bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neogene Tectono‐Stratigraphic Evolution of the Intermontane Tarom Basin: Insights Into Basin Filling and Plateau Building Processes Along the Northern Margin of the Iranian Plateau (Arabia‐Eurasia Collision Zone)
Authors: Paknia M. , Ballato P. , Heidarzadeh G. , Cifelli F. , Hassanzadeh J. , Vezzoli G. , Mirzaie Ataabadi M. , Ghassemi M. R. , Mattei M. 
Published: February 2021

AbstractThe intermontane Tarom Basin of NW Iran (Arabia‐Eurasia collision zone) is located at the transition between the Iranian Plateau (IP) to the SW and the Alborz Mountains to the NE. This basin was filled by upper Cenozoic synorogenic red beds that retain first‐order information on the erosional history of adjacent topography, the vertical growth of the plateau margin and its orogen perpendicular expansion. Here, we perform a multidisciplinary study including magnetostratigraphy, sedimentology, geochronology and sandstone petrography on these red beds. Our data show that Eocene arc volcanism in the region terminated at 38‐36 Ma, while intrabasinal synorogenic sedimentation (endorheic conditions) occurred from at least 16.2 to <7.6 Ma, implying that the red beds are stratigraphically equivalent to the Upper Red Formation. After 7.6 Ma, the basin experienced intrabasinal deformation, uplift and erosion with the establishment of external drainage. Fluvial connectivity with the Caspian Sea, however, was interrupted by at least four episodes of basin aggradation. During endorheic conditions, the basin fill did not reach the elevation of the plateau interior and hence the Tarom Basin was never integrated into the plateau. Furthermore, our provenance data indicate that the northern margin of the basin (Alborz Mountains) experienced a greater magnitude of Miocene deformation and erosional exhumation than the southern one (IP margin). This agrees with recent Moho depth estimates, suggesting that crustal shortening and thickening cannot be responsible for the vertical growth of the northern margin of the IP, and hence surface uplift must have been driven by deep‐seated processes.
Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab
Authors: Zhu Andrew X. , Finn Richard S. , Kang Yoon-Koo , Yen Chia-Jui , Galle Peter R. , Llovet Josep M. , Assenat Eric , Brandi Giovanni , Motomura Kenta , Ohno Izumi , Daniele Bruno , Vogel Arndt , Yamashita Tatsuya , Hsu Chih-Hung , Gerken Guido , Bilbruck John , Hsu Yanzhi , Liang Kun , Widau Ryan C. , Wang Chunxiao , Abada Paolo , Kudo Masatoshi 
Published: February 2021

Abstract
Background
Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).

Methods
Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.

Results
Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).

Conclusions
AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.

Clinical Trial Registration
ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).
CREPT/RPRD1B promotes tumorigenesis through STAT3-driven gene transcription in a p300-dependent manner
Authors: Zhai Wanli , Ye Xiongjun , Wang Yinyin , Feng Yarui , Wang Ying , Lin Yuting , Ding Lidan , Yang Liu , Wang Xuning , Kuang Yanshen , Fu Xinyuan , Eugene Chin Y. , Jia Baoqing , Zhu Bingtao , Ren Fangli , Chang Zhijie 
Published: February 2021

Abstract
Background
Signal transducer and activator of transcription 3 (STAT3) has been shown to upregulate gene transcription during tumorigenesis. However, how STAT3 initiates transcription remains to be exploited. This study is to reveal the role of CREPT (cell cycle-related and elevated-expression protein in tumours, or RPRD1B) in promoting STAT3 transcriptional activity.

Methods
BALB/c nude mice, CREPT overexpression or deletion cells were employed for the assay of tumour formation, chromatin immunoprecipitation, assay for transposase-accessible chromatin using sequencing.

Results
We demonstrate that CREPT, a recently identified oncoprotein, enhances STAT3 transcriptional activity to promote tumorigenesis. CREPT expression is positively correlated with activation of STAT3 signalling in tumours. Deletion of CREPT led to a decrease, but overexpression of CREPT resulted in an increase, in STAT3-initiated tumour cell proliferation, colony formation and tumour growth. Mechanistically, CREPT interacts with phosphorylated STAT3 (p-STAT3) and facilitates p-STAT3 to recruit p300 to occupy at the promoters of STAT3-targeted genes. Therefore, CREPT and STAT3 coordinately facilitate p300-mediated acetylation of histone 3 (H3K18ac and H3K27ac), further augmenting RNA polymerase II recruitment. Accordingly, depletion of p300 abolished CREPT-enhanced STAT3 transcriptional activity.

