Primary extra-cranial meningioma in the right submandibular region of an 18-year-old woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Extra-cranial meningioma or ectopic meningioma is a rare tumor. This tumor has been reported in various anatomic sites in the head and neck, mediastinum, skin and soft tissues. We report a rare case of ectopic meningioma in the submandibular region detected by using fine-needle aspiration cytology, histopathology and immunohistochemistry. This case represents another unusual site for extra-cranial meningioma, which prompted us to report it.</p> <p>Case presentation</p> <p>An 18-year-old Dravidian woman presented with swelling in the right submandibular region. The computed tomographic scan findings were suggestive of a neoplastic mass lesion in the right submandibular region. Fine-needle aspiration cytology led to the differential diagnosis of a monomorphic adenoma of a salivary gland or an ectopic meningioma. The patient underwent excision of the submandibular gland and tumor. The histological examination and immunohistochemistry studies confirmed that the lesion was an extra-cranial meningioma. At her two-year follow-up examination, there was no recurrence of the tumor.</p> <p>Conclusion</p> <p>Our experience with this case indicates that, although rare, meningioma should be entertained in the differential diagnosis of a mass lesion in the head and neck region.</p

Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis

Megakaryocytopoiesis is a complex differentiation process driven by the hormone thrombopoietin by which haematopoietic progenitor cells give rise to megakaryocytes, the giant bone marrow cells that in turn break down to form blood platelets. The Tribbles Pseudokinase 3 gene (TRIB3) encodes a pleiotropic protein increasingly implicated in the regulation of cellular differentiation programmes. Previous studies have hinted that TRIB3 could be also involved in megakaryocytopoiesis but its role in this process has so far not been investigated. Using cellular model systems of haematopoietic lineage differentiation here we demonstrate that TRIB3 is a negative modulator of megakaryocytopoiesis. We found that in primary cultures derived from human haematopoietic progenitor cells, thrombopoietin-induced megakaryocytic differentiation led to a time and dosedependent decrease in TRIB3 mRNA levels. In the haematopoietic cell line UT7/mpl, silencing of TRIB3 increased basal and thrombopoietin-stimulated megakaryocyte antigen expression, as well as basal levels of ERK1/2 phosphorylation. In primary haematopoietic cell cultures, silencing of TRIB3 facilitated megakaryocyte differentiation. In contrast, over-expression of TRIB3 in these cells inhibited the differentiation process. The in-vitro identification of TRIB3 as a negative regulator of megakaryocytopoiesis suggests that in-vivo this gene could be important for the regulation of platelet production

Initial clinical experience with frameless optically guided stereotactic radiosurgery/radiotherapy in pediatric patients

The objective of this study is to report our initial experience treating pediatric patients with central nervous system tumors using a frameless, optically guided linear accelerator. Pediatric patients were selected for treatment after evaluation by a multidisciplinary neuro-oncology team including neurosurgery, neurology, pathology, oncology, and radiation oncology. Prior to treatment, all patients underwent treatment planning using magnetic resonance imaging (MRI) and treatment simulation on a standard computed tomography scanner (CT). For CT simulation, patients were fitted with a customized plastic face mask with a bite block attached to an optical array with four reflective markers. After ensuring adequate reproducibility, these markers were tracked during treatment by an infra-red camera. All treatments were delivered on a Varian Trilogy linear accelerator. The follow-up period ranges from 1–18 months, with a median follow-up of 6 months. Nine patients, ages ranging from 12 to 19 years old (median age 15 years old), with a variety of tumors have been treated. Patients were treated for juvenile pilocytic astrocytoma (JPA; n = 2), pontine low-grade astrocytoma (n = 1), pituitary adenoma (n = 3), metastatic medulloblastoma (n = 1), acoustic neuroma (n = 1), and pineocytoma (n = 1). We followed patients for a median of 12 months (range 3–18 months) with no in-field failures and were able to obtain encouraging toxicity profiles. Frameless stereotactic optically guided radiosurgery and radiotherapy provides a feasible and accurate tool to treat a number of benign and malignant tumors in children with minimal treatment-related morbidity

Mechanical and kinetic effects of shortened tropomyosin reconstituted into myofibrils

