Objective:To examine the effects of psychological and physiological stress on hippocampal extracellular monoamine content under simulated high-altitude hypobaric hypoxia.Methods:The male SD rats were randomly divided into ten groups:control(Con group), hypoxia(Hy group), psychological stress(twice/day)(Ps1group), psychological stress(twice/day?2day)(Ps2 group), psychological stress(twice/day) + hypoxia(Ps1+Hy group), psychological stress(twice/day? 2day) +hypoxia(Ps2+Hy group), physiological stress(twice/day)(Ph1group), physiological stress(twice/day?2day)(Ph2 group), physiological stress(twice/day) + hypoxia(Ph1+Hy group), physiological stress(twice/day?2day) + hypoxia(Ph2+Hy group).The contents of norepinephrine(NE), dopamine(DA) and 5-hydroxytryptamine(5-HT) in extracellular fluid of hippocampus collected by push-pull perfusion were determined by high performance liquid chromatography with electrichemical detection(HPLC-ECD).Results:①Compared with the Con group, the content of NE was significantly lower in Hy, Ps1+Hy and Ph2+Hy groups(P

ObjectiveTo evaluate the feasibility of constructing tissue engineering cardiac patch with photooxidationfixed acellular bovine pericardium.MethodsFresh bovine pericardia were treated by dye-mediated photooxidation after decellularization.Some of them were seeded with bone marrow stromal cells(MSCs) isolated from male SD rats to construct cardiac patches.Myocardial infarction(MI) model was made in female SD rats by left anterior descending coronary ligation(LAD).One week later, the confirmed MI rats were divided into three groups randomly, group MI (n = 15)without any treatment; group P (n = 18) with photooxidated pericardia implantation ; group P + C (n = 18) with seeded pericardia implantation.A sham group (n = 10) was also performed with opening and closing chest twice only.The heart were explanted at 2 or 4 weeks after implantation, and examined histologically and immunohistochemically.The heart function was evaluated by echocardiography at 4 weeks before excising the rats.ResultsThere were no cells or cell debris remained in bovine pericardium tissue.The fiber structure became condensed after photooxidation.The seeded cells formed a continuous layer on the surface of the tissue.The pericardial degradation level and newly formed microvessel density were larger in group P + C than in group P after 2 [ (13.7 ±5.2)个/mm2 vs (7.1 ±3.1)个/mm2, P＜0.05]and4 [(22.6 ±4.9)个/mrn2 vs (14.1 ±5.3)个/mm2, P＜0.05]weeks.Four weeks after transplantation, cardiac echocardiography showed left ventricular ejection fraction(LVEF) was lower in group MI (44.8 ± 4.4) ％ and group P (48.4 ± 5.0) ％ compared with group P + C (49.3 ± 4.8) ％, left ventricular fractional shorterning(LVFS) was lower in group MI (18.0 ± 2.2) ％ and group P (19.8 ± 2.5) ％ compared with group P + C (20.4 ±2.5) ％, the difference between P + C and MI was significant.ConclusionTransplantation of the tissue engineered bovine pericardial patches with dye-mediated photooxidation can improve heart function in MI rats.This kind of patches demonstrates a promising prospect in the future.

BACKGROUND:During the outbreak of severe acute respiratory syndrome(SARS),certain people had been isolated by various reasons and appeared a series of psychological, physical and behavioral reactions. OBJECTIVE:To understand the different defensive features in people with different level of mental health in the isolated population, and explore the relationship between defensive style and mental health. DESIGN:An in investigative study taking the isolated population during outbreak of SARS as the subjects. SETTING:A psychiatric department of a military hospital. PARTICIPANTS:Totally 187 people of different sex,age and education, who were isolated during April and May 2003 due to SARS outbreak in a city of northwest China,were selected as the subjects. INTERVENTIONS:The 187 subjects,who were isolated due to SARS outbreak,were evaluated by using the symptom checklist(SCL 90) and defense style questionnaire(DSQ). RESULTS:About 36.4% people of this population had distinct mental or physical health problems that were characterized by anxiety,horror,depression,hostility and compulsion.There was difference in defensive styles between the high symptom group and low symptom group,among which the score of DSQ factors in the immature type of high and low symptom groups were 5.72± 1.56 and 4.35± 0.96 respectively while the scores in the intermediate type defense were 4.98± 1.44 and 3.72± 0.89 respectively(P< 0.01).Mental health problem was positively correlated with the application of immature defensive style,but had negative correlation with application of mature defensive means. CONCLUSION:There is difference in the defensive styles among the isolated people with different mental health status,and their defensive strategies are closely related to the mental health.

