353 research outputs found
Microcystic adnexal carcinoma of the centrofacial region: a case report
Microcystic adnexal carcinoma is a rare, locally aggressive neoplasm with both eccrine and follicular differentiation and a high probability
of perineural invasion of the centrofacial region. Given the histopathological features of this tumour, early diagnosis is essential for
adequate management. This report refers to a case of microcystic adnexal carcinoma of the nasogenial region, with infiltration of the deep
planes extending to the anterior wall of the maxillary sinus. Surgical treatment involved wide demolition of the centrofacial region followed
by reconstruction using four locoregional flaps: an Indian flap and a Mustardé flap were used for cutaneous reconstruction; a septal flap to
support the maxillogenial region; a mucosal flap to separate the nasal cavities
The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells
Interleukin-12 (IL-12), produced by dendritic cells in response to activation, is central to pathogen eradication and tumor rejection. The trafficking pathways controlling spatial distribution and intracellular transport of IL-12 vesicles to the cell surface are still unknown. Here, we show that intracellular IL-12 localizes in late endocytic vesicles marked by the SNARE VAMP7. Dendritic cells (DCs) from VAMP7-deficient mice are partially impaired in the multidirectional release of IL-12. Upon encounter with antigen-specific T cells, IL-12-containing vesicles rapidly redistribute at the immune synapse and release IL-12 in a process entirely dependent on VAMP7 expression. Consistently, acquisition of effector functions is reduced in T cells stimulated by VAMP7-null DCs. These results provide insights into IL-12 intracellular trafficking pathways and show that VAMP7-mediated release of IL-12 at the immune synapse is a mechanism to transmit innate signals to T cells
Acoustic Phonon-Assisted Resonant Tunneling via Single Impurities
We perform the investigations of the resonant tunneling via impurities
embedded in the AlAs barrier of a single GaAs/AlGaAs heterostructure. In the
characteristics measured at 30mK, the contribution of individual donors
is resolved and the fingerprints of phonon assistance in the tunneling process
are seen. The latter is confirmed by detailed analysis of the tunneling rates
and the modeling of the resonant tunneling contribution to the current.
Moreover, fluctuations of the local structure of the DOS (LDOS) and Fermi edge
singularities are observed.Comment: accepted in Phys. Rev.
Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells
Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins
Biocompatible Packagings for Fully Implantable Multi-Panel Devices for Remote Monitoring of Metabolism
This paper compares three different biocompatible packagings suitable to support full implantation of multi-panel sensors for remote monitoring of metabolism. The three packagings have been designed, realized and implanted in mice for 30 days. ATP and neutrophil concentrations have been measured at the implant site after the device was explanted, to assess the level of biocompatibility of the device
Coexistence of Anomalous Hall Effect and Weak Net Magnetization in Collinear Antiferromagnet MnTe
Anomalous Hall effect (AHE) plays important role in the rapidly developing
field of antiferromagnetic spintronics. It has been recently discussed that it
can be a feature of not only uncompensated magnetic systems but also in
altermagnetic materials. Hexagonal MnTe belongs to this appealing group of
compounds exhibiting AHE and is commonly perceived as magnetically compensated.
Here, we demonstrate that bulk form of MnTe exhibits small but detectable
magnetic moment correlating with hysteretic behaviour of the AHE. We formulate
a phenomenological model which explains how this feature allows to create a
disbalance between states with opposite N\'eel vector and prevent the AHE
signal from averaging out to zero. Moreover, we show how the dependence of AHE
on the N\'eel vector arises on microscopical level and highlight the
differences in Berry curvature between magnetically compensated and
uncompensated systems
A functional variant at a prostate cancer predisposition locus at 8q24 is associated with PVT1 expression
Genetic mapping studies have identified multiple cancer susceptibility regions at chromosome 8q24, upstream of the MYC oncogene. MYC has been widely presumed as the regulated target gene, but definitive evidence functionally linking these cancer regions with MYC has been difficult to obtain. Here we examined candidate functional variants of a haplotype block at 8q24 encompassing the two independent risk alleles for prostate and breast cancer, rs620861 and rs13281615. We used the mapping of DNase I hypersensitive sites as a tool to prioritise regions for further functional analysis. This approach identified rs378854, which is in complete linkage disequilibrium (LD) with rs620861, as a novel functional prostate cancer-specific genetic variant. We demonstrate that the risk allele (G) of rs378854 reduces binding of the transcription factor YY1 in vitro. This factor is known to repress global transcription in prostate cancer and is a candidate tumour suppressor. Additional experiments showed that the YY1 binding site is occupied in vivo in prostate cancer, but not breast cancer cells, consistent with the observed cancer-specific effects of this single nucleotide polymorphism (SNP). Using chromatin conformation capture (3C) experiments, we found that the region surrounding rs378854 interacts with the MYC and PVT1 promoters. Moreover, expression of the PVT1 oncogene in normal prostate tissue increased with the presence of the risk allele of rs378854, while expression of MYC was not affected. In conclusion, we identified a new functional prostate cancer risk variant at the 8q24 locus, rs378854 allele G, that reduces binding of the YY1 protein and is associated with increased expression of PVT1 located 0.5 Mb downstream.This work was funded by Cancer Research UK (http://www.cancerresearchuk.org/) and by the Intramural Research Program, Division of Cancer Epidemiology and Genetics and Centre for Cancer Research, National Cancer Institute, National Institutes of Health, United States of America (http://www.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Reducing suicidal thoughts in the Australian general population through web-based self-help: study protocol for a randomized controlled trial
EUROmediCAT signal detection: an evaluation of selected congenital anomaly-medication associations
To evaluate congenital anomaly (CA)-medication exposure associations produced by the new EUROmediCAT signal detection system and determine which require further investigation.
Data from 15 EUROCAT registries (1995-2011) with medication exposures at the chemical substance (5th level of Anatomic Therapeutic Chemical classification) and chemical subgroup (4th level) were analysed using a 50% false detection rate. After excluding antiepileptics, antidiabetics, antiasthmatics and SSRIs/psycholeptics already under investigation, 27 associations were evaluated. If evidence for a signal persisted after data validation, a literature review was conducted for prior evidence of human teratogenicity.
Thirteen out of 27 CA-medication exposure signals, based on 389 exposed cases, passed data validation. There was some prior evidence in the literature to support six signals (gastroschisis and levonorgestrel/ethinylestradiol (OR 4.10, 95% CI 1.70-8.53; congenital heart disease/pulmonary valve stenosis and nucleoside/tide reverse transcriptase inhibitors (OR 5.01, 95% CI 1.99-14.20/OR 28.20, 95% CI 4.63-122.24); complete absence of a limb and pregnen (4) derivatives (OR 6.60, 95% CI 1.70-22.93); hypospadias and pregnadien derivatives (OR 1.40, 95% CI 1.10-1.76); hypospadias and synthetic ovulation stimulants (OR 1.89, 95% CI 1.28-2.70). Antipropulsives produced a signal for syndactyly while the literature revealed a signal for hypospadias. There was no prior evidence to support the remaining six signals involving the ordinary salt combinations, propulsives, bulk-forming laxatives, hydrazinophthalazine derivatives, gonadotropin releasing hormone analogues and selective serotonin agonists.
Signals which strengthened prior evidence should be prioritized for further investigation, and independent evidence sought to confirm the remaining signals. Some chance associations are expected and confounding by indication is possible
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