bluuebunny/crossref_metadata_2025 huggingface dataset:
Lis1 promotes the formation of maximally activated cytoplasmic dynein-1 complexes
Authors: Htet Zaw Min , Gillies John P. , Baker Richard W. , Leschziner Andres E. , DeSantis Morgan E. , Reck-Peterson Samara L.
Published: June 2019

Cytoplasmic dynein-1 is a molecular motor that drives nearly all minus-end-directed microtubule-based transport in human cells, performing functions ranging from retrograde axonal transport to mitotic spindle assembly1,2. Activated dynein complexes consist of one or two dynein dimers, the dynactin complex, and an “activating adaptor”, with maximal velocity seen with two dimers present (Fig. 1a)3-6. Little is known about how this massive ∼4MDa complex is assembled. Using purified recombinant human proteins, we uncovered a novel role for the dynein-binding protein, Lis1, in the formation of fully activated dynein complexes containing two dynein dimers. Lis1 is required for maximal velocity of complexes activated by proteins representing three different families of activating adaptors: BicD2, Hook3, and Ninl. Once activated dynein complexes have formed, they do not require the presence of Lis1 for sustained maximal velocity. Using cryo-electron microscopy we show that human Lis1 binds to dynein at two sites on dynein’s motor domain, similar to yeast dynein7. We propose that the ability of Lis1 to bind at these sites may function in multiple stages of assembling the motile human dynein/ dynactin/ activating adaptor complex.
Ciliary photoreceptors in sea urchin larvae indicate pan-deuterostome cell type conservation
Authors: Valencia Jonathan E. , Feuda Roberto , Mellott Dan O. , Burke Robert D. , Peter Isabelle S.
Published: June 2019

One of the signatures of evolutionarily related cell types is the expression of similar combinations of transcription factors in distantly related animals. Here we present evidence that sea urchin larvae possess bilateral clusters of ciliary photoreceptors that are positioned in the oral/anterior apical neurogenic domain and associated with pigment cells. The expression of synaptotagmin indicates that the photoreceptors are neurons. Immunostaining shows that the sea urchin photoreceptors express an RGR/GO-opsin, opsin3.2, which co-localizes with tubulin on immotile cilia on the cell surface. Furthermore, orthologs of several transcription factors expressed in vertebrate photoreceptors are expressed in sea urchin ciliary photoreceptors, including Otx, Six3, Tbx2/3, and Rx, a transcription factor typically associated with ciliary photoreceptors. Analysis of gene expression during sea urchin development indicates that the photoreceptors derive from the anterior apical neurogenic domain. Thus, based on location, developmental origin, and transcription factor expression, sea urchin ciliary photoreceptors are likely homologous to vertebrate rods and cones. However, we found that genes typically involved in eye development in many animals, includingpax6,six1/2,eya, anddac, are not expressed in sea urchin ciliary photoreceptors. Instead, all four genes are co-expressed in the hydropore canal, indicating that these genes operate as a module in an unrelated developmental context. Thus, based on current evidence, we conclude that at least within deuterostomes, ciliary photoreceptors share a common evolutionary origin and express a shared regulatory state that includes Rx, Otx, and Six3, but not transcription factors that are commonly associated with the retinal determination circuit.
Evolutionary success of a parasitic B chromosome rests on gene content
Authors: Ruiz-Ruano Francisco J. , Navarro-Domínguez Beatriz , López-León María Dolores , Cabrero Josefa , Camacho Juan Pedro M.
Published: June 2019

Supernumerary (B) chromosomes are dispensable genomic elements found in most kinds of eukaryotic genomes. Many show drive mechanisms that give them an advantage in transmission, but how they achieve it remains a mystery. The recent finding of protein-coding genes in B chromosomes has opened the possibility that their evolutionary success is based on their genetic content. Using a protocol based on mapping genomic DNA Illumina reads from B-carrying and B-lacking individuals on the coding sequences ofde novotranscriptomes from the same individuals, we identified 25 protein-coding genes in the B chromosome of the migratory locust, 15 of which showed a full coding region. Remarkably, one of these genes (apc1) codes for the large subunit of the Anaphase Promoting Complex or Cyclosome (APC/C), an E3 ubiquitin ligase involved in the metaphase-anaphase transition. Sequence comparison of A and B chromosome gene paralogs showed that the latter show B-specific nucleotide changes, neither of which putatively impairs protein function. These nucleotide signatures allowed identifying B-derived transcripts in B-carrying transcriptomes, and demonstrated that they show about similar frequency as A-derived ones. Since B-carrying individuals show higher amounts ofapc1transcripts than B-lacking ones, the putatively higher amount of APC1 protein might induce a faster metaphase-anaphase transition in spite of orientation of the two B chromosome chromatids towards the same pole during metaphase, thus facilitating B chromosome non-disjunction. Therefore,apc1is the first protein-coding gene uncovered in a B chromosome that might be responsible for B chromosome drive.

Significance Statement

The genome of the migratory locust harbors a parasitic chromosome that arose about 2 million years ago. It is widespread in natural populations from Asia, Africa, Australia and Europe, i.e. all continents where this species lives. The secret for such an extraordinary evolutionary success is unveiled in this report, as B chromosomes in this species contain active protein-coding genes whose transcripts might interfere with gene expression in the host genome (the A chromosomes), thus facilitating B chromosome mitotic and meiotic drive to provide the transmission advantage which grants its success. One of the B-chromosomal genes (apc1) codes for the large subunit of the Anaphase Promoting Complex or Cyclosome (APC/C) whose expression might provide a mechanistic explanation for B chromosome drive.
‘The Bold are the Sociable’: Personality, sociability and lateralized utilization of brain hemisphere in the juveniles of a megafish Deccan Mahseer (Tor khudree)
Authors: Varma Vishwanath , Vasoya Harsh , Jain Anushka , Binoy VV
Published: June 2019

The present study explored relationships between personality traits; boldness, activity and sociability, and lateralized utilization of brain hemispheres in the hatchery reared juveniles of Deccan Mahseer (Tor khudree), a game fish inhabiting the rivers of central and southern India. Our results revealed a significant positive correlation between boldness and activity in this species when tested in isolation. However, boldness was positively correlated with the time spent near the individual conspecific but not with the individual alien invasive heterospecific tilapia (Oreochromis mossambicus). Although juvenile Deccan mahseer exhibited significant variation in the preference towards conspecific over heterospecific, no divergence in the utilization of right or left eye was seen while observing these individuals suggesting the lack of lateralized utilization of the brain hemispheres. Furthermore, laterality in visual preference failed to show any significant correlation with any of the personality traits tested in this species. Results are discussed in the light of the existing literature on the impact of life in homogenous hatchery conditions on the behaviour, personality traits and cognitive abilities of fishes.

Significance statement

The present study is one of the first that focuses on personality and lateralization in Deccan Mahseers, an endangered freshwater megafish. We report a positive linkage between boldness and sociability but do not find any correlation of personality with lateralized utilization of brain hemispheres in diverse social contexts. These findings have implications in the conservation and cultivation of this ecologically, culturally and economically important indigenous fish.
Human condensin I and II drive extensive ATP–dependent compaction of nucleosome–bound DNA
Authors: Kong Muwen , Cutts Erin , Pan Dongqing , Beuron Fabienne , Kaliyappan Thangavelu , Xue Chaoyou , Morris Ed , Musacchio Andrea , Vannini Alessandro , Greene Eric C.
Published: June 2019

Structural maintenance of chromosomes (SMC) complexes are essential for genome organization from bacteria to humans, but their mechanisms of action remain poorly understood. Here, we characterize human SMC complexes condensin I and II and unveil the architecture of the human condensin II complex, revealing two putative DNA–binding sites. Using single–molecule imaging, we demonstrate that both condensin I and II exhibit ATP-dependent motor activity and promote extensive and reversible compaction of double–stranded DNA. Nucleosomes are incorporated into DNA loops during compaction without being displaced from the DNA, indicating that condensin complexes can readily act upon nucleosome fibers. These observations shed light on critical processes involved in genome organization in human cells.

One Sentence Summary

ATP–dependent DNA compaction by human condensin complexes.
Large-scale dissection suggests that ultraconserved elements are dispensable for mouse embryonic stem cell survival and fitness
Authors: Schneider Aksana , Hiller Michael , Buchholz Frank
Published: June 2019

Withdrawal statement

The authors have withdrawn their manuscript from bioRxiv regretfully. During additional experiments for the revision we noticed inconsistencies in some results, which may affect the main conclusion of the manuscript. In particular, we noticed that using different primer pairs, some clones that were classified as homozygous knockouts, are actually not knockouts. These were unexpected findings, but might reflect the recently described larger rearrangements observed using CRISPR technology1,2,3,4. Follow up experiments are ongoing, but we would like to withdraw the manuscript at this point in time to avoid misunderstandings. Therefore, the manuscript should currently not be cited. Any questions regarding the manuscript should be addressed to the corresponding author.
Human Milk Oligosaccharides modulate the risk for preterm birth in a microbiome dependent and independent manner
Authors: Pausan Manuela-Raluca , Kolovetsiou-Kreiner Vassiliki , Richter Gesa Lucia , Madl Tobias , Giselbrecht Elisabeth , Weiss Eva-Christine , Jantscher-Krenn Evelyn , Moissl-Eichinger Christine
Published: June 2019

Background

Preterm birth is one of the leading causes of neonatal mortality. The causes for spontaneous preterm birth (PTB) are multifactorial and remain often unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB. We analyzed the vaginal and urinary microbiome of a cross-sectional cohort of women with and without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood.

Results

We identified several microbial signatures associated with short cervix, PTB and/or preterm contractions such asLactobacillus jensenii,L. gasseri,Ureaplasma sp. andGardnerella sp..Additionally, we observed associations between sialylated HMOs, in particular 3’-sialyllactose, with PTB, short cervix and increased inflammation and confirmed an influence of HMOs on the microbiome profile.

