Nutrients such as amino acids play key roles in shaping the metabolism of microorganisms in natural environments and in host–pathogen interactions. Beyond taking part to cellular metabolism and to ...protein synthesis, amino acids are also signaling molecules able to influence group behavior in microorganisms, such as biofilm formation. This lifestyle switch involves complex metabolic reprogramming controlled by local variation of the second messenger 3′, 5′‐cyclic diguanylic acid (c‐di‐GMP). The intracellular levels of this dinucleotide are finely tuned by the opposite activity of dedicated diguanylate cyclases (GGDEF signature) and phosphodiesterases (EAL and HD‐GYP signatures), which are usually allosterically controlled by a plethora of environmental and metabolic clues. Among the genes putatively involved in controlling c‐di‐GMP levels in P. aeruginosa, we found that the multidomain transmembrane protein PA0575, bearing the tandem signature GGDEF‐EAL, is an l‐arginine sensor able to hydrolyse c‐di‐GMP. Here, we investigate the basis of arginine recognition by integrating bioinformatics, molecular biophysics and microbiology. Although the role of nutrients such as l‐arginine in controlling the cellular fate in P. aeruginosa (including biofilm, pathogenicity and virulence) is already well established, we identified the first l‐arginine sensor able to link environment sensing, c‐di‐GMP signaling and biofilm formation in this bacterium.
Reprogramming of cellular metabolism towards de novo serine production fuels the growth of cancer cells, providing essential precursors such as amino acids and nucleotides and controlling the ...antioxidant and methylation capacities of the cell. The enzyme serine hydroxymethyltransferase (SHMT) has a key role in this metabolic shift, and directs serine carbons to one-carbon units metabolism and thymidilate synthesis. While the mitochondrial isoform of SHMT (SHMT2) has recently been identified as an important player in the control of cell proliferation in several cancer types and as a hot target for anticancer therapies, the role of the cytoplasmic isoform (SHMT1) in cancerogenesis is currently less defined. In this paper we show that SHMT1 is overexpressed in tissue samples from lung cancer patients and lung cancer cell lines, suggesting that, in this widespread type of tumor, SHMT1 plays a relevant role. We show that SHMT1 knockdown in lung cancer cells leads to cell cycle arrest and, more importantly, to p53-dependent apoptosis. Our data demonstrate that the induction of apoptosis does not depend on serine or glycine starvation, but is because of the increased uracil accumulation during DNA replication.
The clinical manifestations of ADPKD are related to the growth of renal cysts. Renal volume has been recognised as the biomarker that is able to identify those patients at risk of complications ...(hypertension and haematuria) and at risk of progression to End Stage Renal Disease (ESRD). Recently, several scores have been introduced to predict the evolution of ADPKD. The Mayo Clinic Group developed a classification based on renal volume as measured by CT or MRI and corrected for age and height (Ht-TKV); this allowed predicting the evolution of the disease, but it has not been fully validated so far. In addition, it is used to identify patients labelled as “fast progressors” and eligible for Tolvaptan therapy according to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) recommendations. We studied 80 patients who underwent MRI and had been classified as ADPKD typical form (class 1A-1E). A significant correlation between renal volume, hypertension, and low GFR was found (p<0.005). A progressive increase in disease severity has been found across the different Mayo classes; 41.2% were eligible for Tolvaptan therapy. The results demonstrate that the Mayo method is easy to perform and provides valid information in order to identify with rapidly progressing disease.
The Campanian Volcanic Subprovince is part of the classic western potassic volcanic province of the Italian Peninsula. The Campanian volcanic products show the effects of shallow assimilation and ...fractional crystallisation, and the contribution of regional crustal sources (e.g., Hercynian basement–Calabrian crust). The Roccamonfina, Campi Flegrei, and Ventotene volcanic rocks are characterised by wide isotopic and geochemical variations. Such variations appear to reflect both AFC processes and chemical heterogeneity in the upper mantle that may be linked to subduction processes. Mixing curves (Th/Ce–, Ba/K– and Eu/Eu*–
143Nd/
144Nd) linking sediments and mantle end-members account for the variations in the Campanian Subprovince volcanic rocks with a sediment contribution of 2-10%. The upper mantle sources for the low- and high-K rocks at Roccamonfina have been constrained on the basis of a multi-element normalised diagram. The two sources require different amounts of sediment in the mantle wedge (LK∼2% versus HK∼10%) and a fluid component probably from altered ocean crust to explain the fluid mobile elements. Low-K Roccamonfina rocks are geochemically similar to those from Campi Flegrei, Ventotene, and Somma-Vesuvius, suggesting a similar proportion of sediment in their upper mantle source regions.
