bluuebunny/crossref_metadata_2025 huggingface dataset:
Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury
Authors: Lee Sang-Min , McLaughlin Joseph N. , Frederick Daniel R. , Zhu Lin , Thambiayya Kalidasan , Wasserloos Karla J. , Kaminski Iris , Pearce Linda L. , Peterson Jim , Li Jin , Latoche Joseph D. , Peck Palmer Octavia M. , Stolz Donna Beer , Fattman Cheryl L. , Alcorn John F. , Oury Tim D. , Angus Derek C. , Pitt Bruce R. , Kaynar A. Murat
Published: December 2012

Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury.
Distinct patterns of leukocyte recruitment in the pulmonary microvasculature in response to local and systemic inflammation
Authors: Wang Yongzhi , Roller Jonas , Slotta Jan E. , Zhang Su , Luo Lingtao , Rahman Milladur , Syk Ingvar , Menger Michael D. , Thorlacius Henrik
Published: December 2012

The mechanisms of leukocyte recruitment in the pulmonary microvasculature in response to local and systemic inflammation remain elusive. Male C57BL/6 mice received lipopolysaccharide (LPS) intrapulmonary (intratracheally, it) or systemically (intravenously, iv) for 1–18 h. Leukocyte responses in lung were analyzed by use of intravital fluorescence microscopy. Plasma and lung levels of CXC chemokines as well as Mac-1 and F-actin expression in leukocytes and bronchoalveolar leukocytes were quantified. Venular leukocyte rolling was markedly increased in response to local LPS but only marginally after systemic LPS. Leukocyte adhesion in venules was enhanced in both groups although adhesion was higher in mice receiving LPS intratracheally compared with LPS intravenously. Systemic LPS caused more leukocytes trapping in capillaries compared with local LPS. The ratio of adherent leukocytes in venules compared with capillaries was higher in response to local LPS, suggesting that leukocytes were more prone to accumulate in venules in local inflammation and in capillaries in systemic inflammation. Systemic LPS triggered higher F-actin formation and Mac-1 expression in leukocytes compared with local LPS. Local and systemic LPS caused similar increases in CXC chemokines in the lung whereas intravenous endotoxin provoked higher levels of CXC chemokines in the circulation. Interestingly, intratracheal LPS increased recruitment of leukocytes in the alveolar space whereas intravenous LPS was ineffective in promoting leukocyte accumulation in the bronchoalveolar space. In conclusion, our data demonstrate that pulmonary microvascular recruitment of leukocytes differs in local and systemic inflammation, which might be related to premature activation and stiffening of circulating leukocytes in endotoxemia.
Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles
Authors: Sindler Amy L. , Reyes Rafael , Chen Bei , Ghosh Payal , Gurovich Alvaro N. , Kang Lori S. , Cardounel Arturo J. , Delp Michael D. , Muller-Delp Judy M.
Published: January 2013

Exercise training ameliorates age-related impairments in endothelium-dependent vasodilation in skeletal muscle arterioles. Additionally, exercise training is associated with increased superoxide production. The purpose of this study was to determine the role of superoxide and superoxide-derived reactive oxygen species (ROS) signaling in mediating endothelium-dependent vasodilation of soleus muscle resistance arterioles from young and old, sedentary and exercise-trained rats. Young (3 mo) and old (22 mo) male rats were either exercise trained or remained sedentary for 10 wk. To determine the impact of ROS signaling on endothelium-dependent vasodilation, responses to acetylcholine were studied under control conditions and during the scavenging of superoxide and/or hydrogen peroxide. To determine the impact of NADPH oxidase-derived ROS, endothelium-dependent vasodilation was determined following NADPH oxidase inhibition. Reactivity to superoxide and hydrogen peroxide was also determined. Tempol, a scavenger of superoxide, and inhibitors of NADPH oxidase reduced endothelium-dependent vasodilation in all groups. Similarly, treatment with catalase and simultaneous treatment with tempol and catalase reduced endothelium-dependent vasodilation in all groups. Decomposition of peroxynitrite also reduced endothelium-dependent vasodilation. Aging had no effect on arteriolar protein content of SOD-1, catalase, or glutathione peroxidase-1; however, exercise training increased protein content of SOD-1 in young and old rats, catalase in young rats, and glutathione peroxidase-1 in old rats. These data indicate that ROS signaling is necessary for endothelium-dependent vasodilation in soleus muscle arterioles, and that exercise training-induced enhancement of endothelial function occurs, in part, through an increase in ROS signaling.
The role of spectral composition of sounds on the localization of sound sources by cats
Authors: Tollin Daniel J. , Ruhland Janet L. , Yin Tom C. T.
Published: December 2012

