The Periaqueductal Gray (PAG)

This issue covers a broad territory of PAG function: neuropharmacology, functional organization, and PAG plasticity in adaptive behavior, emotion, anxiety, and the less-studied plasticity of the PAG function in females

Predicting Impaired Extinction of Traumatic Memory and Elevated Startle

Emotionally traumatic experiences can lead to debilitating anxiety disorders, such as phobias and Post-Traumatic Stress Disorder (PTSD). Exposure to such experiences, however, is not sufficient to induce pathology, as only up to one quarter of people exposed to such events develop PTSD. These statistics, combined with findings that smaller hippocampal size prior to the trauma is associated with higher risk of developing PTSD, suggest that there are pre-disposing factors for such pathology. Because prospective studies in humans are limited and costly, investigating such pre-dispositions, and thus advancing understanding of the genesis of such pathologies, requires the use of animal models where predispositions are identified before the emotional trauma. Most existing animal models are retrospective: they classify subjects as those with or without a PTSD-like phenotype long after experiencing a traumatic event. Attempts to create prospective animal models have been largely unsuccessful.Here we report that individual predispositions to a PTSD-like phenotype, consisting of impaired rate and magnitude of extinction of an emotionally traumatic event coupled with long-lasting elevation of acoustic startle responses, can be revealed following exposure to a mild stressor, but before experiencing emotional trauma. We compare, in rats, the utility of several classification criteria and report that a combination of criteria based on acoustic startle responses and behavior in an anxiogenic environment is a reliable predictor of a PTSD-like phenotype.There are individual predispositions to developing impaired extinction and elevated acoustic startle that can be identified after exposure to a mildly stressful event, which by itself does not induce such a behavioral phenotype. The model presented here is a valuable tool for studying the etiology and pathophysiology of anxiety disorders and provides a platform for testing behavioral and pharmacological interventions that can reduce the probability of developing pathologic behaviors associated with such disorders

Ensemble Kalman filter assimilation of temperature and altimeter data with bias correction and application to seasonal prediction

To compensate for a poorly known geoid, satellite altimeter data is usually analyzed in terms of anomalies from the time mean record. When such anomalies are assimilated into an ocean model, the bias between the climatologies of the model and data is problematic. An ensemble Kalman filter (EnKF) is modified to account for the presence of a forecast-model bias and applied to the assimilation of TOPEX/Poseidon (T/P) altimeter data. The online bias correction (OBC) algorithm uses the same ensemble of model state vectors to estimate biased-error and unbiased-error covariance matrices. Covariance localization is used but the bias covariances have different localization scales from the unbiased-error covariances, thereby accounting for the fact that the bias in a global ocean model could have much larger spatial scales than the random error.The method is applied to a 27-layer version of the Poseidon global ocean general circulation model with about 30-million state variables. Experiments in which T/P altimeter anomalies are assimilated show that the OBC reduces the RMS observation minus forecast difference for sea-surface height (SSH) over a similar EnKF run in which OBC is not used. Independent in situ temperature observations show that the temperature field is also improved. When the T/P data and in situ temperature data are assimilated in the same run and the configuration of the ensemble at the end of the run is used to initialize the ocean component of the GMAO coupled forecast model, seasonal SSH hindcasts made with the coupled model are generally better than those initialized with optimal interpolation of temperature observations without altimeter data. The analysis of the corresponding sea-surface temperature hindcasts is not as conclusive

Effects of exposure to hypoxia on the signal-averaged electrocardiogram in healthy subjects

The effects of hypoxia on the signal-averaged ECG (SAECG) were investigated in 26 healthy active subjects with no suggestion of cardiac disease. The SAECG was recorded in each resting subject in normoxic and hypoxic normobaric conditions (inspired O2 fraction 20.7 vs 10.0%) which lowered resting arterial O2 saturation from 98.6 +0.6% to 77.7 ± 8%. Recordings from four subjects (three men) met the definition of abnormal late potentials at baseline; in all these subjects but one, who exhibited an improved but still abnormal QRS duration, these parameters returned to normal in hypoxic conditions. The duration of the filtered QRS was significantly reduced (from 107.6 ±13.2 to 101.6 ± 11.3 ms, P<001), the duration of the low amplitude signals in the terminal portion of the QRS <40 μ V (LAS) significantly decreased (from 26.5 ± 9.5 to 22.7 ± 7.9 ms, P<005) and the root mean square voltage in the last 40 ms (Term-RMS) increased non-significantly (from 55.8±40.2 to 69.1±38.3 μV, P=0.058). Hypoxia determined a higher (P<0.05) heart rate increase in subjects with abnormal records than in normal subjects. These data could be related to a sympathic discharge. They suggest that: (1) variation in heart rate could affect the SAECG; (2) exposure to hypoxia improves SAECG parameters in healthy subjects, possibly related to sympathetic discharge; (3) abnormal records collected during sinus bradycardia could represent a type of false-positive expression of late potentials in young active adult

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

Coagulation activity of stored blood at +4°C

U ovom je radu ispitana koagulaciona aktivnost uskladištene krvi na +4°C. Primijenjeno je osam koagulacionih testova, a promjene koagulacione aktivnosti prikazane su grafički. Testiranje je izvršeno odmah nakon vađenja krvi, te drugi, sedmi i četrnaesti dan. Rezultati autora uspoređeni su s rezultatima iz literature.The coagulation activity of blood stored at 4°C was investigated. Eight different clotting tests were used. The changes in the coagulation activity are presented graphically. The testing was performed .immediately after the blood was taken from the vein and then after the first, seventh and forteenth day of storage. The authors compare their results with the data reported in literature. On each figure the time of storage in days is marked on the abscissa. The ordinate indicates the clotting time in sec. (Fig. 1), the prothrombin time in sec. (Fig. 2), the prothrombin consumption test in sec. (Fig. 3), the number of platelets x 10-3 (Fig. 4), the tromboplastin generation test, % activity (Fig. 5), the antihemophilic globulin % (Fig. 6), factor V activity % (Fig. 7), factor VII activity % (Fig. 8)

