bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-specific iPSC-derived cardiomyocytes reveal abnormal regulation of FGF16 in a familial atrial septal defect
Authors: Ye Lingqun , Yu You , Zhao Zhen-Ao , Zhao Dandan , Ni Xuan , Wang Yong , Fang Xing , Yu Miao , Wang Yongming , Tang Jun-Ming , Chen Ying , Shen Zhenya , Lei Wei , Hu Shijun 
Published: May 2021

Abstract

Aims
Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human-induced pluripotent stem cells (iPSCs) from a family cohort with ASD.

Methods and results
Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro, thus presenting a promising approach for disease modelling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4T280M) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4T280M) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4T280M-mutant iPSCs (iPSC-G4T280M-CMs) and ESCs (ESC-G4T280M-CMs), while the impaired proliferation ability of iPSC-G4T280M-CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4T280M and ASD was demonstrated in a human iPSC model for the first time.

Conclusions
In summary, our study revealed the molecular mechanism of the GATA4T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.
A non-parametric framework to estimate fertilization response in loblolly pine plantations using environmental covariates
Authors: Kinane Stephen M , Montes Cristian R , Bullock Bronson P 
Published: May 2021

AbstractFertilization is a common practice to increase the productivity and the stand value in the southeastern US. The decision to fertilize a given site is driven by site characteristics and the expected magnitude of response. To determine the magnitude, forest researchers typically rely on fertilization trials established throughout the region of interest and derive growth equations to reflect an increase in either site index or volume. Such equations lack an explicit spatial prediction component. To bridge this gap, we developed a modeling framework that explicitly evaluates the likelihood of a fertilization response as a binary process and the magnitude of such response as a separate model. The methodology relies on the non-parametric interpolator thin plate spines. To test the efficacy of this framework, both percent volume and dominant height response to repeated fertilizer treatments were estimated using data from long-term research trials in Georgia. Several environmental covariates were evaluated on their ability to reduce the models’ root mean square error and account for more of the variation in percent gain from fertilization regimes. Results showed that the inclusion of such covariates improved the model performance and reduced errors associated with interpolation. Thresholding expected responses from fertilization treatments allows practitioners to evaluate the probability of achieving a given response.
An evolutionary genomic approach reveals both conserved and species-specific genetic elements related to human disease in closely related Aspergillus fungi
Authors: Mead Matthew E , Steenwyk Jacob L , Silva Lilian P , de Castro Patrícia A , Saeed Nauman , Hillmann Falk , Goldman Gustavo H , Rokas Antonis 
Published: May 2021

Abstract
Aspergillosis is an important opportunistic human disease caused by filamentous fungi in the genus Aspergillus. Roughly 70% of infections are caused by Aspergillus fumigatus, with the rest stemming from approximately a dozen other Aspergillus species. Several of these pathogens are closely related to A. fumigatus and belong in the same taxonomic section, section Fumigati. Pathogenic species are frequently most closely related to nonpathogenic ones, suggesting Aspergillus pathogenicity evolved multiple times independently. To understand the repeated evolution of Aspergillus pathogenicity, we performed comparative genomic analyses on 18 strains from 13 species, including 8 species in section Fumigati, which aimed to identify genes, both ones previously connected to virulence as well as ones never before implicated, whose evolution differs between pathogens and nonpathogens. We found that most genes were present in all species, including approximately half of those previously connected to virulence, but a few genes were section- or species-specific. Evolutionary rate analyses identified over 1700 genes whose evolutionary rate differed between pathogens and nonpathogens and dozens of genes whose rates differed between specific pathogens and the rest of the taxa. Functional testing of deletion mutants of 17 transcription factor-encoding genes whose evolution differed between pathogens and nonpathogens identified eight genes that affect either fungal survival in a model of phagocytic killing, host survival in an animal model of fungal disease, or both. These results suggest that the evolution of pathogenicity in Aspergillus involved both conserved and species-specific genetic elements, illustrating how an evolutionary genomic approach informs the study of fungal disease.
Constraint and Function in the Predefinitive Plumages of Manakins (Aves: Pipridae)
Authors: Schaedler Laura M , Taylor Liam U , Prum Richard O , Anciães Marina 
Published: May 2021