Sound localization along the azimuthal dimension depends on interaural time and level disparities, whereas localization in elevation depends on broadband power spectra resulting from the filtering properties of the head and pinnae. We trained cats with their heads unrestrained, using operant conditioning to indicate the apparent locations of sounds via gaze shift. Targets consisted of broadband (BB), high-pass (HP), or low-pass (LP) noise, tones from 0.5 to 14 kHz, and 1/6 octave narrow-band (NB) noise with center frequencies ranging from 6 to 16 kHz. For each sound type, localization performance was summarized by the slope of the regression relating actual gaze shift to desired gaze shift. Overall localization accuracy for BB noise was comparable in azimuth and in elevation but was markedly better in azimuth than in elevation for sounds with limited spectra. Gaze shifts to targets in azimuth were most accurate to BB, less accurate for HP, LP, and NB sounds, and considerably less accurate for tones. In elevation, cats were most accurate in localizing BB, somewhat less accurate to HP, and less yet to LP noise (although still with slopes ∼0.60), but they localized NB noise much worse and were unable to localize tones. Deterioration of localization as bandwidth narrows is consistent with the hypothesis that spectral information is critical for sound localization in elevation. For NB noise or tones in elevation, unlike humans, most cats did not have unique responses at different frequencies, and some appeared to respond with a “default” location at all frequencies.
Comparison of auditory-vocal interactions across multiple types of vocalizations in marmoset auditory cortex
Authors: Eliades Steven J. , Wang Xiaoqin
Published: December 2012

Auditory-vocal interaction, the modulation of auditory sensory responses during vocal production, is an important but poorly understood neurophysiological phenomenon in nonhuman primates. This sensory-motor processing has important behavioral implications for self-monitoring during vocal production as well as feedback-mediated vocal control for both animals and humans. Previous studies in marmosets have shown that a large portion of neurons in the auditory cortex are suppressed during self-produced vocalization but have primarily focused on a single type of isolation vocalization. The present study expands previous analyses to compare auditory-vocal interaction of cortical responses between different types of vocalizations. We recorded neurons from the auditory cortex of unrestrained marmoset monkeys with implanted electrode arrays and showed that auditory-vocal interactions generalize across vocalization types. We found the following: 1) Vocal suppression and excitation are a general phenomenon, occurring for all four major vocalization types. 2) Within individual neurons, suppression was the more general response, occurring for multiple vocalization types, while excitation tended to be more specific to a single vocalization type. 3) A subset of neurons changed their responses between different types of vocalization, most often from strong suppression or excitation for one vocalization to unresponsive for another, and only rarely from suppression to excitation. 4) Differences in neural responses between vocalization types were weakly correlated with passive response properties, measured by playbacks of acoustic stimuli including recorded vocalizations. These results indicate that vocalization-induced modulation of the auditory cortex is a general phenomenon applicable to all vocalization types, but variations within individual neurons suggest possible vocalization-specific coding.
A Review of Solar Radiation Models—Part I
Authors: Katiyar A. K. , Pandey C. K.
Published: December 2012

Energy is considered as a key source for the future and plays a pivotal role in its socioeconomic development by raising the standard of living and the quality of life, not only for India but also for the world. In view of the scarce fossil fuel reserves, solar energy is one of the important sources of renewable energy used in India because of the suitable climate conditions. It receives about 5485.17 Wh/m2day of solar insolation with an annual total of about 19, 74, 661.2 Wh/m2. Except for the monsoon months, solar radiation incidence is very encouraging, from the application point of view. For the efficient functioning and better performance of solar energy device, the information of solar radiation and its components at particular location is very essential for designing the solar energy devices. Therefore, over the years, several empirical correlations have been developed in order to estimate the more appropriate solar radiation in India as well as around the world. Here we present a review of different solar radiation models which predict global solar radiation and discussed the long-term plan to meet future energy demand with renewable energy due to economy growth.
In VitroOvicidal and Cestocidal Effects of Toxins fromBacillus thuringiensison the Canine and Human ParasiteDipylidium caninum
Authors: Peña Guadalupe , Aguilar Jiménez Fortino Agustín , Hallal-Calleros Claudia , Morales-Montor Jorge , Hernández-Velázquez Víctor Manuel , Flores-Pérez Fernando Iván
Published: December 2012

Bacillus thuringiensisis a gram-positive soil-dwelling bacterium that is commonly used as a biological pesticide. This bacterium may also be used for biological control of helminth parasites in domestic animals. In this study, we evaluated the possible ovicidal and cestocidal effects of a total protein extract ofB. thuringiensisnative strains on the zoonotic cestode parasite of dogs,Dipylidium caninum(D. caninum). Dose and time response curves were determined by coincubatingB. thuringiensisproteins at concentration ranging from 100 to 1000 μg/mL along with 4000 egg capsules ofD. caninum. Egg viability was evaluated using the trypan blue exclusion test. The lethal concentration of toxins on eggs was 600 μg/ml, and the best incubation time to produce this effect was 3 h. In the adult stage, the motility and the thickness of the tegument were used as indicators of damage. The motility was inhibited by 100% after 8 hours of culture compared to the control group, while the thickness of the cestode was reduced by 34%. Conclusively, proteins of the strain GP526 ofB. thuringiensisdirectly act uponD. caninumshowing ovicidal and cestocidal effects. Thus,B. thuringiensisis proposed as a potential biological control agent against this zoonosis.
Glucocorticoid-Induced Osteoporosis in Children with 21-Hydroxylase Deficiency
Authors: Ventura Annamaria , Brunetti Giacomina , Colucci Silvia , Oranger Angela , Ladisa Filomena , Cavallo Luciano , Grano Maria , Faienza Maria Felicia
Published: December 2012

