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athological literature reveals the complexity of AD reactive astrogliosis. We have shared these findings as an online resource available at www.astrocyteatlas.org.

Reasons for first trimester noninvasive prenatal screening (NIPS) test failure in obese women remain elusive. As dilution from maternal sources may be explanatory, we determined the relationship between obesity, fetal fraction (FF), and total cell-free DNA (cfDNA) using our NIPS platform.

We assessed differences in first trimester (≤14weeks) FF, indeterminate rate, and total cfDNA between obese (n=518) and normal-weight women (n=237) after exclusion of confounders (anticoagulation, autoimmunity, aneuploidy) and controlling for covariates.

Fetal fraction was lower, and the indeterminate rate higher, in obese compared to controls (9.2%±4.4 vs. 12.5%±4.5, p<0.001 and 8.4 vs. 1.7%, p<0.001, respectively), but total cfDNA was not different (92.0 vs. 82.1 pg/µl, p=0.10). For each week, the FF remained lower in obese women (all p<0.01) but did not increase across the first trimester for either group. Obesity increased the likelihood of indeterminate result (OR 6.1, 95% CI 2.5, 14.8; p<0.001) and maternal body mass index correlated with FF (β -0.27, 95% CI -0.3, -0.22; p<0.001), but not with total cfDNA (β 0.49, 95% CI -0.55, 1.53; p=0.3).

First trimester obese women have persistently low FF and higher indeterminate rates, without differences in total cfDNA, suggesting placental-specific mechanisms versus dilution from maternal sources as a potential etiology.

First trimester obese women have persistently low FF and higher indeterminate rates, without differences in total cfDNA, suggesting placental-specific mechanisms versus dilution from maternal sources as a potential etiology.

Cutaneous T-cell lymphomas are a heterogenous group of T-cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS).

The diagnosis of MF or SS requires the integration of clinical and histopathologic data.

TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a "risk-adapted," multi-disciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or blood involvement are generally approached with systemic therapies, including biologic-response modifiers, histone deacetylase inhibitors, or antibody-based strategies, in an escalating fashion. In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients.

TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a "risk-adapted," multi-disciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin-directed therapies is preferred, as both disease-specific and overall survival for these patients is favorable. In contrast, patients with advanced-stage disease with significant nodal, visceral or blood involvement are generally approached with systemic therapies, including biologic-response modifiers, histone deacetylase inhibitors, or antibody-based strategies, in an escalating fashion. TM-MMF In highly-selected patients, allogeneic stem-cell transplantation may be considered, as this may be curative in some patients.Bag3 has been implicated in a wide variety of physiological processes from autophagy to aggresome formation and from cell transformation to survival. We argue that involvement of Bag3 in many of these processes is due to its distinct function in cell signaling. The structure of Bag3 suggests that it can serve as a scaffold that links molecular chaperones Hsp70 and small Hsps with components of a variety of signaling pathways. Major protein-protein interaction motifs of Bag3 that recruit components of signaling pathways are WW domain and PXXP motif that interacts with SH3-domain proteins. Furthermore, Hsp70-Bag3 appears to be a sensor of abnormal polypeptides during the proteotoxic stress. It also serves as a sensor of a mechanical force during mechanotransduction. Common feature of these and probably certain other sensory mechanisms is that they represent responses to specific kinds of abnormal proteins, i.e. unfolded filamin A in case of mechanotransduction or stalled translating polypeptides in case of sensing proteasome inhibition. Overall Hsp70-Bag3 module represents a novel signaling node that responds to multiple stimuli and controls multiple physiological processes.

ZEB1 is a transcription factor that promotes metastatic and stem cell features, which has been associated with poor prognosis in cholangiocarcinoma (CCA), a desmoplastic cancer enriched in cancer-associated fibroblasts (CAF). Here, we aimed to define ZEB1 regulatory functions in malignant and stroma compartments of CCA.

Bioinformatic and immunohistochemical analyses were performed to determine correlations between ZEB1 and markers of progressiveness in human intrahepatic CCA (iCCA). Gain/loss of function models were generated in CCA cells, and liver myofibroblasts, as a model of CAF. Conditioned media (CM) was used to unravel tumor-stroma interplay. In vivo experiments were performed using xenograft CCA model. ZEB1 expression in tumor cells of human iCCA was associated with undifferentiated tumor and vascular invasion. In vitro, ZEB1 promoted epithelial-mesenchymal transition and stemness in tumor cells leading to cell migration and spheroid formation. In vivo, ZEB1-overexpressing CCA cells formed larger tumors with more abundant stroma. CCN2/CTGF expression was increased in tumor cells from ZEB1-overexpressing xenografts and correlated with ZEB1 expression in human tumors. In vitro, CM from ZEB1-overexpressing tumor cells or recombinant CTGF induced myofibroblast proliferation. ZEB1 was also expressed by CAF in human CCA and its expression correlated with CCN2 in myofibroblast and CCA stroma. In mice, co-transplantation of CCA cells with ZEB1-depleted myofibroblasts reduced CCA progressiveness compared to CCA cells/ZEB1-expressing myofibroblasts. Furthermore, ZEB1 controls the expression of paracrine signals (i.e. HGF and IL6) in tumor cells and myofibroblasts.

