bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrino flares of radio blazars observed from TeV to PeV
Authors: Suray Alisa , Troitsky Sergey 
Published: September 2023

ABSTRACT
Radio blazars have been linked both to individual high-energy neutrino events and to excesses in likelihood sky maps constructed from lower-energy neutrino data. However, the exact mechanism by which neutrinos are produced in these sources is still unknown. Here, we demonstrate that IceCube neutrinos with energies over 200 TeV, which were previously associated with bright radio blazars, are significantly more likely to be accompanied by flares of lower-energy events, compared to those lacking blazar counterparts. The parsec-scale core radio flux density of blazars, positioned within the error regions of energetic events, is strongly correlated with the likelihood of a day-scale lower-energy neutrino flare in directional and temporal coincidence with the high-energy event, reported by IceCube. The probability of a chance correlation is 3.6 × 10−4. This confirms the neutrino-blazar connection in a new and independent way, and provides valuable clues to understanding the origin of astrophysical neutrinos.
A Chromosome-Level Genome Assembly of the Reef Stonefish (Synanceia verrucosa) Provides Novel Insights into Stonustoxin (sntx) Genes
Authors: Tang Tianle , Huang Yu , Peng Chao , Liao Yanling , Lv Yunyun , Shi Qiong , Gao Bingmiao 
Published: September 2023

Abstract
Reef stonefish (Synanceia verrucosa) is one of the most venomous fishes, but its biomedical study has been restricted to molecular cloning and purification of its toxins, instead of high-throughput genetic research on related toxin genes. In this study, we constructed a chromosome-level haplotypic genome assembly for the reef stonefish. The genome was assembled into 24 pseudo-chromosomes, and the length totaled 689.74 Mb, reaching a contig N50 of 11.97 Mb and containing 97.8% of complete BUSCOs. A total of 24,050 protein-coding genes were annotated, of which metalloproteinases, C-type lectins, and stonustoxins (sntx) were the most abundant putative toxin genes. Multitissue transcriptomic and venom proteomic data showed that sntx genes, especially those clustered within a 50-kb region on the chromosome 2, had higher transcription levels than other types of toxins as well as those sntx genes scatteringly distributed on other chromosomes. Further comparative genomic analysis predicted an expansion of sntx-like genes in the Percomorpha lineage including nonvenomous fishes, but Scorpaenoidei species experienced extra independent sntx duplication events, marking the clear-cut origin of authentic toxic stonustoxins. In summary, this high-quality genome assembly and related comparative analysis of toxin genes highlight valuable genetic differences for potential involvement in the evolution of venoms among Scorpaeniformes fishes.
Radiotherapy-induced vascular cognitive impairment 20 years after childhood brain tumor
Authors: Remes Tiina Maria , Suo-Palosaari Maria Helena , Arikoski Pekka Matti , Harila Marika , Koskenkorva Päivi Katri Tuulikki , Lähteenmäki Päivi Maria , Lönnqvist Tuula Riitta Irmeli , Ojaniemi Marja Katariina , Pohjasniemi Heli , Puosi Riina , Ritari Niina , Sirkiä Kirsti Helena , Sutela Anna Kaarina , Toiviainen-Salo Sanna-Maria , Rantala Heikki Markku Johannes , Harila Arja Helena 
Published: September 2023

Abstract

Background
Studies have established that radiotherapy for childhood brain tumors (BTs) increases the risk of cerebrovascular disease (CVD); however, it is unclear how this will affect cognitive function. This study aimed to investigate the associations between radiotherapy-induced CVD, white matter hyperintensities (WMHs), and neurocognitive outcomes in adult survivors of childhood BTs.

Methods
In a cross-sectional setting, we conducted a national cohort that included 68 radiotherapy-treated survivors of childhood BTs after a median follow-up of 20 years. Markers of CVD and WMHs were evaluated using brain MRI, and the sum of CVD-related findings was calculated. Additionally, the associations among CVD findings, WMHs, and neuropsychological test results were analyzed.

Results
Of the 68 childhood BT survivors, 54 (79%) were diagnosed with CVD and/or WMHs at a median age of 27 years. CVD and/or WMHs were associated with lower scores for verbal intelligence quotient, performance intelligence quotient (PIQ), executive function, memory, and visuospatial ability (P &lt; .05). Additionally, survivors with microbleeds had greater impairments in the PIQ, processing speed, executive function, and visuospatial ability (P &lt; .05). WMHs and CVD burden were associated with greater difficulties in memory function and visuospatial ability (P &lt; .05). Small-vessel disease burden was associated with PIQ scores, processing speed, working memory, and visuospatial ability.