21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), resulting from deletions or mutations of the P450 21-hydroxylase gene (CYP21A2). Children with 21-OHD need chronic glucocorticoid (cGC) therapy, both to replace congenital deficit in cortisol synthesis and to reduce androgen secretion by adrenal cortex. GC-induced osteoporosis (GIO) is the most common form of secondary osteoporosis that results in an early, transient increase in bone resorption accompanied by a decrease in bone formation, maintained for the duration of GC therapy. Despite the conflicting results in the literature about the bone status on GC-treated patients with 21-OHD, many reports consider these subjects to be at risk for osteoporosis and fractures. In bone cells, at the molecular level, GCs regulate various functions including osteoblastogenesis, osteoclastogenesis, and the apoptosis of osteoblasts and osteocytes. In this paper, we focus on the physiology and biosynthesis of endogenous steroid hormones as well as on the effects of GCs on bone cells, highlighting the pathogenetic mechanism of GIO in children with 21-OHD.
ALX1 Induces Snail Expression to Promote Epithelial-to-Mesenchymal Transition and Invasion of Ovarian Cancer Cells
Authors: Yuan Hong , Kajiyama Hiroaki , Ito Satoko , Yoshikawa Nobuhisa , Hyodo Toshinori , Asano Eri , Hasegawa Hitoki , Maeda Masao , Shibata Kiyosumi , Hamaguchi Michinari , Kikkawa Fumitaka , Senga Takeshi
Published: January 2013

Ovarian cancer is a highly invasive and metastatic disease with a poor prognosis if diagnosed at an advanced stage, which is often the case. Recent studies argue that ovarian cancer cells that have undergone epithelial-to-mesenchymal transition (EMT) acquire aggressive malignant properties, but the relevant molecular mechanisms in this setting are not well-understood. Here, we report findings from an siRNA screen that identified the homeobox transcription factor ALX1 as a novel regulator of EMT. RNA interference–mediated attenuation of ALX1 expression restored E-cadherin expression and cell–cell junction formation in ovarian cancer cells, suppressing cell invasion, anchorage-independent growth, and tumor formation. Conversely, enforced expression of ALX1 in ovarian cancer cells or nontumorigenic epithelial cells induced EMT. We found that ALX1 upregulated expression of the key EMT regulator Snail (SNAI1) and that it mediated EMT activation and cell invasion by ALX1. Our results define the ALX1/Snail axis as a novel EMT pathway that mediates cancer invasion. Cancer Res; 73(5); 1581–90. ©2012 AACR.
Evidence for a Role of the PD-1:PD-L1 Pathway in Immune Resistance of HPV-Associated Head and Neck Squamous Cell Carcinoma
Authors: Lyford-Pike Sofia , Peng Shiwen , Young Geoffrey D. , Taube Janis M. , Westra William H. , Akpeng Belinda , Bruno Tullia C. , Richmon Jeremy D. , Wang Hao , Bishop Justin A. , Chen Lieping , Drake Charles G. , Topalian Suzanne L. , Pardoll Drew M. , Pai Sara I.
Published: January 2013

Human papillomavirus-associated head and neck squamous cell carcinomas (HPV-HNSCC) originate in the tonsils, the major lymphoid organ that orchestrates immunity to oral infections. Despite its location, the virus escapes immune elimination during malignant transformation and progression. Here, we provide evidence for the role of the PD-1:PD-L1 pathway in HPV-HNSCC immune resistance. We show membranous expression of PD-L1 in the tonsillar crypts, the site of initial HPV infection. In HPV-HNSCCs that are highly infiltrated with lymphocytes, PD-L1 expression on both tumor cells and CD68+ tumor-associated macrophages is geographically localized to sites of lymphocyte fronts, whereas the majority of CD8+ tumor-infiltrating lymphocytes express high levels of PD-1, the inhibitory PD-L1 receptor. Significant levels of mRNA for IFN-γ, a major cytokine inducer of PD-L1 expression, were found in HPV+ PD-L1(+) tumors. Our findings support the role of the PD-1:PD-L1 interaction in creating an “immune-privileged” site for initial viral infection and subsequent adaptive immune resistance once tumors are established and suggest a rationale for therapeutic blockade of this pathway in patients with HPV-HNSCC. Cancer Res; 73(6); 1733–41. ©2012 AACR.
Acidity Generated by the Tumor Microenvironment Drives Local Invasion
Authors: Estrella Veronica , Chen Tingan , Lloyd Mark , Wojtkowiak Jonathan , Cornnell Heather H. , Ibrahim-Hashim Arig , Bailey Kate , Balagurunathan Yoganand , Rothberg Jennifer M. , Sloane Bonnie F. , Johnson Joseph , Gatenby Robert A. , Gillies Robert J.
Published: January 2013