Conclusions

Identifying serum and urinary HMOs and several key microorganisms associated with PTB, our findings point at two distinct processes modulating the risk for PTB. One process seems to be driven by sterile inflammation, characterized by increased concentrations of sialylated HMOs in serum. Another process might be microbiome-mediated, potentially driven by secretor-active HMOs in urine. Our results support current efforts to improve diagnostics and therapeutic strategies.
Guilty by association: How group-based (collective) guilt arises in the brain
Authors: Li Zhiai , Yu Hongbo , Zhou Yongdi , Kalenscher Tobias , Zhou Xiaolin
Published: June 2019

People do not only feel guilty for transgressions of social norms/expectations that they are causally responsible for, but they also feel guilty for transgressions committed by those they identify as in-group (i.e., collective or group-based guilt). However, the neurocognitive basis of group-based guilt and its relation to personal guilt are unknown. To address these questions, we combined functional MRI with an interaction-based minimal group paradigm in which participants either directly caused harm to victims (i.e., personal guilt), or observed in-group members cause harm to the victims (i.e., group-based guilt). In three experiments (N = 90), we demonstrated that perceived shared responsibility with in-group members in the transgression predicted behavioral and neural manifestations of group-based guilt. Multivariate pattern analysis of the functional MRI data showed that group-based guilt recruited a similar brain representation in anterior middle cingulate cortex as personal guilt. These results have broaden our understanding of how group membership is integrated into social emotions.
Investigating the physical effects in bacterial therapies for avascular tumors
Authors: Mascheroni Pietro , Meyer-Hermann Michael , Hatzikirou Haralampos
Published: June 2019

Tumor-targeting bacteria elicit anticancer effects by infiltrating hypoxic regions, releasing toxic agents and inducing immune responses. Although current research has largely focused on the influence of chemical and immunological aspects on the mechanisms of bacterial therapy, the impact of physical effects is still elusive. Here, we propose a mathematical model for the anti-tumor activity of bacteria in avascular tumors that takes into account the relevant chemo-mechanical effects. We consider a time-dependent administration of bacteria and analyze the impact of bacterial chemotaxis and killing rate. We show that active bacterial migration towards tumor hypoxic regions provides optimal infiltration and that high killing rates combined with high chemotactic values provide the smallest tumor volumes at the end of the treatment. We highlight the emergence of steady states in which a small population of bacteria is able to constrain tumor growth. Finally, we show that bacteria treatment works best in the case of tumors with high cellular proliferation and low oxygen consumption.
Single-cell analysis of childhood leukemia reveals a link between developmental states and ribosomal protein expression as a source of intra-individual heterogeneity
Authors: Caron Maxime , St-Onge Pascal , Sontag Thomas , Wang Yu Chang , Richer Chantal , Ragoussis Ioannis , Sinnett Daniel , Bourque Guillaume
Published: June 2019

Childhood acute lymphoblastic leukemia (cALL) is the most common pediatric cancer. It is characterized by bone marrow lymphoid precursors that acquire genetic alterations, resulting in disrupted maturation and uncontrollable proliferation. More than a dozen molecular subtypes of variable severity can be used to classify cALL cases. Modern therapy protocols currently cure 85-90% of cases, but other patients are refractory or will relapse and eventually succumb to their disease. To better understand these difficult cases, we investigated the nature and extent of intra-individual transcriptional heterogeneity of cALL at the cellular level by sequencing the transcriptomes of 39,375 individual cells in eight patients (six pre-B and two pre-T) and three healthy pediatric controls. We observed intra-individual transcriptional clusters in five out of the eight patients. Using pseudotime maturation trajectories of healthy B and T cells, we obtained the predicted developmental state of each leukemia cell and observed distribution shifts within patients. We showed that the predicted developmental states of these cancer cells are inversely correlated with ribosomal protein expression levels, which could be a common contributor to intra-individual heterogeneity in cALL patients.
Fighting the spread of antibiotic resistance with bacterial competence inhibitors
Authors: Domenech Arnau , Brochado Ana Rita , Sender Vicky , Hentrich Karina , Henriques-Normark Birgitta , Typas Athanasios , Veening Jan-Willem
Published: June 2019

Streptococcus pneumoniaeis a commensal of the human nasopharynx, but it can also cause severe life-threatening antibiotic-resistant infections. Antibiotic consumption drives the spread of resistance by inducingS. pneumoniaecompetence leading to the uptake of exogenous DNA and horizontal gene transfer (HGT). We have identified potent inhibitors of competence, collectively called COM-blockers. We show that COM-blockers inhibit HGT by perturbing the proton motive force, thereby disrupting the export of the peptide that regulates competence. COM-blockers do not affect growth or compromise antibiotic activity at their active concentrations, and we did not observe any resistance development against them. Used as adjuvants of antibiotics, COM-blockers provide a strategy to reduce the spread of virulence factors and antibiotic resistance in human pathogens.

