Bisabolane type sesquiterpenes from a marine Didiscus sponge

Two bisabolane type sesquiterpene phenols, (+)-curcuphenol (1) and (+)-curcudiol (2), were isolated from a Philippine marine sponge, Didiscus sp., in addition to b -sitosterol (3) and phenethylamine (4). The structures of the metabolites were established on the basis of spectral evidence (1D- and 2D NMR, [a]D, EIMS). (+)-Curcuphenol (1) showed cytotoxicity, which is indicative of a p53 independent mechanism

Cytotoxic bromoindole derivatives and terpenes from the Philippine marine sponge Smenospongia sp.

A detailed chemical analysis of a Philippine marine sponge Smenospongia sp. has been performed. This study yielded four new metabolites, 5-bromo-l-tryptophan (1), 5-bromoabrine (2), 5,6-dibromoabrine (3) and 5-bromoindole-3-acetic acid (4). The pyrroloiminoquinone alkaloid, makaluvamine O (5) as well as 5,6-dibromotryptamine (6), aureol (7) and furospinulosin 1 (8) were also isolated. Although 1 and 4 have been synthesized previously, this is the first report on the isolation of these compounds from a natural source. The furanosesterterpene furospinulosin 1 (8) was obtained for the first time from the genus Smenospongia. The structures of all compounds were established by spectroscopic methods (UV, IR, 1D and 2D NMR, MS, [α]D). The cytotoxic potential of 1Ð8 was evaluated in a panel of isogenic HCT-116 human colon tumor cell lines

Bilateral Talus and Navicular Fractures accompanied with Unilateral Calcaneal Fracture: A Case Report

An 18-year old male patient, with a history of paragliding accident, sustaining a coronal shear fracture of the body of the talus, an anterior process fracture of the calcaneus extending to the calcaneocuboid joint and a nondisplaced navicular body fracture at the right foot and a displaced fracture of the navicular body accompanied with posteromedial process fracture of the talus at the left side was referred to our emergency clinic. For the right foot, the coronal plane fracture of the talar body was anatomically reduced and fixed with screws. For the left foot, screw fixation was performed through the lateral aspect to fix the large posteromedial fragment. Small bone fragments were removed from the left navicular fracture, and the main fragments were also fixed with screw. The talo-navicular joint was stabilised with a Kirschner wire. At 36 months follow-up, bilateral foot and ankle functions were satisfactory, Maryland scores of the right and left foot were 85 (good) and 90 (excellent), respectively, and the patient regained his full activity level by the 5th month postoperatively. With reference to the number and types of fractures in this one patient, we present a standard protocol for treatment of isolated talus, navicular and calcaneal fractures presenting together in a single foot injury

Comparative Microbiome and Metabolome Analyses of the Marine Tunicate Ciona intestinalis from Native and Invaded Habitats

Massive fouling by the invasive ascidian Ciona intestinalis in Prince Edward Island (PEI, Canada) has been causing devastating losses to the local blue mussel farms. In order to gain first insights into so far unexplored factors that may contribute to the invasiveness of C. intestinalis in PEI, we undertook comparative microbiome and metabolome studies on specific tissues from C. intestinalis populations collected in invaded (PEI) and native regions (Helgoland and Kiel, Germany). Microbial community analyses and untargeted metabolomics revealed clear location- and tissue-specific patterns showing that biogeography and the sampled tissue shape the microbiome and metabolome of C. intestinalis. Moreover, we observed higher microbial and chemical diversity in C. intestinalis from PEI than in the native populations. Bacterial OTUs specific to C. intestinalis from PEI included Cyanobacteria (e.g., Leptolyngbya sp.) and Rhodobacteraceae (e.g., Roseobacter sp.), while populations from native sampling sites showed higher abundances of e.g., Firmicutes (Helgoland) and Epsilonproteobacteria (Kiel). Altogether 121 abundant metabolites were putatively annotated in the global ascidian metabolome, of which 18 were only detected in the invasive PEI population (e.g., polyketides and terpenoids), while six (e.g., sphingolipids) or none were exclusive to the native specimens from Helgoland and Kiel, respectively. Some identified bacteria and metabolites reportedly possess bioactive properties (e.g., antifouling and antibiotic) that may contribute to the overall fitness of C. intestinalis. Hence, this first study provides a basis for future studies on factors underlying the global invasiveness of Ciona species

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Long term survival after coronary endarterectomy in patients undergoing combined coronary and valvular surgery – a fifteen year experience

<p>Abstract</p> <p>Background</p> <p>Coronary Endarterectomy (CE) in patients undergoing coronary artery bypass graft (CABG) surgery has been shown to be beneficial in those with diffuse coronary artery disease. There are no published data on its role and benefit in patients undergoing more complex operations. We present our experience with CE in patients undergoing valve surgery with concomitant CABG.</p> <p>Materials and methods</p> <p>Between 1989 and 2003, 237 patients underwent CABG with valve surgery under a single surgeon at our institution. Of these, 41 patients needed CE. Data was retrospectively obtained from hospital records and database. Further follow-up was obtained by telephone interview. All variables were analyzed by univariate analysis for significant factors relating to hospital mortality. Morbidity and long term survival was also studied. There were 29 males and 12 females with a mean age of 67.4 ± 8.1 and body mass index of 26.3 ± 3.3. Their mean euroscore was 7.6 ± 3.2 and the log euro score was 12.2 ± 16.1.</p> <p>Results</p> <p>Thirty-two patients were discharged from the intensive therapy unit within 48 hours after surgery. Average hospital stay was 12.7 ± 10.43 days. Thirty day mortality was 9.8%. Six late deaths occurred during the 14 year follow up. Ten year survival was 57.2% (95% CL 37.8%–86.6%). Three of the survivors had Class II symptoms, with one requiring nitrates. None required further percutaneous or surgical intervention. We compared the result with the available mortality figure from the SCTS database.</p> <p>Conclusion</p> <p>Compared to the SCTS database for these patients, we have observed that CE does not increase the mortality in combined procedures. By accomplishing revascularization in areas deemed ungraftable, we have shown an added survival benefit in this group of patients.</p

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Steganalysis of 3D objects using statistics of local feature sets

3D steganalysis aims to identify subtle invisible changes produced in graphical objects through digital watermarking or steganography. Sets of statistical representations of 3D features, extracted from both cover and stego 3D mesh objects, are used as inputs into machine learning classifiers in order to decide whether any information was hidden in the given graphical object. The features proposed in this paper include those representing the local object curvature, vertex normals, the local geometry representation in the spherical coordinate system. The effectiveness of these features is tested in various combinations with other features used for 3D steganalysis. The relevance of each feature for 3D steganalysis is assessed using the Pearson correlation coefficient. Six different 3D watermarking and steganographic methods are used for creating the stego-objects used in the evaluation study