Translocating the Caribbean, Positioning Im/Mobilities: The Sonic Politics of Las Krudas from Cuba

Roth J. Translocating the Caribbean, Positioning Im/Mobilities: The Sonic Politics of Las Krudas from Cuba. In: Graham M, Raussert W, eds. Mobile and Entangled America(s). Interamerican Research: Contact, Communication, Conflict. Oxford: Routledge; 2016: 103-130

Competition between diffusion and advection may mediate self-repair of wax microstructures on plant surfaces

Cuticles are extracellular membranes covering the primary aerial parts of vascular plants. They consist of a multifunctional polymeric material with embedded soluble components, called waxes and serve as the interface between plants and their atmospheric environment, first of all protecting them from desiccation. Waxes are produced within the epidermal cells, then transported to the leaf surface and finally integrated into the polymer or deposited upon the cuticle. Remarkably, damaged wax layers may become repaired within a few hours. Base on an earlier hypothesis we present a theoretical framework explaining how waxes are transported through the plant epidermis by a combination of advection and diffusion. This combination suggests also a self-regulating repair mechanism, based on the assumption that intact cuticles induce an antagonistic equilibrium between advection and diffusion: whenever a wax layer is damaged, the equilibrium is disturbed in favour of advection, starting a repair process, which is intrinsically coming to an end after the cuticle has gained its original thickness

MicroRNA-210 induces apoptosis in colorectal cancer via induction of reactive oxygen

Additional file 2: Figure S2. Representative flow cytometric histograms of CRC cell lines 72 h post transfection with pre-miR-210 and a control miRNA, respectively. Cells were stained with by PI staining and subjected to FACS analysis

Mutations in POLE and survival of colorectal cancer patients – link to disease stage and treatment

Recent molecular profiling studies reported a new class of ultramutated colorectal cancers (CRCs), which are caused by exonuclease domain mutations (EDMs) in DNA polymerase ϵ (POLE). Data on the clinical implications of these findings as to whether these mutations define a unique CRC entity with distinct clinical outcome are lacking. We performed Sanger sequencing of the POLE exonuclease domain in 431 well-characterized patients with microsatellite stable (MSS) CRCs of a population-based patient cohort. Mutation data were analyzed for associations with major epidemiological, clinical, genetic, and pathological parameters including overall survival (OS) and disease-specific survival (DSS). In 373 of 431 MSS CRC, all exons of the exonuclease domain were analyzable. Fifty-four mutations were identified in 46 of these samples (12.3%). Besides already reported EDMs, we detected many new mutations in exons 13 and 14 (corresponding to amino acids 410–491) as well as in exon 9 and exon 11 (corresponding to aa 268–303 and aa 341–369). However, we did not see any significant associations of EDMs with clinicopathological parameters, including sex, age, tumor location and tumor stage, CIMP, KRAS, and BRAF mutations. While with a median follow-up time of 5.0 years, survival analysis of the whole cohort revealed nonsignificantly different adjusted hazard ratios (HRs) of 1.35 (95% CI: 0.82–2.25) and 1.44 (0.81–2.58) for OS and DSS indicating slightly impaired survival of patients with EDMs, subgroup analysis for patients with stage III/IV disease receiving chemotherapy revealed a statistically significantly increased adjusted HR (1.87; 95%CI: 1.02–3.44). In conclusion, POLE EDMs do not appear to define an entirely new clinically distinct disease entity in CRC but may have prognostic or predictive implications in CRC subgroups, whose significance remains to be investigated in future studies

The macrocyclic lactone oxacyclododecindione reduces fibrosis progression

Background: Renal fibrosis is one of the most important triggers of chronic kidney disease (CKD), and only a very limited number of therapeutic options are available to stop fibrosis progression. As fibrosis is characterized by inflammation, myofibroblast activation, and extracellular matrix (ECM) deposition, a drug that can address all these processes might be an interesting therapeutic option.Methods: We tested in vivo in an ischemia–reperfusion (I/R) model in C57BL/6 mice and in kidney tubular epithelial cells (TEC) (HK2 cell line and primary cells) whether the natural product oxacyclododecindione (Oxa) reduces fibrosis progression in kidney disease. This was evaluated by Western blot, mRNA expression, and mass spectrometry secretome analyses, as well as by immunohistochemistry.Results: Indeed, Oxa blocked the expression of epithelial–mesenchymal transition marker proteins and reduced renal damage, immune cell infiltration, and collagen expression and deposition, both in vivo and in vitro. Remarkably, the beneficial effects of Oxa were also detected when the natural product was administered at a time point of established fibrotic changes, a situation close to the clinical situation. Initial in vitro experiments demonstrated that a synthetic Oxa derivative possesses similar features.Conclusion: Although open questions such as possible side effects need to be investigated, our results indicate that the combination of anti-inflammatory and anti-fibrotic effects of Oxa make the substance a promising candidate for a new therapeutic approach in fibrosis treatment, and thus in the prevention of kidney disease progression

PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity

The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC)

Visual feedback explains why propointing is better than antipointing in spatial neglect

Kathrin S. Utz held a post-doctoral research fellowship of the Friedrich-AlexanderUniversity Erlangen-Nuremberg (program for the promotion of equal opportunities of women in science) at the time of data collection. Thomas Schenk was supported by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG, grant no’s: DFG-SCHE 735/2-1 and DFG-SCHE 735/3-1).Peer reviewedPostprin

pT3 colorectal cancer revisited: a multicentric study on the histological depth of invasion in more than 1000 pT3 carcinomas—proposal for a new pT3a/pT3b subclassification

BACKGROUND: Pathological TNM staging (pTNM) is the strongest prognosticator in colorectal carcinoma (CRC) and the foundation of its post-operative clinical management. Tumours that invade pericolic/perirectal adipose tissue generally fall into the pT3 category without further subdivision. METHODS: The histological depth of invasion into the pericolic/perirectal fat was digitally and conventionally measured in a training cohort of 950 CRCs (Munich). We biostatistically calculated the optimal cut-off to stratify pT3 CRCs into novel pT3a (≤3 mm)/pT3b (>3 mm) subgroups, which were then validated in two independent cohorts (447 CRCs, Bayreuth/542 CRCs, Mainz). RESULTS: Compared to pT3a tumours, pT3b CRCs showed significantly worse disease-specific survival, including in pN0 vs pN+ and colonic vs. rectal cancers (DSS: P < 0.001, respectively, pooled analysis of all cohorts). Furthermore, the pT3a/pT3b subclassification remained an independent predictor of survival in multivariate analyses (e.g. DSS: P < 0.001, hazard ratio: 4.41 for pT3b, pooled analysis of all cohorts). While pT2/pT3a CRCs showed similar survival characteristics, pT3b cancers remained a distinct subgroup with dismal survival. DISCUSSION: The delineation of pT3a/pT3b subcategories of CRC based on the histological depth of adipose tissue invasion adds valuable prognostic information to the current pT3 classification and implementation into current staging practices of CRC should be considered