162 research outputs found
Hygrotermic Treatment of Chesnut Logs Infected with Cryphonectria parasitica
Due to the reduced availability of large-sized chestnut logs in Europe, many European timber industries
currently get their supplies from non-European countries, mainly from the Caucasian region, which are often not
immune to chestnut blight. Given the high risk of introducing new virulent strains incompatible with local hypovirulent
ones, the European Union regulation requires that chestnut logs, imported from so-called “third party” nations where
Cryphonectria parasitica is present, reach the European boundaries bark free: this prevents the production of veneers,
which are highly remunerative, but whose first workmanship phases require barked logs. Following a multilevel
investigation, the authors propose a stem-flow protocol that can devitalise the parasite in barked logs while
preserving the commodity characteristics of the wood, through a fast, simple and low-cost treatment, that can be
performed at the European borders whenever C. parasitica is or might be present
Correction: JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction
This Article was originally published under Nature Researchʼs License to Publish, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the Article have been modified accordingly
JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction
The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Here, we found that such alterations do not depend on the Fas/FasL pathway, which is instead only lately activated to amplify the cell death cascade. Instead, such alterations are primarily dependent on the MAPK proteins JNK1 and ERK1/2, which, in turn, regulate the activity of the pro-fission protein Drp1 and the pro-apoptotic factor Bim. The latter regulates cristae disassembly and cooperate with Drp1 to mediate the Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome-C release. Interestingly, we found that Bim is also downregulated in T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, this alteration favouring their escape from AICD-mediated control
Choline Kinase Alpha Inhibition by EB-3D Triggers Cellular Senescence, Reduces Tumor Growth and Metastatic Dissemination in Breast Cancer
Choline kinase (ChoK) is the first enzyme of the Kennedy pathway leading to the
biosynthesis of phosphatidylcholine (PtdCho), the most abundant phospholipid in eukaryotic cell
membranes. EB-3D is a novel choline kinase 1 (ChoK 1) inhibitor with potent antiproliferative
activity against a panel of several cancer cell lines. ChoK 1 is particularly overexpressed and
hyperactivated in aggressive breast cancer. By NMR analysis, we demonstrated that EB-3D is able to
reduce the synthesis of phosphocholine, and using flow cytometry, immunoblotting, and q-RT-PCR
as well as proliferation and invasion assays, we proved that EB-3D strongly impairs breast cancer cell
proliferation, migration, and invasion. EB-3D induces senescence in breast cancer cell lines through
the activation of the metabolic sensor AMPK and the subsequent dephosphorylation of mTORC1
downstream targets, such as p70S6K, S6 ribosomal protein, and 4E-BP1. Moreover, EB-3D strongly
synergizes with drugs commonly used for breast cancer treatment. The antitumorigenic potential
of EB-3D was evaluated in vivo in the syngeneic orthotopic E0771 mouse model of breast cancer,
where it induces a significant reduction of the tumor mass at low doses. In addition, EB-3D showed
an antimetastatic effect in experimental and spontaneous metastasis models. Altogether, our results
indicate that EB-3D could be a promising new anticancer agent to improve aggressive breast cancer
treatment protocols.This work was supported by funds from Istituto di Ricerca Pediatrica (IRP)-Città della Speranza and
Cassa di Risparmio di Padova e Rovigo—CARIPARO Foundation (project IRP13/05) and by the University of
Granada, (Cei-Biotic project CEI2013-MP-1), and Associazione Italiana per la Ricerca sul Cancro (AIRC) MFAG
18459 grant (R.R.). E.M. was supported by AIRC (21101) and V.S. by FIRC (16616) fellowships
Annexin 2A sustains glioblastoma cell dissemination and proliferation.
