bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neogene Mass Accumulation Rate of Carbonate Sediment Across Northern Zealandia, Tasman Sea, Southwest Pacific
Authors: Sutherland R. , Dos Santos Z. , Agnini C. , Alegret L. , Lam A. R. , Westerhold T. , Drake M. K. , Harper D. T. , Dallanave E. , Newsam C. , Cramwinckel Marlow J. , Dickens G. R. , Collot J. , Etienne S. J. G. , Bordenave A. , Stratford W. R. , Zhou X. , Li H. , Asatryan G. 
Published: January 2022

AbstractSediment mass accumulation rate (MAR) is a proxy for paleoceanographic conditions, especially if biological productivity generated most of the sediment. We determine MAR records from pelagic calcareous sediments in Tasman Sea based on analysis of 11 boreholes and >3 million seismic reflection horizon picks. Seismic data from regions of 10,000–30,000 km2 around each borehole were analyzed using data from International Ocean Discovery Program Expedition 371 and other boreholes. Local MAR was affected by deepwater currents that winnowed, eroded, or deposited seafloor sediment. Therefore, it is necessary to average MARs across regions to test paleoceanographic and productivity models. MARs during the Miocene Climate optimum (18–14 Ma) were slightly lower than Quaternary values but increased on southern Lord Howe Rise at 14–13 Ma, when global climate became colder. Intensification of the Indian and East Asian monsoons at ∼8 Ma and ∼3.6 Ma approximately corresponds to the start and end, respectively, of the Biogenic Bloom, which had MARs at least double Quaternary values. On northern Lord Howe Rise, we recognize peak MARs at∼7 Ma and ∼5 Ma. There is no correlation between Neogene MAR and ocean pH or atmospheric CO2 concentration. Neogene MARs are on average higher than Quaternary values. We posit that future long‐term productivity in the southwest Pacific could be higher than Quaternary values, but new computer models that can fit our observations are required to test this hypothesis.
Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption
Authors: Yu Fanyuan , Huo Fengli , Li Feifei , Zuo Yanqin , Wang Chenglin , Ye Ling 
Published: January 2022

AbstractInflammation-associated proteinase functions are key determinants of inflammatory stromal tissues deconstruction. As a specialized inflammatory pathological process, dental internal resorption (IR) includes both soft and hard tissues deconstruction within the dentin-pulp complex, which has been one of the main reasons for inflammatory tooth loss. Mechanisms of inflammatory matrix degradation and tissue resorption in IR are largely unclear. In this study, we used a combination of Cre-loxP reporter, flow cytometry, cell transplantation, and enzyme activities assay to mechanistically investigate the role of regenerative cells, odontoblasts (ODs), in inflammatory mineral resorption and matrices degradation. We report that inflamed ODs have strong capabilities of matrix degradation and tissue resorption. Traditionally, ODs are regarded as hard-tissue regenerative cells; however, our data unexpectedly present ODs as a crucial population that participates in IR-associated tissue deconstruction. Specifically, we uncovered that nuclear factor-kappa b (NF-κB) signaling orchestrated Tumor necrosis factor α (TNF-α)-induced matrix metalloproteinases (Mmps) and Cathepsin K (Ctsk) functions in ODs to enhance matrix degradation and tissue resorption. Furthermore, TNF-α increases Rankl/Opg ratio in ODs via NF-κB signaling by impairing Opg expression but increasing Rankl level, which utterly makes ODs cell line 17IIA11 (A11) become Trap+and Ctsk+multinucleated cells to perform resorptive actions. Blocking of NF-κB signaling significantly rescues matrix degradation and resorptive functions of inflamed ODs via repressing vital inflammatory proteinases Mmps and Ctsk. Utterly, via utilizing NF-κB specific small molecule inhibitors we satisfactorily attenuated inflammatory ODs-associated human dental IR in vivo. Our data reveal the underlying mechanisms of inflammatory matrix degradation and resorption via proteinase activities in IR-related pathological conditions.
Putting the “mental” back in “mental disorders”: a perspective from research on fear and anxiety
Authors: Taschereau-Dumouchel Vincent , Michel Matthias , Lau Hakwan , Hofmann Stefan G. , LeDoux Joseph E. 
Published: January 2022