The effects of tropomyosin on muscle mechanics and kinetics were examined in skeletal myofibrils using a novel method to remove tropomyosin (Tm) and troponin (Tn) and then replace these proteins with altered versions. Extraction employed a low ionic strength rigor solution, followed by sequential reconstitution at physiological ionic strength with Tm then Tn. SDS-PAGE analysis was consistent with full reconstitution, and fluorescence imaging after reconstitution using Oregon-green-labeled Tm indicated the expected localization. Myofibrils remained mechanically viable: maximum isometric forces of myofibrils after sTm/sTn reconstitution (control) were comparable (~84%) to the forces generated by non-reconstituted preparations, and the reconstitution minimally affected the rate of isometric activation (kact), calcium sensitivity (pCa50), and cooperativity (nH). Reconstitutions using various combinations of cardiac and skeletal Tm and Tn indicated that isoforms of both Tm and Tn influence calcium sensitivity of force development in opposite directions, but the isoforms do not otherwise alter cross-bridge kinetics. Myofibrils reconstituted with Δ23Tm, a deletion mutant lacking the second and third of Tm’s seven quasi-repeats, exhibited greatly depressed maximal force, moderately slower kact rates and reduced nH. Δ23Tm similarly decreased the cooperativity of calcium binding to the troponin regulatory sites of isolated thin filaments in solution. The mechanisms behind these effects of Δ23Tm also were investigated using Pi and ADP jumps. Pi and ADP kinetics were indistinguishable in Δ23Tm myofibrils compared to controls. The results suggest that the deleted region of tropomyosin is important for cooperative thin filament activation by calcium

G12/13 Signaling Pathways Substitute for Integrin αIIbβ3-Signaling for Thromboxane Generation in Platelets

We have previously shown that ADP-induced TXA(2) generation requires signaling from αIIbβ3 integrin in platelets. Here we observed that, unlike ADP, protease-activated receptor (PAR)-mediated TXA(2) generation occurs independently of αIIbβ3. PAR agonists, but not ADP, activate G(12/13) signaling pathways. Hence, we evaluated the role of these pathways in TXA(2) generation.Inhibition of ADP-induced thromboxane generation by fibrinogen receptor antagonist SC57101 was rescued by co-stimulation of G(12/13) pathways with YFLLRNP. This observation suggested an existence of a common signaling effector downstream of integrins and G(12/13) pathways. Hence, we evaluated role of three potential tyrosine kinases; c-Src, Syk and FAK (Focal Adhesion Kinase) that are known to be activated by integrins. c-Src and Syk kinase did not play a role in ADP-induced functional responses in platelets. Selective activation of G(12/13) pathways resulted in the activation of FAK, in the absence of integrin signaling. Interestingly, αIIbβ3-mediated FAK activation occurred in a Src family kinase (SFK)-independent manner whereas G(12/13) pathway caused FAK activation in a SFK and RhoA-dependent manner. A FAK selective inhibitor TAE-226, blocked TXA(2) generation. However, in comparison to WT mice, Pf4-Cre/Fak-Floxed mice did not show any difference in platelet TXA(2) generation.Therefore, we conclude that differential activation of FAK occurs downstream of Integrins and G(12/13) pathways. However, the common effector molecule, possibly a tyrosine kinase downstream of integrins and G(12/13) pathways contributing to TXA(2) generation in platelets remains elusive

Small chromosomes among Danish Candida glabrata isolates originated through different mechanisms

We analyzed 192 strains of the pathogenic yeast Candida glabrata from patients, mainly suffering from systemic infection, at Danish hospitals during 1985-1999. Our analysis showed that these strains were closely related but exhibited large karyotype polymorphism. Nine strains contained small chromosomes, which were smaller than 0.5 Mb. Regarding the year, patient and hospital, these C. glabrata strains had independent origin and the analyzed small chromosomes were structurally not related to each other (i.e. they contained different sets of genes). We suggest that at least two mechanisms could participate in their origin: (i) through a segmental duplication which covered the centromeric region, or (ii) by a translocation event moving a larger chromosome arm to another chromosome that leaves the centromere part with the shorter arm. The first type of small chromosomes carrying duplicated genes exhibited mitotic instability, while the second type, which contained the corresponding genes in only one copy in the genome, was mitotically stable. Apparently, in patients C. glabrata chromosomes are frequently reshuffled resulting in new genetic configurations, including appearance of small chromosomes, and some of these resulting "mutant" strains can have increased fitness in a certain patient "environment"

Playing with networks : How economists explain

Peer reviewe

A Bioelectrochemical Approach to Characterize Extracellular Electron Transfer by Synechocystis sp. PCC6803

