AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major components, collagen IV and laminin. We used this model to demonstrate that antibody targeted blockade of CTLD2, the second of eight C-type lectin-like domains in Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) that can recognize glycosylated collagens, reversed actinomyosin-based contractility [myosin-light chain-2 (MLC2) phosphorylation], loss of cell polarity, loss of cell–cell junctions, luminal infiltration and basal invasion induced by AGE-modified basal lamina matrix in PEC acini. Our in vitro results were concordant with luminal occlusion of acini in the prostate glands of adult Endo180ΔEx2–6/ΔEx2–6 mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour in non-transformed PECs via a molecular mechanism linked to cancer progression. This study provides a rationale for targeting CTLD2 in Endo180 in prostate cancer and other pathologies in which increased basal lamina thickness and tissue stiffness are driving factors

Nonlinear modeling of venous leg ulcer healing rates

<p>Abstract</p> <p>Background</p> <p>The purpose of this manuscript was to determine whether the change in wound surface area over time could be described through nonlinear mathematics.</p> <p>Methods</p> <p>We studied 3,588 serial wound tracings of 338 venous leg ulcers (VLUs) that had been followed during a controlled, prospective, randomized trial of two topical wound treatments.</p> <p>Results</p> <p>A majority (72%) of VLUs exhibited surface area reduction via an exponential decay model, particularly during the early stages of healing. These results were consistent with the mechanics of wound contraction and epithelial cell proliferation, supported by the higher frequency at which exponential surface area reduction associated with full wound closure (35% of wounds that fit the exponential model healed vs. 21% of wounds that did not fit the exponential model completely healed during the study period, p = 0.018). Goodness-of-fit statistics suggested that much of the individual variation in healing could be described as nonlinear variation from the exponential model.</p> <p>Conclusion</p> <p>We believe that parameter estimates from a mathematical model may provide a more accurate quantification of wound healing rates, and that similar models may someday reach routine use in comparing the efficacy of various treatments in routine practice and in product registration trials.</p

Correcting PCR amplification errors in unique molecular identifiers to generate accurate numbers of sequencing molecules

Unique molecular identifiers are random oligonucleotide sequences that remove PCR amplification biases. However, the impact that PCR associated sequencing errors have on the accuracy of generating absolute counts of RNA molecules is underappreciated. We show that PCR errors are a source of inaccuracy in both bulk and single-cell sequencing data, and synthesizing unique molecular identifiers using homotrimeric nucleotide blocks provides an error-correcting solution that allows absolute counting of sequenced molecules

Seasonal benefits of farmland pond management for birds

Capsule: There is seasonal variation in the benefits that birds can take from restored farmland ponds. Aims: To evaluate season-specific benefits of farmland pond restoration for local bird communities. Methods: Bird communities were recorded at unmanaged overgrown and managed open-canopy farmland ponds over the breeding, post-breeding and winter seasons. Results were compared and related to seasonal variation in environmental conditions of within-pond and marginal habitats to identify predictors of local bird communities. Results: Bird communities at managed open-canopy ponds showed a higher abundance and species richness over all seasons and displayed pronounced seasonal shifts in composition. Warblers and other specialised bird species were frequently observed at open-canopy sites over the breeding and post-breeding seasons but were generally absent from overgrown ponds. While pond management and landscape connectivity had a consistent positive influence on bird communities over all seasons, the importance of other predictors such as bramble area varied seasonally. Conclusions: Our study highlights a key role of pond management for farmland bird conservation. In addition, the identified seasonal predictors of bird assemblages provide valuable lessons for the design of agri-environment prescriptions for farmland ponds, highlighting the importance of bramble-dominated patches and pond marginal habitat over the breeding season and of a strong connectivity between pond margins and surrounding semi-natural habitats throughout the year

Aerosol-forced AMOC changes in CMIP6 historical simulations

The Atlantic Meridional Overturning Circulation (AMOC) has been, and will continue to be, a key factor in the modulation of climate change both locally and globally. However, there remains considerable uncertainty in recent AMOC evolution. Here, we show that the multi-model mean AMOC strengthened by approximately 10% from 1850-1985 in new simulations from the 6th Coupled Model Inter-comparison Project (CMIP6), a larger change than was seen in CMIP5. Across the models, the strength of the AMOC trend up to 1985 is related to a proxy for the strength of the aerosol forcing. Therefore, the multi-model difference is a result of stronger anthropogenic aerosol forcing on average in CMIP6 than CMIP5, which is primarily due to more models including aerosol-cloud interactions. However, observational constraints - including a historical sea surface temperature fingerprint and shortwave radiative forcing in recent decades - suggest that anthropogenic forcing and/or the AMOC response may be overestimated

