bluuebunny/crossref_metadata_2025 huggingface dataset:
Premature Infant with Haemophilus parainfluenzae Sepsis: Case Report and Literature Review
Authors: Alsuhaibani Mohammed A
Published: February 2019

Haemophilus parainfluenzae is an unusual causative organism of invasive bacterial infection in adults and children. Mortality and morbidity secondary to Haemophilus parainfluenzae have been documented in the literature. We present a rare case of a premature infant with early onset sepsis caused by Haemophilus parainfluenzae, who was born to a primigravida with chorioamnionitis. The infant was successfully treated for 10 days with antibiotics with no complications.
RETRACTED: Hedgehog pathway permissive conditions allow generation of immortal cell lines from granule cells derived from cancerous and non-cancerous cerebellum
Authors: Heil Constantin
Published: February 2019

Cerebellar granule cell progenitors (GCPs) undergo proliferation in the post-natal cerebellum that is dependent on sonic hedgehog (SHH) signalling. Deregulated SHH signalling leads to type 2 medulloblastoma (MB). In this work, a novel cell culture protocol is described, which is suitable for the establishment and long-term maintenance of GCP-derived cells. This method is first applied to SHH pathway active MB cells from
Atoh1
-cre;
Ptch1
FL/FL
tumours, which leads to the generation of neurosphere-like cell lines expressing GCP markers and an active SHH signalling pathway. These cells also show high sensitivity to the Smoothened inhibitor vismodegib, therefore recapitulating the SHH pathway requirement for survival shown by type 2 MB. Analysis of culture supplements reveals that bFGF and fetal bovine serum act as inhibitors of the SHH pathway and therefore preclude generation of cell lines that are relevant to the study of the SHH pathway. Consequently, these insights are transferred from the context of MB to non-transformed, post-natal day 7 cerebellum-derived cellular explants. In contrast to other, previously used methods, these GCP cultures proliferate indefinitely and depend on SHH pathway activation, either by means of the small molecule SAG or through genetic ablation of
Ptch1
. This culture method therefore leads to the generation of immortal neurosphere-like cell lines, that are named murine SAG-dependent spheres (mSS). Despite long-term culture, mSS cells remain dependent on continuous stimulation of the SHH pathway. Further, mSS cells maintain their lineage after extensive periods
in vitro,
as demonstrated by their differentiation towards the neural lineage. Herein a simple method for the generation of immortal cell lines from murine cerebella is defined. These lines can be maintained indefinitely through hedgehog pathway activation and maintain the GCP lineage.
Opportunities and challenges for the use of induced pluripotent stem cells in modelling neurodegenerative disease
Authors: Wu Yi-Ying , Chiu Feng-Lan , Yeh Chan-Shien , Kuo Hung-Chih
Published: February 2019

Adult-onset neurodegenerative diseases are among the most difficult human health conditions to model for drug development. Most genetic or toxin-induced cell and animal models cannot faithfully recapitulate pathology in disease-relevant cells, making it excessively challenging to explore the potential mechanisms underlying sporadic disease. Patient-derived induced pluripotent stem cells (iPSCs) can be differentiated into disease-relevant neurons, providing an unparalleled platform for
in vitro
modelling and development of therapeutic strategies. Here, we review recent progress in generating Alzheimer's, Parkinson's and Huntington's disease models from patient-derived iPSCs. We also describe novel discoveries of pathological mechanisms and drug evaluations that have used these patient iPSC-derived neuronal models. Additionally, current human iPSC technology allows researchers to model diseases with 3D brain organoids, which are more representative of tissue architecture than traditional neuronal cultures. We discuss remaining challenges and emerging opportunities for the use of three-dimensional brain organoids in modelling brain development and neurodegeneration.
Thermal sensors improve wrist-worn position tracking
Authors: Son Jake J. , Clucas Jon C. , White Curt , Krishnakumar Anirudh , Vogelstein Joshua T. , Milham Michael P. , Klein Arno
Published: February 2019

Wearable devices provide a means of tracking hand position in relation to the head, but have mostly relied on wrist-worn inertial measurement unit sensors and proximity sensors, which are inadequate for identifying specific locations. This limits their utility for accurate and precise monitoring of behaviors or providing feedback to guide behaviors. A potential clinical application is monitoring body-focused repetitive behaviors (BFRBs), recurrent, injurious behaviors directed toward the body, such as nail biting and hair pulling, that are often misdiagnosed and undertreated. Here, we demonstrate that including thermal sensors achieves higher accuracy in position tracking when compared against inertial measurement unit and proximity sensor data alone. Our Tingle device distinguished between behaviors from six locations on the head across 39 adult participants, with high AUROC values (best was back of the head: median (1.0), median absolute deviation (0.0); worst was on the cheek: median (0.93), median absolute deviation (0.09)). This study presents preliminary evidence of the advantage of including thermal sensors for position tracking and the Tingle wearable device’s potential use in a wide variety of settings, including BFRB diagnosis and management.
Mutational burden of hepatoblastomas: a role for the CX3CL1/CX3CR1 chemokine signaling pathway
Authors: Marques Aguiar Talita Ferreira , Rivas Maria Prates , Costa Silvia , Rodrigues Tatiane , de Barros Juliana Sobral , Barbosa Anne Caroline , Maschietto Mariana , Valieris Renan , Fernandes Gustavo Ribeiro , Cypriano Monica , de Toledo Silvia Regina Caminada , Major Angela , Tojal Israel , de Pinho Apezzato Maria Lúcia , Carraro Dirce Maria , Rosenberg Carla , da Costa Cecilia Maria Lima , da Cunha Isabela Werneck , Sarabia Stephen Frederick , Terrada Dolores-López , Krepischi Ana Cristina Victorino
Published: February 2019

