bluuebunny/crossref_metadata_2025 huggingface dataset:
A quantitative map of human Condensins provides new insights into mitotic chromosome architecture
Authors: Walther Nike , Hossain M. Julius , Politi Antonio Z. , Koch Birgit , Kueblbeck Moritz , Ødegård-Fougner Øyvind , Lampe Marko , Ellenberg Jan
Published: April 2018

The two Condensin complexes in human cells are essential for mitotic chromosome structure. We used homozygous genome editing to fluorescently tag Condensin I and II subunits and mapped their absolute abundance, spacing, and dynamic localization during mitosis by fluorescence correlation spectroscopy (FSC)–calibrated live-cell imaging and superresolution microscopy. Although ∼35,000 Condensin II complexes are stably bound to chromosomes throughout mitosis, ∼195,000 Condensin I complexes dynamically bind in two steps: prometaphase and early anaphase. The two Condensins rarely colocalize at the chromatid axis, where Condensin II is centrally confined, but Condensin I reaches ∼50% of the chromatid diameter from its center. Based on our comprehensive quantitative data, we propose a three-step hierarchical loop model of mitotic chromosome compaction: Condensin II initially fixes loops of a maximum size of ∼450 kb at the chromatid axis, whose size is then reduced by Condensin I binding to ∼90 kb in prometaphase and ∼70 kb in anaphase, achieving maximum chromosome compaction upon sister chromatid segregation.
An Axiomatic Theory of Inductive Inference
Authors: Pomatto Luciano , Sandroni Alvaro
Published: April 2018

This article develops an axiomatic theory of induction that speaks to the recent debate on Bayesian orgulity. It shows the exact principles associated with the belief that data can corroborate universal laws. We identify two types of disbelief about induction: skepticism that the existence of universal laws of nature can be determined empirically, and skepticism that the true law of nature, if it exists, can be successfully identified. We formalize and characterize these two dispositions toward induction by introducing novel axioms for subjective probabilities. We also relate these dispositions to the (controversial) axiom of σ-additivity.
The Childhood Role in Development of Primary Hypertension
Authors: Falkner Bonita
Published: April 2018

Primary hypertension is not just an adult disorder. Current US population data on children and adolescents demonstrate a prevalence of elevated blood pressure (BP) and hypertension combined of over 10%. Recent reports from prospective cohort studies describe an association of high BP in childhood with hypertension in young adulthood. Excess adiposity is strongly associated with higher BP in childhood and increases risk for hypertension in adulthood. In addition to overweight/obesity, other exposures that raise the risk for high BP include low birthweight, dietary sodium, and stress. Using intermediate markers of cardiovascular injury, studies on hypertensive children report findings of cardiac hypertrophy, vascular stiffness, and early atherosclerotic changes. Impaired cognitive function has also been demonstrated in hypertensive children. Recent advances in clinical and translational research support the concept that the evolution of primary hypertension begins in childhood.
Force Modulating Tissue Bridges for Reduction of Tension and Scar: Finite Element and Image Analysis of Preclinical Incisional and Nonincisional Models
Authors: Kazmer David O , Eaves Felmont F
Published: April 2018

Background

Force modulating tissue bridges (FMTB) represent a new class of combined wound closure and scar reduction device designed to optimize the tension milieu of the healing wound.

Objectives

Engineering analysis and testing in both intact skin and incisional models was undertaken to assess changes in tissue tension associated with device placement and compare to standard suture closure.

Methods

Nonlinear, large deformation finite element analyses (FEA) were performed to compare the strains applied to tissues with sutures and FMTB. In the incisional model, a freshly euthanized Yorkshire pig received full thickness cutaneous incisions followed by alternating closure with sutures and FMTBs. FMTBs were also applied to intact adult human skin after pattern application. In each of the experiments, photographs were taken preapplication and postapplication and the resultant dot grid pattern changes were analyzed by image recognition algorithms to calculate applied strains.

