bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Response Patterns of Major Rainfed Crops to Adaptation by Maintaining Current Growing Periods and Irrigation
Authors: Minoli Sara , Müller Christoph , Elliott Joshua , Ruane Alex C. , Jägermeyr Jonas , Zabel Florian , Dury Marie , Folberth Christian , François Louis , Hank Tobias , Jacquemin Ingrid , Liu Wenfeng , Olin Stefan , Pugh Thomas A. M. 
Published: October 2019

AbstractIncreasing temperature trends are expected to impact yields of major field crops by affecting various plant processes, such as phenology, growth, and evapotranspiration. However, future projections typically do not consider the effects of agronomic adaptation in farming practices. We use an ensemble of seven Global Gridded Crop Models to quantify the impacts and adaptation potential of field crops under increasing temperature up to 6 K, accounting for model uncertainty. We find that without adaptation, the dominant effect of temperature increase is to shorten the growing period and to reduce grain yields and production. We then test the potential of two agronomic measures to combat warming‐induced yield reduction: (i) use of cultivars with adjusted phenology to regain the reference growing period duration and (ii) conversion of rainfed systems to irrigated ones in order to alleviate the negative temperature effects that are mediated by crop evapotranspiration. We find that cultivar adaptation can fully compensate global production losses up to 2 K of temperature increase, with larger potentials in continental and temperate regions. Irrigation could also compensate production losses, but its potential is highest in arid regions, where irrigation expansion would be constrained by water scarcity. Moreover, we discuss that irrigation is not a true adaptation measure but rather an intensification strategy, as it equally increases production under any temperature level. In the tropics, even when introducing both adapted cultivars and irrigation, crop production declines already at moderate warming, making adaptation particularly challenging in these areas.
Thunderstorm Efficiency Regimes in South America as Observed by STARNET and TRMM
Authors: Morales Rodriguez C.A. 
Published: October 2019

AbstractSix years of cloud to ground lighting strokes from Sferics Timing And Ranging NETwork (STARNET) and rain estimates from Tropical Rainfall Measuring Mission (TRMM 3B42) gridded in a box of 1° × 1° of longitude by latitude have been combined to investigate how thunderstorm efficiency (rain yield − daily rain accumulations/daily number of strokes) varies spatially and seasonally over South America. Based on daily rain yields, 98% of the thunderstorms can be represented by four regimes: continental‐arid (106.5–107.5 kg per stroke), continental (107.5–108.5 kg per stroke), continental‐maritime (green‐ocean; 108.5–109.5 kg per stroke), and maritime (109.5–1010.5 kg per stroke). The continental‐arid regimes are found over the Andes Mountains while the continental regimes extend from southern to central northern South America. The continental‐maritime regime runs from the Amazon basin to northern South America, and the maritime regime is found over the ocean and along the coastline. Mean radar reflectivity profiles from coincident measurements of 2A25 TRMM‐Precipitation Radar obtained for each rain yield regimes show that (a) the continental regimes have a higher concentration of ice and supercooled water droplets above the 0 °C isotherm height; (b) maritime regimes have larger rain volumes in the warmer phase; (c) the continental‐arid regime shows the highest concentration of ice and supercooled water droplets at temperatures below −20 °C; (d) the continental‐maritime and maritime regimes are similar, but the continental‐maritime regime has slightly higher reflectivities (1–2 dBZ) and has greater 30‐dBZ height; and (e) the partition of ice and supercooled water droplets between 0 and −40 °C influences the lightning frequency.
ERK-dependent phosphorylation of the linker and substrate-binding domain of HSP70 increases folding activity and cell proliferation
Authors: Lim Semi , Kim Dae Gyu , Kim Sunghoon 
Published: October 2019

