bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Hybrid Machine Learning Framework for Enhancing the Prediction Power in Large Scale Population Studies: The ATHLOS Project
Authors: Barmpas Petros , Tasoulis Sotiris , Vrahatis Aristidis G. , Prina Matthew , Ayuso-Mateos José Luis , Bickenbach Jerome , Bayes Ivet , Bobak Martin , Félix Caballero Francisco , Chatterji Somnath , Egea-Cortés Laia , García-Esquinas Esther , Leonardi Matilde , Koskinen Seppo , Koupil Ilona , Pająk Andrzej , Prince Martin , Sanderson Warren , Scherbov Sergei , Tamosiunas Abdonas , Galas Aleksander , Haro Josep Maria , Sanchez-Niubo Albert , Plagianakos Vassilis , Panagiotakos Demosthenes 
Published: January 2021

AbstractThe ATHLOS cohort is composed of several harmonized datasets of international cohorts related to health and aging. The healthy aging scale has been constructed based on a selection of particular variables from 16 individual studies. In this paper, we consider a selection of additional variables found in ATHLOS and investigate their utilization for predicting the healthy aging. For this purpose motivated by the dataset’s volume and diversity we focus our attention upon the clustering for prediction scheme, where unsupervised learning is utilized to enhance prediction power, showing the predictive utility of exploiting structure in the data by clustering. We show that imposed computation bottlenecks can be surpassed when using appropriate hierarchical clustering within a clustering for ensemble classification scheme while retaining prediction benefits. We propose a complete methodology which is evaluated against baseline methods and the original concept. The results are very encouraging suggesting further developments in this direction along with applications in tasks with similar characteristics. A strait-forward open source implementation is provided for the R project.
The Forgotten Tract of Vision in Multiple Sclerosis: Vertical Occipital Fasciculus, Its Integrity, and Visuospatial Memory
Authors: Abdoalizadeh AmirHussein , Mohammadi Soheil , Aarabi Mohammad Hadi 
Published: January 2021

AbstractBackgroundVisual disturbances are a common disease manifestation and a major patient complaint in Multiple Sclerosis (MS) due to lesions damaging white matter tracts involved in vision. Vertical Occipital Fasciculus (VOF) connects ventral and dorsal visual streams and was neglected for more than a century. It has recently become under focus in brain-related disorders. Thus, its role in the visual dysfunction in MS needs to be clarified.ObjectiveEvaluate the integrity of bilateral VOFs in MS and its association with clinical and visual evaluations.Methods56 relapsing-remitting MS (RRMS) and 25 healthy controls (HC) were recruited. We acquired MS Functional Composite, Expanded Disability Status Scale (EDSS), and Brief Visuospatial Memory Test – Revised (BVMT-R), and structural and diffusion MRI scans. After VOF tractography, its integrity markers were statistically tested for between-group differences and clinical and visual tests associations.ResultsRRMS patients had lower fiber integrity in bilateral VOFs compared to HC. Lower integrity of bilateral VOFs was associated with poor clinical outcomes, higher visual score in EDSS, and lower total immediate and delayed recall in BVMT-R.ConclusionVOF damage is seen in RRMS and is associated with visual symptoms and visuospatial learning impairments.
BNP facilitates NMB-mediated histaminergic itch via NPRC-NMBR crosstalk
Authors: Meng Qing-Tao , Liu Xian-Yu , Liu Xue-Ting , Barry Devin M. , Jin Hua , Sun Yu , Yang Qianyi , Wan Li , Jin Jin-Hua , Shen Kai-Feng , Munanairi Admire , Kim Ray , Yin Jun , Tao Ailin , Chen Zhou-Feng 
Published: January 2021

AbstractB-type natriuretic peptide (BNP) binds to its two cognate receptors NPRA and NPRC, encoded byNpr1andNpr3, respectively, with equal potency and both are expressed in the spinal cord. Moreover, natriuretic peptides (NP) signal through the inhibitory cGMP pathway, raising the question of how BNP may transmit itch information. We report thatNpr3is highly restricted to laminae I-II of the dorsal horn, and partially overlaps with neuromedin B receptor (NMBR) that encodes histaminergic itch. Functional studies indicate that NPRC is required for itch evoked by histamine but not chloroquine (CQ), a nonhistaminergic pruritogen. Importantly, BNP significantly facilitates scratching behaviors mediated by NMB, but not gastrin releasing peptide (GRP) that encodes nonhistaminergic itch. Consistently, BNP evoked Ca2+response in NMBR/NPRC HEK 293 cells and BNP-saporin that ablated bothNpr1andNpr3neurons impaired histamine-, but not CQ-evoked, itch. These results reveal a previously unknown mechanism by which BNP changes its inhibitory mode of action to the facilitation of itch through a novel NPRC-NMBR cross-talk. Our studies suggest that neuropeptides encode histaminergic and nonhistaminergic itch not only through distinct modes but also in synergy.
Commensal bacterial-derived retinoic acid primes host defense to intestinal infection
Authors: Woo Vivienne , Eshleman Emily M. , Whitt Jordan , Hashimoto-Hill Seika , Wu Shu-en , Engleman Laura , Rice Taylor , Karns Rebekah , Vallance Bruce A. , Alenghat Theresa 
Published: January 2021