AbstractMental health problems often involve clusters of symptoms that include subjective (conscious) experiences as well as behavioral and/or physiological responses. Because the bodily responses are readily measured objectively, these have come to be emphasized when developing treatments and assessing their effectiveness. On the other hand, the subjective experience of the patient reported during a clinical interview is often viewed as a weak correlate of psychopathology. To the extent that subjective symptoms are related to the underlying problem, it is often assumed that they will be taken care of if the more objective behavioral and physiological symptoms are properly treated. Decades of research on anxiety disorders, however, show that behavioral and physiological symptoms do not correlate as strongly with subjective experiences as is typically assumed. Further, the treatments developed using more objective symptoms as a marker of psychopathology have mostly been disappointing in effectiveness. Given that “mental” disorders are named for, and defined by, their subjective mental qualities, it is perhaps not surprising, in retrospect, that treatments that have sidelined mental qualities have not been especially effective. These negative attitudes about subjective experience took root in psychiatry and allied fields decades ago when there were few avenues for scientifically studying subjective experience. Today, however, cognitive neuroscience research on consciousness is thriving, and offers a viable and novel scientific approach that could help achieve a deeper understanding of mental disorders and their treatment.
De novo expression of gastrokines in pancreatic precursor lesions impede the development of pancreatic cancer
Authors: Steiner Sabrina , Seleznik Gitta M. , Reding Theresia , Stopic Matea , Lenggenhager Daniela , ten Buren Emiel , Eshmuminov Dilmurodjon , Endhardt Katharina , Hagedorn Catherine , Heidenblut Anna M. , Bratus-Neuenschwander Anna , Grossmann Jonas , Trachsel Christian , Jabbar Karolina S. , Hahn Stephan A. , Berg Johannes vom , Graf Rolf , Gupta Anurag 
Published: January 2022

AbstractMolecular events occurring in stepwise progression from pre-malignant lesions (pancreatic intraepithelial neoplasia; PanIN) to the development of pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Thus, characterization of early PanIN lesions may reveal markers that can help in diagnosing PDAC at an early stage and allow understanding the pathology of the disease. We performed the molecular and histological assessment of patient-derived PanINs, tumor tissues and pancreas from mouse models with PDAC (KC mice that harbor K-RAS mutation in pancreatic tissue), where we noted marked upregulation of gastrokine (GKN) proteins. To further understand the role of gastrokine proteins in PDAC development, GKN-deficient KC mice were developed by intercrossing gastrokine-deficient mice with KC mice. Panc-02 (pancreatic cancer cells of mouse origin) were genetically modified to express GKN1 for further in vitro and in vivo analysis. Our results show that gastrokine proteins were absent in healthy pancreas and invasive cancer, while its expression was prominent in low-grade PanINs. We could detect these proteins in pancreatic juice and serum of KC mice. Furthermore, accelerated PanIN and tumor development were noted in gastrokine deficient KC mice. Loss of gastrokine 1 protein delayed apoptosis during carcinogenesis leading to the development of desmoplastic stroma while loss of gastrokine 2 increased the proliferation rate in precursor lesions. In summary, we identified gastrokine proteins in early pancreatic precursor lesions, where gastrokine proteins delay pancreatic carcinogenesis.
Whole-genome sequencing reveals the evolutionary trajectory of HBV-related hepatocellular carcinoma early recurrence
Authors: Zhou Shao-Lai , Zhou Zheng-Jun , Song Cheng-Li , Xin Hao-Yang , Hu Zhi-Qiang , Luo Chu-Bin , Luo Yi-Jie , Li Jia , Dai Zhi , Yang Xin-Rong , Shi Ying-Hong , Wang Zheng , Huang Xiao-Wu , Fan Jia , Zhou Jian 
Published: January 2022

AbstractPatients with hepatocellular carcinoma (HCC) have poor long-term survival following curative resection because of the high rate of tumor early recurrence. Little is known about the trajectory of genomic evolution from primary to early-recurrent HCC. In this study, we performed whole-genome sequencing (WGS) on 40 pairs of primary and early-recurrent hepatitis B virus (HBV)-related HCC tumors from patients who received curative resection, and from four patients whose primary and recurrent tumor were extensively sampled. We identified two recurrence patterns: de novo recurrence (18/40), which developed genetically independently of the primary tumor and carried different HCC drivers, and ancestral recurrence (22/40), which was clonally related to the primary tumor and progressed more rapidly than de novo recurrence. We found that the recurrence location was predictive of the recurrence pattern: distant recurrence tended to display the de novo pattern, whereas local recurrence tended to display the ancestral pattern. We then uncovered the evolutionary trajectories based on the subclonal architecture, driver-gene mutations, and mutational processes observed in the primary and recurrent tumors. Multi-region WGS demonstrated spatiotemporal heterogeneity and polyclonal, monophyletic dissemination in HCC ancestral recurrence. In addition, we identified recurrence-specific mutations and copy-number gains in BCL9, leading to WNT/β-catenin signaling activation and an immune-excluded tumor microenvironment, which suggests that BCL9 might serve as a new therapeutic target for recurrent HCC. Collectively, our results allow us to view with unprecedented clarity the genomic evolution during HBV-related HCC early recurrence, providing an important molecular foundation for enhanced understanding of HCC with implications for personalized therapy to improve patient survival.
Niche differentiation of sulfur-oxidizing bacteria (SUP05) in submarine hydrothermal plumes
Authors: Dede Bledina , Hansen Christian T , Neuholz Rene , Schnetger Bernhard , Kleint Charlotte , Walker Sharon , Bach Wolfgang , Amann Rudolf , Meyerdierks Anke 
Published: January 2022