The pH of solid tumors is acidic due to increased fermentative metabolism and poor perfusion. It has been hypothesized that acid pH promotes local invasive growth and metastasis. The hypothesis that acid mediates invasion proposes that H+ diffuses from the proximal tumor microenvironment into adjacent normal tissues where it causes tissue remodeling that permits local invasion. In the current work, tumor invasion and peritumoral pH were monitored over time using intravital microscopy. In every case, the peritumoral pH was acidic and heterogeneous and the regions of highest tumor invasion corresponded to areas of lowest pH. Tumor invasion did not occur into regions with normal or near-normal extracellular pH. Immunohistochemical analyses revealed that cells in the invasive edges expressed the glucose transporter-1 and the sodium–hydrogen exchanger-1, both of which were associated with peritumoral acidosis. In support of the functional importance of our findings, oral administration of sodium bicarbonate was sufficient to increase peritumoral pH and inhibit tumor growth and local invasion in a preclinical model, supporting the acid-mediated invasion hypothesis. Cancer Res; 73(5); 1524–35. ©2012 AACR.
Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling
Authors: Guo Kun , Ma Qingyong , Li Junhui , Wang Zheng , Shan Tao , Li Wei , Xu Qinhong , Xie Keping
Published: January 2013

Perineural invasion (PNI) is one of the most important causes of local recurrence and poor survival in pancreatic cancer. However, the exact mechanism of PNI is still not clear. In this study, we sought to identify the reciprocal signaling interactions between sympathetic nerves and pancreatic cancer cells and the underlying mechanisms. We used mouse dorsal root ganglia and pancreatic cancer cells cocultured in vitro, cellular and molecular biology, and animal models to evaluate the function of the sympathetic neurotransmitter norepinephrine (NE) in PNI progression and pathogenesis. NE promoted PNI of pancreatic cancer cells and increased levels of phosphorylated STAT3 in a concentration-dependent manner. NE-mediated activation of STAT3 was inhibited by blocking β-adrenergic receptors (AR) and by blocking protein kinase A, but not through blocking α-AR. Blocking STAT3 could inhibit NE-induced NGF, MMP2, and MMP9 expression and attenuate the migratory, invasive ability and PNI of pancreatic cancer cells. Furthermore, PNI of pancreatic cancer cells was blocked by treatment with a STAT3 phosphorylation inhibitor in vivo. These studies show that NE plays a critical role in pancreatic cancer PNI development and progression through the β-AR/PKA/STAT3 signaling pathway. Reciprocal signaling interactions between the sympathetic nerves and pancreatic cancer cells critically contribute to pancreatic cancer PNI pathogenesis. Inhibition of the activity of sympathetic nerves or STAT3 may be potential strategies for pancreatic cancer PNI therapy. Mol Cancer Ther; 12(3); 264–73. ©2012 AACR.
Intestinal Absorption and Vitamin Levels: Is a New Focus Needed?
Authors: Vavricka Stephan R. , Rogler Gerhard
Published: January 2013

Vitamins are micronutrient chemical compounds that cannot be synthesized by an organism but are essential for human metabolism and life. They act as required intermediaries, cofactors or coenzymes in many of the reactions of normal metabolism. In addition, anti-inflammatory effects have been reported for specific vitamins. In inflammatory bowel disease (IBD), vitamin deficiency is often due to malnutrition (due to a decreased food intake) or malabsorption (due to inflamed, malfunctioning mucosa and diarrhea) which results in anemia. Vitamin B12 and folic acid supplementation may be necessary in IBD patients, especially those with Crohn’s disease (CD) with either inflammation of the terminal ileum or after resection of the terminal ileum. It is also recommended during therapy with sulfasalazine as this compound inhibits the absorption of vitamin B12. Patients with high or continuous inflammatory CD activity and frequent therapy with steroids have an increased risk of low bone mineral density and vitamin D deficiency. These should be monitored regularly and vitamin D should be supplemented. In a recent trial, a trend towards a reduced risk of relapses in CD patients treated with vitamin D was reported. Only limited studies and case reports exist on other vitamin deficiencies, e.g. vitamins A, B1, B2, niacine, B6, C, E and K, found in IBD patients. These are summarized in this review. Regular nutritional monitoring in IBD patients is warranted and requires the special attention of treating physicians and dieticians.
Deep Remission: A New Concept?
Authors: Colombel Jean-Frédéric , Louis Edouard , Peyrin-Biroulet Laurent , Sandborn William J. , Panaccione Remo
Published: January 2013

Crohn’s disease (CD) is a chronic inflammatory disorder characterized by periods of clinical remission alternating with periods of relapse defined by recurrent clinical symptoms. Persistent inflammation is believed to lead to progressive bowel damage over time, which manifests with the development of strictures, fistulae and abscesses. These disease complications frequently lead to a need for surgical resection, which in turn leads to disability. So CD can be characterized as a chronic, progressive, destructive and disabling disease. In rheumatoid arthritis, treatment paradigms have evolved beyond partial symptom control alone toward the induction and maintenance of sustained biological remission, also known as a ‘treat to target’ strategy, with the goal of improving long-term disease outcomes. In CD, there is currently no accepted, well-defined, comprehensive treatment goal that entails the treatment of both clinical symptoms and biologic inflammation. It is important that such a treatment concept begins to evolve for CD. A treatment strategy that delays or halts the progression of CD to increasing damage and disability is a priority. As a starting point, a working definition of sustained deep remission (that includes long-term biological remission and symptom control) with defined patient outcomes (including no disease progression) has been proposed. The concept of sustained deep remission represents a goal for CD management that may still evolve. It is not clear if the concept also applies to ulcerative colitis. Clinical trials are needed to evaluate whether treatment algorithms that tailor therapy to achieve deep remission in patients with CD can prevent disease progression and disability.
Biological Treatment of Crohn’s Disease
Authors: Nielsen Ole Haagen , Bjerrum Jacob Tveiten , Seidelin Jakob Benedict , Nyberg Caroline , Ainsworth Mark
Published: January 2013