Conclusions
The study results suggest that markers of radiotherapy-induced CVD, the additive effect of CVD markers, and risk factors of dementia are associated with cognitive impairment, which may suggest that the survivors are at a high risk of developing early-onset dementia.
Branched-chain amino acid transaminase 1 regulates glioblastoma cell plasticity and contributes to immunosuppression
Authors: Boskovic Pavle , Wilke Nathalie , Man Ka-Hou , Lichter Peter , Francois Liliana , Radlwimmer Bernhard 
Published: September 2023

Abstract

Background
Glioblastoma is the most common malignant brain tumor in adults. Cellular plasticity and the poorly differentiated features result in a fast relapse of the tumors following treatment. Moreover, the immunosuppressive microenvironment proved to be a major obstacle to immunotherapeutic approaches. Branched-chain amino acid transaminase 1 (BCAT1) was shown to drive the growth of glioblastoma and other cancers;however, its oncogenic mechanism remains poorly understood.

Methods
Using human tumor data, cell line models and orthotopic immuno-competent and -deficient mouse models, we investigated the phenotypic and mechanistic effects of BCAT1 on glioblastoma cell state and immunomodulation.

Results
Here, we show that BCAT1 is crucial for maintaining the poorly differentiated state of glioblastoma cells and that its low expression correlates with a more differentiated glioblastoma phenotype. Furthermore, orthotopic tumor injection into immunocompetent mice demonstrated that the brain microenvironment is sufficient to induce differentiation of Bcat1-KO tumors in vivo. We link the transition to a differentiated cell state to the increased activity of ten-eleven translocation demethylases and the hypomethylation and activation of neuronal differentiation genes. In addition, the knockout of Bcat1 attenuated immunosuppression, allowing for an extensive infiltration of CD8+ cytotoxic T-cells and complete abrogation of tumor growth. Further analysis in immunodeficient mice revealed that both tumor cell differentiation and immunomodulation following BCAT1-KO contribute to the long-term suppression of tumor growth.

Conclusions
Our study unveils BCAT1’s pivotal role in promoting glioblastoma growth by inhibiting tumor cell differentiation and sustaining an immunosuppressive milieu. These findings offer a novel therapeutic avenue for targeting glioblastoma through the inhibition of BCAT1.
UV RESISTANCE LOCUS 8–Mediated UV-B Response Is Required Alongside CRYPTOCHROME 1 for Plant Survival in Sunlight under Field Conditions
Authors: Stockenhuber Reinhold , Akiyama Reiko , Tissot Nicolas , Milosavljevic Stefan , Yamazaki Misako , Wyler Michele , Arongaus Adriana B , Podolec Roman , Sato Yasuhiro , Widmer Alex , Ulm Roman , Shimizu Kentaro K 
Published: September 2023

Abstract
As sessile, photoautotrophic organisms, plants are subjected to fluctuating sunlight that includes potentially detrimental ultraviolet-B (UV-B) radiation. Experiments under controlled conditions have shown that the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) controls acclimation and tolerance to UV-B in Arabidopsis thaliana; however, its long-term impact on plant fitness under naturally fluctuating environments remain poorly understood. Here, we quantified the survival and reproduction of different Arabidopsis mutant genotypes under diverse field and laboratory conditions. We found that uvr8 mutants produced more fruits than wild type when grown in growth chambers under artificial low-UV-B conditions but not under natural field conditions, indicating a fitness cost in the absence of UV-B stress. Importantly, independent double mutants of UVR8 and the blue light photoreceptor gene CRYPTOCHROME 1 (CRY1) in two genetic backgrounds showed a drastic reduction in fitness in the field. Experiments with UV-B attenuation in the field and with supplemental UV-B in growth chambers demonstrated that UV-B caused the cry1 uvr8 conditional lethal phenotype. Using RNA-seq data of field-grown single and double mutants, we explicitly identified genes showing significant statistical interaction of UVR8 and CRY1 mutations in the presence of UV-B in the field. They were enriched in Gene Ontology categories related to oxidative stress, photoprotection and DNA damage repair in addition to UV-B response. Our study demonstrates the functional importance of the UVR8-mediated response across life stages in natura, which is partially redundant with that of cry1. Moreover, these data provide an integral picture of gene expression associated with plant responses under field conditions.
Heat shock–inducible clonal analysis reveals the stepwise establishment of cell fate in the rice stem
Authors: Tsuda Katsutoshi , Maeno Akiteru , Nonomura Ken-Ichi 
Published: September 2023

