bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceptions of regional origin and social attributes of phonetic variants used in Iberian Spanish
Authors: Henriksen Nicholas , García-Amaya Lorenzo , Fischer Micha , Czapla Jessica , Dakki Natalie , Galvano Amber , Khansa Sarah , Maly Ellie G. , Phillips Zoe , Premkumar Vidhya , Topouzian Stepan , Wiaduck Thomas 
Published: September 2023

AbstractSociodemographic information, such as a speaker’s regional origin, is intimately related to the judgments and social evaluations that listeners assign to that speaker. This association between linguistic form and social information can also lead to linguistic profiling, a harmful form of discrimination. The present study examines the geographic classifications and social attitudes attributed to ten phonetic variants used within regional varieties of Iberian (i.e., European) Spanish. We are specifically interested in understanding listeners’ geographical classifications and language attitudes held toward Andalusian Spanish, which is a less privileged regional variety spoken in Spain’s southern region, as compared to north-central Peninsular Spanish (NCPS). The results of an online survey show that 165 listeners were fairly consistent when geographically classifying Andalusian-sounding stimuli as originating from the south of Spain. Importantly, the respondents also attributed less favorable social meaning to the Andalusian-sounding stimuli in comparison to the NCPS-sounding stimuli. We link the findings to broader themes in sociolinguistics, such as language-based discrimination, linguistic insecurity, and the social motivations of language change.
Using morphological, chemical, and molecular data to study the diversity of Xanthoparmelia species from South Africa (Ascomycota, Parmeliaceae)
Authors: Barcenas-Peña Alejandrina , Sipman Harrie J. M. , Wirth Volkmar , Grewe Felix , Lumbsch H. Thorsten 
Published: September 2023

AbstractThere is still a high diversity of lichen-forming fungi that remains undescribed, especially cryptic lineages at the species level. Integrating morphological, chemical, and DNA sequence data has proved useful in corroborating species descriptions and delimitations. Here we reviewed morphological features, secondary metabolites and the DNA sequences of ITS, mtSSU and nuLSU markers to study the diversity of Xanthoparmelia in southern Africa. A total of 37 species were recorded. Three of these appear undescribed, and we therefore describe them here as new: Xanthoparmelia nimisii, with a sorediate thallus and broad lobes, is well supported as a clade separate from X. annexa; X. pseudochalybaeizans with a white medulla is phylogenetically distinct from the otherwise similar X. chalybaeizans; and X. sipmaniana, well supported as a separate clade from the similar X. hypoprocetrarica. In addition, the separation of Xanthoparmelia capensis and X. tinctina requires further studies.
Nimisora (Lecanoraceae, Ascomycota), a new genus for a common lecideoid epiphytic species from the central Iberian Peninsula
Authors: Pérez-Ortega Sergio , Turégano Yolanda , Svensson Måns , Zamora Juan Carlos 
Published: September 2023

AbstractThe new genus Nimisora Pérez-Ort., M. Svenss. & J. C. Zamora is introduced to accommodate a puzzling lecideoid epiphyte common in the central Iberian Peninsula. Nimisora is characterized by the following combination of characters: lecideoid apothecia, excipulum composed of sparingly branched radiating hyphae with narrow lumina, thick walls and swollen terminal cells, the presence of a brown K+ olivaceous green pigment in the epihymenium, an ascus tip similar to the Bacidia-type, and the presence of simple ellipsoid ascospores. Molecular analyses based on nrITS, nrLSU and mtSSU sequences unequivocally place the new genus within the Lecanoraceae; however, its phylogenetic affinities with other genera of the family remain largely unresolved. Comparisons with the morphologically closest genera are provided. The single species of the genus, Nimisora iberica Pérez-Ort., Turégano, M. Svenss. & J. C. Zamora sp. nov., is also described as new to science.
From pets to plates: network analysis of trafficking in tortoises and freshwater turtles representing different types of demand
Authors: Sengottuvel Ramya Roopa , Mendis Aristo , Sultan Nazneen , Shukla Shivira , Chaudhuri Anirban , Mendiratta Uttara 
Published: September 2023