Abstract
Hydrothermal plumes transport reduced chemical species and metals into the open ocean. Despite their considerable spatial scale and impact on biogeochemical cycles, niche differentiation of abundant microbial clades is poorly understood. Here, we analyzed the microbial ecology of two bathy- (Brothers volcano; BrV-cone and northwest caldera; NWC) and a mesopelagic (Macauley volcano; McV) plumes on the Kermadec intra-oceanic arc in the South Pacific Ocean. The microbial community structure, determined by a combination of 16S rRNA gene, fluorescence in situ hybridization and metagenome analysis, was similar to the communities observed in other sulfur-rich plumes. This includes a dominance of the vent characteristic SUP05 clade (up to 22% in McV and 51% in BrV). In each of the three plumes analyzed, the community was dominated by a different yet uncultivated chemoautotrophic SUP05 species, here, provisionally named, Candidatus Thioglobus vadi (McV), Candidatus Thioglobus vulcanius (BrV-cone) and Candidatus Thioglobus plumae (BrV-NWC). Statistical analyses, genomic potential and mRNA expression profiles suggested a SUP05 niche partitioning based on sulfide and iron concentration as well as water depth. A fourth SUP05 species was present at low frequency throughout investigated plume samples and may be capable of heterotrophic or mixotrophic growth. Taken together, we propose that small variations in environmental parameters and depth drive SUP05 niche partitioning in hydrothermal plumes.
Cytokines and tryptophan metabolites can predict depressive symptoms in pregnancy
Authors: Sha Qiong , Madaj Zach , Keaton Sarah , Escobar Galvis Martha L , Smart LeAnn , Krzyzanowski Stanislaw , Fazleabas Asgerally T. , Leach Richard , Postolache Teodor T. , Achtyes Eric D. , Brundin Lena 
Published: January 2022

AbstractDepression during and after pregnancy affects up to 20% of pregnant women, but the biological underpinnings remain incompletely understood. As pregnancy progresses, the immune system changes to facilitate fetal development, leading to distinct fluctuations in the production of pro-inflammatory factors and neuroactive tryptophan metabolites throughout the peripartum period. Therefore, it is possible that depression in pregnancy could constitute a specific type of inflammation-induced depression. Both inflammatory factors and kynurenine metabolites impact neuroinflammation and glutamatergic neurotransmission and can therefore affect mood and behavior. To determine whether cytokines and kynurenine metabolites can predict the development of depression in pregnancy, we analyzed blood samples and clinical symptoms in 114 women during each trimester and the postpartum. We analyzed plasma IL-1β, IL-2, -6, -8, -10, TNF, kynurenine, tryptophan, serotonin, kynurenic- quinolinic- and picolinic acids and used mixed-effects models to assess the association between biomarkers and depression severity. IL-1β and IL-6 levels associated positively with severity of depressive symptoms across pregnancy and the postpartum, and that the odds of experiencing significant depressive symptoms increased by >30% per median absolute deviation for both IL-1β and IL-6 (both P = 0.01). A combination of cytokines and kynurenine metabolites in the 2nd trimester had a >99% probability of accurately predicting 3rd trimester depression, with an ROC AUC > 0.8. Altogether, our work shows that cytokines and tryptophan metabolites can predict depression during pregnancy and could be useful as clinical markers of risk. Moreover, inflammation and kynurenine pathway enzymes should be considered possible therapeutic targets in peripartum depression.
Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma
Authors: Martello M. , Poletti A. , Borsi E. , Solli V. , Dozza L. , Barbato S. , Zamagni E. , Tacchetti P. , Pantani L. , Mancuso K. , Vigliotta I. , Rizzello I. , Rocchi S. , Armuzzi S. , Testoni N. , Marzocchi G. , Martinelli G. , Cavo M. , Terragna C. 
Published: January 2022