Background

Hepatoblastoma is an embryonal liver tumor supposed to arise from the impairment of hepatocyte differentiation during embryogenesis. CTNNB1 is the only recurrently mutated gene, and this relative paucity of somatic mutations poses a challenge to risk stratification and development of targeted therapies.

Methods

In this study, we investigated by exome sequencing the burden of somatic mutations in a cohort of 10 hepatoblastomas, including a congenital case.

Results

Our data disclosed a low mutational background with only three recurrently mutated genes: CTNNB1 and two novel candidates, CX3CL1 and CEP164. The major finding was a recurrent mutation (A235G) identified in two hepatoblastomas at the CX3CL1 gene; evaluation of RNA and protein expression revealed up-regulation of CX3CL1 in tumors. The analysis was replicated in two independents cohorts, substantiating that an activation of the CX3CL1/CX3CR1 pathway occurs in hepatoblastomas, with a predominance of these proteins in the cytoplasm of tumor cells. These proteins were not detected in the infiltrated lymphocytes of inflammatory regions of the tumors, in which they should be expressed in normal conditions, whereas necrotic regions exhibited negative tumor cells, but strongly positive infiltrated lymphocytes. Our data suggested that CX3CL1/CX3CR1 upregulation may be a common feature of hepatoblastomas, potentially related to chemotherapy response and progression. In addition, three mutational signatures were identified in hepatoblastomas, two of them with predominance of either the COSMIC signatures 1 and 6, found in all cancer types, or the COSMIC signature 29, related only with tobacco chewing habit; a third novel mutational signature presented an unspecific pattern with an increase of C>A mutations.

Conclusions

Overall, we present here evidence that CX3CL1/CX3CR1 chemokine signaling pathway is likely involved with hepatoblastoma tumorigenesis or progression, besides reporting a novel mutational signature specific to a hepatoblastoma subset.
Manipulating patterns of dynamic deformation elicits the impression of cloth with varying stiffness
Authors: Bi Wenyan , Jin Peiran , Nienborg Hendrikje , Xiao Bei
Published: February 2019

Cloth is a common material and humans can visually estimate its mechanical properties by observing how it deforms under external forces. Here we ask whether, and how, dynamic deformation can affect the perception of mechanical properties of cloth. In Experiment 1, we find that both intrinsic mechanical properties and optical properties affect stiffness perception when the stimuli are presented as images. By contrast, in videos, humans can partially discount the effect of optical appearances and exhibit higher sensitivity to stiffness. We further identified an idiosyncratic deformation pattern (i.e., movement uniformity) to differentiate stiffness, which can be reliably measured by six optical flow features. In Experiment 2, we isolate the deformation by creating dynamic dot stimuli from the 3D mesh of the cloth. We directly alter the movement pattern by manipulating the uniformity of the displacement vectors on the dot stimuli, and show that changing the pattern of dynamic deformation alone can alter the perceived stiffness of cloth in a variety of scene set-ups. Furthermore, by analyzing optical flow fields extracted from the manipulated dynamic dot stimuli, we confirmed the same six optical flow features can be diagnostic of the degree of stiffness of moving cloth across different scenes. Overall, our study demonstrates that manipulating patterns of dynamic deformation alone can elicit the impression of cloth with varying stiffness, suggesting that human visual system might rely on the idiosyncratic pattern of dynamic deformation for estimating stiffness.
The relationship of body condition, superoxide dismutase and superoxide with sperm performance
Authors: Friesen Christopher R. , de Graaf Simon P. , Olsson Mats
Published: February 2019

Sperm competition theory predicts a negative correlation between somatic investment in traits that aid in pre- and postcopulatory sexual selection. Sperm performance is critical for postcopulatory success but are susceptible to damage by free radicals such as superoxide radicals generated during mitochondrial respiration (mtSOx). Males can ameliorate damage to spermatozoa by investing in the production of antioxidants, like superoxide dismutase (SOD), which may act as a mechanistic link for pre and postcopulatory trade-offs. Some male Australian, colour-polymorphic painted dragon lizards (Ctenophorus pictus) possess a yellow throat patch (bib) that females prefer over non-bibbed males and are also more likely to win male-male contests indicating that males with bibs are better at monopolizing females. We tested whether the sperm performance in non-bibbed males was superior to that of bibbed males as predicted by sperm competition theory. We show that blood cell mtSOx levels are negatively correlated with SOD activity in the plasma in all males early in the breeding season but SOD was lower in bibbed males. Non-bibbed males maintain a positive correlation between body condition and SOD activity over time while bibbed males do not. Overall sperm performance was not different between the bib-morphs, however, higher mtSOx levels were negatively correlated with sperm performance in bibbed males, but not of non-bibbed males. Together these data suggest physiological associations between body condition, SOD activity and sperm performance are linked to the expression of a yellow gular patch, which may be related to intrinsic differences in metabolism of bibbed versus non-bibbed males.

