bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome Sequence of the Curdlan-Producing Agrobacterium sp. Strain ATCC 31749
Authors: Ruffing Anne M. , Castro-Melchor Marlene , Hu Wei-Shou , Chen Rachel R.
Published: June 2011

Agrobacterium
sp. ATCC 31749 is an industrial strain for the commercial production of curdlan, an important exopolysaccharide with food and medical applications. Here we report the genome sequence of the curdlan-producing strain ATCC 31749. Genome sequencing is the first step toward the understanding of regulation of curdlan biosynthesis.
De Novo
Sequencing and Assembly of the Whole Genome of Novosphingobium sp. Strain PP1Y
Authors: D'Argenio V. , Petrillo M. , Cantiello P. , Naso B. , Cozzuto L. , Notomista E. , Paolella G. , Di Donato A. , Salvatore F.
Published: June 2011

Novosphingobium
sp. strain PP1Y is a marine bacterium specifically adapted to use fuels as an energy source. We sequenced and assembled its entire genome using the Roche 454 genome sequencer system, which led to the identification of two plasmids and one megaplasmid, besides a 3.9-Mb circular chromosome.
Complete Genome Sequence and Updated Annotation of Desulfovibrio alaskensis G20
Authors: Hauser Loren J. , Land Miriam L. , Brown Steven D. , Larimer Frank , Keller Kimberly L. , Rapp-Giles Barbara J. , Price Morgan N. , Lin Monica , Bruce David C. , Detter John C. , Tapia Roxanne , Han Cliff S. , Goodwin Lynne A. , Cheng Jan-Fang , Pitluck Samuel , Copeland Alex , Lucas Susan , Nolan Matt , Lapidus Alla L. , Palumbo Anthony V. , Wall Judy D.
Published: June 2011

Desulfovibrio alaskensis
G20 (formerly
Desulfovibrio desulfuricans
G20) is a Gram-negative mesophilic sulfate-reducing bacterium (SRB), known to corrode ferrous metals and to reduce toxic radionuclides and metals such as uranium and chromium to sparingly soluble and less toxic forms. We present the 3.7-Mb genome sequence to provide insights into its physiology.
Draft Genome Sequence of Methylophaga aminisulfidivorans MP
T
Authors: Han Gui Hwan , Kim Wonduck , Chun Jongsik , Kim Si Wouk
Published: June 2011

Methylophaga aminisulfidivorans
MP
T
is a restricted facultatively marine methylotrophic bacterium that grows on methanol, methylated amines, dimethyl sulfide, and dimethyl sulfoxide. Here we present the high-quality draft genome sequence of
M. aminisulfidivorans
MP
T
(KCTC 12909
T
= JCM 14647
T
), consisting of a chromosome (3,092,085 bp) and a plasmid (16,875 bp).
Genome of Multidrug-Resistant Uropathogenic Escherichia coli Strain NA114 from India
Authors: Avasthi Tiruvayipati Suma , Kumar Narender , Baddam Ramani , Hussain Arif , Nandanwar Nishant , Jadhav Savita , Ahmed Niyaz
Published: June 2011

Uropathogenic
Escherichia coli
(UPEC) causes serious infections in people at risk and has a significant environmental prevalence due to contamination by human and animal excreta. In developing countries, UPEC assumes importance in certain dwellings because of poor community/personal hygiene and exposure to contaminated water or soil. We report the complete genome sequence of
E. coli
strain NA114 from India, a UPEC strain with a multidrug resistance phenotype and the capacity to produce extended-spectrum beta-lactamase. The genome sequence and comparative genomics emanating from it will be significant in under-standing the genetic makeup of diverse UPEC strains and in boosting the development of new diagnostics/vaccines.
Evaluation of Oral Antiseptic Rinsing before Sputum Collection To Reduce Contamination of Mycobacterial Cultures
Authors: Peres Renata L. , Palaci Moisés , Loureiro Rafaela B. , Dietze Reynaldo , Johnson John L. , Golub Jonathan E. , Ruffino-Netto A. , Maciel Ethel L.
Published: June 2011

To assess whether rinsing with oral antiseptics before sputum collection would reduce contamination of mycobacterial cultures, 120 patients with suspected tuberculosis were randomly assigned to rinse with chlorhexidine or cetylpyridinium mouthwash before collection. The culture contamination rate was significantly lower after rinsing with chlorhexidine before collection, especially for cultures grown in MGIT medium.
Emerging Severe and Fatal Infections Due to Klebsiella pneumoniae in Two University Hospitals in France
Authors: Decré Dominique , Verdet Charlotte , Emirian Aurélie , Le Gourrierec Thibault , Petit Jean-Claude , Offenstadt Georges , Maury Eric , Brisse Sylvain , Arlet Guillaume
Published: June 2011

Severe infections caused by hypermucoviscous
Klebsiella
pneumoniae
have been reported in Southeast Asian countries over the past several decades. This report shows their emergence in France, with 12 cases observed during a 2-year period in two university hospitals. Two clones (sequence type 86 [ST86] and ST380) of serotype K2 caused five rapidly fatal bacteremia cases, three of which were associated with pneumonia, whereas seven liver abscess cases were caused by K1 strains of ST23.
An approach to preparation of trans-DHQs via ring-opening of meso-N-sulfonylaziridines
Authors: Nolsøe Jens , Riegert David , Müller Paul , Tanner David
Published: June 2011