SynopsisBirds with delayed plumage maturation exhibit a drab predefinitive plumage, often despite gonad maturation, before developing the definitive plumage associated with increased reproductive success. Manakins are a diverse clade of neotropical lekking birds with extreme sexual dichromatism, radical sexual displays, and a unique diversity in the predefinitive plumages of males across species. Here, we provide the first full review of the natural history of manakin predefinitive plumages as the basis for qualitatively addressing the six major hypotheses about the production and function of predefinitive plumages. We find little evidence to support the possibilities that manakin predefinitive plumages are directly constrained by inflexible molt schedules, resource limitations to definitive coloration, or hormonal ties to reproductive behaviors. There is little evidence that could support a crypsis function, although direct experimentation is needed, and mimicry is refuted except for one unusual species in which predefinitive males sire young. Instead, evidence from a handful of well-studied species suggests that predefinitive plumages help young males explicitly signal their social status, and thereby gain entry to the social hierarchies which dictate future reproductive success. Our conclusions are especially influenced by the unique fact that males of at least 11 species throughout the family exhibit multiple predefinitive plumage stages with distinctively male patches. For each hypothesis, we highlight ways in which a better knowledge of female and young male birds offers critical opportunities for the use of manakins as a model clade.
Error estimates for the Cahn–Hilliard equation with dynamic boundary conditions
Authors: Harder Paula , Kovács Balázs 
Published: May 2021

AbstractA proof of convergence is given for a bulk–surface finite element semidiscretisation of the Cahn–Hilliard equation with Cahn–Hilliard-type dynamic boundary conditions in a smooth domain. The semidiscretisation is studied in an abstract weak formulation as a second-order system. Optimal-order uniform-in-time error estimates are shown in the $L^2$- and $H^1$-norms. The error estimates are based on a consistency and stability analysis. The proof of stability is performed in an abstract framework, based on energy estimates exploiting the anti-symmetric structure of the second-order system. Numerical experiments illustrate the theoretical results.
The role of microRNAs on doxorubicin drug resistance in breast cancer
Authors: Jamialahmadi Khadijeh , Zahedipour Fatemeh , Karimi Gholamreza 
Published: May 2021

Abstract

Objectives
Resistance to chemotherapeutic drugs is a serious challenge for effective therapy of cancers. Doxorubicin is a drug which is typically used for breast cancer treatment. Several mechanisms are involved in resistance to doxorubicin including overexpression of ATP-binding cassette (ABC) transporters, altering apoptosis, autophagy and cell cycle arrest. In this review, we focus on the potential effects of microRNAs on doxorubicin resistance in breast cancer.

Methods
Literature review focusing on the ‘microRNAs and doxorubicin drug resistance in breast cancer’ was conducted comprehensively. The search was performed in PubMed, Scopus, Google and Google Scholar databases and reference lists of relevant articles were also included.

Key ﬁndings
MicroRNAs play essential role in resistance of breast cancer to doxorubicin by affecting several key cellular pathways, including overexpression of ABC transporters, altering apoptosis, autophagy and cell signaling pathways, cell cycle arrest, epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs).

Conclusions
Cancer treatment methods are moving from conventional therapies to targeted therapies such as using microRNAs. MiRNAs can act as regulatory molecules to overcome breast cancer doxorubicin resistance by controlling the expression levels of genes involved in different cellular pathways. Thus, exact elucidation of their role in different cellular processes can help overcome the breast cancer development and drug resistance.
Survey on utilization of flattening filter-free photon beams in Japan
Authors: Kodama Takumi , Yasui Keisuke , Nishioka Shie , Miyaura Kazunori , Takakura Toru , Katayose Tetsurou , Nakamura Mitsuhiro 
Published: May 2021

Abstract
To understand the current state of flattening filter-free (FFF) beam implementation in C-arm linear accelerators (LINAC) in Japan, the quality assurance (QA)/quality control (QC) 2018–2019 Committee of the Japan Society of Medical Physics (JSMP) conducted a 37-question survey, designed to investigate facility information and specifications regarding FFF beam adoption and usage. The survey comprised six sections: facility information, devices, clinical usage, standard calibration protocols, modeling for treatment planning (TPS) systems and commissioning and QA/QC. A web-based questionnaire was developed. Responses were collected between 18 June and 18 September 2019. Of the 846 institutions implementing external radiotherapy, 323 replied. Of these institutions, 92 had adopted FFF beams and 66 had treated patients using them. FFF beams were used in stereotactic radiation therapy (SRT) for almost all disease sites, especially for the lungs using 6 MV and liver using 10 MV in 51 and 32 institutions, respectively. The number of institutions using FFF beams for treatment increased yearly, from eight before 2015 to 60 in 2018. Farmer-type ionization chambers were used as the standard calibration protocol in 66 (72%) institutions. In 73 (80%) institutions, the beam-quality conversion factor for FFF beams was calculated from TPR20,10, via the same protocol used for beams with flattening filter (WFF). Commissioning, periodic QA and patient-specific QA for FFF beams also followed the procedures used for WFF beams. FFF beams were primarily used in high-volume centers for SRT. In most institutions, measurement and QA was conducted via the procedures used for WFF beams.
The Pop-Gen Pipeline Platform: A Software Platform for Population Genomic Analyses
Authors: Webb Andrew , Knoblauch Jared , Sabankar Nitesh , Kallur Apeksha Sukesh , Hey Jody , Sethuraman Arun 
Published: May 2021