AbstractAberrations on TP53, either as deletions of chromosome 17p (del17p) or mutations, are associated with poor outcome in multiple myeloma (MM), but conventional detection methods currently in use underestimate their incidence, hindering an optimal risk assessment and prognostication of MM patients. We have investigated the altered status of TP53 gene by SNPs array and sequencing techniques in a homogenous cohort of 143 newly diagnosed MM patients, evaluated both at diagnosis and at first relapse: single-hit on TP53 gene, either deletion or mutation, detected both at clonal and sub-clonal level, had a minor effect on outcomes. Conversely, the coexistence of both TP53 deletion and mutation, which defined the so-called double-hit patients, was associated with the worst clinical outcome (PFS: HR 3.34 [95% CI: 1.37–8.12] p = 0.008; OS: HR 3.47 [95% CI: 1.18–10.24] p = 0.02). Moreover, the analysis of longitudinal samples pointed out that TP53 allelic status might increase during the disease course. Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients.
Neonatal-lethal dilated cardiomyopathy due to a homozygous LMOD2 donor splice-site variant
Authors: Yuen Michaela , Worgan Lisa , Iwanski Jessika , Pappas Christopher T. , Joshi Himanshu , Churko Jared M. , Arbuckle Susan , Kirk Edwin P. , Zhu Ying , Roscioli Tony , Gregorio Carol C. , Cooper Sandra T. 
Published: January 2022

AbstractDilated cardiomyopathy (DCM) is characterized by cardiac enlargement and impaired ventricular contractility leading to heart failure. A single report identified variants in leiomodin-2 (LMOD2) as a cause of neonatally-lethal DCM. Here, we describe two siblings with DCM who died shortly after birth due to heart failure. Exome sequencing identified a homozygous LMOD2 variant in both siblings, (GRCh38)chr7:g.123656237G > A; NM_207163.2:c.273 + 1G > A, ablating the donor 5′ splice-site of intron-1. Pre-mRNA splicing studies and western blot analysis on cDNA derived from proband cardiac tissue, MyoD-transduced proband skin fibroblasts and HEK293 cells transfected with LMOD2 gene constructs established variant-associated absence of canonically spliced LMOD2 mRNA and full-length LMOD2 protein. Immunostaining of proband heart tissue unveiled abnormally short actin-thin filaments. Our data are consistent with LMOD2 c.273 + 1G > A abolishing/reducing LMOD2 transcript expression by: (1) variant-associated perturbation in initiation of transcription due to ablation of the intron-1 donor; and/or (2) degradation of aberrant LMOD2 transcripts (resulting from use of alternative transcription start-sites or cryptic splice-sites) by nonsense-mediated decay. LMOD2 expression is critical for life and the absence of LMOD2 is associated with thin filament shortening and severe cardiac contractile dysfunction. This study describes the first splice-site variant in LMOD2 and confirms the role of LMOD2 variants in DCM.
Utilizing museomics to trace the complex history and species boundaries in an avian-study system of conservation concern
Authors: Ernst Mario , Jønsson Knud A. , Ericson Per G. P. , Blom Mozes P. K. , Irestedt Martin 
Published: January 2022

AbstractA taxonomic classification that accurately captures evolutionary history is essential for conservation. Genomics provides powerful tools for delimiting species and understanding their evolutionary relationships. This allows for a more accurate and detailed view on conservation status compared with other, traditionally used, methods. However, from a practical and ethical perspective, gathering sufficient samples for endangered taxa may be difficult. Here, we use museum specimens to trace the evolutionary history and species boundaries in an Asian oriole clade. The endangered silver oriole has long been recognized as a distinct species based on its unique coloration, but a recent study suggested that it might be nested within the maroon oriole-species complex. To evaluate species designation, population connectivity, and the corresponding conservation implications, we assembled a de novo genome and used whole-genome resequencing of historical specimens. Our results show that the silver orioles form a monophyletic lineage within the maroon oriole complex and that maroon and silver forms continued to interbreed after initial divergence, but do not show signs of recent gene flow. Using a genome scan, we identified genes that may form the basis for color divergence and act as reproductive barriers. Taken together, our results confirm the species status of the silver oriole and highlight that taxonomic revision of the maroon forms is urgently needed. Our study demonstrates how genomics and Natural History Collections (NHC) can be utilized to shed light on the taxonomy and evolutionary history of natural populations and how such insights can directly benefit conservation practitioners when assessing wild populations.
Differential roles for DNAJ isoforms in HTT-polyQ and FUS aggregation modulation revealed by chaperone screens
Authors: Rozales Kinneret , Younis Amal , Saida Naseeb , Meller Anatoly , Goldman Hodaya , Kellerman Lior , Heinrich Ronit , Berlin Shai , Shalgi Reut 
Published: January 2022

