Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70–75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70–80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.Cancer Research UK, Grant/Award Number: FC001003; Changzhou Science and Technology Bureau, Grant/Award Number: CE20200503; Department of Energy and Climate Change, Grant/Award Numbers: DE-AR001213, DE-SC0020400, DE-SC0021303; H2020 European Institute of Innovation and Technology, Grant/Award Numbers: 675728, 777536, 823830; Institut national de recherche en informatique et en automatique (INRIA), Grant/Award Number: Cordi-S; Lietuvos Mokslo Taryba, Grant/Award Numbers: S-MIP-17-60, S-MIP-21-35; Medical Research Council, Grant/Award Number: FC001003; Japan Society for the Promotion of Science KAKENHI, Grant/Award Number: JP19J00950; Ministerio de Ciencia e Innovación, Grant/Award Number: PID2019-110167RB-I00; Narodowe Centrum Nauki, Grant/Award Numbers: UMO-2017/25/B/ST4/01026, UMO-2017/26/M/ST4/00044, UMO-2017/27/B/ST4/00926; National Institute of General Medical Sciences, Grant/Award Numbers: R21GM127952, R35GM118078, RM1135136, T32GM132024; National Institutes of Health, Grant/Award Numbers: R01GM074255, R01GM078221, R01GM093123, R01GM109980, R01GM133840, R01GN123055, R01HL142301, R35GM124952, R35GM136409; National Natural Science Foundation of China, Grant/Award Number: 81603152; National Science Foundation, Grant/Award Numbers: AF1645512, CCF1943008, CMMI1825941, DBI1759277, DBI1759934, DBI1917263, DBI20036350, IIS1763246, MCB1925643; NWO, Grant/Award Number: TOP-PUNT 718.015.001; Wellcome Trust, Grant/Award Number: FC00100

Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin’s lymphoma characterised by overexpression of cyclin D1.Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease withmedian survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators inprogressive MCL. We have used the human MCL cell lines REC1 G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expres-sion of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18–20 and 28–30 kDa) decreasedwith disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21CIP1and p27KIP1)are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27KIP1followed a similar profile of expression as cyclin D1.Conversely, p21CIP1was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellularlocalization detected p21CIP1/p27KIP1primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction withreduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease andtreatment resistance

Kalibracja przenośnego spektrometru fluorescencji rentgenowskiej (XRF) na granitach zawierających Sn-W ze złoża Cínovec (Erzgebirge/Krušné Hory Mts., Republika Czeska)

This study evaluates the suitability of portable X-Ray fluorescence spectrometry (PXRF) in the environment of granites and greisens with Sn-W and secondary mineralization of other important elements (Rb,Y, La, Ce, Nb, Ta and Tl). International certificated reference materials (CRM), historical data from the sixties based on the borehole CS-1, current analyses in accredited laboratory and data measured by a portable X-ray fluorescence spectrometer (PXRF) with factory settings were evaluated in this study. Powder CRMs and samples from borehole CS-1 were analysed by PXRF. The results of PXRF analysis were then tested for reliability, credibility, accuracy and precision. The accuracy was calculated as a relative percent difference (RPD), regression equations and correlation coefficients. A detailed statistical evaluation of the results proves, that PXRF can be a very useful method for a primary determination of main, secondary and trace elements. Comparison of the conventional methods and the PXRF shows a good correlation of different analytical methods and a good possibility of using the PXRF method for a future selection of samples for subsequent more demanding and expensive conventional and special analyses. A calibration of the PXRF spectrometer to the lithological environment of Sn-W ore-bearing granites and greisens was made by the statistical comparison of the methods.Niniejsze badania sprawdzają przydatność przenośnego spektrometru fluorescencji rentgenowskiej (ang. skrót PXRF) w warunkach występowania granitów i grejzenów z Sn-W oraz wtórnej mineralizacji innych pierwiastków (Rb, Y, La, Ce, Nb, Ta i Tl). W badaniach uwzględniono międzynarodowe certyfikowane materiały odniesienia (ang. skrót CRM), dane historyczne z lat 60 oparte na odwiertach CS-1, bieżące analizy w akredytowanych laboratoriach i dane uzyskane z przenośnego spektrometru fluorescencji rentgenowskiej (PXRF) z ustawieniami fabrycznymi. CRM proszkowe oraz próbki pobrane z odwiertu CS-1 przeanalizowano w PXRF. Wyniki analizy PXRF zostały następnie poddane testom na niezawodność, wiarygodność, dokładność i precyzję. Dokładność została policzona jako względna różnica procentowa (RPD), równania regresyjne i współczynniki korelacji. Szczegółowa ocena statystyczna wyników dowodzi, że PXRF może być pomocną metodą we wstępnym określaniu zawartości pierwiastków głównych, wtórnych i śladowych. Porównanie metod konwencjonalnych z metodą PXRF pokazało pozytywną korelację różnych metod analitycznych i możliwość stosowania metody PXRF do przyszłych doborów próbek w celu dalszych trudniejszych i droższych analiz konwencjonalnych i specjalistycznych. Kalibracja spektrometru PXRF do warunków występowania litu w granitach i grejzenach zawierających rudę Sn-W została sporządzona została na podstawie statystycznego porównania wymienionych metod

Multiple Hypersensitivities Including Recurrent Airway Obstruction, Insect Bite Hypersensitivity, and Urticaria in 2 Warmblood Horse Populations.

BACKGROUND Multiple hypersensitivities (MHS) have been described in humans, cats, and dogs, but not horses. HYPOTHESES Horses suffering from recurrent airway obstruction (RAO), insect bite hypersensitivity (IBH), or urticaria (URT) will have an increased risk of also being affected by another one of these hypersensitivities. This predisposition for MHS also will be associated with decreased shedding of strongylid eggs in feces and with a single nucleotide polymorphism (SNP BIEC2-224511), previously shown to be associated with RAO. ANIMALS The first population (P1) included 119 randomly sampled horses representative of the Swiss sporthorse population; the replication population (P2) included 210 RAO-affected Warmblood horses and 264 RAO-unaffected controls. All horses were Warmbloods, 14 years or older. METHODS Associations between disease phenotypes (RAO, IBH, URT, MHS) fecal egg counts, the SNP BIEC2-224511 as well as management and environmental factors were investigated. RESULTS In P1, RAO-affected horses had a 13.1 times higher odds ratio (OR) of also suffering from IBH (P = .004). In P2, the respective OR was 7.4 (P = .002) and IBH-affected horses also showed a 7.1 times increased OR of concomitantly suffering from URT (P < .001). IBH, URT, and MHS phenotypes were significantly associated with the absence of nematode eggs in the feces. CONCLUSIONS AND CLINICAL IMPORTANCE This is the first report of MHS in horses. Specifically, an increased risk for IBH should be expected in RAO-affected horses