Mechanical shock during egg de-adhesion and post-ovulatory ageing contribute to spontaneous autopolyploidy in white sturgeon culture (Acipenser transmontanus)

Spontaneous autopolyploidy, a 1.5x increase in genome size resulting from second polar body retention after fertilization, has been documented in cultured sturgeons, with the proportion of spontaneous autopolyploid progeny ranging widely among maternal families. Sturgeon farms wish to reduce the number of spontaneous autopolyploids because their progeny, when crossed with a normal ploidy parent, exhibit intermediate ploidies, resulting in reproductive abnormalities. However, there is limited knowledge of the causes of the second polar body retention in sturgeon culture. In this study, we report the results of experiments performed from 2015 to 2019 aimed at identifying the sources of spontaneous autopolyploidy in white sturgeon (Acipenser transmontanus) culture. In collaboration with several sturgeon farms, we tested whether post-ovulatory ageing, mechanical shock during egg de-adhesion, and the combined effects of both factors increased spontaneous autopolyploidy. To test the effect of post-ovulatory ageing, eggs were collected from females and either fertilized at the industry normative time (2–5 h post-oviposition) or stored in ovarian fluid at 15 °C for 6–8 h before fertilization. To test the effect of mechanical shock, eggs were collected, fertilized 2–5 h post-oviposition and exposed to either gentle or vigorous mixing during the 60 min de-adhesion treatment. Results from this work reveal that post-ovulatory ageing does increase the incidence of spontaneous autopolyploidy in some females, but overall the proportions produced were low (range 0–15%). Proportions of spontaneous autopolyploids in eggs exposed to vigorous mixing were also variable (1–92%) but significantly higher in 75% of the females when compared to their respective controls or gentle mixing treatments, indicating that mechanical shock during egg de-adhesion is likely the primary cause of spontaneous autopolyploidy. To our knowledge this is the first study to document mechanical shock to eggs during de-adhesion as a cause of abnormal ploidy in cultured fishes. We observed high variability in egg quality among females and a significant relationship between embryo mortality and the incidence of spontaneous autopolyploidy when eggs were exposed to mechanical shock. Repeated spawning of a female that produced a high proportion of spontaneous autopolyploids provided preliminary evidence that genetic background may influence the likelihood that a female's eggs will be prone to second polar body retention when subjected to mechanical shock. Although spontaneous autopolyploidy in sturgeon culture will likely never be eliminated entirely, we provide practical recommendations to sturgeon producers to reduce its incidence in a production setting

Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

Towards an empirical test of realism in cognition

We review recent progress in designing an empirical test of (temporal) realism in cognition. Realism in this context is the property that cognitive variables always have well defined (if possibly unknown) values at all times. We focus most of our attention in this contribution on discussing the exact notion of realism that is to be tested, as we feel this issue has not received enough attention to date. We also give a brief outline of the empirical test, including some comments on an experimental realisation, and we discuss what we should conclude from any purported experimental ‘disproof’ of realism. This contribution is based on Yearsley and Pothos (2014)

A framework for protein structure classification and identification of novel protein structures

BACKGROUND: Protein structure classification plays a central role in understanding the function of a protein molecule with respect to all known proteins in a structure database. With the rapid increase in the number of new protein structures, the need for automated and accurate methods for protein classification is increasingly important. RESULTS: In this paper we present a unified framework for protein structure classification and identification of novel protein structures. The framework consists of a set of components for comparing, classifying, and clustering protein structures. These components allow us to accurately classify proteins into known folds, to detect new protein folds, and to provide a way of clustering the new folds. In our evaluation with SCOP 1.69, our method correctly classifies 86.0%, 87.7%, and 90.5% of new domains at family, superfamily, and fold levels. Furthermore, for protein domains that belong to new domain families, our method is able to produce clusters that closely correspond to the new families in SCOP 1.69. As a result, our method can also be used to suggest new classification groups that contain novel folds. CONCLUSION: We have developed a method called proCC for automatically classifying and clustering domains. The method is effective in classifying new domains and suggesting new domain families, and it is also very efficient. A web site offering access to proCC is freely available a