AbstractProtein aggregation is a hallmark of neurodegeneration. Here, we find that Huntington’s disease-related HTT-polyQ aggregation induces a cellular proteotoxic stress response, while ALS-related mutant FUS (mutFUS) aggregation leads to deteriorated proteostasis. Further exploring chaperone function as potential modifiers of pathological aggregation in these contexts, we reveal divergent effects of naturally-occurring chaperone isoforms on different aggregate types. We identify a complex of the full-length (FL) DNAJB14 and DNAJB12, that substantially protects from mutFUS aggregation, in an HSP70-dependent manner. Their naturally-occurring short isoforms, however, do not form a complex, and lose their ability to preclude mutFUS aggregation. In contrast, DNAJB12-short alleviates, while DNAJB12-FL aggravates, HTT-polyQ aggregation. DNAJB14-FL expression increases the mobility of mutFUS aggregates, and restores the deteriorated proteostasis in mutFUS aggregate-containing cells and primary neurons. Our results highlight a maladaptive cellular response to pathological aggregation, and reveal a layer of chaperone network complexity conferred by DNAJ isoforms, in regulation of different aggregate types.
Mapping molecular subtype specific alterations in breast cancer brain metastases identifies clinically relevant vulnerabilities
Authors: Cosgrove Nicola , Varešlija Damir , Keelan Stephen , Elangovan Ashuvinee , Atkinson Jennifer M. , Cocchiglia Sinéad , Bane Fiona T. , Singh Vikrant , Furney Simon , Hu Chunling , Carter Jodi M. , Hart Steven N. , Yadav Siddhartha , Goetz Matthew P. , Hill Arnold D. K. , Oesterreich Steffi , Lee Adrian V. , Couch Fergus J. , Young Leonie S. 
Published: January 2022

AbstractThe molecular events and transcriptional plasticity driving brain metastasis in clinically relevant breast tumor subtypes has not been determined. Here we comprehensively dissect genomic, transcriptomic and clinical data in patient-matched longitudinal tumor samples, and unravel distinct transcriptional programs enriched in brain metastasis. We report on subtype specific hub genes and functional processes, central to disease-affected networks in brain metastasis. Importantly, in luminal brain metastases we identify homologous recombination deficiency operative in transcriptomic and genomic data with recurrent breast mutational signatures A, F and K, associated with mismatch repair defects, TP53 mutations and homologous recombination deficiency (HRD) respectively. Utilizing PARP inhibition in patient-derived brain metastatic tumor explants we functionally validate HRD as a key vulnerability. Here, we demonstrate a functionally relevant HRD evident at genomic and transcriptomic levels pointing to genomic instability in breast cancer brain metastasis which is of potential translational significance.
Hierarchical and nonhierarchical features of the mouse visual cortical network
Authors: D’Souza Rinaldo D. , Wang Quanxin , Ji Weiqing , Meier Andrew M. , Kennedy Henry , Knoblauch Kenneth , Burkhalter Andreas 
Published: January 2022

AbstractNeocortical computations underlying vision are performed by a distributed network of functionally specialized areas. Mouse visual cortex, a dense interareal network that exhibits hierarchical properties, comprises subnetworks interconnecting distinct processing streams. To determine the layout of the mouse visual hierarchy, we have evaluated the laminar patterns formed by interareal axonal projections originating in each of ten areas. Reciprocally connected pairs of areas exhibit feedforward/feedback relationships consistent with a hierarchical organization. Beta regression analyses, which estimate a continuous hierarchical distance measure, indicate that the network comprises multiple nonhierarchical circuits embedded in a hierarchical organization of overlapping levels. Single-unit recordings in anaesthetized mice show that receptive field sizes are generally consistent with the hierarchy, with the ventral stream exhibiting a stricter hierarchy than the dorsal stream. Together, the results provide an anatomical metric for hierarchical distance, and reveal both hierarchical and nonhierarchical motifs in mouse visual cortex.