This work integrates new geochemical data with the numerous published analyses on rocks from the Mt. Somma-Vesuvius volcano. New quantitative models for the evolution of magma source regions and ...magma at different depths are proposed. The origin of the Somma-Vesuvius parental magma is modeled as 0.05-0.1 melt fractions of a MORB-type source composed of 54% olivine, 30% orthopyroxene, 10% clinopyroxene, 1% garnet, and 4% amphibole, and 1-5% sediment introduced through the adjacent arc system. The excess concentrations of Rb, Ba, K, and Sr are attributed to a subduction-related fluid phase. Major and trace element concentrations, coupled with Sr-Nd-Pb isotope signatures suggest that the bulk composition of sediments being subducted below southern Italy is similar to that of the carbonate rich sediment columns described by Plank and Langmuir (1998) and Vroon et al. (1995). Furthermore, it appears that the sediment contribution was introduced as a partial melt, which would account for some geochemical patterns, such as 143 Nd/ 144 Nd versus Th/Ce. The EC-AFC model (Spera and Bohrson, 2001) is then used to track the evolution of Somma-Vesuvius magmas. The results are consistent with the melting of crustal Hercynian basement at depths of 12 and >20 km (De Natale et al., 2001). Such a model is also consistent with the thermal model of Annen and Sparks (2002) for the evolution of magmatic provinces. Here, magmas from the upper mantle form a melt intrusion and storage zone at 12 to >20 km allowing for crustal melting to take place. At Vesuvius, Plinian eruptions involve the first magma withdrawn from a deep magma reservoir. Interplinian eruptions involve reduced volumes of magma stored over a larger depth range until the volcanic activity stops. This suggests that little magma is left in the melt intrusion and storage zone. A new cycle is started by a Plinian event when new magma rises from the upper mantle and is emplaced in the lower crust. PUBLICATION ABSTRACT
Somma-Vesuvius is a composite volcano on the southern margin of the Campanian Plain which has been active during the last 39 ka BP and which poses a hazard and risk for the main population center ...situated around its base. The fieldwork and data analysis on which this report is based are related to the eight Plinian eruptions that have occurred in the last 25 ka. For six of these eruptions, the fallout products were dispersed to the east–northeast, whereas deposits from the 25 ka Codola and AD 79 eruptions were dispersed in a south-easterly direction. During the AD 79 eruption, in particular, the dispersal axis migrated from the east–southeast to south–southeast. New high level wind data collected at the weather stations of the Aereonautica Militare data centres at Pratica di Mare (Rome) and Brindisi have been compiled to characterize the prevailing wind condition in the Somma-Vesuvius region. The common north-easterly dispersal directions of the Plinian eruptions are consistent with the distribution of ash by high-altitude winds from October to June. In contrast, the south-easterly trend of the AD 79 products appears to be anomalous, because the eruption is conventionally believed to have occurred on the 24th of August, when its southeast dispersive trend falls in a transitional period from the Summer to Autumnal wind regimes. In fact, the AD 79 tephra dispersive direction towards the southeast is not in agreement with the June–August high-altitude wind directions that are toward the west. This poses serious doubt about the date of the eruption and the mismatch raises the hypothesis that the eruption occurred in the Autumnal climatic period, when high-altitude winds were also blowing towards the southeast. New archaeological findings presented in this study definitively place the date of eruption in the Autumn, in good agreement with the prevailing high-altitude wind directions above Somma-Vesuvius.
Moreover, wind data and past eruptive behaviour indicate that a future subplinian–Plinian eruption at Somma-Vesuvius has a good chance to occur when winds are blowing toward the eastern sectors (northeast–southeast), in the Autumnal–Winter period, and only a slightest chance in Summer, when winds are blowing toward the west, depositing ash fallout on the Neapolitan community.