SummaryInteractions between the microbiota and mammalian host are essential for effective defense against pathogenic infection; however, the microbial-derived cues that mediate this beneficial relationship remain unclear. Here, we find that the intestinal epithelial cell (IEC)-associated commensal bacteria, Segmented Filamentous Bacteria (SFB), promotes early protection against the bacterial pathogen,Citrobacter rodentium, independently of CD4+T cells. Global analyses demonstrated that SFB induced histone modifications in IECs at sites enriched for the retinoic acid receptor (RAR) motif. Interestingly, SFB-colonized mice exhibited greater expression of RAR targets during infection relative to germ-free mice, suggesting SFB may enhance defense through retinoic acid (RA) signaling. Consistent with this, supplementing germ-free mice with RA decreased pathogen levels. Further, mice with impaired RA-responsiveness in IECs displayed increased susceptibility toC. rodentiuminfection. RA was elevated in the intestine of mice colonized with SFB, indicating that the presence of commensal bacteria can modulate intestinal RA levels. However, this regulation by SFB was not dependent on mammalian RA production. Sequence analyses suggested that RA-generating enzymes are expressed by a subset of commensal bacteria. Remarkably, RA was produced by intestinal bacteria including SFB, and inhibiting RA signaling blocked SFB-induced protection againstC. rodentiuminfection. These data collectively reveal RA as an unexpected microbiota-derived metabolite that primes innate intestinal defense and suggests that pre- and probiotic approaches to elevate RA could prevent or combat pathogenic infection.
USP47 regulates a 53BP1-based complex function in DNA DSB repair
Authors: Sadideen Doraid T. , Chen Baowei , Basili Manal , Hromas Robert , Shaheen Montaser 
Published: January 2021

Abstract53BP1 is a key DNA repair protein that regulates double strand break (DSB) repair pathway choice. It assembles a complex, whose loss reverses BRCA1 deficient cells sensitivity to PARP1 inhibitors potentially by antagonizing DSB end resection. 53BP1 is critical for immunoglobulin heavy chain class switch recombination (CSR), that is mediated by the generation and repair of DSBs. Here we identify a deubiquitylase, USP47, as a 53BP1 associated protein that regulates its function in these processes. USP47 loss results in 53BP1 protein instability in a proteasome dependent manner and in reduced 53BP1 ionizing radiation induced foci (IRIF). Like 53BP1, USP47 depletion results in enhanced homologous recombination repair, and defective immunoglobulin CSR. It is also required for resistance to DNA damaging agents. We identify a complex of 53BP1, USP47, Fen1, and Recql1 that regulates a microhomology mediated end joining (MMEJ), a repair pathway that is involved in CSR. Altogether, our findings implicate USP47 in DNA DSB repair at least through regulating a novel 53BP1 associated complex.
AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa
Authors: Xue Yunlu , Wang Sean K. , Rana Parimal , West Emma R. , Hong Christin M. , Feng Helian , Wu David M. , Cepko Constance L. 
Published: January 2021

AbstractRetinitis pigmentosa (RP) is an inherited retinal disease, affecting >20 million people worldwide. Loss of daylight vision typically occurs due to the dysfunction/loss of cone photoreceptors, the cell type that initiates our color and high acuity vision. Currently, there is no effective treatment for RP, other than gene therapy for a limited number of specific disease genes. To develop a gene-agnostic therapy, we screened ≈20 genes for their ability to prolong cone photoreceptor survivalin vivo. Here, we report an adeno-associated virus (AAV) vector expressing Txnip, which prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models. A Txnip allele, C247S, which blocks the association of Txnip with thioredoxin, provides an even greater benefit. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb), and correlates with the presence of healthier mitochondria, suggesting that Txnip saves RP cones by enhancing their lactate catabolism.
Astrocytic VMAT2 in the developing prefrontal cortex is required for normal grooming behavior in mice
Authors: Petrelli Francesco , Zehnder Tamara , Pucci Luca , Cali Corrado , Bondiolotti Bianca Maria , Perez Alicia Molinero , Dallerac Glenn , Déglon Nicole , Giros Bruno , Magara Fulvio , Magrassi Lorenzo , Mothet Jean-Pierre , Simmler Linda , Bezzi Paola 
Published: January 2021