AbstractDespite being protected under the law, illegal trade in tortoises and freshwater turtles is common in India, with different species being trafficked for different markets. Indian species of tortoises and hard-shell turtles are predominantly trafficked for the pet trade and soft-shell turtles for the meat trade. Given their distinct markets, the operation of trade may vary between these different groups of tortoises and freshwater turtles, thereby necessitating different types of interventions. However, a systematic examination of illegal trade in tortoises and freshwater turtles that takes into account the differences between these markets is currently lacking. Here we compare the supply networks of tortoises/hard-shell turtles (in demand for pet trade) vs soft-shell turtles (meat trade), using information from 78 and 64 seizures, respectively, that were reported in the media during 2013–2019. We used social network analysis to compare the two networks and the role of individual nodes (defined as locations at the district or city scale) within these networks. We found that the tortoise/hard-shell turtle network had a larger geographical scale, with more international trafficking links, than the soft-shell turtle network. We recorded convoluted smuggling routes in tortoise/hard-shell turtle trafficking, whereas soft-shell turtle trafficking was uni-directional from source to destination. Within both networks, we found that a few nodes played disproportionately important roles as key exporting, importing or transit nodes. Our study provides insights into the similarities and differences in the illegal supply networks of different groups of tortoises and freshwater turtles, in demand for different markets. We highlight the need for intervention strategies tailored to address the illegal trade in each of these groups.
Comparison of Empirical and Theoretical Models of the Thermospheric Density Enhancement During the 3–4 February 2022 Geomagnetic Storm
Authors: He Jianhui , Astafyeva Elvira , Yue Xinan , Pedatella Nicholas M. , Lin Dong , Fuller‐Rowell Timothy J. , Fedrizzi Mariangel , Codrescu Mihail , Doornbos Eelco , Siemes Christian , Bruinsma Sean , Pitout Frederic , Kubaryk Adam 
Published: September 2023

AbstractOn 3 February 2022, at 18:13 UTC, SpaceX launched and a short time later deployed 49 Starlink satellites at an orbit altitude between 210 and 320 km. The satellites were meant to be further raised to 550 km. However, the deployment took place during the main phase of a moderate geomagnetic storm, and another moderate storm occurred on the next day. The resulting increase in atmospheric drag led to 38 out of the 49 satellites reentering the atmosphere in the following days. In this work, we use both observations and simulations to perform a detailed investigation of the thermospheric conditions during this storm. Observations at higher altitudes, by Swarm‐A (∼438 km, 09/21 Local Time [LT]) and the Gravity Recovery and Climate Experiment Follow‐On (∼505 km, 06/18 LT) missions show that during the main phase of the storms the neutral mass density increased by 110% and 120%, respectively. The storm‐time enhancement extended to middle and low latitudes and was stronger in the northern hemisphere. To further investigate the thermospheric variations, we used six empirical and first‐principle numerical models. We found the models captured the upper and lower thermosphere changes, however, their simulated density enhancements differ by up to 70%. Further, the models showed that at the low orbital altitudes of the Starlink satellites (i.e., 200–300 km) the global averaged storm‐time density enhancement reached up to ∼35%–60%. Although such storm effects are far from the largest, they seem to be responsible for the reentry of the 38 satellites.
A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir
Authors: Zhang Yumin , Sun Yuan , Xie Yuanchao , Shang Weijuan , Wang Zhen , Jiang Hualiang , Shen Jingshan , Xiao Gengfu , Zhang Leike 
Published: September 2023