Abstract
The Pop-Gen Pipeline Platform (PPP) is a software platform for population genomic analyses. The PPP was designed as a collection of scripts that facilitate common population genomic workflows in a consistent and standardized Python environment. Functions were developed to encompass entire workflows, including input preparation, file format conversion, various population genomic analyses, and output generation. The platform has also been developed with reproducibility and extensibility of analyses in mind. The PPP is an open-source package that is available for download and use at https://ppp.readthedocs.io/en/latest/PPP_pages/install.html.
Evolutionary Dynamics of the OR Gene Repertoire in Teleost Fishes: Evidence of an Association with Changes in Olfactory Epithelium Shape
Authors: Policarpo Maxime , Bemis Katherine E , Tyler James C , Metcalfe Cushla J , Laurenti Patrick , Sandoz Jean-Christophe , Rétaux Sylvie , Casane Didier 
Published: May 2021

Abstract
Teleost fishes perceive their environment through a range of sensory modalities, among which olfaction often plays an important role. Richness of the olfactory repertoire depends on the diversity of receptors coded by homologous genes classified into four families: OR, TAAR, VR1, and VR2. Herein, we focus on the OR gene repertoire. While independent large contractions of the OR gene repertoire associated with ecological transitions have been found in mammals, little is known about the diversity of the OR gene repertoire and its evolution in teleost fishes, a group that includes more than 34,000 living species. We analyzed genomes of 163 species representing diversity in this large group. We found a large range of variation in the number of functional OR genes, from 15 in the Broad-nose Pipefish Syngnathus typhle and the Ocean Sunfish Mola mola, to 429 in the Zig-zag Eel Mastacembelus armatus. The number of OR genes was higher in species when a multilamellar olfactory rosette was present. Moreover, the number of lamellae was correlated with the richness of the OR gene repertoire. While a slow and balanced birth-and-death process generally drives the evolution of the OR gene repertoire, we inferred several episodes of high rates of gene loss, sometimes followed by large gains in the number of OR genes. These gains coincide with morphological changes of the olfactory organ and suggest a strong functional association between changes in the morphology and the evolution of the OR gene repertoire.
A forgotten subspecies of the land snail speciesArianta arbustorumfrom a Pleistocene refuge in the Western Alps
Authors: Hausdorf Bernhard , Walther Frank 
Published: May 2021

ABSTRACTAlpine Arianta populations from the Biellese Alps in Italy are characterized by imperforate, thin-shelled, dark brown shells without or with sparse light spots that resemble widespread phenotypes of Arianta arbustorum arbustorum found in calcium-deficient areas. Therefore, they were not considered a distinct taxon. However, molecular phylogenetic analyses show that they belong to a group of subspecies of A. arbustorum from the Western Alps and the Pyrenees. We classify them as a distinct subspecies, Arianta a. doriae (Paulucci, 1878), which reduces the geographical gap between the western group of subspecies of A. arbustorum and the Eastern Alps where Arianta originated. This subspecies survived the glacials in a peripheral mountain refuge at the southern margin of the Biellese Alps.
Insight into the adaptive evolution of mitochondrial genomes in intertidal chitons
Authors: Dhar Dipanjana , Dey Debayan , Basu Soumalee , Fortunato Helena 
Published: May 2021

ABSTRACT
The intertidal zone is one of the most stressful environments, with extreme shifts in temperature, salinity, pH and oxygen concentration. Marine molluscs, particularly chitons that belong to the category of ecologically significant organisms, survive in this extreme environment, and are ideal systems for studying stress adaptation. Mitochondria are known to be critical for energy homeostasis, and changes in environmental factors result in their dysfunction and consequent injury to the organism. Intertidal organisms are exception in this respect because they are capable of maintaining mitochondrial integrity. Here, we used mitochondrial genetic components from seven chitons of the intertidal zone to infer phylogenetic relationships. Selection analyses on individual protein-coding genes (PCGs) were performed to identify and map potentially adaptive residues in the modelled structures of the mitochondrial respiratory chain complexes. The results showed significant amino acid changes in sites under diversifying selection for all the PCGs, indicating that the mitochondrial genome in chitons is undergoing adaptive evolution. Such sites were observed in the proton pump as well as in the translocation channel of the transmembrane helices and the surrounding loop regions, thus implying functional modification of the mitochondrial proteins essential for survival in the dynamic environment of the intertidal zone.
Graphery: interactive tutorials for biological network algorithms
Authors: Zeng Heyuan , Zhang Jinbiao , Preising Gabriel A , Rubel Tobias , Singh Pramesh , Ritz Anna 
Published: May 2021