As an approach to the enantioselective synthesis of trans-decahydroquinolines (DHQs), desymmetrization of meso-aziridine (5) with various carbon nucleophiles under catalytic conditions was investigated. By applying TMSCN in the presence of YbCl3 and chiral non-racemic ligands, nitrile 13 was obtained with an ee up to 40%. Nitrile 13 was a key intermediate in a novel route to trans-DHQs.
Hamstring strain injuries: are we heading in the right direction?
Authors: Mendiguchia Jurdan , Alentorn-Geli Eduard , Brughelli Matt
Published: June 2011

Acute hamstring injuries are the most prevalent muscle injuries reported in sport. Despite a thorough and concentrated effort to prevent and rehabilitate hamstring injuries, injury occurrence and re-injury rates have not improved over the last three decades. This failure is most likely due to the following: (1) a lack of studies with high level of evidence into the identification and prevention of hamstring injuries and (2) a reductionist approach of the current literature. The objectives of this article are to review and critique the current literature regarding isolated risk factors, and introduce a new concept for a more comprehensive scientific understanding of how multiple risk factors contribute to hamstring strain injury. The authors hope that this new conceptual model can serve as a foundation for future evidence-based research and aid in the development of new prevention methods to decrease the high incidence of this type of injury.
Abortion decisions as inclusion and exclusion criteria in research involving pregnant women and fetuses
Authors: Strong Carson
Published: June 2011

From the perspective of investigators conducting research involving pregnant women and fetuses, a woman's decision about whether to have an abortion can sometimes be relevant to the suitability of the woman and fetus as research subjects. However, prominent ethicists disagree over whether it is permissible for a woman's decision about abortion to be an inclusion or exclusion criterion for participation in research. A widely held view is that fetuses to be aborted and fetuses to be carried to term should be treated equally as research subjects. Some hold that this principle implies that a woman's decision about whether to have an abortion should not be an inclusion or exclusion criterion. This paper identifies types of research in which investigators might want to have inclusion or exclusion criteria based on decisions about abortion. It examines the arguments for and against having the woman's decision about abortion included in such criteria. It is argued that there are types of research in which such criteria are ethically permissible.
Computed tomographic perfusion imaging of non-hemorrhagic cerebral hyperperfusion syndrome and reversal following medical treatment after carotid artery angioplasty and stenting
Authors: Vasquez Raul A , Waters Michael F , Skowlund Christopher J , Mocco J , Hoh Brian L
Published: June 2011

Objective and importance

Cerebral hyperperfusion syndrome (CHS) is an infrequent syndrome observed in carotid endarterectomy and carotid angioplasty and stenting (CAS). The case history is presented of a patient with CT perfusion imaging of non-hemorrhagic CHS and reversal following medical treatment after CAS.

Clinical presentation

A right-handed Caucasian man in his late 70s presented with sudden onset right upper extremity plegia and anesthesia and right facial parasthesias with complete resolution within 24 h. CT angiography (CTA) revealed 75% left cervical carotid artery stenosis. The patient underwent uneventful left CAS. Six hours after the procedure he developed verbal perseveration and right upper extremity paresis. CT perfusion imaging showed increased mean transient time in the left parieto-occipital lobe without changes in cerebral blood flow or cerebral blood volume. A clinical diagnosis of CHS was suspected. Several hours after lowering the blood pressure his symptoms improved. A follow-up CTA with CT perfusion was performed which showed complete resolution of the previously observed changes in mean transient time. The patient was discharged home without neurological sequelae.

Conclusion

This is the first report to our knowledge of CT perfusion imaging for CHS with post-symptomatic imaging following clinical resolution. Prompt CHS evaluation may include CT perfusion imaging to assist diagnostic accuracy. Rigorous blood pressure control remains the mainstay of treatment.
Infectious mid basilar artery aneurysm fromPseudomonasmeningitis: Figure 1
Authors: Yu Wengui , Rickert Kim , Flores Bruno , Samson Duke
Published: June 2011

Pseudomonas aeruginosameningitis is an uncommon complication of neurosurgical procedures or head trauma. Here, a case of infectious mid basilar artery aneurysm fromPseudomonasmeningitis, and its angiographic remission from timely antibiotic therapy, is reported.
Anomalous course of the intracranial internal carotid artery into the orbit: case report
Authors: Blackburn Spiros L , Dannenbaum Mark , Schuette Albert J , Dion Jacques
Published: June 2011

In this report, a case of anomalous internal carotid artery looping into the orbital apex is presented. The patient was a 41-year-old man with sudden onset headache, suggestive of aneurysmal subarachnoid hemorrhage (SAH). Imaging with CT demonstrated a perimesencephalic distribution of blood. Cerebral angiography confirmed non-aneurysmal, perimesencephalic SAH, but incidentally noted an anomalous left internal carotid artery with a course into the orbital cone. This is the only known example of this anatomic variation. Potential embryological explanations are discussed.
Over-the-catheter retrieval of a retained microcatheter following Onyx embolization: a technical report
Authors: Newman C Benjamin , Park Min S , Kerber Charles W , Levy Michael L , Barr John D , Pakbaz R Sean
Published: June 2011

Background

Brain arteriovenous malformations are vascular lesions that are increasingly being treated with endovascular embolization. A potential complication with endovascular embolization is microcatheter entrapment within the embolic material. In the present report, a novel technique for the retrieval of microcatheters retained during Onyx embolization of intracranial lesions is described.

Clinical presentation

Two patients (one boy and one girl, aged 13 and 15 years, respectively) with arteriovenous malformations (one unruptured, one ruptured; Spetzler–Martin grades 4 and 3) presented for embolization.

