bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic interaction between the non‐homologous end‐joining factors during B and T lymphocyte development: In vivo mouse models
Authors: Castañeda‐Zegarra Sergio , Fernandez‐Berrocal Marion , Tkachov Max , Yao Rouan , Upfold Nikki Lyn Esnardo , Oksenych Valentyn 
Published: July 2020

AbstractNon‐homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double‐strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA‐PKcs, Artemis, PAXX, MRI) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.
The relationship between peak fat oxidation and prolonged double‐poling endurance exercise performance
Authors: Rømer Tue , Thunestvedt Hansen Mikkel , Frandsen Jacob , Larsen Steen , Dela Flemming , Wulff Helge Jørn 
Published: July 2020

The peak fat oxidation rate (PFO) and the exercise intensity that elicits PFO (Fatmax) are associated with endurance performance during exercise primarily involving lower body musculature, but it remains elusive whether these associations are present during predominant upper body exercise. The aim was to investigate the relationship between PFO and Fatmax determined during a graded exercise test on a ski‐ergometer using double‐poling (GET‐DP) and performance in the long‐distance cross‐country skiing race, Vasaloppet. Forty‐three healthy men completed GET‐DP and Vasaloppet and were divided into two subgroups: recreational (RS, n = 35) and elite (ES, n = 8) skiers. Additionally, RS completed a cycle‐ergometer GET (GET‐Cycling) to elucidate whether the potential relationships were specific to exercise modality. PFO (r2 = .10, P = .044) and Fatmax (r2 = .26, P < .001) were correlated with performance; however, was the only independent predictor of performance (adj. R2 = .36) across all participants. In ES, Fatmax was the only variable associated with performance (r2 = .54, P = .038). Within RS, DP (r2 = .11, P = .047) and ski‐specific training background (r2 = .30, P = .001) were associated with performance. Between the two GETs, Fatmax (r2 = .20, P = .006) but not PFO (r2 = .07, P = .135) was correlated. Independent of exercise mode, neither PFO nor Fatmax were associated with performance in RS (P > .05). These findings suggest that prolonged endurance performance is related to PFO and Fatmax but foremost to during predominant upper body exercise. Interestingly, Fatmax may be an important determinant of performance among ES. Among RS, DP , and skiing experience appeared as performance predictors. Additionally, whole‐body fat oxidation seemed specifically coupled to exercise modality.
Characterization of elemental ratios and oxidative ratio of horticultural peat
Authors: Byrne Kenneth A. , Efretuei Arit , Walz Kilian , Clay Gareth D. 
Published: July 2020

AbstractPeatlands occupy 20% of the land area of Ireland and store over half of soil carbon stocks. Over 80% of these peatlands have been disturbed by human activity such as drainage for peat extraction, afforestation and agriculture. In this study, peat samples were collected from 12 horticultural peat extraction sites in the Irish midlands. The carbon (C), nitrogen (N), hydrogen and sulphur content were determined, and from these, the carbon oxidation state (Cox) and oxidative ratio (OR) were calculated. The carbon oxidation ratio reflects organic matter synthesis and degradation, and is thus an important parameter in understanding terrestrial carbon cycling, whilst OR represents the molar ratio of oxygen (O2) and carbon dioxide (CO2) fluxes associated with net ecosystem exchange. Elemental concentrations and ratios were typical for Irish horticultural peat (e.g. carbon concentrations 54%–57%), though showed site to site variability. Cox and OR values varied between −0.22 and −0.11, and 1.04 and 1.07, respectively, and were comparable to United Kingdom peat soils. All values for OR were lower than 1.1, the value commonly used in global CO2 partitioning studies. Further research should investigate OR values in peatland which has not been studied to date. Across all sites, measures of increased decomposition (i.e. C/N ratios) significantly correlated with increasing OR reflecting more reduced organic matter. This study provides data in temperate peat soils that increases the coverage of Cox and OR values and will inform global CO2 partitioning studies.
10Be surface exposure dating reveals unexpected high deformation rates in the central Andean wedge interior
Authors: García Morabito Ezequiel , Terrizzano Carla M. , Zech Roland , Yamin Marcela , Wüthrich Lorenz , Christl Marcus , Ramos Víctor A. , Haghipour Negar , Cortés José M. 
Published: July 2020