AbstractDuring the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage of SARS-CoV-2 infection has been a priority for controlling COVID-19. Although Paxlovid and molnupiravir have received emergency approval from the FDA, some side effect concerns have emerged, and the possible oral agents are still limited, resulting in optimized drug development becoming an urgent requirement. An oral remdesivir derivative, VV116, has been reported to have promising antiviral effects against SARS-CoV-2 and positive therapeutic outcomes in clinical trials. However, whether VV116 has broad-spectrum anti-coronavirus activity and potential synergy with other drugs is not clear. Here, we uncovered the broad-spectrum antiviral potency of VV116 against SARS-CoV-2 variants of concern (VOCs), HCoV-OC43, and HCoV-229E in various cell lines. In vitro drug combination screening targeted RdRp and proteinase, highlighting the synergistic effect of VV116 and nirmatrelvir on HCoV-OC43 and SARS-CoV-2. When co-administrated with ritonavir, the combination of VV116 and nirmatrelvir showed significantly enhanced antiviral potency with noninteracting pharmacokinetic properties in mice. Our findings will facilitate clinical treatment with VV116 or VV116+nirmatrelvir combination to fight coronavirus infection.
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Authors: Gao Chao , Jiang Jingwen , Tan Yuyan , Chen Shengdi 
Published: September 2023

AbstractMicroglia activation is observed in various neurodegenerative diseases. Recent advances in single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity. Some identified microglia in specific states correlate with pathological hallmarks and are associated with specific functions. Microglia both exert protective function by phagocytosing and clearing pathological protein aggregates and play detrimental roles due to excessive uptake of protein aggregates, which would lead to microglial phagocytic ability impairment, neuroinflammation, and eventually neurodegeneration. In addition, peripheral immune cells infiltration shapes microglia into a pro-inflammatory phenotype and accelerates disease progression. Microglia also act as a mobile vehicle to propagate protein aggregates. Extracellular vesicles released from microglia and autophagy impairment in microglia all contribute to pathological progression and neurodegeneration. Thus, enhancing microglial phagocytosis, reducing microglial-mediated neuroinflammation, inhibiting microglial exosome synthesis and secretion, and promoting microglial conversion into a protective phenotype are considered to be promising strategies for the therapy of neurodegenerative diseases. Here we comprehensively review the biology of microglia and the roles of microglia in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and Huntington’s disease. We also summarize the possible microglia-targeted interventions and treatments against neurodegenerative diseases with preclinical and clinical evidence in cell experiments, animal studies, and clinical trials.
Tauopathy promotes spinal cord-dependent production of toxic amyloid-beta in transgenic monkeys
Authors: Tu Zhuchi , Yan Sen , Han Bofeng , Li Caijuan , Liang Weien , Lin Yingqi , Ding Yongyan , Wei Huiyi , Wang Lu , Xu Hao , Ye Jianmeng , Li Bang , Li Shihua , Li Xiao-Jiang 
Published: September 2023

AbstractTauopathy, characterized by the hyperphosphorylation and accumulation of the microtubule-associated protein tau, and the accumulation of Aβ oligomers, constitute the major pathological hallmarks of Alzheimer’s disease. However, the relationship and causal roles of these two pathological changes in neurodegeneration remain to be defined, even though they occur together or independently in several neurodegenerative diseases associated with cognitive and movement impairment. While it is widely accepted that Aβ accumulation leads to tauopathy in the late stages of the disease, it is still unknown whether tauopathy influences the formation of toxic Aβ oligomers. To address this, we generated transgenic cynomolgus monkey models expressing Tau (P301L) through lentiviral infection of monkey embryos. These monkeys developed age-dependent neurodegeneration and motor dysfunction. Additionally, we performed a stereotaxic injection of adult monkey and mouse brains to express Tau (P301L) via AAV9 infection. Importantly, we found that tauopathy resulting from embryonic transgenic Tau expression or stereotaxic brain injection of AAV-Tau selectively promoted the generation of Aβ oligomers in the monkey spinal cord. These Aβ oligomers were recognized by several antibodies to Aβ1–42 and contributed to neurodegeneration. However, the generation of Aβ oligomers was not observed in other brain regions of Tau transgenic monkeys or in the brains of mice injected with AAV9-Tau (P301L), suggesting that the generation of Aβ oligomers is species- and brain region-dependent. Our findings demonstrate for the first time that tauopathy can trigger Aβ pathology in the primate spinal cord and provide new insight into the pathogenesis and treatment of tauopathy.
Loss of PDE4D7 expression promotes androgen independence, neuroendocrine differentiation and alterations in DNA repair: implications for therapeutic strategies
Authors: Gulliver Chloe , Huss Sebastian , Semjonow Axel , Baillie George S. , Hoffmann Ralf 
Published: September 2023

Abstract
Background
Androgen signalling remains the seminal therapeutic approach for the management of advanced prostate cancer. However, most tumours eventually shift towards an aggressive phenotype, characterised by androgen independence and treatment resistance. The cyclic adenosine monophosphate (cAMP) pathway plays a crucial role in regulating various cellular processes, with the phosphodiesterase PDE4D7 being a vital modulator of cAMP signalling in prostate cancer cells.

Methods
Using shRNA-mediated PDE4D7 knockdown in LNCaP cells and downstream analysis via RNA sequencing and phenotypic assays, we replicate clinical observations that diminished PDE4D7 expression promotes an aggressive prostate cancer phenotype.

Results
Our study provides evidence that loss of PDE4D7 expression represents a pivotal switch driving the transition from an androgen-sensitive state to hormone unresponsiveness and neuroendocrine differentiation. In addition, we demonstrate that PDE4D7 loss affects DNA repair pathways, conferring resistance to poly ADP ribose polymerase (PARP) inhibitors.

Conclusion
Reinstating PDE4D7 expression sensitises prostate cancer cells to anti-androgens, DNA damage response inhibitors, and cytotoxic therapies. These findings provide significant insight into the regulatory role of PDE4D7 in the development of lethal prostate cancer and the potential of its modulation as a novel therapeutic strategy.
Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level
Authors: Atallah N. M. , Alsaleem M. , Toss M. S. , Mongan N. P. , Rakha E. 
Published: September 2023

Abstract
Background
Increasing data indicate that HER2-positive (HER2 + ) breast cancer (BC) subtypes exhibit differential responses to targeted anti-HER2 therapy. This study aims to investigate these differences and the potential underlying molecular mechanisms.

Methods
A large cohort of BC patients (n = 7390) was utilised. The clinicopathological characteristics and differential gene expression (DGE) of HER2+ immunohistochemical (IHC) subtypes, specifically HER2 IHC 3+ and IHC 2 + /Amplified, were assessed and correlated with pathological complete response (pCR) and survival in the neoadjuvant and adjuvant settings, respectively. The role of oestrogen receptor (ER) status was also investigated.

Results
Compared to HER2 IHC 3+ tumours, BC patients with IHC 2 + /Amplified showed a significantly lower pCR rate (22% versus 57%, P < 0.001), shorter survival regardless of HER2 gene copy number, were less classified as HER2 enriched, and enriched for trastuzumab resistance and ER signalling pathway genes. ER positivity significantly decreased response to anti-HER2 therapy in IHC 2 + /Amplified, but not in IHC 3 + BC patients.

Conclusion
In HER2 + BC, overexpression of HER2 protein is the driver of the oncogenic pathway, and it is the main predictor of response to anti-HER2 therapy. ER signalling pathways are more dominant in BC with equivocal HER2 expression. personalised anti-HER2 therapy based on IHC classes should be considered.
Seasonal pigment fluctuation in diploid and polyploid Arabidopsis revealed by machine learning-based phenotyping method PlantServation
Authors: Akiyama Reiko , Goto Takao , Tameshige Toshiaki , Sugisaka Jiro , Kuroki Ken , Sun Jianqiang , Akita Junichi , Hatakeyama Masaomi , Kudoh Hiroshi , Kenta Tanaka , Tonouchi Aya , Shimahara Yuki , Sese Jun , Kutsuna Natsumaro , Shimizu-Inatsugi Rie , Shimizu Kentaro K. 
Published: September 2023

