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Background: Hypoxic pulmonary vasoconstriction (HPV) is a reflex constriction of vascular smooth muscle. This study aims to investigate the role of Salidroside (Sal) in pulmonary arterial dilatation and the potential mechanism of Sal regulating hypoxic pulmonary hypertension in vitro and in vivo., Methods: A rat model of hypoxic pulmonary hypertension (HPH) was constructed using hypoxic chamber. The effect of Sal on HPH were evaluated using vascular ring, whole cell patch-clamp, WGA staining, HE staining, and Sirius Scarlet staining assays., Results: Sal treatment alleviated the injury of acute hypoxia on pulmonary circulation in SD rats. Meanwhile, Sal treatment reduced the pulmonary vascular tone of acute hypoxia in a concentration-dependent manner, which was involved in the TWIK-related acid-sensitive potassium channel 1 (TASK-1) mediating diastolic effect. We found that Sal treatment significantly increased the TASK-1 current of pulmonary artery smooth muscle cells (PASMCs) in a concentration-dependent manner, as well as reversed the inhibitory effect of acute hypoxia on the TASK-1 current. Moreover, Sal treatment improved the TASK-1 current density, suppressed the proliferation, and enhanced the apoptosis of PASMCs in SD rats under continuous hypoxic condition. In addition, we found that the electrophysiological remodeling and pulmonary vascular remodeling of PASMCs were improved by the treatment of Sal through the regulation of TASK-1 channel., Conclusions: Sal could alleviate HPH by restoring the function of TASK-1 channel, which may provide a novel method for the treatment of HPH., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Since their discovery, the Hox genes, with their incredible power to reprogram the identity of complete body regions, a phenomenon called homeosis, have captured the fascination of many biologists. Recent research has provided new insights into the function of Hox proteins in different germ layers and the mechanisms they employ to control tissue morphogenesis. We focus in this review on the ectoderm and mesoderm to highlight new findings and discuss them with regards to established concepts of Hox target gene regulation. Furthermore, we highlight the molecular mechanisms involved the transcriptional repression of specific groups of Hox target genes, and summarize the role of Hox mediated gene silencing in tissue development. Finally, we reflect on recent findings identifying a large number of tissue-specific Hox interactor partners, which open up new avenues and directions towards a better understanding of Hox function and specificity in different tissues., Competing Interests: Conflict of interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Salidroside (Sal) possesses several pharmacological activities, such as antiaging, and anti-inflammatory, antioxidant, anticancer activities, and proliferation-promoting activities, but the effects of Sal on oocytes have rarely been reported. In the present study, we evaluated the beneficial effects of Sal, which is mainly found in the roots of Rhodiola. Porcine cumulus oocyte complexes were cultured in IVM medium supplemented (with 250 μmol/L) with Sal or not supplemented with Sal. The maturation rate in the Sal group increased from 88.34 ± 4.32% to 94.12 ± 2.29%, and the blastocyst rate in the Sal group increased from 30.35 ± 3.20% to 52.14 ± 7.32% compared with that in the control group. The experimental groups showed significant improvements in the cumulus expansion area. Sal reduced oocyte levels of reactive oxygen species (ROS) and enhanced intracellular GSH levels. Sal supplementation enhanced the mitochondrial membrane potential (MMP), ATP level, and mtDNA copy number, which shows that Sal enhances the cytoplasmic maturation of oocytes. Oocytes in the Sal group exhibited slowed apoptosis and reduced DNA breakage. Cell cycle signals and oocyte meiosis play important roles in oocyte maturation. The mRNA expressions of the MAPK pathway and MAPK phosphorylation increased significantly in the Sal group. The mRNA expression of the oocyte meiosis gene also increased significantly. These results show that Sal enhances the nuclear maturation of oocytes. Moreover, Sal increased the number of blastocyst cells, the proliferation of blastocysts, and the expressions of pluripotency genes. Sal down-regulated apoptosis-related genes and the apoptotic cell rate of blastocysts. In summary, our results demonstrate that Sal is helpful to improving the quality of porcine oocytes in vitro, and their subsequent embryonic development.

Background: Deep learning is an important outcome of the higher education and is mostly determined by students' approaches to learning (SALs). The latest version of the Study Process Questionnaire (SPQ) is one of the most used instruments assessing SALs. Many studies from various contexts have either validated or used this famous tool. But none of them-to the best of our knowledge-stem from the Moroccan tertiary context. The current study fills this gap by first: Getting a local translation of the questionnaire following the standardized methodological process and secondly to update the validity and psychometric properties of the construct., Materials and Methods: Arabic back translation was performed. Data were collected among tertiary scientific students. Descriptive statistics, Cronbach's coefficient alpha, and confirmatory factor analysis were carried out under SPSS version 22., Results: A strong fit of the dichotomic construct (deep and surface) was found, whereas the hierarchical models were disappointing., Conclusions: Following the standards of the psychometrics' validation, this Arabic version could be used only in first-order factor model to evaluate the deep and surface approach within tertiary education in Moroccan context., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Education and Health Promotion.)

Objective: Excessive salt intake is associated with higher levels of AHT and prevalence of cardiovascular diseases. WHO recommends consuming less than 5 g/day of salt (equivalent to 2 g Na + /day). Identifying foods and behaviours with greater contribution to excess intake would facilitate preventive dietary advice., Design: Observational study. SITE: Urban Health Center in Cáceres., Main Measurements: We estimated salt consumption using two food consumption frequency (FFQ) questionnaires, one generic and one with high Na+ content, and a 24 h follow-up survey. We use the Evalfinut program for nutritional evaluation of the diet. We analyzed correlations between estimated salt intake and 24-h urine sodium elimination (gold standard)., Results: 92% of the population had consumption higher than the recommendations with intakes equivalent to 9.5 g/day of salt (3.7 g/d of Na + ). When sodium intake is determined by the Na + /K + ratio, 79.54% have high intakes. Sodium elimination follows a slightly increasing trend with BMI. The perception of salt consumption is low, 56.3% consider it "adequate". 32.4% add salt to food once served. FFQ underestimate Na + intake and targeted surveys provide higher values. The correlation between FFQ and Na + urinary elimination is weak., Conclusion: We must reduce salt intake by increasing the perception of consumption, improving knowledge about the salt content in food and identifying target patients of the health council., (Copyright © 2022 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Neurite dystrophy is a pathologic hallmark of Alzheimer's disease (AD). However, drug discovery targeting neurite protection in AD remains largely unexplored., Methods: Aβ-induced neurite and mitochondrial damage assays were used to evaluate Aβ toxicity and the neuroprotective efficacy of a natural compound salidroside (SAL). The 5×FAD transgenic mouse model of AD was used to study the neuroprotective function of SAL. To verify the direct target of SAL, we used surface plasmon resonance and cellular thermal shift assays to analyze the drug-protein interaction., Results: SAL ameliorates Aβ-mediated neurite damage in cell culture. We further reveal that SAL represses mitochondrial damage in neurites by promoting mitophagy and maintaining mitochondrial homeostasis, dependent on an NAD-dependent deacetylase SIRT3. In AD mice, SAL protects neurite morphology, mitigates Aβ pathology, and improves cognitive function, which are all SIRT3-dependent. Notably, SAL directly binds to transcription factor NRF2, inhibits its degradation by blocking its interaction with KEAP1 ubiquitin ligase, and then advances NRF2-mediated SIRT3 transcription., Conclusions: Overall, we demonstrate that SAL, a potential anti-aging drug candidate, attenuates AD pathology by targeting NRF2/SIRT3 pathway for mitochondrial and neurite protection. Drug discovery strategies focusing on SAL may thus provide promising therapeutics for AD., (© 2022. The Author(s).)

This article explores the symbolism of plastic pollution. Plastic and microplastic particles are now found everywhere - in the Arctic, in deep ocean trenches, in human organs - and plastic accumulates in our oceans forming gigantic spiral-shaped garbage patches. Both spiral symbolism and E.A. Poe's 'Maelström' are suggestive of a necessary fundamental ecological-psychological transformation of our one-sidedly logos-dominated civilization. Plastic, the author argues, has become a carrier of our longing for immortality: in plastic, humanity has synthesized an 'immortal', a virtually non-biodegradable substance. To avert what Jung called a 'catastrophic enantiodromia', humanity must relinquish its ecologically and psychologically detrimental consumerist mentality and jump into the unknown towards a less resource-intensive lifestyle. The author's dream about sea salt and spiral-shaped marine animals is interpreted as a compensatory urge from the collective unconscious for humanity to reconnect to inner and outer nature by cultivating the neglected eros principle - feeling-based relatedness - as a felt realization that we are part of nature on which we depend. Instead of succumbing to paralyzing fear or denial, the author argues for facing the abyss of our ecological-psychological crisis and acting, informed by science. For ecological-psychological transformation, Jungian psychology can play an important role., (© 2022 The Society of Analytical Psychology.)

Introduction: This research relates the most important work-related factors affecting the development of hearing loss to the main methods used as medical assessment criteria in the diagnosis of occupational deafness. These criteria are the Speech Average Loss Index (SAL), the Early Loss Index (ELI) and the Percentage of Hearing Loss, and are applied to data obtained from audiograms performed on workers in occupational medical examinations., Method: Depending on the assessment method selected, these often return different results in grading an individual's hearing status and predicting how it will evolve. To address this problem, medical examinations (including audiograms) were carried out on a heterogeneous sample of 1,418 workers in Spain, from which demographic or personal data (gender, age, etc.), occupational data (noise level to which each individual is exposed, etc.) and other non-work-related factors (exposure to noise outside work, family history, etc.) were also gathered. Using Bayesian Networks, the conditional probability of an individual developing hearing loss was obtained taking into account all these factors and, specifically, noise level and length of service in the workplace. Sensitivity analyses were also carried out using the three scales (SAL, ELI and Percentage Hearing Loss Index), proving their suitability as tools the diagnosis and prediction of deafness. These networks were validated under the Receiver Operating Characteristic curve (ROC) criterion and in particular by the Area Under the Curve (AUC)., Results: The results show that all three methods are deficient in so far as detecting preventive hearing problems related to noise in most workplaces., Conclusions: The most restrictive methods for detecting possible cases of deafness are the SAL index and the Percentage Loss Index. The ELI index is the least restrictive of the three methods, but it is not able to discriminate the causes of hearing problems in an individual caused by exposure to noise, either by its intensity level or by the time of exposure to noise. Practical Applications: The use of the three methods in the field of occupational risk prevention is extremely limited and it seems reasonable to think that there is a need for the construction of new scales to correct or improve the existing ones., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest in the publication of this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Illegal use of salbutamol (SAL), a β-adrenergic leanness-enhancing agent, has posed potential threat to human health in China. The excretion and depletion of SAL in pigs and goats were investigated, and the concentration correlations between edible tissues and living samples were analyzed to find out a suitable living sample for pre-slaughter monitoring of SAL in pigs and goats. After a single oral dosage of 1.2 mg/kg SAL, approximately 70% of the dose was excreted by pigs and goats from their excreta. When pigs and goats were supplied feed containing SAL (20 mg/kg) for 14 consecutive days, high concentrations of SAL were observed in the liver and kidneys, and the longest persistence was observed in hair. Unlike pigs, SAL was presented primarily as conjugated SAL in goats. Excellent concentration correlations of SAL were observed between urine and edible tissues both in pigs and goats, and in addition, good correlations also were found between hair and edible tissues in pigs and between feces and edible tissues in goats. Hence, urine and hair could accurately predict SAL concentrations in edible tissues of pigs, whereas feces and urine were satisfactory for predicting SAL concentrations in edible tissues of goats. These data make it possible for pre-slaughter monitoring of SAL residues in the edible tissues of pigs and goats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sun, Zhu, Shi, Mi, Ma, Xu, Wang, Pan, Tao, Liu and Huang.)

Investigating the impact of climate variables on net primary productivity is crucial to evaluate the ecosystem health and the status of forest type response to climate change. The objective of this paper is (1) to estimate spatio-temporal patterns of net primary productivity (NPP) during 2001 to 2010 in a tropical deciduous forest based on the input variable dataset (i.e.meteorological and biophysical) derived from the remote sensing and other sources and (2) to investigate the effects of climate variables on NPP during 2001 to 2010. The study was carried out in Katerniaghat Wildlife Sanctuary that forms a part of a tropical forest and is situated in Uttar Pradesh, India, along the Indo-Nepal border. Mean annual NPP was observed to be highest during 2007 with a value of 878 g C m -2  year -1 and 781.25 g C m -2  year -1 for sal and teak respectively. A decline in mean NPP during 2002-2003, 2005 and 2008-2010 could be attributed to drought, increased temperature and vapour pressure deficit (VPD). The time lag correlation analysis revealed precipitation as the major variables affecting NPP, whereas combination of temperature and VPD showed dominant effect on NPP as revealed by generalized linear modelling. The carbon gain in NPP in sal forest was observed to be marginal higher than that of teak plantation throughout the study period. The decrease in NPP was observed during 2010, pertaining to increased VPD. Contribution of different climatic variables through some link process was revealed in statistical analysis and clearly indicated the co-dominance of all the variables in explaining NPP.

Here we investigate the involvement of the ventral pallidum (VP) in the anti-nausea effect of fatty acid amide hydrolase (FAAH) inhibition with PF-3845, and examine the pharmacological mechanism of such an effect. We explored the potential of intra-VP PF-3845 to reduce the establishment of lithium chloride (LiCl)-induced conditioned gaping (a model of acute nausea) in male Sprague-Dawley rats. As well, the role of the cannabinoid 1 (CB 1 ) receptors and the peroxisome proliferator-activated receptors-α (PPARα) in the anti-nausea effect of PF-3845 was examined. Finally, the potential of intra-VP GW7647, a PPARα agonist, to reduce acute nausea was also evaluated. Intra-VP PF-3845 dose-dependently reduced acute nausea by a PPARα mechanism (and not a CB 1 receptor mechanism). Intra-VP administration of GW7647, similarly attenuated acute nausea. These findings suggest that the anti-nausea action of FAAH inhibition may occur in the VP, and may involve activation of PPARα to suppress acute nausea., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Salidroside, an active component from Traditional Chinese Medicine Rhodiola rosea L., has various pharmacological functions including anti-inflammatory, anti-cancer and anti-oxidative properties. However, whether salidroside plays a beneficial role in diabetic nephropathy is still unclear., Purpose: The objective of this work was to investigate the potential roles of salidroside against diabetic nephropathy and the underlying molecular mechanisms., Methods: Streptozocin was given to obese mice to generate diabetic nephropathy animal model. Salidroside was administered to these mice and proteinuria, podocyte integrity, renal morphology and fibrosis, mitochondrial biogenesis were examined., Results: Our results showed that salidroside treatment greatly attenuates diabetic nephropathy as evidenced by decreased urinary albumin, blood urea nitrogen and serum creatinine. Morphological analysis indicated that salidroside improves renal structures in diabetic nephropathy. The decreases in nephrin and podocin expression were markedly reversed by salidroside. Moreover, kidney fibrosis in diabetic nephropathy mice was largely prevented by salidroside. Mechanistically, in salidroside-treated mice, the mitochondrial DNA copy and electron transport chain proteins were significantly enhanced. Meanwhile, the reduced Sirt1 and PGC-1α expression in diabetic nephropathy was almost completely counteracted in the presence of salidroside., Conclusions: Our data showed that salidroside plays a beneficial role against diabetic nephropathy in mice, which probably via Sirt1/PGC-1α mediated mitochondrial biogenesis., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

There is evidence suggesting that inhibition of apoptosis plays a critical role in preventing neurons from damage and even death, after brain ischemia/reperfusion, which shows therapeutic potential for clinical treatment of brain injury. In this study, We preformed MCAO model in C57BL/6J wild-type (BDNK+/+) and BDNK knockout (BDNF-/-) mice respectively, and investigated the neuroprotective effect of Salidroside (Sal) and its underlying mechanisms. The results showed that Sal reversed brain infarct size, reduced cerebral edema, decreased the neurological deficit score and diminished TUNEL positive cells significantly. However, BDNK deficiency inhibited the neuroprotective effect of Sal. In addition, Sal increased cell viability, ameliorated neuron cell injury by decreasing LDH activity, and inhibited cell apoptotic rate. Sal suppressed apoptotic signaling via DNA-binding-dependent and -independent mechanisms. Furthermore, the neuroprotective effect of Sal on BDNK was mediated by PI3K/Akt pathway, which was proved by the use of PI3K knockout (PI3K-/-) mice and siRNA-PI3K. In summary, these data strongly suggested that Sal could be used as an effective neuroprotective agent to protect against ischemic stroke after cerebral I/R injury through regulating BDNK-mediated PI3K/Akt apoptotic pathway in DNA-binding-dependent and -independent manners., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Common terminal sterilization methods are known to alter the natural structure and properties of soft tissues. One approach to providing safe grafts with preserved biological properties is the combination of a validated chemical sterilization process followed by an aseptic packaging process. This combination of processes is an accepted method for production of sterile healthcare products as described in ANSI/AAMI ST67:2011. This article describes the validation of the peracetic acid and ethanol-based (PAAE) chemical sterilization process for allograft dermal tissues at the Musculoskeletal Transplant Foundation (MTF, Edison, NJ). The sterilization capability of the PAAE solution used during routine production of aseptically processed dermal tissue forms was determined based on requirements of relevant ISO standards, ISO 14161:2009 and ISO 14937:2009. The resistance of spores of Bacillus subtilis, Clostridium sporogenes, Mycobacterium terrae, Pseudomonas aeruginosa, Enterococcus faecium, and Staphylococcus aureus to the chemical sterilization process employed by MTF was determined. Using a worst-case scenario testing strategy, the D value was calculated for the most resistant microorganism, Bacillus. The 12D time parameter determined the minimum time required to achieve a SAL of 10 -6 . Microbiological performance qualification demonstrated a complete kill of 10 6 spores at just a quarter of the full cycle time. The validation demonstrated that the PAAE sterilization process is robust, achieves sterilization of allograft dermal tissue to a SAL 10 -6 , and that in combination with aseptic processing secures the microbiological safety of allograft dermal tissue while avoiding structural and biochemical tissue damage previously observed with other sterilization methods such as ionizing irradiation.

In literature, since many decades, it is often believed and condoned that excessive common salt (Nacl) ingestion can lead to hypertension. Hence, every health organisation, agencies and physicians have been advising salt restriction to hypertensive patients. However, there is no concrete evidence suggesting that salt restriction can reduce the risk of hypertension (HTN). The present article is based on the current literature search which was performed using MEDLINE, EMBASE, Google Scholar and PubMed. The meta-analysis, randomised control trials, clinical trials and review articles were chosen. The present review article suggests that consumption of high salt diet does not lead to hypertension and there are other factors which can lead to hypertension, sugar and fats being the main reasons. Salt can however lead to addiction and generally, these salty food items have a larger proportion of sugar and fats, which if over-consumed has a potential to cause obesity, hyperlipidaemia and subsequently, hypertension and other cardiovascular disorders. Hence, through the present review, I would like to suggest all the physicians to ask the hypertensive patients to cut down the intake of sugar and fat containing food items and keep a check on addiction of salty food items., (Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

Age-related inflammation is the predominant factor for neurodegenerative diseases like Alzheimer's disease (AD). In the present study, we examined memory performance and neuroinflammation in D-galactose (D-gal)-induced sub-acute aging model of rats. Our results demonstrated that chronic administration of D-gal (120 mg/kg) produced cognitive impairment as determined by Morris water maze (MWM) test and step-down passive avoidance test. D-gal also activated nuclear factor kappa B (NF-κB) p65/RelA by down-regulating the expression level of sirtuins 1 (SIRT1) in the hippocampus. Treatment with Salidroside (Sal, 20, 40 mg/kg) for 28 days ameliorated D-gal-induced memory deficits and inflammatory mediators including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Moreover, D-gal-induced activation of NF-κB signaling pathway in the brain was also inhibited by Sal via up-regulating SIRT1. These results suggest that D-gal-triggered memory impairment and inflammatory response may be associated with SIRT1/NF-κB signaling pathway, whereas treatment with Sal could positively affect these changes in hippocampus.

The calcifying Conjugatophyte Oocardium stratum occurs exclusively in spring-associated limestones (SAL) with active meteogene limestone deposition. The macroscopic colonies of Oocardium stratum form hemispherical, pinhead-like structures with a diameter of 0.5-2.0 mm. As its autecology is still poorly understood, we focused on the seasonal development of Oocardium stratum and linked environmental factors to its abundance. The study was conducted in a rivulet in Lunz/See (Austria) for 16 months on a weekly (growing season) to monthly (winter season) basis. Oocardium colonies were found throughout the whole year, with maximum abundance during the mid-summer months July and August. Repeated macro-mapping of three SAL sites measuring 750 cm(2) each showed a maximum Oocardium cover of around 30% in August; two smaller peaks developed in early summer and late autumn with ~10% cover. Diatom mats dominated by Cymbella excisiformis occurred in spring, autumn and winter, with more than 75% cover. The seasonal change between Oocardium and diatoms in limestone-precipitating springs causes a typical sequence pattern of limestone layers. Redundancy analysis revealed water temperature and bicarbonate content as the main structuring factors; these control the occurrence and growth of Oocardium, reflecting season as a background variable. Optimum growth conditions for Oocardium were an alkalinity around 4.7 meq · L(-1) and a water temperature around 13°C. Site openness, nitrate and dissolved carbon dioxide were inversely related to Oocardium biomass, the opposite for diatoms. Other environmental factors such as total ions or soluble reactive phosphorus had no significant influence on Oocardium stratum abundance., (© 2015 Phycological Society of America.)

The purpose of the present study was to investigate possible preventive effects of salidroside (sal) on a rat model of Alzheimer's disease and to explore its possible mechanism. Sub-acute aging was induced in male SD rats by subcutaneous injection of d-gal (120mg/kg) for 42 days, and the rats were treated with sal (20, 40mg/kg) or normal saline for 28 days after 14 days of d-gal injection. Morris water maze (MWM) test and step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in hippocampus were assayed by enzyme-linked immunosorbent assay (ELISA) to assess the anti-inflammatory effect of sal. Further, we estimated the expression levels of thioredoxin (Trx), thioredoxin interacting protein (Txnip/vitamin D3 up-regulated protein/thioredoxin binding protein-2), Bax, Bcl-2, caspase-9 and related-proteins of nuclear factor kappa B (NF-κB) signaling pathway by western blot assay. It showed that administration of sal significantly attenuated all the d-gal-induced changes in the hippocampus, including cognitive impairment and neuroinflammation. These analytical results provides evidence that sal can improve cognitive capacity by inhibiting neuroinflammation and affecting apoptosis-related proteins in hippocampus., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The Ciliophora is one of the most studied protist lineages because of its important ecological role in the microbial loop. While there is an abundance of molecular data for many ciliate groups, it is commonly limited to the 18S ribosomal RNA locus. There is a paucity of data when it comes to availability of protein-coding genes especially for taxa that do not belong to the class Oligohymenophorea. To address this gap, we have sequenced EST libraries for 11 ciliate species. A supermatrix was constructed for phylogenomic analysis based on 158 genes and 42,158 characters and included 16 ciliates, four dinoflagellates and nine apicomplexans. This is the first multigene-based analysis focusing on the phylum Ciliophora. Our analyses reveal two robust superclades within the Intramacronucleata; one composed of the classes Spirotrichea, Armophorea and Litostomatea (SAL) and another with Colpodea and Oligohymenophorea. Furthermore, we provide corroborative evidence for removing the ambiguous taxon Protocruzia from the class Spirotrichea and placing it as incertae sedis in the phylum Ciliophora., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Leaves and assimilative branches are crucial to the life cycle of Alhagi sparsifolia Shap. (Fabaceae), which grows in high-irradiance environments and is the main vegetation in the forelands of the Taklamakan Desert. This plant has an important role in wind protection and sand fixation at the oasis-desert transition zone. The morphology, physiology, and photosynthesis of A. sparsifolia leaves growing under low-light conditions have been extensively investigated. However, whether the plant's assimilative branches adapt similarly to low light levels is unclear, as are its specific light adaptation mechanisms. In this report, we characterized the biomass allocation, morphology, and chlorophyll a fluorescence of leaves and assimilative branches of A. sparsifolia. The results indicated that low-light conditions limited the normal growth of A. sparsifolia. The fraction of biomass allocated to leaves increased, whereas that to assimilative branches decreased. In addition, leaf thickness and assimilative branch diameter decreased, resulting in higher specific leaf area, specific assimilative branch length, and area for higher light absorbing and higher efficiency of light-usage. The assimilative branches and leaves were responded oppositely under low-light conditions in that leaves had lower photosystem II activity and assimilative branches had higher light-use efficiency to maximize light energy absorption for growth of A. sparsifolia., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Reconsolidation refers to the destabilization/re-stabilization process upon memory reactivation. However, the parameters needed to induce reconsolidation remain unclear. Here we evaluated the capacity of memory retrieval to induce reconsolidation of object recognition memory in rats. To assess whether retrieval is indispensable to trigger reconsolidation, we injected muscimol in the perirhinal cortex to block retrieval, and anisomycin (ani) to impede reconsolidation. We observed that ani impaired reconsolidation in the absence of retrieval. Therefore, stored memory underwent reconsolidation even though it was not recalled. These results indicate that retrieval and reconsolidation of object recognition memory are independent processes., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Prolonged and repeated periods of maternal separation produce behavioral phenotype of increased vulnerability to neuropsychiatric disorders and drug abuse. Most of the changes in behavior, corticosterone (CORT) and monoamine levels induced by long maternal separation (LMS) are observed after a challenge, but not in basal conditions. LMS increases ethanol-induced locomotor response and self-administration, possibly due to changes in CORT release and/or monoamine concentrations. This study examined the effects of LMS in association with chronic ethanol treatment on plasma CORT and brain monoamine concentrations in male and female Swiss mice, which were kept undisturbed (animal facility rearing - AFR) or separated from their mothers for 3h/day, from 2 to 14 days of age (LMS). As adults, one set of male and female mice received no drug treatment to assess the effect of LMS per se. Another set of animals received saline injections for 20 days and one ethanol injection (2.2g/kg, i.p.) on day 21 (acute) or ethanol for 21 days (chronic). Locomotor activity, plasma CORT levels and monoamines in the frontal cortex, striatum and hippocampus of AFR and LMS mice were evaluated in non-treated, acute and chronic ethanol-treated animals. In non-treated mice, no differences were found in CORT or locomotor activity, with small changes in monoamines content. In LMS females, chronic ethanol increased dopamine and serotonin concentrations in the frontal cortex, relative to acute ethanol LMS and to chronic ethanol-treated AFR groups (p<0.05). In LMS males, chronic ethanol increased hippocampal noradrenaline, dopamine, serotonin and metabolites when compared to respective AFR controls, as well as acute LMS. Moreover, chronic ethanol treatment resulted in higher CORT concentrations in LMS than in AFR males. Overall, these results indicate that LMS mice were more susceptible to the effects of chronic ethanol administration on CORT and brain monoamine concentrations, and that these effects were sex-dependent., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Episodic hepatic encephalopathy is frequently precipitated by factors that induce circulatory dysfunction, cause oxidative stress-mediated damage or enhance astrocyte swelling. The administration of albumin could modify these factors and improve the outcome of hepatic encephalopathy. The aim of this study is to assess the efficacy of albumin in a multicenter, prospective, double-blind, controlled trial (ClinicalTrials.gov number, NCT00886925)., Methods: Cirrhotic patients with an acute episode of hepatic encephalopathy (grade II-IV) were randomized to receive albumin (1.5g/kg on day 1 and 1.0g/kg on day 3) or isotonic saline, in addition to the usual treatment (laxatives, rifaximin 1200mg per day). The primary end point was the proportion of patients in which encephalopathy was resolved on day 4. The secondary end points included survival, length of hospital stay, and biochemical parameters., Results: Fifty-six patients were randomly assigned to albumin (n=26) or saline (n=30) stratified by the severity of HE. Both groups were comparable regarding to demographic data, liver function, and precipitating factors. The percentage of patients without hepatic encephalopathy at day 4 did not differ between both groups (albumin: 57.7% vs. saline: 53.3%; p>0.05). However, significant differences in survival were found at day 90 (albumin: 69.2% vs. saline: 40.0%; p=0.02)., Conclusions: Albumin does not improve the resolution of hepatic encephalopathy during hospitalization. However, differences in survival after hospitalization suggest that the development of encephalopathy may identify a subgroup of patients with advanced cirrhosis that may benefit from the administration of albumin., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in dopamine synthesis. Dopamine regulates TH as an end-product inhibitor through its binding to a high and low affinity site, the former being abolished by Ser40 phosphorylation only, and the latter able to bind and dissociate according to intracellular dopamine levels. Here, we have investigated TH inhibition by a dopamine metabolite found in dopaminergic brain regions, salsolinol (SAL). SAL is known to decrease dopamine in the nigrostriatal pathway and mediobasal hypothalamus, and to also decrease plasma catecholamines in rat stress models, however a target and mechanism for the effects of SAL have not been found. We found that SAL inhibits TH activity in the nanomolar range in vitro, by binding to both the high and low affinity dopamine binding sites. SAL produces the same level of inhibition as dopamine when TH is non-phosphorylated. However, it produces 3.7-fold greater inhibition of Ser40-phosphorylated TH compared to dopamine by competing more strongly with tetrahydrobiopterin, the cofactor of this enzymatic reaction. SAL's potent inhibition of phosphorylated TH would prevent TH from being fully activated to synthesise dopamine., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Objective: Magnetic resonance (MR) techniques allow noninvasive fat quantification. We aimed to investigate the accuracy of MR imaging (MRI), MR spectroscopy (MRS) and histological techniques to detect early-onset liver steatosis in three rat phenotypes assigned to an experimental glucolipotoxic model or a control group., Materials and Methods: This study was approved by the institutional committee for the protection of animals. Thirty-two rats (13 young Wistar, 6 old Wistar and 13 diabetic Goto-Kakizaki rats) fed a standard diet were assigned to a 72h intravenous infusion of glucose and Intralipid fat emulsion or a saline infusion. Plasma insulin levels were measured. Steatosis was quantified in ex vivo livers with gradient-recalled multi-echo MRI, MRS and histology as fat fractions (FF)., Results: A significant correlation was found between multi-echo MRI-FF and MRS-FF (r=0.81, p<0.01) and a weaker correlation was found between histology and MRS-FF (r=0.60, p<0.01). MRS and MRI accurately distinguished young Wistar and Goto-Kakizaki rats receiving the glucose+Intralipid infusion from those receiving the saline control whereas histology did not. Significant correlations were found between MRI or MRS and insulin plasma level (r=0.63, p<0.01; r=0.57, p<0.01), and between MRI or MRS and C-peptide concentration (r=0.54, p<0.01; r=0.44, p<0.02)., Conclusions: Multi-echo MRI and MRS may be more sensitive to measure early-onset liver steatosis than histology in an experimental glucolipotoxic rat model., (© 2013.)

Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity., (© 2013 Elsevier Inc. All rights reserved.)

A novel analytical method based on the use of a modified dispersive liquid-liquid microextraction (DLLME) technique by ionic liquids has been developed for the first time. This method was applied for the determination of salmeterol in dried blood spot samples from asthmatic patients followed by HPLC system equipped with fluorescence detector. The main novelty of the present work deals with the analysis of salmeterol in dried blood spot with significant advantages with regard to invasive sampling, volume of blood used (<20 μL), storage and transport of biological materials and requirements for special biohazard arrangements. The effects of significant factors in microextraction procedure including extracting and disperser solvents volume, sample pH and salt contents were investigated. Under optimized conditions, the mean recoveries were higher than 90.0% with linear responses about 1.00-500 ng mL(-1) concentration range. The limit of detection (LOD) was 0.30 ng mL(-1) in S/N of 3. Intra-day (n=6) and inter-day (n=3) assay precision showed relative standard deviation lower than 6.0 and 8.5% for studied drug, respectively. The developed microextraction procedure was simpler and faster than conventional extraction techniques and was omitted hazard organic solvents. Finally, the proposed method is suitable for the analysis of salmeterol in dried blood spots from asthmatic patients for therapeutic drug monitoring purpose., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Endothelial cells (ECs) play important roles in cutaneous inflammation, in part, by release of inflammatory chemokines/cytokines. Because dermal blood vessels are innervated by sympathetic nerves, the sympathetic neurotransmitter norepinephrine (NE) and the co-transmitter adenosine-5'-triphosphate (ATP) may regulate expression of EC inflammatory factors. We focused on IL-6 regulation because it has many inflammatory and immune functions, including participation in Th17 cell differentiation. Strikingly, NE and ATP synergistically induced release of IL-6 by a human dermal microvascular endothelial cell line (HMEC-1). Adrenergic antagonist and agonist studies indicated that the effect of NE on induced IL-6 release is primarily mediated by β2-adrenergic receptors (ARs). By real-time PCR IL-6 mRNA was also synergistically induced in HMEC-1 cells. This synergistic effect of NE and ATP was reproduced in primary human dermal endothelial cells (pHDMECs) and is also primarily mediated by β2-ARs. Under conditions of stress, activation of the symphathetic nervous system may lead to release of ATP and NE by sympathetic nerves surrounding dermal blood vessels with induction of IL-6 production by ECs. IL-6 may then participate in immune and inflammatory processes including generation of Th17 cells. Production of IL-6 in this manner might explain stress-induced exacerbation of psoriasis, and perhaps, other skin disorders involving Th17-type immunity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: According to the incentive sensitization theory, addiction is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems. After repeated ethanol administration, some animals develop psychomotor sensitization, a phenomenon which occurs simultaneously with the incentive sensitization. Recent evidence suggests the involvement of norepinephrine (NE) in drug addiction, with a critical role in the ethanol reinforcing properties. In this study we evaluated the influence of an agonist (phenylephrine) and an antagonist (prazosin) of alpha1-adrenergic receptors on the development and expression of behavioral sensitization to ethanol. Male Swiss mice, previously treated with ethanol or saline, were challenged with the combined administration of ethanol (or saline) with alpha1-adrenergic drugs. Prazosin (0.1; 0.5 and 1.0 mg/kg) and phenylephrine (1.0 and 2.0 mg/kg) administration blocked the expression of behavioral sensitization to ethanol. In another set of experiments, mice treated with 0.5mg/kg of prazosin+ethanol did not present the development of behavioral sensitization. However, when challenged with ethanol alone, they showed the same sensitized levels of locomotor activity of those presented by mice previously treated with ethanol and saline. Phenylephrine (1.0 mg/kg) treatment did not affect the development of behavioral sensitization. Based on this data, we concluded that the alteration of alpha1-adrenergic receptors functioning, by the administration agonists or antagonists, affected the locomotor sensitization to the stimulant effect of ethanol, suggesting that the normal functioning of the noradrenergic system is essential to its development and expression., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Recent publications show that heat-mediated tissue tightening is a promising treatment for the lax abdomen and may provide better long-term outcomes than traditional suction-assisted liposuction (SAL)., Objectives: The author evaluates the degree and duration of skin surface area contraction, as well as the influence of anatomic location of the treatment region on the degree of tissue tightening, in a study comparing SAL alone vs SAL plus radiofrequency-assisted liposuction (RFAL)., Methods: In this prospective, randomized, split abdominal study, 12 consecutive patients were treated with SAL alone on 1 side and with SAL plus RFAL on the other side. Each patient had 4 (3 × 3-cm) squares-2 per treatment type-tattooed in the lower abdominal region (2 on the right and 2 on the left). The surface area of these squares was measured with the Vectra computerized measurement system (Canfield, Inc, Fairfield, New Jersey) at pretreatment, at 6 weeks posttreatment, and at 1 year posttreatment. All measurements were subjected to statistical analysis using predictive analytic software and were evaluated for statistical significance., Results: In regions treated with SAL alone, there was a 10.4% mean skin surface area contraction at 6 weeks and 8.3% at 1 year posttreatment. The mean skin surface area reduction was 25.8% in regions treated with radiofrequency plus SAL at 6 weeks and at 1 year. The anatomic location of each square (medial vs lateral) did not statistically correlate with more or less tissue tightening., Conclusions: Radiofrequency-assisted tissue tightening, when applied in conjunction with SAL, is effective in achieving greater skin surface area reduction.

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand., (© 2013 Elsevier B.V. All rights reserved.)

Although extensive evidence demonstrates that repeated administration of amphetamine (AMPH) induces behavioral and neurochemical sensitization, the influence of the developmental timing of AMPH administration is unknown. This is an important issue to address because it could help clarify the influence of early drug exposure on neuronal plasticity and the involvement of dopaminergic sensitization in the etiopathology of neuropsychiatric disorders. Thus, we decided to investigate the molecular alterations induced by the administration of AMPH during adolescence, when repeated exposure to the psychostimulant may interfere with developmental neuroplasticity. We investigated the expression of the neurotrophin brain-derived neurotrophic factor (BDNF) and of two inducible-early genes (arc and cfos) that bridge neuronal activity with long-lasting functional alterations. We found that peri-pubertal treatment with AMPH induces long-lasting changes in the expression of bdnf and of activity-regulated genes in the hippocampus and in the prefrontal/frontal cortex, and leads to alterations of their short-term modulation in response to a subsequent acute AMPH challenge. These data suggest that AMPH exposure in peri-puberty may negatively affect the maturation of brain structures, such as the prefrontal cortex, which facilitate the development of dopamine sensitization and may contribute to dopamine-dependent behavioral dysfunctions and molecular alterations in adulthood., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Lisdexamfetamine dimesylate, which consists of L-lysine covalently bound to D-amfetamine, is the first prodrug for treating ADHD. Its metabolic conversion to yield D-amfetamine by rate-limited, enzymatic hydrolysis is unusual because it is performed by peptidases associated with red blood cells. Other stimulants shown to be effective in managing ADHD include D-amfetamine, methylphenidate and modafinil. All have the potential for misuse or recreational abuse. The discriminative and reinforcing effects of these compounds were determined in rats using a 2-choice, D-amfetamine (0.5 mg/kg, i.p.)-cued drug-discrimination test, and by substitution for intravenous cocaine in self-administration. Lisdexamfetamine (0.5-1.5 mg/kg [D-amfetamine base], p.o.) generalised to saline when tested 15 min post-dosing, but dose-dependently generalised to d-amfetamine at 60 min. At 120 min, its D-amfetamine-like effects were substantially diminished. At 15 min, methylphenidate (3.0-10 mg/kg, p.o.) and D-amfetamine (0.1-1.5 mg/kg, p.o.) dose-dependently generalised to the intraperitoneal D-amfetamine cue. Switching to the intraperitoneal route reduced the interval required for lisdexamfetamine to be recognised as D-amfetamine-like, but did not alter its potency. Switching to intraperitoneal injection increased the potency of methylphenidate and D-amfetamine by 3.4× and 2.2×, respectively. Modafinil (50-200 mg/kg, i.p.) generalised partially, but not fully, to d-amfetamine. Methylphenidate (0.1, 0.3, 1.0 mg/kg/injection, i.v.) maintained robust self-administration at the 2 highest doses. Neither lisdexamfetamine (0.05, 0.15 or 0.5 mg/kg/injection [D-amfetamine base], i.v.) nor modafinil (0.166, 0.498 or 1.66 mg/kg/injection, i.v.) served as reinforcers. The results reveal important differences between the profiles of these stimulants. Lisdexamfetamine did not serve as a positive reinforcer in cocaine-trained rats, and although it generalised fully to D-amfetamine, its discriminative effects were markedly influenced by its unusual pharmacokinetics., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The dorsomedial nucleus of the hypothalamus (DMH) has been proposed to participate in stress-induced hyperalgesia through facilitation of pronociceptive cells in the rostroventromedial medulla (RVM). We hypothesized that the DMH participates in hyperalgesia induced by arthritis. The DMH was pharmacologically manipulated while assessing heat-evoked nociceptive behavior or the discharge rates of pronociceptive RVM ON- and antinociceptive RVM OFF-like cells in NAIVE, SHAM and monoarthritic (ARTH) animals. In NAIVE and SHAM animals, the changes in nociceptive behavior induced by activation of the DMH by glutamate and inhibition by lidocaine were in line with earlier evidence indicating that the DMH has a nociceptive facilitating role. However, in ARTH animals, neither activation nor inhibition of the DMH influenced pain-like behavior evoked by stimulation of an uninflamed skin region (paw and tail). In accordance with these behavioral results, activation or inhibition of the DMH induced pronociceptive changes in the discharge rates of RVM cells in NAIVE and SHAM animals, which suggests that the DMH has a pronociceptive role mediated by the RVM in normal animals. However, in ARTH animals, both glutamate and lidocaine in the DMH failed to influence either pain-like behavior or noxious stimulation-evoked responses of RVM cells, while blocking the DMH increased spontaneous activity in the pronociceptive RVM ON cells. Our data indicate that the DMH participates in descending facilitation of cutaneous nociception in healthy controls, but it is not engaged in the regulation of cutaneous nociception in monoarthritic animals, while a minor role in tonic suppression of nociception in arthritis cannot be discarded., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Injections of noradrenaline into the lateral parabrachial nucleus (LPBN) increase arterial pressure and 1.8% NaCl intake and decrease water intake in rats treated with the diuretic furosemide (FURO) combined with a low dose of the angiotensin converting enzyme inhibitor captopril (CAP). In the present study, we investigated the influence of the pressor response elicited by noradrenaline injected into the LPBN on FURO+CAP-induced water and 1.8% NaCl intake. Male Holtzman rats with bilateral stainless steel guide-cannulas implanted into LPBN were used. Bilateral injections of noradrenaline (40 nmol/0.2 μl) into the LPBN increased FURO+CAP-induced 1.8% NaCl intake (12.2±3.5, vs., saline: 4.2±0.8 ml/180 min), reduced water intake and strongly increased arterial pressure (50±7, vs. saline: 1±1 mmHg). The blockade of the α1 adrenoceptors with the prazosin injected intraperitoneally abolished the pressor response and increased 1.8% NaCl and water intake in rats treated with FURO+CAP combined with noradrenaline injected into the LPBN. The deactivation of baro and perhaps volume receptors due to the cardiovascular effects of prazosin is a mechanism that may facilitate water and NaCl intake in rats treated with FURO+CAP combined with noradrenaline injected into the LPBN. Therefore, the activation of α2 adrenoceptors with noradrenaline injected into the LPBN, at least in dose tested, may not completely remove the inhibitory signals produced by the activation of the cardiovascular receptors, particularly the signals that result from the extra activation of these receptors with the increase of arterial pressure., (© 2013.)

We aimed to determine the potential of various doses of metoclopramide (MCP, a dopamine antagonist) to reduce lithium chloride (LiCl)-induced conditioned gaping (a nausea-induced behaviour) in rats, using the taste reactivity test. We then evaluated whether an ineffective low dose of cannabidiolic acid (CBDA, 0.1 μg/kg, Rock and Parker, 2013), the potent acidic precursor of cannabidiol (CBD, a non-psychoactive component of cannabis) could enhance the anti-nausea effects of an ineffective low dose of MCP. MCP (3.0 mg/kg) reduced conditioned gaping responses. Coadministration of ineffective doses of MCP (0.3 mg/kg) and CBDA (0.1 μg/kg) enhanced the suppression of conditioned gaping, over that of either drug alone, without interfering with conditioned taste avoidance. MCP dose-dependently reduced nausea-induced conditioned gaping in rats. As well, the suppression of conditioned gaping was enhanced when ineffective doses of MCP and CBDA were coadministered. These data suggest that CBDA could be a powerful adjunct treatment to anti-emetic regimens for chemotherapy-induced nausea., (© 2013.)

Methamphetamine (METH) is a central nervous system psychostimulant with a high potential for abuse. At high doses, METH causes a selective degeneration of dopaminergic terminals in the striatum, sparing other striatal terminals and cell bodies. We previously detected a deficit in parkin after binge METH in rat striatal synaptosomes. Parkin is an ubiquitin-protein E3 ligase capable of protecting dopamine neurons from diverse cellular insults. Whether the deficit in parkin mediates the toxicity of METH and whether parkin can protect from toxicity of the drug is unknown. The present study investigated whether overexpression of parkin attenuates degeneration of striatal dopaminergic terminals exposed to binge METH. Parkin overexpression in rat nigrostriatal dopamine system was achieved by microinjection of adeno-associated viral transfer vector 2/6 encoding rat parkin (AAV2/6-parkin) into the substantia nigra pars compacta. The microinjections of AAV2/6-parkin dose-dependently increased parkin levels in both the substantia nigra pars compacta and striatum. The levels of dopamine synthesizing enzyme, tyrosine hydroxylase, remained at the control levels; therefore, tyrosine hydroxylase immunoreactivity was used as an index of dopaminergic terminal integrity. In METH-exposed rats, the increase in parkin levels attenuated METH-induced decreases in striatal tyrosine hydroxylase immunoreactivity in a dose-dependent manner, indicating that parkin can protect striatal dopaminergic terminals against METH neurotoxicity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Violence has been observed in humans and animals alike, indicating its evolutionary/biological significance. However, violence in animals has often been confounded with functional forms of aggressive behavior. Currently, violence in animals is identified primarily as either a quantitative behavior (an escalated, pathological and abnormal form of aggression characterized primarily by short attack latencies, and prolonged and frequent harm-oriented conflict behaviors) or a qualitative one (characterized by attack bites aimed at vulnerable parts of the opponent's body and context independent attacks regardless of the environment or the sex and type of the opponent). Identification of an operational definition for violence thus not only helps in understanding its potential differences from adaptive forms of aggression but also in the selection of appropriate animal models for both. We address this issue theoretically by drawing parallels from research on aggression and appeasement in humans and other animals. We also provide empirical evidences for violence in mice selected for high aggression by comparing our findings with other currently available potentially violent rodent models. The following violence-specific features namely (1) Display of low levels of pre-escalatory/ritualistic behaviors. (2) Immediate and escalated offense durations with low withdrawal rates despite the opponent's submissive supine and crouching/defeat postures. (3) Context independent indiscriminate attacks aimed at familiar/unfamiliar females, anaesthetized males and opponents and in neutral environments. (4) Orientation of attack-bites toward vulnerable body parts of the opponent resulting in severe wounding. (5) Low prefrontal serotonin (5-HT) levels upon repeated aggression. (6) Low basal heart rates and hyporesponsive hypothalamus-pituitary-adrenocortical (HPA) axis were identified uniquely in the short attack latency (SAL) mice suggesting a qualitative difference between violence and adaptive aggression in animals.