Glioblastoma (GBM) is the most devastating tumor of the brain, characterized by an almost inevitable tendency to recur after intensive treatments and a fatal prognosis. Indeed, despite recent technical improvements in GBM surgery, the complete eradication of cancer cell disseminated outside the tumor mass still remains a crucial issue for glioma patients management. In this context, Annexin 2A (ANXA2) is a phospholipid-binding protein expressed in a variety of cell types, whose expression has been recently associated with cell dissemination and metastasis in many cancer types, thus making ANXA2 an attractive putative regulator of cell invasion also in GBM.Here we show that ANXA2 is over-expressed in GBM and positively correlates with tumor aggressiveness and patient survival. In particular, we associate the expression of ANXA2 to a mesenchymal and metastatic phenotype of GBM tumors. Moreover, we functionally characterized the effects exerted by ANXA2 inhibition in primary GBM cultures, demonstrating its ability to sustain cell migration, matrix invasion, cytoskeletal remodeling and proliferation. Finally, we were able to generate an ANXA2-dependent gene signature with a significant prognostic potential in different cohorts of solid tumor patients, including GBM.In conclusion, we demonstrate that ANXA2 acts at multiple levels in determining the disseminating and aggressive behaviour of GBM cells, thus proving its potential as a possible target and strong prognostic factor in the future management of GBM patients
A Cretaceous carbonate delta drift in the Montagna della Maiella, Italy
The Upper Cretaceous (Campanian\u2013Maastrichtian) bioclastic wedge of the Orfento Formation in the Montagna della Maiella, Italy, is compared to newly discovered contourite drifts in the Maldives. Like the drift deposits in the Maldives, the Orfento Formation fills a channel and builds a Miocene delta-shaped and mounded sedimentary body in the basin that is similar in size to the approximately 350 km 2 large coarse-grained bioclastic Miocene delta drifts in the Maldives. The composition of the bioclastic wedge of the Orfento Formation is also exclusively bioclastic debris sourced from the shallow-water areas and reworked clasts of the Orfento Formation itself. In the near mud-free succession, age-diagnostic fossils are sparse. The depositional textures vary from wackestone to float-rudstone and breccia/conglomerates, but rocks with grainstone and rudstone textures are the most common facies. In the channel, lensoid convex-upward breccias, cross-cutting channelized beds and thick grainstone lobes with abundant scours indicate alternating erosion and deposition from a high-energy current. In the basin, the mounded sedimentary body contains lobes with a divergent progradational geometry. The lobes are built by decametre thick composite megabeds consisting of sigmoidal clinoforms that typically have a channelized topset, a grainy foreset and a fine-grained bottomset with abundant irregular angular clasts. Up to 30 m thick channels filled with intraformational breccias and coarse grainstones pinch out downslope between the megabeds. In the distal portion of the wedge, stacked grainstone beds with foresets and reworked intraclasts document continuous sediment reworking and migration. The bioclastic wedge of the Orfento Formation has been variously interpreted as a succession of sea-level controlled slope deposits, a shoaling shoreface complex, or a carbonate tidal delta. Current-controlled delta drifts in the Maldives, however, offer a new interpretation because of their similarity in architecture and composition. These similarities include: (i) a feeder channel opening into the basin; (ii) an excavation moat at the exit of the channel; (iii) an overall mounded geometry with an apex that is in shallower water depth than the source channel; (iv) progradation of stacked lobes; (v) channels that pinch out in a basinward direction; and (vi) smaller channelized intervals that are arranged in a radial pattern. As a result, the Upper Cretaceous (Campanian\u2013Maastrichtian) bioclastic wedge of the Orfento Formation in the Montagna della Maiella, Italy, is here interpreted as a carbonate delta drift
Functional Protein Network Activation Mapping Reveals New Potential Molecular Drug Targets for Poor Prognosis Pediatric BCP-ALL
Background: In spite of leukemia therapy improvements obtained over the last decades, therapy is not yet effective in all cases. Current approaches in Acute Lymphoblastic Leukemia (ALL) research focus on identifying new molecular targets to improve outcome for patients with a dismal prognosis. In this light phosphoproteomics seems to hold great promise for the identification of proteins suitable for targeted therapy.
Methodology/Principal Findings: We employed Reverse Phase Protein Microarrays to identify aberrantly activated proteins in 118 pediatric B-cell precursor (BCP)-ALL patients. Signal transduction pathways were assayed for activation/expression status of 92 key signalling proteins. We observed an increased activation/expression of several pathways involved in cell proliferation in poor clinical prognosis patients. MLL-rearranged tumours revealed BCL-2 hyperphosphorylation through AMPK activation, which indicates that AMPK could provide a functional role in inhibiting apoptosis in MLL-rearranged patients, and could be considered as a new potential therapeutic target. Second, in patients with poor clinical response to prednisone we observed the up-modulation of LCK activity with respect to patients with good response. This tyrosine-kinase can be down-modulated with clinically used inhibitors, thus modulating LCK activity could be considered for further studies as a new additional therapy for prednisone-resistant patients. Further we also found an association between high levels of CYCLIN E and relapse incidence. Moreover, CYCLIN E is more expressed in early relapsed patients, who usually show an unfavourable prognosis.