Abstract
The enhanced productive folding of translated polypeptides by heat shock protein 70 (HSP70) is often required for the survival of cancer cells. Although the folding activity of HSP70 is considered a significant determinant of the progression of cancer cells, it is still unknown how this activity could be regulated. Here, we report that the phosphorylation of HSP70 facilitates its folding activity, enhancing cell proliferation. Mass spectrometry identified the serine residues at positions 385 and 400 in the linker and substrate-binding domains of HSP70, respectively, as sites of phosphorylation mediated by EGF signaling, and this result was further confirmed by site-directed mutagenesis. ERK is known to be a specific kinase. The phosphorylation of the two sites induces the extended conformation of HSP70 via the regulation of the binding of the linker to the nucleotide- and substrate-binding domains, augmenting the binding affinity of HSP70 to substrates and enhancing its folding activity; this ultimately results in pro-proliferative effects. Cell lines harboring activated ERK showed increased phosphorylation of HSP70, and a positive correlation between the phosphorylation of HSP70 and the activity of ERK was observed. Thus, this study demonstrated that the ERK-dependent phosphorylation of HSP70 facilitated its folding activity and cellular proliferative function.
Advancing antimicrobial strategies for managing oral biofilm infections
Authors: Jiao Yang , Tay Franklin R. , Niu Li-na , Chen Ji-hua 
Published: October 2019

AbstractEffective control of oral biofilm infectious diseases represents a major global challenge. Microorganisms in biofilms exhibit increased drug tolerance compared with planktonic cells. The present review covers innovative antimicrobial strategies for controlling oral biofilm-related infections published predominantly over the past 5 years. Antimicrobial dental materials based on antimicrobial agent release, contact-killing and multi-functional strategies have been designed and synthesized for the prevention of initial bacterial attachment and subsequent biofilm formation on the tooth and material surface. Among the therapeutic approaches for managing biofilms in clinical practice, antimicrobial photodynamic therapy has emerged as an alternative to antimicrobial regimes and mechanical removal of biofilms, and cold atmospheric plasma shows significant advantages over conventional antimicrobial approaches. Nevertheless, more preclinical studies and appropriately designed and well-structured multi-center clinical trials are critically needed to obtain reliable comparative data. The acquired information will be helpful in identifying the most effective antibacterial solutions and the most optimal circumstances to utilize these strategies.
Functional characterization of BRCC3 mutations in acute myeloid leukemia with t(8;21)(q22;q22.1)
Authors: Meyer Tatjana , Jahn Nikolaus , Lindner Stefanie , Röhner Linda , Dolnik Anna , Weber Daniela , Scheffold Annika , Köpff Simon , Paschka Peter , Gaidzik Verena I. , Heckl Dirk , Wiese Sebastian , Ebert Benjamin L. , Döhner Hartmut , Bullinger Lars , Döhner Konstanze , Krönke Jan 
Published: October 2019

Abstract
BRCA1/BRCA2-containing complex 3 (BRCC3) is a Lysine 63-specific deubiquitinating enzyme (DUB) involved in inflammasome activity, interferon signaling, and DNA damage repair. Recurrent mutations in BRCC3 have been reported in myelodysplastic syndromes (MDS) but not in de novo AML. In one of our recent studies, we found BRCC3 mutations selectively in 9/191 (4.7%) cases with t(8;21)(q22;q22.1) AML but not in 160 cases of inv(16)(p13.1q22) AML. Clinically, AML patients with BRCC3 mutations had an excellent outcome with an event-free survival of 100%. Inactivation of BRCC3 by CRISPR/Cas9 resulted in improved proliferation in t(8;21)(q22;q22.1) positive AML cell lines and together with expression of AML1-ETO induced unlimited self-renewal in mouse hematopoietic progenitor cells in vitro. Mutations in BRCC3 abrogated its deubiquitinating activity on IFNAR1 resulting in an impaired interferon response and led to diminished inflammasome activity. In addition, BRCC3 inactivation increased release of several cytokines including G-CSF which enhanced proliferation of AML cell lines with t(8;21)(q22;q22.1). Cell lines and primary mouse cells with inactivation of BRCC3 had a higher sensitivity to doxorubicin due to an impaired DNA damage response providing a possible explanation for the favorable outcome of BRCC3 mutated AML patients.
CM-Path Molecular Diagnostics Forum—consensus statement on the development and implementation of molecular diagnostic tests in the United Kingdom
Authors:   on behalf of the CM-Path Molecular Diagnostics working group, Macklin Philip S. , Pillay Nischalan , Lee Jessica L. , Pitman Helen , Scott Sophie , Wang Jayson , Craig Clare , Jones J. Louise , Oien Karin A. , Colling Richard , Coupland Sarah E. , Verrill Clare 
Published: October 2019

Abstract

Background
Pathology has evolved from a purely morphological description of cellular alterations in disease to our current ability to interrogate tissues with multiple ‘omics’ technologies. By utilising these techniques and others, ‘molecular diagnostics’ acts as the cornerstone of precision/personalised medicine by attempting to match the underlying disease mechanisms to the most appropriate targeted therapy.

