bluuebunny/crossref_metadata_2025 huggingface dataset:
No association of TNFRSF1B variants with type 2 diabetes in Indians of Indo-European origin
Authors: Tabassum Rubina , Mahajan Anubha , Chauhan Ganesh , Dwivedi Om Prakash , Dubey Himanshu , Sharma Vasudha , Kundu Bratashree , Ghosh Saurabh , Tandon Nikhil , Bharadwaj Dwaipayan
Published: August 2011

Background

There has been no systematic evaluation of the association between genetic variants of type 2 receptor for TNFα (TNFR2) and type 2 diabetes, despite strong biological evidence for the role of this receptor in the pathogenesis of this complex disorder. In view of this, we performed a comprehensive association analysis of TNFRSF1B variants with type 2 diabetes in 4,200 Indo-European subjects from North India.

Methods

The initial phase evaluated association of seven SNPs viz. rs652625, rs496888, rs6697733, rs945439, rs235249, rs17883432 and rs17884213 with type 2 diabetes in 2,115 participants (1,073 type 2 diabetes patients and 1,042 control subjects). Further, we conducted replication analysis of three associated SNPs in 2,085 subjects (1,047 type 2 diabetes patients and 1,038 control subjects).

Results

We observed nominal association of rs945439, rs235249 and rs17884213 with type 2 diabetes (P < 0.05) in the initial phase. Haplotype CC of rs945439 and rs235249 conferred increased susceptibility for type 2 diabetes [OR = 1.19 (95%CI 1.03-1.37), P = 0.019/P
perm = 0.076] whereas, TG haplotype of rs235249 and rs17884213 provided protection against type 2 diabetes [OR = 0.83 (95%CI 0.72-0.95, P = 7.2 × 10-3/P
perm = 0.019]. We also observed suggestive association of rs496888 with plasma hsCRP levels [P = 0.042]. However, the association of rs945439, rs235249 and rs17884213 with type 2 diabetes was not replicated in the second study population. Meta-analysis of the two studies also failed to detect any association with type 2 diabetes.

Conclusions

Our two-stage association analysis suggests that TNFRSF1B variants are not the determinants of genetic risk of type 2 diabetes in North Indians.
Evaluation of Abelmoschus moschatus extracts for antioxidant, free radical scavenging, antimicrobial and antiproliferative activities using in vitro assays
Authors: Gul Mir Z , Bhakshu Lepakshi M , Ahmad Farhan , Kondapi Anand K , Qureshi Insaf A , Ghazi Irfan A
Published: August 2011

Background

Abelmoschus moschatus Medik. leaves and seeds are considered as valuable traditional medicine. The aromatic seeds of this plant are aphrodisiac, ophthalmic, cardio tonic, antispasmodic and used in the treatment of intestinal complaints and check queasiness. To give a scientific basis for traditional usage of this medicinal plant, the seed and leaf extracts were evaluated for their antioxidant, free radical scavenging, antimicrobial and antiproliferative activities.

Methods

In this study, antioxidant, antimicrobial and antiproliferative activities of A. moschatus extracts were evaluated in a series of in vitro assay involving free radicals, reactive oxygen species and their IC50 values were also determined. The antioxidant activities of the seed and leaf extracts of A. moschatus were determined by total antioxidant, DPPH, and ferrous reducing antioxidant property (FRAP) methods. In addition, the antiproliferative activity was also evaluated using colorectal adenocarcinoma and retinoblastoma human cancer cell lines. Moreover, six bacterial reference strains, two gram-positive (Bacillus subtilis and Staphylococcus aureus), four gram-negative (Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Salmonella enterica paratyphi) and one fungal strain (Candida albicans) were used to evaluate its antimicrobial activity.

Results

The results from this study showed that the antioxidant activities of A. moschatus as determined by the total phenol, flavonoids, total antioxidant and FRAP methods were higher in leaf than that of the seed extracts. On the other hand, the aqueous overnight seed extract (AMS-I) has shown significant radical scavenging activity as in 1, 1- Diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide, hydroxyl radical, superoxide and lipid peroxidation as compared to other seed and leaf extracts. The AMS-I and AML-IV have shown activity against six and seven microorganisms respectively. Simulteneously, AMS-IV and AML-IV have demonstrated potential antiproliferative activity against two human cell lines - Colorectal adenocarcinoma (COLO-205) and retinoblastoma (Y79).

Conclusion

The seed and leaf extracts of A. moschatus possess significant antioxidant activity and could serve as free radical inhibitors or scavenger, or substitute, probably as primary antioxidants. The plant possesses moderate antibacterial activity against bacterial strains used in this study. Hydroalcoholic seed and leaf extracts also exhibited antiproliferative activity against two human cancer cell lines. A. moschatus may therefore, be a good candidate for functional foods as well as pharmaceutics.
Performance of the international physical activity questionnaire (short form) in subgroups of the Hong Kong chinese population
Authors: Lee Paul H , Yu YY , McDowell Ian , Leung Gabriel M , Lam TH , Stewart Sunita M
Published: August 2011

Background

The International Physical Activity Questionnaire (IPAQ-SF) has been validated and recommended as an efficient method to assess physical activity, but its validity has not been investigated in different population subgroups. We examined variations in IPAQ validity in the Hong Kong Chinese population by six factors: sex, age, job status, educational level, body mass index (BMI), and visceral fat level (VFL).

Methods

A total of 1,270 adults (aged 42.9 ± SD 14.4 years, 46.1% male) completed the Chinese version of IPAQ (IPAQ-C) and wore an accelerometer (ActiGraph) for four days afterwards. The IPAQ-C and the ActiGraph were compared in terms of estimated Metabolic Equivalent Task minutes per week (MET-min/wk), minutes spent in activity of moderate or vigorous intensity (MVPA), and agreement in the classification of physical activity.

Results

The overall Spearman correlation (ρ) of between the IPAQ-C and ActiGraph was low (0.11 ± 0.03; range in subgroups 0.06-0.24) and was the highest among high VFL participants (0.24 ± 0.05). Difference between self-reported and ActiGraph-derived MET-min/wk (overall 2966 ± 140) was the smallest among participants with tertiary education (1804 ± 208). When physical activity was categorized into over or under 150 min/wk, overall agreement between self-report and accelerometer was 81.3% (± 1.1%; subgroup range: 77.2%-91.4%); agreement was the highest among those who were employed full-time in physically demanding jobs (91.4% ± 2.7%).

Conclusions

Sex, age, job status, educational level, and obesity were found to influence the criterion validity of IPAQ-C, yet none of the subgroups showed good validity (ρ = 0.06 to 0.24). IPAQ-SF validity is questionable in our Chinese population.
PKIS: practical keyword index search on cloud datacenter
Authors: Park Hyun-A , Park Jae Hyun , Lee Dong Hoon
Published: August 2011

This paper highlights the importance of the interoperability of the encrypted DB in terms of the characteristics of DB and efficient schemes. Although most prior researches have developed efficient algorithms under the provable security, they do not focus on the interoperability of the encrypted DB. In order to address this lack of practical aspects, we conduct two practical approaches--efficiency and group search in cloud datacenter. The process of this paper is as follows: first, we create two schemes of efficiency and group search--practical keyword index search--I and II; second, we define and analyze group search secrecy and keyword index search privacy in our schemes; third, we experiment on efficient performances over our proposed encrypted DB. As the result, we summarize two major results: (1)our proposed schemes can support a secure group search without re-encrypting all documents under the group-key update and (2)our experiments represent that our scheme is approximately 935 times faster than Golle's scheme and about 16 times faster than Song's scheme for 10,000 documents. Based on our experiments and results, this paper has the following contributions: (1) in the current cloud computing environments, our schemes provide practical, realistic, and secure solutions over the encrypted DB and (2) this paper identifies the importance of interoperability with database management system for designing efficient schemes.
Autologous bone marrow stem cell intralesional transplantation repairing bisphosphonate related osteonecrosis of the jaw
Authors: Cella Luigi , Oppici Aldo , Arbasi Mariacristina , Moretto Mauro , Piepoli Massimo , Vallisa Daniele , Zangrandi Adriano , Di Nunzio Camilla , Cavanna Luigi
Published: August 2011

Purpose

Bisphosphonate - related osteonecrosis of the JAW (BRONJ) is a well known side effect of bisphosphonate therapies in oncologic and non oncologic patients. Since to date no definitive consensus has been reached on the treatment of BRONJ, novel strategies for the prevention, risk reduction and treatment need to be developed. We report a 75 year old woman with stage 3 BRONJ secondary to alendronate and pamidronate treatment of osteoporosis. The patient was unresponsive to recommended treatment of the disease, and her BRONJ was worsening. Since bone marrow stem cells are know as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone and other tissue, we performed autologous bone marrow stem cell transplantation into the BRONJ lesion of the patient.

Methods

Under local anesthesia a volume of 75 ml of bone marrow were harvested from the posterior superior iliac crest by aspiration into heparinized siringes. The cell suspension was concentrated, using Ficoll - Hypaque® centrifugation procedures, in a final volume of 6 ml. Before the injection of stem cells into the osteonecrosis, the patient underwent surgical toilet, local anesthesia was done and spongostan was applied as a carrier of stem cells suspension in the bone cavity, then 4 ml of stem cells suspension and 1 ml of patient's activated platelet-rich plasma were injected in the lesion of BRONJ.

Results

A week later the residual spongostan was removed and two weeks later resolution of symptoms was obtained. Then the lesion improved with progressive superficialization of the mucosal layer and CT scan, performed 15 months later, shows improvement also of bone via concentric ossification: so complete healing of BRONJ (stage 0) was obtained in our patient, and 30 months later the patient is well and without signs of BRONJ.

Conclusion

To our knowledge this is the first case of BRONJ successfully treated with autologous stem cells transplantation with a complete response.
Functional characterization of cellulases identified from the cow rumen fungus Neocallimastix patriciarum W5 by transcriptomic and secretomic analyses
Authors: Wang Tzi-Yuan , Chen Hsin-Liang , Lu Mei-Yeh J , Chen Yo-Chia , Sung Huang-Mo , Mao Chi-Tang , Cho Hsing-Yi , Ke Huei-Mien , Hwa Teh-Yang , Ruan Sz-Kai , Hung Kuo-Yen , Chen Chih-Kuan , Li Jeng-Yi , Wu Yueh-Chin , Chen Yu-Hsiang , Chou Shao-Pei , Tsai Ya-Wen , Chu Te-Chin , Shih Chun-Chieh A , Li Wen-Hsiung , Shih Ming-Che
Published: August 2011

Background

Neocallimastix patriciarum is one of the common anaerobic fungi in the digestive tracts of ruminants that can actively digest cellulosic materials, and its cellulases have great potential for hydrolyzing cellulosic feedstocks. Due to the difficulty in culture and lack of a genome database, it is not easy to gain a global understanding of the glycosyl hydrolases (GHs) produced by this anaerobic fungus.

Results

We have developed an efficient platform that uses a combination of transcriptomic and proteomic approaches to N. patriciarum to accelerate gene identification, enzyme classification and application in rice straw degradation. By conducting complementary studies of transcriptome (Roche 454 GS and Illumina GA IIx) and secretome (ESI-Trap LC-MS/MS), we identified 219 putative GH contigs and classified them into 25 GH families. The secretome analysis identified four major enzymes involved in rice straw degradation: β-glucosidase, endo-1,4-β-xylanase, xylanase B and Cel48A exoglucanase. From the sequences of assembled contigs, we cloned 19 putative cellulase genes, including the GH1, GH3, GH5, GH6, GH9, GH18, GH43 and GH48 gene families, which were highly expressed in N. patriciarum cultures grown on different feedstocks.

Conclusions

These GH genes were expressed in Pichia pastoris and/or Saccharomyces cerevisiae for functional characterization. At least five novel cellulases displayed cellulytic activity for glucose production. One β-glucosidase (W5-16143) and one exocellulase (W5-CAT26) showed strong activities and could potentially be developed into commercial enzymes.
Accuracy of 64-multidetector computed tomography in diagnosis of adnexal tumors
Authors: Gatreh-Samani Fatemeh , Tarzamni Mohammad Kazem , Olad-Sahebmadarek Elaheh , Dastranj Ali , Afrough Aimaz
Published: August 2011

Background

Adnexal cancers are in fifth place among the tumors with the highest mortality in the female population. The aim of the present study was to evaluate the accuracy of Multi-detector computed tomography (MDCT) on a 64-multislice CT scanner in the detection and differentiation of adnexal masses stages.

Methods

During the present prospective study, 95 women with a primary diagnosis of ovarian mass in base of clinical examination and ultrasonographic findings underwent preoperative evaluation by a 64-slice MDCT with a section thickness of 0.6 mm, 50% overlap and reconstructed images. Afterward, results of MDCT were compared with surgical and histopathological findings, and the sensitivity, specificity, positive and negative predictive value and accuracy were determined.

Results

The mean age of patients was 48.63 ± 13.93 years. MDCT diagnosed 25 (26.3%) masses to be benign and 70 (73.7%) to be malignant (sensitivity, specificity, positive and negative predictive value and accuracy were 92.8%, 88.0%, 95.5%, 81.4% and 91.5% respectively). The sensitivity and specificity of MDCT in determining local extension was 72.2% and 93.4% respectively. And the sensitivity and specificity of MDCT in determining peritoneal seeding and liver extension was 81.8% and 93% respectively. Estimated stage was significantly agreed with the surgical (Cohen's Kappa (κ) = 0.891) and histopathological findings (κ = 0.858).

Conclusion

MDCT is a highly sensitive and specific diagnostic method in evaluation of adnexal masses and successfully stage the tumor in consistent with surgery and histopathology.
Inhibition of Renin Release by Arachidonic Acid Metabolites, 12(s)-HPETE and 12-HETE: Role of TRPV1 Channels
Authors: Xie Chaoqin , Wang Donna H.
Published: August 2011

We test the hypothesis that 12-hydroperoxyeicosatetraenoic acid (12(s)-HPETE) and 12-hydroxyeicosatetraenoic acid (12-HETE) perfused into the renal pelvis increase afferent renal nerve activity (ARNA) and suppress renin release in rats fed a low-salt (LS) diet via activation of the transient receptor potential vanilloid type 1 (TRPV1) expressed in renal sensory nerves. 12(s)-HPETE or 12-HETE given into the left renal pelvis dose-dependently increased ARNA, which was abolished by AMG9810, a selective TRPV1 antagonist, or by RP67580, a selective neurokinin 1 receptor antagonist, in normal salt or LS-treated rats. 12(s)-HPETE, 12-HETE, or substance P perfused into the left renal pelvis suppressed plasma angiotensin I (Ang I) levels in LS rats, which was abolished by AMG9810 or attenuated by ipsilateral renal denervation (RD). 12(s)-HPETE or 12-HETE increased release of substance P and calcitonin gene-related peptide from the ipsilateral kidney, which was abolished by AMG9810 but not RP67580, RD, or RP67580 plus RD. Immunofluorescence staining showed that TRPV1-positive nerve fibers located in the renal cortex, medulla, and pelvis, and that the sympathetic nerve marker, neuropeptide Y, but not neurokinin 1 receptors expressed in the juxtaglomerular region colocalized with renin. Thus, our data show that 12(s)-HPETE and 12-HETE enhance ARNA and substance P/calcitonin gene-related peptide release but suppress renin activity in LS rats, and these effects are abolished when TRPV1 is blocked. These results indicate that TRPV1 mediates 12(s)-HPETE and 12-HETE action in the kidney in such a way that dysfunction in TRPV1 may lead to disintegrated regulation of renin and renal function.
Exposure to Chronic Pregnancy Stress Reverses Peripartum-Associated Adaptations: Implications for Postpartum Anxiety and Mood Disorders
Authors: Hillerer Katharina M. , Reber Stefan O. , Neumann Inga D. , Slattery David A.
Published: August 2011

Maternal adaptations, such as decreased anxiety and attenuated stress responsiveness, are necessary to enable successful postnatal development of the offspring. However, there is growing evidence that they are also required to protect the mental health of the mother and that exposure to chronic stress during pregnancy may prevent such adaptations. Overcrowding stress (24 h) and restraint stress (2 × 1 h) were employed on alternate days between pregnancy d 4–16 to examine the impact of chronic pregnancy stress on relevant behavioral, neuroendocrine, and neuronal peripartum adaptations. To determine whether the chronic stress-induced alterations were specific to the peripartum period, we included virgins as controls. Validating the stress procedure, we demonstrated decreased body-weight gain and increased adrenal weight in stressed dams, relative to their nonstressed controls. Chronic stress prevented a number of peripartum adaptations, including basal plasma hypercorticosterone levels, increased oxytocin mRNA expression in the hypothalamic paraventricular nucleus, and anxiolysis. However, chronic stress did not prevent the peripartum-associated decrease in CRH mRNA expression or attenuate corticosterone response to an acute stressor, nor did it affect hypothalamic vasopressin mRNA expression. Illustrating the specificity of these stress-induced changes to the peripartum period, none of these parameters were affected in stressed virgins. Although chronic stress did not alter depression-related behavior, it reversed the response to acute imipramine treatment and increased active maternal behavior in lactation. Thus, prevention of the peripartum-associated increases in basal corticosterone and oxytocin system activity by pregnancy stress reveal two alterations that may increase the risk of postpartum psychiatric disorders, particularly anxiety.
NF-κB-Inducing Kinase (NIK) Mediates Skeletal Muscle Insulin Resistance: Blockade by Adiponectin
Authors: Choudhary Sanjeev , Sinha Sandeep , Zhao Yanhua , Banerjee Srijita , Sathyanarayana Padma , Shahani Sadeka , Sherman Vadim , Tilton Ronald. G. , Bajaj Mandeep
Published: August 2011

Enhanced levels of nuclear factor (NF)-κB-inducing kinase (NIK), an upstream kinase in the NF-κB pathway, have been implicated in the pathogenesis of chronic inflammation in diabetes. We investigated whether increased levels of NIK could induce skeletal muscle insulin resistance. Six obese subjects with metabolic syndrome underwent skeletal muscle biopsies before and six months after gastric bypass surgery to quantitate NIK protein levels. L6 skeletal myotubes, transfected with NIK wild-type or NIK kinase-dead dominant negative plasmids, were treated with insulin alone or with adiponectin and insulin. Effects of NIK overexpression on insulin-stimulated glucose uptake were estimated using tritiated 2-deoxyglucose uptake. NF-κB activation (EMSA), phosphatidylinositol 3 (PI3) kinase activity, and phosphorylation of inhibitor κB kinase β and serine-threonine kinase (Akt) were measured. After weight loss, skeletal muscle NIK protein was significantly reduced in association with increased plasma adiponectin and enhanced AMP kinase phosphorylation and insulin sensitivity in obese subjects. Enhanced NIK expression in cultured L6 myotubes induced a dose-dependent decrease in insulin-stimulated glucose uptake. The decrease in insulin-stimulated glucose uptake was associated with a significant decrease in PI3 kinase activity and protein kinase B/Akt phosphorylation. Overexpression of NIK kinase-dead dominant negative did not affect insulin-stimulated glucose uptake. Adiponectin treatment inhibited NIK-induced NF-κB activation and restored insulin sensitivity by restoring PI3 kinase activation and subsequent Akt phosphorylation. These results indicate that NIK induces insulin resistance and further indicate that adiponectin exerts its insulin-sensitizing effect by suppressing NIK-induced skeletal muscle inflammation. These observations suggest that NIK could be an important therapeutic target for the treatment of insulin resistance associated with inflammation in obesity and type 2 diabetes.
Fas-Associated Factor 1 as a Regulator of Olfactory Axon Guidance
Authors: Cheng Kai , Bai Li , Belluscio Leonardo
Published: August 2011

Axon guidance is a crucial part of neural circuit formation. While precise axonal targeting forms the basis of accurate information delivery, the mechanisms that regulate this process are still unclear. Apoptotic signaling molecules have been identified in the axon terminal, but their specific role in axon guidance is not well understood. Here we use the mouse olfactory system as anin vivomodel to demonstrate that by modulating Fas-associated factor 1 (FAF1), an apoptosis regulatory molecule, we can rewire axonal projections. Interestingly, FAF1 is highly expressed in the developing mouse olfactory system, but its expression is downregulated postnatally. Using a tetracycline-inducible promoter Tet-Off system, we generated transgenic mice in which FAF1 is specifically expressed in immature olfactory sensory neurons (OSNs) and show that overexpression of FAF1 not only misroutes OSN axons to deep layers of the olfactory bulb but also leads to widespread disruption of the glomerular layer. In addition, we also demonstrate that the specific convergence of P2 receptor OSN axons is completely distorted in the FAF1 mice. Strikingly, all of the mutant phenotypes can be recovered by shutting down FAF1 expression through the administration of doxycycline. Together, our study provides clearin vivoevidence that an apoptotic molecule can indeed regulate axon targeting and that OSNs can restore their organization even after broad disruption.
Descending Corticospinal Control of Intersegmental Dynamics
Authors: Gritsenko Valeriya , Kalaska John F. , Cisek Paul
Published: August 2011

To make an accurate movement, the CNS has to overcome the inherent complexities of the multijoint limb. For example, interaction torques arise when motion of individual arm segments propagates to adjacent segments causing their movement without any muscle contractions. Since these passive joint torques significantly add to the overall torques generated by active muscular contractions, they must be taken into account during planning or execution of goal-directed movements. We investigated the role of the corticospinal tract in compensating for the interaction torques during arm movements in humans. Twelve subjects reached to visual targets with their arm supported by a robotic exoskeleton. Reaching to one target was accompanied by interaction torques that assisted the movement, while reaching to the other target was accompanied by interaction torques that resisted the movement. Corticospinal excitability was assessed at different times during movement using single-pulse transcranial magnetic stimulation (TMS) over the upper-arm region of M1 (primary motor cortex). We found that TMS responses in shoulder monoarticular and elbow–shoulder biarticular muscles changed together with the interaction torques during movements in which the interaction torques were resistive. In contrast, TMS responses did not correlate with assistive interaction torques or with co-contraction. This suggests that the descending motor command includes compensation for passive limb dynamics. Furthermore, our results suggest that compensation for interaction torques involves the biarticular muscles, which span both shoulder and elbow joints and are in a biomechanically advantageous position to provide such compensation.
Cellular-Resolution Population Imaging Reveals Robust Sparse Coding in theDrosophilaMushroom Body
Authors: Honegger Kyle S. , Campbell Robert A. A. , Turner Glenn C.
Published: August 2011

Sensory stimuli are represented in the brain by the activity of populations of neurons. In most biological systems, studying population coding is challenging since only a tiny proportion of cells can be recorded simultaneously. Here we used two-photon imaging to record neural activity in the relatively simpleDrosophilamushroom body (MB), an area involved in olfactory learning and memory. Using the highly sensitive calcium indicator GCaMP3, we simultaneously monitored the activity of >100 MB neuronsin vivo(∼5% of the total population). The MB is thought to encode odors in sparse patterns of activity, but the code has yet to be explored either on a population level or with a wide variety of stimuli. We therefore imaged responses to odors chosen to evaluate the robustness of sparse representations. Different odors activated distinct patterns of MB neurons; however, we found no evidence for spatial organization of neurons by either response probability or odor tuning within the cell body layer. The degree of sparseness was consistent across a wide range of stimuli, from monomolecular odors to artificial blends and even complex natural smells. Sparseness was mainly invariant across concentrations, largely because of the influence of recent odor experience. Finally, in contrast to sensory processing in other systems, no response features distinguished natural stimuli from monomolecular odors. Our results indicate that the fundamental feature of odor processing in the MB is to create sparse stimulus representations in a format that facilitates arbitrary associations between odor and punishment or reward.
Oxygen/Glucose Deprivation Induces a Reduction in Synaptic AMPA Receptors on Hippocampal CA3 Neurons Mediated by mGluR1 and Adenosine A3Receptors
Authors: Dennis Siobhan H. , Jaafari Nadia , Cimarosti Helena , Hanley Jonathan G. , Henley Jeremy M. , Mellor Jack R.
Published: August 2011

Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage, whereas neighboring CA3 pyramidal neurons are less susceptible. It is proposed that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during anin vitromodel of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced permeability of AMPARs to Ca2+, resulting in delayed cell death. However, it is unclear whether the same mechanisms exist in CA3 neurons and whether this underlies the differential sensitivity to ischemia. Here, we investigated the consequences of OGD for AMPAR function in CA3 neurons using electrophysiological recordings in rat hippocampal slices. Following a 15 min OGD protocol, a substantial depression of AMPAR-mediated synaptic transmission was observed at CA3 associational/commissural and mossy fiber synapses but not CA1 Schaffer collateral synapses. The depression of synaptic transmission following OGD was prevented by metabotropic glutamate receptor 1 (mGluR1) or A3receptor antagonists, indicating a role for both glutamate and adenosine release. Inhibition of PLC, PKC, or chelation of intracellular Ca2+also prevented the depression of synaptic transmission. Inclusion of peptides to interrupt the interaction between GluA2 and PICK1 or dynamin and amphiphysin prevented the depression of transmission, suggesting a dynamin and PICK1-dependent internalization of AMPARs after OGD. We also show that a reduction in surface and total AMPAR protein levels after OGD was prevented by mGluR1 or A3receptor antagonists, indicating that AMPARs are degraded following internalization. Thus, we describe a novel mechanism for the removal of AMPARs in CA3 pyramidal neurons following OGD that has the potential to reduce excitotoxicity and promote neuroprotection.
Macroglial Plasticity and the Origins of Reactive Astroglia in Experimental Autoimmune Encephalomyelitis
Authors: Guo Fuzheng , Maeda Yoshiko , Ma Joyce , Delgado Monica , Sohn Jiho , Miers Laird , Ko Emily Mills , Bannerman Peter , Xu Jie , Wang Yazhou , Zhou Chengji , Takebayashi Hirohide , Pleasure David
Published: August 2011

Accumulations of hypertrophic, intensely glial fibrillary acidic protein-positive (GFAP+) astroglia, which also express immunoreactive nestin and vimentin, are prominent features of multiple sclerosis lesions. The issues of the cellular origin of hypertrophic GFAP+/vimentin+/nestin+“reactive” astroglia and also the plasticities and lineage relationships among three macroglial progenitor populations—oligodendrocyte progenitor cells (OPCs), astrocytes and ependymal cells—during multiple sclerosis and other CNS diseases remain controversial. We used genetic fate-mappings with a battery of inducible Cre drivers (Olig2-Cre-ERT2, GFAP-Cre-ERT2, FoxJ1-Cre-ERT2and Nestin-Cre-ERT2) to explore these issues in adult mice with myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis (EAE). The proliferative rate of spinal cord OPCs rose fivefold above control levels during EAE, and numbers of oligodendroglia increased as well, but astrogenesis from OPCs was rare. Spinal cord ependymal cells, previously reported to be multipotent, did not augment their low proliferative rate, nor give rise to astroglia or OPCs. Instead, the hypertrophic, vimentin+/nestin+, reactive astroglia that accumulated in spinal cord in this multiple sclerosis model were derived by proliferation and phenotypic transformation of fibrous astroglia in white matter, and solely by phenotypic transformation of protoplasmic astroglia in gray matter. This comprehensive analysis of macroglial plasticity in EAE helps to clarify the origins of astrogliosis in CNS inflammatory demyelinative disorders.
Downregulation of the Posterior Medial Frontal Cortex Prevents Social Conformity
Authors: Klucharev Vasily , Munneke Moniek A. M. , Smidts Ale , Fernández Guillén
Published: August 2011

