Effect of active immunization against growth hormone releasing factor on concentrations of somatotropin and insulin-like growth factor I in lactating beef cows

Two experiments were conducted to determine the effects of immunoneutralization of growth hormone-releasing factor [GRF(1–29)-NH2] on concentrations of somatotropin (ST) and insulin-like growth factor I (IGF-I) in lactating beef cows. In Experiment 1, multiparous Hereford cows were immunized against 2 mg GRF(1–29)-(Gly)4-Cys-NH2 conjugated to human serum albumin (GRFi, n=3) or 2 mg human serum albumin (HSAi, n=3) at 52 ± 1 d prior to parturition. Boosters (1 mg) were administered on days 12, 40 and 114 postpartum (pp). Serum samples were collected at 15-min intervals for 5 hr on days 18, 46 and 120 pp, followed by administration (IV) of an opioid agonist (FK33-824; 10 μg/kg) and an antagonist (naloxone; .5 mg/kg) at hours 5 and 7, respectively. A GRF-analog ([desamino-Tyr1, D-Ala2, Ala15] GRF (1–29)-NH2; 3.5 μg/kg) and arginine (.5 g/kg) were administered at hour 10 on days 47 and 121, respectively. Percentage binding of [125I]GRF (1:100 dilution of serum) 28 d after primary immunization was greater in GRFi (14.3 ± 4.9) than in HSAi (.7 ± .3) cows. Binding increased to 29.3 ± 6.5% after first booster in GRFi cows. Episodic release of ST was abolished by immunization against GRF; concentration and frequency of release of ST were lower (P125I]GRF, absence of pulsatile release of ST, low concentrations of ST and IGF-I and failure of ST to increase after IV opioid agonist or arginine

Evaluating the sensitivity of hybridization-based epigenotyping using a methyl binding domain protein

Hypermethylation of CpG islands in gene promoter regions has been shown to be a predictive biomarker for certain diseases. Most current methods for methylation profiling are not well-suited for clinical analysis. Here, we report the development of an inexpensive device and an epigenotyping assay with a format conducive to multiplexed analysis.David H. Koch Institute for Integrative Cancer Research at MIT (First-year Graduate Fellowship)National Science Foundation (U.S.). Graduate Research FellowshipBurroughs Wellcome Fund (Career Award at the Scientific Interface)National Institute of Environmental Health Sciences (Grant P30-ES002109)Massachusetts Institute of Technology. James H. Ferry Fund for Innovation in Research Educatio

The Impact of the Laterality on Radiographic Outcomes of the Bernese Periacetabular Osteotomy

The purpose of this study was to compare the pre and postoperative radiographic findings and analyze the complication rate with respect to the laterality in periacetabular osteotomy in right-handed surgeons. Satisfaction rate and radiographic findings were prospectively collected between 2017 and 2019 and retrospectively reviewed. For analysis, all measurements of the CT scans were performed by a musculoskeletal fellowship-trained radiologist. Complications were classified into two categories: perioperative or postoperative. All surgeries were performed by three right-hand dominant hip surgeons. A total of 41 dysplastic hips (25 right and 16 left hips) in 33 patients were included. Postoperatively, a significantly lower acetabular index angle on the left side was observed at -2.6 +/- 4.3 as compared to the right side at 1.6 +/- 6.5 (p < 0.05). The change in Center edge (CE) angle was significantly lower for the left side 13.7 +/- 5.5 degrees than on the right side, measured at 18.4 +/- 7.3 (p < 0.001); however, the overall CE angle was comparable at 38.5 +/- 8.9 degrees without any significant difference between the operated hips (left side at 37.8 +/- 6.1 degrees versus right side at 39.0 +/- 10.3; p = 0.340). No significant differences in other radiographic measurements or surgical time were observed. For complications, the right side was more commonly affected, which may also explain a higher satisfaction rate in patients who were operated on the left hip with 92.3%. The change in lateral CE angle was significantly lower for the left side and the right hip seems to be predisposed to complications, which correlate with a lower satisfaction rate in right-handed surgeons