Lay summary

Damage-inducing reactive oxygen species (ROS) are a by-product of oxygen-based energy production that are quenched by energetically expensive antioxidants. Male sexual colouration requires investment of energy and resources, which may constrain allocation to other functions like antioxidant production or spermatogenesis. Here we explored whether the body condition of colourful male lizards reflected their investment in antioxidants and reduction of ROS, which may influence sperm performance. We found that drab males in better condition had more antioxidants. Colourful males had lower levels of antioxidants and their sperm performed poorly at higher ROS levels. These results suggest a trade-off between colour maintenance and sperm performance.
Spatiotemporal empirical mode decomposition of resting-state fMRI signals: application to global signal regression
Authors: Moradi Narges , Dousty Mehdy , Sotero Roberto C.
Published: February 2019

Resting-state functional connectivity MRI (rs-fcMRI) is a common method for mapping functional brain networks. However, estimation of these networks is affected by the presence of a common global systemic noise, or global signal (GS). Previous studies have shown that the common preprocessing steps of removing the GS may create spurious correlations between brain regions. In this paper, we decompose fMRI signals into 5 spatial and 3 temporal intrinsic mode functions (SIMF and TIMF, respectively) by means of the empirical mode decomposition (EMD), which is an adaptive data-driven method widely used to analyze nonlinear and nonstationary phenomena. For each SIMF, brain connectivity matrices were computed by means of the Pearson correlation between TIMFs of different brain areas. Thus, instead of a single connectivity matrix, we obtained 5 × 3 = 15 functional connectivity matrices. Given the high value obtained for large-scale topological measures such as transitivity, in the low spatial maps (SIMF3, SIMF4, and SIMF5), our results suggest that these maps can be considered as spatial global signal masks. Thus, the spatiotemporal EMD of fMRI signals automatically regressed out the GS, although, interestingly, the removed noisy component was voxel-specific. We compared the performance of our method with the conventional GS regression and to the results when the GS was not removed. While the correlation pattern identified by the other methods suffers from a low level of precision, our approach demonstrated a high level of accuracy in extracting the correct correlation between different brain regions.
Delta and theta neural entrainment during phonological and semantic processing in speech perception
Authors: Mai Guangting , Wang William S-Y.
Published: February 2019

Neural entrainment of acoustic envelopes is important for speech intelligibility in spoken language processing. However, it is unclear how it contributes to processing at different linguistic hierarchical levels. The present EEG study investigated this issue when participants responded to stimuli that dissociated phonological and semantic processing (real-word, pseudo-word and backward utterances). Multivariate Temporal Response Function (mTRF) model was adopted to map speech envelopes from multiple spectral bands onto EEG signals, providing a direct approach to measure neural entrainment. We tested the hypothesis that entrainment at delta (supra-syllabic) and theta (syllabic and sub-syllabic) bands take distinct roles at different hierarchical levels. Results showed that both types of entrainment involve speech-specific processing, but their underlying mechanisms were different. Theta-band entrainment was modulated by phonological but not semantic contents, reflecting the possible mechanism of tracking syllabic- and sub-syllabic patterns during phonological processing. Delta-band entrainment, on the other hand, was modulated by semantic information, indexing more attention-demanding, effortful phonological encoding when higher-level (semantic) information is deficient. Interestingly, we further demonstrated that the statistical capacity of mTRFs at the delta band and theta band to classify utterances is affected by their semantic (real-word vs. pseudo-word) and phonological (real-word and pseudo-word vs. backward) contents, respectively. Moreover, analyses on the response weighting of mTRFs showed that delta-band entrainment sustained across neural processing stages up to higher-order timescales (~ 300 ms), while theta-band entrainment occurred mainly at early, perceptual processing stages (< 160 ms). This indicates that, compared to theta-band entrainment, delta-band entrainment may reflect increased involvement of higher-order cognitive functions during interactions between phonological and semantic processing. As such, we conclude that neural entrainment is not only associated with speech intelligibility, but also with the hierarchy of linguistic (phonological and semantic) content. The present study thus provide a new insight into cognitive mechanisms of neural entrainment for spoken language processing.

Highlights

Low-frequency neural entrainment was examined via mTRF models in EEG during phonological and semantic processing.

