Calcium/calmodulin-dependent kinases can regulate the TSH expression in the rat pituitary.

PURPOSE: The endocrine secretion of TSH is a finely orchestrated process controlled by the thyrotropin-releasing hormone (TRH). Its homeostasis and signaling rely on many calcium-binding proteins belonging to the "EF-hand" protein family. The Ca2+/calmodulin (CaM) complex is associated with Ca2+/CaM-dependent kinases (Ca2+/CaMK). We have investigated Ca2+/CaMK expression and regulation in the rat pituitary. METHODS: The expression of CaMKII and CaMKIV in rat anterior pituitary cells was shown by immunohistochemistry. Cultured anterior pituitary cells were stimulated by TRH in the presence and absence of KN93, the pharmacological inhibitor of CaMKII and CaMKIV. Western blotting was then used to measure the expression of these kinases and of the cAMP response element-binding protein (CREB). TSH production was measured by RIA after time-dependent stimulation with TRH. Cells were infected with a lentiviral construct coding for CaMKIV followed by measurement of CREB phosphorylation and TSH. RESULTS: Our study shows that two CaM kinases, CaMKII and CaMKII, are expressed in rat pituitary cells and their phosphorylation in response to TRH occurs at different time points, with CaMKIV being activated earlier than CaMKII. TRH induces CREB phosphorylation through the activity of both CaMKII and CaMKIV. The activation of CREB increases TSH gene expression. CaMKIV induces CREB phosphorylation while its dominant negative and KN93 exert the opposite effects. CONCLUSION: Our data indicate that the expression of Ca2+/CaMK in rat anterior pituitary are correlated to the role of CREB in the genetic regulation of TSH, and that TRH stimulation activates CaMKIV, which in turn phosphorylates CREB. This phosphorylation is linked to the production of thyrotropin

Production of Succinic Acid From Basfia succiniciproducens

Basfia succiniciproducens is a facultative anaerobic capnophilic bacterium, isolated from rumen, that naturally produces high amounts of succinic acid by fixing CO2 and using fumarate as final electron acceptor. This metabolic feature makes it one of the ideal candidates for developing biotechnological industrial routes that could eventually replace the polluting and environment unfriendly petrochemical ones that are still main sources for the production of this value-added compound. In fact, due to the large number of applications of succinic acid that range from the more traditional ones as food additive or pharmaceutical intermediate to the most recent as building block for biopolymers and bioplastic, increasing demand and market size growth are expected in the next years. In line with a “green revolution” needed to preserve our environment, the great challenge is the establishment of commercially viable production processes that exploit renewable materials and in particular preferably non-food lignocellulosic biomasses and waste products. In this review, we describe the currently available literature concerning B. succiniciproducens since the strain was first isolated, focusing on the different renewable materials and fermentation strategies used to improve succinic acid production titers to date. Moreover, an insight into the metabolic engineering approaches and the key physiological characteristics of B. succiniciproducens deduced from the different studies are presented

Forecast indices from a ground-based microwave radiometer for operational meteorology

Abstract. Today, commercial microwave radiometer profilers (MWRPs) are robust and unattended instruments providing real-time, accurate atmospheric observations at ~ 1 min temporal resolution under nearly all weather conditions. Common commercial units operate in the 20–60 GHz frequency range and are able to retrieve profiles of temperature, vapour density, and relative humidity. Temperature and humidity profiles retrieved from MWRP data are used here to feed tools developed for processing radiosonde observations to obtain values of forecast indices (FIs) commonly used in operational meteorology. The FIs considered here include K index, total totals, KO index, Showalter index, T1 gust, fog threat, lifted index, S index (STT), Jefferson index, microburst day potential index (MDPI), Thompson index, TQ index, and CAPE (convective available potential energy). Values of FIs computed from radiosonde and MWRP-retrieved temperature and humidity profiles are compared in order to quantitatively demonstrate the level of agreement and the value of continuous FI updates. This analysis is repeated for two sites at midlatitude, the first one located at low altitude in central Europe (Lindenberg, Germany) and the second one located at high altitude in North America (Whistler, Canada). It is demonstrated that FIs computed from MWRPs well correlate with those computed from radiosondes, with the additional advantage of nearly continuous updates. The accuracy of MWRP-derived FIs is tested against radiosondes, taken as a reference, showing different performances depending upon index and environmental situation. Overall, FIs computed from MWRP retrievals agree well with radiosonde values, with correlation coefficients usually above 0.8 (with few exceptions). We conclude that MWRP retrievals can be used to produce meaningful FIs, with the advantage (with respect to radiosondes) of nearly continuous updates

