c myc deregulation is involved in melphalan resistance of multiple myeloma role of pdgf bb

Oncogenes are important regulators of cancer growth and progression and their action may be modulated by proteins of the growth factor family, such as angiogenic cytokines, known to be strongly involved in neoplastic evolution. Reciprocal interactions between oncogenes and angiogenic modulators may represent, in haematological neoplasms, including multiple myeloma (MM), a possible mechanism of drug resistance. The aim of this work is to investigate in vitro and in vivo whether or not c-myc deregulation is involved in the melphalan resistance elicited by myeloma patients and consequently to clarify the role of the angiogenic factor PDGF-BB in modulating c-myc protein expression. Fifty-one MM patients on chemotherapy with melphalan were analyzed for structural alterations of the c-myc gene, c-Myc protein expression, as well as for serum PDGF-BB release. For the in vitro study, two M14-derived established cell clones, differing for the c-Myc protein expression (c-Myc low -expressing or constitutively express..

Homogénéisation des signaux isotopiques, 18O et 3H, dans un système hydrologique de haute montagne : la Vallée d'Aoste (Italie)

L'analyse de l'origine et de la dynamique des écoulements souterrains dans l'aquifère du milieu alluvial de la plaine d'Aoste (Italie) a été menée en étudiant les teneurs isotopiques (18O et 3H) des eaux sur l'ensemble du système hydrologique. La démarche a consisté en un suivi isotopique des précipitations pluvio-neigeuses, des sources de versants, du réseau de surface et de l'aquifère alluvial, complété par des analyses ponctuelles concernant l'horizon superficiel des glaciers et les sous-écoulements glaciaires. Le signal d'entrée en 18O porté par les précipitations présente une grande variabilité liée au contexte orographique (effet d'écran) et climatique (pluie ou neige). Celle-ci est mise en évidence par les changements saisonniers du gradient 18O/altitude. En moyenne annuelle (1994), ce gradient établi en Vallée d'Aoste à partir de mesures sur les précipitations récoltées entre 300 et 3500 m d'altitude (sur huit stations) est de - 0.18 ± 0.02 ‰ pour 100 m, avec un écart-type (s) des valeurs de ± 4,8 ‰. L'ensemble des résultats en 18O montre au cours du cycle hydrologique, un amortissement à la fois important et progressif du signal d'entrée fourni par les précipitations. Cet amortissement, de l'ordre de 30 fois dans l'aquifère alluvial (sigma=± 0.15 ‰), est particulièrement sensible au niveau de la glace et des sous-écoulements glaciaires. En ce qui concerne les résultats en 3H, les teneurs mesurées dans les précipitations se révèlent être étroitement liées avec l'origine et la trajectoire des masses d'air humide. Par ailleurs, on note une bonne concordance entre les temps de séjour des eaux dans l'aquifère alluvial calculés à partir des valeurs en 18O et ceux fournis par le 3H.The hydrogeological study of the alluvial aquifer of the Aosta plain (Italy) is chosen as one of the most appropriate examples representative of the Italian-French-Swiss Alps. This study has been carried out using two environmental isotopes (18O and 3H) for groundwater samples taken from this aquifer in order to shed light on the origin of water and the hydrodynamic characteristics of the aquifer.The surface area of this aquifer is 70 km_ and mean elevation ranges between 400 and 700 m (asl). This surface area constitutes a part of the watershed area that amounts 2400 km_ with a mean elevation of 2200 m (asl). The watershed possesses several mountain peaks, Mt. Blanc, Mt. Cervin, Mt. Grand Paradis, the elevation of which rise to over 4000 m.The input signal, quantitative and qualitative as well, provided by the precipitation shows a wide variability linked to both orographic (screen effect) and climatic (rain or snow) influences. This variability is marked by differences in the 18O/altitude gradient, which is seasonally dependent. A unique and linear relation is observed during spring and summer ; in autumn and winter results show an important gradient up to 2000 m but a less important one for higher altitudes.The mean annual (1994) gradient of - 0.18 ± 0.02 ‰ for 100 m is determined in Aosta valley for altitudes between 300 and 3500 m, and the standard deviation (sigma) of the mean volume-weighted value for precipitation is ± 4.8 ‰. Furthermore, the 18O values measured in the alluvial aquifer have shown a very low dispersion (sigma=± 0.15 ‰), which corresponds to a buffering effect of a factor 30. These results evidenced, thus, an homogenization process within the different water bodies.To analyze this homogenization process, the different components of the hydrologic system have been studied, i.e. the monitoring of the springs and runoff waters, with complementary local measurements of the upper part of ice cores and the glacier underflows. Using standard deviations (sigma) as criteria for the homogenization process, one can see a large and progressive decrease along the hydrological cycle, with a special amplitude in ice cores and glacier underflows : precipitation (± 4.8 ‰), ice core (± 0.8 ‰), glacier underflow (± 0.10 ‰), spring (± 0.15 ‰), surface runoff network (± 0.3 ‰), alluvial aquifer (± 0.15 ‰).In ice cores, the different process : freezing and thawing, compression, and vapor / liquid / solid exchanges have caused the 18O homogenization. Dealing with the springs on the slopes of the valley, the preferential flow paths linked to the fracturation lead to a mixing of waters and hence to a very buffered outflow signal. The combined effect of all these explains the stability and the uniformity of the data found in the alluvial water body.As far as the 3H concentrations are concerned, the values measured are tightly linked with the origin and the transport of humid air masses. For closely spaced stations, a significant difference in the input signal has been correlated to various climatic influences. Using 3H data from the Thonon-les-Bains station (included in the WMO-IAEA observation network) as input, the calculated transit times of 2.5 to 7.5 years are very close to those calculated with 18O, i.e. 4 to 7 years

