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1.
Animals (Basel) ; 14(7)2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38612321

ABSTRACT

Functional brain connectivity based on resting-state functional magnetic resonance imaging (fMRI) has been shown to be correlated with human personality and behavior. In this study, we sought to know whether capabilities and traits in dogs can be predicted from their resting-state connectivity, as in humans. We trained awake dogs to keep their head still inside a 3T MRI scanner while resting-state fMRI data was acquired. Canine behavior was characterized by an integrated behavioral score capturing their hunting, retrieving, and environmental soundness. Functional scans and behavioral measures were acquired at three different time points across detector dog training. The first time point (TP1) was prior to the dogs entering formal working detector dog training. The second time point (TP2) was soon after formal detector dog training. The third time point (TP3) was three months' post detector dog training while the dogs were engaged in a program of maintenance training for detection work. We hypothesized that the correlation between resting-state FC in the dog brain and behavior measures would significantly change during their detection training process (from TP1 to TP2) and would maintain for the subsequent several months of detection work (from TP2 to TP3). To further study the resting-state FC features that can predict the success of training, dogs at TP1 were divided into a successful group and a non-successful group. We observed a core brain network which showed relatively stable (with respect to time) patterns of interaction that were significantly stronger in successful detector dogs compared to failures and whose connectivity strength at the first time point predicted whether a given dog was eventually successful in becoming a detector dog. A second ontologically based flexible peripheral network was observed whose changes in connectivity strength with detection training tracked corresponding changes in behavior over the training program. Comparing dog and human brains, the functional connectivity between the brain stem and the frontal cortex in dogs corresponded to that between the locus coeruleus and left middle frontal gyrus in humans, suggestive of a shared mechanism for learning and retrieval of odors. Overall, the findings point toward the influence of phylogeny and ontogeny in dogs producing two dissociable functional neural networks.

2.
Arch Sex Behav ; 51(6): 2813-2821, 2022 08.
Article in English | MEDLINE | ID: mdl-34791579

ABSTRACT

Life history theory proposes that it is adaptive for older people to shift investment away from reproductive effort (such as mating) to survivorship. However, it remains unclear whether the shift is also present at the psychological level. We investigated this question by comparing preferences for mate choice-relevant cues, sexually dimorphic facial images, between older (60 years and older, n = 92) and younger adults (18-40 years, n = 86). Results showed that older adults had significantly smaller preferences for sexually dimorphic faces of both sexes than young adults. Specifically, both older men and women showed no significant preferences for sexually dimorphic traits when judging opposite-sex faces, and smaller preferences for masculine male faces and feminine female faces when judging same-sex faces. Young adults generally showed strong preferences for masculine male faces and feminine female faces. In Study 2, we confirmed that the absent/reduced preferences in older adults for sexually dimorphic faces did not result from poor visual ability. The smaller preferences for sexually dimorphic facial cues in older adults compared to young adults suggest that older adults may shift away from mating-oriented psychology as they become less fertile.


Subject(s)
Face , Masculinity , Aged , Choice Behavior , Female , Humans , Male , Sex Characteristics , Sexual Behavior , Young Adult
3.
Int J Sports Med ; 42(10): 930-935, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33607666

ABSTRACT

Concussion is the most common match injury in rugby union. Some players wear padded headgear, but whether this protects against concussion is unclear. In professional male rugby union players, we examined: (i) the association between the use of headgear and match concussion injury incidence, and (ii) whether wearing headgear influenced time to return to play following concussion. Using a nested case-control within a cohort study, four seasons (2013-2017) of injury data from 1117 players at the highest level of rugby union in England were included. Cases were physician-diagnosed concussion injuries. Controls were other contact injuries (excluding all head injuries). We determined headgear use by viewing video footage. Sixteen percent of cases and controls wore headgear. Headgear use had no significant effect on concussion injury incidence (adjusted odds ratio=1.05, 95% CI: 0.71-1.56). Median number of days absent for concussion whilst wearing headgear was 8 days, compared with 7 days without headgear. Having sustained a concussion in the current or previous season increased the odds of concussion more than four-fold (odds ratio=4.55, 95% CI: 3.77-5.49). Wearing headgear was not associated with lower odds of concussions or a reduced number of days' absence following a concussion.


Subject(s)
Athletic Injuries/epidemiology , Brain Concussion/epidemiology , Football/injuries , Head Protective Devices , Athletic Injuries/prevention & control , Brain Concussion/prevention & control , Case-Control Studies , England/epidemiology , Humans , Incidence , Longitudinal Studies , Male
4.
Anat Rec (Hoboken) ; 304(1): 210-221, 2021 01.
Article in English | MEDLINE | ID: mdl-31714028

ABSTRACT

Canine ß-defensin 103 (cBD103) and its common variant cBD103ΔG23 are multitasking polypeptides. As a ß-defensin, cBD103 is one of many antimicrobial agents used by the innate immunity to thwart pathogenic colonization. In this study, we showed that cBD103 was expressed throughout the nasal cavity, with primary expression in the nares as well as respiratory and olfactory epithelia. In the rostral nasal concha, cBD103 was expressed in the epithelium, and to a lesser degree in the lamina propria, but was absent in goblet cells. In the main olfactory epithelium, virtually all cells in the epithelial layer and select cells associated with Bowman's glands expressed cBD103. We also showed that the ΔG23 mutation did not appreciably alter the antimicrobial activity of the peptide against several species of microorganisms tested in nutrient-rich or minimal media or minimal media with salt added. Moreover, we showed antimicrobial activity in minimal media did not necessarily predict the inhibitory action of the peptide in nutrient-rich media. Both forms of cBD103 caused ultrastructural changes (membrane blebbing, condensation of intracellular contents and cell wall lysis) in Escherichia coli and Staphylococcus aureus. As a ligand of the melanocortin receptors, we showed that cBD103ΔG23 increased ERK1/2 activation and cAMP accumulation when bound to the human or canine melanocortin-4 receptor, acting as a weak allosteric agonist.


Subject(s)
Mutation , Nasal Cavity/metabolism , Olfactory Mucosa/metabolism , Receptor, Melanocortin, Type 4/metabolism , beta-Defensins/metabolism , Animals , Cyclic AMP/metabolism , Dogs , Escherichia coli Infections/genetics , Escherichia coli Infections/metabolism , Receptor, Melanocortin, Type 4/genetics , Signal Transduction/physiology , Staphylococcal Infections/genetics , Staphylococcal Infections/metabolism , beta-Defensins/genetics
5.
Cereb Circ Cogn Behav ; 2: 100015, 2021.
Article in English | MEDLINE | ID: mdl-36324721

ABSTRACT

Background: Blood pressure-lowering medications, antiplatelet drugs and statins are often prescribed to asymptomatic patients with white matter hyperintensities (WMH). A clinical trial is needed, but potential trial participants would be excluded if they already had another indication to take the medication. It is likely that many patients with WMH would already have a recognised vascular-related indication for these drugs.We used data from the UK Biobank study to determine what proportion of people with WMH were not taking these drugs and would be potentially able to enter a clinical trial of antiplatelet drugs, statins, or BP-lowering medication. Methods: We used the UK Biobank MRI sub-study of healthy volunteers aged 40-70 years as our cohort. We considered that WMH volumes in the top quartile (2.7-89 mls) were severe enough for a patient to be at risk of progression and be offered treatment. Such patients could also be included in a hypothetical clinical trial if there were no contraindications. Using the product licenses, we defined exclusion criteria for four hypothetical clinical trials of aspirin, clopidogrel, statins, and tight BP control. We then calculated what proportion of patients would still be eligible if these criteria were applied. Results: 5794/23,179 patients had WMH in the top quartile. Of these, 4006/5794 69% (95% CI 68-70%) would be eligible for a trial of aspirin; with 81% (95% CI 80-82%) eligible for a trial of clopidogrel; 56% (95% CI 55-58%) of patients would be eligible to enter into a trial of a lower BP target, and 58% (95%CI 57-59%) would be able to enter a trial of a statin. Conclusions: Over 80% of patients with WMH in the UK biobank would be eligible to enter a trial of an antiplatelet and just over half would be eligible to enter a trial of a statin or BP-lowering medication.

6.
Psychoneuroendocrinology ; 115: 104630, 2020 05.
Article in English | MEDLINE | ID: mdl-32120018

ABSTRACT

Sex hormones are thought to influence human mate preferences. Previous studies have reported mixed results regarding the association between men's testosterone levels and their mate preferences. The present study investigated the effect of testosterone administration on men's facial femininity preference. Heterosexual Chinese male participants (n = 140) received a single dose of 150 mg testosterone or placebo gel in a double-blind, placebo-controlled, between-participant design. Results showed that Chinese men demonstrated general preferences for feminized women's faces, consistent with previous results from the Western population. More importantly, men showed stronger attraction to femininity in women's faces three hours after testosterone administration than at the beginning of the session. In the placebo group, no significant change in facial femininity preferences was found between time points. These results indicate that exogenous testosterone increases men's facial femininity preferences in a Chinese population.


Subject(s)
Choice Behavior/drug effects , Facial Recognition/drug effects , Femininity , Heterosexuality/drug effects , Masculinity , Sex Characteristics , Sexual Behavior/drug effects , Testosterone/pharmacology , Adolescent , Adult , China , Humans , Male , Testosterone/administration & dosage , Young Adult
7.
Anat Rec (Hoboken) ; 303(2): 318-329, 2020 02.
Article in English | MEDLINE | ID: mdl-30614661

ABSTRACT

The colonial naked mole rat Heterocephalus glaber is a subterranean, eusocial rodent. The H. glaber vomeronasal organ neuroepithelium (VNE) displays little postnatal growth. However, the VNE remains neuronal in contrast to some mammals that possess nonfunctional vomeronasal organ remnants, for example, catarrhine primates and some bats. Here, we describe the vomeronasal organ (VNO) microanatomy in the naked mole rat and we make preliminary observations to determine if H. glaber shares its minimal postnatal VNE growth with other African mole rats. We also determine the immunoreactivity to the mitotic marker Ki67, growth-associated protein 43 (GAP43), and olfactory marker protein (OMP) in six adult and three subadult H. glaber individuals. VNE volume measurements on a small sample of Cryptomys hottentotus and Fukomys damarensis indicate that the VNE of those African mole rat species are also likely to be growth-deficient. Ki67(+) cells show that the sensory epithelium is mitotically active. GAP43 labelling indicates neurogenesis and OMP(+) cells are present though less numerous compared to GAP43(+) cells. In this respect, the VNO of H. glaber does not appear vestigial. The African mole rat VNE may be unusually variable, perhaps reflecting reduced selection pressure on the vomeronasal system. If so, African mole rats may provide a useful genetic model for understanding the morphological variability observed in the mammalian VNO. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc. Anat Rec, 303:318-329, 2020. © 2019 American Association for Anatomy.


Subject(s)
Mole Rats/anatomy & histology , Vomeronasal Organ/anatomy & histology , Animals , Mole Rats/physiology , Neurons/physiology , Olfactory Mucosa/anatomy & histology , Olfactory Mucosa/physiology , Vomeronasal Organ/physiology
8.
Drug Alcohol Depend ; 206: 107780, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31835186

ABSTRACT

BACKGROUND: Alcohol intoxication has been associated with increases in risk taking behavior and more ambiguously, alterations in emotional perception. In the first study of its kind, we examine how theories of disgust can be used to help explain these effects. METHODS: Using a single-blind procedure, participants (n = 73) were randomly allocated to an alcohol (Males: 0.68 g/kg; Females: 0.60 g/kg) or placebo condition and then completed a psychometric measure of disgust (TDDS). RESULTS: Results revealed a non-significant trend toward lower disgust sensitivity in the alcohol versus placebo condition. We did however find a significant negative correlation, whereby increases in breath alcohol level were associated with decreased pathogen disgust. CONCLUSIONS: These findings demonstrate a relationship between breath alcohol level and disgust sensitivity which could help explain differences in risk associated behavior.


Subject(s)
Alcohol Drinking/psychology , Alcoholic Beverages/adverse effects , Disgust , Social Behavior , Adolescent , Adult , Alcohol Drinking/metabolism , Alcoholic Beverages/analysis , Breath Tests/methods , Emotions/drug effects , Emotions/physiology , Female , Humans , Male , Middle Aged , Psychometrics , Single-Blind Method , Young Adult
9.
Biochemistry ; 58(41): 4236-4245, 2019 10 15.
Article in English | MEDLINE | ID: mdl-31549502

ABSTRACT

NeuB is a bacterial sialic acid synthase used by neuroinvasive bacteria to synthesize N-acetylneuraminate (NeuNAc), helping them to evade the host immune system. NeuNAc oxime is a potent slow-binding NeuB inhibitor. It dissociated too slowly to be detected experimentally, with initial estimates of its residence time in the active site being >47 days. This is longer than the lifetime of a typical bacterial cell, meaning that inhibition is effectively irreversible. Inhibition data fitted well to a model that included a pre-equilibration step with a Ki of 36 µM, followed by effectively irreversible conversion to an E*·I complex, with a k2 of 5.6 × 10-5 s-1. Thus, the inhibitor can subvert ligand release and achieve extraordinary residence times in spite of a relatively modest initial dissociation constant. The crystal structure showed the oxime functional group occupying the phosphate-binding site normally occupied by the substrate PEP and the tetrahedral intermediate. There was an ≈10% residual rate at high inhibitor concentrations regardless of how long NeuB and NeuNAc oxime were preincubated together. However, complete inhibition was achieved by incubating NeuNAc oxime with the actively catalyzing enzyme. This requirement for the enzyme to be actively turning over for the inhibitor to bind to the second subunit demonstrated an important role for intersubunit communication in the inhibitory mechanism.


Subject(s)
N-Acetylneuraminic Acid/chemistry , Oximes/chemistry , Oximes/pharmacology , Oxo-Acid-Lyases/antagonists & inhibitors , Oxo-Acid-Lyases/chemistry , 3-Deoxy-7-Phosphoheptulonate Synthase/chemistry , Aldehyde-Lyases/chemistry , Catalytic Domain , Crystallization , Crystallography, X-Ray , Genetic Vectors , Kinetics , Neisseria meningitidis/genetics , Oximes/chemical synthesis , Oxo-Acid-Lyases/isolation & purification , Protein Binding , Time Factors , Triose-Phosphate Isomerase/chemistry
10.
J Cancer ; 9(23): 4536-4546, 2018.
Article in English | MEDLINE | ID: mdl-30519360

ABSTRACT

Background: Docetaxel (DOC), or Taxotere, is an anthracycline antibiotic used to treat multiple types of cancer. It is a first-line chemotherapy treatment for patients with metastasized, hormone-resistant prostate cancer (PCa) or for patients with high-risk, localized PCa that could benefit from early chemotherapy treatment. Previously, we showed that stearidonic acid (SDA), an omega-3 fatty acid, enhances the cytotoxicity of doxorubicin (DOX) in human PCa cells. This observation suggests that PCa therapies using SDA and chemotherapeutic drugs in combination offer attractive possibilities for developing treatments that ameliorate toxic side effects of some commonly used chemotherapy drugs. Objectives: We used androgen-resistant PC3 and DU 145 cells derived from human prostate cancer to quantify the effects of combined SDA and DOC on proliferation/viability and on the production of pro-apoptotic caspases 9 and 3. We also compared the effects of SDA with those of BAY, a pharmacological inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), in androgen-sensitive LNCaP cells. Finally, we qualitatively and quantitatively assessed the drug combination on androgen receptor (AR) and peroxisome proliferator-activated receptor gamma (PPARγ) expression in LNCaP and PC3 cells, respectively. Methods: The half maximal inhibitory concentration (IC50) and combination indices of SDA and DOC in PC3 and DU 145 cells were determined using the MTT cell viability assay. To quantify the effects of SDA and BAY on NF-ĸB activity, we used luciferase reporter assays in LNCaP cells that were stably transduced with lentiviral vectors carrying NF-ĸB response element sequence upstream of the luciferase gene sequence. AR and PPARγ expression were assessed by western blotting and immunocytochemistry. We considered caspase 9 and 3 cleavage to be apoptosis markers and determined the drug combination effect on the extent of that cleavage by western blot analysis. Results: The cytotoxic effects of DOC were synergistically enhanced by SDA when the two were added to DU145 and PC3 cell cultures. Combination index (CI) analyses based on the Chou-Talalay method and mass action law showed synergistic interaction with CI <1. SDA suppressed TNFα-induced NF-κB activity similarly to BAY. The SDA/DOC combination down regulated testosterone (T)-induced AR and troglitazone-induced PPARγ protein expression when compared to using the drugs singly. Similarly, the SDA/DOC combination induced caspase 9 and 3 production and cleavage suggesting apoptosis induction. Like our DOX studies, this work provides proof-of-concept for using SDA and DOC in combination to reduce the dose, and therefore the toxicity, of DOC and possibly increasing the survival benefit in DOC clinical translation studies.

11.
Front Vet Sci ; 5: 127, 2018.
Article in English | MEDLINE | ID: mdl-30013977

ABSTRACT

Prior functional Magnetic Resonance Imaging (fMRI) studies have indicated increased neural activation when zinc nanoparticles are added to odorants in canines. Here we demonstrate that zinc nanoparticles up-regulate directional brain connectivity in parts of the canine olfactory network. This provides an explanation for previously reported enhancement in the odor detection capability of the dogs in the presence of zinc nanoparticles. In this study, we obtained fMRI data from awake and unrestrained dogs while they were being exposed to odorants with and without zinc nanoparticles, zinc nanoparticles suspended in water vapor, as well as just water vapor alone. We obtained directional connectivity between the brain regions of the olfactory network that were significantly stronger for the condition of odorant + zinc nanoparticles compared to just odorants, water vapor + zinc nanoparticles and water vapor alone. We observed significant strengthening of the paths of the canine olfactory network in the presence of zinc nanoparticles. This result indicates that zinc nanoparticles could potentially be used to increase canine detection capabilities in the environments of very low concentrations of the odorants, which would have otherwise been undetected.

12.
PLoS One ; 12(12): e0189273, 2017.
Article in English | MEDLINE | ID: mdl-29261701

ABSTRACT

Olfactory responses are intensely enhanced with the addition of endogenous and engineered primarily-elemental small zinc nanoparticles (NPs). With aging, oxidation of these Zn nanoparticles eliminated the observed enhancement. The design of a polyethylene glycol coating to meet storage requirements of engineered zinc nanoparticles is evaluated to achieve maximal olfactory benefit. The zinc nanoparticles were covered with 1000 g/mol or 400 g/mol molecular weight polyethylene glycol (PEG). Non-PEGylated and PEGylated zinc nanoparticles were tested by electroolfactogram with isolated rat olfactory epithelium and odorant responses evoked by the mixture of eugenol, ethyl butyrate and (±) carvone after storage at 278 K (5 oC), 303 K (30 oC) and 323 K (50 oC). The particles were analyzed by atomic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and laser Doppler velocimetry. Our data indicate that stored ZnPEG400 nanoparticles maintain physiologically-consistent olfactory enhancement for over 300 days. These engineered Nanoparticles support future applications in olfactory research, sensitive detection, and medicine.


Subject(s)
Metal Nanoparticles/chemistry , Odorants , Olfactory Mucosa/drug effects , Polyethylene Glycols/chemistry , Zinc/chemistry , Microscopy, Atomic Force , Microscopy, Electron, Transmission , Photoelectron Spectroscopy
13.
Biochem Biophys Res Commun ; 490(2): 202-208, 2017 08 19.
Article in English | MEDLINE | ID: mdl-28606474

ABSTRACT

Adiponectin is a protein secreted by white adipocytes that plays an important role in insulin action, energy homeostasis and the development of atherosclerosis. The intracellular localization and trafficking of GLUT4 and leptin in adipocytes has been well studied, but little is known regarding the intracellular trafficking of adiponectin. Recent studies have demonstrated that constitutive adiponectin secretion is dependent on PIP2 levels and the integrity of cortical F-actin. Non-muscle myosin II is an actin-based motor that is associated with membrane vesicles and participates in vesicular trafficking in mammalian cells. Therefore, we investigated the role of myosin II in the trafficking and secretion of adiponectin in 3T3-L1 adipocytes. Confocal microscopy revealed that myosin IIA and IIB were dispersed throughout the cytoplasm of the adipocyte. Both myosin isoforms were localized in the Golgi/TGN region as evidenced by colocalization with the cis-Golgi marker, p115 and the trans-Golgi marker, γ-adaptin. Inhibition of myosin II activity by blebbistatin or actin depolymerization by latrunculin B dispersed myosin IIA and IIB towards the periphery while significantly inhibiting adiponectin secretion. Therefore, the constitutive trafficking and secretion of adiponectin in 3T3-L1 adipocytes occurs by an actin-dependent mechanism that involves the actin-based motors, myosin IIA and IIB.


Subject(s)
Adiponectin/metabolism , Nonmuscle Myosin Type IIA/metabolism , Nonmuscle Myosin Type IIB/metabolism , 3T3-L1 Cells , Adipocytes/drug effects , Adipocytes/metabolism , Adiponectin/antagonists & inhibitors , Animals , Biological Transport/drug effects , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cells, Cultured , Dose-Response Relationship, Drug , Heterocyclic Compounds, 4 or More Rings/pharmacology , Mice , Nonmuscle Myosin Type IIA/antagonists & inhibitors , Nonmuscle Myosin Type IIB/antagonists & inhibitors , Structure-Activity Relationship , Thiazolidines/pharmacology
14.
Neuroscience ; 340: 117-125, 2017 01 06.
Article in English | MEDLINE | ID: mdl-27793778

ABSTRACT

Sandhoff disease (SD) is a lysosomal storage disorder characterized by the absence of hydrolytic enzyme ß-N-acetylhexosaminidase (Hex), which results in storage of GM2 ganglioside in neurons and unremitting neurodegeneration. Neuron loss initially affects fine motor skills, but rapidly progresses to loss of all body faculties, a vegetative state, and death by five years of age in humans. A well-established feline model of SD allows characterization of the disease in a large animal model and provides a means to test the safety and efficacy of therapeutic interventions before initiating clinical trials. In this study, we demonstrate a robust central nervous system (CNS) inflammatory response in feline SD, primarily marked by expansion and activation of the microglial cell population. Quantification of major histocompatibility complex II (MHC-II) labeling revealed significant up-regulation throughout the CNS with areas rich in white matter most severely affected. Expression of the leukocyte chemokine macrophage inflammatory protein-1 alpha (MIP-1α) was also up-regulated in the brain. SD cats were treated with intracranial delivery of adeno-associated viral (AAV) vectors expressing feline Hex, with a study endpoint 16weeks post treatment. AAV-mediated gene delivery repressed the expansion and activation of microglia and normalized MHC-II and MIP-1α levels. These data reiterate the profound inflammatory response in SD and show that neuroinflammation is abrogated after AAV-mediated restoration of enzymatic activity.


Subject(s)
Brain/immunology , Genetic Therapy , Sandhoff Disease/immunology , Sandhoff Disease/therapy , Adaptor Proteins, Signal Transducing/metabolism , Animals , Astrocytes/immunology , Astrocytes/pathology , Brain/pathology , Cats , Dependovirus/genetics , Disease Models, Animal , Genes, MHC Class II/physiology , Genetic Vectors , Gliosis/immunology , Gliosis/pathology , Gliosis/therapy , Immunohistochemistry , Microglia/immunology , Microglia/pathology , Neurons/immunology , Neurons/pathology , Polymerase Chain Reaction , Sandhoff Disease/pathology , Transcription Factors/genetics , Transcription Factors/metabolism
15.
Sci Rep ; 6: 36851, 2016 11 25.
Article in English | MEDLINE | ID: mdl-27886204

ABSTRACT

Diffusion tensor imaging (DTI) provides us an insight into the micro-architecture of white-matter tracts in the brain. This method has proved promising in understanding and investigating the neuronal tracts and structural connectivity between the brain regions in primates as well as rodents. The close evolutionary relationship between canines and humans may have spawned a unique bond in regard to social cognition rendering them useful as an animal model in translational research. In this study, we acquired diffusion data from anaesthetized dogs and created a DTI-based atlas for a canine model which could be used to investigate various white matter diseases. We illustrate the application of this atlas by calculating DTI tractography based structural connectivity between the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) regions of the default mode network (DMN) in dogs. White matter connectivity was investigated to provide structural basis for the functional dissociation observed between the anterior and posterior parts of DMN. A comparison of the integrity of long range structural connections (such as in the DMN) between dogs and humans is likely to provide us with new perspectives on the neural basis of the evolution of cognitive functions.


Subject(s)
Diffusion Tensor Imaging , Gyrus Cinguli/anatomy & histology , Gyrus Cinguli/diagnostic imaging , Neural Pathways/anatomy & histology , Neural Pathways/diagnostic imaging , White Matter/anatomy & histology , White Matter/diagnostic imaging , Animals , Dogs
16.
Biometals ; 29(6): 1005-1018, 2016 12.
Article in English | MEDLINE | ID: mdl-27649965

ABSTRACT

Electrical responses of olfactory sensory neurons to odorants were examined in the presence of zinc nanoparticles of various sizes and degrees of oxidation. The zinc nanoparticles were prepared by the underwater electrical discharge method and analyzed by atomic force microscopy and X-ray photoelectron spectroscopy. Small (1.2 ± 0.3 nm) zinc nanoparticles significantly enhanced electrical responses of olfactory neurons to odorants. After oxidation, however, these small zinc nanoparticles were no longer capable of enhancing olfactory responses. Larger zinc oxide nanoparticles (15 nm and 70 nm) also did not modulate responses to odorants. Neither zinc nor zinc oxide nanoparticles produced olfactory responses when added without odorants. The enhancement of odorant responses by small zinc nanoparticles was explained by the creation of olfactory receptor dimers initiated by small zinc nanoparticles. The results of this work will clarify the mechanisms for the initial events in olfaction, as well as to provide new ways to alleviate anosmia related to the loss of olfactory receptors.


Subject(s)
Metal Nanoparticles/chemistry , Odorants , Olfactory Receptor Neurons/drug effects , Zinc/chemistry , Zinc/pharmacology , Animals , Electrophysiology/methods , Male , Microscopy, Atomic Force , Microscopy, Electron, Transmission , Olfactory Receptor Neurons/physiology , Photoelectron Spectroscopy , Rats, Sprague-Dawley , Receptors, Odorant/chemistry , Zinc Oxide/chemistry , Zinc Oxide/pharmacology
17.
Acta Pharmacol Sin ; 37(2): 187-95, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26616727

ABSTRACT

AIM: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. METHODS: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- and 9-weeks following fistula. The protein expression of adiponectin, adiponectin receptors (AdipoR1/R2 and T-cadherin) and AMPK activity were measured using Western blot analyses. Isolated ventricular myocytes were prepared at 12 weeks post-fistula to examine the contractile performance of myocytes and intracellular Ca(2+) transient. RESULTS: A-V fistula resulted in significant reductions in serum and myocardial adiponectin levels, myocardial adiponectin receptor (AdipoR1/R2 and T-cadherin) levels, as well as myocardial AMPK activity. Consistent with these changes, the isolated myocytes exhibited significant depression in cell shortening and intracellular Ca(2+) transient. Administration of adenoviral adiponectin significantly increased serum adiponectin levels and prevented myocyte contractile dysfunction in fistula rats. Furthermore, pretreatment of isolated myocytes with recombinant adiponectin (2.5 µg/mL) significantly improved their contractile performance in fistula rats, but had no effects in control or adenoviral adiponectin-administered rats. CONCLUSION: These results demonstrate a positive correlation between adiponectin downregulation and volume overload-induced ventricular remodeling. Adiponectin plays a protective role in volume overload-induced heart failure.


Subject(s)
Adiponectin/blood , Down-Regulation , Heart Failure/blood , Heart Failure/pathology , Myocytes, Cardiac/pathology , AMP-Activated Protein Kinases/metabolism , Adiponectin/metabolism , Animals , Calcium/metabolism , Cells, Cultured , Heart Failure/etiology , Heart Failure/metabolism , Male , Myocytes, Cardiac/metabolism , Rats , Rats, Sprague-Dawley
18.
Chem Senses ; 41(1): 53-67, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26464498

ABSTRACT

Using noninvasive in vivo functional magnetic resonance imaging (fMRI), we demonstrate that the enhancement of odorant response of olfactory receptor neurons by zinc nanoparticles leads to increase in activity in olfaction-related and higher order areas of the dog brain. To study conscious dogs, we employed behavioral training and optical motion tracking for reducing head motion artifacts. We obtained brain activation maps from dogs in both anesthetized state and fully conscious and unrestrained state. The enhancement effect of zinc nanoparticles was higher in conscious dogs with more activation in higher order areas as compared with anesthetized dogs. In conscious dogs, voxels in the olfactory bulb and hippocampus showed higher activity to odorants mixed with zinc nanoparticles as compared with pure odorants, odorants mixed with gold nanoparticles as well as zinc nanoparticles alone. These regions have been implicated in odor intensity processing in other species including humans. If the enhancement effect of zinc nanoparticles observed in vivo are confirmed by future behavioral studies, zinc nanoparticles may provide a way for enhancing the olfactory sensitivity of canines for detection of target substances such as explosives and contraband substances at very low concentrations, which would otherwise go undetected.


Subject(s)
Brain/drug effects , Brain/physiology , Consciousness/physiology , Magnetic Resonance Imaging , Metal Nanoparticles/administration & dosage , Odorants , Zinc/administration & dosage , Animals , Brain Mapping , Dogs , Olfactory Receptor Neurons/physiology , Zinc/pharmacology
19.
Psychoneuroendocrinology ; 62: 89-95, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26263545

ABSTRACT

Previous correlational research shows that childhood adversity is associated with earlier age of reproduction in humans and other species. Such studies, however, cannot show that stressful conditions cause earlier reproduction. Using the cold-pressor task, we built on previous work to test the idea that acute stress influences human reproductive and marital ideals, and that individual stress responses depend on adaptive life history strategies shaped by exposure to adversity during childhood. Acute stress shifted ideal ages of first birth and marriage to earlier ages. We also tested a competing hypothesis, whether stress had a more general impact on time preference, but found no evidence that it did. Furthermore, there was an interaction between childhood adversity and acute stress. Individuals who reported more exposure to childhood adversity responded to acute stress by reporting even earlier reproductive ideals. These findings offer experimental evidence that physiological stress can alter reproductive decision making in humans.


Subject(s)
Decision Making , Marriage/psychology , Reproduction/physiology , Stress, Physiological/physiology , Stress, Psychological/psychology , Adolescent , Adult , Female , Humans , Young Adult
20.
Brain Struct Funct ; 220(2): 1063-76, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24399180

ABSTRACT

The default mode network (DMN) in humans has been extensively studied using seed-based correlation analysis (SCA) and independent component analysis (ICA). While DMN has been observed in monkeys as well, there are conflicting reports on whether they exist in rodents. Dogs are higher mammals than rodents, but cognitively not as advanced as monkeys and humans. Therefore, they are an interesting species in the evolutionary hierarchy for probing the comparative functions of the DMN across species. In this study, we sought to know whether the DMN, and consequently its functions such as self-referential processing, are exclusive to humans/monkeys or can we also observe the DMN in animals such as dogs. To address this issue, resting state functional MRI data from the brains of lightly sedated dogs and unconstrained and fully awake dogs were acquired, and ICA and SCA were performed for identifying the DMN. Since anesthesia can alter resting state networks, confirming our results in awake dogs was essential. Awake dog imaging was accomplished by training the dogs to keep their head still using reinforcement behavioral adaptation techniques. We found that the anterior (such as anterior cingulate and medial frontal) and posterior regions (such as posterior cingulate) of the DMN were dissociated in both awake and anesthetized dogs.


Subject(s)
Behavior, Animal , Cerebral Cortex/physiology , Models, Neurological , Nerve Net/physiology , Animals , Behavior, Animal/drug effects , Brain Mapping/methods , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Consciousness , Dogs , Hypnotics and Sedatives/pharmacology , Magnetic Resonance Imaging , Nerve Net/cytology , Nerve Net/drug effects , Reinforcement, Psychology , Time Factors
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