One Sentence Summary

Antibiotic adjuvants block competence
Compounds without borders: a novel paradigm for quantifying complex odors and responses to scent-pollution in bumblebees
Authors: Sprayberry Jordanna D. H.
Published: June 2019

Bumblebees are critical pollinators whose populations have been experiencing troubling declines over the past several decades. Successful foraging improves colony fitness, thus understanding how anthropogenic influences modulate foraging behavior may aid conservation efforts. Odor pollution can have negative impacts on bumble- and honey-bees foraging behavior. However, given the vast array of potential scent contaminants, individually testing pollutants is an ineffective approach. The ability to quantitatively measure how much scent-pollution of a floral-odor bumblebees can tolerate would represent a paradigm shift in odor-pollution studies. Current statistical methods for analyzing complex odors have poor predictive power because statistically-derived odor-spaces are rewritten when new odors are added. This study presents an alternative method of analyzing complex odor blends based on the encoding properties of insect olfactory systems. This “Compounds Without Borders” (CWB) method vectorizes odors in a multidimensional space representing relevant functional group and carbon characteristics of their component odorants. A single vector can be built for any scent, which allows the angular distance between any two odors to be calculated – including a learned odor and its polluted counterpart. Data presented here indicate that CWB-angles are capable of both describing and predicting bumblebee odor-discrimination behavior: odor pairs with angular distances in the 20-29° range are generalized, while odor pairs over 30 degrees are differentiated. The neurophysiological properties underlying CWB-vectorization of odors are not unique to bumblebees; CWB-angle analysis of published data on a hawkmoth supports the idea that this method may have broader applications.
Pac1/LIS1 promotes an uninhibited conformation of dynein that coordinates its localization and activity
Authors: Marzo Matthew G. , Griswold Jacqueline M. , Markus Steven M.
Published: June 2019

Cytoplasmic dynein is a minus end-directed microtubule motor that transports myriad cargos in various cell types and contexts. How dynein is regulated to perform all these activities with a high degree of spatial and temporal precision is unclear. Recent studies have revealed that human dynein-1 and dynein-2 can be regulated by a mechanism of autoinhibition, whereby intermolecular contacts limit motor activity. Whether this autoinhibitory mechanism is conserved throughout evolution, whether it can be affected by extrinsic factors, and its precise role in regulating cellular dynein activity remain unknown. Here, we use a combination of negative stain EM, single molecule motility assays, genetic, and cell biological techniques to show that the autoinhibitory conformation is conserved in budding yeast, and it plays an important role in coordinating dynein localization and function in cells. Moreover, we find that the Lissencephaly-related protein, LIS1 (Pac1 in yeast) plays an important role in regulating this autoinhibitory conformation of dynein. Specifically, our studies demonstrate that rather than inhibiting dynein motility, Pac1/LIS1 promotes dynein activity by stabilizing the uninhibited conformation, which ensures appropriate localization and activity of dynein in cells.
Movement patterns of free-roaming dogs on heterogeneous urban landscapes: implications for rabies control
Authors: Raynor Brinkley , De la Puente-León Micaela , Johnson Andrew , Díaz-Espinoza Elvis , Levy Michael Z. , Recuenco Sergio E. , Castillo-Neyra Ricardo
Published: June 2019

In 2015, a case of canine rabies in Arequipa, Peru indicated the re-emergence of rabies virus in the city. Despite mass dog vaccination campaigns across the city and reactive ring vaccination and other control activities around positive cases (e.g. elimination of unowned dogs), the outbreak has spread. Here we explore how the urban landscape of Arequipa affects the movement patterns of free-roaming dogs, the main reservoirs of the rabies virus in the area. We tracked 23 free-roaming dogs using Global Positioning System (GPS) collars. We analyzed the spatio-temporal GPS data using the time- local convex hull method. Dog movement patterns varied across local environments. We found that water channels, an urban feature of Arequipa that are dry most of the year, promote movement. Dogs that used the water channels move further, faster and more directionally than dogs that do not. Our findings suggest that water channels can be used by dogs as ‘highways’ to transverse the city and have the potential to spread disease far beyond the radius of control practices. Control efforts should focus on a robust vaccination campaign attuned to the geography of the city, and not limited to small-scale rings surrounding cases.
Tel1 activation by the MRX complex is sufficient for telomere length regulation but not for the DNA damage response inS. cerevisiae
Authors: Keener Rebecca , Connelly Carla J. , Greider Carol W.
Published: June 2019

Previous models suggested that regulation of telomere length inS. cerevisiaeby Tel1(ATM) and Mec1(ATR) parallel the established pathways regulating the DNA damage response. Here we provide evidence that telomere length regulation differs from the DNA damage response in both the Tel1 and Mec1 pathways. We found that Rad53 mediates a Mec1 telomere length regulation pathway but is dispensable for Tel1 telomere length regulation, whereas in the DNA damage response Rad53 is regulated by both Mec1 and Tel1. Using epistasis analysis with a Tel1 hypermorphic allele, Tel1-hy909, we found that the MRX complex is not required downstream of Tel1 for telomere elongation but is required downstream of Tel1 for the DNA damage response. Since models that invoke a required end processing event for telomerase elongation are primarily based on the yeast pathways, our data call for a re-examination of the requirement for telomere end processing in both yeast and mammalian cells.
Transcription reinitiation by recycling RNA polymerase that diffuses on DNA after releasing terminated RNA
Authors: Kang Wooyoung , Ha Kook Sun , Uhm Heesoo , Park Kyuhyong , Lee Ja Yil , Hohng Sungchul , Kang Changwon
Published: June 2019

(Abstract)

Despite extensive studies on transcription mechanisms, it is unknown how termination complexes are disassembled, especially in what order the components dissociate. Our single-molecule fluorescence study unveils that RNA transcript release precedes RNA polymerase (RNAP) dissociation from DNA template in bacterial intrinsic termination of transcription much more often than concurrent dissociation. As termination is defined by release of product RNA from transcription complex, the subsequent retention of RNAP on DNA constitutes a previously unidentified stage, termed here as ‘recycling.’ During the recycling stage, RNAPs one-dimensionally diffuse on DNA in downward and upward directions, and these RNAPs can initiate transcription again at nearby promoters in case of retaining a sigma factor. The efficiency of this event, termed here as ‘reinitiation,’ increases with supplement of a sigma factor. In summary, after releasing RNA product at intrinsic termination, recycling RNAP diffuses on DNA template for reinitiation most times.
Towards a Better Estimation of Functional Brain Network for Mild Cognitive Impairment Identification: A Transfer Learning View
Authors: Li Weikai , Zhang Limei , Qiao Lishan , Shen Dinggang
Published: June 2019

Mild cognitive impairment (MCI) is an intermediate stage of brain cognitive decline, associated with increasing risk of developing Alzheimer’s disease (AD). It is believed that early treatment of MCI could slow down the progression of AD, and functional brain network (FBN) could provide potential imaging biomarkers for MCI diagnosis and response to treatment. However, there are still some challenges to estimate a “good” FBN, particularly due to the poor quality and limited quantity of functional magnetic resonance imaging (fMRI) data from thetarget domain(i.e., MCI study). Inspired by the idea of transfer learning, we attempt to transfer information in high-quality data fromsource domain(e.g., human connectome project in this paper) into thetarget domaintowards a better FBN estimation, and propose a novel method, namely NERTL (Network Estimation via Regularized Transfer Learning). Specifically, we first construct a high-quality network “template” based on thesourcedata, and then use the template to guide or constrain thetargetof FBN estimation by a weightedl1-norm regularizer. Finally, we conduct experiments to identify subjects with MCI from normal controls (NCs) based on the estimated FBNs. Despite its simplicity, our proposed method is more effective than the baseline methods in modeling discriminative FBNs, as demonstrated by the superior MCI classification accuracy of 82.4% and the area under curve (AUC) of 0.910.
CHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation
Authors: Zhong Yichen , Paudel Bishnu Prasad , Ryan Daniel P. , Low Jason K. K. , Franck Charlotte , Patel Karishma , Bedward Max J. , Payne Richard J. , van Oijen Antoine M. , Mackay Joel P.
Published: June 2019

Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. The mechanism, however, is only partially resolved, and unclear if it is conserved among the four remodeller families. Here we use single-molecule assays to examine the mechanism of action of CHD4, which is part of the least well understood family of remodellers. We demonstrate that the binding energy for CHD4-nucleosome complex formation – even in the absence of nucleotide – triggers significant conformational changes in DNA at the entry side, effectively priming the system for remodelling. During remodelling, flanking DNA enters the nucleosome in a continuous, gradual manner but exits in concerted 4–6 base-pair steps. This decoupling of entry- and exit-side translocation suggests that ATP-driven movement of entry-side DNA builds up strain inside the nucleosome that is subsequently released at the exit side by DNA expulsion. We propose a mechanism for nucleosome sliding based on these and published data.
Orbitofrontal cortex promotes trial-by-trial learning of risky, but not spatial, biases
Authors: Constantinople Christine M. , Piet Alex T. , Bibawi Peter , Akrami Athena , Kopec Charles D. , Brody Carlos D.
Published: June 2019

Individual choices are not made in isolation but are embedded in a series of past experiences, decisions, and outcomes. The effects of past experiences on choices, often called sequential biases, are ubiquitous in perceptual and value-based decision-making, but their neural substrates are unclear. We trained rats to choose between explicitly cued guaranteed and probabilistic rewards in a task in which outcomes on each trial were independent. Behavioral variability often reflected the effects of previous trials, including increased willingness to take risks following risky wins, and spatial “win-stay/lose-shift” biases. Electrophysiological recordings from lateral orbitofrontal cortex (lOFC) revealed strong encoding of reward history and receipt, and optogenetic inhibition of lOFC during choice reporting eliminated rats’ increased preference for risk on subsequent trials following risky wins, but spared other sequential effects. Our data show that different sequential biases are neurally dissociable, and that the lOFC’s role in adaptive behavior promotes learning of more abstract, task-specific biases (here, biases for the risky option), but not spatial ones. These data are consistent with proposals that the OFC represents the animal’s location in an abstract representation of task states, and highlight the lOFC’s role in learning.
A bHLH interaction code controls bipotential differentiation and self-renewal in theDrosophilagut
Authors: Puig-Barbe Aleix , Dettmann Svenja , Nirello Vinicius Dias , Moor Helen , Azami Sina , Edgar Bruce A. , Varga-Weisz Patrick , Korzelius Jerome , de Navascués Joaquín
Published: June 2019

Multipotent adult stem cells balance self-renewal with differentiation into various cell types. How this balance is regulated at the transcriptional level is poorly understood. Here we show that a network of basic Helix-Loop-Helix (bHLH) transcription factors controls both stemness and bi-potential differentiation in theDrosophilaadult intestine. We find that homodimers of Daughterless (Da), homolog of mammalian E proteins, maintain self-renewal of intestinal stem cells (ISCs), antagonising the Enteroendocrine fate promoted by heterodimers of Da and Scute (Sc, homolog of ASCL). The HLH factor Extramacrochaetae (Emc, homologous to Id proteins) promotes absorptive differentiation by titrating Da and Sc. Emc prevents the committed absorptive progenitor from de-differentiating, underscoring the plasticity of these cells. Switching physical interaction partners in this way enables the active maintenance of stemness while priming stem cells for differentiation along two alternative fates. Such regulatory logic is likely operative in other bipotent stem cell systems.
Non-additive effects of changing the cytochrome P450 ensemble: incorporation of CYP2E1 into human liver microsomes and its impact on CYP1A2
Authors: Davydova Nadezhda Y. , Dangi Bikash , Maldonado Marc A. , Vavilov Nikita E. , Zgoda Victor G. , Davydov Dmitri R.
Published: June 2019

The aim of this study is to investigate the ability of ethanol-inducible CYP2E1 to interact with other cytochrome P450 species and affect the metabolism of their substrates. As a model system we used CYP2E1-enriched microsomes obtained by incorporation of purified CYP2E1 protein into HLM. Using the method based on homo-FRET in homo-oligomers of CYP2E1 labeled with BODIPY 577/618 maleimide we demonstrated that the interactions of CYP2E1 with microsomes result in dissociation of the protein homo-oligomers. The finding that this effect is much better pronounced in HLM as compared to the microsomes containing no P450 proteins indicates the formation of mixed oligomers of CYP2E1 with other P450 species that takes place in expense of dissociation of the homo-oligomers.

Incorporation of CYP2E1 into HLM results in a multifold increase in the rate of metabolism of CYP2E1-specific substratesp-Nitrophenol (pNP) and Chlorzaxozone (CLZ). The rate of their oxidation remains proportional to the amount of incorporated CYP2E1 up to the content of 0.3-0.4 nmol/mg protein (or about 50% CYP2E1 in the P450 pool). These results demonstrate that the incorporated CYP2E1 becomes a fully-functional member of the P450 ensemble and do not exhibit any detectable functional differences with the endogenous CYP2E1 in HLM.

Enrichment of HLM with CYP2E1 results in a pronounced alteration of the metabolism of 7-etoxy-4-cyanocoumarin (CEC), the substrate of CYP2C19 and CYP1A2, that suggests an important augmentation of the involvement of CYP1A2 in its metabolism. This effect goes together with a remarkable increase in the rate of dealkylation of CYP1A2-specific substrate 7-ethoxyresorufin by CYP2E1-enriched HLM. Furthermore, probing the interactions of CYP2E1 with model microsomes (Supersomes™) containing individual P450 enzymes we found that CYP2E1 efficiently interacts with CYP1A2, but lacks any ability to form complexes with CYP2C19. This finding goes inline with CYP2E1-induced redirection of the main route of CEC metabolism from CYP2C19 to CYP1A2.
Kinesin-8B controls basal body function and flagellum formation and is key to malaria parasite transmission
Authors: Zeeshan Mohammad , Ferguson David J. P. , Abel Steven , Burrrell Alana , Rea Edward , Brady Declan , Daniel Emilie , Delves Michael , Vaughan Sue , Holder Anthony A. , Le Roch Karine G. , Moores Carolyn A. , Tewari Rita
Published: June 2019

Eukaryotic flagella are conserved microtubule-based organelles that drive cell motility. Plasmodium, the causative agent of malaria, has a single flagellate stage: the male gamete in the mosquito. Three rounds of endomitotic division together with an unusual mode of flagellum assembly rapidly produce eight motile gametes. These processes are tightly coordinated but their regulation is poorly understood. To understand this important developmental stage, we studied the function and location of the microtubule-based motor kinesin-8B, using gene-targeting, electron microscopy and live cell imaging. Deletion of the kinesin-8B gene showed no effect on mitosis but disrupted 9+2 axoneme assembly and flagellum formation during male gamete development and also completely ablated parasite transmission. Live cell imaging showed that kinesin-8B-GFP did not colocalise with kinetochores in the nucleus but instead revealed dynamic, cytoplasmic localisation with the basal bodies and the assembling axoneme during flagellum formation. We thus uncovered an unexpected role for kinesin-8B in parasite flagellum formation that is vital for the parasite life cycle.
Challenging behaviour or untreated ADHD?
Authors: Korb Laura , Perera Bhathika , Courtenay Ken
Published: June 2019

Purpose

The purpose of this paper is to illustrate the possible basis of challenging behaviour (CB) can lie in a treatable neurodevelopmental disorder.

Design/methodology/approach

Two case studies were used to illustrate the clinical characteristics of attention deficit hyperactivity disorder (ADHD) presenting as CB in people with intellectual disability (ID).

Findings

The findings of this paper show that the appropriate use of drug therapy for ADHD effectively reduced the behavioural challenges.

Research limitations/implications

Limited by two cases. Application of the findings of this paper is limited given it is a case study. This paper highlights an important clinical implications which need to be studied in a larger scale to make clinical recommendations.

Practical implications

Findings from the two case studies may be used when making decisions in clinical practice.

Originality/value

The paper explores the possibility of ADHD presenting as CB in people with ID.
Numerical simulation for Darcy-Forchheimer flow of carbon nanotubes due to convectively heated nonlinear curved stretching surface
Authors: Khan Muhammad Ijaz , Muhammad Khursheed , Hayat Tasawar , Farooq Shahid , Alsaedi Ahmed
Published: June 2019

Purpose

This paper aims to discuss the salient aspects of the Darcy–Forchheimer flow of viscous liquid in carbon nanotubes (CNTs). CNTs are considered as nanofluid, and water is taken as the continuous phase liquid. The flow features are discussed via curved surface. Water is taken as the base liquid. Flow is generated via nonlinear stretching. Energy expression is modeled subject to heat generation/absorption. Furthermore, convective conditions are considered at the boundary. The Xue model is used in the mathematical modeling which describes the features of nanomaterials. Both types of CNTs are considered, i.e. single-walled CNTs and multi-walled CNTs.

Design/methodology/approach

Appropriate transformations are used to convert the flow expressions into dimensionless differential equations. The bvp4c method is used for solution development.

Findings

Velocity enhances via higher estimations of nanoparticles volume fraction while decays for higher Forchheimer number, curvature parameter, behavior index and porosity parameter. Furthermore, thermal field is an increasing function of nanoparticle volume fraction, behavior index, Forchheimer number and porosity parameter.

Originality/value

Here, the authors have discussed two-dimensional CNTs-based nanomaterial Darcy–Forchheimer flow of viscous fluid over a curved surface. The authors believe that all the outcomes and numerical techniques are original and have not been published elsewhere.
Investigation of enclosure aspect ratio effects on melting heat transfer characteristics of metal foam/phase change material composites
Authors: Samimi Behbahan Amin , Noghrehabadi Aminreza , Wong C.P. , Pop Ioan , Behbahani-Nejad Morteza
Published: June 2019

Purpose

The purpose of this paper is to study thermal performance of metal foam/phase change materials composite under the influence of the enclosure aspect ratios (ratio of enclosure height: length). In this study, a compound metal foam/phase change material (PCM), which has been proved to be one of the most promising approaches for thermal conductivity promotion on PCMs, was used.

Design/methodology/approach

The PCM is considered initially at its melting temperature. The enclosure for all the cases has a constant volume with various aspect ratios. The left side of the enclosure is suddenly exposed to a thermal source having a constant heat flux, while the other three surfaces are kept thermally insulated. A two-dimensional numerical model considering the non-equilibrium thermal factor, non-Darcy effect and local natural convection was proposed. The coupling between velocity and pressure is solved using the SIMPLEC, and the Rhie and Chow interpolation is used to avoid the checker-board solutions for the pressure.

Findings

The effects of foam porosity and aspect ratio of the enclosure on the PCM’s melting time were investigated. The results indicated that enclosure aspect ratio plays a fundamental role in phase change of copper foam/PCM composites. For higher porosities, enclosures with bigger aspect ratios proved to led to optimal melting time. Besides, the best enclosure aspect ratio and foam porosity for a fixed-volume enclosure to have the shortest melting time are 2.1 and 91.66 per cent, respectively. However, for a specific amount of PCM inside a variable volume enclosure, the optimal melting time was for foam with ε = 95 per cent. The achieved results prove the great importance of selection of aspect ratio to benefit both conduction and convection heat transfer simultaneously.

Originality/value

The area of energy storage systems is original.
Kombucha bacterial cellulose for sustainable fashion
Authors: Domskiene Jurgita , Sederaviciute Florentina , Simonaityte Judita
Published: June 2019

Purpose

The purpose of this paper is to analyse the properties of bacterial cellulose (BC) film, obtained through Kombucha tea fermentation.