[turner Syndrome: Psychosocial Aspects].

Turner syndrome's (TS) incidence is about 1:2,130 live female births and its most important clinical features are short stature and gonadal dysgenesis, leading to primary amenorrhea, delayed pubertal development and infertility. Congenital and acquired anomalies and a great variety of dysmorphic signs can also be observed. Thus, many characteristics and symptoms may have bad consequences in the psychosocial aspects of the patients with TS. The objective of this paper is to review the literature on psychosocial aspects of TS, mainly the psychological effect caused by short stature, delayed pubertal development and infertility, self-esteem, social aspects, gender identity, sexual functioning, love relationships, family relationships, cognitive functioning, psychiatric diseases and the presence of a chronic disease. General remarks on psychological follow-up of the patients are also made.49157-6

Quantitative Metabolomics by 1H-NMR and LC-MS/MS Confirms Altered Metabolic Pathways in Diabetes

Insulin is as a major postprandial hormone with profound effects on carbohydrate, fat, and protein metabolism. In the absence of exogenous insulin, patients with type 1 diabetes exhibit a variety of metabolic abnormalities including hyperglycemia, glycosurea, accelerated ketogenesis, and muscle wasting due to increased proteolysis. We analyzed plasma from type 1 diabetic (T1D) humans during insulin treatment (I+) and acute insulin deprivation (I-) and non-diabetic participants (ND) by 1H nuclear magnetic resonance spectroscopy and liquid chromatography-tandem mass spectrometry. The aim was to determine if this combination of analytical methods could provide information on metabolic pathways known to be altered by insulin deficiency. Multivariate statistics differentiated proton spectra from I- and I+ based on several derived plasma metabolites that were elevated during insulin deprivation (lactate, acetate, allantoin, ketones). Mass spectrometry revealed significant perturbations in levels of plasma amino acids and amino acid metabolites during insulin deprivation. Further analysis of metabolite levels measured by the two analytical techniques indicates several known metabolic pathways that are perturbed in T1D (I-) (protein synthesis and breakdown, gluconeogenesis, ketogenesis, amino acid oxidation, mitochondrial bioenergetics, and oxidative stress). This work demonstrates the promise of combining multiple analytical methods with advanced statistical methods in quantitative metabolomics research, which we have applied to the clinical situation of acute insulin deprivation in T1D to reflect the numerous metabolic pathways known to be affected by insulin deficiency

The chemistry and isotopic composition of waters in the low-enthalpy geothermal system of Cimino-Vico Volcanic District, Italy

Geothermal energy exploration is based in part on interpretation of the chemistry, temperature, and discharge rate of thermal springs. Here we present the major element chemistry and the δD, δ18O, 87Sr/86Sr and δ11B isoto- pic ratio of groundwater from the low-enthalpy geothermal system near the city of Viterbo in the Cimino-Vico volcanic district of west-Central Italy. The geothermal system hosts many thermal springs and gas vents, but the resource is still unexploited. Water chemistry is controlled by mixing between low salinity,HCO3-rich fresh waters (b24.2 °C) flowing in shallow volcanic rocks and SO4-rich thermal waters (25.3 °C to 62.2 °C) ascending from deep, high permeability Mesozoic limestones. The (equivalent) SO4/Cl (0.01–0.02), Na/Cl (2.82–5.83) and B/Cl ratios (0.02–0.38) of thermal waters differs from the ratios in other geothermal systems from Central Italy, probably implying a lack of hydraulic continuity across the region. The δ18O (−6.6‰ to −5.9‰) and δD (− 40.60‰ to − 36.30‰) isotopic composition of spring water suggest that the recharge area for the geothermal system is the summit region of Mount Cimino. The strontium isotope ratios (87Sr/86Sr) of thermal waters (0.70797–0.70805) are consistent with dissolution of the Mesozoic evaporite-carbonate units that constitute the reservoir, and the ratios of cold fresh waters mainly reflect shallow circulation through the volcanic cover and some minor admixture (b10%) of thermal water as well. The boron isotopic composition (δ11B) of fresh waters (−5.00 and 6.12‰) is similar to that of the volcanic cover, but the δ11B of thermal waters (−8.37‰ to − 4.12‰) is a mismatch for the Mesozoic reservoir rocks and instead reflects dissolution of secondary boron min- erals during fluid ascent through flysch units that overlie the reservoir. A slow and tortuous ascent enhances ex- traction of boron but also promotes conductive cooling, partially masking the heat present in the reservoir. Overall data from this study is consistent with previous studies that concluded that the geothermal system has a large energy potential

Incorporating the social dimension into hydrogeochemical investigations for rural development: the Bir Al-Nas approach for socio-hydrogeology

A replicable multidisciplinary approach is presented for science-based groundwater management practices: Bir Al-Nas (Bottom-up IntegRated Approach for sustainabLe grouNdwater mAnagement in rural areaS). This approach provides a practical example of the concept of “socio-hydrogeology”, a way of incorporating the social dimension into hydrogeological investigations, as reinforced by the translation of the Arabic bir al-nas: “the people’s well”. To achieve this, hydrogeologists act as “social hydrologists” during their monitoring activities, which often bring them into contact with local communities and end users (and polluters) of water. Not only can they retrieve reliable information about traditional know-how and local issues, but they can also change the public perception of science/scientists to create the basis for mutual collaboration and understanding in view of implementing improved integrated groundwater management. The final outcomes are expected to be an increased awareness of communities at the local level and a clear understanding of their water issues and needs from the very early stages of the investigation. Although the importance of using such methods in groundwater analysis and management is widely recognized, hydrogeological investigations are currently dominated by sectorial approaches that are easier to implement but less sustainable. The pressure of population growth, the shift towards more water-dependent economies, climate change and its impact on water availability will require scientists to use a more integrated approach, such as Bir Al-Nas, when dealing with increasing water pollution and water-scarcity issues.A replicable multidisciplinary approach is presented for science-based groundwater management practices: Bir Al-Nas (Bottom-up IntegRated Approach for sustainabLe grouNdwater mAnagement in rural areaS). This approach provides a practical example of the concept of "socio-hydrogeology", a way of incorporating the social dimension into hydrogeological investigations, as reinforced by the translation of the Arabic bir al-nas: "the people's well". To achieve this, hydrogeologists act as "social hydrologists" during their monitoring activities, which often bring them into contact with local communities and end users (and polluters) of water. Not only can they retrieve reliable information about traditional know-how and local issues, but they can also change the public perception of science/scientists to create the basis for mutual collaboration and understanding in view of implementing improved integrated groundwater management. The final outcomes are expected to be an increased awareness of communities at the local level and a clear understanding of their water issues and needs from the very early stages of the investigation. Although the importance of using such methods in groundwater analysis and management is widely recognized, hydrogeological investigations are currently dominated by sectorial approaches that are easier to implement but less sustainable. The pressure of population growth, the shift towards more water-dependent economies, climate change and its impact on water availability will require scientists to use a more integrated approach, such as Bir Al-Nas, when dealing with increasing water pollution and water-scarcity issues