Biophotovoltaic devices employ photosynthetic organisms at the anode of a microbial fuel cell to generate electrical power. Although a range of cyanobacteria and algae have been shown to generate photocurrent in devices of a multitude of architectures, mechanistic understanding of extracellular electron transfer by phototrophs remains minimal. Here we describe a mediatorless bioelectrochemical device to measure the electrogenic output of a planktonically grown cyanobacterium, Synechocystis sp. PCC6803. Light dependent production of current is measured, and its magnitude is shown to scale with microbial cell concentration and light intensity. Bioelectrochemical characterization of a Synechocystis mutant lacking Photosystem II demonstrates conclusively that production of the majority of photocurrent requires a functional water splitting aparatus and electrons are likely ultimately derived from water. This shows the potential of the device to rapidly and quantitatively characterize photocurrent production by genetically modified strains, an approach that can be used in future studies to delineate the mechanisms of cyanobacterial extracellular electron transport

Variable, but not free-weight, resistance back squat exercise potentiates jump performance following a comprehensive task-specific warm-up

Studies examining acute, high-speed movement performance enhancement following intense muscular contractions (frequently called "post-activation potentiation"; PAP) often impose a limited warm-up, compromizing external validity. In the present study, the effects on countermovement vertical jump (CMJ) performance of back squat exercises performed with or without elastic bands during warm-up were compared. After familiarization, fifteen active men visited the laboratory on two occasions under randomized, counterbalanced experimental squat warm-up conditions: (a) free-weight resistance (FWR) and (b) variable resistance (VR). After completing a comprehensive task-specific warm-up, three maximal CMJs were performed followed by three back squat repetitions completed at 85% of 1-RM using either FWR or VR Three CMJs were then performed 30 seconds, 4 minutes, 8 minutes, and 12 minutes later. During CMJ trials, hip, knee, and ankle joint kinematics, ground reaction force data and vastus medialis, vastus lateralis, and gluteus maximus electromyograms (EMG) were recorded simultaneously using 3D motion analysis, force platform, and EMG techniques, respectively. No change in any variable occurred after FWR (P > 0.05). Significant increases (P < 0.05) were detected at all time points following VR in CMJ height (5.3%-6.5%), peak power (4.4%-5.9%), rate of force development (12.9%-19.1%), peak concentric knee angular velocity (3.1%-4.1%), and mean concentric vastus lateralis EMG activity (27.5%-33.4%). The lack of effect of the free-weight conditioning contractions suggests that the comprehensive task-specific warm-up routine mitigated any further performance augmentation. However, the improved CMJ performance following the use of elastic bands is indicative that specific alterations in force-time properties of warm-up exercises may further improve performance

Comparative Lipidomics of Azole Sensitive and Resistant Clinical Isolates of Candida albicans Reveals Unexpected Diversity in Molecular Lipid Imprints

Although transcriptome and proteome approaches have been applied to determine the regulatory circuitry behind multidrug resistance (MDR) in Candida, its lipidome remains poorly characterized. Lipids do acclimatize to the development of MDR in Candida, but exactly how the acclimatization is achieved is poorly understood. In the present study, we have used a high-throughput mass spectrometry-based shotgun approach and analyzed the lipidome of genetically matched clinical azole-sensitive (AS) and -resistant (AR) isolates of C. albicans. By comparing the lipid profiling of matched isolates, we have identified major classes of lipids and determined more than 200 individual molecular lipid species among these major classes. The lipidome analysis has been statistically validated by principal component analysis. Although each AR isolate was similar with regard to displaying a high MIC to drugs, they had a distinct lipid imprint. There were some significant commonalities in the lipid profiles of these pairs, including molecular lipid species ranging from monounsaturated to polyunsaturated fatty acid-containing phosphoglycerides. Consistent fluctuation in phosphatidyl serine, mannosylinositolphosphorylceramides, and sterol esters levels indicated their compensatory role in maintaining lipid homeostasis among most AR isolates. Notably, overexpression of either CaCdr1p or CaMdr1p efflux pump proteins led to a different lipidomic response among AR isolates. This study clearly establishes the versatility of lipid metabolism in handling azole stress among various matched AR isolates. This comprehensive lipidomic approach will serve as a resource for assessing strategies aimed at disrupting the functions of Candida lipids, particularly the functional interactions between lipids and MDR determinants