ZEB1 plays a key role in CCA progression by regulating tumor cell-CAF cross-talk, leading to tumor dedifferentiation and CAF activation.

ZEB1 plays a key role in CCA progression by regulating tumor cell-CAF cross-talk, leading to tumor dedifferentiation and CAF activation.IRE1 is an important central regulator of unfolded protein response (UPR) in the endoplasmic reticulum (ER) because of its ability to regulate cell fate as a function of stress sensing. When misfolded proteins accumulated in chondrocytes ER, IRE1 disintegrates with BIP/GRP78 and undergoes dimer/oligomerization and transautophosphorylation. These two processes are mediated through an enzyme activity of IRE1 to activate endoribonuclease and generates XBP1 by unconventional splicing of XBP1 messenger RNA. Thereby promoting the transcription of UPR target genes and apoptosis. The deficiency of inositol-requiring enzyme 1α (IRE1α) in chondrocytes downregulates prosurvival factors XBP1S and Bcl-2, which enhances the apoptosis of chondrocytes through increasing proapoptotic factors caspase-3, p-JNK, and CHOP. Meanwhile, the activation of IRE1α increases chondrocyte viability and reduces cell apoptosis. However, the understanding of IRE1 responses and cell death fate remains controversial. This review provides updated data about the role IRE1 plays in chondrocytes and new insights about the potential efficacy of IRE1 regulation in cartilage repair and osteoarthritis treatment.

To describe and compare onset and intensity of thoracic duct (TD) coloration in healthy dogs after intrahepatic injection of either indocyanine green (ICG) visualized by intraoperative near-infrared fluorescence lymphography (NIRFL) or direct thoracoscopic visualization of methylene blue dye (MB).

Prospective study.

Healthy adult Beagle dogs (n=5).

All dogs had biochemical panels and complete blood counts preoperatively. Computed tomography lymphography (CTL) was performed prior to a standard 3-port thoracoscopic approach. A mixture of MB and ICG was injected by ultrasound-guided percutaneous injection into right or left-sided hepatic lobes. Data collected included dose of contrast agent (MB vs. ICG), injection site, timing, and quality of operative TD identification. Potential hepatic injury was assessed by repeat laboratory evaluation and abdominal ultrasound 14 days postoperatively.

Preoperative CTL provided a diagnostic study in 5/5 dogs. After intrahepatic injection of combined dyes, NIRFL allowed visualization of TDs in 5/5 dogs, but MB did not result in visible TD coloration in any dog. Intrahepatic injection of ICG achieved successful NIRFL in a median time of 6minutes and persisted for the 20 minute observation period in all five dogs. All dogs recovered without complication and were subsequently adopted.

NIRFL of the TD can be achieved with intraoperative hepatic injection of ICG. Intrahepatic injection of MB did not result in visible TD coloration.

Hepatic intra-parenchymal injection is a reliable alternative portal into the TD system for intraoperative visualization of TD anatomy using ICG in dogs.

Hepatic intra-parenchymal injection is a reliable alternative portal into the TD system for intraoperative visualization of TD anatomy using ICG in dogs.Reliability of forensic evidences for presence of inorganic gunshot residue (iGSR) on a given surface strongly depends on the performance of scanning electron microscopy/energy dispersive X-ray spectrometry (SEM-EDS) method. This article presents the results from a study of the effect of SEM/EDS working parameters on the method performance and quality of iGSR data, as well as a development of a database of iGSR encountered in R Kosovo. The optimal working parameters of SEM/EDS were established by one-variable-at-a-time approach and the method was validated according to ASTM1588-10. The precision, trueness, and expanded uncertainty for PbBaSb particles were estimated and the method was assessed as a "fit for purpose" with a satisfactory performance (z-score less then 2). Expended uncertainty of quantification of GSR particles estimated by single laboratory and quality control approach was 6% (k = 2). The validated SEM/EDS method was applied for identification of characteristic iGSR particles in samples from shooting events in Kosovo. The method was demonstrated to be capable of providing a legal proof for iGSR existence on a specific surface. The quality of the results was not influenced by the origin of iGSR. Five hundred fifty-five samples from 144 cases occurred during the last 3 years were analyzed and 14% rate of positive results was found.In this work, a biosensor based on surface plasmon field-enhanced florescence spectroscopy (SPFS) method was successfully constructed to detect the truncated form of cholera toxin, that is, its beta subunit (CTX-B). CTX-B is a relatively small molecule (12 kDa) and it was chosen as model analyte for the detection of protein toxins originated from waterborne pathogens. Recognition layer was prepared on gold-coated LaSFN9 glasses modified with 11-mercaptoundecanoic acid (11-MUA). Biotin-conjugated anti-CTX-B polyclonal antibody (B-Ab) was immobilized on streptavidin (SA) layer constructed on the 11-MUA-modified surface. CTX-B amount was determined with direct assay using B-Ab in surface plasmon resonance (SPR) mode and with sandwich assay in SPFS mode using Cy5-conjugated anti-CTX-B polyclonal antibody. Minimum detected CTX-B concentrations were 10 and 0.01 μg/ml with SPR and SPFS, respectively, showing the sensitivity of the SPFS system over the conventional one. The detection was done in 2-6 h, which was faster than both culture and polymerase chain reaction (PCR)-based methods.