AbstractLong-term field monitoring of leaf pigment content is informative for understanding plant responses to environments distinct from regulated chambers but is impractical by conventional destructive measurements. We developed PlantServation, a method incorporating robust image-acquisition hardware and deep learning-based software that extracts leaf color by detecting plant individuals automatically. As a case study, we applied PlantServation to examine environmental and genotypic effects on the pigment anthocyanin content estimated from leaf color. We processed >4 million images of small individuals of fourArabidopsisspecies in the field, where the plant shape, color, and background vary over months. Past radiation, coldness, and precipitation significantly affected the anthocyanin content. The synthetic allopolyploidA. kamchaticarecapitulated the fluctuations of natural polyploids by integrating diploid responses. The data support a long-standing hypothesis stating that allopolyploids can inherit and combine the traits of progenitors. PlantServation facilitates the study of plant responses to complex environments termed “in natura”.
Manipulation of nonlinear optical responses in layered ferroelectric niobium oxide dihalides
Authors: Ye Liangting , Zhou Wenju , Huang Dajian , Jiang Xiao , Guo Qiangbing , Cao Xinyu , Yan Shaohua , Wang Xinyu , Jia Donghan , Jiang Dequan , Wang Yonggang , Wu Xiaoqiang , Zhang Xiao , Li Yang , Lei Hechang , Gou Huiyang , Huang Bing 
Published: September 2023

AbstractRealization of highly tunable second-order nonlinear optical responses, e.g., second-harmonic generation and bulk photovoltaic effect, is critical for developing modern optical and optoelectronic devices. Recently, the van der Waals niobium oxide dihalides are discovered to exhibit unusually large second-harmonic generation. However, the physical origin and possible tunability of nonlinear optical responses in these materials remain to be unclear. In this article, we reveal that the large second-harmonic generation in NbOX2 (X = Cl, Br, and I) may be partially contributed by the large band nesting effect in different Brillouin zone. Interestingly, the NbOCl2 can exhibit dramatically different strain-dependent bulk photovoltaic effect under different polarized light, originating from the light-polarization-dependent orbital transitions. Importantly, we achieve a reversible ferroelectric-to-antiferroelectric phase transition in NbOCl2 and a reversible ferroelectric-to-paraelectric phase transition in NbOI2 under a certain region of external pressure, accompanied by the greatly tunable nonlinear optical responses but with different microscopic mechanisms. Our study establishes the interesting external-field tunability of NbOX2 for nonlinear optical device applications.
A conserved membrane protein negatively regulates Mce1 complexes in mycobacteria
Authors: Chen Yushu , Wang Yuchun , Chng Shu-Sin 
Published: September 2023

AbstractTuberculosis continues to pose a serious threat to global health. Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen that relies on various mechanisms to survive and persist within the host. Among their many virulence factors, mycobacteria encode Mce systems. Some of these systems are implicated in lipid uptake, but the molecular basis for Mce function(s) is poorly understood. To gain insights into the composition and architecture of Mce systems, we characterized the putative Mce1 complex involved in fatty acid transport. We show that the Mce1 system in Mycobacterium smegmatis comprises a canonical ATP-binding cassette transporter associated with distinct heterohexameric assemblies of substrate-binding proteins. Furthermore, we establish that the conserved membrane protein Mce1N negatively regulates Mce1 function via a unique mechanism involving blocking transporter assembly. Our work offers a molecular understanding of Mce complexes, sheds light on mycobacterial lipid metabolism and its regulation, and informs future anti-mycobacterial strategies.
Integrated inflammatory signaling landscape response after delivering Elovanoid free-fatty-acid precursors leading to experimental stroke neuroprotection
Authors: Reid Madigan M. , Belayev Ludmila , Khoutorova Larissa , Mukherjee Pranab K. , Obenaus Andre , Shelvin Kierany , Knowles Stacey , Hong Sung-Ha , Bazan Nicolas G. 
Published: September 2023

AbstractDespite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in the subcortex. Additionally, the FFAs elicit a comprehensive downregulation of inflammatory microglia/monocyte-derived macrophages and astrocyte-associated genes in the subcortical region. Functional analysis reveals inhibition of immune-related pathways and production of upstream molecules related to detrimental signaling events in post-stroke acute and subacute phases.