AbstractUnderstanding deformation associated with active thrust wedges is essential to evaluate seismic hazards. In this study, we investigate the spatial distribution, timing, and rates of deformation across the central Andean backarc of Argentina, where deformation and shortening have been assumed to occur within a narrow wedge‐front zone. The combined results of our geomorphic mapping, topographic surveying, and10Be exposure dating demonstrate that fault activity related to the growth of the Andean orogenic wedge is not only limited to a narrow thrust front zone but also occurs in the Andean wedge interior. There, internal structures with deformation rates of ca. 1.3 mm/year have been active during the last ~140 ka. Widely distributed deformation implies that seismic hazards may have been underestimated in the internal part of the Andean orogen.
Disseminated histoplasmosis in a kidney transplant patient
Authors: Angsutararux Taksaon , Chongtrakool Piriyaporn , Sukpanichnant Sanya , Wongwaipijarn Kornpawee , Wangchinda Walaiporn 
Published: July 2020

AbstractPatients with impaired cell‐mediated immunity have a higher risk of developing histoplasmosis; however, histoplasmosis after solid organ transplantation is rare. In Thailand, histoplasmosis cases are sporadic, and most cases are associated with human immunodeficiency virus (HIV) infection. Herein, we report a case of disseminated histoplasmosis in a kidney transplant Thai recipient diagnosed by fungal staining of fungal culture from bronchoalveolar lavage and bone marrow biopsy. Liposomal amphotericin B was given followed by oral itraconazole. The patient's clinical condition was improved; however, his graft function was irreversibly declined. The majority of histoplasmosis cases after solid organ transplant presented with disseminated disease with pulmonary involvement. Even in a non‐endemic area of histoplasmosis, suspected cases should be early diagnosed and promptly managed in order to reduce morbidity and mortality, especially in cell‐mediated immunity defect patients like solid organ transplant recipients.
COVID‐19 in solid organ transplant recipients: Dynamics of disease progression and inflammatory markers in ICU and non‐ICU admitted patients
Authors: Roberts Matthew B. , Izzy Saef , Tahir Zabreen , Al Jarrah Ali , Fishman Jay A. , El Khoury Joseph 
Published: July 2020

AbstractBackgroundCOVID‐19 infection varies in severity from minimal symptoms to critical illness associated with a hyperinflammatory response. Data on disease progression in immunosuppressed solid organ transplant (SOT) recipients are limited.MethodsWe examined the electronic medical records of all SOT recipients with COVID‐19 from 12 Massachusetts hospitals between February 1, and May 6, 2020. We analyzed the demographics, clinical parameters, course, and outcomes of illness in these patients.ResultsOf 52 COVID‐19‐positive SOT patients, 77% were hospitalized and 35% required ICU admission. Sixty‐nine percent of hospitalized patients had immunosuppression reduced, 6% developed suspected rejection. Co‐infections occurred in 45% in ICU vs 5% in non‐ICU patients (P = .037). A biphasic pattern of evolution of laboratory tests was observed. In the first 5 days of illness, inflammatory markers were moderately increased. Subsequently, WBC, CRP, ferritin, and D Dimer increased with increasing stay in the ICU, and lymphocyte counts were similar. Five patients (16%) died.ConclusionsOur data indicate that SOT is associated with high rate of hospitalization, ICU admission, and death from COVID‐19 compared to data in the general population of patients with COVID‐19. Despite reduction in immunosuppression, suspected rejection was rare. The clinical course and trend of laboratory biomarkers is biphasic with a later, pronounced peak in inflammatory markers seen in those admitted to an ICU. CRP is a useful marker to monitor disease progression in SOT.
Impact of neutropenia evaluated in terms of the D‐index on invasive fungal disease while on empiric or preemptive antifungal treatment strategy in the early phase after allogeneic hematopoietic stem cell transplantation
Authors: Kimura Shun‐ichi , Nakamura Yuhei , Kawamura Masakatsu , Takeshita Junko , Kawamura Shunto , Yoshino Nozomu , Misaki Yukiko , Yoshimura Kazuki , Matsumi Shimpei , Gomyo Ayumi , Akahoshi Yu , Tamaki Masaharu , Kusuda Machiko , Kameda Kazuaki , Wada Hidenori , Sato Miki , Terasako‐Saito Kiriko , Tanihara Aki , Nakasone Hideki , Kako Shinichi , Kanda Yoshinobu 
Published: July 2020