Introduction of biological agents for the treatment of Crohn’s disease (CD) has led to a transformation of the treatment paradigm. Several biological compounds have been approved for patients with CD refractory to conventional treatment: infliximab, adalimumab and certolizumab pegol (and natalizumab in several countries outside the European Union). However, despite the use of biologics for more than a decade, questions still remain about the true efficacy and the best treatment regimens – especially about when to discontinue treatment. Furthermore, a need for optimizing treatment with biologics still exists, as 20–40% of patients with CD (depending on selection criteria) do not have any relevant response to the current biological agents (i.e. primary failures). A better patient selection might maximize the clinical outcome while minimizing the complications associated with this type of therapy. However, the clinical tools capable of identifying such patients are still unavailable, and the trough level strategy may help the clinician to optimize therapy and to avoid loss of response and/or immunogenicity (i.e. a low but measurable antibody level exists just before the periodic administration of the biological agent). On the other hand, peak levels and average levels should not exceed concentrations associated with increased toxicity. Randomized, controlled studies focusing on trough levels and antibodies towards the biological agent in routine clinical situations may add important pieces to the puzzle for a more rational treatment algorithm of CD patients. In some situations, the risks (i.e. immunogenicity, serious infections and the promotion of neoplasia) may, however, not outweigh the benefits of biological treatment.
A Similar but Distinctive Pattern of Impaired Cortical Excitability in First-Episode Schizophrenia and ADHD
Authors: Hasan Alkomiet , Schneider Marc , Schneider-Axmann Thomas , Ruge Diane , Retz Wolfgang , Rösler Michael , Falkai Peter , Wobrock Thomas
Published: January 2013

Background: First-episode schizophrenia (FE-SZ) and attention deficit hyperactivity disorder (ADHD) are both neuropsychiatric disorders associated with an impaired dopaminergic transmission. Though displaying different clinical phenotypes, a common pathophysiological pathway is discussed controversially. Several studies using transcranial magnetic stimulation (TMS) revealed abnormalities in human motor cortex excitability in both schizophrenia and ADHD patients. Studies on cortical excitability comparing these two diseases directly are lacking. Method: In this study, a total of 94 subjects were analyzed. Twenty-five FE-SZ patients were directly compared with 28 ADHD patients and 41 healthy controls (HC). We investigated cortical excitability (inhibitory and facilitatory networks) with single- and paired-pulse TMS to the left and right motor cortex. Results: Compared to HC, FE-SZ/ADHD patients displayed an impaired cortical inhibition over the left hemisphere. Apart from an enhanced intracortical facilitation, FE-SZ patients did not differ compared to ADHD patients in the main outcome measures. Both patient groups presented a dysfunctional hemispheric pattern of cortical inhibition and facilitation in comparison with HC. Conclusion: The results of this study indicate a pattern of cortical disinhibition and abnormal hemispheric balance of intracortical excitability networks in two different psychiatric diseases. These effects might be associated with an imbalance in GABAergic and dopaminergic transmission and might provide evidence for a common pathophysiological pathway of both diseases.
Intra-Individual Changes of Active Matrix Metalloproteinase-9 Are Associated with Clinical In-Stent Restenosis of Bare Metal Stents
Authors: Tarr G.P. , Williams M.J.A. , Wilkins G.T. , Chen V.H.T. , Phillips L.V. , van Rij A.M. , Jones G.T.
Published: January 2013

Objectives: Increased chronic postprocedural levels of active matrix metalloproteinase-9 (MMP-9) have been associated retrospectively with a history of in-stent restenosis (ISR). This study aimed to determine whether index or post-percutaneous coronary intervention (PCI) plasma levels of active MMP-9 are a predictor of subsequent clinical ISR, in a standard population of patients treated with bare metal coronary stents. Methods: Four hundred thirty-two patients were prospectively recruited and sampled at index and 3 and 6 months after PCI. Those who developed symptomatic angiographically confirmed ISR were compared to randomly selected, asymptomatic controls, stratified by index presentation in a nested case-control design. Plasma samples were analyzed for the active form of MMP-9. Results: In all, 35 patients (8.1%) developed ISR, and these were compared to 98 controls. The increase in active MMP-9 over 3 months was significantly greater in the ISR group (p = 0.030) and independent of the established risk factors. Index clinical presentation was not associated with acute changes in active MMP-9; however, patients with ST-elevation myocardial infarction had greater increases in active MMP-9 at 3 months. Conclusions: The change in active MMP-9 over 3 months after bare metal coronary stent placement appears to be independently associated with the development of ISR in a standard PCI population.
Two Cycles of Cisplatin-Based Chemotherapy for Low-Volume Stage II Seminoma: Results of a Retrospective, Single-Center Case Series
Authors: Pichler Renate , Leonhartsberger Nicolai , Stöhr Brigitte , Horninger Wolfgang , Steiner Hannes
Published: January 2013

Background: To report on the oncological outcome and toxicity of patients treated with 2 cycles of cisplatin-based chemotherapy for low-volume metastatic stage II seminoma. Methods: We retrospectively identified a case series of 15 patients with seminoma stage IIA (26.7%) and IIB (73.3%) who underwent chemotherapy consisting of 2 cycles of cisplatin, etoposide and bleomycin (PEB) (cisplatin 20 mg/m2 on days 1–5, etoposide 100 mg/m2 on days 1–5, bleomycin 30 mg on days 1, 8 and 15) according to patient preference (refusing a 3rd cycle of PEB) or institutional practice in the last decades. Complete staging before chemotherapy was available in all patients. Patient age, the side and diameter of the primary tumor, the size of the lymph nodes before and after chemotherapy, acute and late toxicity of chemotherapy, the incidence of second malignancies, the relapse-free rate and cancer-specific mortality were recorded. Results: Chemotherapy was well tolerated and no episode of febrile neutropenia occurred. Thrombocytopenia grade 4 was not seen in any patient, while leukopenia grade 4 was observed in 4 (26.6%) patients. The mean (range) lymph node size decreased significantly from 2.54 cm (1.1–4.0) before chemotherapy to 0.75 cm (0.4–2.2) after chemotherapy (p < 0.001). After a median (range) follow-up of 60 (13–185) months, no patient had relapsed, no patient had died as a result of seminoma and second malignancy was seen in only 1 (6.6%) patient. Conclusions: These excellent long-term results from a retrospective case series of 2 cycles of PEB in stage IIA/IIB seminoma patients represent a hint for further research with a view to reducing treatment burden. However, these incidental findings should be studied in prospective trials prior to drawing any conclusions.
Aluminum Citrate Blocks Toxicity of Calcium Oxalate Crystals by Preventing Binding with Cell Membrane Phospholipids
Authors: Guo Chungang , Dugas Tammy , Scates Clinton , Garcia-Villarreal Maria , Ticich Thomas , McMartin Kenneth E.
Published: January 2013

Background/Aims: Renal damage from ethylene glycol and primary hyperoxaluria is linked to accumulation of calcium oxalate monohydrate (COM) crystals in the renal proximal tubule (PT). In vitro studies have shown that aluminum citrate (AC), uniquely among citrate salts, blocks COM cytotoxicity to tubular cells. These studies were designed to evaluate the interaction of COM with membrane phospholipids and the ability of AC to reduce COM toxicity by interfering with this interaction. Methods: Interaction of COM with phospholipids was assessed using differential scanning calorimetric analysis of structural changes in specific liposomes. Interaction of COM with cell membranes was studied by measuring binding of radiolabeled crystals by human PT (HPT) cells. Results: Analysis of liposomes prepared from phosphatidylserine (PS) or phosphatidylcholine (PC) showed that COM interfered with the gel-liquid transition of PS liposomes, but not that of PC liposomes. AC reversed the COM-induced changes in liposomal structure. AC inhibited the binding of [14C]-COM by HPT cells in a concentration-dependent manner. AC blocked COM binding by interacting with the crystal surface and not the cell membrane. Conclusion: These results indicate that AC blocks the binding of COM by PT cells, and consequently its cytotoxicity, by attaching to the surface of the crystal. Thus, AC, or a related compound that works by the same mechanism, could be a useful adjunct therapy to reduce the renal damage produced by severe hyperoxaluria.
Increased Interstitial Protein Because of Impaired Lymph Drainage Does Not Induce Fibrosis and Inflammation in Lymphedema
Authors: Markhus C.E. , Karlsen T.V. , Wagner M. , Svendsen Ø.S. , Tenstad O. , Alitalo K. , Wiig H.
Published: January 2013

Objective—

The pathophysiology of lymphedema is incompletely understood. We asked how transcapillary fluid balance parameters and lymph flow are affected in a transgenic mouse model of primary lymphedema, which due to an inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) signaling lacks dermal lymphatics, and whether protein accumulation in the interstitium occurring in lymphedema results in inflammation.

Methods and Results—

As estimated using a new optical-imaging technique, we found that this signaling defect resulted in lymph drainage in hind limb skin of K14-VEGFR-3-Ig mice that was 34% of the corresponding value in wild-type. The interstitial fluid pressure and tissue fluid volumes were significantly increased in the areas of visible swelling only, whereas the colloid osmotic pressure in plasma, and thus the colloid osmotic pressure gradient, was reduced compared to wild-type mice. An acute volume load resulted in an exaggerated interstitial fluid pressure response in transgenic mice. There was no accumulation of collagen or lipid in skin, suggesting that chronic edema presented in the K14-VEGFR-3-Ig mouse was not sufficient to induce changes in tissue composition. Proinflammatory cytokines (interleukin-2, interleukin-6, interleukin-12) in subcutaneous interstitial fluid and macrophage infiltration in skin of the paw were lower, whereas the monocyte/macrophage cell fraction in blood and spleen was higher in transgenic compared with wild-type mice.

