25 microns has been integrated onto a single chip, each channel has a metal anode to collect the electrons as they emerge from the microchannel plate electron multiplier (MCP); a charge sensitive amplifier to produce a digital signal in response to the electron pulse and a 16-bit counter associated with it to accumulate the counts as they arrive and circuitry to read out the data sequentially from all channels in the microcircuit. The VLSI chip is designed according to the design rules standard 1,0 µm CMOS process. The speed of the microcircuit in the counting mode is at least 15 MHz, in the mode of reading information from the counters — more than 10 MHz.
The output from the 16-bit counters on the detectors is presented via an 8-bit port and is read into the control electronics sequentially from each counter in turn in low-byte, high-byte order.
The circuit has been designed in such a way that an arbitrary number of detector chips may be abutted together on a substrate behind the MCP, allowing for long focal plane detectors to be built, limited only by the size of MCPs available.
Formation of specific afferent connections in organotypic slice cultures from rat visual cortex cocultured with lateral geniculate nucleus
Authors: Bolz J , Novak N , Staiger V
Published: April 2018

The development of the cerebral cortex involves the specification of intrinsic circuitry and extrinsic connections, the pattern of inputs and outputs. To investigate the development of a major afferent input to the cortex, we studied the formation of thalamocortical connections in an organotypic culture system. Slices from the lateral thalamus of young rats were cocultured with slices from the visual cortex. Thalamocortical projections in vitro were examined anatomically with fluorescent dyes and physiologically with electrophysiological and optical recording techniques. Axons emerged from thalamic explants radially in all directions. The outgrowth of thalamic fibers and the course of the axonal trajectories were not influenced by the presence of the cocultured cortex. Only those thalamic axons that happened to grow toward the cortical slices invaded their target tissue. Thalamocortical projection cell in vitro had the characteristic morphology of thalamic relay neurons. Cells with the morphology of interneurons were present in thalamic explants, but these neurons did not project to the cocultured cortex. Thalamocortical axons in vitro terminated in their appropriate cortical target layer, formed axonal arbors, and made functional synaptic contacts. Such specific connections between thalamic neurons and their cortical target cells were established regardless of whether thalamocortical axons invaded the cortex from the white matter side or from the pial surface. These results suggest that thalamic projection neurons have an innate mechanism that allows them to recognize their cortical target cells. Thus, intrinsic factors play a significant role in the laminar specification of cortical connections during development.
Synaptic pharmacology of the superior olivary complex studied in mouse brain slice
Authors: Wu SH , Kelly JB
Published: April 2018

The synaptic pharmacology of the lateral superior olive (LSO) and medial nucleus of the trapezoid body (MNTB) was examined in a brain slice preparation of the mouse superior olivary complex (SOC). Physiological responses in SOC were elicited by electrical stimulation of the trapezoid body ipsilateral or contralateral to the recording site, and bilateral interactions were investigated by combined ipsilateral and contralateral stimulation. Pharmacological effects were tested by bath application of amino acid agonists and antagonists. Neurons in MNTB were excited by contralateral stimulation and unaffected by ipsilateral stimulation. Excitatory amino acid (EAA) agonists--kainic acid (KA), quisqualic acid (QA), or L-glutamate-- caused spontaneous firing at low concentrations and eliminated responses at higher concentrations in MNTB. The EAA agonist NMDA had relatively little effect at comparable concentrations. Stimulus- elicited responses were blocked by non-NMDA antagonists 6-cyano-7- nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitro-quinoxaline-2,3-dione (DNQX) and by the nonspecific EAA antagonist kynurenic acid, but were unaffected by the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV). LSO neurons were typically excited by ipsilateral stimulation and inhibited by contralateral stimulation. In LSO, KA, QA, and L- glutamate caused spontaneous firing at low concentrations and eliminated responses at higher concentrations, and NMDA had relatively little effect. Excitatory responses in the vast majority of LSO neurons were blocked by CNQX, DNQX, or kynurenic acid. Some responses were also blocked by APV. LSO neurons were affected by glycine, and contralateral inhibition in LSO was completely blocked by strychnine. NMDA also blocked inhibition in LSO. These results indicate that excitation of both MNTB and LSO neurons is mediated primarily by an EAA neurotransmitter through non-NMDA receptors and that contralateral inhibition of LSO cells is mediated through strychnine-dependent glycine receptors. NMDA receptors may play a role in binaural processing by modulating contralateral inhibitory input to LSO.
Long-term and short-term electrophysiological effects of estrogen on the synaptic properties of hippocampal CA1 neurons
Authors: Wong M , Moss RL
Published: April 2018