AbstractBackgroundWe retrospectively evaluated the association between the D‐index, which reflects both the depth and duration of neutropenia, and proven/probable invasive fungal disease (IFD) early after allogeneic hematopoietic stem cell transplantation (HSCT) at our center (n = 394).MethodsThe D‐index was defined as the area over the neutrophil curve during neutropenia. The cumulative D‐index from the start of neutropenia until the development of infection (c‐D‐index) was also evaluated as a real‐time assessment of neutropenia.ResultsThere were 19 cases of early proven/probable IFD before and within 1 week after engraftment. Fifteen cases (78.9%) were seen as breakthrough infection while on empiric (n = 7), preemptive (n = 4) or prophylactic (n = 4) antifungal administration with mold‐active agents. The c‐D‐index and lower performance status were identified as independent significant predictive factors for IFD. A receiver operating characteristic (ROC) curve analysis showed that the D‐index and c‐D‐index were more accurate than the simple duration of neutropenia and as accurate as the duration of profound neutropenia for predicting IFD. The sensitivity, specificity, and positive and negative predictive values of the c‐D‐index using an appropriate cutoff (CO) value (10 644) determined by ROC curve analysis were 73.1%, 63.2%, 9.1%, and 97.9%, respectively. The advantage of the c‐D‐index to cumulative days of neutropenia in terms of positive and negative predictive values seemed to be small.ConclusionsThe appropriate CO value for the c‐D‐index for predicting IFD was as high as 10 644 in allogeneic HSCT with a more frequent use of empiric antifungal therapy. The c‐D‐index is useful for assessing the risk of breakthrough IFD.
Discordant courses of COVID‐19 in a cohabiting couple of lung transplant recipients
Authors: Desmazes‐Dufeu Nadine , Coltey Bérengère , Amari Lyria , Gouitaa Marion , Touzery Camille , Reynaud‐Gaubert Martine , Chanez Pascal , Cassir Nadim 
Published: July 2020

AbstractCOVID‐19 is a novel infectious disease caused by SARS‐CoV‐2 that emerged in late 2019 and which is now a pandemic. Solid organ transplant recipients are perceived to be at increased risk of severe COVID‐19 due to their chronic use of immunosuppressive drugs (ISDs) and to their associated conditions. Scarce data are available on the optimized management of ISDs in these patients and on its impact on presentation, clinical course, viral shedding, and outcome. We report here two cases of COVID‐19 in a cohabiting couple of lung transplant recipients for cystic fibrosis, who had different ISDs management and who developed discordant courses of their disease. Our findings suggest that the degree of their immunosuppression might be a reason for their different course and that ISDs might prove partially protective.
Unique organization of photosystem II supercomplexes and megacomplexes in Norway spruce
Authors: Kouřil Roman , Nosek Lukáš , Opatíková Monika , Arshad Rameez , Semchonok Dmitry A. , Chamrád Ivo , Lenobel René , Boekema Egbert J. , Ilík Petr 
Published: July 2020

