The competitive NMDA antagonist CPP protects substantia nigra neurons from MPTP-induced degeneration in primates

Degeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of Parkinson's disease. The neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces a neurological syndrome in man and non-human primates very similar to idiopathic Parkinson's disease by selectively destroying dopaminergic nigrostriatal neurons. This gives rise to the hypothesis that Parkinson's disease may be caused by endogenous or environmental toxins. Endogenous excitatory amino acids (EAAs) such as L-glutamate could be involved in neurodegenerative disorders including Parkinson's disease. We report in this study that the competitive NMDA antagonist CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) protects nigral tyrosine hydroxylase (TH) positive neurons from degeneration induced by systemic treatment with MPTP in common marmosets. This indicates that EAAs are involved in the pathophysiological cascade of MPTP-induced neuronal cell death and that EAA antagonists may offer a neuroprotective therapy for Parkinson's disease

Οutcomes for patients who are diagnosed with breast and endometrial cancer

The present study sought to determine the survival outcomes for women diagnosed with breast and endometrial cancer. Using SEER data, a population-based cohort study of women diagnosed with breast and endometrial cancer was conducted. Kaplan-Meier survival curves were created for disease-specific survival rates. A total of 2,027 women diagnosed with breast and endometrial cancer were identified. Of these, 1,296 (63.9%) developed breast cancer first and 731 (36.1%) developed endometrial cancer first. Regional lymph node involvement was significantly more common with a breast cancer diagnosis [522 (25.8%) women] compared with an endometrial cancer diagnosis [87 (4.3%) women] (P<0.05). Factors associated with decreased survival included a high tumor grade in endometrial cancer, nodal positivity and estrogen receptor-negative breast cancer (P<0.05 for each). There were 83 (4.1%) mortalities due to breast cancer, 63 (3.1%) mortalities due to endometrial cancer and 178 (8.8%) mortalities due to other causes (P<0.05). In conclusion, for women diagnosed with breast and endometrial cancer, the cumulative risk of mortality at five years following the second cancer diagnosis is nearly four times more likely to be due to breast cancer than endometrial cancer

The neuropeptide complement of the marine annelid Platynereis dumerilii.

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: The marine annelid Platynereis dumerilii is emerging as a powerful lophotrochozoan experimental model for evolutionary developmental biology (evo-devo) and neurobiology. Recent studies revealed the presence of conserved neuropeptidergic signaling in Platynereis, including vasotocin/neurophysin, myoinhibitory peptide and opioid peptidergic systems. Despite these advances, comprehensive peptidome resources have yet to be reported. RESULTS: The present work describes the neuropeptidome of Platynereis. We established a large transcriptome resource, consisting of stage-specific next-generation sequencing datasets and 77,419 expressed sequence tags. Using this information and a combination of bioinformatic searches and mass spectrometry analyses, we increased the known proneuropeptide (pNP) complement of Platynereis to 98. Based on sequence homology to metazoan pNPs, Platynereis pNPs were grouped into ancient eumetazoan, bilaterian, protostome, lophotrochozoan, and annelid families, and pNPs only found in Platynereis. Compared to the planarian Schmidtea mediterranea, the only other lophotrochozoan with a large-scale pNP resource, Platynereis has a remarkably full complement of conserved pNPs, with 53 pNPs belonging to ancient eumetazoan or bilaterian families. Our comprehensive search strategy, combined with analyses of sequence conservation, also allowed us to define several novel lophotrochozoan and annelid pNP families. The stage-specific transcriptome datasets also allowed us to map changes in pNP expression throughout the Platynereis life cycle. CONCLUSION: The large repertoire of conserved pNPs in Platynereis highlights the usefulness of annelids in comparative neuroendocrinology. This work establishes a reference dataset for comparative peptidomics in lophotrochozoans and provides the basis for future studies of Platynereis peptidergic signaling.This work was supported by Max Planck Society Sequencing Grant M.IF.A.ENTW8050 to GJ. The research leading to these results was supported by the European Research Council under European Union Seventh Framework Program FP7/2007–2013 and European Research Council Grant Agreement 260821

A scalable methodology for modeling cities as systems of systems

Thesis (S.M.)--Massachusetts Institute of Technology, Computation for Design and Optimization Program, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 144-146).As cities evolve in size and complexity, their component systems become more interconnected. Comprehensive modeling and simulation is needed to capture interactions and correctly assess the impact of changes. This thesis presents a methodology for modeling cities from a systems of systems perspective. The framework supplies general modeling guidelines and key steps. Also addressed are the importance of stakeholder interactions, creating the model structure, using smart city sensor data, and applying the methodology to larger, traditional cities. As an initial step, four city modeling including CityNet, CityOne, Sim City 4, and SoSAT software programs were evaluated from both a user and mathematical perspective. From the assessments, a list was developed of features critical to successful city modeling software including visualization, a streamlined user interface, accurate mathematics, the ability to specify systems and attributes, and the ability to model interconnections between systems. SoSAT was selected as the modeling tool for the case study, which involved modeling the Army's Base Camp Integration Laboratory. A model of the camp's baseline configuration was built and the camp was simulated for 30 days with results recorded at one hour intervals. 100 trials were run with averaged results presented by time intervals and for the total simulation time. Results were presented at all levels of structural aggregation. Two sensitivity analyses were conducted to analyze the impact of maintenance personnel and the frequency of potable water deliveries. Adding or subtracting a maintenance person impacted the availability of the generator systems that were being serviced, in turn impacting the performance of the micro grid. Extending the time between deliveries by 24 and 48 hours revealed two systems experienced resource depletions. Lastly, two technology insertions cases were conducted to assess the impact of adding a laundry water reuse system (LWRS) and a solar powered hot water heater (SHWH). The LWRS provided 70% of the laundry system's water needs, significantly reducing dependency upon deliveries. The SHWH was expected to decrease electricity consumption and increase fuel consumption. However, the reduction in energy demand meant fewer generators were needed to power the micro grid and both electricity and fuel consumption decreased.by Amanda M. Wachtel.S.M