Sonic Hedgehog and Notch Signaling Can Cooperate to Regulate Neurogenic Divisions of Neocortical Progenitors

Innate lymphoid cells (ILCs) and innate-like lymphocytes have important roles in immune responses in the context of infection, cancer, and autoimmunity. The factors involved in driving the differentiation and function of these cell types remain to be clearly defined. There are several cellular signaling pathways involved in embryogenesis, which continue to function in adult tissue. In particular, the WNT, NOTCH, and Hedgehog signaling pathways are emerging as regulators of hematopoietic cell development and differentiation. This review discusses the currently known roles of WNT, NOTCH, and Hedgehog signaling in the differentiation and function of ILCs and innate-like lymphocytes

Measurement of the W-boson mass in pp collisions at √s=7 TeV with the ATLAS detector

A measurement of the mass of the W boson is presented based on proton–proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to 4.6 fb−1 of integrated luminosity. The selected data sample consists of 7.8×106 candidates in the W→μν channel and 5.9×106 candidates in the W→eν channel. The W-boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the W boson transverse mass in the electron and muon decay channels, yielding mW=80370±7 (stat.)±11(exp. syst.) ±14(mod. syst.) MeV =80370±19MeV, where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty. A measurement of the mass difference between the W+ and W−bosons yields mW+−mW−=−29±28 MeV

Communicative competence as a basis for the creative interaction of the professional (vocational-technical) education institution's subjects: the special course for the audience members of the advanced training classes of professional education administra

Матеріали спецкурсу присвячено проблемі комунікативної компетентності керівників, новопризначених керівників та педагогічних працівників обласних навчально-(науково)-методичних центрів (кабінетів), закладів професійної (професійно-технічної) освіти для удосконалення власного досвіду та педагогічної майстерності. Зміст спецкурсу спрямовано на розвиток комунікативної взаємодії суб’єктів освітнього процесу, професійно-особистісного розвитку педагогічних кадрів. Спецкурс підготовлений для слухачів курсів підвищення кваліфікації керівних та педагогічних кадрів професійної (професійно-технічної) освіти у Центральному інституті післядипломної освіти ДВНЗ «Університет менеджменту освіти».The materials of special course are devoted to the problem of communicative competence of managers, newly appointed managers and pedagogical workers of regional educational (scientific) -methodic centers (offices), institutions of professional (vocational-technical) education for improving their own experience and pedagogical skills. The content of the special course aims to develop the communicative interaction between the subjects of the educational process, professional and personal development of teaching staff. The special course has been developed for management and pedagogical staff of vocational (vocational-technical) education refresher training at the Central Institute of Postgraduate Education "University of Education Management"

Inclusive and differential cross-section measurements of t\bartZ production in pp collisions at √s=13 TeV with the ATLAS detector, including EFT and spin-correlation interpretations

Measurements of both the inclusive and differential production cross sections of a top-quark-top-antiquark pair in association with a Z boson (tt¯Z) are presented. Final states with two, three or four isolated leptons (electrons or muons) are targeted. The measurements use the data recorded by the ATLAS detector in pp collisions at s√=13 TeV at the Large Hadron Collider during the years 2015-2018, corresponding to an integrated luminosity of 140 fb−1. The inclusive cross section is measured to be σtt¯Z=0.86±0.04 (stat.)±0.04 (syst.) pb and found to be in agreement with the most advanced Standard Model predictions. The differential measurements are presented as a function of a number of observables that probe the kinematics of the tt¯Z system. Both the absolute and normalised differential cross-section measurements are performed at particle level and parton level for specific fiducial volumes, and are compared with NLO+NNLL theoretical predictions. The results are interpreted in the framework of Standard Model effective field theory and used to set limits on a large number of dimension-6 operators involving the top quark. The first measurement of spin correlations in tt¯Z events is presented: the results are in agreement with the Standard Model expectations, and the null hypothesis of no spin correlations is disfavoured with a significance of 1.8 standard deviations