AbstractAstrocytes control synaptic activity by modulating peri-synaptic concentrations of ion and neurotransmitters including dopamine and, as such, can be critically involved in the modulation of some aspect of mammalian behavior. Here we report that genetic mouse model with a reduced medial prefrontal cortex (mPFC) dopamine levels, arising from astrocyte-specific conditional deletion of vesicular monoamine transporter 2 (VMAT2; aVMTA2cKO mice) shows excessive grooming and anxiety-like behaviour. The VMAT2cKO mice also develop a synaptic pathology, expressed through increased relative AMPA vs. NMDA receptor currents in synapses of the dorsal striatum receiving inputs from the mPFC. Importantly, behavioural and synaptic phenotypes are prevented by reexpression of mPFC VMAT2, showing that the deficits are driven by mPFC astrocytes. By analysing human tissue samples, we found that VMAT2 is expressed in human mPFC astrocytes, corroborating the potential translational relevance of our observations in mice. Our study shows that impairments of the astrocytic-control of dopamine in the mPFC has a profound impact on circuit function and behaviours, which resemble symptoms of anxiety disorders and obsessive compulsive disorder (OCD).
The neural response to the temporal fine structure of continuous musical pieces is not affected by selective attention
Authors: Etard Octave , Messaoud Rémy Ben , Gaugain Gabriel , Reichenbach Tobias 
Published: January 2021

AbstractSpeech and music are spectro-temporally complex acoustic signals that a highly relevant for humans. Both contain a temporal fine structure that is encoded in the neural responses of subcortical and cortical processing centres. The subcortical response to the temporal fine structure of speech has recently been shown to be modulated by selective attention to one of two competing voices. Music similarly often consists of several simultaneous melodic lines, and a listener can selectively attend to a particular one at a time. However, the neural mechanisms that enable such selective attention remain largely enigmatic, not least since most investigations to date have focussed on short and simplified musical stimuli. Here we study the neural encoding of classical musical pieces in human volunteers, using scalp electroencephalography (EEG) recordings. We presented volunteers with continuous musical pieces composed of one or two instruments. In the latter case, the participants were asked to selectively attend to one of the two competing instruments and to perform a vibrato identification task. We used linear encoding and decoding models to relate the recorded EEG activity to the stimulus waveform. We show that we can measure neural responses to the temporal fine structure of melodic lines played by one single instrument, at the population level as well as for most individual subjects. The neural response peaks at a latency of 7.6 ms and is not measurable past 15 ms. When analysing the neural responses elicited by competing instruments, we find no evidence of attentional modulation. Our results show that, much like speech, the temporal fine structure of music is tracked by neural activity. In contrast to speech, however, this response appears unaffected by selective attention in the context of our experiment.
D614G Substitution of SARS-CoV-2 Spike Protein Increases Syncytium Formation and Viral Transmission via Enhanced Furin-mediated Spike Cleavage
Authors: Cheng Ya-Wen , Chao Tai-Ling , Li Chiao-Ling , Wang Sheng-Han , Kao Han-Chieh , Tsai Ya-Min , Wang Hurng-Yi , Hsieh Chi-Ling , Chen Pei-Jer , Chang Sui-Yuan , Yeh Shiou-Hwei 
Published: January 2021

ABSTRACTSince the D614G substitution in the spike (S) of SARS-CoV-2 emerged, the variant strain underwent rapid expansion to become the most abundant strain worldwide. Therefore, this substitution may provide an advantage of viral spreading. To explore the mechanism, we analyzed 18 viral isolates containing S proteins with either G614 or D614. Both the virus titer and syncytial phenotype were significantly increased in S-G614 than in S-D614 isolates. We further showed increased cleavage of S at the furin substrate site, a key event that promotes syncytium, in S-G614 isolates. These functions of the D614G substitution were validated in cells expressing S protein. The effect on syncytium was abolished by furin inhibitor treatment and mutation of the furin-cleavage site, suggesting its dependence on cleavage by furin. Our study provides a mechanistic explanation for the increased transmissibility of S-G614 containing SARS-CoV-2 through enhanced furin-mediated S cleavage, which increases membrane fusion and virus infectivity.
Megakaryocyte Progenitor Cell Function is Enhanced Upon Aging Despite the Functional Decline of Aged Hematopoietic Stem Cells
Authors: Poscablo Donna M. , Worthington Atesh K. , Smith-Berdan Stephanie , Forsberg E. Camilla 
Published: January 2021