Delta entrainment take roles in effortful listening for phonological recognition

Theta entrainment take roles in tracking syllabic and subsyllabic patterns for phonological processing

Delta and theta entrainment sustain at different timescales of neural processing
Novel polygenic risk score as a translational tool linking depression-related changes in the corticolimbic transcriptome with neural face processing and anhedonic symptoms
Authors: Mareckova Klara , Hawco Colin , Dos Santos Fernanda C. , Bakht Arin , Calarco Navona , Miles Amy E. , Voineskos Aristotle N. , Sibille Etienne , Hariri Ahmad R. , Nikolova Yuliya.S.
Published: February 2019

Convergent data from imaging and postmortem brain transcriptome studies implicate corticolimbic circuit (CLC) dysregulation in the pathophysiology of depression. To more directly bridge these lines of work, we generated a novel transcriptome-based polygenic risk score (T-PRS), capturing subtle shifts towards depression-like gene expression patterns in key CLC regions, and mapped this T-PRS onto brain function and related depressive symptoms in a non-clinical sample of 478 young adults (225 men; age 19.79+/−1.24) from the Duke Neurogenetics Study. First, T-PRS was generated based on common functional SNPs shifting CLC gene expression towards a depression-like state. Next, we used multivariate partial least squares regression to map T-PRS onto whole-brain activity patterns during perceptual processing of social stimuli (i.e., human faces). For validation, we conducted a comparative analysis with a PRS summarizing depression risk variants identified by the Psychiatric Genomics Consortium (PGC-PRS). Sex was modeled as moderating factor. We showed that T-PRS was associated with widespread reductions in neural response to neutral faces in women and to emotional faces and shapes in men (multivariate p<0.01). This female-specific reductions in neural response to neutral faces was also associated with PGC-PRS (multivariate p<0.03). Reduced reactivity to neutral faces was further associated with increased self-reported anhedonia. We conclude that women with functional alleles mimicking the postmortem transcriptomic CLC signature of depression have blunted neural activity to social stimuli, which may be expressed as higher anhedonia.
Marine deep biosphere microbial communities assemble in near-surface sediments in Aarhus Bay
Authors: Petro Caitlin , Zäncker Birthe , Starnawski Piotr , Jochum Lara M. , Ferdelman Timothy G. , Jørgensen Bo Barker , Røy Hans , Kjeldsen Kasper U. , Schramm Andreas
Published: February 2019

Analyses of microbial diversity in marine sediments have identified a core set of taxa unique to the marine deep biosphere. Previous studies have suggested that these specialized communities are shaped by processes in the surface seabed, in particular that their assembly is associated with the transition from the bioturbated upper zone to the nonbioturbated zone below. To test this hypothesis, we performed a fine-scale analysis of the distribution and activity of microbial populations within the upper 50 cm of sediment from Aarhus Bay (Denmark). Sequencing and qPCR were combined to determine the depth distributions of bacterial and archaeal taxa (16S rRNA genes) and sulfate-reducing microorganisms (dsrBgene). Mapping of radionuclides throughout the sediment revealed a region of intense bioturbation at 0-6 cm depth. The transition from bioturbated sediment to the subsurface below (7 cm depth) was marked by a shift from dominant surface populations to common deep biosphere taxa (e.g. Chloroflexi & Atribacteria). Changes in community composition occurred in parallel to drops in microbial activity and abundance caused by reduced energy availability below the mixed sediment surface. These results offer direct evidence for the hypothesis that deep subsurface microbial communities present in Aarhus Bay mainly assemble already centimeters below the sediment surface, below the bioturbation zone.
ILT7 activation and plasmacytoid dendritic cell response are governed by BST2 determinants that are structurally-distinct
Authors: Bego Mariana G. , Miguet Nolwenn , Laliberté Alexandre , Aschman Nicolas , Gerard Francine , Merakos Angelique A. , Weissenhorn Winfried , Cohen Éric A.
Published: February 2019

The interaction of the human pDC receptor ILT7 with its ligand, BST2, significantly regulates pDC’s TLR-induced innate immune responses. This interaction has critical biological consequences, yet, its structural requirements are not fully characterized. The BST2 ectodomain can be divided in structurally and functionally distinct regions; while the coiled-coil region contains a newly-defined ILT7 binding surface, the N-terminal region appears to negatively modulate ILT7 activation. A stable BST2 homodimer binds to ILT7 but post-binding events associated to the unique BST2 coiled-coil plasticity are required to trigger receptor signaling. Hence, BST2 with an unstable or with a rigid coiled-coil fails to activate ILT7, whereas mutations in the N-terminal region enhance activation. Importantly, the biological relevance of these newly defined domains of BST2 is underscored by the identification of mutations with opposed potential to activate ILT7, which are selected under pathological malignant conditions.
Combinatorial mutagenesis of rapidly-evolving residues yields super-restrictor antiviral proteins
Authors: Colón-Thillet Rossana , Hsieh Emily , Graf Laura , McLaughlin Richard N , Young Janet M. , Kochs Georg , Emerman Michael , Malik Harmit S.
Published: February 2019

Antagonistic interactions drive host-virus evolutionary arms-races, which often manifest as recurrent amino acid changes (i.e., positive selection) at their protein-protein interaction interfaces. Here, we investigated whether combinatorial mutagenesis of positions under positive selection in a host antiviral protein could enhance its restrictive properties. We tested ~700 variants of human MxA, generated by combinatorial mutagenesis, for their ability to restrict Thogoto orthomyxovirus (THOV). We identified MxA super-restrictors with increased binding to THOV NP target protein and 10-fold higher anti-THOV restriction relative to wild-type human MxA, the most potent naturally-occurring anti-THOV restrictor identified. Our findings reveal a means to elicit super-restrictor antiviral proteins by leveraging signatures of positive selection. Although some MxA super-restrictors of THOV were impaired in their restriction of H5N1 influenza A virus (IAV), other super-restrictor variants increased THOV restriction without impairment of IAV restriction. Thus, broadly acting antiviral proteins such as MxA mitigate breadth-versus-specificity tradeoffs that could otherwise constrain their adaptive landscape.
The milk protein alpha-casein suppresses triple negative breast cancer stem cell activity via STAT and HIF-1alpha signalling pathways in breast cancer cells and fibroblasts
Authors: Garner Kirsten EL , Lamb Rebecca , Sims Andrew H , Clarke Robert B
Published: February 2019

Triple negative breast cancer (TNBC) is the most lethal breast cancer subtype. Extended periods of lactation protect against breast cancer development, but the mechanisms underlying this protection are unknown.
We examined the effects of the milk protein alpha-casein over expression in the triple negative MDA-MB-231 breast cancer cell line. The effects of recombinant alpha-casein added exogenously to MDA-MB-231 breast cancer cells, and immortalised human fibroblasts were also investigated. We used transcriptional reporters to understand the signalling pathways downstream of alpha-casein in breast cancer cells and these fibroblasts that were activated by breast cancer cells. To extend our findings to the clinical setting, we analysed public gene expression datasets to further understand the relevance of these signalling pathways in triple negative breast cancer cells and patient samples. Finally, we used small molecular inhibitors to target relevant pathways and highlight these as potential candidates for the treatment of TN breast cancer.
High levels of alpha-casein gene expression were predictive of good prognosis across 263 TNBC patient tumour samples. Alpha-casein over expression or exogenous addition reduces cancer stem cell (CSC) activity. HIF-1alpha was identified to be a key downstream target of alpha-casein, in both breast cancer cells and activated fibroblasts, and STAT transcription factors to be upstream of HIF-1alpha. Interestingly, HIF-1alpha is regulated by STAT3 in breast cancer cells, but STAT1 is the regulator of HIF-1alpha in activated fibroblasts. In analysis of 573 TNBC patient samples, alpha-casein expression, inversely correlated to HIF-1alpha, STAT3 and STAT1. STAT1 and STAT3 inhibitors target HIF-1alpha signalling in activated fibroblasts and MDA-MB-231 breast cancer cells respectively, and also abrogate CSC activities.
Our findings provide an explanation for the protective effects of lactation in TNBC. Clinical data correlates high alpha-casein expression with increased recurrence-free survival in TNBC patients. Mechanistically, alpha-casein reduces breast cancer stem cell activity in vitro, and STAT3 and STAT1 were identified as regulators of pro-tumorigenic HIF-1alpha signalling in breast cancer cells and fibroblasts respectively.
Consciousness as a Concrete Physical Phenomenon
Authors: Jylkkä Jussi , Railo Henry
Published: February 2019

Why any type of neural activation is associated with subjective, conscious experience is a fundamental unsolved question in neuroscience. To bridge the gap between neural activity and conscious experience, one seemingly must tie together two very different entities. The paradigmatic view in consciousness science is that subjective experiences are private and cannot be scientifically observed or described: science can only discover correlations between subjective experiences and their neural realizers, but never observe or describe the experiences themselves. We present a metatheory of consciousness that explains how subjective experiences are related to empirical observations and models, and why the two appear so different from each other. We argue that consciousness is a concrete physical process that causally interacts with other physical phenomena. This entails that consciousness can be empirically observed and characterized. The reason why subjective experiences and empirical observations and models of them appear so different is explained by what we call the observer-observed distinction. Empirical observations are always distinct from the observer, but a subject and her experiences constitute a single physical-biological system. We argue that once science has completely described 1) the constitutive neural mechanisms that are isomorphic with experiences, 2) the etiological mechanisms that experiences are based on, and 3) their causal power, then science has provided an exhaustive description of phenomenology. Our conclusion is that, if we accept this framework we call Naturalistic Monism, consciousness collapses into a standard problem of science.
MAP7 recruits kinesin-1 to microtubules to direct organelle transport
Authors: Chaudhary Abdullah R. , Lu Hailong , Krementsova Elena B. , Bookwalter Carol S. , Trybus Kathleen M. , Hendricks Adam G.
Published: February 2019

Microtubule-associated proteins (MAPs) play well-characterized roles in regulating microtubule polymerization, dynamics, and organization. In addition, MAPs control trans-port along microtubules by regulating the motility of kinesin and dynein. MAP7 (ensconsin, E-MAP-115) is a ubiquitous MAP that organizes the microtubule cytoskeleton in mitosis and neuronal branching. MAP7 also promotes the interaction of kinesin-1 with microtubules. We expressed and purified full-length kinesin-1 and MAP7 in Sf9 cells. In single-molecule motiity assays, MAP7 recruits kinesin-1 to microtubules, increasing the frequency of both diffusive and processive runs. Optical trapping assays on beads transported by single and teams of kinesin-1 motors indicate that MAP7 increases the relative binding rate of kinesin-1 and the number of motors simultaneously engaged in ensembles. To examine the role of MAP7 in regulating bidirectional transport, we isolated late phagosomes along with their native set of kinesin-1, kinesin-2, and dynein motors. Bidirectional cargoes exhibit a clear shift towards plus-end directed motility on MAP7-decorated microtubules due to increased forces exerted by kinesin teams. Collectively, our results indicate that MAP7 enhances kinesin-1 recruitment to microtubules and targets organelle transport to the plus end.
Dynamics of Sox2 expression during rat germ cell development and its relationship with emergence of spermatogonia
Authors: Oliveira Ticiana Volpato de , Tesser Renato Borges , Nunes Marina , Stumpp Taiza
Published: February 2019

1.

The gonocytes represent a specific phase of male gem cell development that precedes spermatogonial stem cell differentiation. Here, we describe the expression of Sox2, an OCT4 partner, during rat germ cell development. Our hypothesis is that SOX2 has a cytoplasmic role during gonocyte-to-spermatogonia transition. Male rat embryos and testes were submitted to the analysis of Sox2 expression. Sox2 was detected in germ cells from 14 days post-conception (dpc) to 8dpp. SOX2 was present in 14dpc and 15dpc embryos and absent at 17 and 19dpc; however, it did not show direct correlation with mRNA. SOX2 labelling was detected after birth and its expression increased from 1dpp to 5dpp. SOX2 was localized in the cytoplasm and showed a granulated pattern similar to P-bodies. Indeed, GW182/SOX2 and LIN28/SOX2 double-labelling showed that SOX2 partially co-localized with the P-bodies components GW182 and LIN28. At 8dpp SOX2 was detected in the nucleus and/or in the cytoplasm of spermatogonia, whereas at 25dpp it was detected in the nucleus of rare spermatogonia. This suggests that SOX2 localization changes during gonocytes to spermatogonia transition.
A comparative anatomy of protein crystals: lessons from the automatic processing of 56,000 samples
Authors: Svensson Olof , Gilski Maciej , Nurizzo Didier , Bowler Matthew W.
Published: February 2019

Synopsis

The automatic processing of over 56,000 crystals by the autonomous ESRF beamline MASSIF-1 has provided a data set of crystal characteristics and properties that allows many theoretical proposals and assumptions to be evaluated experimentally.

The fully automatic processing of crystals of macromolecules has presented a unique opportunity to gather information on the samples that is not usually recorded. This has proved invaluable in improving the sample location, characterisation and data collection algorithms. After operating for four years, MASSIF-1 has now processed over 56,000 samples, gathering information at each stage, from the volume of the crystal to the unit cell dimensions, space group, quality of the data collected and the reasoning behind the decisions made in data collection. This provides an unprecedented opportunity to analyse these data together, providing a detailed landscape of macromolecular crystals and intimate details of their contents and, importantly, how the two are related. The data show that mosaic spread is unrelated to the size or shape of crystals and demonstrate experimentally that diffraction intensities scale in proportion to crystal volume and molecular weight. It is also shown that crystal volume scales inversely with molecular weight. The results set the scene for the development of X-ray crystallography in a changing environment for structural biology.
Role of DNA methylation dynamics in desiccation and salinity stress responses in rice cultivars
Authors: Rajkumar Mohan Singh , Shankar Rama , Garg Rohini , Jain Mukesh
Published: February 2019

DNA methylation is an epigenetic mark that controls gene expression in response to internal and environmental cues. In this study, we sought to understand the role of DNA methylation in response to desiccation and salinity stresses in three rice cultivars (IR64, stress-sensitive; Nagina 22, drought-tolerant and Pokkali, salinity-tolerant) via bisulphite sequencing. We identified DNA methylation patterns in different genomic/genic regions and analysed their correlation with gene expression. Methylation in CG context within gene body and methylation in CHH context in distal promoter regions were positively correlated with gene expression. However, methylation in other sequence contexts and genic regions was negatively correlated with gene expression. DNA methylation was found to be most dynamic in CHH context under stress condition(s) in the rice cultivars. The expression profiles of genes involved inde-novomethylation were correlated with methylation dynamics. Hypomethylation in Nagina 22 and hypermethylation in Pokkali in response to desiccation and salinity stress, respectively, were correlated with higher expression of abiotic stress response related genes. Our results suggest an important role of DNA methylation in abiotic stress responses in rice in cultivar-specific manner. This study provides useful resource of DNA methylomes that can be integrated with other data to understand abiotic stress response in rice.