Methods
Despite the promises of molecular diagnostics, significant barriers have impeded its widespread clinical adoption. Thus, the National Cancer Research Institute (NCRI) Cellular Molecular Pathology (CM-Path) initiative convened a national Molecular Diagnostics Forum to facilitate closer collaboration between clinicians, academia, industry, regulators and other key stakeholders in an attempt to overcome these.

Results
We agreed on a consensus ‘roadmap’ that should be followed during development and implementation of new molecular diagnostic tests. We identified key barriers to efficient implementation and propose possible solutions to these. In addition, we discussed the recent reconfiguration of molecular diagnostic services in NHS England and its likely impacts.

Conclusions
We anticipate that this consensus statement will provide practical advice to those involved in the development of novel molecular diagnostic tests. Although primarily focusing on test adoption within the United Kingdom, we also refer to international guidelines to maximise the applicability of our recommendations.
The ubiquitin-like modifier FAT10 interferes with SUMO activation
Authors: Aichem Annette , Sailer Carolin , Ryu Stella , Catone Nicola , Stankovic-Valentin Nicolas , Schmidtke Gunter , Melchior Frauke , Stengel Florian , Groettrup Marcus 
Published: October 2019

AbstractThe covalent attachment of the cytokine-inducible ubiquitin-like modifier HLA-F adjacent transcript 10 (FAT10) to hundreds of substrate proteins leads to their rapid degradation by the 26 S proteasome independently of ubiquitylation. Here, we identify another function of FAT10, showing that it interferes with the activation of SUMO1/2/3 in vitro and down-regulates SUMO conjugation and the SUMO-dependent formation of promyelocytic leukemia protein (PML) bodies in cells. Mechanistically, we show that FAT10 directly binds to and impedes the activity of the heterodimeric SUMO E1 activating enzyme AOS1/UBA2 by competing very efficiently with SUMO for activation and thioester formation. Nevertheless, activation of FAT10 by AOS1/UBA2 does not lead to covalent conjugation of FAT10 with substrate proteins which relies on its cognate E1 enzyme UBA6. Hence, we report that one ubiquitin-like modifier (FAT10) inhibits the conjugation and function of another ubiquitin-like modifier (SUMO) by impairing its activation.
Functional recruitment of dynamin requires multimeric interactions for efficient endocytosis
Authors: Rosendale Morgane , Van Thi Nhu Ngoc , Grillo-Bosch Dolors , Sposini Silvia , Claverie Léa , Gauthereau Isabel , Claverol Stéphane , Choquet Daniel , Sainlos Matthieu , Perrais David 
Published: October 2019

AbstractDuring clathrin mediated endocytosis (CME), the concerted action of dynamin and its interacting partners drives membrane scission. Essential interactions occur between the proline/arginine-rich domain of dynamin (dynPRD) and the Src-homology domain 3 (SH3) of various proteins including amphiphysins. Here we show that multiple SH3 domains must bind simultaneously to dynPRD through three adjacent motifs for dynamin’s efficient recruitment and function. First, we show that mutant dynamins modified in a single motif, including the central amphiphysin SH3 (amphSH3) binding motif, partially rescue CME in dynamin triple knock-out cells. However, mutating two motifs largely prevents that ability. Furthermore, we designed divalent dynPRD-derived peptides. These ligands bind multimers of amphSH3 with >100-fold higher affinity than monovalent ones in vitro. Accordingly, dialyzing living cells with these divalent peptides through a patch-clamp pipette blocks CME much more effectively than with monovalent ones. We conclude that dynamin drives vesicle scission via multivalent interactions in cells.
Non-cytotoxic hydroxyl-functionalized exfoliated boron nitride nanoflakes impair the immunological function of insect haemocytes in vivo
Authors: Czarniewska Elżbieta , Mrówczyńska Lucyna , Jędrzejczak-Silicka Magdalena , Nowicki Patryk , Trukawka Martyna , Mijowska Ewa 
Published: October 2019