We often change our behavior to conform to real or imagined group pressure. Social influence on our behavior has been extensively studied in social psychology, but its neural mechanisms have remained largely unknown. Here we demonstrate that the transient downregulation of the posterior medial frontal cortex by theta-burst transcranial magnetic stimulation reduces conformity, as indicated by reduced conformal adjustments in line with group opinion. Both the extent and probability of conformal behavioral adjustments decreased significantly relative to a sham and a control stimulation over another brain area. The posterior part of the medial frontal cortex has previously been implicated in behavioral and attitudinal adjustments. Here, we provide the first interventional evidence of its critical role in social influence on human behavior.
ERK2 Contributes to the Control of Social Behaviors in Mice
Authors: Satoh Yasushi , Endo Shogo , Nakata Takahiro , Kobayashi Yasushi , Yamada Kazuyuki , Ikeda Toshio , Takeuchi Atsuya , Hiramoto Takeshi , Watanabe Yasuhiro , Kazama Tomiei
Published: August 2011

Signaling through extracellular signal-regulated kinase (ERK) is important in multiple signal transduction networks in the CNS. However, the specific role of ERK2 inin vivobrain functions is not fully understood. Here we show that ERK2 play a critical role in regulating social behaviors as well as cognitive and emotional behaviors in mice. To study the brain function of ERK2, we used a conditional, region-specific, genetic approach to targetErk2using the Cre/loxP strategy with anestinpromoter-drivencretransgenic mouse line to induce recombination in the CNS. The resultingErk2conditional knock-out (CKO) mice, in whichErk2was abrogated specifically in the CNS, were viable and fertile with a normal appearance. These mice, however, exhibited marked anomalies in multiple aspects of social behaviors related to facets of autism-spectrum disorders: elevated aggressive behaviors, deficits in maternal nurturing, poor nest-building, and lower levels of social familiarity and social interaction.Erk2CKO mice also exhibited decreased anxiety-related behaviors and impaired long-term memory. Pharmacological inhibition of ERK1 phosphorylation inErk2CKO mice did not affect the impairments in social behaviors and learning disabilities, indicating that ERK2, but not ERK1 plays a critical role in these behaviors. Our findings suggest that ERK2 has complex and multiple roles in the CNS, with important implications for human psychiatric disorders characterized by deficits in social behaviors.
Cyclin-Dependent Kinase 5 Regulates PSD-95 Ubiquitination in Neurons
Authors: Bianchetta Michael J. , Lam TuKiet T. , Jones Stephen N. , Morabito Maria A.
Published: August 2011

Cyclin-dependent kinase 5 (Cdk5) and its activator p35 have been implicated in drug addiction, neurodegenerative diseases such as Alzheimer's, learning and memory, and synapse maturation and plasticity. However, the molecular mechanisms by which Cdk5 regulates synaptic plasticity are still unclear. PSD-95 is a major postsynaptic scaffolding protein of glutamatergic synapses that regulates synaptic strength and plasticity. PSD-95 is ubiquitinated by the ubiquitin E3 ligase Mdm2, and rapid and transient PSD-95 ubiquitination has been implicated in NMDA receptor-induced AMPA receptor endocytosis. Here we demonstrate that genetic or pharmacological reduction of Cdk5 activity increases the interaction of Mdm2 with PSD-95 and enhances PSD-95 ubiquitination without affecting PSD-95 protein levelsin vivoin mice, suggesting a nonproteolytic function of ubiquitinated PSD-95 at synapses. We show that PSD-95 ubiquitination correlates with increased interaction with β-adaptin, a subunit of the clathrin adaptor protein complex AP-2. This interaction is increased by genetic reduction of Cdk5 activity or NMDA receptor stimulation and is dependent on Mdm2. Together these results support a function for Cdk5 in regulating PSD-95 ubiquitination and its interaction with AP-2 and suggest a mechanism by which PSD-95 may regulate NMDA receptor-induced AMPA receptor endocytosis.
Palmitoyl Acyltransferase zD17 Mediates Neuronal Responses in Acute Ischemic Brain Injury by Regulating JNK Activation in a Signaling Module
Authors: Yang Guang , Cynader Max S.
Published: August 2011

Although the palmitoyl acyltransferase (PAT) zinc-finger DHHC containing 17 (zD17) has been implicated in genetic neurological disorders by regulating protein palmitoylation, the role of zD17 in acute brain injury remains unknown. Here, we report that zD17 contributes to acute ischemic brain injury via a mechanism independent of its PAT activity. We have found that zD17 directly interacts with c-Jun N terminus kinase (JNK) to form a signaling module for JNK activation. Pathological stressors induce the zD17–JNK interaction, which promotes downstream neuronal cell death signals. We have developed novel peptides targeting the JNK-interacting motif on zD17 to selectively block the enhancement of the zD17–JNK interaction and the activation of JNK isoforms 2 and 3. Application of these peptides successfully blocks JNK activation and neuronal cell death pathways, protects cultured neurons from excitotoxicity, and dramatically reduces brain damage and behavioral deficits in a rat model of focal ischemic stroke. Our findings indicate zD17 as a key player in ischemic stroke and suggest the potential therapeutic value of targeting the zD17–JNK interaction for acute brain injury.
Dynamics of Executive Control and Motor Deficits in Parkinsonian Rats
Authors: Courtière Alain , Hardouin Jeanine , Burle Borís , Vidal Franck , Turle-Lorenzo Nathalie , Amalric Marianne , Hasbroucq Thierry
Published: August 2011

While there is general agreement that in Parkinson's disease (PD), striatal dopamine (DA) depletion causes motor deficits, the origin of the associated cognitive impairments remains a matter of debate. The present study aimed to decipher the influence of a partial 6-hydroxydopamine (6-OHDA) lesion of striatal DA nerve terminals in rats performing a reaction time task previously used to assess cognitive deficits in PD patients. The effects of two behavioral manipulations—foreperiod duration and stimulus–response congruence—known to affect motor processes and executive control, respectively, were studied over 8 weeks postsurgery in control and lesion animals.

Two weeks after surgery, the lesion abolished the effect of foreperiod, confirming the direct involvement of striatal DA in motor processes, but failed to alter the effect of congruence. During the following weeks, the effect of foreperiod was reinstated, indicating a recovery of lesion-induced motor symptoms. This recovery was accompanied by a progressive increase of the congruence effect, signaling an executive control deficit in lesion animals. This result provides the first evidence that 6-OHDA lesioned rats exhibit the same cognitive impairment as PD patients in this task. The deficit, however, built up progressively after the lesion and may result from adaptations mitigating lesion-induced motor deficits.
TrkB as a Potential Synaptic and Behavioral Tag
Authors: Lu Yuan , Ji Yuanyuan , Ganesan Sundar , Schloesser Robert , Martinowich Keri , Sun Mu , Mei Fan , Chao Moses V. , Lu Bai
Published: August 2011

Late-phase long-term potentiation (L-LTP), a cellular model for long-term memory (LTM), requiresde novoprotein synthesis. An attractive hypothesis for synapse specificity of long-term memory is “synaptic tagging”: synaptic activity generates a tag, which “captures” the PRPs (plasticity-related proteins) derived outside of synapses. Here we provide evidence that TrkB, the receptor of BDNF (brain-derived neurotrophic factor), may serve as a “synaptic tag.” TrkB is transiently activated by weak theta-burst stimulation (TBS) that induces only early-phase LTP (E-LTP). This TrkB activation is independent of protein synthesis, and confined to stimulated synapses. Induction of L-LTP by strong stimulation in one synaptic pathway converts weak TBS-induced E-LTP to L-LTP in a second, independent pathway. Transient inhibition of TrkB around the time of weak TBS to the second pathway diminished L-LTP in that pathway without affecting the first one. Behaviorally, weak training, which induces short-term memory (STM) but not LTM, can be consolidated into LTM by exposing animals to novel but not familiar environment 1 h before training. Inhibition of TrkB during STM training blocked such consolidation. These results suggest TrkB as a potential tag for synapse-specific expression of L-LTP and LTM.
The General and Outcome-Specific Forms of Pavlovian-Instrumental Transfer Are Differentially Mediated by the Nucleus Accumbens Core and Shell
Authors: Corbit Laura H. , Balleine Bernard W.
Published: August 2011

Tests of Pavlovian–instrumental transfer (PIT) demonstrate that reward-predictive stimuli can exert a powerful motivational influence on the performance of instrumental actions. Recent evidence suggests that predictive stimuli produce this effect through either the general arousal (general PIT) or the specific predictions (outcome-specific PIT) produced by their association with reward. In two experiments, we examined the effects of pretraining lesions (Experiment 1) or muscimol-induced inactivation (Experiment 2) of either the core or shell regions of the nucleus accumbens (NAC) on these forms of PIT. Rats received Pavlovian training in which three auditory stimuli each predicted the delivery of a distinct food outcome. Separately, the rats were trained to perform two instrumental actions, each of which earned one of the outcomes used in Pavlovian conditioning. Finally, the effects of the three stimuli on performance of the two actions were assessed in extinction. Here we report evidence of a double dissociation between general and outcome-specific PIT at the level of the accumbens. Shell lesions eliminated outcome-specific PIT but spared general PIT, whereas lesions of the core abolished general PIT but spared outcome-specific PIT. Importantly, the infusion of muscimol into core or shell made immediately before the PIT tests produced a similar pattern of results. These results suggest that whereas the NAC core mediates the general excitatory effects of reward-related cues, the NAC shell mediates the effect of outcome-specific reward predictions on instrumental performance, and thereby serve to clarify reported discrepancies regarding the role of the NAC core and shell in PIT.
Dual Regulation of Anterograde and Retrograde Transmission by Endocannabinoids
Authors: Iremonger Karl J. , Kuzmiski J. Brent , Baimoukhametova Dinara V. , Bains Jaideep S.
Published: August 2011

Endocannabinoids (eCBs) are feedback messengers in the nervous system that act at the presynaptic nerve terminal to inhibit transmitter release. Here we report that in brain slices from rat, eCBs are released from vasopressin (VP) neurons in the paraventricular nucleus of the hypothalamus following coincident bursts of presynaptic and postsynaptic spiking. eCBs transiently depress glutamate release from excitatory terminals and, in doing so, prevent the synapses from undergoing long-term depression (LTD). Specifically, we show that blockade of CB1 receptors unmasks LTD following coincident presynaptic and postsynaptic activity. This LTD is presynaptic in nature, but requires the release of the opioid peptide dynorphin from the postsynaptic neuron. Dynorphin release and subsequent LTD require the activation of postsynaptic metabotropic glutamate receptors (mGluRs). Our findings indicate that eCBs, by transiently depressing glutamate release, limit mGluR activation and indirectly gate release of dynorphin from the postsynaptic neuron. We propose that eCBs, in addition to their well described role in the rapid modulation of transmitter release from the nerve terminal, also regulate the release of other retrograde transmitters and thus encode for multiple temporal windows of synaptic plasticity.
Extra-Classical Tuning Predicts Stimulus-Dependent Receptive Fields in Auditory Neurons
Authors: Schneider David M. , Woolley Sarah M. N.
Published: August 2011

The receptive fields of many sensory neurons are sensitive to statistical differences among classes of complex stimuli. For example, excitatory spectral bandwidths of midbrain auditory neurons and the spatial extent of cortical visual neurons differ during the processing of natural stimuli compared to the processing of artificial stimuli. Experimentally characterizing neuronal nonlinearities that contribute to stimulus-dependent receptive fields is important for understanding how neurons respond to different stimulus classes in multiple sensory modalities. Here we show that in the zebra finch, many auditory midbrain neurons have extra-classical receptive fields, consisting of sideband excitation and sideband inhibition. We also show that the presence, degree, and asymmetry of stimulus-dependent receptive fields during the processing of complex sounds are predicted by the presence, valence, and asymmetry of extra-classical tuning. Neurons for which excitatory bandwidth expands during the processing of song have extra-classical excitation. Neurons for which frequency tuning is static and for which excitatory bandwidth contracts during the processing of song have extra-classical inhibition. Simulation experiments further demonstrate that stimulus-dependent receptive fields can arise from extra-classical tuning with a static spike threshold nonlinearity. These findings demonstrate that a common neuronal nonlinearity can account for the stimulus dependence of receptive fields estimated from the responses of auditory neurons to stimuli with natural and non-natural statistics.
Hong Kong's Transformation into a Service Hub
Authors: Ramón-Berjano Carola B. , Xiaobin Simon Zhao , Ming Chan Ying
Published: August 2011

Following the return of Hong Kong to Chinese jurisdiction in 1997, there has been concern about the potential marginalization of Hong Kong within China's development. We argue that far from being marginalized, Hong Kong together with the Pearl River Delta is becoming the most dynamic region within China.
Hong Kong-Mainland Innovations in Environmental Protection since 1980
Authors: Loh Christine
Published: August 2011

Cross-boundary collaboration in environmental protection between Hong Kong and mainland China from the mid-1980s to the transfer of sovereignty in 1997, and during the post-reunification years, is examined. Emphasis is put on the respective roles of governments, the private sector, and non-governmental organization initiatives focused on air quality management, a key to public health.
Hong Kong's Contribution to Mainland China's Property Sector
Authors: Liu Mei Heung Amy , Zweig David
Published: August 2011

Hong Kong property developers helped Shanghai become a "global city," revitalizing the city core, hosting multinational corporations, and attracting global talent. They transformed the property sector's standards, urban life, and government revenues. Ironically, Shanghai's challenge to Hong Kong is derived from innovations by the same developers who created Hong Kong's remarkable property market.
High allele frequency of the p.Q258X mutation and identification of a novel mis-splicing mutation in the STAR gene in Korean patients with congenital lipoid adrenal hyperplasia
Authors: Kim Jae-Min , Choi Jin-Ho , Lee Jung Hyun , Kim Gu-Hwan , Lee Beom Hee , Kim Hae Soon , Shin Jeh-Hoon , Shin Choong-Ho , Kim Chan Jong , Yu Jeesuk , Lee Dae-Yeol , Cho Won Kyoung , Suh Byung-Kyu , Lee Ji Eun , Chung Hye Rim , Yoo Han-Wook
Published: August 2011

Objective

Steroidogenic acute regulatory (STAR) protein plays a crucial role in steroidogenesis, and mutations in the STAR gene cause congenital lipoid adrenal hyperplasia (CLAH). This study investigated the STAR mutation spectrum and functionally analyzed a novel STAR mutation in Korean patients with CLAH.

Methods

Mutation analysis of STAR was carried out in 25 unrelated Korean CLAH patients. A region of STAR comprising exons 4–7 was cloned from human genomic DNA into an expression vector, followed by site-directed mutagenesis and transient expression in COS7 cells. The splicing pattern was analyzed by in vitro transcription, and each transcript was functionally characterized by measuring pregnenolone production in COS7 cells cotransfected with the cholesterol side chain cleavage system.

Results

Mutation p.Q258X was identified in 46 of 50 alleles (92%); mutation c.653C>T was detected in two alleles (4%); and mutations p.R182H and c.745–6_810del were found in one allele (2%). Reverse transcriptase-PCR products amplified from a patient heterozygous for compound c.653C>T and c.745–6_810del mutation revealed multiple alternatively spliced mRNAs. In vitro expression analysis of a minigene consisting of exons 4–7 containing the c.653C>T yielded two transcripts in which exon 6 or exons 5 and 6 were skipped. The encoded proteins exhibited defective pregnenolone-producing ability. The c.745–6_810del mutation led to full and partial intron retention.

Conclusions

p.Q258X is the most common STAR mutation in Korea. A previously reported c.653C>T variant was found to cause aberrant splicing at the mRNA level, resulting in perturbation of STAR function. The c.745–6_810del mutation also resulted in aberrant splicing.