Abstract
The stem, consisting of nodes and internodes, is the shoot axis, which supports aboveground organs and connects them to roots. In contrast to other organs, developmental processes of the stem remain elusive, especially those initiating nodes and internodes. By introducing an intron into the Cre recombinase gene, we established a heat shock–inducible clonal analysis system in a single binary vector and applied it to the stem in the flag leaf phytomer of rice (Oryza sativa). With detailed characterizations of stem structure and development, we show that cell fate acquisition for each domain of the stem occurs stepwise. Cell fate for a single phytomer was established in the shoot apical meristem (SAM) by one plastochron before leaf initiation. Cells destined for the foot (nonelongating domain at the stem base) also started emerging before leaf initiation. Cell fate acquisition for the node began just before leaf initiation at the flank of the SAM, separating cell lineages for leaves and stems. Subsequently, cell fates for the axillary bud were established in early leaf primordia. Finally, cells committed to the internode emerged from, at most, a few cell tiers of the 12- to 25-cell stage stem epidermis. Thus, internode cell fate is established last during stem development. This study provides the groundwork to unveil underlying molecular mechanisms in stem development and a valuable tool for clonal analysis, which can be applied to various species.
Na+-preferential ion transporter HKT1;1 mediates salt tolerance in blueberry
Authors: Song Huifang , Cao Yibo , Zhao Xinyan , Zhang Lingyun 
Published: September 2023

Abstract
Soil salinity is a major environmental factor constraining growth and productivity of highbush blueberry (Vaccinium corymbosum). Leaf Na+ content is associated with variation in salt tolerance among blueberry cultivars; however, the determinants and mechanisms conferring leaf Na+ exclusion are unknown. Here, we observed that the blueberry cultivar ‘Duke’ was more tolerant than ‘Sweetheart’ and accumulated less Na+ in leaves under salt stress conditions. Through transcript profiling, we identified a member of the high-affinity K+ transporter (HKT) family in blueberry, VcHKT1;1, as a candidate gene involved in leaf Na+ exclusion and salt tolerance. VcHKT1;1 encodes a Na+-preferential transporter localized to the plasma membrane and is preferentially expressed in the root stele. Heterologous expression of VcHKT1;1 in Arabidopsis (Arabidopsis thaliana) rescued the salt hypersensitivity phenotype of the athkt1 mutant. Decreased VcHKT1;1 transcript levels in blueberry plants expressing antisense-VcHKT1;1 led to increased Na+ concentrations in xylem sap and higher leaf Na+ contents compared with wild-type plants, indicating that VcHKT1;1 promotes leaf Na+ exclusion by retrieving Na+ from xylem sap. A naturally occurring 8-bp insertion in the promoter increased the transcription level of VcHKT1;1, thus promoting leaf Na+ exclusion and blueberry salt tolerance. Collectively, we provide evidence that VcHKT1;1 promotes leaf Na+ exclusion and propose natural variation in VcHKT1;1 will be valuable for breeding Na+-tolerant blueberry cultivars in the future.
C-terminally encoded peptides act as signals to increase cotton root nitrate uptake under nonuniform salinity
Authors: Li Chenyang , Hu Qiuyue , Luo Zhen , Wang Xiaowen , Tang Wei , Lu Hequan , Ma Changle , Kong Xiangqiang 
Published: September 2023