SUMMARYPhotosystem II (PSII) complexes are organized into large supercomplexes with variable amounts of light‐harvesting proteins (Lhcb). A typical PSII supercomplex in plants is formed by four trimers of Lhcb proteins (LHCII trimers), which are bound to the PSII core dimer via monomeric antenna proteins. However, the architecture of PSII supercomplexes in Norway spruce[Picea abies (L.) Karst.] is different, most likely due to a lack of two Lhcb proteins, Lhcb6 and Lhcb3. Interestingly, the spruce PSII supercomplex shares similar structural features with its counterpart in the green alga Chlamydomonas reinhardtii [Kouřil et al. (2016) New Phytol. 210, 808–814]. Here we present a single‐particle electron microscopy study of isolated PSII supercomplexes from Norway spruce that revealed binding of a variable amount of LHCII trimers to the PSII core dimer at positions that have never been observed in any other plant species so far. The largest spruce PSII supercomplex, which was found to bind eight LHCII trimers, is even larger than the current largest known PSII supercomplex from C. reinhardtii. We have also shown that the spruce PSII supercomplexes can form various types of PSII megacomplexes, which were also identified in intact grana membranes. Some of these large PSII supercomplexes and megacomplexes were identified also in Pinus sylvestris, another representative of the Pinaceae family. The structural variability and complexity of LHCII organization in Pinaceae seems to be related to the absence of Lhcb6 and Lhcb3 in this family, and may be beneficial for the optimization of light‐harvesting under varying environmental conditions.
Interaction of the Xanthomonas effectors XopQ and XopX results in induction of rice immune responses
Authors: Deb Sohini , Ghosh Palash , Patel Hitendra K. , Sonti Ramesh V. 
Published: July 2020

SUMMARYXanthomonas oryzae pv. oryzae uses several type III secretion system (T3SS) secreted effectors, namely XopN, XopQ, XopX and XopZ, to suppress rice immune responses that are induced following treatment with cell wall degrading enzymes. Here we show that a T3SS secreted effector XopX interacts with two of the eight rice 14‐3‐3 proteins. Mutants of XopX that are defective in 14‐3‐3 binding are also defective in suppression of immune responses, suggesting that interaction with 14‐3‐3 proteins is required for suppression of host innate immunity. However, Agrobacterium‐mediated delivery of both XopQ and XopX into rice cells results in induction of rice immune responses. These immune responses are not observed when either protein is individually delivered into rice cells. XopQ‐XopX‐induced rice immune responses are not observed with a XopX mutant that is defective in 14‐3‐3 binding. Yeast two‐hybrid, bimolecular fluorescence complementation and co‐immunoprecipitation assays indicate that XopQ and XopX interact with each other. A screen for Xanthomonas effectors that can suppress XopQ‐XopX‐induced rice immune responses led to the identification of five effectors, namely XopU, XopV, XopP, XopG and AvrBs2, that could individually suppress these immune responses. These results suggest a complex interplay of Xanthomonas T3SS effectors in suppression of both pathogen‐triggered immunity and effector‐triggered immunity to promote virulence on rice.
FORGETTER2 protein phosphatase and phospholipase D modulate heat stress memory in Arabidopsis
Authors: Urrea Castellanos Reynel , Friedrich Thomas , Petrovic Nevena , Altmann Simone , Brzezinka Krzysztof , Gorka Michal , Graf Alexander , Bäurle Isabel 
Published: July 2020

SUMMARYPlants can mitigate environmental stress conditions through acclimation. In the case of fluctuating stress conditions such as high temperatures, maintaining a stress memory enables a more efficient response upon recurring stress. In a genetic screen for Arabidopsis thaliana mutants impaired in the memory of heat stress (HS) we have isolated the FORGETTER2 (FGT2) gene, which encodes a type 2C protein phosphatase (PP2C) of the D‐clade. Fgt2 mutants acquire thermotolerance normally; however, they are defective in the memory of HS. FGT2 interacts with phospholipase D α2 (PLDα2), which is involved in the metabolism of membrane phospholipids and is also required for HS memory. In summary, we have uncovered a previously unknown component of HS memory and identified the FGT2 protein phosphatase and PLDα2 as crucial players, suggesting that phosphatidic acid‐dependent signaling or membrane composition dynamics underlie HS memory.
Genomic basis of white pine blister rust quantitative disease resistance and its relationship with qualitative resistance
Authors: Weiss Matthew , Sniezko Richard A. , Puiu Daniela , Crepeau Marc W. , Stevens Kristian , Salzberg Steven L. , Langley Charles H. , Neale David B. , De La Torre Amanda R. 
Published: July 2020