Highlight

Bisulphite sequencing revealed single base resolution DNA methylation, and cultivar-specific differential methylation patterns and correlation with gene expression that control desiccation and salinity stress response in the rice cultivars.
Sustained Ca2+mobilizations: a quantitative approach to predict their importance in cell-cell communication and wound healing
Authors: Lee Yoonjoo , Kim Min Tae , Rhodes Garrett , Sack Kelsey , Son Sung Jun , Rich Celeste B. , Kolachalama Vijaya B. , Gabel Christopher V , Trinkaus-Randall Vickery
Published: February 2019

Epithelial wound healing requires the coordination of cells to migrate as a unit over the basement membrane after injury. To understand the process of this coordinated movement, it is critical to study the dynamics of cell-cell communication. We developed a method to characterize the injury-induced sustained Ca2+mobilizations that travel between cells for periods of time up to several hours. These events of communication are concentrated along the wound edge and are reduced in cells further away from the wound. Our goal was to delineate the role and contribution of these sustained mobilizations and using MATLAB analyses, we determined the probability of cell-cell communication events in in vitro models and ex vivo organ culture models. We demonstrated that the injury response was complex and represented the activation of a number of receptors. In addition, we found that pannexin channels mediated the cell-cell communication and motility. Furthermore, the sustained Ca2+mobilizations are associated with changes in cell morphology and motility during wound healing. The results demonstrate that both purinoreceptors and pannexins regulate the sustained Ca2+mobilization necessary for cell-cell communication in wound healing.
Biophotons: low signal/noise ratio reveals crucial events
Authors: Benfatto Maurizio , Pace Elisabetta , Curceanu Catalina , Scordo Alessandro , Clozza Alberto , Davoli Ivan , Lucci Massimiliano , Francini Roberto , De Matteis Fabio , Grandi Maurizio , Tuladhar Rohisha , Grigolini Paolo
Published: February 2019

We study the emission of photons from germinating seeds using an experimental technique designed to detect photons of extremely small intensity when the signal/noise ratio is low. We analyze the dark count signal in the absence of germinating seeds as well as the photon emission during the germination process. The technique of analysis adopted here was originally designed to measure the temporal complexity of astrophysical, sociological and physiological processes. The foundation of this method, called Diffusion Entropy Analysis (DEA), rests on Kolmogorov complexity. The updated version of DEA used in this paper is designed to determine if the signal complexity is generated by either non-ergodic crucial events with a non-stationary correlation function or by the infinite memory of a stationary but non-integrable correlation function or by a mixture of both processes. We find that dark count yields the ordinary scaling, thereby showing that no complexity of either kinds may occur in the absence of any seeds in the chamber. In the presence of seeds in the chamber anomalous scaling emerges, reminiscent of that found in neuro-physiological processes. However, this is a mixture of both processes and with the progress of germination the non-ergodic component tends to vanish and complexity is dominated by the stationary infinite memory. We argue that this may be a sign of quantum coherence that according to some authors is the important ingredient of cognition.
A multi-scale coevolutionary approach to predict interactions between protein domains
Authors: Croce Giancarlo , Gueudré Thomas , Cuevas Maria Virginia Ruiz , Keidel Victoria , Figliuzzi Matteo , Szurmant Hendrik , Weigt Martin
Published: February 2019

Interacting proteins and protein domains coevolve on multiple scales, from their correlated presence across species, to correlations in amino-acid usage. Genomic databases provide rapidly growing data for variability in genomic protein content and in protein sequences, calling for computational predictions of unknown interactions. We first introduce the concept ofdirect phyletic couplings, based on global statistical models of phylogenetic profiles. They strongly increase the accuracy of predicting pairs of related protein domains beyond simpler correlation-based approaches like phylogenetic profiling (80% vs. 30-50% positives out of the 1000 highest-scoring pairs). Combined with the direct coupling analysis of inter-protein residue-residue coevolution, we provide multi-scale evidence for direct but unknown interaction between protein families. An in-depth discussion shows these to be biologically sensible and directly experimentally testable. Negative phyletic couplings highlight alternative solutions for the same functionality, including documented cases of convergent evolution. Thereby our work proves the strong potential of global statistical modeling approaches to genome-wide coevolutionary analysis, far beyond the established use for individual protein complexes and domain-domain interactions.

Author summary

Interactions between proteins and their domains are at the basis of almost all biological processes. To complement labor intensive and error-prone experimental approaches to the genome-scale characterization of such interactions, we propose a computational approach based upon rapidly growing protein-sequence databases. To maintain interaction in the course of evolution, proteins and their domains are required to coevolve: evolutionary changes in the interaction partners appear correlated across several scales, from correlated presence-absence patterns of proteins across species, up to correlations in the amino-acid usage. Our approach combines these different scales within a common mathematical-statistical inference framework, which is inspired by the so-called direct coupling analysis. It is able to predict currently unknown, but biologically sensible interaction, and to identify cases of convergent evolution leading to alternative solutions for a common biological task. Thereby our work illustrates the potential of global statistical inference for the genome-scale coevolutionary analysis of interacting proteins and protein domains.
A machine learning tool for interpreting differences in cognition using brain features
Authors: Azevedo Tiago , Passamonti Luca , Lió Pietro , Toschi Nicola
Published: February 2019

Predicting variability in cognition traits is an attractive and challenging area of research, where different approaches and datasets have been implemented with mixed results. Some powerful Machine Learning algorithms employed before are difficult to interpret, while other algorithms are easy to interpret but might not be as powerful. To improve understanding of individual cognitive differences in humans, we make use of the most recent developments in Machine Learning in which powerful prediction models can be interpreted with confidence. We used neuroimaging data and a variety of behavioural, cognitive, affective and health measures from 905 people obtained from the Human Connectome Project (HCP). As a main contribution of this paper, we show how one could interpret the neuroanatomical basis of cognition, with recent methods which we believe are not yet fully explored in the field. By reducing neuroimages to a well characterised set of features generated from surface-based morphometry and cortical myelin estimates, we make the interpretation of such models easier as each feature is self-explanatory. The code used in this tool is available in a public repository: https://github.com/tjiagoM/interpreting-cognition-paper-2019
Multiple-beamline operation of SACLA
Authors: Tono Kensuke , Hara Toru , Yabashi Makina , Tanaka Hitoshi
Published: February 2019

The SPring-8 Ångstrom Compact free-electron LAser (SACLA) began parallel operation of three beamlines (BL1–3) in autumn 2017 to increase the user beam time of the X-ray free-electron laser. The success of the multiple-beamline operation is based on two technological achievements: (i) the fast switching operation of the SACLA main linear accelerator, which provides BL2 and BL3 with pulse-by-pulse electron beams, and (ii) the relocation and upgrade of the SPring-8 Compact SASE Source for BL1, for the generation of a soft X-ray free-electron laser. Moreover, the photon beamlines and experimental stations were upgraded to facilitate concurrent user experiments at the three beamlines and accommodate more advanced experiments.
Time-resolved grazing-incidence pair distribution functions during deposition by radio-frequency magnetron sputtering
Authors: Roelsgaard Martin , Dippel Ann-Christin , Borup Kasper Andersen , Nielsen Ida Gjerlevsen , Broge Nils Lau Nyborg , Röh Jan Torben , Gutowski Olof , Iversen Bo Brummerstedt
Published: February 2019

Characterization of local order in thin films is challenging with pair distribution function (PDF) analysis because of the minute mass of the scattering material. Here, it is demonstrated that reliable high-energy grazing-incidence total X-ray scattering data can be obtained in situ during thin-film deposition by radio-frequency magnetron sputtering. A benchmark system of Pt was investigated in a novel sputtering chamber mounted on beamline P07-EH2 at the PETRA III synchrotron. Robust and high-quality PDFs can be obtained from films as thin as 3 nm and atomistic modelling of the PDFs with a time resolution of 0.5 s is possible. In this way, it was found that a polycrystalline Pt thin film deposits with random orientation at 8 W and 2 × 10−2 mbar at room temperature. From the PDF it was found that the coherent-scattering domains grow with time. While the first layers are formed with a small tensile strain this relaxes towards the bulk value with increasing film thickness.
Fixed-target serial oscillation crystallography at room temperature
Authors: Wierman Jennifer L. , Paré-Labrosse Olivier , Sarracini Antoine , Besaw Jessica E. , Cook Michael J. , Oghbaey Saeed , Daoud Hazem , Mehrabi Pedram , Kriksunov Irina , Kuo Anling , Schuller David J. , Smith Scott , Ernst Oliver P. , Szebenyi Doletha M. E. , Gruner Sol M. , Miller R. J. Dwayne , Finke Aaron D.
Published: February 2019

A fixed-target approach to high-throughput room-temperature serial synchrotron crystallography with oscillation is described. Patterned silicon chips with microwells provide high crystal-loading density with an extremely high hit rate. The microfocus, undulator-fed beamline at CHESS, which has compound refractive optics and a fast-framing detector, was built and optimized for this experiment. The high-throughput oscillation method described here collects 1–5° of data per crystal at room temperature with fast (10° s−1) oscillation rates and translation times, giving a crystal-data collection rate of 2.5 Hz. Partial datasets collected by the oscillation method at a storage-ring source provide more complete data per crystal than still images, dramatically lowering the total number of crystals needed for a complete dataset suitable for structure solution and refinement – up to two orders of magnitude fewer being required. Thus, this method is particularly well suited to instances where crystal quantities are low. It is demonstrated, through comparison of first and last oscillation images of two systems, that dose and the effects of radiation damage can be minimized through fast rotation and low angular sweeps for each crystal.
Crystal structure, Hirshfeld surface analysis and DFT study of (2Z)-2-(4-fluorobenzylidene)-4-(prop-2-yn-1-yl)-3,4-dihydro-2H-1,4-benzothiazin-3-one
Authors: Hni Brahim , Sebbar Nada Kheira , Hökelek Tuncer , Ouzidan Younes , Moussaif Ahmed , Mague Joel T. , Essassi El Mokhtar
Published: February 2019

The title compound, C18H12FNOS, is built up from a 4-fluorobenzylidene moiety and a dihydrobenzothiazine unit with a propynyl substituent, with the heterocyclic portion of the dihydrobenzothiazine unit adopting a shallow boat conformation with the propynyl substituent nearly perpendicular to it. The two benzene rings are oriented at a dihedral angle of 43.02 (6)°. In the crystal, C—HFlurphen...FFlurphen (Flurphen = fluorophenyl) hydrogen bonds link the molecules into inversion dimers, enclosing R
2
2(8) ring motifs, with the dimers forming oblique stacks along the a-axis direction. Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H...H (33.9%), H...C/C...H (26.7%), H...F/F...H (10.9%) and C...C (10.6%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. Density functional theory (DFT) optimized structures at the B3LYP/6–311 G(d,p) level are compared with the experimentally determined molecular structure in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap.