bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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>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

Mitochondrial 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>C, p.30Y>H) in the Mitochondrial (MT)-ND1 gene. The incidence of m.3394T>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>C mutation, while 21 families bearing m.3394T>C, together with m.11778G>A or m.14484T>C mutation, exhibited higher penetrance of LHON than those in families carrying single mtDNA mutation(s). The m.3394T>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>C mutation caused mild mitochondrial dysfunctions and those harboring both m.3394T>C and m.11778G>A mutations exhibited greater mitochondrial dysfunctions than cybrids carrying only m.11778G>A mutation. In particular, the m.3394T>C mutation altered the stability of p.MT-ND1 and complex I assembly. Furthermore, the m.3394T>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>C mutation-induced alterations aggravated mitochondrial dysfunctions associated with the m.11778G>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

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.
Characterization of the Papain-Like Protease p29 of the Hypovirus CHV1-CN280 in Its Natural Host Fungus Cryphonectria parasitica and Nonhost Fungus Magnaporthe oryzae
Authors: Xiong Qin , Zhang Linqiao , Waletich Justin , Zhang Linlin , Zhang Chen , Zheng Xinyue , Qian Yulin , Zhang Zhengguang , Wang Yuanchao , Cheng Qiang
Published: December 2018

Cryphonectria hypovirus 1 strain CN280 (CHV1-CN280) was isolated from North China and exhibited typical hypovirulence-associated traits. We previously reported that CHV1-CN280 was more aggressive and had a higher horizontal transmission ability between Cryphonectria parasitica isolates belonging to different vegetative compatibility groups than two other CHV1 hypoviruses (namely, CHV1-EP713 and CHV1-Euro7), thus displaying greater potential for biological control of chestnut blight. The genome sequence of CHV1-CN280 shared approximately 70% identity with three other hypoviruses (CHV1-EP713, CHV1-Euro7, and CHV1-EP721). The coding region for p29, a papain-like protease encoded by CHV1-CN280 hypovirus, displayed an average of only approximately 60% amino acid identity among them, while the identity between the other three CHV1 isolates was higher than 89%. Protease p29 acted as a virus-encoded determinant responsible for altering fungal host phenotypes in other CHV1 isolates. In this study, the impacts of CHV1-CN280 p29 expression in virus-free C. parasitica were investigated. CHV1-CN280 p29 expression in C. parasitica resulted in significantly reduced sporulation, pigmentation, extracellular laccase activities, and pathogenicity, which is consistent with previous investigations. Subsequently, the potential of CHV1-CN280 p29 as a viral determinant responsible for suppression of host phenotypes in other phytopathogenic fungi such as Magnaporthe oryzae, the causal agent of rice blast disease, was discussed. However, heterologous expression of p29 in M. oryzae induced the opposite effect on sporulation, extracellular laccase activities, and pathogenicity; had no significant effect on pigmentation and mycelial growth; and contributed to extracellular peroxidase activities, suggesting that CHV1-CN280 p29 may disturb a unique regulatory pathway in C. parasitica, rather than a basic regulatory pathway conserved in diverse range of fungi. Alternatively, CHV1-CN280 p29-mediated modulation of fungal phenotypes may be facilitated by the specific interaction between p29 and a special fungal-host component, which exists only with C. parasitica but not M. oryzae.
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

1

An 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.

2

Author Summary

TMS 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.
The MooSciTIC project: a booster shot of science for West African research and higher education actors
Authors: Atindehou Ménonvè , Adéoti Kifouli , Loko Laura Estelle Yêyinou , Beulé Thierry , Paradis Emmanuel , Djedatin Gustave , Christine Tranchant-Dubreuil , Sabot François , Lagnika Latifou , Jaligot Estelle
Published: December 2018

In this paper, we describe the implementation of the MooSciTIC summer schools, a capacity-building initiative targeting West African research scientists and higher education teachers. Throughout the three years of the project, we provided on-site courses and practicals on cross-disciplinary aspects such as scientific writing, communication and integrity, in the aim of improving the self-reliance of researchers and upgrading research practices throughout the sub-region. We explain how the program was designed and implemented and we show the positive outcomes it generated for our former trainees within a relatively short period, hoping to inspire similar initiatives to follow our steps.
Are signals of aggressive intent less honest in urban habitats?
Authors: Akçay Çağlar , Beck Michelle L. , Sewall Kendra B.
Published: December 2018

The 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

Information 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 SUMMARY

Epilepsy 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.
A Mathematical Modeling Approach to The Cort-Fitness Hypothesis
Authors: El Moustaid Fadoua , Lane Samuel , Moore Ignacio , Johnson Leah
Published: December 2018

The Cort-Fitness hypothesis has generated much interest from investigators integrating field endocrinology with evolutionary biology, ecology, and conservation. The hypothesis was developed on the assumption that if glucocorticoid levels increase with environmental challenges and fitness decreases with environmental challenges, then there should be a negative relationship between glucocorticoid levels and fitness. However, studies across diverse taxa have found that the relationship between glucocorticoid levels and fitness is not consistent: some studies show a positive relationship, others negative, and some show no correlation. Hence, support for the hypothesis is not consistent and thus a deeper understanding of the mechanisms underlying the relationship between glucocorticoid levels, environmental pressures, and fitness is needed. We propose a mathematical model representing the links between glucocorticoid levels, environmental challenges, and fitness. Our model explores how variation in the predictability and intensity of environmental challenges, reproductive strategies, and fitness metrics can all contribute to the variability observed in empirical tests of the Cort-Fitness hypothesis. We provide qualitative results showing the Cort-Fitness relationship for different environmental scenarios and discuss how the model can be used to inform future Cort-Fitness studies.
How differing modes of transgenerational inheritance affect population viability in fluctuating environments
Authors: Proulx Stephen R , Dey Snigdhadip , Guzella Thiago , Teotonio Henrique
Published: December 2018

Different modes of transgenerational inheritance are expected to affect population persistence in fluctuating environments. We here analyze Caenorhabiditis elegans density-independent per capita growth rate time series on 36 populations experiencing 6 controlled sequences of challenging oxygen level fluctuations across 60 generations, and parameterize competing models of transgenerational inheritance that do not involve genetic changes in order to explain observed dynamics. Our analysis shows that phenotypic plasticity and anticipatory maternal effects are sufficient to explain growth rate dynamics, but that a carryover model where epigenetic memory is imperfectly transmitted and might be reset at each generation is a better fit to the data. After validating the models, we use the fitted transgenerational inheritance parameters to forecast population growth rates and find that it is negatively related to the degree of environmental autocorrelation.
“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

The 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

Epigenetic 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

Colour 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.

Highlights

Differences in plumage colour in Atlantic common murres are associated with different thermal adaptations

A single region is highly differentiated between bridled and unbridled morphs

A complex copy number variant in a non-coding region underlies the dimorphism

Transposable elements and adaptive introgression from the thick-billed murre seem to explain the origin of the dimorphism
Tissue repair in the mouse liver following acute carbon tetrachloride depends on injury-induced Wnt/β-catenin signaling
Authors: Zhao Ludan , Jin Yinhua , Donahue Katie , Tsui Margaret , Fish Matt , Logan Catriona , Wang Bruce , Nusse Roel
Published: December 2018

In the liver, Wnt/β-catenin signaling is involved in regulating zonation and hepatocyte proliferation during homeostasis. We have examined Wnt gene expression and signaling after injury and we show by in situ hybridization that Wnts are activated by acute carbon tetrachloride (CCl4) toxicity. Following injury, peri-injury hepatocytes become Wnt-responsive, expressing the Wnt target gene Axin2. Lineage tracing of peri-injury Axin2+ hepatocytes shows that during recovery, the injured parenchyma becomes repopulated and repaired by Axin2+ descendants. Using single cell RNA sequencing (scRNA-seq), we show that endothelial cells are the major source of Wnts following acute CCl4 toxicity. Induced loss of β-catenin in peri-injury hepatocytes results in delayed repair and ultimately to injury-induced lethality, while loss of Wnt production from endothelial cells leads to a delay in the proliferative response after injury. Conclusion: Our Findings highlight the importance of the Wnt/β-catenin signaling pathway in restoring tissue integrity following acute liver toxicity and establishes a role of endothelial cells as an important Wnt-producing regulator of liver tissue repair following localized liver injury.
Compress global, dilate local: Intentional binding in action–outcome alternations
Authors: Imaizumi Shu , Tanno Yoshihiko , Imamizu Hiroshi
Published: December 2018

Intentional binding refers to subjective temporal attraction between an action and its outcome. However, the nature of intentional binding in multiple actions remains unclear. We examined intentional binding in alternated action–outcome dyads. Participants actively or passively pressed a key, followed by a tone, and they again pressed the key; resulting in four keypress–tone dyads in a trial. Participants reproduced the duration of alternated keypress–tone dyads or the temporal interval between a dyad embedded in the alternations. The reproduced duration was shorter in the active than in the passive condition, suggesting the intentional binding in action–outcome alternations. In contrast, the reproduced interval between a dyad was longer in the active condition and did not correlate with the reproduced duration. These results suggest that subjective time during actions relies not only on an internal clock but also on postdictive biases that are switched based on what we recall.
Spontaneous Resolution in Racemic Solutions of N-trifluoroacetylated α-aminoalcohols
Authors: Zlenko Dmitry V , Zanin Anatoly , Skoblin Aleksey , Tverdislov Vsevolod , Stovbun Sergey
Published: December 2018

The spontaneous resolution was observed in the racemic solution of N-trifluoroacetylated α-aminoalcohol (TFAAA-6) in CCl4. In against other cases of the conglomerates formation, the TFAAA-6 forms highly anisometric crystalline structures (strings). Herewith, the spontaneous resolution was not observed in the racemic solution of TFAAA-5 in heptane, where the isometric precipitate was formed. The latter was also observed in the TFAAA-5 solutions in heptane with small enantiomeric excess (EE), down to 2 %. With that, the homochiral strings formed in the TFAAA-5 solutions in heptane with larger EEs. In this case, the strings formed from the excess of one of the enantiomers remained in solution after precipitation of the racemic residual. This process leads to the enhancement of chiral polarization in systems close to racemic and can explain the chiral purity of the living cell.
A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis, to couple metabolism to cell cycle progression.
Authors: Gupta Ritu , Walvekar Adhish , Liang Shun , Rashida Zeenat , Shah Premal , Laxman Sunil
Published: December 2018

Cells must appropriately sense and integrate multiple metabolic resources to commit to proliferation. Here, we report that cells regulate carbon and nitrogen metabolic homeostasis through tRNA U34-thiolation. Despite amino acid sufficiency, tRNA-thiolation deficient cells appear amino acid starved. In these cells, carbon flux towards nucleotide synthesis decreases, and trehalose synthesis increases, resulting in a starvation-like metabolic signature. Thiolation mutants have only minor translation defects. However, these cells exhibit strongly decreased expression of phosphate homeostasis genes, resulting in an effectively phosphate-limited state. Reduced phosphate enforces a metabolic switch, where glucose-6-phosphate is routed towards storage carbohydrates. Notably, trehalose synthesis, which releases phosphate and thereby restores phosphate availability, is central to this metabolic rewiring. Thus, cells use thiolated tRNAs to perceive amino acid sufficiency, and balance carbon and amino acid metabolic flux to maintain metabolic homeostasis, by controlling phosphate availability. These results further biochemically explain how phosphate availability determines a switch to a starvation-state.
Distinguishing among complex evolutionary models using unphased whole-genome data through Approximate Bayesian Computation
Authors: Ghirotto Silvia , Vizzari Maria Teresa , Tassi Francesca , Barbujani Guido , Benazzo Andrea
Published: December 2018

Inferring past demographic histories is crucial in population genetics, and the amount of complete genomes now available should in principle facilitate this inference. In practice, however, the available inferential methods suffer from severe limitations. Although hundreds complete genomes can be simultaneously analyzed, complex demographic processes can easily exceed computational constraints, and the procedures to evaluate the reliability of the estimates contribute to increase the computational effort. Here we present an Approximate Bayesian Computation (ABC) framework, based on the Random Forest algorithm, to infer complex past population processes using complete genomes. To do this, we propose to summarize the data by the full genomic distribution of the four mutually exclusive categories of segregating sites (FDSS), a statistic fast to compute from unphased genome data. We constructed an efficient ABC pipeline and tested how accurately it allows one to recognize the true model among models of increasing complexity, using simulated data and taking into account different sampling strategies in terms of number of individuals analyzed, number and size of the genetic loci considered. We tested the power of theFDSSto be informative about even complex evolutionary histories and compared the results with those obtained summarizing the data through the unfolded Site Frequency Spectrum, thus highlighting for both statistics the experimental conditions maximizing the inferential power. Finally, we analyzed two datasets, testing models (a) on the dispersal of anatomically modern humans out of Africa and (b) the evolutionary relationships of the three species of Orangutan inhabiting Borneo and Sumatra.
Distinct molecular etiologies of male and female hepatocellular carcinoma
Authors: Natri Heini M. , Wilson Melissa A. , Buetow Kenneth
Published: December 2018

Sex-differences in cancer occurrence and mortality are evident across tumor types; men exhibit higher rates of incidence and often poorer responses to treatment. Targeted approaches to the treatment of tumors that account for these sex-differences require the characterization and understanding of the fundamental biological mechanisms that differentiate them. Hepatocellular Carcinoma (HCC) is the second leading cause of cancer death worldwide, with the incidence rapidly rising. HCC exhibits a male-bias in occurrence and mortality, but previous studies have failed to explore the sex-specific dysregulation of gene expression in HCC. Here, we characterize the sex-shared and sex-specific regulatory changes in HCC tumors in the TCGA LIHC cohort. By using a sex-specific differential expression analysis of tumor and tumor-adjacent samples, we uncovered etiologically relevant genes and pathways differentiating male and female HCC. While both sexes exhibited activation of pathways related to apoptosis and cell cycle, males and females differed in the activation of several signaling pathways, with females showing PPAR pathway enrichment while males showed PI3K, 305 PI3K/AKT, FGFR, EGFR, NGF, GF1R, Rap1, DAP12, and IL-2 signaling pathway enrichment. Using eQTL analyses, we discovered germline variants with differential effects on tumor gene expression between the sexes. 24.3% of the discovered eQTLs exhibit differential effects between the sexes, illustrating the substantial role of sex in modifying the effects of eQTLs in HCC. The genes that showed sex-specific dysregulation in tumors and those that harbored a sex-specific eQTL converge in clinically relevant pathways, suggesting that the molecular etiologies of male and female HCC are partially driven by differential genetic effects on gene expression. Overall, our results provide new insight into the role of inherited genetic regulation of transcription in modulating sex-differences in HCC etiology and provide a framework for future studies on sex-biased cancers.
Taylor series approximation and unbiased GM(1,1) based hybrid statistical approach for forecasting daily gold price demands
Authors: Rathnayaka R.M. Kapila Tharanga , Seneviratna D.M.K.N.
Published: December 2018

Purpose

The time series analysis is an essential methodology which comprises the tools for analyzing the time series data to identify the meaningful characteristics for making future ad-judgments. The purpose of this paper is to propose a Taylor series approximation and unbiased GM(1,1) based new hybrid statistical approach (HTS_UGM(1,1)) for forecasting time series data under the poor, incomplete and uncertain information systems in a short period of time manner.

Design/methodology/approach

The gray forecasting is a dynamical methodology which can be classified into different categories based on their respective functions. The new proposed methodology is made up of three different methodologies including the first-order unbiased GM(1,1), Markov chain and Taylor approximation. In addition to that, two different traditional gray operational mechanisms include GM(1,1) and unbiased GM(1,1) used as the comparisons. The main objective of this study is to forecast gold price demands in a short-term manner based on the data which were taken from the Central Bank of Sri Lanka from October 2017 to December 2017.

Findings

The error analysis results suggested that the new proposed HTS_UGM(1,1) is highly accurate (less than 10 percent) with lowest RMSE error values in a one head as well as weakly forecasting’s than separate gray forecasting methodologies.

Originality/value

The findings suggested that the new proposed hybrid approach is more suitable and effective way for forecasting time series indices than separate time series forecasting methodologies in a short-term manner.
Multicultural teaching efficacy and cultural intelligence of teachers
Authors: Kang Hye-Seung (Theresa) , Kim Eun-Jee , Park Sunyoung
Published: December 2018

Purpose

The purpose of this paper is to examine the impact of learning goal orientation and training readiness on teachers’ multicultural teaching efficacy and cultural intelligence.

Design/methodology/approach

A total of 182 responses from secondary schools in midwest and southern areas of the USA were analyzed using the hierarchical multiple regression.

Findings

The findings indicated that learning goal orientation positively influenced both teachers’ multicultural teaching efficacy and cultural intelligence, while training readiness did not significantly affect them. In addition, teachers’ multicultural teaching efficacy positively influenced their cultural intelligence.

Research limitations/implications

The study implied that high-level learning goal orientation can contribute to enhance multicultural teaching efficacy and cultural intelligence for teachers.

Practical implications

By conducting needs analysis of participants in advance, trainers can reflect what teachers want and need when designing and implementing a workshop. In addition, trainers could prepare for interventions to improve the participation rate of multicultural workshops and the quality of existing workshop programs.

Originality/value

This study is important in that it will help to develop culturally sensitive workshop/training programs that can prepare teachers for diverse classroom environments and face potential issues that may arise.
A look into the past and future: theories within supply chain management, marketing and management
Authors: Gligor David , Bozkurt Siddik , Russo Ivan , Omar Ayman
Published: December 2018

Purpose

Although supply chain scholars have acknowledged the fundamental disruptive changes experienced by today’s supply chains and the ensuing novelty of the research problems worthy of investigation, they have primarily relied on a limited number of theories to help explain the phenomena of interest. The purpose of this paper is to use a systematic literature review to address this gap and propose additional theories that supply chain researchers can use to help address novel supply chain phenomena, such as those caused by technological disruptions.

Design/methodology/approach

The authors use a systematic literature review to examine the studies published over the last 10 years in six of the top supply chain management journals (411 articles) and six of the top marketing and management journals (1,214 articles).

Findings

First, the findings show that 15 theories have been relied upon by over 95 per cent of the studies within supply chain management that use formal theories. Second, the authors identify the most frequently used theories within marketing and management (217 theories). Third, as space limitations make it impossible to offer a rich description of each of the 217 theories, the authors identify 30 theories that they considered to be the most salient to supply chain research and suggest areas where supply chain scholars can apply these theoretical lenses.

Originality/value

The research effort allowed the authors to map the current use of theories within the field to gain a better understanding of what other theories could augment the body of theories used within supply chain management. Thus, the current study is a “one stop shop” that supply chain scholars can consult when in a quandary about what theoretical lens to utilize.
The effect of vacancy on the interfacial diffusion in Cu/Sn lead-free solder joints
Authors: Yang Li , Xiaoyan Li , Yao Peng
Published: December 2018

Purpose

The purpose of this paper is to investigate the diffusion behaviors of different atoms at the Cu/Cu3Sn interface and the vacancy formation energy, diffusion energy barrier and vacancy diffusion activation energy.

Design/methodology/approach

The diffusion behaviors of different atoms at the Cu/Cu3Sn interface are analyzed, and the vacancy formation energy, diffusion energy barrier and vacancy diffusion activation energy are obtained using molecular dynamics simulation. The nudged elastic band method is used to evaluate diffusion energy barrier for Cu/Cu3Sn system.

Findings

It is found that the vacancies in the Cu/Cu3Sn interface promote the interfacial diffusion, and the formation energy of Cu vacancy in the Cu crystal is larger than that in Cu3Sn crystal. In addition, the formation energies of Cu1 vacancy and Cu2 vacancy are close to each other in Cu3Sn crystal, and they are all less than the formation energy of Sn vacancy. Furthermore, the vacancy diffusion barrier and vacancy diffusion activation energy of the Cu/Cu3Sn interface are calculated, and the results show that the vacancy diffusion activation energy of Sn was higher than that of Cu. Finally, by comparison of diffusion activation energies of different diffusion mechanisms, Cu→Cu1vac is the most possible migration path at all temperatures.

Originality/value

It is concluded that the vacancies in Cu/Cu3Sn interface promote interfacial diffusion, and the activation energy of vacancy diffusion in most diffusion mechanisms decreases with the increase of temperature.
The Transforming Care agenda: admissions and discharges in two English learning disability assessment and treatment units
Authors: Washington Francine , Bull Samantha , Woodrow Ceri
Published: December 2018

Purpose

The purpose of this paper is to evaluate whether two regional intellectual disability (ID) assessment and treatment (A&T) units in England were meeting the recommended length of stay stipulated by the Learning Disability Professional Senate, in line with the Transforming Care (TC) agenda. A secondary purpose of the study was to evaluate the reasons for admissions and delayed discharges in order to inform how to reduce these.

Design/methodology/approach

A retrospective evaluation of 85 admissions across two A&T units was conducted over a three-year period (2013–2016) following publication of the TC agenda.

Findings

There were 85 admissions compared to 71 discharges. Of the 85 admissions, 11 were readmissions. The most common factors thought necessary to prevent admission were early support for care providers or alternative service provision. There were barriers to discharge in over half of admissions; the main reason was a lack of suitable service provision.

Practical implications

The study suggests that providing specific support or training to care providers could prevent (re)admission and ensure shorter admissions. Further research to establish reasons for the reported lack of suitable providers would be beneficial.

Originality/value

This study provides current admission and discharge rates for regional A&T units, as recommended by the TC national guidance. It also provides potential reasons underlying preventable admissions and delayed discharges and therefore indicates what might be necessary to prevent admissions and reduce the length of inpatient stays for people with ID and/or autism.
Positive Behavioural Support as an alternative to medication
Authors: Lee Ruth M. , Rhodes Jennifer A. , Gerrard David
Published: December 2018

Purpose

The purpose of this paper is to demonstrate how Positive Behavioural Support (PBS) can be used as an alternative to psychotropic medication to improve the quality of life of an individual with a learning disability and behaviour described as challenging.

Design/methodology/approach

A single case design was utilised. A unique PBS stopping over medication of people with a learning disability, autism or both (STOMP) clinic model was developed and PBS was used in line with National Institute for Health and Care Excellence (NICE) guidance. This included functional behavioural assessment, to support understanding of the reasons behind behaviour described as challenging, and a gradual medication reduction.

Findings

This case study found that antipsychotic medication used to manage behaviour that challenges could be safely reduced and individual quality of life increased when PBS was used as an alternative.

Originality/value

STOMP is a project supported by NHS England aimed at reducing the inappropriate prescribing of psychotropic medication to manage behaviour that challenges. NICE guidance recommends that behaviour should be more appropriately understood through PBS. More research is needed to demonstrate how the two work together for safe medication reduction and improved quality of life.
Vitamin D status in Thai dermatologists and working‐age Thai population
Authors: Rajatanavin Natta , Kanokrungsee Silada , Aekplakorn Wichai
Published: December 2018

This study aimed to determine the prevalence of vitamin D insufficiency among Thai dermatologists compared with the general working‐age population in Bangkok. A cross‐sectional study was conducted in healthy Thai physicians who had at least 1 years’ experience in dermatology practise and a subsample of the general Thai population from the Fourth National Health Survey. Serum 25‐hydroxyvitamin D (25[OH]D), a combination of 25(OH)D2 and 25(OH)D3, levels in both groups were measured using liquid chromatography coupled with mass spectrometry. The majority of dermatologists were of Fitzpatrick skin type III (n = 61, 61.3%) or IV (n = 32, 33.3%). The mean serum 25(OH)D and 25(OH)D3 levels were 18.9 and 18.2 ng/mL, respectively, whereas the corresponding levels in the general population were 26.5 and 25.8 ng/mL. None of the dermatologist had serum 25(OH)D sufficiency (>30 ng/mL), 38 (38.78%) had vitamin D insufficiency (20–30 ng/mL) and 60 (61.22%) had vitamin D deficiency (<20 ng/mL). The frequency of vitamin D deficiency in dermatologists was significantly higher than in the general population (61.2% vs 19.2%, P < 0.001). Ninety percent of dermatologists used sunscreen daily and spent time mostly indoors. Dermatologists used physical sun‐protection more than half of the time when outdoors, for example, a book or paper as a sunshade (70.3%), an umbrella (48.4%), a long‐sleeved shirt (20.4%) or a hat (9.7%). In conclusion, dermatologists showed a remarkably high prevalence of vitamin D deficiency which may be due to inadequate exposure to sunlight, regular use of sunscreen and practicing various sun‐protection activities.