Abstract
Soil salinity is often heterogeneous in saline fields. Nonuniform root salinity increases nitrate uptake into cotton (Gossypium hirsutum) root portions exposed to low salinity, which may be regulated by root portions exposed to high salinity through a systemic long-distance signaling mechanism. However, the signals transmitted between shoots and roots and their precise molecular mechanisms for regulating nitrate uptake remain unknown. Here, we showed that nonuniform root salinity treatment using split-root systems increases the expression of C-TERMINALLY ENCODED PEPTIDE (GhCEP) genes in high-saline-treated root portions. GhCEP peptides originating in high-saline-treated root portions act as ascending long-distance mobile signals transported to the shoots to promote the expression of CEP DOWNSTREAM (GhCEPD) genes by inducing the expression of CEP receptor (GhCEPR) genes. The shoot-derived GhCEPD polypeptides act as descending mobile signals transported to the roots through the phloem, increasing the expression of nitrate transport genes NITRATE TRANSPORTER 1.1 (GhNRT1.1), GhNRT2.1, and GhNRT1.5 in nonsaline-treated root portions, thereby increasing nitrate uptake in the nonsaline-treated root portions. This study indicates that GhCEP and GhCEPD signals are transported between roots and shoots to increase nitrate uptake in cotton, and the transport from the nonsaline root side is in response to nonuniform root salinity distribution.
Sensory neuron activation from topical treatments modulates the sensorial perception of human skin
Authors: Bennett-Kennett Ross , Pace Joseph , Lynch Barbara , Domanov Yegor , Luengo Gustavo S , Potter Anne , Dauskardt Reinhold H 
Published: September 2023

Abstract
Neural signaling of skin sensory perception from topical treatments is often reported in subjective terms such as a sensation of skin “tightness” after using a cleanser or “softness” after applying a moisturizer. However, the mechanism whereby cutaneous mechanoreceptors and corresponding sensory neurons are activated giving rise to these perceptions has not been established. Here, we provide a quantitative approach that couples in vitro biomechanical testing and detailed computational neural stimulation modeling along with a comprehensive in vivo self-assessment survey to demonstrate how cutaneous biomechanical changes in response to treatments are involved in the sensorial perception of the human skin. Strong correlations are identified between reported perception up to 12 hours post treatment and changes in the computed neural stimulation from mechanoreceptors residing deep under the skin surface. The study reveals a quantitative framework for understanding the biomechanical neural activation mechanism and the subjective perception by individuals.
Low-rate smartphone videoscopy for microsecond luminescence lifetime imaging with machine learning
Authors: Wang Yan , Sadeghi Sina , Velayati Alireza , Paul Rajesh , Hetzler Zach , Danilov Evgeny , Ligler Frances S , Wei Qingshan 
Published: September 2023

Abstract
Time-resolved techniques have been widely used in time-gated and luminescence lifetime imaging. However, traditional time-resolved systems require expensive lab equipment such as high-speed excitation sources and detectors or complicated mechanical choppers to achieve high repetition rates. Here, we present a cost-effective and miniaturized smartphone lifetime imaging system integrated with a pulsed ultraviolet (UV) light-emitting diode (LED) for 2D luminescence lifetime imaging using a videoscopy-based virtual chopper (V-chopper) mechanism combined with machine learning. The V-chopper method generates a series of time-delayed images between excitation pulses and smartphone gating so that the luminescence lifetime can be measured at each pixel using a relatively low acquisition frame rate (e.g. 30 frames per second [fps]) without the need for excitation synchronization. Europium (Eu) complex dyes with different luminescent lifetimes ranging from microseconds to seconds were used to demonstrate and evaluate the principle of V-chopper on a 3D-printed smartphone microscopy platform. A convolutional neural network (CNN) model was developed to automatically distinguish the gated images in different decay cycles with an accuracy of &gt;99.5%. The current smartphone V-chopper system can detect lifetime down to ∼75 µs utilizing the default phase shift between the smartphone video rate and excitation pulses and in principle can detect much shorter lifetimes by accurately programming the time delay. This V-chopper methodology has eliminated the need for the expensive and complicated instruments used in traditional time-resolved detection and can greatly expand the applications of time-resolved lifetime technologies.
Broadening the public health approach to policing
Authors: Sidebottom Aiden , Tilley Nick 
Published: September 2023

Abstract
There is growing interest in a public health approach to policing. In Britain, it has attracted major government investment and is advocated as a way to improve understanding and prevention of violence. We largely support efforts better to integrate public health and policing. We do, however, argue in this paper that the current conception of public health is unduly narrow, focussing overwhelmingly on early intervention and paying little attention to situational measures directed at more immediate causes of crime. We argue that the neglect of situational intervention rests on a partial interpretation of the public health literature, and ignores a long history of situational measures being effectively used to reduce harmful behaviours. If a public health approach is to generate improvements in policing and crime prevention, we argue that a broader conception of public health is needed.
Long-term in vivo chimeric cells tracking in non-human primate
Authors: Wu Junmo , Kang Yu , Luo Xiang , Dai Shaoxing , Shi Yuxi , Li Zhuoyao , Tang Zengli , Chen Zhenzhen , Zhu Ran , Yang Pengpeng , Li Zifan , Wang Hong , Chen Xinglong , Zhao Ziyi , Ji Weizhi , Niu Yuyu 
Published: September 2023