Intervention

During Onyx 18 embolization of the arteriovenous malformations, Echelon-10 microcatheters became entrapped into the arterial feeders by casts of the Onyx. Initial attempts to remove the microcatheters by traction were unsuccessful. The hubs of the microcatheters were transected and Concentric Medical Outreach distal access catheters were then advanced over the microcatheters and positioned at the proximal aspects of the microcatheter-Onyx plugs. Using the Outreach catheters for countertraction, the Echelon-10 microcatheters were then successfully released from the Onyx plugs under fluoroscopic visualization without significant distortion of the arteries. There were no complications related to the microcatheter extractions.

Conclusions

A novel technique, which may be useful in the removal of retained microcatheters during Onyx embolization of Brain arteriovenous malformations, is presented.
Economic and public health impact of 2007–2010 tobacco tax increases in Ukraine
Authors: Ross Hana , Stoklosa Michal , Krasovsky Konstantin
Published: June 2011

Objective

To evaluate the impact of the dynamic 2007–2010 tobacco tax policy in Ukraine on cigarette prices, cigarette consumption, tobacco tax revenue and the tobacco industry's price strategy.

Methods

Using data on cigarette sales, cigarette prices, income and tobacco control policies, price elasticities of cigarette demand in Ukraine were estimated using two methods. Annual data were used to generate point price elasticity estimates, while monthly data were used in a two-step Engle–Granger procedure.

Results

The point price elasticity estimate is data sensitive and ranges from −0.11 to −0.62, centring around −0.32. The regression model estimates a long-run price elasticity of −0.28. Cigarette consumption fell by 13% in 2009 and 15% in 2010 while the tax revenue increased by US$700 million and by US$500 million in 2009 and 2010, respectively, compared to the previous year. Tax increases have changed the tobacco industry's price strategy from one of shielding consumers from the impact of smaller tax hikes in 2007–2008, to one of increasing industry net-of-tax prices, after recent, larger tax increases.

Conclusions

The higher real tobacco excise taxes of 2009 and 2010 have significantly reduced tobacco consumption in Ukraine, resulting in encouraging public health and fiscal gains. It will be important for cigarette prices/taxes to keep pace with inflation and income growth for this impact to be sustained.
Surveillance programme for important equine infectious respiratory pathogens in the USA
Authors: Pusterla N. , Kass P. H. , Mapes S. , Johnson C. , Barnett D. C. , Vaala W. , Gutierrez C. , McDaniel R. , Whitehead B. , Manning J.
Published: June 2011

The prevalence and epidemiology of important viral (equine influenza virus [EIV], equine herpesvirus type 1 [EHV‐1] and EHV‐4) and bacterial (Streptococcus equisubspeciesequi) respiratory pathogens shed by horses presented to equine veterinarians with upper respiratory tract signs and/or acute febrile neurological disease were studied. Veterinarians from throughout the USA were enrolled in a surveillance programme and were asked to collect blood and nasal secretions from equine cases with acute infectious upper respiratory tract disease and/or acute onset of neurological disease. A questionnaire was used to collect information pertaining to each case and its clinical signs. Samples were tested by real‐time PCR for the presence of EHV‐1, EHV‐4, EIV andS equisubspeciesequi. A total of 761 horses, mules and donkeys were enrolled in the surveillance programme over a 24‐month study period. In total, 201 (26.4 per cent) index cases tested PCR‐positive for one or more of the four pathogens. The highest detection rate was for EHV‐4 (82 cases), followed by EIV (60 cases),S equisubspeciesequi(49 cases) and EHV‐1 (23 cases). There were 15 horses with double infections and one horse with a triple infection. The detection rate by PCR for the different pathogens varied with season and with the age, breed, sex and use of the animal.
Infection with Brucella ceti and high levels of polychlorinated biphenyls in bottlenose dolphins (Tursiops truncatus) stranded in south‐west England
Authors: Davison N. J. , Perrett L. L. , Law R. J. , Dawson C. E. , Stubberfield E. J. , Monies R. J. , Deaville R. , Jepson P. D.
Published: June 2011

Eight bottlenose dolphins (Tursiops truncatus) that stranded in Cornwall, south‐west England, between June 2004 and December 2007 were examined using standardised postmortem examination and bacteriological methods. Evidence of Brucella species infection was found in four of these dolphins on culture. In addition, of the eight dolphins, four were positive and two were weakly positive for antibodies to Brucella species on serological analyses of pericardial and other fluids using a competitive ELISA and two indirect ELISAs. High or very high levels of the sum of 25 individual chlorobiphenyl congeners (∑25CBs) were also determined in blubber samples from two of the dolphins (45.5 and 446.6 mg/kg lipid weight).
NON-STATISTICAL FLUCTUATIONS OF PIONS FOR RING- AND JET-LIKE EVENTS AT CERN SPS ENERGY — AN IN-DEPTH ANALYSIS WITH FACTORIAL CORRELATOR
Authors: HALDAR PRABIR KUMAR , MANNA SANJIB KUMAR , SAHA PROSENJIT , GHOSH DIPAK
Published: June 2011