The ovarian steroids exert both long-term and short-term actions on neurons involving different cellular mechanisms. We have investigated the long-term and short-term effects of estrogen on the electrophysiological properties of CA1 neurons utilizing intracellular recordings in hippocampal slices prepared from ovariectomized female rats. An in vivo estrogen-priming paradigm was used to examine long- term genomic actions of estrogen. Subcutaneous estrogen injections 2 d prior to recording had no effect on the intrinsic membrane properties of CA1 neurons, but increased synaptic excitability by prolonging the EPSP and inducing repetitive firing in response to Schaffer collateral stimulation. Short-term effects of estrogen that presumedly involve direct membrane interactions were tested by application of steroids directly to the slice. Superfusion of 17 beta-estradiol, but not 17 alpha-estradiol, caused a rapid and reversible increase in the amplitude of the Schaffer collateral-activated EPSP. This potentiation of the EPSP by 17 beta-estradiol still occurred in the presence of the NMDA antagonist 2-amino-5-phosphonovalerate, but was blocked by the non- NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Depolarizing responses to iontophoretic pulses of exogenous glutamate were also potentiated by 17 beta-estradiol, suggesting a post-synaptic site of action. In addition, 17 beta-estradiol potentiated the responses to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainate, and quisqualate, but not NMDA, further implicating non-NMDA receptors in the short-term action of estrogen. In contrast, 17 beta-estradiol had no effect on responses to exogenous GABA or on the Schaffer collateral- induced late IPSP.(ABSTRACT TRUNCATED AT 250 WORDS)
Habenula and thalamus cell transplants mediate different specific patterns of innervation in the interpeduncular nucleus
Authors: Eckenrode TC , Murray M , Haun F
Published: April 2018

Innervation of specific peptidergic and cholinergic compartments of the interpeduncular nucleus (IPN) was investigated using embryonic cell suspension transplants immunoreactive for substance P (SP) and ChAT. In both neonatal and adult host rats, the IPN was first denervated of its normal SP and cholinergic input from the medial habenula by bilateral lesions of the fasciculi retroflexi (FR). In adult hosts, transplants of embryonic habenular cells placed near the denervated IPN mediated a return of the normal pattern of SP staining restricted to habenula- target subnuclei, plus an increase in staining intensity of SP cells intrinsic to the IPN. There was no recovery of ChAT staining. A similar pattern of SP staining resulted following habenular transplants into neonatal hosts, but in addition there was a partial recovery of normal ChAT staining in cholinergic subnuclei and anomalous ChAT staining in normally peptidergic subnuclei. Control transplants of embryonic thalamus cells placed into adult hosts produced a surprising pattern of ChAT staining in the IPN identical to that seen with habenula transplants placed into neonatal hosts; the adult IPN was thus able to support reinnervation mediated by an aberrant cholinergic source while being refractory to its normal habenular cholinergic afferents. This pattern of results implies regulation by the IPN of habenular SP and cholinergic innervation, and some interaction between the maturing normal cholinergic afferents and their targets that is missing when these afferent sources are abnormal.
Habenula and thalamus cell transplants restore normal sleep behaviors disrupted by denervation of the interpeduncular nucleus
Authors: Haun F , Eckenrode TC , Murray M
Published: April 2018