AbstractTo induce the water solubility of hexagonal boron nitride (h-BN), we exfoliated and functionalized bulk h-BN with hydroxyl groups (h-BN-OH-n). Short-term studies showed that h-BN-OH-n induced low cytotoxicity in different models: insect haemocytes (in vivo), human erythrocytes and mouse fibroblasts (in vitro). We also demonstrated that Alexa Fluor 647-h-BN-OH-n administered topically to the insects passed through the cuticle barrier and was phagocytosed by haemocytes. Nanoflakes did not affect the haemocyte cell membrane and did not interfere with the phagocytosis of latex beads. Long-term immunoassays showed that h-BN-OH-n, despite not inducing haemocytotoxicity, impaired nodulation, the most important cellular immune response in insects. The haemocytes exposed to h-BN-OH-n and then to bacteria differed in morphology and adhesiveness from the haemocytes exposed only to bacteria and exhibited the same morphology and adhesiveness as the control haemocytes. The h-BN-OH-n-induced decrease in nodulation can therefore result from the reduced ability of haemocytes to recognize bacteria, migrate to them or form microaggregates around them, which can lead to dysfunction of the immune system during pathogen infection. Long-term in vivo studies with animal models are still necessary to unambiguously confirm that h-BN is biocompatible and useful for application as a platform for drug delivery or for bioimaging.
Proton transport modeling in a realistic biological environment by using TILDA-V
Authors: Alcocer-Ávila Mario E. , Quinto Michele A. , Monti Juan M. , Rivarola Roberto D. , Champion Christophe 
Published: October 2019

AbstractWhether it is in radiobiology to identify DNA lesions or in medicine to adapt the radiotherapeutic protocols, a detailed understanding of the radiation-induced interactions in living matter is required. Monte Carlo track-structure codes have been successfully developed to describe these interactions and predict the radiation-induced energy deposits at the nanoscale level in the medium of interest. In this work, the quantum-mechanically based Monte Carlo track-structure code TILDA-V has been used to compute the slowing-down of protons in water and DNA. Stopping power and range are then reported and compared with existing data. Then, a first application of TILDA-V to cellular irradiations is also reported in order to highlight the absolute necessity of taking into account a realistic description of the cellular environment in microdosimetry.
mTORC1-mediated polarization of M1 macrophages and their accumulation in the liver correlate with immunopathology in fatal ehrlichiosis
Authors: Haloul Mohamed , Oliveira Edson R. A. , Kader Muhamuda , Wells Jakob Z. , Tominello Tyler R. , El Andaloussi Abdeljabar , Yates Cecelia C. , Ismail Nahed 
Published: October 2019

AbstractA polarized macrophage response into inflammatory (M1) or regenerative/anti-inflammatory (M2) phenotypes is critical in host response to multiple intracellular bacterial infections. Ehrlichia is an obligate Gram-negative intracellular bacterium that causes human monocytic ehrlichiosis (HME): a febrile illness that may progress to fatal sepsis with multi-organ failure. We have shown that liver injury and Ehrlichia-induced sepsis occur due to dysregulated inflammation. Here, we investigated the contribution of macrophages to Ehrlichia-induced sepsis using murine models of mild and fatal ehrlichiosis. Lethally-infected mice showed accumulation of M1 macrophages (iNOS-positive) in the liver. In contrast, non-lethally infected mice showed polarization of M2 macrophages and their accumulation in peritoneum, but not in the liver. Predominance of M1 macrophages in lethally-infected mice was associated with expansion of IL-17-producing T, NK, and NKT cells. Consistent with the in vivo data, infection of bone marrow-derived macrophages (BMM) with lethal Ehrlichia polarized M0 macrophages into M1 phenotype under an mTORC1-dependent manner, while infection with non-lethal Ehrlichia polarized these cells into M2 types. This work highlights that mTORC1-mediated polarization of macrophages towards M1 phenotype may contribute to induction of pathogenic immune responses during fatal ehrlichiosis. Targeting mTORC1 pathway may provide a novel aproach for treatment of HME.
HLA class I-restricted T cell epitopes isolated and identified from myeloid leukemia cells
Authors: Nyambura Lydon Wainaina , Muñoz Alejandro Azorin , le Coutre Philipp , Walden Peter 
Published: October 2019