Nanoparticles of Cerium Oxide Targeted to an Amyloid-Beta Antigen of Alzheimer\u27s Disease and Associated Methods

Disclosed is a composition immunologically targeted to Alzheimer’s disease (AD), the composition containing amine functionalized nanoparticles of Cerium oxide coated with polyethylene glycol and bearing an antibody specific for an amyloid-beta antigen associated with AD. The invention also includes a medication manufactured with the targeted nanoceria particles and methods of treatment by administering the targeted nanoceria particles to patients in need thereof

Multipolar Spindle Pole Coalescence Is a Major Source of Kinetochore Mis-Attachment and Chromosome Mis-Segregation in Cancer Cells

Many cancer cells display a CIN (Chromosome Instability) phenotype, by which they exhibit high rates of chromosome loss or gain at each cell cycle. Over the years, a number of different mechanisms, including mitotic spindle multipolarity, cytokinesis failure, and merotelic kinetochore orientation, have been proposed as causes of CIN. However, a comprehensive theory of how CIN is perpetuated is still lacking. We used CIN colorectal cancer cells as a model system to investigate the possible cellular mechanism(s) underlying CIN. We found that CIN cells frequently assembled multipolar spindles in early mitosis. However, multipolar anaphase cells were very rare, and live-cell experiments showed that almost all CIN cells divided in a bipolar fashion. Moreover, fixed-cell analysis showed high frequencies of merotelically attached lagging chromosomes in bipolar anaphase CIN cells, and higher frequencies of merotelic attachments in multipolar vs. bipolar prometaphases. Finally, we found that multipolar CIN prometaphases typically possessed γ-tubulin at all spindle poles, and that a significant fraction of bipolar metaphase/early anaphase CIN cells possessed more than one centrosome at a single spindle pole. Taken together, our data suggest a model by which merotelic kinetochore attachments can easily be established in multipolar prometaphases. Most of these multipolar prometaphase cells would then bi-polarize before anaphase onset, and the residual merotelic attachments would produce chromosome mis-segregation due to anaphase lagging chromosomes. We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells

Network Sensitivity of Systemic Risk

A growing body of studies on systemic risk in financial markets has emphasized the key importance of taking into consideration the complex interconnections among financial institutions. Much effort has been put in modeling the contagion dynamics of financial shocks, and to assess the resilience of specific financial markets - either using real network data, reconstruction techniques or simple toy networks. Here we address the more general problem of how shock propagation dynamics depends on the topological details of the underlying network. To this end we consider different realistic network topologies, all consistent with balance sheets information obtained from real data on financial institutions. In particular, we consider networks of varying density and with different block structures, and diversify as well in the details of the shock propagation dynamics. We confirm that the systemic risk properties of a financial network are extremely sensitive to its network features. Our results can aid in the design of regulatory policies to improve the robustness of financial markets

Microbioreactor (micro-Matrix) potential in aerobic and anaerobic conditions with different industrially relevant microbial strains

Microscale fermentation systems are important high throughput tools in clone selection, and bioprocess set up and optimization, since they provide several parallel experiments in controlled conditions of pH, temperature, agitation, and gas flow rate. In this work we evaluated the performance of biotechnologically relevant strains with different respiratory requirements in the micro-Matrix microbioreactor. In particular Escherichia coli K4 requires well aerated fermentation conditions to improve its native production of chondroitin-like capsular polysaccharide, a biomedically attractive polymer. Results from batch and fed-batch experiments demonstrated high reproducibility with those obtained on 2 L reactors, although highlighting a pronounced volume loss for longer-term experiments. Basfia succiniciproducens and Actinobacillus succinogenes need CO2 addition for the production of succinic acid, a building block with several industrial applications. Different CO2 supply modes were tested for the two strains in 24 h batch experiments and results well compared with those obtained on lab-scale bioreactors. Overall, it was demonstrated that the micro-Matrix is a useful scale-down tool that is suitable for growing metabolically different strains in simple batch process, however, a series of issues should still be addressed in order to fully exploit its potential

Heterogeneity, quality, and reputation in an adaptive recommendation model

Abstract.: Recommender systems help people cope with the problem of information overload. A recently proposed adaptive news recommender model [M. Medo, Y.-C. Zhang, T. Zhou, Europhys. Lett. 88, 38005 (2009)] is based on epidemic-like spreading of news in a social network. By means of agent-based simulations we study a "good get richer” feature of the model and determine which attributes are necessary for a user to play a leading role in the network. We further investigate the filtering efficiency of the model as well as its robustness against malicious and spamming behaviour. We show that incorporating user reputation in the recommendation process can substantially improve the outcom

A statistical approach for rain intensity differentiation using Meteosat Second Generation-Spinning Enhanced Visible and InfraRed Imager observations

Abstract. This study exploits the Meteosat Second Generation (MSG)–Spinning Enhanced Visible and Infrared Imager (SEVIRI) observations to evaluate the rain class at high spatial and temporal resolutions and, to this aim, proposes the Rain Class Evaluation from Infrared and Visible observation (RainCEIV) technique. RainCEIV is composed of two modules: a cloud classification algorithm which individuates and characterizes the cloudy pixels, and a supervised classifier that delineates the rainy areas according to the three rainfall intensity classes, the non-rainy (rain rate value < 0.5 mm h-1) class, the light-to-moderate rainy class (0.5 mm h−1 ≤ rain rate value < 4 mm h-1), and the heavy–to-very-heavy-rainy class (rain rate value ≥ 4 mm h-1). The second module considers as input the spectral and textural features of the infrared and visible SEVIRI observations for the cloudy pixels detected by the first module. It also takes the temporal differences of the brightness temperatures linked to the SEVIRI water vapour channels as indicative of the atmospheric instability strongly related to the occurrence of rainfall events. The rainfall rates used in the training phase are obtained through the Precipitation Estimation at Microwave frequencies, PEMW (an algorithm for rain rate retrievals based on Atmospheric Microwave Sounder Unit (AMSU)-B observations). RainCEIV's principal aim is that of supplying preliminary qualitative information on the rainy areas within the Mediterranean Basin where there is no radar network coverage. The results of RainCEIV have been validated against radar-derived rainfall measurements from the Italian Operational Weather Radar Network for some case studies limited to the Mediterranean area. The dichotomous assessment related to daytime (nighttime) validation shows that RainCEIV is able to detect rainy/non-rainy areas with an accuracy of about 97% (96%), and when all the rainy classes are considered, it shows a Heidke skill score of 67% (62%), a bias score of 1.36 (1.58), and a probability of detection of rainy areas of 81% (81%)

3DVAR assimilation of SSM/I data over the sea for the IOP2b MAP case

International audienceData assimilation by 3DVAR of data from the Special Sensor Microwave/Imager (SSM/I) has been performed to study the IOP2b case (19-21 September 1999) of the Mesoscale Alpine Programme (MAP). Only data over the sea surface are used to avoid the contamination of the surface emissivity. Moreover, the rainy data are filtered out because the assimilation algorithm of 3DVAR does not take into account the scattering processes. SSM/I data are assimilated in two different ways: as Brightness Temperature directly, or as Precipitable Water and surface wind speed retrieved from the Brightness Temperature. The effect of the thinning of the observations has been studied and a set of sensitivity test cases has been carried out; the one by one removal of the SSM/I frequencies from the initial dataset allows to evaluate their impact on the Initial Conditions. A few experiments are performed using these new Initial Conditions to initialize the MM5 (PSU/NCAR) model. The results show that the assimilation of the retrieved quantities, i.e. Precipitable Water and surface wind speed, does not produces large improvement in the Initial Conditions. Vice versa, the assimilation of the Brightness temperatures produces a large variability of the Initial Conditions. The forecast experiments show that the model is very sensitive to the 22GHz and 37GHz frequencies