The preceding companion study (Eckenrode et al., 1992) showed that cell suspension transplants of fetal habenula cells placed near the interpeduncular nucleus (IPN) following lesions of the fasciculus retroflexus (FR) restore the normal pattern of substance P (SP) staining in habenular target subnuclei of the IPN in both perinatal and adult hosts, and restore ChAT staining in the IPN of perinatal hosts. Similarly placed transplants of fetal thalamus cells only restore ChAT staining in the IPN of adult hosts. In this study, we examined the functional significance of these restored staining patterns. We used a behavioral measure of the integrity of REM-stage and non-REM-stage sleep, the “flower pot” test, and assayed (1) normal adult rats, (2) FR- lesioned control animals (neonatal or adult operates), (3) animals receiving FR lesions and transplants of fetal habenula cells (perinatal or adult hosts), and (4) animals receiving FR lesions and transplants of fetal thalamus cells (adult hosts). FR lesions decrease markedly the muscle atonia component of REM sleep and reduce duration of sleep episodes. Transplants that restore SP staining in the IPN (habenular transplants into either perinatal or adult lesion hosts) restore normal frequency of REM atonia; transplants that restore ChAT staining (habenular transplants into perinatal hosts or thalamic transplants into adult hosts) restore normal duration of sleep episodes. The number of SP-immunoreactive cells in the transplants predicts recovery of REM atonia, and the number of ChAT cells in habenular (but not thalamic) transplants predicts restoration of sleep duration.(ABSTRACT TRUNCATED AT 250 WORDS)
Neural computations for sound pattern recognition: evidence for summation of an array of frequency filters in an echolocating bat
Authors: Roverud RC
Published: April 2018

Microchiropteran bats use an auditory sonar system for orientation and prey capture. Many bats use highly structured constant-frequency (CF) and frequency-modulated (FM) sonar orientation signals. Mechanisms for sound pattern recognition are important for the perception of these and other types of auditory signals. The processing and recognition of FM sound components appears to be important for certain complex perceptual tasks, including target distance perception. I have conducted behavioral studies using artificial echoes to simulate the conditions of a bat flying toward a target. An innate vocalization response of the bat to the simulated approaching target was used to assess the ability of the bat to analyze the structure of and extract distance information from different types of synthetic FM sound patterns. The bat's performance depended on the structure of the artificial echo. The pattern recognition performance of the bats was similar when they were presented with either a naturally structured artificial CF/FM echo or an artificial CF/FM echo containing an FM component consisting of a series of pure tone steps. The ability of the bats to recognize appropriately the structure of an FM signal constructed from a sequence of pure tones depended on the number of pure tone steps in the series. Noctilio was able to recognize FM sound patterns containing 99 or greater pure tone steps. The minimum required number of pure tone steps could be distributed over different frequency ranges. The bats were able to resolve individual tone steps in the series that were separated by at least 100 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)
Selective loss of hippocampal granule cells following adrenalectomy: implications for spatial memory
Authors: Conrad CD , Roy EJ
Published: April 2018

We examined the effects of long-term adrenalectomy (ADX) on hippocampal anatomy and behavioral learning in two spatial memory tasks. We assessed damage throughout the hippocampus by stereological analysis of the dentate gyrus and Ammon's horn. Rats were ADX or sham operated, and then tested in the Morris water maze 12 weeks after surgery, followed by testing on an eight-arm, alternating-baited radial maze at 22 weeks postsurgery. Animals were killed 7 1/2 months after surgery. ADX rats had selective volume reduction in the dentate gyrus with no changes in pyramidal regions CA1, CA2, CA3, or CA4. Dentate gyrus damage in some cases occurred throughout the entire rostrocaudal extent of the hippocampus. Analysis of corticosterone serum levels, serum Na+/K+ ratios, and body weight gain suggested that individual differences in dentate gyrus damage appear to be due to incomplete adrenalectomies or remaining ectopic tissue. ADX rats were able to learn in both the Morris water maze and eight-arm radial maze, even when the dentate gyrus was severely damaged (80% volume reduction). However, in the Morris water maze, the ADX rats' learning rate was significantly slower compared to controls. There was no difference between ADX and controls during reversal in either task. These data indicate that damage to the dentate gyrus following long-term ADX is severe enough to cause learning impairment in selected learning tasks. Such damage is restricted to the dentate gyrus and can occur throughout the rostrocaudal regions of the hippocampus.
Temporal changes in beta-tubulin and neurofilament mRNA levels after transection of adult rat retinal ganglion cell axons in the optic nerve
Authors: McKerracher L , Essagian C , Aguayo AJ
Published: April 2018