Conclusion—

Our data suggest that a high interstitial protein concentration and longstanding edema is not sufficient to induce fibrosis and inflammation characteristic for the human condition and may have implications for our understanding of the pathophysiology of this condition.
Pioglitazone Attenuates Valvular Calcification Induced by Hypercholesterolemia
Authors: Chu Yi , Lund Donald D. , Weiss Robert M. , Brooks Robert M. , Doshi Hardik , Hajj Georges P. , Sigmund Curt D. , Heistad Donald D.
Published: January 2013

Objective—

Development of calcific aortic valve stenosis involves multiple signaling pathways, which may be modulated by peroxisome proliferator-activated receptor-γ). This study tested the hypothesis that pioglitazone (Pio), a ligand for peroxisome proliferator-activated receptor-γ, inhibits calcification of the aortic valve in hypercholesteremic mice.

Methods and Results—

Low density lipoprotein receptor
–/–
/apolipoprotein B
100/100
mice were fed a Western-type diet with or without Pio (20 mg/kg per day) for 6 months. Pio attenuated lipid deposition and calcification in the aortic valve, but not aorta. In the aortic valve, Pio reduced levels of active caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Valve function (echocardiography) was significantly improved by Pio. To determine whether changes in gene expression are associated with differential effects of Pio on aortic valves versus aorta, Reversa mice were fed Western diet with or without Pio for 2 months. Several procalcific genes were increased by Western diet, and the increase was attenuated by Pio, in aortic valve, but not aorta.

Conclusion—

Pio attenuates lipid deposition, calcification, and apoptosis in aortic valves of hypercholesterolemic mice, improves aortic valve function, and exhibits preferential effects on aortic valves versus aorta. We suggest that Pio protects against calcific aortic valve stenosis, and Pio or other peroxisome proliferator-activated receptor-γ ligands may be useful for early intervention to prevent or slow stenosis of aortic valves.
Claudin-5 Controls Intercellular Barriers of Human Dermal Microvascular but Not Human Umbilical Vein Endothelial Cells
Authors: Kluger Martin S. , Clark Paul R. , Tellides George , Gerke Volker , Pober Jordan S.
Published: January 2013

Objective—

To assess the role claudin-5, an endothelial cell (EC) tight junction protein, plays in establishing basal permeability levels in humans by comparing claudin-5 expression levels in situ and analyzing junctional organization and function in 2 widely used models of cultured ECs, namely human dermal microvascular (HDM)ECs and human umbilical vein (HUV)ECs.

Methods and Results—

By immunofluorescence microscopy, ECs more highly express claudin-5 (but equivalently express vascular endothelial-cadherin) in human dermal capillaries versus postcapillary venules and in umbilical and coronary arteries versus veins, correlating with known segmental differences in tight junction frequencies and permeability barriers. Postconfluent cultured HDMECs express more claudin-5 (but equivalent vascular endothelial-cadherin) and show higher transendothelial electric resistance and lower macromolecular flux than similarly cultured HUVECs. HDMEC junctions are more complex by transmission electron microscopy and show more continuous claudin-5 immunofluorescence than HUVEC junctions. Calcium chelation or dominant negative vascular endothelial-cadherin overexpression decreases transendothelial electric resistance and disrupts junctions in HUVECs, but not in HDMECs. Claudin-5 overexpression in HUVECs fails to increase transendothelial electric resistance or claudin-5 continuity, whereas claudin-5 knockdown in HDMECs, but not in HUVECs, reduces transendothelial electric resistance and increases antibody accessibility to junctional proteins.

Conclusion—

Claudin-5 expression and junctional organization control HDMEC and arteriolar-capillary paracellular barriers, whereas HUVEC and venular junctions use vascular endothelial-cadherin.
Separate Presentation of Additional Accelerating Motion Does not Enhance Visually Induced Self-Motion Perception
Authors: Nakamura Shinji
Published: December 2012

It has been repeatedly reported that visual stimuli containing a jittering/oscillating motion component can induce self-motion perception more strongly than a pure radial expansion pattern. A psychophysical experiment with 11 observers revealed that the additional accelerating components of the visual motion have to be convoluted with the motion of the main-axis to facilitate self-motion perception; additional motion presented in an isolated fashion impairs the perception of self-motion. These results are inconsistent with a simple hypothesis about the perceptual mechanism underlying the advantage of jitter/oscillation, which assumes that the accelerating component induces an additional self-motion independently of the main motion at the first stage, and then the two self-motions induced by the main motion and the additional component become integrated.
Landfalling Tropical Cyclones along the Eastern Pacific Coast between the Sixteenth and Twentieth Centuries
Authors: Pazos Marni , Mendoza Blanca
Published: January 2013