AbstractLeukemia-associated antigens (LAAs) and HLA-I epitopes published previously have shown promise in inducing leukemia-specific T cell responses. However, the clinical responses are limited, and clinical effectiveness is yet to be achieved. Limitations, among others, being the LAAs themselves, the indirect approach to HLA-I epitope identification by reverse immunology, and the use of single or few LAAs and HLA-I epitopes, which limits the spectrum of inducible tumor-specific T cells. Use of a direct approach to identify naturally processed and presented HLA-I epitopes from LAAs, and higher numbers of antigens for T cell-mediated immunotherapy for leukemia may enhance clinical responses and broaden clinical effectiveness. In a prior study we used immunoaffinity purification of HLA-I peptide complexes from the differentiated myeloid tumor cell lines MUTZ3 and THP1 coupled to high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). From this we identified in the current study seven new HLA-I epitopes and the corresponding LAAs for myeloid leukemia. In comparison, the myeloid HLA-I epitopes reported here were generally stronger HLA-binders that induce stronger T cell responses than those previously published, and their source LAAs had higher immunogenicity, higher expression levels in myeloid tumors cells compared to normal hemopoietin and other major normal tissues, and more protein interaction partners, and they are targeted by CD8 T cells in CML patients. This study analyses and compares the LAAs and HLA-I epitopes based on various immunotherapeutic targets selection criteria, and highlights new targets for T cell-mediated immunotherapy for leukemia.
Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein
Authors: Milev Miroslav P. , Stanga Daniela , Schänzer Anne , Nascimento Andrés , Saint-Dic Djenann , Ortez Carlos , Natera-de Benito Daniel , Barrios Desiré González , Colomer Jaume , Badosa Carmen , Jou Cristina , Gallano Pia , Gonzalez-Quereda Lidia , Töpf Ana , Johnson Katherine , Straub Volker , Hahn Andreas , Sacher Michael , Jimenez-Mallebrera Cecilia 
Published: October 2019

AbstractTRAPPC11 was identified as a component of the TRAPP III complex that functions in membrane trafficking and autophagy. Variants in TRAPPC11 have been reported to be associated with a broad spectrum of phenotypes but all affected individuals display muscular pathology. Identifying additional variants will further our understanding of the clinical spectrum of phenotypes and will reveal regions of the protein critical for its functions. Here we report three individuals from unrelated families that have bi-allellic TRAPPC11 variants. Subject 1 harbors a compound heterozygous variant (c.1287 + 5G > A and c.3379_3380insT). The former variant results in a partial deletion of the foie gras domain (p.Ala372_Ser429del), while the latter variant results in a frame-shift and extension at the carboxy terminus (p.Asp1127Valfs*47). Subjects 2 and 3 both harbour a homozygous missense variant (c.2938G > A; p.Gly980Arg). Fibroblasts from all three subjects displayed membrane trafficking defects manifested as delayed endoplasmic reticulum (ER)-to-Golgi transport and/or a delay in protein exit from the Golgi. All three individuals also show a defect in glycosylation of an ER-resident glycoprotein. However, only the compound heterozygous subject displayed an autophagic flux defect. Collectively, our characterization of these individuals with bi-allelic TRAPPC11 variants highlights the functional importance of the carboxy-terminal portion of the protein.
Spatio-temporal dynamics of neocortical presynaptic terminal development using multi-photon imaging of the corpus callosum in vivo
Authors: Evans Teresa A. , Bury Luke A. , Huang Alex Y. , Sabo Shasta L. 
Published: October 2019

AbstractWithin the developing central nervous system, the dynamics of synapse formation and elimination are insufficiently understood. It is ideal to study these processes in vivo, where neurons form synapses within appropriate behavioral and anatomical contexts. In vivo analysis is particularly important for long-range connections, since their development cannot be adequately studied in vitro. The corpus callosum (CC) represents a clinically-relevant long-range connection since several neurodevelopmental diseases involve CC defects. Here, we present a novel strategy for in vivo longitudinal and rapid time-lapse imaging of CC presynaptic terminal development. In postnatal mice, the time-course of CC presynaptic terminal formation and elimination was highly variable between axons or groups of axons. Young presynaptic terminals were remarkably dynamic – moving, dividing to generate more boutons, and merging to consolidate small terminals into large boutons. As synaptic networks matured, presynaptic mobility decreased. These rapid dynamics may be important for establishing initial synaptic contacts with postsynaptic partners, refining connectivity patterns or modifying synapse strength during development. Ultimately, this in vivo imaging approach will facilitate investigation of synapse development in other long-range connections and neurodevelopmental disease models.