Axons of adult mammalian retinal ganglion cells (RGCs) do not regenerate spontaneously after injury in the optic nerve and show a persistent decrease in the rate of transport of tubulin and neurofilament proteins. To investigate further the expression of cytoskeletal proteins in these axotomized CNS neurons, mRNA levels of beta-tubulin and the 150 kDa neurofilament subunit (NF-M) were measured after interrupting the optic nerve 9 mm from the eye. Northern blots of RNA extracted from whole retinas after optic nerve transection showed that the total level of both of these mRNAs fell after injury. To determine if this decrease was a result of the death of axotomized RGCs or reflected changes in individual neurons, RNA probes were hybridized to radial cryostat sections of normal and axotomized retinas from 1 d to 6 months after injury. Grain counts revealed two trends of tubulin expression in RGCs. An early increase in tubulin mRNAs in the axotomized RGCs was followed by a later decrease. Such an increase in tubulin mRNA levels has been correlated with regenerative growth in other neurons. By 1 week after injury, the beta-tubulin mRNA levels decreased to 70% of the control value. Moreover, the time of this fall coincided with the onset of a marked slowing of cytoskeletal transport that follows injury in the optic nerve. In contrast, NF-M mRNA levels dropped immediately after axotomy, and remained at 80% of the control level. It is suggested that the transient increase in tubulin mRNAs may reflect an early regenerative response whose persistence depends on further growth cone interactions with the substrate.
Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures
Authors: Dawson VL , Dawson TM , Bartley DA , Uhl GR , Snyder SH
Published: April 2018

In addition to mediating several physiological functions, nitric oxide (NO) has been implicated in the cytotoxicities observed following activation of macrophages or excess stimulation of neurons by glutamate. We extend our previous observations of glutamate-stimulated, NO-mediated neurotoxicity in primary cultures of rat fetal cortical, striatal, and hippocampal neurons. Neurotoxicity elicited by either NMDA or sodium nitroprusside (SNP) exhibits a similar concentration- effect relationship and time course. The concentration-effect curve of NMDA-induced neurotoxicity is shifted to the right in the presence of nitro-L-arginine and farther to the right in arginine-free media. The rank order of potency of several NO synthase (NOS) inhibitors in preventing neurotoxicity is the same as the rank order of these compounds in inhibiting NOS, and this inhibition is stereospecific. NMDA neurotoxicity is also prevented by flavoprotein inhibitors and calmodulin inhibitors, fitting with the roles of flavoproteins and calmodulin as NOS regulators. 8-Bromo-cGMP and guanylyl cyclase inhibitors do not affect neurotoxicity, while superoxide dismutase attenuates neurotoxicity. NOS neurons appear to be the source of neurotoxic NO in culture, as lesions of these neurons with 20 microM quisqualate diminish subsequent NMDA neurotoxicity. Moreover, NMDA neurotoxicity develops over time in culture coincident with the expression of NOS. Immunohistochemical localization of NOS in cultures and intact brain demonstrates widespread distribution of the cell processes suggesting that NOS neurons contact the majority of cortical neurons and so could mediate widespread neurotoxicity.
Patterns of increased brain activity indicative of pain in a rat model of peripheral mononeuropathy
Authors: Mao J , Mayer DJ , Price DD
Published: April 2018