The Impact of Hip Dysplasia on CAM Impingement

Predisposing factors for CAM-type femoroacetabular impingement (FAI) include acetabular protrusion and retroversion; however, nothing is known regarding development in dysplastic hips. The purpose of this study was to determine the correlation between CAM-type FAI and developmental dysplastic hips diagnosed using X-ray and rotational computed tomography. In this retrospective study, 52 symptomatic hips were included, with a mean age of 28.8 +/- 7.6 years. The inclusion criteria consisted of consecutive patients who suffered from symptomatic dysplastic or borderline dysplastic hips and underwent a clinical examination, conventional radiographs and rotational computed tomography. Demographics, standard measurements and the rotational alignments were recorded and analyzed between the CAM and nonCAM groups. Among the 52 patients, 19 presented with CAM impingement, whereas, in 33 patients, no signs of CAM impingement were noticed. For demographics, no significant differences between the two groups were identified. On conventional radiography, the acetabular hip index as well as the CE angle for the development of CAM impingement were significantly different compared to the nonCAM group with a CE angle of 21.0 degrees +/- 5.4 degrees vs. 23.7 degrees +/- 5.8 degrees (p = 0.050) and an acetabular hip index of 25.6 +/- 5.7 vs. 21.9 +/- 7.3 (p = 0.031), respectively. Furthermore, a crossing over sign was observed to be more common in the nonCAM group, which is contradictory to the current literature. For rotational alignment, no significant differences were observed. In dysplastic hips, the CAM-type FAI correlated to a lower CE angle and a higher acetabular hip index. In contrast to the current literature, no significant correlations to the torsional alignment or to crossing over signs were observed

Ontogeny of synaptophysin and synaptoporin in the central nervous system

The expression of the synaptic vesicle antigens synaptophysin (SY) and synaptoporin (SO) was studied in the rat striatum, which contains a nearly homogeneous population of GABAergic neurons. In situ hybridization revealed high levels of SY transcripts in the striatal anlage from embryonic day (E) 14 until birth. In contrast. SO hybridization signals were low, and no immunoreactive cell bodies were detected at these stages of development. At E 14, SY-immunoreactivity was restricted to perikarya. In later prenatal stages of development SY-immunoreactivity appeared in puncta (identified as terminals containing immunostained synaptic vesicles), fibers, thick fiber bundles and ‘patches’. In postnatal and adult animals, perikarya of striatal neurons exhibited immunoreaction for SO; ultrastructurally SO antigen was found in the Golgi apparatus and in multivesicular bodies. SO-positive boutons were rare in the striatum. In the neuropil, numerous presynaptic terminals positive for SY were observed. Our data indicate that the expression of synaptic vesicle proteins in GABAergic neurons of the striatum is developmentally regulated. Whereas SY is prevalent during embryonic development, SO is the major synaptic vesicle antigen expressed postnatally by striatal neurons which project to the globus pallidus and the substantia nigra. In contrast synapses of striatal afferents (predominantly from cortex, thalamus and substantia nigra) contain SY

Consistency and diversity of spike dynamics in the neurons of bed nucleus of Stria Terminalis of the rat: a dynamic clamp study

Neurons display a high degree of variability and diversity in the expression and regulation of their voltage-dependent ionic channels. Under low level of synaptic background a number of physiologically distinct cell types can be identified in most brain areas that display different responses to standard forms of intracellular current stimulation. Nevertheless, it is not well understood how biophysically different neurons process synaptic inputs in natural conditions, i.e., when experiencing intense synaptic bombardment in vivo. While distinct cell types might process synaptic inputs into different patterns of action potentials representing specific "motifs'' of network activity, standard methods of electrophysiology are not well suited to resolve such questions. In the current paper we performed dynamic clamp experiments with simulated synaptic inputs that were presented to three types of neurons in the juxtacapsular bed nucleus of stria terminalis (jcBNST) of the rat. Our analysis on the temporal structure of firing showed that the three types of jcBNST neurons did not produce qualitatively different spike responses under identical patterns of input. However, we observed consistent, cell type dependent variations in the fine structure of firing, at the level of single spikes. At the millisecond resolution structure of firing we found high degree of diversity across the entire spectrum of neurons irrespective of their type. Additionally, we identified a new cell type with intrinsic oscillatory properties that produced a rhythmic and regular firing under synaptic stimulation that distinguishes it from the previously described jcBNST cell types. Our findings suggest a sophisticated, cell type dependent regulation of spike dynamics of neurons when experiencing a complex synaptic background. The high degree of their dynamical diversity has implications to their cooperative dynamics and synchronization

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis