bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of small extracellular vesicles isolated from plasma by ultracentrifugation or size‐exclusion chromatography: yield, purity and functional potential
Authors: Takov Kaloyan , Yellon Derek M. , Davidson Sean M. 
Published: December 2018

ABSTRACTInterest in small extracellular vesicles (sEVs) as functional carriers of proteins and nucleic acids is growing continuously. There are large numbers of sEVs in the blood, but lack of standardised methods for sEV isolation greatly limits our ability to study them. In this report, we use rat plasma to systematically compare two commonly used techniques for isolation of sEVs: ultracentrifugation (UC‐sEVs) and size‐exclusion chromatography (SEC‐sEVs). SEC‐sEVs had higher particle number, protein content, particle/protein ratios and sEV marker signal than UC‐sEVs. However, SEC‐sEVs also contained greater amounts of APOB+ lipoproteins and large quantities of non‐sEV protein. sEV marker signal correlated very well with both particle number and protein content in UC‐sEVs but not in all of the SEC‐sEV fractions. Functionally, both UC‐sEVs and SEC‐sEVs isolates contained a variety of proangiogenic factors (with endothelin‐1 being the most abundant) and stimulated migration of endothelial cells. However, there was no evident correlation between the promigratory potential and the quantity of sEVs added, indicating that non‐vesicular co‐isolates may contribute to the promigratory effects. Overall, our findings suggest that UC provides plasma sEVs of lower yields, but markedly higher purity compared to SEC. Furthermore, we show that the functional activity of sEVs can depend on the isolation method used and does not solely reflect the sEV quantity. These findings are of importance when working with sEVs isolated from plasma‐ or serum‐containing conditioned medium.
Facile sonochemical synthesis of artichoke-like Co3O4-graphene nanocomposites
Authors: Kamar E M , El-Dek S I 
Published: December 2018

Abstract
Facile sonochemical technique was used for the first time to synthesize Co3O4-graphene nanocomposites at room temperature. The nanocomposites under investigation were prepared with different Co3O4 molar ratios of nanoparticles. The samples were characterized by X-ray diffraction (XRD), field emission scanning electron microscope (FESEM), Fourier transform infrared spectroscopy (FT-IR) and UV-vis spectroscopy. The results show that Co3O4 nanoparticles were distributed uniformly on the surface of graphene sheet. This work reports a simple preparation approach and recommends the described methodology for the decoration of graphene sheet surface with miscellaneous metal oxide nanoparticles.
Assessment of myocardial oxygenation, strain, and diastology in MYBPC3-related hypertrophic cardiomyopathy: a cardiovascular magnetic resonance and echocardiography study
Authors: Grover Suchi , Lloyd Rachael , Perry Rebecca , Lou Pey Wen , Haan Eric , Yeates Laura , Woodman Richard , Atherton John J , Semsarian Chris , Selvanayagam Joseph B 
Published: December 2018

Abstract

Aims
Myocardial oxygenation is impaired in hypertrophic cardiomyopathy (HCM) patients with left ventricular hypertrophy (LVH), and possibly also in HCM gene carriers without LVH. Whether these oxygenation changes are also associated with abnormalities in diastolic function or left ventricular (LV) strain are unknown.

Methods and results
We evaluated 60 subjects: 20 MYBPC3 gene positive patients with LVH (G+LVH+), 18 MYBPC3 gene positive without LVH (G+LVH−), 11 gene negative siblings (G−), and 11 normal controls (NC). All subjects underwent 2D transthoracic echocardiography and cardiovascular magnetic resonance imaging for assessment of ventricular volumes, mass, and myocardial oxygenation at rest and adenosine stress using the blood oxygen level dependent (BOLD) technique. Maximal septal thickness was 20 mm in the G+LVH+ group, vs. 9 mm for the G+LVH− group. As expected, the G+LVH+ group had a more blunted myocardial oxygenation response to stress when compared with the G+LVH− group (−5% ± 3% vs. 2% ± 4%, P < 0.05), G− siblings (−5% ± 3% vs. 11% ± 4%, P < 0.0001) and NC (−5% ± 3% vs. 15% ± 4%, P < 0.0001). A blunted BOLD response to stress was also seen in G+LVH− subjects when compared with gene negative siblings (2% ± 4% vs. 11% ± 4%, P < 0.05) and NC (15% ± 4%, P < 0.050). G+LVH+ patients exhibited abnormal diastolic function including lower Eʹ, higher E to Eʹ ratio and greater left atrial area compared with the G+LVH− subjects who all had normal values for these indices.

Conclusion
Myocardial deoxygenation during stress is observed in MYBPC3 HCM patients, even in the presence of normal LV diastolic function, LV global longitudinal strain, and LV wall thickness.
Libra: scalable k-mer–based tool for massive all-vs-all metagenome comparisons
Authors: Choi Illyoung , Ponsero Alise J , Bomhoff Matthew , Youens-Clark Ken , Hartman John H , Hurwitz Bonnie L 
Published: December 2018

Abstract

Background
Shotgun metagenomics provides powerful insights into microbial community biodiversity and function. Yet, inferences from metagenomic studies are often limited by dataset size and complexity and are restricted by the availability and completeness of existing databases. De novo comparative metagenomics enables the comparison of metagenomes based on their total genetic content.

Results
We developed a tool called Libra that performs an all-vs-all comparison of metagenomes for precise clustering based on their k-mer content. Libra uses a scalable Hadoop framework for massive metagenome comparisons, Cosine Similarity for calculating the distance using sequence composition and abundance while normalizing for sequencing depth, and a web-based implementation in iMicrobe (http://imicrobe.us) that uses the CyVerse advanced cyberinfrastructure to promote broad use of the tool by the scientific community.

Conclusions
A comparison of Libra to equivalent tools using both simulated and real metagenomic datasets, ranging from 80 million to 4.2 billion reads, reveals that methods commonly implemented to reduce compute time for large datasets, such as data reduction, read count normalization, and presence/absence distance metrics, greatly diminish the resolution of large-scale comparative analyses. In contrast, Libra uses all of the reads to calculate k-mer abundance in a Hadoop architecture that can scale to any size dataset to enable global-scale analyses and link microbial signatures to biological processes.
Contribution of mitochondrial ND1 3394T&gt;C mutation to the phenotypic manifestation of Leber’s hereditary optic neuropathy
Authors: Ji Yanchun , Zhang Juanjuan , Yu Jialing , Wang Ying , Lu Yuanyuan , Liang Min , Li Qiang , Jin Xiaofen , Wei Yinsheng , Meng Feilong , Gao Yinglong , Cang Xiaohui , Tong Yi , Liu Xiaoling , Zhang Minglian , Jiang Peifang , Zhu Tao , Mo Jun Qin , Huang Taosheng , Jiang Pingping , Guan Min-Xin 
Published: December 2018

AbstractMitochondrial DNA (mtDNA) mutations have been associated with Leber’s hereditary optic neuropathy (LHON) and their pathophysiology remains poorly understood. In this study, we investigated the pathophysiology of a LHON susceptibility allele (m.3394T&gt;C, p.30Y&gt;H) in the Mitochondrial (MT)-ND1 gene. The incidence of m.3394T&gt;C mutation was 2.7% in the cohort of 1741 probands with LHON. Extremely low penetrances of LHON were observed in 26 pedigrees carrying only m.3394T&gt;C mutation, while 21 families bearing m.3394T&gt;C, together with m.11778G&gt;A or m.14484T&gt;C mutation, exhibited higher penetrance of LHON than those in families carrying single mtDNA mutation(s). The m.3394T&gt;C mutation disrupted the specific electrostatic interactions between Y30 of p.MT-ND1 with the sidechain of E4 and backbone carbonyl group of M1 of NDUFA1 (NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1) of complex I, thereby altering the structure and function of complex I. We demonstrated that these cybrids bearing only m.3394T&gt;C mutation caused mild mitochondrial dysfunctions and those harboring both m.3394T&gt;C and m.11778G&gt;A mutations exhibited greater mitochondrial dysfunctions than cybrids carrying only m.11778G&gt;A mutation. In particular, the m.3394T&gt;C mutation altered the stability of p.MT-ND1 and complex I assembly. Furthermore, the m.3394T&gt;C mutation decreased the activities of mitochondrial complexes I, diminished mitochondrial ATP levels and membrane potential and increased the production of reactive oxygen species in the cybrids. These m.3394T&gt;C mutation-induced alterations aggravated mitochondrial dysfunctions associated with the m.11778G&gt;A mutation. These resultant biochemical defects contributed to higher penetrance of LHON in these families carrying both mtDNA mutations. Our findings provide new insights into the pathophysiology of LHON arising from the synergy between mitochondrial ND1 and ND4 mutations.
Comorbidities Rather Than Age Are Associated With the Use of Immunomodulators in Elderly-onset Inflammatory Bowel Disease
Authors: Kariyawasam Viraj C , Kim Shin , Mourad Fadi H , Selinger Christian P , Katelaris Peter H , Brian Jones D , McDonald Charles , Barr Gavin , Chapman Grace , Colliwshaw James , Lunney Paul C , Middleton Kate , Wang Rosy R , Huang Tony , Andrews Jane , Pathirana Priyanthi W , Leong Rupert W 
Published: December 2018

Abstract

Background and Aim
The use of immunomodulators (IMs) is often avoided in elderly patients with inflammatory bowel disease (IBD) due to concerns about complications. Our aim is to compare the use of IMs in elderly and younger patients with Crohn’s disease (CD) or ulcerative colitis (UC) and identify markers that predict their use.

Methods
In this retrospective cohort study, patients diagnosed with IBD from 1970 to 2009 were recruited from the “Sydney IBD Cohort.” Patients diagnosed at age 60 years old or older and between 16 and old 40 years were classified as “elderly-onset” and “young-onset” respectively.

Results
A total of 255 elderly-onset patients (115 CD, 140 UC) and 1244 young-onset patients (657 CD, 587 UC) were recruited. Most elderly-onset patients had colonic CD (61.4%), whereas young-onset patients had predominantly ileocolonic CD (42.8%, P < 0.0001). Left-sided UC was the most common disease localization for both elderly-onset (52.1%) and young-onset patients (42.2%, P = 0.013). The cumulative probability of IM exposure at 5 years post-diagnosis was significantly less in elderly-onset patients compared with young-onset patients for CD (20.0% vs 33.4%, P = 0.0002) and UC (7.8% vs 13.4%, P = 0.0007). Age at diagnosis was not associated with the time to IMs introduction. Charlson Comorbidity Index was shown to delay IM introduction in CD (hazard ratio [HR] 0.863; 95% CI, 0.787–0.946; P = 0.002) and UC (HR 0.807; 95% CI, 0.711–0.917; P = 0.001). Early IM use was associated with reduced need for abdominal and perianal surgery in CD (HR 0.177; 95% CI, 0.089–0.351; P < 0.0001).

Conclusions
Comorbidity and not age at diagnosis is associated with IM introduction. Early IM is associated with reduced surgery in both young- and elderly-onset CD but not UC.
Reconfigurations within resonating communities of brain regions following TMS reveal different scales of processing
Authors: Garcia Javier O. , Ashourvan Arian , Thurman Steven M. , Srinivasan Ramesh , Bassett Danielle S. , Vettel Jean M. 
Published: December 2018

1AbstractAn overarching goal of neuroscience research is to understand how heterogeneous neuronal ensembles cohere into networks of coordinated activity to support cognition. To investigate how local activity harmonizes with global signals, we measured electroencephalography (EEG) while single pulses of transcranial magnetic stimulation (TMS) perturbed occipital and parietal cortices. We estimate the rapid network reconfigurations in dynamic network communities within specific frequency bands of the EEG, and characterize two distinct features of network reconfiguration, flexibility and allegiance, among spatially distributed neural sources following TMS. Using distance from the stimulation site to infer local and global effects, we find that alpha activity (8-12Hz) reflects concurrent local and global effects on network dynamics. Pair-wise allegiance of brain regions to communities on average increased near the stimulation site, whereas TMS-induced changes to flexibility were generally invariant to distance and stimulation site. In contrast, communities within the beta (13-20Hz) band demonstrated a high level of spatial specificity, particularly within a cluster comprising paracentral areas. Together, these results suggest that focal magnetic neurostimulation to distinct cortical sites can help identify both local and global effects on brain network dynamics, and highlight fundamental differences in the manifestation of network reconfigurations within alpha and beta frequency bands.2Author SummaryTMS may be used to probe the causal link between local regional activity and global brain dynamics. Using simultaneous TMS-EEG and dynamic community detection, we introduce what we call “resonating clusters”, or frequency band-specific communities in the brain, as a way to index local and global processing. These resonating clusters within the alpha and beta bands brain display both global (or integrating) behavior and local specificity, highlighting fundamental differences in the manifestation of network reconfigurations.
Are signals of aggressive intent less honest in urban habitats?
Authors: Akçay Çağlar , Beck Michelle L. , Sewall Kendra B. 
Published: December 2018

AbstractThe effect of urban noise on animal communication systems is one of the best examples of how anthropogenic change affects animal social behaviour. Urban noise often drives shifts in acoustic properties of signals but the consequences of noise for the honesty of signals – that is, how well they predict signaler behaviour, is unclear. Here we examine whether honesty of aggressive signaling changes in urban living song sparrows (Melospiza melodia). Aggressive signaling in song sparrows consists of close-range signals in two modalities that predict a subsequent attack: the low amplitude soft songs (an acoustic signal) and wing waves (a visual signal). Male song sparrows living in urban habitats display more territorial aggression than males living in rural habitats, but whether the honesty of close-range signals is affected by urbanization has not been examined. If soft songs are less effective in urban noise, we predict that they would be less reliably associated with attack in these habitats compared to rural habitats. We found that while acoustic noise was higher in urban habitats, the urban birds still sang more soft songs than rural birds during a simulated territorial intrusion. Furthermore, high rates of soft songs and low rates of loud songs predicted attacks in both habitats. Finally, we found evidence for a potential multimodal shift: urban birds tended to give proportionally more wing waves than soft songs than rural birds. These results indicate that urbanization might have a limited effect on the overall honesty of aggressive signals in song sparrows.
Controlling seizure propagation in large-scale brain networks
Authors: Olmi Simona , Petkoski Spase , Guye Maxime , Bartolomei Fabrice , Jirsa Viktor 
Published: December 2018

AbstractInformation transmission in the human brain is a fundamentally dynamic network process. In partial epilepsy, this process is perturbed and highly synchronous seizures originate in a local network, the so-called epileptogenic zone (EZ), before recruiting other close or distant brain regions. We studied patient-specific brain network models of 15 drug-resistant epilepsy patients with implanted stereotactic electroencephalography (SEEG) electrodes. Each personalized brain model was derived from structural data of magnetic resonance imaging (MRI) and diffusion tensor weighted imaging (DTI), comprising 88 nodes equipped with region specific neural mass models capable of demonstrating a range of epileptiform discharges. Each patient’s virtual brain was further personalized through the integration of the clinically hypothesized EZ. Subsequent simulations and connectivity modulations were performed and uncovered a finite repertoire of seizure propagation patterns. Across patients, we found that (i) patient-specific network connectivity is predictive for the subsequent seizure propagation pattern; (ii) seizure propagation is characterized by a systematic sequence of brain states; (iii) propagation can be controlled by an optimal intervention on the connectivity matrix; (iv) the degree of invasiveness can be significantly reduced via the proposed seizure control as compared to traditional resective surgery. To stop seizures, neurosurgeons typically resect the EZ completely. We showed that stability analysis of the network dynamics, employing structural and dynamical information, estimates reliably the spatiotemporal properties of seizure propagation. This suggests novel less invasive paradigms of surgical interventions to treat and manage partial epilepsy.PACS numbers:I.AUTHOR SUMMARYEpilepsy is characterized by perturbed dynamics that originate in a local network before spreading to other brain regions. We studied patient-specific brain network models of epilepsy patients, comprising 88 nodes equipped with region specific neural mass models capable of demonstrating epileptiform discharges. Applying stability analysis led to a seizure control strategy that is significantly less invasive than the traditional surgery, which typically resects the epileptogenic regions. The invasiveness of the procedure correlates with graph theoretical importance of the nodes. The novel method subsequently removes the most unstable links, a procedure possible by advent of novel surgery techniques. Our approach is entirely based on structural data, allowing creation of a brain model based on purely non-invasive data prior to any surgery.
“Extensive Transmission of Microbes along the Gastrointestinal Tract”
Authors: Schmidt TSB , Hayward MR , Coelho LP , Li SS , Costea PI , Voigt AY , Wirbel J , Maistrenko OM , Alves RJ , Bergsten E , de Beaufort C , Sobhani I , Heintz-Buschart A , Sunagawa S , Zeller G , Wilmes P , Bork P 
Published: December 2018

AbstractThe gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
Super-enhancer impairment is a link between MLL4-inactivated lung tumors and their vulnerability to glycolysis pathway inhibition
Authors: Alam Hunain , Tang Ming , Maitituoheti Mayinuer , Dhar Shilpa S. , Amin Samir , Gu Bingnan , Chen Tsai-Yu , Lin Yu-His , Chen Jichao , Muller Florian , DeMayo Francesco J. , Baseler Laura , Rai Kunal , Lee Min Gyu 
Published: December 2018

AbstractEpigenetic modifiers often harbor loss-of-function mutations in lung cancer, but their tumor-suppressive roles are poorly characterized. Here we show that lung-specific loss of the gene encoding the histone methyltransferase MLL4 (alias KMT2D; a COMPASS-like enzyme), which is ranked the most highly inactivated epigenetic modifier in lung cancer, strongly promotes lung adenocarcinoma in mice. Mll4 loss upregulated tumor-promoting programs, including glycolysis. The pharmacological inhibition of glycolysis preferentially impeded tumorigenic growth of human lung cancer cells bearing MLL4-inactivating mutations. Mll4 loss widely impaired epigenomic signals for super-enhancers and enhancers, including the super-enhancer for the circadian rhythm repressor gene Per2, and decreased Per2 expression. Per2 downregulated several glycolytic pathway genes. These findings uncover a distinct tumor-suppressive epigenetic mechanism in which MLL4 enhances Per2-mediated repression of pro-tumorigenic glycolytic genes via super-enhancer activation to suppress lung adenocarcinoma tumorigenesis and also implicate a glycolysis-targeting strategy as a therapeutic intervention for the treatment of MLL4- mutant lung cancer.
A complex copy number variant underlies differences in both colour plumage and cold adaptation in a dimorphic seabird
Authors: Tigano Anna , Reiertsen Tone K. , Walters James R. , Friesen Vicki L. 
Published: December 2018

SUMMARYColour morphs associated with different physiological adaptations offer unique opportunities to study the genomic basis of otherwise elusive adaptive traits. These complex balanced polymorphisms are often controlled by groups of tightly linked genes, and understanding how these ‘supergenes’ evolve and are maintained is an active area of research in evolutionary biology (Schwanderet al. 2014, Thompson and Jiggins 2014). Within the Atlantic, the common murre (Uria aalge, a colonial seabird) displays a plumage colour dimorphism (‘bridled’ and ‘unbridled’) that seems to be associated with differences in thermal adaptation (Birkhead 1984; Reiertsenet al. 2012). The genes associated with bridling and how these genes affect thermal adaptation are unknown. Using whole genome resequencing, we investigate the genomic basis of differences in colouration and thermal adaptation between the two morphs, and how the association between the two traits is maintained despite random mating. We identify a 60 kb genomic region of high differentiation laying in the intergenic area amongst three candidate genes for colouration and thermal adaptation:retinoic acid receptor beta(RARB),thyroid hormone receptor beta(THRB), andnuclear receptor subfamily 1 group D member 2(NR1D2orRev-erbβ). Differentiation is due to a complex copy number variant (CNV) that suppresses recombination locally. We show that this CNV acts as a ‘supergene’ and maintain association between regulatory elements likely affecting gene expression of one or more of the identified candidate genes. Our analyses also provide insights into the origin of the dimorphism: while copy number proliferation in the unbridled haplotype was potentially mediated by transposable elements (TEs), the bridled haplotype seems to have introgressed from the more cold-adapted sister species, the thick-billed murre (U. lomvia). Our results highlight the role of copy number variants in adaptation, especially when association among traits is maintained in the face of gene flow. They also shed light into the molecular mechanisms of adaptive thermogenesis in birds, which is poorly understood.HighlightsDifferences in plumage colour in Atlantic common murres are associated with different thermal adaptationsA single region is highly differentiated between bridled and unbridled morphsA complex copy number variant in a non-coding region underlies the dimorphismTransposable elements and adaptive introgression from the thick-billed murre seem to explain the origin of the dimorphism