Panic results in unique molecular and network changes in the amygdala that facilitate fear responses.

Recurrent panic attacks (PAs) are a common feature of panic disorder (PD) and post-traumatic stress disorder (PTSD). Several distinct brain regions are involved in the regulation of panic responses, such as perifornical hypothalamus (PeF), periaqueductal gray, amygdala and frontal cortex. We have previously shown that inhibition of GABA synthesis in the PeF produces panic-vulnerable rats. Here, we investigate the mechanisms by which a panic-vulnerable state could lead to persistent fear. We first show that optogenetic activation of glutamatergic terminals from the PeF to the basolateral amygdala (BLA) enhanced the acquisition, delayed the extinction and induced the persistence of fear responses 3 weeks later, confirming a functional PeF-amygdala pathway involved in fear learning. Similar to optogenetic activation of PeF, panic-prone rats also exhibited delayed extinction. Next, we demonstrate that panic-prone rats had altered inhibitory and enhanced excitatory synaptic transmission of the principal neurons, and reduced protein levels of metabotropic glutamate type 2 receptor (mGluR2) in the BLA. Application of an mGluR2-positive allosteric modulator (PAM) reduced glutamate neurotransmission in the BLA slices from panic-prone rats. Treating panic-prone rats with mGluR2 PAM blocked sodium lactate (NaLac)-induced panic responses and normalized fear extinction deficits. Finally, in a subset of patients with comorbid PD, treatment with mGluR2 PAM resulted in complete remission of panic symptoms. These data demonstrate that a panic-prone state leads to specific reduction in mGluR2 function within the amygdala network and facilitates fear, and mGluR2 PAMs could be a targeted treatment for panic symptoms in PD and PTSD patients.

Potential of in-plant intramuscular fat predictions to enable sheep breeders to incorporate consumer preferences in breeding programmes.

The inclusion of eating quality traits in sheep genetic improvement programmes is desirable. Intramuscular fat (IMF) plays a key role in ensuring consumer satisfaction when eating lamb, but genetic progress for IMF is constrained by a lack of routine data collection. This study investigated the potential for IMF predictor traits to substitute for measured IMF in genetic improvement programmes. Carcass and predicted IMF (near-infrared estimated IMF and marbling score) data were available on 10,113 New Zealand lambs, 1678 of which also had measured chemical IMF on a slice of M. longissimus lumborum on which the predictions of IMF had been made. Genetic antagonisms were observed between carcass lean traits and IMF. The genetic correlation between the predictors and measured IMF approached one, indicating that predictors of IMF can be used in genetic improvement programmes. Through using selection indexes, simultaneous increases in IMF and the existing terminal selection index are possible, provided all traits are measured. This study highlights the importance and potential of predicted IMF to achieve genetic improvement in traits of importance to consumers.

Can we have our steak and eat it: The impact of breeding for lowered environmental impact on yield and meat quality in sheep.

Global agreements in place to reduce methane emissions in livestock are a potential threat to food security. Successful but independent breeding strategies for improved production and lower methane are in place. The unanswered questions are whether these strategies can be combined and how they impact one another, physically and economically. The New Zealand economy is largely dependent on pastoral agriculture from grazing ruminants. The sheep industry produces ∼20 million lamb carcasses for export each year primarily from grass. Methane emitted from the fermentation of forage by grazing ruminants accounts for one-third of all New Zealand's greenhouse gas emissions. Here, we use sheep selection lines bred for divergent methane production and large numbers of their relatives to determine the genetic and phenotypic correlations between enteric methane emissions, carcass yield, and meat quality. The primary objectives were to determine whether previously shown physiological differences between methane selection lines (differing by ∼12% in methane) result in a negative impact on meat production and quality by measuring close relatives. The results show no negative effects of breeding for lowered methane on meat and carcass quality. Gross methane emissions were highly correlated with liveweight and measures of carcass weight and negatively correlated with dressing-out percentage and fat yield (GR). Trends were similar but not significant for methane yield (g CH4/kg DMI). Preliminary evidence, to date, shows that breeding for low methane may result in animals with higher lean yields that are economically favorable even before carbon costs and environmental benefits are taken into account. These benefits were seen in animals measured for methane on fixed intakes and require validation on intakes that are allowed to vary.