Results

FEA indicate compressive stresses at the tissue:suture interface on the order of 4000 mmHg and 20 mmHg at the tissue:FMTB interface. Strain analysis of the sutures and FMTBs applied in the incisional lab testing indicated imposed strains on the tissues of around 40%, with FMTBs providing 10% more compression than sutures and 25% more compression between the applied devices (P = 0.000057). In the longitudinal study, tension reduction of the order of 30% was maintained over the treatment period of 10 days to verify device efficacy.

Conclusions

FMTBs provide wounds while simultaneously modulating skin tension and thus have the potential to improve scar appearance.
Breast Implant-Associated Bilateral B-Cell Lymphoma
Authors: Chen Vivi W , Hoang Don , Clancy Sharon
Published: April 2018

Lymphomas associated with implants are predominantly of T-cell type—with anaplastic large cell lymphoma (ALCL) being most reported. That said, to date, 6 cases of B-cell lymphoma associated with breast implants have been reported. All cases exhibited unilateral breast involvement. Here, the authors report a case of low-grade B-cell lymphoma occurring bilaterally in a 34-year-old woman with a history of Poly Implant Prosthese silicone implants at age 20, T-cell angioimmunoblastic lymphoma, and subsequent myeloablative double cord blood transplantation. Lymphoma cells were positive for CD20, CD5, BCL-2, CD21, CD23, IgD, IgM, with very low Ki-67 of 1%. Nevertheless, cases of ALCL associated with breast implants are rare but much more documented in the literature than B-cell lymphomas associated with breast implants, as in this patient. Identification of a relationship between breast cancer and silicone is still ongoing in the literature, with long-term clinical follow up required. More research will be necessary to fully characterize the occurrence, course, and association of this disease with breast implants in order to properly guide diagnosis and management.

Level of Evidence: 5
A full general relativistic neutrino radiation-hydrodynamics simulation of a collapsing very massive star and the formation of a black hole
Authors: Kuroda Takami , Kotake Kei , Takiwaki Tomoya , Thielemann Friedrich-Karl
Published: April 2018

We study the final fate of a very massive star by performing full general relativistic (GR), three-dimensional (3D) simulation with three-flavour multi-energy neutrino transport. Utilizing a 70 solar mass zero-metallicity progenitor, we self-consistently follow the radiation-hydrodynamics from the onset of gravitational core-collapse until the second collapse of the proto-neutron star (PNS), leading to black hole (BH) formation. Our results show that the BH formation occurs at a post-bounce time of Tpb ∼ 300 ms for the 70 M⊙ star. This is significantly earlier than those in the literature where lower mass progenitors were employed. At a few ∼10 ms before BH formation, we find that the stalled bounce shock is revived by intense neutrino heating from the very hot PNS, which is aided by violent convection behind the shock. In the context of 3D-GR core-collapse modelling with multi-energy neutrino transport, our numerical results present the first evidence to validate a fallback BH formation scenario of the 70 M⊙ star.
Epidemiology of Symptomatic Chiari Malformation in Tatarstan: Regional and Ethnic Differences in Prevalence
Authors: Bogdanov Enver I , Faizutdinova Aisylu T , Mendelevich Elena G , Sozinov Alexey S , Heiss John D
Published: April 2018

BACKGROUND

Epidemiology can assess the effect of Chiari I malformation (CM1) on the neurological health of a population and evaluate factors influencing CM1 development.

OBJECTIVE

To analyze the regional and ethnic differences in the prevalence of CM1.

METHODS

The population of the Republic of Tatarstan (RT) in the Russian Federation was evaluated for patients with CM1 symptoms over an 11-yr period. Typical symptoms of CM1 were found in 868 patients. Data from neurological examination and magnetic resonance imaging (MRI) measurement of posterior cranial fossa structures were analyzed.

RESULTS

MRI evidence of CM1, defined as cerebellar tonsils lying at least 5 mm inferior to the foramen magnum, was found in 67% of symptomatic patients. Another 33% of symptomatic patients had 2 to 4 mm of tonsillar ectopia, which we defined as “borderline Chiari malformation type 1 (bCM1).” The period prevalence in the entire RT for symptomatic CM1 was 20:100 000; for bCM1 was 10:100 000; and for CM1 and bCM1 together was 30:100 000. Prevalence of patients with CM1 symptoms was greater in the northern than southern districts of Tatarstan, due to a high prevalence (413:100 000) of CM1 in the Baltasy region in one of the northern districts.