Numerous studies have been conducted to document long-term trends in tropical cyclone (TC) activity. However, the eastern Pacific has not received as much attention as other basins. Here the authors attempt the identification of TC formation in the Mexican eastern Pacific Ocean before 1950. Using bibliographical and historical file consultation, they constructed a catalog of events related to intense storms and possible TCs that made landfall on the Mexican Pacific coasts. Between 1536 and 1948 they found a total of 119 events related to TCs. Then, using the Saffir–Simpson scale and the climatology of the region as the criteria to evaluate each event, they found 85 TCs. Furthermore, they constructed a historical time series of TCs between 1701 and 2010. The spectral analysis showed periodicities of ~2.6, 4, 5, 12, 16, 39, and 105 years that coincide with some large-scale climatic phenomena and also with solar activity. In particular, the ~12-yr cycle is the most persistent periodicity in this study.
More Is More or More Is Less? Parental Financial Investments during College
Authors: Hamilton Laura T.
Published: January 2013

Evidence shows that parental financial investments increase college attendance, but we know little about how these investments shape postsecondary achievement. Two theoretical frameworks suggest diametric conclusions. Some studies operate from a more-is-more perspective in which children use calculated parental allocations to make academic progress. In contrast, a more-is-less perspective, rooted in a different model of rational behavior, suggests that parental investments create a disincentive for student achievement. I adjudicate between these frameworks, using data from nationally representative postsecondary datasets to determine what effect financial parental investments have on student GPA and degree completion. The findings suggest seemingly contradictory processes. Parental aid decreases student GPA, but it increases the odds of graduating—net of explanatory variables and accounting for alternative funding. Rather than strategically using resources in accordance with parental goals, or maximizing on their ability to avoid academic work, students are satisficing: they meet the criteria for adequacy on multiple fronts, rather than optimizing their chances for a particular outcome. As a result, students with parental funding often perform well enough to stay in school but dial down their academic efforts. I conclude by highlighting the importance of life stage and institutional context for parental investment.
A Theory of the Majority Canon
Authors: Lim Timothy H.
Published: January 2013

This article proposes a theory of the formation of the Jewish canon. It suggests that the Pharisaic canon became the canon of Rabbinic Judaism, because the majority of those who re-founded the religion after the destruction of the Temple were Pharisees. The theory of the majority canon further advances the view that before the emergence of the one traditional canon Jewish communities held varying collections of texts as authoritative scriptures. The origins and development of the canon were influenced by internal and external factors. There was no central body that pronounced on the canon. Rather the authority arose from the bottom-up as Jews came to regard certain books, but not others, as canonical.
Developing Leaders
Authors: Eddy Pamela L.
Published: January 2013

Pending retirements underscore the need to develop community college campus leaders. Rural community colleges will be particularly hard-hit by changes in leadership as they represent the majority of 2-year colleges and face unique challenges given their location. To help address the anticipated leadership transition, the American Association of Community Colleges developed a set of competencies to frame critical skill areas and guide leadership development efforts. The research reported here showed both resource development and organizational strategy as areas of weakness for rural leaders and, paradoxically, the areas of most need. Leaders acquired competencies predominantly on the job, which has implications in planning development of future leaders.
The Community College Website as Virtual Advisor
Authors: Margolin Jonathan , Miller Shazia Rafiullah , Rosenbaum James E.
Published: January 2013

This study explored whether community college websites are a useful medium for providing knowledge relevant to degree completion. Ten community students used one of three community college websites to answer 10 questions about occupational degree programs. A facilitator asked participants to think aloud while using the website to answer these questions; their responses were video-recorded and coded in terms of correctness of answers and types of usability problems encountered. The findings suggest that participants frequently encountered problems with finding and understanding information needed to understand degree selection and completion. The content analysis of these problems yields several suggestions for improving the usability of community college websites for answering common questions about degree completion.
Mechanical, thermal and morphological properties of poly(lactic acid)/epoxidized natural rubber blends
Authors: Bijarimi Mohd , Ahmad Sahrim , Rasid Rozaidi
Published: December 2012

In this work, we report a melt blend of poly(lactic acid)(PLA)/epoxidized natural rubber (ENR) with liquid natural rubber (LNR). The LNR was synthesized by a photochemical degradation technique and used as a compatibilizer in the PLA/rubber binary blending systems. The PLA/ENR/LNR blends were melt-blended in a Haake internal mixer at 180°C and mixing speed of 50 r. min−1 for 15 min. It was found that the addition of LNR compatibilizer has improved the tensile strength and elongation at break for the compositions of the 40PLA/55ENR/5LNR blend system when compared with a noncompatibilized system (40PLA/55ENR/5NR). The elongation at break for the blend with 5% LNR compatibilizer showed a twofold increment compared with the blend without LNR. The increase in tensile strength and elongation at break were associated with the ability of LNR to promote the uniform dispersion between the natural rubber (NR) and PLA phases as observed in the scanning electron microscopic analysis. Moreover, the differential scanning calorimetric results indicated that the 40PLA/55ENR/5LNR showed the highest degree of crystallinity and thus contributed to improve their mechanical properties. Thermogravimetric analysis showed that two degradation transitions for both compatibilized and noncompatibilized blend systems due to higher degradation temperatures of ENR50 and NR parts. Fourier transform infrared spectroscopic analysis revealed that the PLA/ENR/NR and PLA/ENR/LNR blends were not miscible.