SUMMARYAge-related morbidity is associated with a decline in hematopoietic stem cell (HSC) function, but the mechanisms of HSC aging remain unclear. We performed heterochronic HSC transplants followed by quantitative analysis of cell reconstitution. While young HSCs outperformed old HSCs in young recipients, young HSCs unexpectedly failed to outcompete the old HSCs of aged recipients. Interestingly, despite substantial enrichment of megakaryocyte progenitors (MkPs) in old micein situand reported platelet (Plt) priming with age, transplanted old HSCs were deficient in reconstitution of all lineages, including MkPs and Plts. We therefore performed functional analysis of young and old MkPs. Surprisingly, old MkPs displayed unmistakably greater regenerative capacity compared to young MkPs. Transcriptome analysis revealed putative molecular regulators of old MkP expansion. Collectively, these data demonstrated that aging affects HSCs and megakaryopoiesis in fundamentally different ways: whereas old HSCs functionally decline, MkPs gain expansion capacity upon aging.HIGHLIGHTSFrequencies and total cell numbers of HSCs and MkPs were increased upon agingReconstitution deficit by old HSCs was observed by chimerism and absolute cell numbersYoung HSCs did not have competitive advantage over old HSCs in aged recipient miceOld MkPs display remarkable capacity to engraft, expand, and reconstitute plateletsAging is associated with changes in MkP genome-wide expression signatures
MicroRNA775 targets aβ-(1,3)-galactosyltransferaseto regulate growth and development inArabidopsis thaliana
Authors: Mishra Parneeta , Singh Akanksha , Verma Ashwani Kumar , Singh Rajneesh , Roy Sribash 
Published: January 2021

AbstractMicroRNAs are critical regulators of gene expression in plants and other organisms, and are involved in regulating plethora of developmental processes. Evolutionarily, miRNAs can be ancient and conserved across species or recently evolved and young, which are not conserved across diverse plant groups. miR775 is a non-conserved miRNA identified only inArabidopsis thaliana. Here, we investigated the functional significance of miR775 inA. thalianaand observed that miR775 targets a probableβ-(1,3)-galactosyltransferasegene at post transcriptional level. Phenotypic analysis of miR775 over-expression lines and the target mutant suggested miR775 regulates rosette size by elongating petiole length and increasing leaf area. Further, the expression of miR775 was found to be up-regulated in response to UV-B and hypoxia. Our results also suggest that miR775 regulated β-(1,3)-galactosyltransferase may involve in regulating the β-(1,3)-galactan content of arabinogalactans. Collectively, our findings establish a role of miR775 in regulating growth and development inA. thaliana.HighlightsThe role of an uncharacterized microRNA, miR775 has been exploredmiR775 targets a probable β-(1,3)-galactosyltransferase involved in complex carbohydrate biosynthesismiR775 regulates rosette size inA. thalianaand may play role under UV light and hypoxia
Identification of Gip as a novel phage-encoded gyrase inhibitor protein featuring a broad activity profile
Authors: Kever Larissa , Hünnefeld Max , Brehm Jannis , Heermann Ralf , Frunzke Julia 
Published: January 2021

AbstractBacteriophages represent a powerful source for the identification of novel antimicrobial proteins. In this study, a screening of small cytoplasmic proteins encoded by the CGP3 prophage ofCorynebacterium glutamicum, resulted in the identification of the novelgyrase-inhibitingprotein Cg1978 (Gip), which shows a direct interaction with the gyrase subunit A (GyrA). In vitro supercoiling assays further suggest a stabilization of the cleavage complex by Gip. Overproduction of Gip inC. glutamicumresulted in a severe growth defect as well as an induction of the SOS response. The cells adapted togipoverexpression by increasing expression levels ofgyrABand by reducingtopAexpression reflecting the homeostatic control of DNA topology. Interestingly, Gip features a similar activity profile towards gyrases ofEscherichia coli, Mycobacterium tuberculosisandC. glutamicum. Therefore, the detailed elucidation of the mechanism of Gip action may provide novel directions for the design of drugs targeting DNA gyrase.
Vasodilatory action of trans‐4‐methoxy‐β‐nitrostyrene in rat isolated pulmonary artery
Authors: Arruda‐Barbosa Loeste , Vasconcelos‐Silva Alfredo Augusto , Borges Rosivaldo Santos , Duarte Gloria Pinto , Magalhães Pedro Jorge Caldas , Lahlou Saad 
Published: January 2021