This study reveals the analysis of ring-like and jet-like events in terms of factorial correlations of 16 O – Ag/Br interactions at 60A GeV . The investigation revealed that the correlated moments are found to increase with decreasing bin–bin separation D and follows a power-law which suggests the presence of an intermittent nature of self-similar dynamical fluctuations pattern for ring-like and jet-like events. From the analysis we find that for jet-like events the strength of non-statistical fluctuation is greater than the ring-like and total event set. Jet-like events follow the bin size independence according to α model of intermittency as like total events, whereas ring-like events are not consistent with the prediction of α model of intermittency.
UV-LIGHT-ASSISTED OXIDATIVE sp3 HYBRIDIZATION OF GRAPHENE
Authors: GÜNEŞ FETHULLAH , HAN GANG HEE , SHIN HYEON-JIN , LEE SI YOUNG , JIN MEIHUA , DUONG DINH LOC , CHAE SEUNG JIN , KIM EUN SUNG , YAO FEI , BENAYAD ANASS , CHOI JAE-YOUNG , LEE YOUNG HEE
Published: June 2011

We report the transformation of electronic structures of sp2 graphene to sp3 graphene by UV-light-assisted oxidation. Two distinctive oxidation mechanisms were observed during this metal–insulator transition: (i) At low-oxidation regime, p-doping behavior by oxygen species extracting electrons from graphene and (ii) at high-oxidation regime, n-doping behavior by electron-hopping via strongly localized oxide states. We also found that the dominant oxygen-related functional group by UV-light-assisted oxidation was an epoxide group rather than hydroxyl group, which differed from conventional graphite oxide.
Deficiency of Prdx6 in lens epithelial cells induces ER stress response-mediated impaired homeostasis and apoptosis
Authors: Fatma Nigar , Singh Prerna , Chhunchha Bhavana , Kubo Eri , Shinohara T. , Bhargavan Biju , Singh Dhirendra P.
Published: June 2011

The multifunctional cytoprotective protein peroxiredoxin 6 (Prdx6) maintains cellular homeostasis and membrane integrity by regulating expression of intracellular reactive oxygen species (ROS) and phospholipid turnover. Using cells derived from targeted inactivation of Prdx6 gene or its depletion by RNA interference or aging, we showed that Prdx6 deficiency in cells evoked unfolded protein response (UPR), evidenced by increased expression or activation of proapoptotic factors, CHOP, ATF4, PERK, IRE-α and eIF2-α and by increased caspases 3 and 12 processing. Those cells displayed enhanced and sustained expression of endoplasmic reticulum (ER) stress-related chaperon proteins, Bip/glucose-regulated protein 78, calnexin, and calreticulin. Under cellular stress induced by hypoxia (1% O2 or CoCl2 treatment) or tunicamycin, Prdx6-deficient cells exhibited aberrant activation of ER stress-responsive genes/protein with higher expression of ROS, and died with apoptosis. Wild-type cells exposed to tunicamycin or hypoxia remained relatively insensitive with lower expression of ROS and ER-responsive genes than did Prdx6-deficient cells, but upregulation of ER stress responsive proteins or chaperones mimicked the UPR response of Prdx6-deficient or aging cells. Expression of Prdx6 blocked ER stress-induced deleterious signaling by optimizing physiologically aberrant expression of ER stress responsive genes/proteins in Prdx6-deficient cells or cells facing stressors, and rescued the cells from apoptosis. These findings demonstrate that impaired homeostasis and progression of pathogenesis in Prdx6-deficient lens epithelial cells or in aging cells should be blocked by a supply of Prdx6. The results provide a new molecular basis for understanding the etiology of several age-associated degenerative disorders, and potentially for developing antioxidant Prdx6-based therapeutics.
The rate of O2loss from mesenteric arterioles is not unusually high
Authors: Golub Aleksander S. , Song Bjorn K. , Pittman Roland N.
Published: June 2011

The O2disappearance curve (ODC) recorded in an arteriole after the rapid arrest of blood flow reflects the complex interaction among the dissociation of O2from hemoglobin, O2diffusivity, and rate of respiration in the vascular wall and surrounding tissue. In this study, the analysis of experimental ODCs allowed the estimation of parameters of O2transport and O2consumption in the microcirculation of the mesentery. We collected ODCs from rapidly arrested blood inside rat mesenteric arterioles using scanning phosphorescence quenching microscopy (PQM). The technique was used to prevent the artifact of accumulated O2photoconsumption in stationary media. The observed ODC signatures were close to linear, in contrast to the reported exponential decline of intra-arteriolar Po2. The rate of Po2decrease was 0.43 mmHg/s in 20-μm-diameter arterioles. The duration of the ODC was 290 s, much longer than the 12.8 s reported by other investigators. The arterioles associated with lymphatic microvessels had a higher O2disappearance rate of 0.73 mmHg/s. The O2flux from arterioles, calculated from the average O2disappearance rate, was 0.21 nl O2·cm−2·s−1, two orders of magnitude lower than reported in the literature. The physical upper limit of the O2consumption rate by the arteriolar wall, calculated from the condition that all O2is consumed by the wall, was 452 nl O2·cm−3·s−1. From consideration of the microvascular tissue volume fraction in the rat mesentery of 6%, the estimated respiration rate of the vessel wall was ∼30 nl O2·cm−3·s−1. This result was three orders of magnitude lower than the respiration rate in rat mesenteric arterioles reported by other investigators. Our results demonstrate that O2loss from mesenteric arterioles is small and that the O2consumption by the arteriolar wall is not unusually large.
Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction
Authors: de Beer Vincent J. , Taverne Yannick J. , Kuster Diederik W. , Najafi Aref , Duncker Dirk J. , Merkus Daphne
Published: June 2011

Myocardial infarction (MI) is associated with endothelial dysfunction resulting in an imbalance in endothelium-derived vasodilators and vasoconstrictors. We have previously shown that despite increased endothelin (ET) plasma levels, the coronary vasoconstrictor effect of endogenous ET is abolished after MI. In normal swine, nitric oxide (NO) and prostanoids modulate the vasoconstrictor effect of ET. In light of the interaction among NO, prostanoids, and ET combined with endothelial dysfunction present after MI, we investigated this interaction in control of coronary vasomotor tone in the remote noninfarcted myocardium after MI. Studies were performed in chronically instrumented swine (18 normal swine; 13 swine with MI) at rest and during treadmill exercise. Furthermore, endothelial nitric oxide synthase (eNOS) and cyclooxygenase protein levels were measured in the anterior (noninfarcted) wall of six normal and six swine with MI. eNOS inhibition with Nω-nitro-l-arginine (l-NNA) and cyclooxygenase inhibition with indomethacin each resulted in coronary vasoconstriction at rest and during exercise, as evidenced by a decrease in coronary venous oxygen levels. The effect of l-NNA was slightly decreased in swine with MI, although eNOS expression was not altered. Conversely, in accordance with the unaltered expression of cyclooxygenase-1 after MI, the effect of indomethacin was similar in normal and MI swine. l-NNA enhanced the vasodilator effect of the ETA/Breceptor blocker tezosentan but exclusively during exercise in both normal and MI swine. Interestingly, this effect of l-NNA was blunted in MI compared with normal swine. In contrast, whereas indomethacin increased the vasodilator effect of tezosentan only during exercise in normal swine, indomethacin unmasked a coronary vasodilator effect of tezosentan in MI swine both at rest and during exercise. In conclusion, the present study shows that endothelial control of the coronary vasculature is altered in post-MI remodeled myocardium. Thus the overall vasodilator influences of NO as well as its inhibition of the vasoconstrictor influence of ET on the coronary resistance vessels were reduced after MI. In contrast, while the overall prostanoid vasodilator influence was maintained, its inhibition of ET vasoconstrictor influences was enhanced in post-MI remote myocardium.
Insulin and glucagon share the same mechanism of neuroprotection in diabetic rats: role of glutamate
Authors: Fanne Rami Abu , Nassar Taher , Heyman Samuel N. , Hijazi Nuha , Higazi Abd Al-Roof
Published: June 2011

In patients with acute ischemic stroke, diabetes and hyperglycemia are associated with increased infarct size, more profound neurologic deficits and higher mortality. Notwithstanding extensive clinical and experimental data, treatment of stroke-associated hyperglycemia with insulin is controversial. In addition to hyperglycemia, diabetes and even early prediabetic insulin resistance are associated with increased levels of amino acids, including the neurotoxic glutamate, in the circulation. The pleiotropic metabolic effects of insulin include a reduction in the concentration of amino acids in the circulation. In this article, we show that in diabetic rats exposed to transient middle cerebral artery occlusion, a decrease of plasma glutamate by insulin or glucagon reduces CSF glutamate, improves brain histology, and preserves neurologic function. The neuroprotective effect of insulin and glucagon was similar, notwithstanding their opposite effects on blood glucose. The therapeutic window of both hormones overlapped with the short duration (∼30 min) of elevated brain glutamate following brain trauma in rodents. Similar neuroprotective effects were found after administration of the glutamate scavenger oxaloacetate, which does not affect glucose metabolism. These data indicate that insulin and glucagon exert a neuroprotective effect within a very brief therapeutic window that correlates with their capacity to reduce glutamate, rather than by modifying glucose levels.
Cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in conscious rats
Authors: Lujan Heidi L. , Krishnan Sandhya , DiCarlo Stephen E.
Published: June 2011

The response to myocardial ischemia is complex and involves the cardio-cardiac sympathetic reflex. Specifically, cardiac spinal (sympathetic) afferents are excited by ischemic metabolites and elicit an excitatory sympathetic reflex, which plays a major role in the genesis of ventricular arrhythmias. For example, brief myocardial ischemia leads to ATP release, which activates cardiac spinal afferents through stimulation of P2 receptors. Clinical work with patients and preclinical work with animals document that disruption of this reflex protects against ischemia-induced ventricular arrhythmias. However, the role of afferent signals in the initiation of sustained ventricular tachycardia has not been investigated. Therefore, we tested the hypothesis that cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in adult (12–15 wk of age), conscious, male Sprague-Dawley rats. To test this hypothesis, the susceptibility to ventricular tachyarrhythmias produced by occlusion of the left main coronary artery was determined in two groups of conscious rats: 1) deafferentation (bilateral excision of the T1-T5 dorsal root ganglia) and 2) control (sham deafferentation). The ventricular arrhythmia threshold (VAT) was defined as the time from coronary occlusion to sustained ventricular tachycardia resulting in a reduction in arterial pressure. Results document a significantly higher VAT in the deafferentation group (7.0 ± 0.7 min) relative to control (4.3 ± 0.3 min) rats. The decreased susceptibility to tachyarrhythmias with deafferentation was associated with a reduced cardiac metabolic demand (lower rate-pressure product and ST segment elevation) during ischemia.
Systemic oxytocin induces a prolactin secretory rhythm via the pelvic nerve in ovariectomized rats
Authors: Helena Cleyde V. , Cristancho-Gordo Ruth , Gonzalez-Iglesias Arturo E. , Tabak Joël , Bertram Richard , Freeman Marc E.
Published: June 2011

We have shown previously that an intravenous injection of oxytocin (OT) in ovariectomized (OVX) rats initiates a circadian rhythm of prolactin (PRL) secretion similar to that observed after cervical stimulation (CS). In this study, we investigated the pathway through which OT triggers the PRL rhythm. We first tested whether an intracerebroventricular injection of OT could trigger the PRL secretory rhythm. As it did not, we injected OT intravenously while an OT receptor antagonist was infused intravenously. This antagonist completely abolished the PRL surges, suggesting that a peripheral target of OT is necessary for triggering the PRL rhythm. We hypothesized that OT may induce PRL release, which would be transported into the brain and trigger the rhythm. In agreement with this, OT injection increased circulating PRL by 5 min. To test whether this acute increase in PRL release would induce the PRL rhythm, we compared the effect of intravenously administered thyrotropin-releasing hormone (TRH) and OT. Although TRH injection also increased PRL to a comparable level after 5 min, only OT-injected animals expressed the PRL secretory rhythm. Motivated by prior findings that bilateral resection of the pelvic nerve blocks CS-induced pseudopregnancy and OT-induced facilitation of lordosis, we then hypothesized that the OT signal may be transmitted through the pelvic nerve. In fact, OT injection failed to induce a PRL secretory rhythm in pelvic-neurectomized animals, suggesting that the integrity of the pelvic nerve is necessary for the systemic OT induction of the PRL secretory rhythm in OVX rats.
Identification of a neuronal gene expression signature: role of cell cycle arrest in murine neuronal differentiation in vitro
Authors: Felfly Hady , Xue Jin , Zambon Alexander C. , Muotri Alysson , Zhou Dan , Haddad Gabriel G.
Published: June 2011

Stem cells are a potential key strategy for treating neurodegenerative diseases in which the generation of new neurons is critical. A better understanding of the characteristics and molecular properties of neural stem cells (NSCs) and differentiated neurons can help with assessing neuronal maturity and, possibly, in devising better therapeutic strategies. We have performed an in-depth gene expression profiling study of murine NSCs and primary neurons derived from embryonic mouse brains. Microarray analysis revealed a neuron-specific gene expression signature that distinguishes primary neurons from NSCs, with elevated levels of transcripts involved in neuronal functions, such as neurite development and axon guidance in primary neurons and decreased levels of multiple cytokine transcripts. Among the differentially expressed genes, we found a statistically significant enrichment of genes in the ephrin, neurotrophin, CDK5, and actin pathways, which control multiple neuronal-specific functions. We then artificially blocked the cell cycle of NSCs with mitomycin C (MMC) and examined cellular morphology and gene expression signatures. Although these MMC-treated NSCs displayed a neuronal morphology and expressed some neuronal differentiation marker genes, their gene expression patterns were very different from primary neurons. We conclude that 1) fully differentiated mouse primary neurons display a specific neuronal gene expression signature; 2) cell cycle block at the S phase in NSCs with MMC does not induce the formation of fully differentiated neurons; 3) cytokines change their expression pattern during differentiation of NSCs into neurons; and 4) signaling pathways of ephrin, neurotrophin, CDK5, and actin, related to major neuronal features, are dynamically enriched in genes showing changes in expression level.
Biology's response to dieting: the impetus for weight regain
Authors: MacLean Paul S. , Bergouignan Audrey , Cornier Marc-Andre , Jackman Matthew R.
Published: June 2011

Dieting is the most common approach to losing weight for the majority of obese and overweight individuals. Restricting intake leads to weight loss in the short term, but, by itself, dieting has a relatively poor success rate for long-term weight reduction. Most obese people eventually regain the weight they have worked so hard to lose. Weight regain has emerged as one of the most significant obstacles for obesity therapeutics, undoubtedly perpetuating the epidemic of excess weight that now affects more than 60% of U.S. adults. In this review, we summarize the evidence of biology's role in the problem of weight regain. Biology's impact is first placed in context with other pressures known to affect body weight. Then, the biological adaptations to an energy-restricted, low-fat diet that are known to occur in the overweight and obese are reviewed, and an integrative picture of energy homeostasis after long-term weight reduction and during weight regain is presented. Finally, a novel model is proposed to explain the persistence of the “energy depletion” signal during the dynamic metabolic state of weight regain, when traditional adiposity signals no longer reflect stored energy in the periphery. The preponderance of evidence would suggest that the biological response to weight loss involves comprehensive, persistent, and redundant adaptations in energy homeostasis and that these adaptations underlie the high recidivism rate in obesity therapeutics. To be successful in the long term, our strategies for preventing weight regain may need to be just as comprehensive, persistent, and redundant, as the biological adaptations they are attempting to counter.
Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice
Authors: Andrés-Hernando Ana , Altmann Christopher , Ahuja Nilesh , Lanaspa Miguel A. , Nemenoff Raphael , He Zhibin , Ishimoto Takuji , Simpson Pete A. , Weiser-Evans Mary C. , Bacalja Jasna , Faubel Sarah
Published: June 2011

Patients with acute kidney injury (AKI) have increased serum proinflammatory cytokines and an increased occurrence of respiratory complications. The aim of the present study was to examine the effect of renal and extrarenal cytokine production on AKI-mediated lung injury in mice. C57Bl/6 mice underwent sham surgery, splenectomy, ischemic AKI, or ischemic AKI with splenectomy and kidney, spleen, and liver cytokine mRNA, serum cytokines, and lung injury were examined. The proinflammatory cytokines IL-6, CXCL1, IL-1β, and TNF-α were increased in the kidney, spleen, and liver within 6 h of ischemic AKI. Since splenic proinflammatory cytokines were increased, we hypothesized that splenectomy would protect against AKI-mediated lung injury. On the contrary, splenectomy with AKI resulted in increased serum IL-6 and worse lung injury as judged by increased lung capillary leak, higher lung myeloperoxidase activity, and higher lung CXCL1 vs. AKI alone. Splenectomy itself was not associated with increased serum IL-6 or lung injury vs. sham. To investigate the mechanism of the increased proinflammatory response, splenic production of the anti-inflammatory cytokine IL-10 was determined and was markedly upregulated. To confirm that splenic IL-10 downregulates the proinflammatory response of AKI, IL-10 was administered to splenectomized mice with AKI, which reduced serum IL-6 and improved lung injury. Our data demonstrate that AKI in the absence of a counter anti-inflammatory response by splenic IL-10 production results in an exuberant proinflammatory response and lung injury.
Antecedent acute kidney injury worsens subsequent endotoxin-induced lung inflammation in a two-hit mouse model
Authors: Basu Rajit K. , Donaworth Emily , Wheeler Derek S. , Devarajan Prasad , Wong Hector R.
Published: June 2011

Acute kidney injury (AKI) contributes greatly to morbidity and mortality in critically ill adults and children. Patients with AKI who subsequently develop lung injury are known to suffer worse outcomes compared with patients with lung injury alone. Isolated experimental kidney ischemia alters distal lung water balance and capillary permeability, but the effects of such an aberration on subsequent lung injury are unknown. We present a clinically relevant two-hit murine model wherein a proximal AKI through bilateral renal ischemia (30 min) is followed by a subsequent acute lung injury (ALI) via intratracheal LPS endotoxin (50 μg at 24 h after surgery). Mice demonstrated AKI by elevation of serum creatinine and renal histopathological damage. Mice with ALI and preexisting AKI had increased lung neutrophilia in bronchoalveolar lavage fluid and by myeloperoxidase activity over Sham-ALI mice. Additionally, lung histopathological damage was greater in ALI mice with preexisting AKI than Sham-ALI mice. There was uniform elevation of monocyte chemoattractant protein-1 in kidney, serum, and lung tissue in animals with both AKI and ALI over those with either injury alone. The additive lung inflammation after ALI with antecedent AKI was abrogated in MCP-1-deficient mice. Taken together, our two-hit model demonstrates that kidney injury may prime the lung for a heightened inflammatory response to subsequent injury and MCP-1 may be involved in this model of kidney-lung cross talk. The model holds clinical relevance for patients at risk of lung injury after ischemic injury to the kidney.
Cholinergic microvillous cells in the mouse main olfactory epithelium and effect of acetylcholine on olfactory sensory neurons and supporting cells
Authors: Ogura Tatsuya , Szebenyi Steven A. , Krosnowski Kurt , Sathyanesan Aaron , Jackson Jacqueline , Lin Weihong
Published: June 2011

The mammalian olfactory epithelium is made up of ciliated olfactory sensory neurons (OSNs), supporting cells, basal cells, and microvillous cells. Previously, we reported that a population of nonneuronal microvillous cells expresses transient receptor potential channel M5 (TRPM5). Using transgenic mice and immunocytochemical labeling, we identify that these cells are cholinergic, expressing the signature markers of choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter. This result suggests that acetylcholine (ACh) can be synthesized and released locally to modulate activities of neighboring supporting cells and OSNs. In Ca2+ imaging experiments, ACh induced increases in intracellular Ca2+ levels in 78% of isolated supporting cells tested in a concentration-dependent manner. Atropine, a muscarinic ACh receptor (mAChR) antagonist suppressed the ACh responses. In contrast, ACh did not induce or potentiate Ca2+ increases in OSNs. Instead ACh suppressed the Ca2+ increases induced by the adenylyl cyclase activator forskolin in some OSNs. Supporting these results, we found differential expression of mAChR subtypes in supporting cells and OSNs using subtype-specific antibodies against M1 through M5 mAChRs. Furthermore, we found that various chemicals, bacterial lysate, and cold saline induced Ca2+ increases in TRPM5/ChAT-expressing microvillous cells. Taken together, our data suggest that TRPM5/ChAT-expressing microvillous cells react to certain chemical or thermal stimuli and release ACh to modulate activities of neighboring supporting cells and OSNs via mAChRs. Our studies reveal an intrinsic and potentially potent mechanism linking external stimulation to cholinergic modulation of activities in the olfactory epithelium.
Differences in intersaccadic adaptation transfer between inward and outward adaptation
Authors: Schnier Fabian , Lappe Markus
Published: June 2011

Saccadic adaptation is a mechanism to increase or decrease the amplitude gain of subsequent saccades, if a saccade is not on target. Recent research has shown that the mechanism of gain increasing, or outward adaptation, and the mechanism of gain decreasing, or inward adaptation, rely on partly different processes. We investigate how outward and inward adaptation of reactive saccades transfer to other types of saccades, namely scanning, overlap, memory-guided, and gap saccades. Previous research has shown that inward adaptation of reactive saccades transfers only partially to these other saccade types, suggesting differences in the control mechanisms between these saccade categories. We show that outward adaptation transfers stronger to scanning and overlap saccades than inward adaptation, and that the strength of transfer depends on the duration for which the saccade target is visible before saccade onset. Furthermore, we show that this transfer is mainly driven by an increase in saccade duration, which is apparent for all saccade categories. Inward adaptation, in contrast, is accompanied by a decrease in duration and in peak velocity, but only the peak velocity decrease transfers from reactive saccades to other saccade categories, i.e., saccadic duration remains constant or even increases for test saccades of the other categories. Our results, therefore, show that duration and peak velocity are independent parameters of saccadic adaptation and that they are differently involved in the transfer of adaptation between saccade categories. Furthermore, our results add evidence that inward and outward adaptation are different processes.
Order of operations for decoding superior colliculus activity for saccade generation
Authors: Katnani Husam A. , Gandhi Neeraj J.
Published: June 2011

To help understand the order of events that occurs when generating saccades, we simulated and tested two commonly stated decoding models that are believed to occur in the oculomotor system: vector averaging (VA) and center-of-mass. To generate accurate saccades, each model incorporates two required criteria: 1) a decoding mechanism that deciphers a population response of the superior colliculus (SC) and 2) an exponential transformation that converts the saccade vector into visual coordinates. The order of these two criteria is used differently within each model, yet the significance of the sequence has not been quantified. To distinguish between each decoding sequence and hence, to determine the order of events necessary to generate accurate saccades, we simulated the two models. Distinguishable predictions were obtained when two simultaneous motor commands are processed by each model. Experimental tests of the models were performed by observing the distribution of endpoints of saccades evoked by weighted, simultaneous microstimulation of two SC sites. The data were consistent with the predictions of the VA model, in which exponential transformation precedes the decoding computation.
Keap1 Mutations and Nrf2 Pathway Activation in Epithelial Ovarian Cancer
Authors: Konstantinopoulos Panagiotis A. , Spentzos Dimitrios , Fountzilas Elena , Francoeur Nancy , Sanisetty Srisowmya , Grammatikos Alexandros P. , Hecht Jonathan L. , Cannistra Stephen A.
Published: June 2011

Resistance to platinum-based chemotherapy develops in the majority of patients with epithelial ovarian cancer (EOC). Platinum compounds form electrophilic intermediates that mediate DNA cross-linking and induce double-strand DNA breaks. Because the cellular response to electrophilic xenobiotics is partly mediated by Keap1–Nrf2 pathway, we evaluated the presence of Kelch-like ECH–associated protein 1 (Keap1) mutations and NF-E2–related factor 2 (Nrf2) pathway activation in EOC and correlated these with platinum resistance and clinical outcome. Nrf2 immunohistochemistry revealed nuclear localization (a surrogate of pathway activation) in over half of EOC patient specimens examined, with more common occurrence in the clear cell EOC subtype. Quantitative real-time PCR revealed that Nrf2 target genes were upregulated in tumors with nuclear positivity for Nrf2. Microarray analysis also showed upregulation of Nrf2 target genes in clear cell EOCs compared with other EOC subtypes. In addition, Keap1 sequence analysis revealed genetic mutations in 29% of clear cell samples and 8% of nonclear cell tumors. RNAi-mediated knockdown of Keap1 was associated with Nrf2 pathway activation and resistance to carboplatin in vitro. Importantly, patients with evidence of Nrf2 pathway activation had fewer complete clinical responses to platinum-based therapy, were enriched for platinum resistance, and had shorter median overall survival compared with those who did not show evidence of Nrf2 pathway activation. Our findings identify Keap1 mutations in EOC and they suggest a previously unrecognized role for the Keap1–Nrf2 pathway in mediating chemotherapeutic responses in this disease. Cancer Res; 71(15); 5081–9. ©2011 AACR.
Role of Smac in Determining the Chemotherapeutic Response of Esophageal Squamous Cell Carcinoma
Authors: Xu Yang , Zhou Lanping , Huang Jing , Liu Fang , Yu Jian , Zhan Qimin , Zhang Lin , Zhao Xiaohang
Published: June 2011

Purpose: Second mitochondria-derived activator of caspase (Smac) regulates chemotherapy-induced apoptosis. Smac mimetics have been tested in clinical trials as chemosensitizers. We determined the role of Smac in modulating the chemosensitivity of esophageal squamous cell carcinoma (ESCC).

Experimental Design: Smac expression was evaluated in tissues from ESCC patients with differential chemotherapeutic responses. The effects of Smac knockdown and Smac mimetics on the chemosensitivity of ESCC cells and the molecular mechanisms by which Smac and Smac mimetics modulate chemosensitivity were determined. The therapeutic responses of ESCC cells with different Smac statuses were compared using xenograft models.

Results: We found that Smac was significantly downregulated in most ESCC samples (36.8%, 25/68, P = 0.001), and Smac expression differed significantly (P < 0.05) between chemosensitive and chemoresistant tumors. The associations of tested factors and their responses were examined using logistic regression analysis. In ESCC cells treated with cisplatin, a common chemotherapeutic drug, Smac and cytochrome c were released from mitochondria, and caspase-3 and caspase-9 were activated. Knockdown of Smac abrogated cisplatin-induced apoptosis, mitochondrial dysfunction, cytochrome c release, and caspase activation. Smac deficiency also reduced the effect of cisplatin on long-term cell viability, and led to cisplatin resistance in xenograft tumors in vivo. LBW242, a small molecule Smac mimetic, enhanced cisplatin-induced apoptosis and caspase activation and restored cisplatin sensitivity in Smac-deficient cells.

Conclusion: Our data suggested that downregulation of Smac may be a chemoresistance mechanism in ESCC. Combinations of Smac mimetics with chemotherapeutic agents may have therapeutic benefits for the treatment of esophageal cancer. Clin Cancer Res; 17(16); 5412–22. ©2011 AACR.