Dynamic Interaction of cBid with Detergents, Liposomes and Mitochondria

The BH3-only protein Bid plays a key role in the induction of mitochondrial apoptosis, but its mechanism of action is still not completely understood. Here we studied the two main activation events of Bid: Caspase-8 cleavage and interaction with the membrane bilayer. We found a striking reversible behaviour of the dissociation-association events between the Bid fragments p15 and p7. Caspase-8 cleavage does not induce per se separation of the two Bid fragments, which remain in a stable complex resembling the full length Bid. Detergents trigger a complete dissociation, which can be fully reversed by detergent removal in a range of protein concentrations from 100 µM down to 500 nM. Incubation of cBid with cardiolipin-containing liposomes leads to partial dissociation of the complex. Only p15 (tBid) fragments are found at the membrane, while p7 shows no tendency to interact with the bilayer, but complete removal of p7 strongly increases the propensity of tBid to become membrane-associated. Despite the striking structural similarities of inactive Bid and Bax, Bid does not form oligomers and reacts differently in the presence of detergents and membranes, highlighting clear differences in the modes of action of the two proteins. The partial dissociation of cBid triggered by the membrane is suggested to depend on the strong and specific interaction between p15 and p7. The reversible disassembly and re-assembly of the cBid molecules at the membrane was as well proven by EPR using spin labeled cBid in the presence of isolated mitochondria. The observed dynamic dissociation of the two Bid fragments could allow the assistance to the pore-forming Bax to occur repeatedly and may explain the proposed “hit-and-run" mode of action of Bid at the bilayer

A generic travelling wave solution in dissipative laser cavity

A large family of cosh-Gaussian travelling wave solution of a complex Ginzburg–Landau equation (CGLE), that describes dissipative semiconductor laser cavity is derived. Using perturbation method, the stability region is identified. Bifurcation analysis is done by smoothly varying the cavity loss coefficient to provide insight of the system dynamics. He’s variational method is adopted to obtain the standard sech-type and the notso-explored but promising cosh-Gaussian type, travelling wave solutions. For a given set of system parameters, only one sech solution is obtained, whereas several distinct solution points are derived for cosh-Gaussian case. These solutions yield a wide variety of travelling wave profiles, namely Gaussian, near-sech, flat-top and a cosh-Gaussianwith variable central dip. A split-step Fourier method and pseudospectral method have been used for direct numerical solution of the CGLE and travelling wave profiles identical to the analytical profiles have been obtained. We also identified the parametric zone that promises an extremely large family of cosh-Gaussian travelling wave solutions with tunable shape. This suggests that the cosh-Gaussian profile is quite generic and would be helpful for further theoretical as well as experimental investigation on pattern formation, pulse dynamics andlocalization in semiconductor laser cavity

Mottness at finite doping and charge instabilities in cuprates

The intrinsic instability of underdoped copper oxides towards inhomogeneous states is one of the central puzzles of the physics of correlated materials. The influence of the Mott physics on the doping-temperature phase diagram of copper oxides represents a major issue that is subject of intense theoretical and experimental effort. Here, we investigate the ultrafast electron dynamics in prototypical single-layer Bi-based cuprates at the energy scale of the O-2p\u2192Cu-3d charge-transfer (CT) process. We demonstrate a clear evolution of the CT excitations from incoherent and localized, as in a Mott insulator, to coherent and delocalized, as in a conventional metal. This reorganization of the high-energy degrees of freedom occurs at the critical doping pcr 430.16 irrespective of the temperature, and it can be well described by dynamical mean field theory calculations. We argue that the onset of the low-temperature charge instabilities is the low-energy manifestation of the underlying Mottness that characterizes the p<pcr region of the phase diagram. This discovery sets a new framework for theories of charge order and low-temperature phases in underdoped copper oxides. ArXI

Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells.

Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres