The Viperidae venoms are composed of a mixture of constituents with enzymatic and non-enzymatic actions, which act on ultrastructural components of cells and tissues. Here, the number of ...mitochondria, mitochondrial area and the number of mitochondrial cristae from adrenal glands cortex treated with snake venoms were tested after 3, 6 and 24 hours of venom injections. The mitochondria quantitative changes showed a statistically significant decrease, in the number of mitochondria past 3, 6 and 24 h. There was an increase in the mitochondrial area after 6 h, where Crotalus vegrandis venom did not present significant differences with Crotalus pifanorum or Bothrops venezuelensis venoms. After 24 h, there was an escalation of mitochondrial area in all tested venoms. The number of mitochondrial cristae after 3 h did not present important differences with the control treatment. After 6 h, the number of mitochondrial cristae initiated to decrease under the activities of the 3 venoms action, until 24 h of observation. In the qualitative observations it was possible to witness an intense damage of the mitochondria, with loss and swelling of membranes, disappearance of cristae and the appearance of myelin figures, which started at 3 h after the Crotalus and Bothrops venoms injections. These damages probably were due to cytotoxic effects of phospholipases, metalloproteases and/or other proteolytic activities present in Viperidae snake venoms, being more evident in Crotalus venoms. As far as we know, these results define a novel finding that suggest that Viperidae snake venoms are extremely toxic to mammalian mitochondria.
We present time-delay measurements for the new quadruple imaged quasar DES J0408−5354, the first quadruple imaged quasar found in the Dark Energy Survey (DES). Our result is made possible by ...implementing a new observational strategy using almost daily observations with the MPIA 2.2 m telescope at La Silla observatory and deep exposures reaching a signal-to-noise ratio of about 1000 per quasar image. This data qualityallows us to catch small photometric variations (a few mmag rms) of the quasar, acting on temporal scales much shorter than microlensing, and hence making the time delay measurement very robust against microlensing. In only seven months we very accurately measured one of the time delays in DES J0408−5354: Δ
t
(AB) = −112.1 ± 2.1 days (1.8%) using only the MPIA 2.2 m data. In combination with data taken with the 1.2 m
Euler
Swiss telescope, we also measured two delays involving the D component of the system Δ
t
(AD) = −155.5 ± 12.8 days (8.2%) and Δ
t
(BD) = −42.4 ± 17.6 days (41%), where all the error bars include systematics. Turning these time delays into cosmological constraints will require deep
Hubble
Space Telescope (HST) imaging or ground-based adaptive optics (AO), and information on the velocity field of the lensing galaxy.
The olive tree is one of the most important crops in Spain, and the main one in the region of Andalusia. Most orchards are rain-fed, with high slopes where conventional tillage (CT) is the primary ...soil management system used. These conditions lead to high erosion and a significant transport of organic carbon (OC). Moreover, soil tillage accelerates the oxidation of the OC. Cover crops (CC) are the conservation agriculture (CA) approach for woody crops. They are grown in-between tree rows to protect the soil against water erosion and their organic residues also help to increase the soil carbon (C) sink. Soil and OC losses associated to the sediment were measured over four seasons (2003-07) using micro-plots for the collection of runoff and sediment in five experimental fields located in rain-fed olive orchards in Andalusia. Two soil management systems were followed, CC and CT. Furthermore, the changes in soil C in both systems were analyzed at a depth of 0-25 cm. CC reduced erosion by 80.5%, and also OC transport by 67.7%. In addition, Cover crops increased soil C sink by 12.3 Mg ha-1 year-1 of carbon dioxide (CO2) equivalent, with respect to CT. CC in rainfed olive orchards in a Mediterranean climate could be an environmental friendly and profitable system for reducing erosion and increasing the soil C sink. However, C fixing rate is not regular, being very high for the initial years after shifting from CT to CC and gradually decreasing over time.