Regional changes in brain neural activity were examined in rats with painful peripheral mononeuropathy (chronic constrictive injury, CCI) by using the fully quantitative 14C-2-deoxyglucose (2-DG) autoradiographic technique to measure local glucose utilization rate. CCI rats used in the experiment exhibited demonstrable thermal hyperalgesia and spontaneous pain behaviors 10 d after sciatic nerve ligation when the 2- DG experiment was carried out. In the absence of overt peripheral stimulation, reliable increases in 2-DG metabolic activity were observed in CCI rats as compared to sham-operated rats within extensive brain regions that have been implicated in supraspinal nociceptive processing. These brain regions included cortical somatosensory areas, cingulate cortex, amygdala, ventral posterolateral thalamic nucleus, posterior thalamic nucleus, hypothalamic arcuate nucleus, central gray matter, deep layers of superior colliculus, pontine reticular nuclei, locus coeruleus, parabrachial nucleus, gigantocellular reticular nucleus, and paragigantocellular nucleus. The increase in 2-DG metabolic activity was bilateral in most brain regions of CCI rats. However, somatosensory regions within the thalamus and the cerebral cortex were activated in CCI rats. High levels of 2-DG metabolic activity were observed within the cortical hind limb area, ventral posterolateral thalamic nucleus, and posterior thalamic nucleus contralateral to the ligated sciatic nerve, and these levels were higher than ipsilateral corresponding regions in CCI rats. In addition, patterns of increased neural activity found in the brain of CCI rats showed some similarities and differences to those found in the brain of rats exposed to acute nociception induced by noxious heat or formalin stimulation. Thus, these CCI-induced spontaneous increases in neural activity within extensive brain regions of CCI rats previously implicated in sensory-discriminative and affective-motivational dimensions of pain as well as centrifugal modulation of pain are likely to reflect brain neural processing of spontaneous pain. Implications of increased brain neural activity in mechanisms of neuropathic pain are discussed with emphasis on correlations between spatial patterns of altered brain neural activity and pain-related behaviors in CCI rats and clinical symptoms in neuropathic pain patients.
Motor axons preferentially reinnervate motor pathways
Authors: Brushart TM
Published: April 2018

Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal motor branches and/or muscle, a process termed “preferential motor reinnervation.” Collaterals of a single motor axon often enter both sensory and motor Schwann cell tubes of the distal stump; specificity is generated by pruning collaterals from sensory pathways while maintaining those in motor pathways. Previous experiments in the rat femoral nerve model evaluated reinnervation of the femoral motor branch and quadriceps muscle as a unit. In this study, pathway contributions are analyzed separately by denying muscle contact, or by reinnervating muscle through inappropriate, formerly sensory pathways. Motor axons preferentially reinnervate motor pathways, even when these pathways end blindly in a silicon tube. If the femoral nerve is removed as a graft and reinserted with correct or reversed alignment of the sensory and motor branches, more motoneurons reinnervate muscle through correct motor than through incorrect sensory pathways. Motor pathways thus differ from sensory pathways in ways that survive Wallerian degeneration and transplantation as a graft, and that can be used by regenerating motor axons as a basis for collateral pruning and specificity generation.
The differential expression of 16 NMDA and non-NMDA receptor subunits in the rat spinal cord and in periaqueductal gray
Authors: Tolle TR , Berthele A , Zieglgansberger W , Seeburg PH , Wisden W
Published: April 2018