These days, smartphones are popular commodities among students in high school and college. Students carry their devices all the time, so why not use such a popular electronic device to measure ...physical quantities such as g in physics labs? In this work, we report a “multiple tasking” method, a measurement technique that we came up with, for this very purpose. The method is simple: A person holds a ball using one hand and prepares to activate a recording function using another hand. Then the person drops the metal ball and starts the voice memo simultaneously. The time the ball takes to reach the floor is measured by reviewing the sound amplitude recorded, and the magnitude of g is calculated from the time. The error due to the auditory reaction time alone could be about 0.15 s, but we could measure the time in a 0.02-s range at 95% confidence level. A “using sound” technique to measure g was introduced before, but given that triggers such as a latch or something equivalent could introduce larger errors due to the device resolutions, we came up with our own.
Toll-like receptors (TLRs) are known to play a key role in the innate immune system particularly in inflammatory response against invading pathogens. Recent reports strongly indicate that they play ...important roles in cancer cells. Prostate cancer represents one of the most common cancer for which no cure is available once metastatic and androgen refractory. Since TLR3 has been recently suggested as a possible therapeutic target in some cancer cell lines, we studied TLR3 expression and functionality in two human prostate cancer cell lines, LNCaP and PC3. We report that both cell lines express TLR3 and that the TLR3 agonist poly (I:C) activates mitogen-activated protein kinases and induces inhibition of proliferation as well as caspase-dependent apoptosis. By using pharmacological and genetic approaches, we demonstrate the involvement of TLR3 in poly (I:C)-induced effects. We also show that a novel interferon-independent pathway involving protein kinase C (PKC)-α activation, upstream of p38 and c-jun N-terminal kinase, is responsible for poly (I:C) pro-apoptotic effects on LNCaP cells. To our knowledge, this is the first report describing a role of PKC-α in poly (I:C)-mediated apoptosis. The comprehension of the mechanisms underlying TLR3-mediated apoptosis can contribute tools to develop new agonists useful for the treatment of prostate cancer.
Somma-Vesuvius is an alkaline volcano whose products (pumice, scoria and lava) have alkaline (Na2O + K2O) contents between 6 and 16 wt%, Mg number <50, SiO2 59-47 wt% and MgO 0-7.8 wt% (more than 50% ...of the samples have a content <2 wt%). Immobile-element ratios (Th/Yb, Ta/Yb, Ce/Yb) indicate a shoshonitic character, while the K2O content (4-10 wt%) is characteristic of ultrapotassic rocks. The behavior of selected metals is discussed by grouping them on the basis of the stratigraphic sequence and differentiating the volcanic activity between plinian and interplinian (Rolandi et al., 1998; Ayuso et al., 1998). This allows observation of the variation within each formation from 25.000 y. BP to the last historic eruptive cycle (1631-1944 AD). The main processes to explain the wide distribution of the data presented are fractional crystallization of a mantle-derived magma, magma mixing, and contamination with heterogeneous lower and/or upper crust. Variation diagrams distinguish different behavior for groups of metals: Ag (0.01-0.2 ppm), Mo (1-8.8 ppm), W (1.3-13 ppm), Pb (16-250 ppm), Sb (0.2-2.6 ppm), Sc (0.2-61 ppm), Li (15-140 ppm) and Be (1-31 ppm) increase with increasing differentiation and tend to correlate with the incompatible trace elements (Th, Hf, etc). Cu (10-380 ppm), Au (2-143 ppb), Co (0.7-35.1 ppm) and Fe (1.3-6.2 wt%) decrease towards advanced stage of differentiation. Iron also identifies three magmatic groups. The ratio Fe3+/Fe2+ ranges between 0.2 and 1.8, and Fe2O3/(Fe2O3 + FeO) ranges between 0.2 and 0.8, giving rise to an oxidized environment; exceptions are in the samples belonging to the interplinian formations: I, II, medieval and 1631-1994 AD. Fluorine ranges between 0.1 and 0.4 wt% for the complete Mt. Somma-Vesuvius activity, except for the Ottaviano and Avellino plinian (0.8 wt%) events. Chlorine has a wider range, from 0.1 wt% to 1.6 wt%. Mt Somma-Vesuvius has some features similar to those of mineralized alkaline magmatic systems which coincide with the transition between subduction-related compression and extension-related to continental rifting. We infer that a prospective time for the formation of mineralization at Mt Somma-Vesuvius was during the 1631-1944 eruptive period.
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