AbstractNetworks have been an excellent framework for modeling complex biological information, but the methodological details of network-based tools are often described for a technical audience. We have developed Graphery, an interactive tutorial webserver that illustrates foundational graph concepts frequently used in network-based methods. Each tutorial describes a graph concept along with executable Python code that can be interactively run on a graph. Users navigate each tutorial using their choice of real-world biological networks that highlight the diverse applications of network algorithms. Graphery also allows users to modify the code within each tutorial or write new programs, which all can be executed without requiring an account. Graphery accepts ideas for new tutorials and datasets that will be shaped by both computational and biological researchers, growing into a community-contributed learning platform. Graphery is available at https://graphery.reedcompbio.org/.
Single-cell image analysis reveals a protective role for microglia in glioblastoma
Authors: Woolf Zoe , Swanson Molly E V , Smyth Leon C , Mee Edward W , Schweder Patrick , Heppner Peter , Kim Bernard J H , Turner Clinton , Oldfield Robyn L , Curtis Maurice A , Faull Richard L M , Scotter Emma L , Park Thomas I-H , Dragunow Michael 
Published: May 2021

Abstract

Background
Microglia and tumor-associated macrophages (TAMs) constitute up to half of the total tumor mass of glioblastomas. Despite these myeloid populations being ontogenetically distinct, they have been largely conflated. Recent single-cell transcriptomic studies have identified genes that distinguish microglia from TAMs. Here we investigated whether the translated proteins of genes enriched in microglial or TAM populations can be used to differentiate these myeloid cells in immunohistochemically stained human glioblastoma tissue.

Methods
Tissue sections from resected low-grade, meningioma, and glioblastoma (grade IV) tumors and epilepsy tissues were immunofluorescently triple-labeled for Iba1 (pan-myeloid marker), CD14 or CD163 (preferential TAM markers), and either P2RY12 or TMEM119 (microglial-specific markers). Using a single-cell-based image analysis pipeline, we quantified the abundance of each marker within single myeloid cells, allowing the identification and analysis of myeloid populations.

Results
P2RY12 and TMEM119 successfully discriminated microglia from TAMs in glioblastoma. In contrast, CD14 and CD163 expression were not restricted to invading TAMs and were upregulated by tumor microglia. Notably, a higher ratio of microglia to TAMs significantly correlated with increased patient survival.

Conclusions
We demonstrate the validity of previously defined microglial-specific genes P2RY12 and TMEM119 as robust discriminators of microglia and TAMs at the protein level in human tissue. Moreover, our data suggest that a higher proportion of microglia may be beneficial for patient survival in glioblastoma. Accordingly, this tissue-based method for myeloid population differentiation could serve as a useful prognostic tool.
THREE-POINT AREA METHOD FOR THERMOLUMINESCENCE GLOW CURVE ANALYSIS AND ITS APPLICATION TO THE GLOW PEAK OF K2SRP2O7:PR
Authors: Kundu M , Bhattacharyya S , Karmakar M , Majumdar P S 
Published: May 2021

Abstract
A method has been proposed to evaluate the kinetic parameters, viz. activation energy ($E$) and order of kinetics ($b$) from a single or isolated thermoluminescence (TL) glow peak. Along with the area under the entire curve, this method uses a set of three arbitrary data points and calculates the partial area under the curve from each point to the endpoint. In this way, the entire information associated with the curve is used and the method is named as ‘Three-Point Area’ (TPA) method. We have applied it successfully on a number of theoretically simulated TL curves generated in One Trap One Recombination centre (OTOR) model and General-Order Kinetics (GOK) model under quasi-equilibrium approximations with linear heating scheme. The activation energies are found in good agreement with input values for both the models. For OTOR model, temperature average of order of kinetics is estimated to compare with the present result. Systematic analysis is carried out for estimation of errors inherent in the method in the purview of GOK model. A closer look on the results reveals that any set of three points, preferably chosen from the rising side of the curve, can yield activation energy and order of kinetics. The validity of the method to extract $E$ and $b$ from experimental glow curves is exemplified by considering experimental TL data reported in literature. Finally, a complete study starting from the synthesis of a new phosphor $\mathrm{K_2SrP_2O_7:Pr} $ and analysis of the recorded TL data to estimate $E$ and $b$ employing the TPA method has been reported.