Conclusions
We propose that CREPT is a co-activator of STAT3 for recruiting p300. Our study provides an alternative strategy for the therapy of cancers related to STAT3.
A Sarcina bacterium linked to lethal disease in sanctuary chimpanzees in Sierra Leone
Authors: Owens Leah A. , Colitti Barbara , Hirji Ismail , Pizarro Andrea , Jaffe Jenny E. , Moittié Sophie , Bishop-Lilly Kimberly A. , Estrella Luis A. , Voegtly Logan J. , Kuhn Jens H. , Suen Garret , Deblois Courtney L. , Dunn Christopher D. , Juan-Sallés Carles , Goldberg Tony L. 
Published: February 2021

AbstractHuman and animal infections with bacteria of the genusSarcina(familyClostridiaceae) are associated with gastric dilation and emphysematous gastritis. However, the potential roles of sarcinae as commensals or pathogens remain unclear. Here, we investigate a lethal disease of unknown etiology that affects sanctuary chimpanzees (Pan troglodytes verus) in Sierra Leone. The disease, which we have named “epizootic neurologic and gastroenteric syndrome” (ENGS), is characterized by neurologic and gastrointestinal signs and results in death of the animals, even after medical treatment. Using a case-control study design, we show that ENGS is strongly associated withSarcinainfection. The microorganism is distinct fromSarcina ventriculiand other known members of its genus, based on bacterial morphology and growth characteristics. Whole-genome sequencing confirms this distinction and reveals the presence of genetic features that may account for the unusual virulence of the bacterium. Therefore, we propose that this organism be considered the representative of a new species, named “CandidatusSarcina troglodytae”. Our results suggest that a heretofore unrecognized complex of related sarcinae likely exists, some of which may be highly virulent. However, the potential role of “Ca. S. troglodytae” in the etiology of ENGS, alone or in combination with other factors, remains a topic for future research.
Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia
Authors: Gasca-Salas Carmen , Fernández-Rodríguez Beatriz , Pineda-Pardo José A. , Rodríguez-Rojas Rafael , Obeso Ignacio , Hernández-Fernández Frida , del Álamo Marta , Mata David , Guida Pasqualina , Ordás-Bandera Carlos , Montero-Roblas J. Ignacio , Martínez-Fernández Raúl , Foffani Guglielmo , Rachmilevitch Itay , Obeso José A. 
Published: February 2021

AbstractMR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.
Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment
Authors: Bai Hongzhen , Wang Jianwei , Phan Chi Uyen , Chen Qi , Hu Xiurong , Shao Guoqiang , Zhou Jun , Lai Lihua , Tang Guping 
Published: February 2021

AbstractThe malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG’s anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.
The molecular basis of socially mediated phenotypic plasticity in a eusocial paper wasp
Authors: Taylor Benjamin A. , Cini Alessandro , Wyatt Christopher D. R. , Reuter Max , Sumner Seirian 
Published: February 2021

AbstractPhenotypic plasticity, the ability to produce multiple phenotypes from a single genotype, represents an excellent model with which to examine the relationship between gene expression and phenotypes. Analyses of the molecular foundations of phenotypic plasticity are challenging, however, especially in the case of complex social phenotypes. Here we apply a machine learning approach to tackle this challenge by analyzing individual-level gene expression profiles of Polistes dominula paper wasps following the loss of a queen. We find that caste-associated gene expression profiles respond strongly to queen loss, and that this change is partly explained by attributes such as age but occurs even in individuals that appear phenotypically unaffected. These results demonstrate that large changes in gene expression may occur in the absence of outwardly detectable phenotypic changes, resulting here in a socially mediated de-differentiation of individuals at the transcriptomic level but not at the levels of ovarian development or behavior.
IgA transcytosis and antigen recognition govern ovarian cancer immunity
Authors: Biswas Subir , Mandal Gunjan , Payne Kyle K. , Anadon Carmen M. , Gatenbee Chandler D. , Chaurio Ricardo A. , Costich Tara Lee , Moran Carlos , Harro Carly M. , Rigolizzo Kristen E. , Mine Jessica A. , Trillo-Tinoco Jimena , Sasamoto Naoko , Terry Kathryn L. , Marchion Douglas , Buras Andrea , Wenham Robert M. , Yu Xiaoqing , Townsend Mary K. , Tworoger Shelley S. , Rodriguez Paulo C. , Anderson Alexander R. , Conejo-Garcia Jose R. 
Published: February 2021