Design/methodology/approach

Kombucha fungus was used to produce BC film under static cultivation conditions. Physical and mechanical properties under the influence of drying temperature and durability of BC material were investigated. Tensile properties were estimated by TINIUS OLSEN H10 KT test machine according to ISO 3376:2011, thickness was measured by DPT 60. BC structure was analysed by Scanning Electron Microscopy Quanta 200 FEG.

Findings

BC material with excellent deformation properties in wet state were obtained by fermenting Kombucha tea. Due to the presence of fermentation residues, Kombucha film is sensitive to drying temperature. The best deformation properties retain when BC material is dried at low temperature (about 25°C). BC material becomes stiffer and ruptures at lower deformations due to rapid water evaporation at higher drying temperature. It is confirmed that during time, the properties of BC film changes significantly and there may be problems with the durability of products from this material. BC film has an interesting set of properties, therefore its application to fashion industry without further preparation is limited.

Originality/value

A new approach is based on the evaluation of Kombucha material properties and investigation of BC as new type of material for fashion industry. Some recommendations for Kombucha BC film production are provided, basing on gained experience, experimental results and analysed literature. The advantages and disadvantages of material are discussed in the paper, in order to search for the ways to adapt the new type of material to fashion business.
Energy absorption and thermal comfort of segmented pad for hip protective garment
Authors: Wardiningsih Wiah , Troynikov Olga
Published: June 2019

Purpose

The purpose of this paper is to investigate the influence and relationship of segment area and opening area in segmented protective pad in comparison to non-segmented pad to the energy absorption and performance attributes relevant to thermophysiological wear comfort.

Design/methodology/approach

The compressive stress-strain curves were obtained using Instron Tester and were used to analyse the energy absorption of the pads and the segmented pad assemblies. The dry thermal resistance and evaporative resistance of the non-segmented and segmented protective pads were obtained using MTNW Sweating Guarded Hot Plate.

Findings

The compression test results and performance attributes relevant to thermophysiological wear comfort test result demonstrated that the area segment and opening area of segmented pad influenced their energy absorption value, dry thermal resistance value and evaporative resistance value (permeability index value).

Originality/value

The results are expected to be useful for design and engineering of hip impact protective garments. Hip impact protective pads are used to prevent hip fractures in elderly people as a result of fall.
FoCo system: a tool to bridge the domain gap between fashion and artificial intelligence
Authors: Zou Xingxing , Wong Wai Keung , Gao Can , Zhou Jie
Published: June 2019

Purpose

The deficiency of the mapping between fashion color (FoCo) value and linguistic color expression causes the difficulty of machine-based fashion understanding tasks that are heavily associated with color matching. The purpose of this paper is to propose the FoCo system and construct it with four steps, in order to bridge this gap.

Design/methodology/approach

The color distribution in HSB color space is analyzed to estimate the rough number of color categories. Similar color values are grouped to obtain the initial HSB value range for each color category. The intra-category color differences are calculated to determine their final HSB value ranges and Pantone color is used for fine-tuning.

Findings

With practical applications in mind, the FoCo system is designed as a hierarchical structure with three layers.

Originality/value

The FoCo system is designed as a hierarchical structure with three layers: color units for color matching-related tasks, color categories for style analysis tasks and color tones for color recognition tasks. Extensive experiments demonstrate the effectiveness of the FoCo system.
Development of a new cultural design process using Kansei engineering and fuzzy techniques
Authors: Liu Shuo-Fang , Hsu Yuan-Chin , Tsai Hung-Cheng
Published: June 2019

Purpose

Belief in Mazu has a crucial cultural status in Taiwan and the coastal area of Fujian, China. The design and manufacture of apparel and accessories to be placed on statues of the deity are also considered a sacred and critical part of the religion’s cultural and artistic inheritance. The crown hat of Mazu is one of the most essential elements of the deity’s apparel. The paper aims to discuss these issues.

Design/methodology/approach

This study explored the styles of Mazu crown hats using Kansei engineering (KE). People generally use adjectives words to provide aesthetic evaluations. Fuzzy theory is suitable for processing linguistic problems that include vagueness, thereby providing a reasonable method of quantifying such aesthetic evaluations. Therefore, this study first established a fuzzy positioning model (FPM) of word evaluations for analysis. Factor analysis was used to obtain representative image adjectives that represented Mazu’s image. Fuzzy analysis methods were then employed to rank the various image adjectives through evaluation words and to determine the differences between adjectives. Finally, on the basis of image analysis results and expert suggestions, the crown hat was redesigned and its suitability verified.

Findings

Four results were obtained. First, four image adjectives appropriate for representing Mazu’s image were identified, of which “noble and kind” is the most suitable. Second, fuzzy analysis was found to successfully rank style images. Third, the crown hat style and design characteristics suitable for Mazu were acquired. Fourth, the verification demonstrated that the redesign effectively enhanced the perceived image of the crown hat design.

Originality/value

This study employed KE to improve the design of a Mazu crown hat. The proposed FPM can aid the development of cultural and creative design.