ObjectiveTo explore the change of the event related potential brain topographic map on depression' mental rotation,and to perfect the brain function relation map for depression in space ability.Methods 32 depression and 29 normal healthy people were tested to make mental rotation tasks in the brain ERP system.The distribution of the changing brain topographic map were observed.Results ( 1 ) Compared with the control group ( error rate ( 29±9 ) ％,response time ( 604.74 ± 54.39 ) ms,the error rate was significantly higher and response time was significantly longer in depression (error rate( 33 ± 15 )％,response time(755.22 ± 70.18 )ms,P＜0.05).(2) Compared with the control group (N100:PZ( -3.78 ± 1.05)μV,CZ( -5.67 ±2.21)μV,P3( -2.34 ±0.59) μV,P4( -2.92 ±0.80) μV ;P500:PZ(7.35 ±2.61 ) μV,CZ(7.65 ± 2.42) μV,P3 (6.53 ±2.11 ) μV,P4 ( 7.29 ± 2.57 ) μV ),the total volatility was significantly lower in depression ( N 100:PZ ( - 0.31 ±0.09)μV,CZ( -2.27 ±0.57)μV,P3( -0.30 ±0.07) μV,P4( -0.33 ±0.08) μV;P500:PZ(6.04 ±2.16)μV,CZ ( 5.92 ± 2.01 ) μV,P3 ( 6.02 ± 2.11 ) μV,P4 (6.01 ± 2.34 ) μV,P ＜ 0.05 ) and the excitability difference of the left and right parietal-occipital lobe was disappeared (P＞0.05) ; Compared with the control group,in N100 the normal and mirror excitability was significantly lower,and in P500 the normal excitability was significantly lower,but mirror was significantly higher in depression (P ＜ 0.05 ).Compared with the left and right brain,the normal excitability in the right parietal-occipital lobe was significant higher (P ＜ 0.05 ),but the mirror excitement difference was disappeared in depression (P＞ 0.05 ),and the normal and mirror excitement in the right parietal-occipital lobe was both significantly higher in normal healthy people (P ＜ 0.05 ).ConclusionDepressed patients; mental rotation ability is impaired.And the negative potential for looking forward to reaction is lower and exist the right advantage hemisphere brain in normal,but mirror advantage hemisphere disappears in depressed patients.This study suggests the brain topographic map of mental rotation ability damaged can be used as the clinical auxiliary diagnosis index.

Objective To explore the brain electrophysiological mechanism of object rotation in first-episode schizophrenia.Methods 30 patients with schizophrenia and 28 normal healthy people,who were from the Center for Mental Disease Control and Prevention,Third Hospital of PLA,took part in the mental rotation tasks,then the incubation period and amplitude of P500,and the wrong number and reaction time were measured.Results Compared with control group ( normal:(494.16 ± 34.68 ) ms,( 9.56 ± 2.54) μV; mirror:(496.51 ± 33.10 ) ms,(6.38 ± 2.41 ) μV),schizophrenia' incubation periods were significantly delayed ( normal:( 571.30 ± 51.21 ) ms;mirror:(573.41 ±39.27) ms) and volatility were significantly lower ( normal:(4.26 ± 1.01 ) μV; mirror:(3.61± 1.21 )μV) in normal and mirror rotation (P＜0.05 ).The mirror-normal differences were not significant on the incubation periods of two groups (P ＞ 0.05 ) ; the mirror-normal image differences were not significant on the patient group' volatility (P ＞ 0.05 ) ; the normal volatility was significantly higher than mirror in the control group (P ＜ 0.05).Conclusion Schizophrenia'mental rotation ability is impaired,and mirror-normal differences on mental rotation are disappeared.It can be used as an early-stage clinical auxiliary diagnosis index.

During severe acute respiratory syndrome coronavirus (SARS-CoV) infection, the activity of the replication/transcription complexes (RTC) quickly peaks at 6 hours post infection (h.p.i) and then diminishes significantly in the late post-infection stages. This "down-up-down" regulation of RNA synthesis distinguishes different viral stages: primary translation, genome replication, and finally viron assembly. Regarding the nsp8 as the primase in RNA synthesis, we confirmed that the proteolysis product of the primase (nsp8) contains the globular domain (nsp8C), and indentified the resectioning site that is notably conserved in all the three groups of coronavirus. We subsequently crystallized the complex of SARS-CoV nsp8C and nsp7, and the 3-D structure of this domain revealed its capability to interfuse into the hexadecamer super-complex. This specific proteolysis may indicate one possible mechanism by which coronaviruses to switch from viral infection to genome replication and viral assembly stages.
Amino Acid Sequence ; Crystallography, X-Ray ; DNA Primase ; chemistry ; genetics ; physiology ; Humans ; Isoenzymes ; chemistry ; genetics ; physiology ; Molecular Sequence Data ; Protein Structure, Secondary ; RNA, Viral ; biosynthesis ; SARS Virus ; chemistry ; genetics ; physiology ; Sequence Alignment ; Severe Acute Respiratory Syndrome ; virology ; Virus Replication

Binding Sites ; Cysteine Endopeptidases ; metabolism ; Humans ; Isoxazoles ; chemistry ; pharmacology ; Protease Inhibitors ; chemistry ; metabolism ; pharmacology ; Protein Structure, Tertiary ; Pyrrolidinones ; chemistry ; pharmacology ; Rhinovirus ; drug effects ; SARS Virus ; drug effects ; enzymology ; Severe Acute Respiratory Syndrome ; virology ; Viral Proteins ; antagonists & inhibitors ; metabolism

Ebola virus (EBOV) is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA (-ssRNA) viruses, EBOV possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex (RNP) together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain (NP(core)) possesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an α-helix of EBOV NP(core) itself, which is highly conserved among filoviridae family. Combined with other biochemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.
Crystallography, X-Ray ; Ebolavirus ; physiology ; Humans ; Nucleoproteins ; chemistry ; genetics ; metabolism ; Protein Structure, Tertiary ; Structure-Activity Relationship ; Virus Assembly ; physiology

Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are a type of newly discovered antibioticresistant bacteria. The rapid pandemic spread of NDM-1 bacteria worldwide (spreading to India, Pakistan, Europe, America, and Chinese Taiwan) in less than 2 months characterizes these microbes as a potentially major global health problem. The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations. The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics, allowing the bacteria to escape the action of antibiotics. Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues, the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified. Here, we report the three-dimensional structure of NDM-1 with two catalytic zinc ions in its active site. Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity. The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases (MBLs) and implicate its role in wide spectrum drug resistance. We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria. Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases.
Amino Acid Sequence ; Anti-Bacterial Agents ; metabolism ; Binding Sites ; Captopril ; chemistry ; pharmacology ; Catalytic Domain ; Crystallography, X-Ray ; Drug Resistance, Bacterial ; Enterobacteriaceae ; enzymology ; Molecular Sequence Data ; Sequence Alignment ; Sequence Homology, Amino Acid ; beta-Lactamases ; chemistry ; metabolism

Enterovirus 71 (EV71), one of the major causative agents for hand-foot-and-mouth disease (HFMD), has caused more than 100 deaths among Chinese children since March 2008. The EV71 genome encodes an RNAdependent RNA polymerase (RdRp), denoted 3D(pol), which is central for viral genome replication and is a key target for the discovery of specific antiviral therapeutics. Here we report the crystal structures of EV71 RdRp (3D(pol)) and in complex with substrate guanosine-5'-triphosphate and analog 5-bromouridine-5'-triphosphate best to 2.4 Å resolution. The structure of EV71 RdRp (3D(pol)) has a wider open thumb domain compared with the most closely related crystal structure of poliovirus RdRp. And the EV71 RdRp (3D(pol)) complex with GTP or Br-UTP bounded shows two distinct movements of the polymerase by substrate or analogue binding. The model of the complex with the template:primer derived by superimposition with foot-and-mouth disease virus (FMDV) 3D/RNA complex reveals the likely recognition and binding of template:primer RNA by the polymerase. These results together provide a molecular basis for EV71 RNA replication and reveal a potential target for anti-EV71 drug discovery.
Amino Acid Sequence ; Child ; China ; epidemiology ; Crystallography, X-Ray ; Drug Discovery ; Enterovirus A, Human ; chemistry ; enzymology ; Hand, Foot and Mouth Disease ; drug therapy ; epidemiology ; virology ; Humans ; Models, Molecular ; Molecular Sequence Data ; Molecular Targeted Therapy ; Protein Conformation ; Protein Folding ; RNA Replicase ; chemistry ; genetics ; metabolism ; Sequence Alignment ; Substrate Specificity