AbstractMost ovarian cancers are infiltrated by prognostically relevant activated T cells1–3, yet exhibit low response rates to immune checkpoint inhibitors4. Memory B cell and plasma cell infiltrates have previously been associated with better outcomes in ovarian cancer5,6, but the nature and functional relevance of these responses are controversial. Here, using 3 independent cohorts that in total comprise 534 patients with high-grade serous ovarian cancer, we show that robust, protective humoral responses are dominated by the production of polyclonal IgA, which binds to polymeric IgA receptors that are universally expressed on ovarian cancer cells. Notably, tumour B-cell-derived IgA redirects myeloid cells against extracellular oncogenic drivers, which causes tumour cell death. In addition, IgA transcytosis through malignant epithelial cells elicits transcriptional changes that antagonize the RAS pathway and sensitize tumour cells to cytolytic killing by T cells, which also contributes to hindering malignant progression. Thus, tumour-antigen-specific and -antigen-independent IgA responses antagonize the growth of ovarian cancer by governing coordinated tumour cell, T cell and B cell responses. These findings provide a platform for identifying targets that are spontaneously recognized by intratumoural B-cell-derived antibodies, and suggest that immunotherapies that augment B cell responses may be more effective than approaches that focus on T cells, particularly for malignancies that are resistant to checkpoint inhibitors.
Edge states of Floquet–Dirac semimetal in a laser-driven semiconductor quantum-well
Authors: Zhang Boyuan , Maeshima Nobuya , Hino Ken-ichi 
Published: February 2021

AbstractBand crossings observed in a wide range of condensed matter systems are recognized as a key to understand low-energy fermionic excitations that behave as massless Dirac particles. Despite rapid progress in this field, the exploration of non-equilibrium topological states remains scarce and it has potential ability of providing a new platform to create unexpected massless Dirac states. Here we show that in a semiconductor quantum-well driven by a cw-laser with linear polarization, the optical Stark effect conducts bulk-band crossing, and the resulting Floquet-Dirac semimetallic phase supports an unconventional edge state in the projected one-dimensional Brillouin zone under a boundary condition that an electron is confined in the direction perpendicular to that of the laser polarization. Further, we reveal that this edge state mediates a transition between topological and non-topological edge states that is caused by tuning the laser intensity. We also show that the properties of the edge states are strikingly changed under a different boundary condition. It is found that such difference originates from that nearly fourfold-degenerate points exist in a certain intermediate region of the bulk Brillouin zone between high-symmetry points.
Understanding structure/function relationships in nitrifying microbial communities after cross-transfer between freshwater and seawater
Authors: Gonzalez-Silva Blanca M. , Jonassen Kjell Rune , Bakke Ingrid , Østgaard Kjetill , Vadstein Olav 
Published: February 2021

AbstractIn this study, nitrification before and after abrupt cross-transfer in salinity was investigated in two moving bed biofilm reactors inoculated with nitrifying cultures that had adaptation to freshwater (FR) and seawater salinities (SR). FR and SR MBRRs were exposed to short and long term cross-transfer in salinity, and the functional capacity of nitrifying microbial communities was quantified by the estimation of ammonia and nitrite oxidation rates. Salinity induced successions were evaluated before and after salinity change by deep sequencing of 16S rRNA gene amplicons and statistical analysis. The bacterial community structure was characterized and Venn diagrams were included. The results indicated that after salinity cross-transfer, the FR was not significantly recovered at seawater salinity whereas SR showed high resistance to stress caused by low-salt. Succession and physiological plasticity were the main mechanisms of the long-term adaption of the nitrifying communities exposed to abrupt salinity changes. Independently of salinity, some nitrifiers presented high physiological plasticity towards salinity and were very successful at both zero and full seawater salinity. SR culture is robust and suitable inoculum for ammonium removal from recirculating aquaculture systems and industrial wastewaters with variable and fast salinity changes. Our findings contradict the current perspective of the significance of salinity on the structure of nitrifying communities.
B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF
Authors: Bakhuraysah Maha M. , Theotokis Paschalis , Lee Jae Young , Alrehaili Amani A. , Aui Pei-Mun , Figgett William A. , Azari Michael F. , Abou-Afech John-Paul , Mackay Fabienne , Siatskas Christopher , Alderuccio Frank , Strittmatter Stephen M. , Grigoriadis Nikolaos , Petratos Steven 
Published: February 2021

AbstractWe have previously reported evidence that Nogo-A activation of Nogo-receptor 1 (NgR1) can drive axonal dystrophy during the neurological progression of experimental autoimmune encephalomyelitis (EAE). However, the B-cell activating factor (BAFF/BlyS) may also be an important ligand of NgR during neuroinflammation. In the current study we define that NgR1 and its homologs may contribute to immune cell signaling during EAE. Meningeal B-cells expressing NgR1 and NgR3 were identified within the lumbosacral spinal cords ofngr1+/+EAE-induced mice at clinical score 1. Furthermore, increased secretion of immunoglobulins that bound to central nervous system myelin were shown to be generated from isolated NgR1- and NgR3-expressing B-cells ofngr1+/+EAE-induced mice. In vitro BAFF stimulation of NgR1- and NgR3-expressing B cells, directed them into the cell cycle DNA synthesis phase. However, when we antagonized BAFF signaling by co-incubation with recombinant BAFF-R, NgR1-Fc, or NgR3 peptides, the B cells remained in the G0/G1 phase. The data suggest that B cells express NgR1 and NgR3 during EAE, being localized to infiltrates of the meninges and that their regulation is governed by BAFF signaling.
Specific inhibition of FGF5-induced cell proliferation by RNA aptamers
Authors: Amano Ryo , Namekata Masato , Horiuchi Masataka , Saso Minami , Yanagisawa Takuya , Tanaka Yoichiro , Ghani Farhana Ishrat , Yamamoto Masakuni , Sakamoto Taiichi 
Published: February 2021