In this study, the effect of chitosan alkali treatment supported onto agave fiber‐high density polyethylene composites over their Pb(II) adsorption properties was evaluated. The chitosan was placed ...in a beaker with a solution of NaOH bubbling air for 24 hours and controlling the pH around 10. Afterwards the chitosan was washed, filtered and dried. Composite pellets with 30% of agave fibers and 70% of high density polyethylene (HDPE) were coated with untreated chitosan (UC) and treated chitosan (TC) to be used in batch Pb(II) adsorption experiments. The results showed that the adsorption process was described by the Langmuir behavior and with a pseudo second order kinetics for both, UC and TC composites. The maximum adsorption capacities were obtained at pH = 5 with values of 2.08 and 2.44 mg/g composite for UC and TC composites respectively which represents an improvement of 17% by the alkali treatment. FTIR and NMR analysis were also carried out for a better understanding of the adsorption process.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, requiring novel treatments to target both cancer cells and cancer stem cells (CSCs). Altered splicing is emerging as both a novel ...cancer hallmark and an attractive therapeutic target. The core splicing factor SF3B1 is heavily altered in cancer and can be inhibited by Pladienolide-B, but its actionability in PDAC is unknown. We explored the presence and role of SF3B1 in PDAC and interrogated its potential as an actionable target.
SF3B1 was analyzed in PDAC tissues, an RNA-seq dataset, and publicly available databases, examining associations with splicing alterations and key features/genes. Functional assays in PDAC cell lines and PDX-derived CSCs served to test Pladienolide-B treatment effects in vitro, and in vivo in zebrafish and mice.
SF3B1 was overexpressed in human PDAC and associated with tumor grade and lymph-node involvement. SF3B1 levels closely associated with distinct splicing event profiles and expression of key PDAC players (KRAS, TP53). In PDAC cells, Pladienolide-B increased apoptosis and decreased multiple tumor-related features, including cell proliferation, migration, and colony/sphere formation, altering AKT and JNK signaling, and favoring proapoptotic splicing variants (BCL-XS/BCL-XL, KRASa/KRAS, Δ133TP53/TP53). Importantly, Pladienolide-B similarly impaired CSCs, reducing their stemness capacity and increasing their sensitivity to chemotherapy. Pladienolide-B also reduced PDAC/CSCs xenograft tumor growth in vivo in zebrafish and in mice.
SF3B1 overexpression represents a therapeutic vulnerability in PDAC, as altered splicing can be targeted with Pladienolide-B both in cancer cells and CSCs, paving the way for novel therapies for this lethal cancer.
Neuroblastoma (NB) is a remarkably heterogenic childhood tumor of the sympathetic nervous system with clinical behavior ranging from spontaneous regression to poorly differentiated tumors and ...metastasis. MYCN is amplified in 20% of cases and correlates with an undifferentiated, aggressive phenotype and poor prognosis. Estrogen receptor alpha (ERα) and the nerve growth factor (NGF) receptors TrkA and p75NTR are involved in neuronal differentiation and survival. We have previously shown that MYCN, via miR-18a, targets ERα in NB cells. Here, we demonstrate that interference with miR-18a or overexpression of ERα is sufficient to induce NGF signaling and to modulate both basal and NGF-induced neuronal differentiation in MYCN-amplified NB cells. Proteomic analysis confirmed an increase of neuronal features and showed that processes linked to tumor initiation and progression were inhibited upon ERα overexpression. Indeed, ectopic ERα expression was sufficient to inhibit metabolic activity and tumorigenic processes, including glycolysis, oxidative phosphorylation, cell viability, migration, and anchorage independent growth. Importantly, ERα overexpression reduced tumor burden in NB mouse models and high ERα levels were linked to improved survival in patients. In addition to ERα, several other nuclear hormone receptors (NHRs), including the glucocorticoid and the retinoic acid receptors, correlated with clinical markers for favorable and low-stage NB disease. Our data suggest that MYCN targets ERα and thereby NGF signaling to maintain an undifferentiated and aggressive phenotype. Notably, we identified the estrogen–NGF crosstalk, as well as a set of other NHRs, as potential prognostic markers and targets for therapeutic strategies against NB.
La artroscopia de muñeca ha permitido el diagnóstico y el tratamiento de las fracturas a nivel de la muñeca, así como de las lesiones asociadas a estas.
Existen lesiones asociadas a las fracturas de ...escafoides que pueden condicionar el éxito del tratamiento y llevarnos a resultados poco satisfactorios y a un retraso en la recuperación funcional.
Se estudiaron y cuantificaron las lesiones asociadas encontradas en 17 casos con fractura aguda de cintura de escafoides que fueron tratadas mediante reducción y colocación artroscópica de un tornillo canulado de escafoides. Se analizaron los resultados del tratamiento con la escala de muñeca de la Clínica Mayo (Mayo Wrist Score) y la consolidación con radiografías simples.