Abstract
Non-human primates (NHPs) are increasingly used in preclinical trials to test the safety and efficacy of biotechnology therapies. Nonetheless, given the ethical issues and costs associated with this model, it would be highly advantageous to use NHP cellular models in clinical studies. However, developing and maintaining the naïve state of primate pluripotent stem cells (PSCs) remains difficult as does in vivo detection of PSCs, thus limiting biotechnology application in the cynomolgus monkey. Here, we report a chemically defined, xeno-free culture system for culturing and deriving monkey PSCs in vitro. The cells display global gene expression and genome-wide hypomethylation patterns distinct from monkey-primed cells. We also found expression of signaling pathways components that may increase the potential for chimera formation. Crucially for biomedical applications, we were also able to integrate bioluminescent reporter genes into monkey PSCs and track them in chimeric embryos in vivo and in vitro. The engineered cells retained embryonic and extra-embryonic developmental potential. Meanwhile, we generated a chimeric monkey carrying bioluminescent cells, which were able to track chimeric cells for more than 2 years in living animals. Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models for clinical studies.
“Ethnic Cleansing”: An Analysis of Conceptual and Empirical Ambiguity
Authors: Garrity Meghan M 
Published: September 2023

Abstract
Despite significant scholarly disagreement about its definition, core meaning, and corresponding cases, ethnic cleansing has escaped careful conceptual examination. This article identifies five key areas of conceptual confusion that undermine the integrity and utility of the concept. These include discrepancies over the core meaning of ethnic cleansing; tension between ethnic cleansing as a practice and a policy; the lack of boundedness between ethnic cleansing and other related concepts; the universe of cases that belong together; and disparate subtype classification criteria. This conceptual confusion undermines effective comparative analysis and, in turn, our understanding of the causes of ethnic cleansing and associated policy recommendations. The solution is to abandon the social science usage of ethnic cleansing in favor of alternative concepts defined by the distinct intent of the perpetrator(s): massacre (to annihilate), mass expulsion (to remove), coercive assimilation (to eliminate a unique cultural identity), and control (to subjugate). This eliminates ambiguity, improves theoretical precision, and opens a promising new research agenda.
Aberrant single-subject morphological brain networks in first-episode, treatment-naive adolescents with major depressive disorder
Authors: Qiu Xiaofan , Li Junle , Pan Fen , Yang Yuping , Zhou Weihua , Chen Jinkai , Wei Ning , Lu Shaojia , Weng Xuchu , Huang Manli , Wang Jinhui 
Published: September 2023

Abstract

Background
Neuroimaging-based connectome studies have indicated that major depressive disorder (MDD) is associated with disrupted topological organization of large-scale brain networks. However, the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD.

Objective
To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD.

Methods
Twenty-five first-episode, treatment-naive adolescents with MDD and 19 healthy controls (HCs) underwent T1-weighted magnetic resonance imaging and a battery of neuropsychological tests. Single-subject morphological brain networks were constructed separately based on cortical thickness, fractal dimension, gyrification index, and sulcus depth, and topologically characterized by graph-based approaches. Between-group differences were inferred by permutation testing. For significant alterations, partial correlations were used to examine their associations with clinical and neuropsychological variables in the patients. Finally, a support vector machine was used to classify the patients from controls.

Results
Compared with the HCs, the patients exhibited topological alterations only in cortical thickness-based networks characterized by higher nodal centralities in parietal (left primary sensory cortex) but lower nodal centralities in temporal (left parabelt complex, right perirhinal ectorhinal cortex, right area PHT and right ventral visual complex) regions. Moreover, decreased nodal centralities of some temporal regions were correlated with cognitive dysfunction and clinical characteristics of the patients. These results were largely reproducible for binary and weighted network analyses. Finally, topological properties of the cortical thickness-based networks were able to distinguish the MDD adolescents from HCs with 87.6% accuracy.

Conclusion
Adolescent MDD is associated with disrupted topological organization of morphological brain networks, and the disruptions provide potential biomarkers for diagnosing and monitoring the disease.