Survivin expression in ovarian cancer

Aim: To examine the expression of survivin in benign ovarian tumors, ovarian carcinomas of different stages. Methods: We screened the expression of survivin mRNA by reverse transcription polymerase chain reaction in 114 ovarian tissue samples. Quantitative real-time PCR was used to estimate survivin mRNA levels in the samples with positive survivin expression. Results: No survivin mRNA was expressed in all normal ovarian specimens, while it appeared in 73% of ovarian carcinomas, 47% of borderline ovarian carcinomas and 19% of benign ovarian tumors. The survivin mRNA expression rate was positively associated with clinical stage (P = 0.026) and differentiation grade (P = 0.049). There was notably statistically significant difference in the survivin mRNA expression rate dependent on different histological types (serous, mucinous, endometrioid, P = 0.008), but not – dependent on lymph node metastasis (P = 0.921) and ascites (P = 0.87). In tissues with positive expression of survivin, we also found that mean survivin mRNA expression levels were higher in ovarian carcinomas than that in benign ovarian tumors and borderline ovarian carcinoma tissues (P < 0.001). Among ovarian carcinomas, the high survivin mRNA expression levels correlated with the clinical stages, differentiation grade, lymph node metastasis, but not — with ascites and histological type. Conclusion: Our study suggest that survivin is associated with progression of ovarian carcinoma.Цель: исследовать экспрессию сурвивина в доброкачественных и злокачественных новообразованиях яичника. Методы: экспрессия мРНК сурвивина исследована методом RT-PCR в 114 образах ткани яичника человека. Для установления уровня экспресии мРНК сурвивина применяли количественный PCR в режиме реального времени. Результаты: экспрессия мРНК сурвивина не выявлена в образцах нормальной ткани яичника, но зарегистрирована в 73% случаев рака яичника, 47% случаев серозных опухолей яичника серозного типа и 19% образцов доброкачественных опухолей. Установлена положительная зависимость между уровнем экспрессии мРНК сурвивина и клинической стадией заболевания (P = 0,026), и степенью дифференцировки опухоли (P = 0,049). Выявлена статистически значимая зависимость уровня экспрессии мРНК сурвивина от гистологического типа опухоли (серозного, мукозного, эндометриоидного, P = 0,008) и отсутствие таковой от наличия метастазов в лимфатических узлах (P = 0.921) или асцита (P = 0.87). Также установлено, что средние уровни экспрессии мРНК сурвивина выше при раке яичника, чем в ткани доброкачественных новобразований или серозных опухолей яичника пограничного типа (P < 0,001). При раке яичника высокий уровень экспрессии мРНК сурвивина коррелировал с клинической стадией заболевания, степенью дифференцировки опухолевых клеток, но не коррелировал с гистологическим типом новообразования. Выводы: результаты свидетельствуют о том, что экспрессия сурвивина ассоциирована с прогрессией рака яичника. Ключевые слова: сурвивин, рак яичника, опухолевая прогрессия

Use of the wound healing trajectory as an outcome determinant for acute wound healing

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72454/1/j.1524-475x.2000.00511.x.pd

Cue-induced conditioned activity does not incubate but is mediated by the basolateral amygdala

Re-exposure to drug-associated cues causes significant drug craving in recovering addicts, which may precipitate relapse. In animal models of craving, drug-seeking responses for contingent delivery of drug-associated cues sensitizes or “incubates” across drug withdrawal. To date there is limited evidence supporting an incubation effect for behaviors mediated by non-contingent presentation of drug-associated cues. Here we used a model of cue-induced conditioned activity to determine if the conditioned locomotor response to a non-contingent presentation of a drug-associated cue sensitizes across drug withdrawal. In addition, because cue-induced drug-seeking responses are mediated by the rostral basolateral amygdala (BLA), we investigated whether this structure is critical for the expression of cue-induced conditioned activity. A conditioned association between cocaine (15 mg/kg) and a compound discrete cue (flashing bicycle light + a metronome) was established over 12 conditioning sessions in male Sprague–Dawley rats. In experiment 1, cue-induced conditioned activity was assessed on 3 occasions: 3, 14 and 28 days following the final drug–cue conditioning session. Cocaine-conditioned rats demonstrated reliable cue-induced conditioned activity across all 3 test sessions, however there was no evidence of an incubation effect. To determine whether repeated testing prevented the observation of an incubation effect, rats in experiment 2 were tested either 3 days or 28 days following conditioning; again no incubation effect was observed. In experiment 3, either saline or the GABAA receptor agonist muscimol was infused prior to testing. Intra-BLA infusions of muscimol prevented the expression of cue-induced conditioned activity. These data support the role of the rBLA in mediating conditioned responses to drug-associated cues. The failure to observe an incubation effect for cue-induced conditioned activity may point to a fundamental difference in the manner by which contingent and non-contingent presentations of drug-associated cues influence behavior