SummaryThe genomic architecture and molecular mechanisms controlling variation in quantitative disease resistance loci are not well understood in plant species and have been barely studied in long‐generation trees. Quantitative trait loci mapping and genome‐wide association studies were combined to test a large single nucleotide polymorphism (SNP) set for association with quantitative and qualitative white pine blister rust resistance in sugar pine. In the absence of a chromosome‐scale reference genome, a high‐density consensus linkage map was generated to obtain locations for associated SNPs. Newly discovered associations for white pine blister rust quantitative disease resistance included 453 SNPs involved in wide biological functions, including genes associated with disease resistance and others involved in morphological and developmental processes. In addition, NBS‐LRR pathogen recognition genes were found to be involved in quantitative disease resistance, suggesting these newly reported genes are qualitative genes with partial resistance, they are the result of defeated qualitative resistance due to avirulent races, or they have epistatic effects on qualitative disease resistance genes. This study is a step forward in our understanding of the complex genomic architecture of quantitative disease resistance in long‐generation trees, and constitutes the first step towards marker‐assisted disease resistance breeding in white pine species.
Incorporation of extracorporeal photopheresis into a reduced intensity conditioning regimen in myelodysplastic syndrome and aggressive lymphoma: results from ECOG 1402 and 1902
Authors: Foss Francine M. , Wang Xin Victoria , Luger Selina M. , Jegede Opeyemi , Miller Kenneth B. , Stadtmauer Edward A. , Whiteside Theresa L. , Avigan David E. , Gascoyne Randall D. , Arber Daniel , Wagner Henry , Strair Roger K. , Hogan William J. , Sprague Kellie A. , Lazarus Hillard M. , Litzow Mark R. , Tallman Martin S. , Horning Sandra J. 
Published: July 2020

BackgroundExtracorporeal photopheresis (ECP) is an immunomodulatory cellular therapy which has been shown to induce a tolerogenic state in patients with acute and chronic graft‐vs‐host disease. ECOG‐ACRIN explored the activity of ECP as a part of a reduced intensity conditioning regimen in two multicenter trials in patients with MDS (E1902) and lymphomas (E1402). While both studies closed before completing accrual, we report results in 23 patients (17 MDS and 6 lymphoma).Study Design and MethodsPatients received 2 days of ECP followed by pentostatin 4 mg/m2 /day for two consecutive days, followed by 600 cGy of total body irradiation prior to stem cell infusion. Immunosuppression for aGVHD was infusional cyclosporine A or tacrolimus and methotrexate on day +1, +3, with mycophenolate mofetil starting on day 100 for chronic GVHD prophylaxis.ResultsAll patients engrafted, with median time to neutrophil and platelet engraftment of 15‐18 days and 10‐18 days respectively. Grade 3 or 4 aGVHD occurred in 13% and chronic extensive GVHD in 30%.ConclusionsThese studies demonstrate that ECP/pentostatin/TBI is well tolerated and associated with adequate engraftment of neutrophils and platelets in patients with lymphomas and MDS.
Association between weight change during initial chemotherapy and clinical outcome in dogs with multicentric lymphoma
Authors: Lee Wei‐Shan , Lee Jih‐Jong , Liao Albert Taiching , Kao Chia‐Lien , Wang Shang‐Lin 
Published: July 2020

AbstractThe majority of the known prognostic factors in dogs with lymphoma have been evaluated before treatment commences or at the time of diagnosis. Prognostic factors evaluated during the initial phase of treatment are less described but may provide important clinical information. In this retrospective study, 82 canine lymphoma patients were categorized according to the weight change between diagnosis and after 5 weeks of chemotherapy. Dogs that gained greater than 5% or lost greater than 5% of initial body weight were categorized as increased‐ or decreased‐weight groups, respectively. Those in which weight changed less than 5% were categorized as the maintained‐weight group. The median progression‐free survival (PFS) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 226, 256 and 129 days, respectively. The decreased‐weight group had significantly shorter PFS than the increased and maintained groups (P= .023,P= .003, respectively). The median survival time (ST) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 320, 339 and 222 days, respectively. There was no significant difference in ST among the three groups (P= .128). In Cox‐regression results, weight change group and initial body weight were significant risk factors associated to PFS (P= .007,P= .001, respectively) while only patient's initial body weight was a significant risk factor to ST (P= .013). In conclusion, evaluation of initial body weight and weight changes over time can provide valuable information regarding PFS and ST in dogs with multicentric lymphoma.