Relationships between intramuscular fat percentage and fatty acid composition in M. longissimus lumborum of pasture-finished lambs in New Zealand.

This paper reports relationships between fatty acids (FAs) and intramuscular fat (IMF)% in M. longissimus lumborum samples from 108 pasture-fed ewe lambs. Samples ranged in IMF from 1 to 6%. Relationships between %FA with total IMF% were mainly linear with percentages of saturated and monounsaturated FAs (MUFA), including trans-FAs, increasing and polyunsaturated FAs decreasing as IMF% increased. Normalized FA content data at 5.5% relative to 1.5% IMF, showed the highest relative increase for C14:0 as rates of endogenous synthesis increase with higher IMF deposition. This can be related to enhanced C12:0 elongation and lower rates of C14:0 desaturation, supported by a preferential desaturation of C18:1 trans-11 and C18:0 compared with C14:0 and C16:0 as IMF increased. The greatest normalized increase after C14:0 was anteisoC17:0 followed by other branched chain FAs and then trans-MUFA and C18:2 cis-9,trans-11. Finally, C22:6 and C22:5 showed higher relative increase than C20:5 indicating greater rates of elongation and desaturation past C20:5 at higher levels of fatness.

Consumer liking of M. longissimus lumborum from New Zealand pasture-finished lamb is influenced by intramuscular fat.

Palatability of meat is known to be affected by intramuscular fat (IMF), but the effect in relatively low-fat New Zealand lamb is unknown. This study evaluated the eating quality of 108 loins (M. longissimus lumborum) from a single flock of ewe-lambs. Loins ranged from 1.09-5.68% IMF and were stratified into 6 groups: 1.65, 2.12, 2.65, 3.20, 3.58 and 4.40%. Consumers' (n = 165) overall liking of lamb increased significantly at around 3% IMF, achieving maximum scores at 4% IMF. One consumer cluster (n = 111) showed a linear increase in overall liking with increasing IMF%, regarded as 'IMF lovers: the more the better', while a second cluster (n = 54) preferred 2.5-3.5% IMF, described as 'IMF optimizers: just the right amount'. IMF% was modestly correlated (~ + 0.25) with all sensory attributes except juiciness. Liking scores were modestly correlated with monounsaturated (~ + 0.25) and polyunsaturated (~ - 0.20) fatty acids. Results suggest aiming for IMF% levels in New Zealand lamb beyond 3% to maximize eating quality for premium markets in particular.

A chemically stratified lake in alaska.

A meromictic (chemically stratified) lake occupies a thawed depression in a pingo in interior Alaska, near Circle City. Increased salt concentration and anaerobic conditions characterize the zone extending from a maximum depth of 3 to 8.8 meters. The concentration of strontium and lithium is unusually high for lake water.

PSD95 and nNOS interaction as a novel molecular target to modulate conditioned fear: relevance to PTSD.

Stimulation of N-methyl-D-aspartic acid receptors (NMDARs) and the resulting increase of nitric oxide (NO) production are critical for fear memory formation. Following NMDAR activation, efficient production of NO requires linking the 95 kDa postsynaptic density protein (PSD95), a scaffolding protein to neuronal nitric oxide synthase (nNOS). A variety of previously studied NMDAR antagonists and NOS inhibitors can disrupt fear conditioning, but they also affect many other CNS functions such as motor activity, anxiety, and learning. We hypothesized that disrupting nNOS and PSD95 interaction in the amygdala, a critical site for fear memory formation, will reduce conditioned fear. Our results show that systemic treatment with ZL006, a compound that disrupts PSD95/nNOS binding, attenuates fear memory compared to its inactive isomer ZL007. Co-immunoprecipitation after fear conditioning showed a robust increase in the amygdala PSD95/nNOS binding, which was blocked by systemic pre-administration of ZL006. Treatment of amygdala slices with ZL006 also impaired long-term potentiation (LTP), a cellular signature of synaptic plasticity. Direct intra-amygdala infusion of ZL006 also attenuated conditioned fear. Finally, unlike NMDAR antagonist MK-801, ZL006 does not affect locomotion, social interaction, object recognition memory, and spatial memory. These findings support the hypothesis that disrupting the PSD95/nNOS interaction downstream of NMDARs selectively reduces fear memory, and highlights PSD95/nNOS interaction as a novel target for fear-related disorders, such as posttraumatic stress disorder.

Application of Hyperspectral imaging to predict the pH, intramuscular fatty acid content and composition of lamb M. longissimus lumborum at 24h post mortem.

Cost-effective, rapid and objective measurement of lamb quality on a routine basis is an important step for lamb value chains wishing to manage lamb product quality. Hyperspectral imaging (HSI) technology has shown promise as a solution for objective non-invasive prediction of meat quality. The performance of HSI applied 24h post mortem to lamb M. longissimus lumborum (LL) within a processing plant environment was assessed over two sampling years to evaluate its suitability for an objective lamb meat quality assurance tool. Calibration and validation steps were undertaken to evaluate HSI prediction performance for predicting fatty acid content and composition (n=1020 lambs) and pH (n=2406 lambs). Practical considerations of reference meat quality data quality and validation strategies are discussed. HSI can be used to predict meat quality parameters of lamb LL with varying accuracy levels, but ongoing calibration and validation across seasons is required to improve robustness of HSI for objective non-invasive assessment of lamb meat quality.

Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs.

Serotonergic systems play important roles in modulating behavioral arousal, including behavioral arousal and vigilance associated with anxiety states. To further our understanding of the neural systems associated with increases in anxiety states, we investigated the effects of multiple anxiogenic drugs on topographically organized subpopulations of serotonergic neurons using double immunohistochemical staining for c-Fos and tryptophan hydroxylase combined with topographical analysis of the rat dorsal raphe nucleus (DR). Anxiogenic drugs with diverse pharmacological properties including the adenosine receptor antagonist caffeine, the serotonin 5-HT2A/2C receptor agonist m-chlorophenyl piperazine (mCPP), the alpha2-adrenoreceptor antagonist yohimbine, and the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) induced increases in behavioral arousal and vigilance behaviors consistent with an increase in anxiety state. In addition, these anxiogenic drugs, excluding yohimbine, had convergent actions on an anatomically-defined subset of serotonergic neurons within the middle and caudal, dorsal subdivision of the DR. High resolution topographical analysis revealed that at the mid-rostrocaudal level, caffeine and FG-7142 had convergent effects on c-Fos expression in serotonergic neurons that were restricted to a previously undefined region, which we have named the shell region of the dorsal part of the dorsal raphe nucleus (DRDSh), that overlaps the anatomical border between the dorsal part of the dorsal raphe nucleus, the ventral part of the dorsal raphe nucleus (DRV), and the ventrolateral part of the dorsal raphe nucleus (DRVL). Retrograde tracing methods revealed that DRDSh contains large numbers of neurons projecting to the basolateral amygdaloid nucleus, a forebrain structure important for emotional appraisal and modulation of anxiety-related physiological and behavioral responses. Together these findings support the hypothesis that there is a functional topographical organization in the DR and are consistent with the hypothesis that anxiogenic drugs have selective actions on a subpopulation of serotonergic neurons projecting to a distributed central autonomic and emotional motor control system regulating anxiety states and anxiety-related physiological and behavioral responses.

Carcass composition and meat quality differences between pasture-reared ewe and ram lambs.

Comparisons were made of carcass and meat quality characteristics of pasture-raised Texel-cross ewe (n=269) and ram (n=275) lambs between 5 and 8 months of age with an average carcass weight of 17.2kg. Carcass assessment was based on linear dimensions and dissection of a leg into muscle, fat and bone, and meat quality measurements were made on M. semimembranosus and M. longissimus. At a set carcass weight, ewe lambs had higher dressing percentages (2%), shorter carcasses (0.7cm), and heavier leg cuts (35g) (P<0.01) than males. At the same leg weight, legs of ewe lambs were fatter than males (subcutaneous plus intermuscular fat; 11.2% vs 9.6%; P<0.001), whereas legs of ram lambs contained significantly more muscle and bone than females (P<0.001). Leg muscle to bone ratio (4.7 vs 4.4) and muscularity were higher for females than males (P<0.001). However, the relationship between leg muscle to bone ratio and muscularity was not the same between the sexes, and for any given muscularity value the muscle to bone ratio of ram lambs was lower than females. As a result, if carcass lean meat yield is predicted from a measure of carcass shape, such as muscularity, lean meat yields will be overestimated for males and underestimated for females. Meat quality was lower in ram lambs than in females (P<0.001) as shown by higher Warner-Bratzler shear values (peak value 109.8 vs 97.0N for M. Semimembranosus), higher ultimate meat pH values, and lower redness (a(∗)) and lightness (L(∗), for the longissimus muscle only) values (P<0.001). It is concluded that significant differences between ewe and ram lambs do exist for many carcass and meat quality traits, but for most quality traits the differences are small.

Estimates of genetic parameters for breech strike and potential indirect indicators in sheep.

AIM: To determine flystrike incidence, and estimate genetic parameters and potential indicator traits to reduce breech strike susceptibility in Romney sheep in New Zealand. METHODS: Seventeen Romney-based flocks, on 11 farms from throughout New Zealand, were enrolled in a case-control study in 2009/10 and 2010/11. Farmers observed lambs with flystrike and recorded dag score, breech bareness score and flystrike location for each lamb. Flystrike location was classed as breech, body, belly, shoulders, head or feet. Paternity of lambs was determined from tissue samples collected from lambs and all potential sires on farms. Control lambs without flystrike were selected by matching birth year, flock and sex. Due to the majority of strike occurring in the breech, genetic parameters for breech strike were explored. Dag score and breech bareness were investigated as indirect indicators of breech strike. Heritabilities and genetic and phenotypic correlations were estimated for breech strike, dag score and breech bareness using an animal model. RESULTS: For the 2009/10 season, 484 cases of flystrike were recorded with mean incidence rate per farm of 1.76 (min 0.47, max 2.95)%. For the 2010/11 season, 352 cases were recorded with a mean incidence rate per farm of 2.54 (min 0.43, max 8.18)%. Over both years 694/792 (88%) cases of flystrike occurred on the breech. Heritability on the observed scale for breech strike was 0.32 (SE 0.10). Heritabilities for dag score and breech bareness were 0.23 (SE 0.09) and 0.35 (SE 0.11), respectively. Breech strike had a high positive genetic correlation with dag score (0.71) and a low negative genetic correlation with breech bareness (-0.17). Breech strike had a high phenotypic correlation with dag score (0.62) and negative phenotypic correlation with breech bareness (-0.06). CONCLUSIONS: The high genetic and phenotypic correlations between breech strike and dag score makes dag score a viable option for indirect selection for breech strike resistance in Romney sheep in New Zealand. The heritability, genetic and phenotypic correlations require validation in other dual-purpose breeds, before breeding values for breech strike can be implemented, for use throughout the New Zealand sheep industry.

Effects of accumbens DALA microinjections on brain stimulation reward and behavioral activation in intact and 6-OHDA treated rats.

The effects of bilateral nucleus accumbens microinjections of d-ala-met-enkephalinamide (DALA) were assessed in behavioral activation and lateral hypothalamic self-stimulation (LHSS) rate-frequency curve-shift paradigms in normal and accumbens 6-OHDA (4.0 micrograms) treated rats. Microinjections of DALA (2.5 micrograms/microliters) in the behavioral activation paradigm had little effect on normal activity; however, DALA administered to 6-OHDA treated rats produced a significant overall increase in locomotion. The 6-OHDA DALA-induced locomotion effect peaked at 2 weeks after 6-OHDA treatment and then returned to baseline levels by week 5 post-treatment. Using LHSS, DALA tested over a range of doses (2.5, 5, 10, 20 micrograms/microliters) displayed a weak biphasic reward effect only at the highest dose, which was characterized by an initial suppression followed by an elevation. DALA significantly depressed initial operant motor/performance in LHSS in a dose dependent fashion. Microinjections of the normally ineffective low dose of DALA (2.5 micrograms/microliters) following accumbens 6-OHDA treatment produced a significant LHSS reward decrease 2 weeks post-treatment, while LHSS motor/performance was relatively unaffected. Results are discussed in terms of opiate-dopamine and limbic-motor interactions.

Behavioral components of marital satisfaction: an individualized assessment approach.

This study examined the extent to which spousal behaviors, obtained through a daily checklist of marital activities individualized along an importance dimension, related to global and daily marital satisfaction. Eighty-two marital couples completed daily checklists of spousal behaviors for 7 days using either an individualized or a standardized assessment method. The results demonstrated that the individualized measures of daily behavioral events were significantly related to global and daily measures of marital satisfaction and discriminated distressed from nondistressed spouses. Although the individualized method did not correlate with marital satisfaction to a significantly greater degree than the standardized method, the individualized assessment approach provides a valid, viable, and cost-effective alternative for assessing daily spousal events that relate to marital satisfaction.

Regulation of membrane-mediated chronic muscle degeneration in dystrophic hamsters by calcium-channel blockers: diltiazem, nifedipine and verapamil.

Membrane-mediated excessive intracellular calcium accumulation (EICA) is a fundamental pathogenetic event associated with chronic muscle degeneration in patients with Duchenne muscular dystrophy (DMD), and in animals with hereditary muscular dystrophy (HMD). Because of potential Ca(2+)-channel blocking properties, we investigated the relative efficacies of chronic diltiazem (DTZM) (50 mg/kg/d), nifedipine (NFDN) (6 mg/kg/d), and verapamil (VPML) (25 mg/kg/d) therapies in reducing EICA and improving dystrophic pathobiology beginning in 30-day-old male BIO-14.6 strain dystrophic hamsters (DH). Each agent, and sterile distilled water as vehicle control, was given in a single daily oral dose for 180 days to four groups each of DH and BIO-F1B strain normal hamsters (NH). Plasma [Ca] and [Mg]; plasma aldolase (ALD), creatine kinase (CK), and lactate dehydrogenase (LDH) activities; relative cardiac hypertrophy and relative soleus hypertrophy; tissue [Ca] and [Mg] of the heart and rectus femoris muscle, histology of rectus femoris, and overall mortality rate were quantitated. Muscle Mg was not modified in DH, or by any of these agents. NFDN produced significant edema in the soleus and myocardium. During the 6-month therapeutic trial, 45% DH and 18% NH died on VPML, 27% DH and 9% NH on NFDN, and 20% DH controls on distilled water, but none on DTZM; suggesting that DTZM treated DH lived longer than DH controls. Relative efficacy in regulating EICA in both the cardiac and skeletal muscles; plasma ALD, CK, and LDH; and improving associated dystrophic pathobiology was found to be DTZM >>> NFDN > VPML. DTZM appears to be the most effective and safest agent in mitigating EICA in cardiac and skeletal muscles, efflux of intracellular enzymes, histopathology of dystrophic muscle with sporadic necrosis, and chronic muscle degeneration in DH with HMD. DTZM therapy also halted the high morbidity and mortality associated with the dystrophic pathobiology inherent in DH.

Reversal of impaired oxidative phosphorylation and calcium overloading in the in vitro cardiac mitochondria of CHF-146 dystrophic hamsters with hereditary muscular dystrophy.

Membrane-mediated excessive intracellular calcium accumulation (EICA), and diminished cellular energy charge are invariably present in the myocardium of CHF-146 strain dystrophic hamsters (DH) with hereditary muscular dystrophy (HMD) and hypertrophic cardiomyopathy (HC). Therefore, we investigated respiratory dysfunctions and Ca2+ overloading in the isolated cardiac mitochondria from young and old DH, and whether these abnormalities can be reversed by controlling EICA in the in vitro mitochondria upon chelating excessive Ca2+ from the isolation medium with EDTA. Age- and sex-matched CHF-148 strain albino normal hamsters (NH) served as the disease controls. As an index of membrane-mediated EICA and chronic cellular degeneration, Ca and Mg concentrations were quantitated in the ventricular myocardium and in the cardiac mitochondria harvested in two different isolation media. Mitochondria from young and old DH, isolated in the absence of 10 mM EDTA (B0 medium), revealed poor coupling of oxidative phosphorylation, diminished stimulated oxygen consumption rate, and lower respiratory control and ADP/O ratios, than those seen in NH. However, incorporation of 10 mM EDTA in the isolation medium (B medium) restored the mitochondrial functions and reduced massive Ca(2+)-overloading in the dystrophic organelles. Ca concentration in the in vitro mitochondria from DH was significantly higher than in NH, irrespective of the composition of the isolation medium and age of the hamsters. Furthermore, the dystrophic organelles isolated in B medium had a much lower Ca concentration, and markedly improved oxidative phosphorylation as seen in the cardiac mitochondria from NH, compared to those prepared using B0 medium.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative evaluation of bedside capillary blood glucose monitoring devices designed for hospital use.