AbstractTrans‐4‐methoxy‐β‐nitrostyrene (T4MN) induced more potent vasorelaxant effects in resistance arteries from hypertensive rats than its parent drug, β‐nitrostyrene 1‐nitro‐2‐phenylethene (NPe). To better understand the influence of insertion of the electron‐releasing methoxy group in the aromatic ring of NPe, we investigated vasorelaxant effects of T4MN in isolated pulmonary artery and compared them with those of NPe in view of the potential interest of T4MN in pulmonary arterial hypertension. T4MN and NPe both caused concentration‐dependent vasorelaxation in pulmonary artery rings pre‐contracted with either phenylephrine (1 µmol/L) or KCl (60 mmol/L), an effect unaffected by endothelium removal. In endothelium‐intact preparations pre‐contracted with phenylephrine, the vasorelaxant effect of T4MN was more potent than that of NPe. However, unlike NPe, this effect was significantly reduced following pretreatment with 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) (10 µmol/L, a guanylate cyclase inhibitor) or tetraethylammonium (5 mmol/L, a potassium channel blocker). T4MN abolished the CaCl2‐induced contractions in pulmonary artery preparations stimulated with phenylephrine (PHE) under Ca2+‐free conditions in the presence of verapamil, to preferentially activate receptor‐operated calcium channels. From these findings, we propose that T4MN evokes endothelium‐independent vasorelaxant effects in isolated rat pulmonary artery, partially by inhibiting Ca2+ influx through L‐type Ca2+ channels, as well as by activating soluble guanylate cyclase and potassium channels. The present results suggest the therapeutic potential of T4MN in treating pulmonary arterial hypertension.
Imagining Icarus: Edward Field, Manhood and Authenticity in Post‐war America1
Authors: George Aaron 
Published: January 2021

ABSTRACTWhile the Second World War had profound effects on the way that American men conceived of themselves, for two groups ‐ Jewish men and men who would later identify as gay ‐ the war held a special resonance. Deborah Dash Moore has demonstrated that the Second World War allowed Jewish men to cast off stereotypes and be accepted into the larger American polity, while Alan Berube has written about the ways in which the Second World War created a space where gay men were able to understand themselves as part of a larger community. Historians have looked at the ways service affected these men during the war, however more work needs to be done understanding how these experiences affected men after the war. By examining the life of Edward Field, a Jewish and gay veteran who became a prominent poet in post‐war America, we can understand how experiences of wartime allowed men like Field to construct an alternative idea of masculinity, one based on male camaraderie and emotional authenticity. Edward Field's wartime and post‐war experiences suggest that Jewish and gay identities could intersect in ways that were mutually reinforcing and highlight the complicated nature of the Second World War experience.
Actor perspective and moral reasoning: Do levels of criminal thinking moderate this relationship among non‐criminals?
Authors: K. Miller Olivia , Batastini Ashley B. , L. Standridge Rheanna , Repke Alexandra , S. Mohn Richard 
Published: January 2021

AbstractA large body of literature has explored moral decision‐making; however, fewer have examined the explicit role of criminal thinking (CT). This study sought to determine whether moral judgment is influenced by CT in the general population and if this relationship further depends on the type of scenario (i.e., immoral vs. illegal) and/or the actor orientation (i.e., self vs. other). Using a sample of 239 U.S. adults and hypothetical case vignettes, results showed that those who endorsed higher levels of CT rated socially deviant behaviors, regardless of the type of scenario, as significantly more morally acceptable than participants who endorsed lower levels of CT. However, this difference was more pronounced for the immoral dilemma compared to the illegal dilemma. Specifically, proactive CT processes led to higher justification for the immoral dilemma. Neither general nor reactive CT were significantly associated with moral reasoning for the illegal dilemma. Among a mostly non‐offending sample, this finding makes sense as it appears participants’ levels of criminal thinking may have been high enough to rationalize an immoral dilemma but not so high as to allow for rationalization of an illegal dilemma. No significant differences were found concerning actor orientation. This research not only has important implications for better understanding traits associated with moral decision‐making in everyday choices, but it may also have practical application in legal contexts. However, further research is needed in these contexts. Findings were also limited by a lack of racial diversity among participants.