AbstractFibroblast growth factor 5 (FGF5) is a crucial regulator of hair growth and an oncogenic factor in several human cancers. To generate FGF5 inhibitors, we performed Systematic Evolution of Ligands by EXponential enrichment and obtained novel RNA aptamers that have high affinity to human FGF5. These aptamers inhibited FGF5-induced cell proliferation, but did not inhibit FGF2-induced cell proliferation. Surface plasmon resonance demonstrated that one of the aptamers, F5f1, binds to FGF5 tightly (Kd = 0.7 ± 0.2 nM), but did not fully to FGF1, FGF2, FGF4, FGF6, or FGFR1. Based on sequence and secondary structure similarities of the aptamers, we generated the truncated aptamer, F5f1_56, which has higher affinity (Kd = 0.118 ± 0.003 nM) than the original F5f1. Since the aptamers have high affinity and specificity to FGF5 and inhibit FGF5-induced cell proliferation, they may be candidates for therapeutic use with FGF5-related diseases or hair disorders.
Evidence for strong environmental control on bacterial microbiomes of Antarctic springtails
Authors: Leo Chiara , Nardi Francesco , Cucini Claudio , Frati Francesco , Convey Peter , Weedon James T. , Roelofs Dick , Carapelli Antonio 
Published: February 2021

AbstractCollembola are a key component of the soil biota globally, playing an important role in community and ecosystem dynamics. Equally significant are their associated microbiomes, that can contribute to key metabolic functions. In the present study, we investigated the bacterial community composition of four Antarctic springtail species to assess if and how the extreme Antarctic environment has shaped the collembolans’ microbiomes. Springtails were collected from two biogeographical regions, the maritime and the continental Antarctic. From each region, two endemic species, belonging to the generaCryptopygus(Isotomidae, Entomobryomorpha) andFriesea(Neanuridae, Poduromorpha), were included. This experimental design allowed us to quantify the relative importance of ecological factors (different regions of occurrence) and/or phylogenetic divergence in the host (different Orders) in shaping the Collembola microbiome. The diversity and richness of springtail microbiomes was lower in the Antarctic taxa compared to published information from species from temperate regions. The microbiome composition was predominantly species-specific, with a limited core microbiome shared across the four species examined. While both geographic origin and host species influenced the associated microbiomes, the former was the prevalent driver, with closer similarity between springtails from the same bioregion than between those belonging to the same genus.
Unravelling the local crystallographic structure of ferromagnetic $$\gamma '$$-$$\hbox {Ga}_y \hbox {Fe}_{4-y}$$N nanocrystals embedded in GaN
Authors: Navarro-Quezada Andrea , Gas Katarzyna , Spindlberger Anna , Karimi Fahim , Sawicki Maciej , Ciatto Gianluca , Bonanni Alberta 
Published: February 2021

AbstractIn the Fe-doped GaN phase-separated magnetic semiconductor Ga$$\delta $$
δ
FeN, the presence of embedded $$\gamma '$$

γ
′

-$$\hbox {Ga}_y \hbox {Fe}_{4-y}$$

Ga
y

Fe

4
-
y

N nanocrystals determines the magnetic properties of the system. Here, through a combination of anomalous X-ray diffraction and diffraction anomalous fine structure, the local structure of Ga in self-assembled face-centered cubic (fcc) $$\gamma '$$

γ
′

-$$\hbox {Ga}_y \hbox {Fe}_{4-y}$$

Ga
y

Fe

4
-
y

N nanocrystals embedded in wurtzite GaN thin layers is investigated in order to shed light onto the correlation between fabrication parameters, local structural arrangement and overall magnetic properties of the material system. It is found, that by adjusting the growth parameters and thus, the crystallographic surroundings, the Ga atoms can be induced to incorporate into 3c positions at the faces of the fcc crystal lattice, reaching a maximum occupancy of 30%. The magnetic response of the embedded nanocrystals is ferromagnetic with Curie temperature increasing from 450 to 500 K with the Ga occupation. These results demonstrate the outstanding potential of the employed experimental protocol for unravelling the local structure of magnetic multi-phase systems, even when embedded in a matrix containing the same element under investigation.