bluuebunny/crossref_metadata_2025 huggingface dataset:
Isorhamnetin 3-O-robinobioside from Nitraria retusa leaves enhance antioxidant and antigenotoxic activity in human chronic myelogenous leukemia cell line K562
Authors: Boubaker Jihed , Sghaier Mohammed Ben , Skandrani Ines , Ghedira Kamel , Chekir-Ghedira Leila
Published: August 2012

Background

In this report, the isorhamnetin 3-o-robinobioside and its original extract, the ethyl acetate extract, from Nitraria retusa leaves, were evaluated for their ability to induce antioxidant and antigenotoxic effects in human chronic myelogenous leukemia cell line.

Methods

Nitraria retusa products properties were carried out by firstly evaluating their effects against lipid peroxidation induced by H2O2, using the thiobarbituric acid reactive substances species (TBARS) assay, and proceeding to the assay of cellular antioxidant activity, then doing the comet assay.

Results

The isorhamnetin 3-o-robinobioside showed a protective effect against lipid peroxidation induced by H2O2. The same natural compound and ethyl acetate extract inhibited oxidation induced by 2,2′-azobis (2-amidinopropane) dihydrochloride in human chronic myelogenous leukemia cells with respectively 50% inhibitory concentration values of 0.225 mg/ml and 0.31 mg/ml, reflecting a significant antioxidant potential. The same two products inhibited the genotoxicity induced by hydroxyl radicals in the same human cell line (by 77.77% at a concentration of 800 μg/ml and by 80.55% at a concentration of 1000 μg/ml respectively).

Conclusions

The i sorhamnetin 3- o-robinobioside and its original extract, the ethyl acetate extract, from Nitraria retusa leaves, have a great antioxidant and antigenotoxic potential on human chronic myelogenous leukemia cell line K562.
In vitro and in vivodevelopment of mice morulae after storage in non-frozen conditions
Authors: de Dios Hourcade Juan , Pérez-Crespo Miriam , Serrano Alfredo , Gutiérrez-Adán Alfonso , Pintado Belén
Published: August 2012

Background

Interchange of genetically modified (GM) mice between laboratories using embryos provides several advantages. Not only is transport stress avoided, but also the health status of the recipient colony is not compromised. Embryos do not need to be shipped in frozen stage, which requires expensive packaging in addition to a certain degree of expertise in order to freeze and thaw them correctly. The aim of this study was to examine different storage conditions and their effect on embryo viability in order to establish the feasibility of practical, non-frozen conditions for embryo shipment.

Methods

Mouse morulae developed in vivo (collected from donors 2.5d post coitum) or in vitro (zygotes cultured until morulae stage) were stored, combining two different media (KSOMeq or KSOM-H) and temperatures (4 degrees C, 15 degrees C and 37 degrees C) throughout 24 or 48 hours. After storage in vitro viability was assessed determining percentage of development to blastocyst and total cell number. In vivo viability was determined based on the number of implantations and living fetuses after embryo transfer of stored embryos. The storage effect at the molecular level was assessed by studying a gene pool involved in early development by quantitative RT-PCR.

Results

In vivo-produced morulae stored for 24 hours did not show differences in development up to the blastocyst stage, regardless of the storage type. Even though a decrease in the total cell number in vivo was observed, embryo development after embryo transfer was not affected. All 24 hour storage conditions tested provided a similar number of implantations and fetuses at day 14 of pregnancy. Morulae obtained from in vitro embryo culture collected at the 1-cell stage showed a decreased ability to develop to blastocyst after 24 hours of storage at 15degrees C both in KSOMeq and KSOM-H. Concomitantly, a significant decrease of embryo implantation rates after transfer to recipients was also found. In order to further characterize the effect of non-frozen storage combining a molecular approach with the ordinary in vitro culture evaluation, embryos collected at the morula stage were submitted to the same storage conditions described throughout 48 hours. In vitro culture of those embryos showed a significant decrease in their developmental rate to blastocyst in both KSOMeq and KSOM-H at 15degrees C, which also affected the total number of cells. Gene transcription studies confirmed significant alterations in retrotransposons (Erv4 and Iap) after 48 h of storage at 15degrees C.

Conclusions

Our results show that both KSOMeq and KSOM-H can be equally used, and that several temperature conditions allow good survival rates in vitro and in vivo. Some of these storage conditions can substitute freezing in order to maintain embryo viability for 24–48 hours, providing a reliable and less demanding technical alternative for embryo interchanges.
Identification of swine influenza A virus and Stenotrophomonas maltophilia co-infection in Chinese pigs
Authors: Hou Dongjun , Bi Yuhai , Sun Honglei , Yang Jun , Fu Guanghua , Sun Yipeng , Liu Jinhua , Pu Juan
Published: August 2012

Background

Influenza virus virulence can be exacerbated by bacterial co-infections. Swine influenza virus (SIV) infection together with some bacteria is found to enhance pathogenicity.

Methods

SIV-positive samples suspected of containing bacteria were used for bacterial isolation and identification. Antimicrobial susceptibility testing was performed by disc diffusion methods. To investigate the interaction of SIV and the bacteria in vitro, guinea pigs were used as mammalian hosts to determine the effect on viral susceptibility and transmissibility. Differences in viral titers between groups were compared using Student’s t-test.

Results

During surveillance for SIV in China from 2006 to 2009, seven isolates (24.14%) of 29 influenza A viruses were co-isolated with Stenotrophomonas maltophilia from nasal and tracheal swab samples of pigs. Antimicrobial susceptibility testing showed that the bacteria possessed a high level of resistance towards clinically used antibiotics. To investigate the interaction between these two microorganisms in influencing viral susceptibility and transmission in humans, guinea pigs were used as an infection model. Animals were inoculated with SIV or S. maltophilia alone or co-infected with SIV and S. maltophilia. The results showed that although no transmission among guinea pigs was observed, virus–bacteria co-infections resulted in higher virus titers in nasal washes and trachea and a longer virus shedding period.

Conclusions

This is the first report of influenza virus co-infection with S. maltophilia in the Chinese swine population. Increased replication of virus by co-infection with multidrug resistant bacteria might increase the infection rate of SIV in humans. The control of S. maltophilia in clinics will contribute to reducing the spread of SIV in pigs and humans.
Long-term outcome of irradiation with or without chemotherapy for esophageal squamous cell carcinoma: a final report on a prospective trial
Authors: Liu Mina , Shi Xuehui , Guo Xiaomao , Yao Weiqiang , Liu Yong , Zhao Kuaile , Jiang Guo-Liang
Published: August 2012

Purpose

To investigate the long-term outcome of esophageal squamous cell carcinoma (SCC) treated by irradiation with or without concurrent chemotherapy.

Methods and materials

A prospective clinical trial was carried out from 1998 to 2000. One hundred and eleven patients were randomly enrolled to receive either late course accelerated hyperfractionated irradiation (LCAF) or LCAF with concurrent chemotherapy (LCAF + CT). For LCAF, 41.4 Gy in 23 fractions was first delivered at five fractions per week, followed by 27 Gy in 18 fractions at two 1.5 Gy fractions a day. Concurrent chemotherapy of cis-platinum and 5-fluorouracil was administered for four cycles. Overall survival (OS), locoregional recurrence and distant metastasis were observed. Late toxicity was scored by RTOG criteria, and quality of life (QOL) was also evaluated.

Results

The median follow-up time was 24 months for all patients and 138 months for 17 living patients. Median survival time was 25 months and 32 months in LCAF and LCAF + CT (p = 0.653), respectively. For an entire group of patients, overall survivals were 34%, 27% and 22%; locoregional recurrence rates were 30%, 36% and 41%; and distant metastasis rates were 26%, 28% and 29% at 5-yr, 8-yr and 10-yr, respectively. Incidences of ≥ Grade 3 late toxicity were 29% at 10-yr. There were no statistically significant differences between LCAF and LCAF + CT with respect to the parameters mentioned above. Cumulative incidence of late toxicities of ≥ Grade 3 increased sharply after the attained age of 70 years. Eighty-eight percent of patients lived with good KPS (≥ 90) and 94% could eat regular or soft diet.

Conclusion

The long-term outcome of esophageal SCC patients who received LCAF or LCAF + CT was good. The locoregional and distant failures occurred more often in the first three years after treatment, but could continuously occur up to 10 years. The late toxicity was acceptable. Late toxicities ≥ Grade 3 were more likely to occur in elderly patients. QOL was good in living patients.
Surgical telepresence: the usability of a robotic communication platform
Authors: Marttos Antonio , Kuchkarian Fernanda M , Palaios Emmanouil , Rojas Daniel , Abreu-Reis Phillipe , Schulman Carl
Published: August 2012

Introduction

The benefits of telepresence in trauma and acute surgical care exist, yet its use in a live, operating room (OR) setting with real surgical cases remains limited.

Methods

We tested the use of a robotic telepresence system in the OR of a busy, level 1 trauma center. After each case, both the local and remote physicians completed questionnaires regarding the use of the system using a five point Likert scale. For trauma cases, physicians were asked to grade injury severity according to the American Association for the Surgery of Trauma (AAST) Scaling System.

Results

We collected prospective, observational data on 50 emergent and elective cases. 64% of cases were emergency surgery on trauma patients, almost evenly distributed between penetrating (49%) and blunt injuries (51%). 40% of non-trauma cases were hernia-related. A varied distribution of injuries was observed to the abdomen, chest, extremities, small bowel, kidneys, spleen, and colon. Physicians gave the system high ratings for its audio and visual capabilities, but identified internet connectivity and crowding in the operating room as potential challenges. The loccal clinician classified injuries according to the AAST injury grading system in 63% (n=22) of trauma cases, compared to 54% (n=19) of cases by the remote physicians. The remote physician cited obstruction of view as the main reason for the discrepancy. 94% of remote physicians and 74% of local physicians felt comfortable communicating via the telepresence system. For 90% of cases, both the remote and local physicians strongly agreed that a telepresence system for consultations in the OR is more effective than a telephone conversation.

Conclusions

A telepresence system was tested on a variety of surgical cases and demonstrated that it can be an appropriate solution for use in the operating room. Future research should determine its impact on processes of care and surgical outcomes.
Enhancing trauma education worldwide through telemedicine
Authors: Marttos Antonio C , Kuchkarian Fernanda M , Abreu-Reis Phillipe , Pereira Bruno MT , Collet-Silva Francisco S , Fraga Gustavo P
Published: August 2012

Advances in information and communication technologies are changing the delivery of trauma care and education. Telemedicine is a tool that can be used to deliver expert trauma care and education anywhere in the world. Trauma is a rapidly-evolving field requiring access to readily available sources of information. Through videoconferencing, physicians can participate in continuing education activities such as Grand Rounds, seminars, conferences and journal clubs. Exemplary programs have shown promising outcomes of teleconferences such as enhanced learning, professional collaborations, and networking. This review introduces the concept of telemedicine for trauma education, and highlights efforts of programs that are utilizing telemedicine to unite institutions across the world.
The Mental Capacity Act and mental healthcare in prison: opportunities and challenges
Authors: Davies Sharon , Dimond Claire
Published: August 2012

The UK Mental Health Act 1983 does not apply in prison. The legal framework for the care and treatment of people with mental illness in prison is provided by the Mental Capacity Act 2005. We raise dilemmas about its use. We highlight how assessing best interests and defining harm involves making challenging judgements. How best interests and harm are interpreted has a potentially significant impact on clinical practice within a prison context.
Sector and functional models of consultant care: in-patient satisfaction with psychiatrists
Authors: Laugharne Richard , Pant Milind
Published: August 2012

Aims and method

To investigate in-patient satisfaction with psychiatrists, comparing National Health Service (NHS) trusts with sector consultants against NHS trusts with separate in-patient and community consultants (the functional model). The Care Quality Commission's in-patient survey was used, comparing mean scores on four questions concerning patient satisfaction with consultants.

Results

Patients scored higher for being treated with respect in trusts with sector consultants. In questions concerning trust, being listened to and getting adequate time, patient satisfaction scores were again higher for sector consultants, but did not reach 5% significance.

Clinical implications

Moving to a split between in-patient and community consultants may reduce in-patient satisfaction with care. The continuity of care with sector-based consultants may be a factor in greater in-patient satisfaction.
Zofia Zukowska
Authors: McEwen Bruce
Published: August 2012

The death of Zofia Zukowska, on April 15, 2012, represents the loss of a vibrant and energetic leader in the fields of stress physiology and neuropeptide Y (NPY) biology.
What counts for ants? How return behaviour and food search of Cataglyphis ants are modified by variations in food quantity and experience
Authors: Bolek Siegfried , Wittlinger Matthias , Wolf Harald
Published: August 2012

When finding more food than one is able to carry home, should one come back to the site to exploit it further? This question is crucial for central place foragers that provide for a home place with brood or nest mates. The benefit of returning has to be weighed against the chance of finding food elsewhere and the resources available. Desert ants Cataglyphis fortis are well-studied examples when it comes to navigating back and forth between their nest and a foraging area, due to their primary reliance on path integration in the open and featureless desert habitat. The ants use path integration not only for a safe return from their foraging trips but also for future returns to plentiful feeding sites. The direction from the nest that has previously yielded food items is preferred for future foraging trips, a phenomenon termed sector fidelity. What prompts the ants to return to a particular site, and how faithfully they search for that place, has not been well studied. We examine the evaluation of food sources in channel experiments by varying both the number of food items in a feeder and the number of visits to the feeder before testing search distances of foragers returning to the feeding site. Ants exhibited more focused searches for plentiful food sources than for sources with only few food items upon their first return visit. After several successful visits, the ants always searched thoroughly for the food source, independent of the amount of food offered. Thus, desert ants consider both food abundance and reliability of food encounter, with corroborative learning of reliability gradually overriding the initial preference for plentiful feeders. The density of food items appears to be used by the ants as a proxy for food abundance. On the level of our analysis, the searches performed in the experimental channels are indistinguishable from those performed in the open desert terrain. The present results not only demonstrate how otherwise well-studied desert ants assess yield and experience with reliability of food sources, but also establish a model system for future study of how itemised food sources are exploited.
Temperature dependence of distortion-product otoacoustic emissions in tympanal organs of locusts
Authors: Möckel Doreen , Kössl Manfred , Lang Julian , Nowotny Manuela
Published: August 2012

Distortion-product otoacoustic emissions (DPOAEs) in tympanal organs of insects are vulnerable to manipulations that interfere with the animal's physiological state. Starting at a medium temperature, we raised and lowered the locust's body temperature within the range of 12 to 35°C by changing the temperature of the surrounding air, while recording DPOAEs. These experimental manipulations resulted in reversible amplitude changes of the 2f1–f2 emission, which were dependent on stimulus frequency and level. Using low f2 frequencies of up to 10 kHz, a temperature increase (median +8–9°C) led to an upward shift of DPOAE amplitudes of approximately +10 dB, whereas a temperature decrease (median −7°C) was followed by a reduction of DPOAE amplitudes by 3 to 5 dB. Both effects were only present in the range of the low-level component of DPOAE growth functions below L2 levels (levels of the f2 stimulus) of approximately 30 dB SPL. DPOAEs evoked by higher stimulus levels as well as measurements using higher stimulation frequencies above 10 kHz remained unaffected by any temperature shifts. The Arrhenius activation energy was calculated from the −10 dB SPL thresholds (representing the low-level component) of growth functions, which had been measured with 8 and 10 kHz as f2 frequencies and amounted to up to ~34 and 41 kJ mol−1, respectively. Such activation energy values provide a hint that the dynein-tubulin system within the scolopidial receptors could play an essential part in the DPOAE generation in tympanal organs.
Prevention of renal ischemia-reperfusion injury by short hairpin RNA of endothelin A receptor in a rat model
Authors: Jia Yichen , Zhao Zitong , Xu Ming , Zhao Tian , Qiu Yongyin , Ooi Yitreen , Yang Bin , Rong Ruiming , Zhu Tongyu
Published: August 2012

Endothelin A receptor (ETaR) is a key molecule involved in a variety of biological events such as vessel contraction and inflammatory response in ischemia-reperfusion (I/R) injury. RNA interference using short hairpin RNA (shRNA) is a powerful tool to silence gene expression. Here, the effect of ETaR shRNA on I/R injury in rats was studied. A more effective shRNA sequence out of two constructed into plasmid vectors was selected using the A-10 cell line, and was then applied to a rat model. Twenty-eight male Sprague-Dawley rats were randomized into four groups: Sham, shRNA, vector and phosphate-buffered saline (PBS). Renal I/R injury was induced by clamping the left renal pedicle for one hour followed by reperfusion for 24 h. ETaR shRNA (100 μg) plasmid was administered by renal vein injection 48 h before clamping. The expression of both ETaR mRNA and protein was lowered by ETaR shRNA treatment compared with that in the vector and PBS groups; serum creatinine and blood urea nitrogen were significantly decreased; the semi-quantitative score of renal structural damage was improved; the mRNA level of endothelin 1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), macrophage inflammatory protein 2 (MIP-2) and monocyte chemoattractant protein 1 (MCP-1) was reduced, but nitric oxide (NO) production in kidney tissues was increased ( P < 0.05). In conclusion, ETaR shRNA partially silenced ETaR expression in I/R injury kidneys, reduced the mRNA level of ET-1, inflammatory mediators including TNF-α, IL-6, MIP-2 and MCP-1, increased NO production, and ultimately improved renal function and structure.
Worrying about the wrong thing: Patient mobility versus mobility of health care professionals
Authors: Glinos Irene
Published: August 2012

Patients and health care professionals in the European Union (EU) benefit from legislation on the freedom of movement between Member States. In relative terms, many more doctors and nurses move within the EU than patients. Despite this, patient mobility has attracted more attention from policy-makers and the public while workforce mobility remains largely ignored. This is paradoxical and imprudent. On the one hand, the scope of patient mobility is narrow and self-limited. On the other hand, current and forecasted health care workforce shortages across the EU, global competition for health care professionals, and current economic pressures are all good reasons to start worrying about the mobility of health care professionals and its implications for health systems.
Syndrome of Inappropriate Antidiuretic Hormone Secretion Induced by a Single Dose of Oral Cyclophosphamide
Authors: Gilbar Peter J , Richmond Joshua , Wood John , Sullivan Aimee
Published: August 2012

OBJECTIVE:

To report a case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by a single oral dose of cyclophosphamide.

CASE SUMMARY:

A 69-year-old woman was treated with oral CTD (cyclophosphamide/thalidomide/dexamethasone) chemotherapy for multiple myeloma. Two days after the first dose (including cyclophosphamide 500 mg), the patient developed vomiting, drowsiness, and headache. Medication history included sertraline, started in 2005. On admission, laboratory values were serum sodium 113 mEq/L, serum osmolality 240 mOsm/kg, urinary osmolality 701 mOsm/kg, urinary sodium 91 mEq/L, and serum creatinine 0.71 mg/dL. Thyroid and adrenal function were normal. SIADH was diagnosed. Cyclophosphamide and sertraline were stopped and fluid restriction was commenced. The patient was discharged on day 9 following chemotherapy with serum sodium 132 mEq/L. Sertraline was restarted. Four days later she developed vomiting with serum sodium 119 mEq/L. Fluid restriction, which the woman had not performed, was reinstituted and she was discharged on day 17. Two further cycles of chemotherapy were subsequently given without cyclophosphamide and serum sodium remained within normal limits.

DISCUSSION:

Cyclophosphamide-induced severe hyponatremia and SIADH have been documented in patients receiving treatment for a wide range of malignant and autoimmune disorders. All cases have involved intravenous therapy, with doses ranging from single pulse doses of 500 mg to 3000 mg/m2. Selective serotonin reuptake inhibitors are a common cause of SIADH. Because sertraline was instituted in 2005 and reinstituted without incident, it was eliminated as a contributing factor. Malignancy, tumor lysis syndrome, other medications, hydration to prevent hemorrhagic cystitis, and renal impairment were also ruled out. The Naranjo probability scale indicated a probable association between SIADH and cyclophosphamide administration.

CONCLUSIONS:

To our knowledge, our report represents the first case of SIADH due to a single oral dose of cyclophosphamide. Clinicians should be aware of this rare adverse event, as it can have life-threatening consequences.
The Server and the Served: Food, Feeding, and Consumption in Adoor Gopalakrishnan's Kodiyettam
Authors: Ganguly Suranjan
Published: August 2012

A man sits on the floor wolfing down his food while a woman, seated across, serves him from time to time. Anyone familiar with Adoor Gopalakrishnan's oeuvre would immediately recognize this visual trope since it surfaces in almost all his major films, including his recent Naalu Pennungal/Four Women (2007). Food and its consumption, in fact, are integral to his exploration of gender relations in his native Kerala. Along with the physical act of eating, he seeks to capture the psychological, social, and cultural dynamics of a ritual involving two individuals.
Nuclear Factor κB Activation Impairs Ependymal Ciliogenesis and Links Neuroinflammation to Hydrocephalus Formation
Authors: Lattke Michael , Magnutzki Alexander , Walther Paul , Wirth Thomas , Baumann Bernd
Published: August 2012

Hydrocephalus formation is a frequent complication of neuropathological insults associated with neuroinflammation. However, the mechanistic role of neuroinflammation in hydrocephalus development is unclear. We have investigated the function of the proinflammatory acting inhibitor of κB kinase (IKK)/nuclear factor κB (NF-κB) signaling system in neuroinflammatory processes and generated a novel mouse model that allows conditional activation of the IKK/NF-κB system in astrocytes. Remarkably, NF-κB activation in astrocytes during early postnatal life results in hydrocephalus formation and additional defects in brain development. NF-κB activation causes global neuroinflammation characterized by a strong, astrocyte-specific expression of proinflammatory NF-κB target genes as well as a massive infiltration and activation of macrophages. In this animal model, hydrocephalus formation is specifically induced during a critical time period of early postnatal development, in which IKK/NF-κB-induced neuroinflammation interferes with ependymal ciliogenesis. Our findings demonstrate for the first time that IKK/NF-κB activation is sufficient to induce hydrocephalus formation and provides a potential mechanistic explanation for the frequent association of neuroinflammation and hydrocephalus formation during brain development, namely impairment of ependymal cilia formation. Therefore, our study might open up new perspectives for the treatment of certain types of neonatal and childhood hydrocephalus associated with hemorrhages and infections.
The Spiking Component of Oscillatory Extracellular Potentials in the Rat Hippocampus
Authors: Schomburg Erik W. , Anastassiou Costas A. , Buzsáki György , Koch Christof
Published: August 2012

When monitoring neural activity using intracranial electrical recordings, researchers typically consider the signals to have two primary components: fast action potentials (APs) from neurons near the electrode, and the slower local field potential (LFP), thought to be dominated by postsynaptic currents integrated over a larger volume of tissue. In general, a decrease in signal power with increasing frequency is observed for most brain rhythms. The 100–200 Hz oscillations in the rat hippocampus, including “fast gamma” or “epsilon” oscillations and sharp wave-ripples (SPW-Rs), are one exception, showing an increase in power with frequency within this band. We have used detailed biophysical modeling to investigate the composition of extracellular potentials during fast oscillations in rat CA1. We find that postsynaptic currents exhibit a decreasing ability to generate large-amplitude oscillatory signals at high frequencies, whereas phase-modulated spiking shows the opposite trend. Our estimates indicate that APs and postsynaptic currents contribute similar proportions of the power contained in 140–200 Hz ripples, and the two combined generate a signal that closely resemblesin vivoSPW-Rs. Much of the AP-generated signal originates from neurons further than 100 μm from the recording site, consistent with ripples appearing similarly strong regardless of whether or not they contain recognizable APs. Additionally, substantial power can be generated in the 90–150 Hz epsilon band by the APs of rhythmically firing pyramidal neurons. Thus, high-frequency LFPs may generally contain signatures of local cell assembly activation.
Lipopolysaccharide-Induced Microglial Activation and Neuroprotection against Experimental Brain Injury Is Independent of Hematogenous TLR4
Authors: Chen Zhihong , Jalabi Walid , Shpargel Karl B. , Farabaugh Kenneth T. , Dutta Ranjan , Yin Xinghua , Kidd Grahame J. , Bergmann Cornelia C. , Stohlman Stephen A. , Trapp Bruce D.
Published: August 2012

Intraperitoneal injection of the Gram-negative bacterial endotoxin lipopolysaccharide (LPS) elicits a rapid innate immune response. While this systemic inflammatory response can be destructive, tolerable low doses of LPS render the brain transiently resistant to subsequent injuries. However, the mechanism by which microglia respond to LPS stimulation and participate in subsequent neuroprotection has not been documented. In this study, we first established a novel LPS treatment paradigm where mice were injected intraperitoneally with 1.0 mg/kg LPS for four consecutive days to globally activate CNS microglia. By using a reciprocal bone marrow transplantation procedure between wild-type and Toll-like receptor 4 (TLR4) mutant mice, we demonstrated that the presence of LPS receptor (TLR4) is not required on hematogenous immune cells but is required on cells that are not replaced by bone marrow transplantation, such as vascular endothelia and microglia, to transduce microglial activation and neuroprotection. Furthermore, we showed that activated microglia physically ensheathe cortical projection neurons, which have reduced axosomatic inhibitory synapses from the neuronal perikarya. In line with previous reports that inhibitory synapse reduction protects neurons from degeneration and injury, we show here that neuronal cell death and lesion volumes are significantly reduced in LPS-treated animals following experimental brain injury. Together, our results suggest that activated microglia participate in neuroprotection and that this neuroprotection is likely achieved through reduction of inhibitory axosomatic synapses. The therapeutic significance of these findings rests not only in identifying neuroprotective functions of microglia, but also in establishing the CNS location of TLR4 activation.
A Phosphatidylinositol Lipids System, Lamellipodin, and Ena/VASP Regulate Dynamic Morphology of Multipolar Migrating Cells in the Developing Cerebral Cortex
Authors: Yoshinaga Satoshi , Ohkubo Takahiro , Sasaki Shinji , Nuriya Mutsuo , Ogawa Yukino , Yasui Masato , Tabata Hidenori , Nakajima Kazunori
Published: August 2012

In the developing mammalian cerebral cortex, excitatory neurons are generated in the ventricular zone (VZ) and subventricular zone; these neurons migrate toward the pial surface. The neurons generated in the VZ assume a multipolar morphology and remain in a narrow region called the multipolar cell accumulation zone (MAZ) for ∼24 h, in which they extend and retract multiple processes dynamically. They eventually extend an axon tangentially and begin radial migration using a migratory mode called locomotion. Despite the potential biological importance of the process movement of multipolar cells, the molecular mechanisms remain to be elucidated. Here, we observed that the processes of mouse multipolar cells were actin rich and morphologically resembled the filopodia and lamellipodia in growth cones; thus, we focused on the actin-remodeling proteins Lamellipodin (Lpd) and Ena/vasodilator-stimulated phosphoprotein (VASP). Lpd binds to phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P2] and recruits Ena/VASP, which promotes the assembly of actin filaments, to the plasma membranes.In situhybridization and immunohistochemistry revealed that Lpd is expressed in multipolar cells in the MAZ. The functional silencing of either Lpd or Ena/VASP decreased the number of primary processes. Immunostaining and a Förster resonance energy transfer analysis revealed the subcellular localization of PI(3,4)P2at the tips of the processes. A knockdown experiment and treatment with an inhibitor for Src homology 2-containing inositol phosphatase-2, a 5-phosphatase that produces PI(3,4)P2from phosphatidylinositol (3,4,5)-triphosphate, decreased the number of primary processes. Our observations suggest that PI(3,4)P2, Lpd, and Ena/VASP are involved in the process movement of multipolar migrating cells.
Ryanodine Receptor Blockade Reduces Amyloid-β Load and Memory Impairments in Tg2576 Mouse Model of Alzheimer Disease
Authors: Oulès Bénédicte , Del Prete Dolores , Greco Barbara , Zhang Xuexin , Lauritzen Inger , Sevalle Jean , Moreno Sebastien , Paterlini-Bréchot Patrizia , Trebak Mohamed , Checler Frédéric , Benfenati Fabio , Chami Mounia
Published: August 2012

In Alzheimer disease (AD), the perturbation of the endoplasmic reticulum (ER) calcium (Ca2+) homeostasis has been linked to presenilins, the catalytic core in γ-secretase complexes cleaving the amyloid precursor protein (APP), thereby generating amyloid-β (Aβ) peptides. Here we investigate whether APP contributes to ER Ca2+homeostasis and whether ER Ca2+could in turn influence Aβ production. We show that overexpression of wild-type human APP (APP695), or APP harboring the Swedish double mutation (APPswe) triggers increased ryanodine receptor (RyR) expression and enhances RyR-mediated ER Ca2+release in SH-SY5Y neuroblastoma cells and in APPswe-expressing (Tg2576) mice. Interestingly, dantrolene-induced lowering of RyR-mediated Ca2+release leads to the reduction of both intracellular and extracellular Aβ load in neuroblastoma cells as well as in primary cultured neurons derived from Tg2576 mice. This Aβ reduction can be accounted for by decreased Thr-668-dependent APP phosphorylation and β- and γ-secretases activities. Importantly, dantrolene diminishes Aβ load, reduces Aβ-related histological lesions, and slows down learning and memory deficits in Tg2576 mice. Overall, our data document a key role of RyR in Aβ production and learning and memory performances, and delineate RyR-mediated control of Ca2+homeostasis as a physiological paradigm that could be targeted for innovative therapeutic approaches.
Role of Orbitofrontal Cortex Neuronal Ensembles in the Expression of Incubation of Heroin Craving
Authors: Fanous Sanya , Goldart Evan M. , Theberge Florence R. M. , Bossert Jennifer M. , Shaham Yavin , Hope Bruce T.
Published: August 2012

In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6 h/d for 10 d) and assessed cue-induced heroin seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin seeking increased from 1 to 14 d and was accompanied by increased Fos expression in ∼12% of OFC neurons. Nonselective inactivation of OFC neurons with the GABA agonists baclofen + muscimol decreased cue-induced heroin seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin seeking after 14 withdrawal days. We trainedc-fos–lacZtransgenic rats to self-administer heroin and 11 d later reexposed them to heroin-associated cues or novel cues for 15 min (induction day), followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 d later. Daun02 selectively decreased cue-induced heroin seeking in rats previously reexposed to the heroin-associated cues on induction day but not in rats exposed previously to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving.
Two Cheers for Burma’s Rigged Election
Authors: Englehart Neil A.
Published: August 2012

Burma’s recent election was clearly not free and fair. However, it can also be seen as improving a uniquely unrepresentative government, creating greater pluralism, and institutionalizing differences within the ruling junta. Even the rigged election may have created opportunities for further opening in the future.
Governance through Difference in Singapore
Authors: Vasu Norman
Published: August 2012

Although the normative ideal of multiculturalism is the accommodation of communal differences, Singaporean multiculturalism is instead integral to a corporatist form of governance. This article argues that an emerging Singaporean-ness antithetical to the necessary inter-communal divisions required for corporatism poses a strong challenge to the manner in which the city-state is governed.
The U.S. Military and American Commitment to Taiwan’s Security
Authors: Tsang Steve
Published: August 2012

This article focuses on how the U.S. military assesses the threat of a Taiwan Strait crisis over the next two decades, America’s possible responses, and the U.S. capacity for effective intervention. It examines the drivers behind the U.S. approach, highlighting their implications.
Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women
Authors: Roelfsema Ferdinand , Pijl Hanno , Keenan Daniel M , Veldhuis Johannes D
Published: August 2012

Background

The ACTH–cortisol axis in women is activated and associated with decreased ACTH potency, estimated by relating ACTH and cortisol pulse masses. Recently, a new accurate method for constructing the endogenous dose–response relationship was introduced, which is based on the relation between ACTH concentrations and associated cortisol secretion rates within cortisol bursts.

Hypothesis

The endogenous dose–response relation between ACTH and cortisol in obesity is changed, leading to diminished responsiveness.

Subjects

Twenty-five obese premenopausal women and 16 normal weight premenopausal women were studied by 10-min blood sampling for 24 h.

Outcomes

ACTH and cortisol secretion rates, analytical dose–response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH–cortisol profiles were quantified.

Results

The initial potency (negative logarithm) was −7.83±0.75 (mean±s.e.m.) in obese women and −10.14±1.08 in lean women (P=0.10), and the corresponding values for the recovery phase were −26.62±2.21 and −36.67±1.66 (P=0.004). The sensitivity (curve slope) amounted to 0.468±0.05 in obese women and 0.784±0.09 in normal weight women (P=0.004). The efficacy (maximal value) was 17.6±4.9 nmol/l per min in obese women and 26.3±3.8 nmol/l per min in normal weight women (P=0.009). Basal secretion rate, inflection point, and EC50values were not different. Bromocriptine or acipimox did not change the dose–response curve.

Conclusion

The ACTH–cortisol relation in obesity in women is characterized by decreased sensitivity and efficacy, thus explaining non-elevated serum cortisol concentrations despite increased plasma ACTH levels.
Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress
Authors: Nostramo Regina , Tillinger Andrej , Saavedra Juan M , Kumar Ashok , Pandey Varunkumar , Serova Lidia , Kvetnansky Richard , Sabban Esther L
Published: August 2012

While the renin–angiotensin system is important for adrenomedullary responses to stress, the involvement of specific angiotensin II (Ang II) receptor subtypes is unclear. We examined gene expression changes of angiotensin II type 1A (AT1A) and type 2 (AT2) receptors in rat adrenal medulla in response to immobilization stress (IMO). AT2receptor mRNA levels decreased immediately after a single 2-h IMO. Repeated IMO also decreased AT2receptor mRNA levels, but the decline was more transient. AT1Areceptor mRNA levels were unaltered with either single or repeated IMO, although binding was increased following repeated IMO. These effects of stress on Ang II receptor expression may alter catecholamine biosynthesis, as tyrosine hydroxylase and dopamine β-hydroxylase mRNA levels in PC12 cells are decreased with Ang II treatment in the presence of ZD7155 (AT1receptor antagonist) or with CGP42112 (AT2receptor agonist) treatment. Involvement of stress-triggered activation of the hypothalamic–pituitary–adrenocortical or sympathoadrenal axis in AT2receptor downregulation was examined. Cultured cells treated with the synthetic glucocorticoid dexamethasone displayed a transcriptionally mediated decrease in AT2receptor mRNA levels. However, glucocorticoids are not required for the immediate stress-triggered decrease in AT2receptor gene expression, as demonstrated in corticotropin-releasing hormone knockout (CrhKO) mice and hypophysectomized rats, although they can regulate basal gene expression. cAMP and pituitary adenylate cyclase-activating polypeptide also reduced AT2receptor gene expression and may mediate this response. Overall, the effects of stress on adrenomedullary AT1Aand AT2receptor expression may contribute to allostatic changes, such as regulation of catecholamine biosynthesis.
Electroencephalographic examination of epileptic dogs under propofol restraint
Authors: Ákos Pákozdy , Thalhammer Johann , Leschnik Michael , Halász Péter
Published: August 2012

The main aim of this study was to identify interictal epileptiform discharges in a group of dogs with seizures of known aetiology (symptomatic epilepsy, SE) and in dogs with idiopathic epilepsy (IE). Propofol was used for chemical restraint in all dogs. We found electroencephalographic (EEG) changes that could be considered epileptiform discharges (EDs) in 5 out of 40 dogs (12.5%). The EEG changes identified were spikes in four cases and periodic epileptiform discharges in one case. All EDs were seen in the SE group. We conclude that the interictal electroencephalographic examinations of propofolanaesthetised dogs suffering from IE and SE rarely show epileptic discharges and that the diagnostic value of such EEGs in the work-up for epilepsy seems to be low as epileptic discharges were unlikely to be detected. However, positive findings are more likely to be connected with SE. We found frequent, transient EEG phenomena (spindles, K-complexes, vertex waves, positive occipital sharp transients of sleep, cyclic alternating patterns), which are non-epileptic but their differentiation from epileptic phenomena is challenging.
Upregulation of LENK and VIP in paracervical ganglion neurons supplying the urinary bladder of tetrodotoxin- and resiniferatoxin-treated female pigs
Authors: Burliński Piotr , Czujkowska Agnieszka , Arciszewski Marcin , Całka Jarosław
Published: August 2012

Both resiniferatoxin (RTX) and tetrodotoxin (TTX) have been reported to be effective in several clinical trials aiming to cure urinary bladder dysfunction. The goal of this experiment was to study the effect of intravesical administration of RTX and TTX on the chemical coding of paracervical ganglion (PCG) neurons that supply the urinary bladder in pigs. The vasoactive intestinal peptide (VIP) and the opioid family member Leu5-enkephalin (LENK) are both known for their regulatory effects in the function of the porcine genitourinary tract. The PCG neurons innervating the urinary bladder were identified by application of the retrograde tracer Fast Blue (FB), injected into the bladder wall prior to intravesical RTX or TTX administration. Immunocytochemical detection of LENK and VIP expression in the FB-labelled perikarya revealed that in the control group 25.15% of the FB-positive PCG neurons contained LENK, and 9.22% of them expressed VIP. Intravesical infusion of RTX resulted in an increase in the number of LENKIR neurons to 48.19% and VIP-IR perikarya to 11.25%. Optional treatment with TTX induced increase of LENK-IR neurons up to 81.67% and VIP-IR population to 16.46% of the FB-positive PCG cells. The present results show that both neurotoxins affect the chemical coding of PCG nervous cells supplying the porcine urinary bladder and that they stimulate both LENK and VIP expression. Furthermore, the results indicate a possible involvement of LENK and VIP neurons in the mechanisms of action of RTX and TTX in the therapy of overactive bladder disorder.
Enzymatic catalysed synthesis and gelation of ionic peptides for 3D cell culture applications.
Authors: Guilbaud Jean-Baptiste , Szkolar Laura , Miller Aline F. , Saiani Alberto
Published: August 2012

The enzymatic catalyzed synthesis and gelation of an ionic peptide and its use to create hydrogels for 3D cell culture is discussed. Time resolved small angle scattering in conjunction with imaging technique allowed the structural changes occurring through this enzymatic reaction to be assessed. In turn, the structural information about the fibrillar network and its local density proved key in facilitating the understanding of the relationships between self-assembly behavior, local nanostructure and final physical properties of the materials. The understanding of the gelation process of these materials allowed the design of a simple and efficient methodology to prepare gels for cell culture. Tetrapeptide/enzyme solution containing cells could be injected into cell culture plate with subsequent gelation of the materials leading to encapsulation of the cells into a 3D network. This system was evaluated for the 3D cell culture of human dermal fibroblasts (HDF). Microscopy showed that cells were uniformly distributed within the gel matrix. Cell counting and live/dead staining showed proliferation of HDF with limited cell death over 10 days.
Ultraviolet (UV) photodetectors fabricated from multi-walled carbon nanotubes (MWCNTs) and polyvinyl-alcohol (PVA) coated ZnO nanoparticles
Authors: Shao Dali , Qin Liqiao , Sawyer Shayla
Published: August 2012

Enhanced near band-edge (NBE) emission was observed from composite structures fabricated from a PVA coated ZnO (PVA-ZnO) nanoparticle thin film embedded with multi-walled carbon nanotubes (MWCNTs). The enhancement is attributed to the resonant coupling between the bandgap transition of the semiconductor and the surface plasmon (SP) of MWCNTs. Moreover, the PVA-ZnO/MWCNTs/PVA-ZnO composite structures show faster transient response, which is due to the carrier transportation process in the composite structure. Reductions are observed for both photocurrent to dark current ratio and intensity of photoresponsivity, demonstrating a tradeoff between the time transient response and the detectivity.
Preparation of Bi Superconducting Grains Including Seed Crystals by Shock Compaction
Authors: Kezuka Hiroshi , Endo Kazuhiro , Kameya Takaki , Itoh Mineo , Matsumoto Hitoshi , Kishimura Hiroaki , Endo Tamio , Arisawa Shunichi
Published: August 2012

We have fabricated Bi2212 and Bi2223 bulk samples by shock compaction technique. Seed crystals were added to the starting materials in order to promote crystallization. The grain size of the prepared sample was increased by the addition of seed crystals to the starting material.
Sensitivity of UO2 Stability in a Reducing Environment on Radiolysis Model Parameters
Authors: Wittman Richard S. , Buck Edgar C.
Published: August 2012

Results for a radiolysis model sensitivity study of radiolytically produced H2O2 are presented as they relate to Spent (or Used) Light Water Reactor uranium oxide (UO2) nuclear fuel (UNF) oxidation in a low oxygen environment. The model builds on previous reaction kinetic studies to represent the radiolytic processes occurring at the nuclear fuel surface. Hydrogen peroxide (H2O2) is the dominant oxidant for spent nuclear fuel in an O2-depleted water environment. The most sensitive parameters have been identified with respect to predictions under typical conditions. As compared with the full model with about 100 reactions, it was found that only 30 to 40 of the reactions are required to determine [H2O2] to one part in 10–5 and to preserve most of the predictions for major species. This allows a systematic approach for model simplification and offers guidance in designing experiments for validation.