Se diagnosticaron lesiones asociadas de tejidos blandos y/o condrales/osteocondrales en 14 casos, lo que supone un 82% de los casos. Las lesiones más frecuentemente encontradas fueron las lesiones del ligamento escafolunar (53%) en diferentes grados, las lesiones del fibrocartílago triangular (35,3%) y las lesiones osteocondrales (35,3%). Los resultados funcionales (Mayo Wrist Score) fueron excelentes o buenos en 13 de los pacientes (76,5%), en 3 casos (17,5%) los resultados fueron regulares y solo un caso (5,9%) tuvo un pobre resultado.
La artroscopia ofrece una valoración completa de la muñeca y consigue diagnosticar lesiones asociadas a las fracturas de cuello de escafoides que pueden condicionar el resultado final del tratamiento.
Arthroscopy has enabled wrist fractures and the injuries associated with them to be diagnosed and treated. There are injuries associated with scaphoid fractures, which may influence the success of treatment and can lead to an unsatisfactory result and delay in the functional recovery.
A prospective study was conducted on 17 cases with acute scaphoid body fractures treated by arthroscopic reduction and placement of a cannulated scaphoid screw. Systematic arthroscopy evaluation (radiocarpal and midcarpal) was performed, recording the presence or absence of associated lesions in each case. Treatment outcome was measured using the Mayo Wrist Score, and the fracture consolidation evaluated with plain x-rays.
Associated soft tissues injuries and/or chondral/osteochondral injuries were diagnosed in 14 (82%) cases. The most frequently found lesions were scapholunate ligament injuries (53%) in different degrees, triangular fibrocartilage complex (TFCC) lesions (35.3%), and osteochondral lesions (35.3%). Functional outcomes (Mayo Wrist Score) were excellent or good in 13 patients (76.5%), and in 3 cases (17.5%) the results were fair, and only 1 case (5.9%) had a poor outcome.
Wrist arthroscopy is a valuable tool for the diagnosis and treatment of wrist injuries. There are associated injuries in acute scaphoid body fractures that could influence treatment outcomes.
This paper describes a methodological protocol to project a terrestrial photograph of a coastal area – or whatever indicator is contained on it – in a georeferenced plane taking advantage of the ...terrestrial horizon as a geometric key. This feature, which appears in many beach photos, helps in camera repositioning and as a constraint in collinearity adjustment. This procedure is implemented in a tool called Coastal Projector (C-Pro) that is based on Matlab and adapts its methodology in accordance with the input data and the available parameters of the acquisition system. The method is tested in three coastal areas to assess the influence that the horizon constraint presents in the results. The proposed methodology increases the reliability and efficient use of existing recreational cameras (with non-optimal requirements, unknown image calibration, and at elevations lower than 7m) to provide quantitative coastal data.
One of the major drawbacks that hinder the industrial competitiveness of the calcium looping (CaL) process for CO
2
capture is the high temperature (∼930-950 °C) needed in practice to attain full ...calcination of limestone in a high CO
2
partial pressure environment for short residence times as required. In this work, the multicycle CO
2
capture performance of dolomite and limestone is analysed under realistic CaL conditions and using a reduced calcination temperature of 900 °C, which would serve to mitigate the energy penalty caused by integration of the CaL process into fossil fuel fired power plants. The results show that the fundamental mechanism of dolomite decomposition under CO
2
has a major influence on its superior performance compared to limestone. The inert MgO grains resulting from dolomite decomposition help preserve a nanocrystalline CaO structure wherein carbonation in the solid-state diffusion controlled phase is promoted. The major role played by the dolomite decomposition mechanism under CO
2
is clearly demonstrated by the multicycle CaO conversion behaviour observed for samples decomposed at different preheating rates. Limestone decomposition at slow heating rates yields a highly crystalline and poorly reactive CaCO
3
structure that requires long periods to fully decarbonate and shows a severely reduced capture capacity in subsequent cycles. On the other hand, the nascent CaCO
3
produced after dolomite half-decomposition consists of nanosized crystals with a fast decarbonation kinetics regardless of the preheating rate, thus fully decomposing from the very first cycle at a reduced calcination temperature into a CaO skeleton with enhanced reactivity as compared to limestone derived CaO.
The mechanism of dolomite decomposition under CO
2
is responsible for its superior CO
2
capture performance as compared to limestone.