Diverse arrays of glutamate-gated channels in the spinal cord and associated pathways are partly responsible for sensory input, for altered sensitivity to peripheral stimuli during inflammation, and for generation of motor patterns. The expression of 16 genes, encoding all known subunits for the NMDA receptor (NR1, NR2A to NR2D), AMPA/low- affinity kainate (GluR-A to -D), high-affinity kainate ionotropic receptors (KA-1, -2, GluR-5 to -7) and two orphan receptor subunits (delta-1 and -2) was examined by in situ hybridization in rat lumbar spinal cord, and in the periaqueductal gray. Subunit mRNAs for GluR-A, - B Flip, KA-2, and NR1 were abundant in the dorsal horn, with NR2D lightly expressed. Occasional cells in lamina II contained NR2C mRNA. While the GluR-A gene was preferentially expressed in laminae I and II- outer, GluR-B mRNA was evenly expressed throughout all superficial laminae (I, II-outer, II-inner, and III). Large neurons in laminae IV and V expressed mainly NR1, GluR-C, and to lesser extents the GluR-B, GluR-D, and NR2D genes. Lamina I contained occasional cells expressing the GluR-5 gene, whereas GluR-7 mRNA was present in scattered cells in all superficial laminae. In motor neurons, GluR-B Flip, -C Flip, -D Flip, and NR1 mRNAs were expressed heavily, and those of NR2D and KA-1 weakly. Possibly connected to the RNA editing mechanism, GluR-B was the only subunit whose RNA was concentrated in motor neuron cell nuclei in addition to the cytoplasm. delta-1 and -2 mRNAs were found at low levels throughout the gray matter. NR2A, NR2B, and GluR-6 mRNAs were undetectable. For the periaqueductal gray, prominent mRNAs were GluR-A, -B, and NR1. An en passant observation concerned high levels of NR2C mRNA in the pineal gland.
Cloning and differentiation-induced expression of a murine serotonin1A receptor in a septal cell line
Authors: Charest A , Wainer BH , Albert PR
Published: April 2018

A neuronal cell model endogenously expressing the 5-HT1A receptor, in which to study the function and regulation of this gene, has yet to be identified. We examined murine SN-48 cells, a septum x neuroblastoma fusion cell line that proliferates in a nondifferentiated state but can be induced to differentiate into neurofilament-positive cells following 24–96 hr treatment with 10 microM retinoic acid in low serum. Northern blot analysis demonstrated the presence of a single 10.9 kilobase (kb) 5-HT1A receptor RNA species in differentiated SN-48 cells, which was not detected in undifferentiated SN-48 cells. The presence of receptor RNA in differentiated SN-48 cells correlated with the appearance of functional responses (i.e., pertussis toxin-sensitive inhibition of cAMP accumulation) to 5-HT1A agonists in differentiated but not in undifferentiated cells. In order to verify that the large 10.9 kb RNA species in SN-48 cells truly corresponded to the mouse 5-HT1A receptor RNA, a cDNA fragment from differentiated SN-48 cells was used to clone the corresponding mouse brain cDNA. The 2.4 kb cDNA contained a single open reading frame that displayed high (> 85% predicted amino acid identity) homology to the human and rat 5-HT1A receptor genes. When transfected into receptor-negative Ltk- cells, this cDNA was found to direct expression of a murine 5-HT1A receptor. Thus, we conclude that upon differentiation SN-48 cells express RNA encoding functional 5-HT1A receptors. The SN-48 septal cells will provide a useful cellular model system for investigating aspects of neuronal differentiation leading to the development of sensitivity to serotonergic input.
Glutamate-activated currents in outside-out patches from spiny versus aspiny hilar neurons of rat hippocampal slices
Authors: Livsey CT , Costa E , Vicini S
Published: April 2018

The desensitization rate of non-NMDA glutamate receptors was investigated in outside-out membrane patches obtained from morphologically identified spiny “mossy cells” (SMCs) and aspiny hilar interneurons (AHIs) in young rat hippocampal slices. The fast application of a 1 mM step of L-glutamate for 50–100 msec in the presence of TTX and dizolcipine (MK-801) onto patches excised from these neurons produced large glutamate-activated currents (GACs) that decayed with a single or double exponential time course despite the continued presence of agonist. These desensitization rates of alpha- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate- sensitive receptors differed markedly between patches obtained from the two cell types. The fast time constant of desensitization in AHIs (n = 34) averaged 3.3 +/- 0.93 msec (mean +/- SD), while that of SMCs (n = 57) averaged 6.8 +/- 2.0 msec. Current-voltage relationships of the GACs did not differ between SMCs and AHIs, with comparable reversal potentials and no evidence of inward rectification. We also failed to observe significant Ca2+ permeability in either cell type. However, brief (< 1 msec) pulses of 1 mM glutamate produced rapidly decaying GACs with distinct kinetics in the two neuronal classes. Furthermore, analysis of the single glutamate-activated channel currents in outside- out patches from hilar neurons revealed a larger predominant single- channel current in AHIs versus SMCs. Lastly, we observed a greater sensitivity to cyclothiazide in SMCs versus AHIs, with half-maximal removal of desensitization being 90 mM and 200 mM, respectively. Taken together, these differences in GACs between SMCs and AHIs might indicate a functional correlate to the substantial heterogeneity in the molecular structure of glutamate receptor subunits or might be related to posttranslational modifications of these subunits, perhaps provided by the unique microenvironment in the spines covering SMCs.
Effects of the excitatory amino acid receptor antagonists kynurenate and indole-2-carboxylic acid on behavioral and neurochemical outcome following experimental brain injury
Authors: Smith DH , Okiyama K , Thomas MJ , McIntosh TK
Published: April 2018

The overactivation of the NMDA receptor is thought to be a major contributor to the pathophysiologic sequelae of traumatic brain injury (TBI), which commonly includes memory dysfunction. Uniquely, potentiation of the NMDA receptor is dependent on the binding of glycine to a distinct site on the receptor. Despite the potential role of the NMDA receptor in the development of post-TBI cognitive deficits, no studies to date have evaluated the efficacy of NMDA receptor antagonists on memory dysfunction after brain injury. Moreover, glycine site antagonists have not been employed as potential therapeutic agents in models of TBI. In the present study, we evaluated the effects of two glycine site antagonists, kynurenate (KYNA) and indole-2-carboxylic acid (I2CA), on memory and motor dysfunction, cerebral edema formation, and changes in regional total tissue brain [Na], [K], [Ca], [Mg], and [Zn], following lateral fluid-percussion brain injury in the rat. We found that both KYNA (300 mg/kg) and I2CA (50 mg/kg and 20 mg/kg) administered 15 min postinjury dramatically attenuated trauma-induced cognitive dysfunction (p < 0.01). In addition, both compounds improved neurologic motor deficits measured at 2 weeks following injury (p < 0.05). KYNA (300 mg/kg) reduced edema in the cortex, hippocampus, and thalamus, while I2CA (20 mg/kg) reduced edema formation only in the thalamus. Differential effects of KYNA and I2CA on cation concentrations were also noted. KYNA attenuated the postinjury increase in regional tissue [Ca]; however, it had little effect on other cation concentrations. I2CA reversed the postinjury regional increases in [Na] and decreases in [K], [Mg], and [Zn], but had little effect on [Ca] changes. These results indicate that KYNA and I2CA may have differential, but beneficial effects on both behavioral and neurochemical sequelae of TBI.
Differential expression of Shaw-related K+ channels in the rat central nervous system
Authors: Weiser M , Vega-Saenz de Miera E , Kentros C , Moreno H , Franzen L , Hillman D , Baker H , Rudy B
Published: April 2018

The family of mammalian genes related to the Drosophila Shaker gene, consisting of four subfamilies, is thought to encode subunits of tetrameric voltage-gated K+ channels. There is compelling evidence that subunits of the same subfamily, but not of different subfamilies, form heteromultimeric channels in vitro, and thus, each gene subfamily is postulated to encode components of an independent channel system. In order to identify cells with native channels containing subunits of one of these subfamilies (Shaw-related or ShIII), the cellular distribution of ShIII transcripts was examined by Northern blot analysis and in situ hybridization. Three of four ShIII genes (KV3.1, KV3.2, and KV3.3) are expressed mainly in the CNS. KV3.4 transcripts are also present in the CNS but are more abundant in skeletal muscle. In situ hybridization studies in the CNS reveal discrete and specific neuronal populations that prominently express ShIII mRNAs, both in projecting and in local circuit neurons. In the cerebral cortex, hippocampus, and caudate- putamen, subsets of neurons can be distinguished by the expression of specific ShIII mRNAs. Each ShIII gene exhibits a unique pattern of expression; however, many neuronal populations expressing KV3.1 transcripts also express KV3.3 mRNAs. Furthermore, KV3.4 transcripts are present, albeit at lower levels, in several of the neuronal populations that also express KV3.1 and/or KV3.3 mRNAs, revealing a high potential for heteromultimer formation between the products of three of the four genes. Expression of ShIII cRNAs in Xenopus oocytes was used to explore the functional consequences of heteromultimer formation between ShIII subunits. Small amounts of KV3.4 cRNA, which expresses small, fast-inactivating currents when injected alone, produced fast-inactivating currents that are severalfold larger when coinjected with an excess of KV3.1 or KV3.3 cRNA. This amplification is due to both an increase in single-channel conductance in the heteromultimeric channels and the observation that less than four, perhaps even a single KV3.4 subunit is sufficient to impart fast- inactivating properties to the channel. The oocyte experiments indicate that the apparently limited, low-level expression of KV3.4 in the CNS is potentially significant. The anatomical studies suggest that heteromultimer formation between ShIII proteins might be a common feature in the CNS. Moreover, the possibility that the subunit composition of heteromultimers varies in different neurons should be considered, since the ratios of overlapping signals change from one neuronal population to another. In order to proceed with functional analysis of native ShIII channels, it is important to known which subunit compositions might occur in vivo. The studies presented here provide important clues for the identification of native homo- and heteromultimeric ShIII channels in neurons.
Development of subcellular mRNA compartmentation in hippocampal neurons in culture
Authors: Kleiman R , Banker G , Steward O
Published: April 2018

Neurons possess an RNA transport system that is present in dendrites (but not axons) and sort mRNAs so that some mRNAs are restricted to cell bodies while a few others (like the mRNA for MAP2) are present in dendrites. The present study evaluates when dendrite-specific RNA transport and mRNA sorting into cell body and somatodendritic compartments first appear in developing hippocampal neurons maintained in culture. A 3H-uridine pulse-chase paradigm was used to evaluate transport of newly synthesized RNA from the site of synthesis in the nucleus into the developing neurites. The intracellular distribution of mRNAs encoding actin, tubulin, GAP-43, and MAP2 as well as polyA RNA and rRNA was evaluated by in situ hybridization at different stages of development. Newly synthesized RNA was translocated into both developing axons and dendrites early in development, but only into dendrites as the neurons matured. Tubulin, GAP-43, and actin mRNAs, which are restricted to cell bodies in mature neurons, were found exclusively in neuronal cell bodies at all developmental stages. MAP2 mRNA, which is present in the dendrites of mature neurons, was present at very low levels in neurons at 2 or 3 d in culture and was not detectable within dendrites. The overall levels of MAP2 mRNA increased over time, and by 5–7 d in culture, MAP2 mRNA was detectable in some dendrites. PolyA RNA and rRNA were detectable in developing neurites including axons. Levels of polyA and rRNA increased in dendrites as neurons matured while labeling of axons diminished. By 10 d in culture, axonal labeling for polyA and rRNA had virtually disappeared. The increase in the levels of polyA, rRNA, and MAP2 mRNA in dendrites between 5 and 7 d in culture corresponds roughly with the appearance of other dendritic characteristics and the beginning of dendritic outgrowth.