Capillary blood glucose monitoring devices (CBGMs) that incorporate "wipeless" technology recently have been designed and marketed for hospital use. Our objective was to evaluate three such devices for accuracy and precision, comparing them to a popular device that utilizes older technology and to a reference standard. Blood glucose level was simultaneously determined on the CBGMs and a reference standard. Results were analyzed for precision by performing repeated measurements of a single sample and for accuracy across the entire range of determinations. Clinically relevant subsets of the entire range also were determined and arbitrarily defined as low (< 60 mg/dL), normal (60 to 140 mg/dL), high (141 to 300 mg/dL), and very high (> 300 mg/dL). We found that accuracy and precision of these devices varied considerably. Lack of accuracy was particularly evident upon analysis of the clinically relevant subset ranges of blood glucose levels. Consequently, routine evaluation of CBGMs should include analysis of clinically relevant subset ranges of blood glucose levels. The marked differences in accuracy and precision between CBGMs that are currently.

Parental behavior patterns and conduct disorders in girls.

Conduct-disordered (CD) girls, 9 to 11 years old, were compared to nonconduct-disordered (NCD) girls of the same age using parental reports about themselves and their children and child reports of themselves and their parents. Correlations were obtained between parental behavior patterns and the behavior patterns of the girls as perceived by three family members: mother, father, and the target child. The results indicated that (1) parents of CD girls were more hostile in some contexts than parents of NCD girls, (2) relationships between parental behavioral characteristics and children's behavioral characteristics were stronger and more numerous for mothers than for fathers, and (3) the children's perception of their own behaviors and the parents' marriages tended to correspond with their parents' perceptions. In general, the pattern of results suggests that, in terms of aggressive behavior patterns, female children may be modeling the behavior of their parents, particularly that of their mothers.

Laparoscopy. Gasless vs. CO2 pneumoperitoneum.

OBJECTIVE: To compare gasless laparoscopy with conventional laparoscopy using CO2 pneumoperitoneum. STUDY DESIGN: Women undergoing bilateral laparoscopic tubal coagulation (LTC) were randomly assigned to one of two laparoscopy procedures: (1) a gasless laparoscopy system consisting of an intraabdominal fan retractor and electrically powered mechanical arm, and (2) standard CO2 pneumoperitoneum laparoscopy. The two laparoscopic procedures were compared on the basis of intraoperative visualization, operation duration, procedural difficulty, ventilatory parameters, hemodynamic stability, and postoperative pain and nausea. RESULTS: Significant disadvantages for the surgeon (increased technical difficulty, poorer visualization, longer operative times) and patient (greater postoperative pain and nausea) were seen with the gasless system. Because of these findings, the study was prematurely terminated after only 18 patients had participated. Intraoperative ventilatory and hemodynamic parameters were more stable in the gasless laparoscopy groups; however, the differences were not clinically significant in this population of healthy patients. CONCLUSION: The markedly increased technical difficulty and absence of clear clinical benefits for the healthy patient led to the conclusion that laparoscopy with CO2 pneumoperitoneum is preferable for routine LTC and most laparoscopic procedures in the pelvis. Gasless laparoscopy may be of benefit for the fragile patient with a compromised cardiovascular system who may suffer complications from hypercarbenemia.

Evaluation of U.S. Public Health Service programs. Organization and management.

This article provides an overview of evaluation in the Public Health Service (PHS) of the U.S. Department of Health and Human Services. The kinds of evaluation activities are outlined with illustrations of recently completed studies. The overview includes information on resources, policies, and management of evaluations conducted by the various PHS agencies and programs. In particular, the department's new efforts to better disseminate evaluation results through the Internet are described. The article concludes with a discussion of future prospects of how PHS evaluations will play a role in implementation of the Government Performance and Results Act (GPRA).