Adenosine has two faces: Regionally dichotomous adenosine tone in a model of epilepsy with comorbid sleep disorders

Objective: Adenosine participates in maintaining the excitatory/inhibitory balance in neuronal circuits. Studies indicate that adenosine levels in the cortex and hippocampus increase and exert sleep pressure in sleep-deprived and control animals, whereas in epilepsy reduced adenosine tone promotes hyperexcitability. To date, the role of adenosine in pathological conditions that result in both seizures and sleep disorders is unknown. Here, we determined adenosine tone in sleep and seizure regulating brain regions of Kv1.1 knockout (KO) mice, a model of temporal epilepsy with comorbid sleep disorders. Methods: 1) Reverse phase-high performance liquid chromatography (RP-HPLC) was performed on brain tissue to determine levels of adenosine and adenine nucleotides. 2) Multi-electrode array extracellular electrophysiology was used to determine adenosine tone in the hippocampal CA1 region and the lateral hypothalamus (LH). Results: RP-HPLC indicated a non-significant decrease in adenosine (~50%, p = 0.23) in whole brain homogenates of KO mice. Regional examination of relative levels of adenine nucleotides indicated decreased ATP and increased AMP in the cortex and hippocampus and increased adenosine in cortical tissue. Using electrophysiological and pharmacological techniques, estimated adenosine levels were ~35% lower in the KO hippocampal CA1 region, and 1–2 fold higher in the KO LH. Moreover, the increased adenosine in KO LH contributed to lower spontaneous firing rates of putative wake-promoting orexin/hypocretin neurons. Interpretation: This is the first study to demonstrate a direct correlation of regionally distinct dichotomous adenosine levels in a single model with both epilepsy and comorbid sleep disorders. The weaker inhibitory tone in the dorsal hippocampus is consistent with lower seizure threshold, whereas increased adenosine in the LH is consistent with chronic partial sleep deprivation. This work furthers our understanding of how adenosine may contribute to pathological conditions that underlie sleep disorders within the epileptic brain

Patterns and correlates of claims for brown bear damage on a continental scale

Wildlife damage to human property threatens human-wildlife coexistence. Conflicts arising from wildlife damage in intensively managed landscapes often undermine conservation efforts, making damage mitigation and compensation of special concern for wildlife conservation. However, the mechanisms underlying the occurrence of damage and claims at large scales are still poorly understood. Here, we investigated the patterns of damage caused by brown bears Ursus arctos and its ecological and socio-economic correlates at a continental scale. We compiled information about compensation schemes across 26 countries in Europe in 2005-2012 and analysed the variation in the number of compensated claims in relation to (i) bear abundance, (ii) forest availability, (iii) human land use, (iv) management practices and (v) indicators of economic wealth. Most European countries have a posteriori compensation schemes based on damage verification, which, in many cases, have operated for more than 30 years. On average, over 3200 claims of bear damage were compensated annually in Europe. The majority of claims were for damage to livestock (59%), distributed throughout the bear range, followed by damage to apiaries (21%) and agriculture (17%), mainly in Mediterranean and eastern European countries. The mean number of compensated claims per bear and year ranged from 0·1 in Estonia to 8·5 in Norway. This variation was not only due to the differences in compensation schemes; damage claims were less numerous in areas with supplementary feeding and with a high proportion of agricultural land. However, observed variation in compensated damage was not related to bear abundance. Synthesis and applications. Compensation schemes, management practices and human land use influence the number of claims for brown bear damage, while bear abundance does not. Policies that ignore this complexity and focus on a single factor, such as bear population size, may not be effective in reducing claims. To be effective, policies should be based on integrative schemes that prioritize damage prevention and make it a condition of payment of compensation that preventive measures are applied. Such integrative schemes should focus mitigation efforts in areas or populations where damage claims are more likely to occur. Similar studies using different species and continents might further improve our understanding of conflicts arising from wildlife damage

Coordinated regulation of transcription by CcpA and the \u3ci\u3eStaphylococcus aureus\u3c/i\u3e twocomponent system HptRS

The success of Staphylococcus aureus as a pathogen is due in part to its ability to adapt to changing environmental conditions using signal transduction pathways, such as metaboliteresponsive regulators and two-component systems. S. aureus has a two-component system encoded by the gene pair sav0224 (hptS) and sav0223 (hptR) that regulate the hexose phosphate transport (uhpT) system in response to extracellular glucose-6-phosphate. Glycolytic intermediates such as glucose-6-phosphate are important carbon sources that also modulate the activity of the global metabolite-responsive transcriptional regulator CcpA. Because uhpT has a putative CcpA binding site in its promoter and it is regulated by HptR, it was hypothesized the regulons of CcpA and HptR might intersect. To determine if the regulatory domains of CcpA and HptRS overlap, ccpA was deleted in strains SA564 and SA564- ΔhptRS and growth, metabolic, proteomic, and transcriptional differences were assessed. As expected, CcpA represses hptS and hptR in a glucose dependent manner; however, upon CcpA derepression, the HptRS system functions as a transcriptional activator of metabolic genes within the CcpA regulon. Importantly, inactivation of ccpA and hptRS altered sensitivity to fosfomycin and ampicillin in the absence of exogenous glucose-6-phosphate, indicating that both CcpA and HptRS modulate antibiotic susceptibility