Conclusions/Significance: We conclude that functional protein pathway activation mapping revealed specific deranged signalling networks in BCP-ALL that could be potentially modulated to produce a better clinical outcome for patients resistant to standard-of-care therapies
Trophic strategy of Atlantirivulus riograndensis (Cyprinodontiformes: Rivulidae), a non-annual rivulid threatened by extinction, in a perennial environment, Brazil)
Rivulidae includes non-annual fish of perennial habitats and annual fish of temporary wetlands. The objective of this research was to investigate the trophic strategy of Atlantirivulus riograndensis in a perennial environment. Sampling occurred in an environmental conservation unit in the Pampa biome, Brazil. Quantification of the diet followed the volumetric method. Consumption of autochthonous material as the main food source of the species followed the pattern of Rivulidae. Species is zooplanktonic when young. Food spectrum is broadened and insectivorousness increases with ontogeny, revealing a specialist trend in the feeding strategy of A. riograndensis. The most diverse feeding occurs in the spring and summer seasons in which the presence of larger fish was more frequent than in other seasons. The increased consumption of microcrustaceans in the fall was related to smaller individuals, captured in greater quantities in this post-reproductive period. The lowest diversity of dietary items occurs during the winter and may reflect the lower diversity of food resources available in this season or the transition from juvenile to adult diet, with consumption of autochthonous Diptera by medium sized fish.Rivulidae inclui peixes não anuais de habitats perenes e peixes anuais de alagados temporários. O objetivo desta pesquisa foi investigar a estratégia trófica de Atlantirivulus riograndensis em um ambiente perene. A amostragem ocorreu em uma unidade de conservação ambiental no bioma Pampa, Brasil. A quantificação da dieta seguiu o método volumétrico. O consumo de material autóctone como principal recurso alimentar da espécie seguiu o padrão da família Rivulidae. A espécie é zooplanctívora quando juvenil. O espectro alimentar é ampliado e a tendência à insetivoria aumenta com a ontogenia, revelando traços especialistas na estratégia alimentar de A. riograndensis. A alimentação mais diversificada ocorreu na primavera e no verão, estações em que a presença dos peixes maiores foi frequente que em outras estações. O aumento no consumo de microcrustáceos no inverno foi relacionado aos indivíduos menores, capturados em maior quantidade neste período pós-reprodutivo. A menor diversidade de itens alimentares ocorreu durante o inverno e pode refletir uma menor diversidade de recursos alimentares disponíveis nesta época do ano ou a transição da dieta de juvenil para adulto, com consumo de Diptera autóctone por peixes de tamanho médio
The behaviour of giant clams (Bivalvia: Cardiidae: Tridacninae)
Giant clams, the largest living bivalves, live in close association with coral reefs throughout the Indo-Pacific. These iconic invertebrates perform numerous important ecological roles as well as serve as flagship species—drawing attention to the ongoing destruction of coral reefs and their associated biodiversity. To date, no review of giant clams has focussed on their behaviour, yet this component of their autecology is critical to their life history and hence conservation. Almost 100 articles published between 1865 and 2014 include behavioural observations, and these have been collated and synthesised into five sections: spawning, locomotion, feeding, anti-predation, and stress responses. Even though the exact cues for spawning in the wild have yet to be elucidated, giant clams appear to display diel and lunar periodicities in reproduction, and for some species, peak breeding seasons have been established. Perhaps surprisingly, giant clams have considerable mobility, ranging from swimming and gliding as larvae to crawling in juveniles and adults. Chemotaxis and geotaxis have been established, but giant clams are not phototactic. At least one species exhibits clumping behaviour, which may enhance physical stabilisation, facilitate reproduction, or provide protection from predators. Giant clams undergo several shifts in their mode of acquiring nutrition; starting with a lecithotrophic and planktotrophic diet as larvae, switching to pedal feeding after metamorphosis followed by the transition to a dual mode of filter feeding and phototrophy once symbiosis with zooxanthellae (Symbiodinium spp.) is established. Because of their shell weight and/or byssal attachment, adult giant clams are unable to escape rapidly from threats using locomotion. Instead, they exhibit a suite of visually mediated anti-predation behaviours that include sudden contraction of the mantle, valve adduction, and squirting of water. Knowledge on the behaviour of giant clams will benefit conservation and restocking efforts and help fine-tune mariculture techniques. Understanding the repertoire of giant clam behaviours will also facilitate the prediction of threshold levels for sustainable exploitation as well as recovery rates of depleted clam populations
- …