CONCLUSION

One-third of patients with typical symptoms of CM1 had less than 5 mm of tonsillar ectopia (bCM1). Assessments of the health impact of CM1-type symptoms on a patient population should include the bCM1 patient group. A regional disease cluster of patients with Chiari malformation was found in Baltasy district of RT and needs further study.
Influences of the Menstrual Phase on Cortisol Response to Stress in Nicotine Dependent Women: A Preliminary Examination
Authors: Nakajima Motohiro , Allen Sharon , al’Absi Mustafa
Published: April 2018

Introduction

Evidence indicates that menstrual cycle phase plays a role in smoking withdrawal symptoms and craving. Stress increases these symptoms. Whether the stress regulatory mechanism is associated with menstrual phase and withdrawal symptoms is not well understood.

Methods

Thirty-seven female smokers and 16 female nonsmokers were asked to complete a laboratory session. In each group, approximately half of the participants were tested when they were in the follicular phase and the other half was tested in the luteal phase. The session included resting baseline, stress, and recovery periods. Saliva samples for the measurement of cortisol and subjective measures of craving and withdrawal symptoms were collected at the end of each period.

Results

A series of repeated measures analysis of covariance found a significant smoking group × menstrual phase × sampling time interaction in cortisol levels (p < .05). Follow-up analyses indicated a reduced cortisol stress response in the luteal group relative to the follicular group in smokers (p < .02). This difference was not found in nonsmokers.

Conclusions

Menstrual cycle phase is related to hormonal stress response and smoking withdrawal symptomatology.

Implications

We show influences of the menstrual cycle phase on stress response among smokers. This is demonstrated by a reduced cortisol response to stress in the luteal group relative to the follicular group among smokers. This menstrual phase difference was not found in nonsmokers.
Use of genomics to design a diagnostic assay to discriminate between Streptococcus pneumoniae and Streptococcus pseudopneumoniae
Authors: Croxen Matthew A. , Lee Tracy D. , Azana Robert , Hoang Linda M.
Published: April 2018

Distinuishing the species of mitis group streptococci is challenging due to ambiguous phenotypic characteristics and high degree of genetic similarity. This has been particularly true for resolving atypical Streptococcus pneumoniae and Streptococcus pseudopneumoniae. We used phylogenetic clustering to demonstrate specific and separate clades for both S. pneumoniae and S. pseudopneumoniae genomes. The genomes that clustered within these defined clades were used to extract species-specific genes from the pan-genome. The S. pneumoniae marker was detected in 8027 out of 8051 (>99.7 %) S. pneumoniae genomes. The S. pseudopneumoniae marker was specific for all genomes that clustered in the S. pseudopneumoniae clade, including unresolved species of the genus Streptococcus sequenced by the BC Centre for Disease Control Public Health Laboratory that previously could not be distinguished by other methods. Other than the presence of the S. pseudopneumoniae marker in six of 8051 (<0.08 %) S. pneumoniae genomes, both the S. pneumoniae and S. pseudopneumoniae markers showed little to no detectable cross-reactivity to the genomes of any other species of the genus Streptococcus or to a panel of over 46 000 genomes from viral, fungal, bacterial pathogens and microbiota commonly found in the respiratory tract. A real-time PCR assay was designed targeting these two markers. Genomics provides a useful technique for PCR assay design and development.
Heritability and genome-wide association study of diffusing capacity of the lung
Authors: Terzikhan Natalie , Sun Fangui , Verhamme Fien M. , Adams Hieab H.H. , Loth Daan , Bracke Ken R. , Stricker Bruno H. C. , Lahousse Lies , Dupuis Josée , Brusselle Guy G. , O’Connor George T.
Published: April 2018

Background

Although several genome wide association studies (GWAS) have investigated the genetics of pulmonary ventilatory function, little is known about the genetic factors that influence gas exchange.

Aim

To investigate the heritability of, and genetic variants associated with the diffusing capacity of the lung.

Methods

GWAS was performed on diffusing capacity, measured by carbon monoxide uptake (DLCO) and per alveolar volume (DLCO/VA) using the single-breath technique, in 8,372 individuals from two population-based cohort studies, the Rotterdam Study and the Framingham Heart Study. Heritability was estimated in related (n=6,246) and unrelated (n=3,286) individuals.

Results

Heritability of DLCO and DLCO/VA ranged between 23% and 28% in unrelated individuals and between 45% and 49% in related individuals. Meta-analysis identified a genetic variant in GPR126 that is significantly associated with DLCO/VA. Gene expression analysis of GPR126 in human lung tissue revealed a decreased expression in patients with COPD and subjects with decreased DLCO/VA.

Conclusion

DLCO and DLCO/VA are heritable traits, with a considerable proportion of variance explained by genetics. A functional variant in GPR126 gene region was significantly associated with DLCO/VA. Pulmonary GPR126 expression was decreased in patients with COPD.
Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death
Authors: Rausch Rebecca L. , Syc-Mazurek Stephanie B. , Fernandes Kimberly A. , Wilson Michael P. , Libby Richard T.
Published: April 2018

The mitogen activated protein kinase (MAPK) pathway has been shown to be involved in both neurodevelopment and neurodegeneration. c-Jun N-terminal kinase (JNK), a MAPK shown to be important in retinal development and after optic nerve crush injury, is regulated by two upstream kinases: MKK4 and MKK7. The specific requirements of MKK4 and MKK7 in retinal development and retinal ganglion cell (RGC) death after axonal injury, however, are currently undefined. Optic nerve injury is an important insult in many neurologic conditions including traumatic, ischemic, inflammatory, and glaucomatous optic neuropathies. Mice deficient in Mkk4, Mkk7, and both Mkk4 and Mkk7 were generated. Immunohistochemistry was used to study the distribution and structure of retinal cell types and to assess RGC survival after optic nerve injury (mechanical controlled optic nerve crush; CONC). Adult Mkk4 and Mkk7 deficient retinas had all retinal cell types. With the exception of small areas of lamination defects with photoreceptors in Mkk4 deficient mice, the retinas of both mutants were grossly normal. Deficiency of Mkk4 or Mkk7 reduced JNK signaling after axonal injury in RGCs. Mkk4 and Mkk7 deficient retinas had a significantly greater percentage of surviving RGCs 35 days after CONC as compared to wildtype controls (Mkk4: 51.5%, Mkk7: 29.1% WT: 15.2%; p<0.001). Combined deficiency of Mkk4 and Mkk7 caused failure of optic nerve formation, irregular retinal axonal trajectories, disruption of retinal lamination, clumping of RGC cell bodies, and dendritic fasciculation of dopaminergic amacrine cells. These results suggest that MKK4 and MKK7 may serve redundant and unique roles in molecular signaling important for retinal development and injury response following axonal insult.
Octopaminergic neurons have multiple targets inDrosophilalarval mushroom body calyx and regulate behavioral odor discrimination
Authors: Hilary Wong J Y , Wan Bo Angela , Bland Tom , Montagnese Marcella , McLachlan Alex , O’Kane Cahir J , Zhang Shuo Wei , Masuda-Nakagawa Liria M
Published: April 2018

Discrimination of sensory signals is essential for an organism to form and retrieve memories of relevance in a given behavioural context. Sensory representations are modified dynamically by changes in behavioral state, facilitating context-dependent selection of behavior, through signals carried by noradrenergic input in mammals, or octopamine (OA) in insects. To understand the circuit mechanisms of this signaling, we characterized the function of two OA neurons, sVUM1 neurons, that originate in the subesophageal zone (SEZ) and target the input region of the memory center, the mushroom body (MB) calyx, in larvalDrosophila. We find that sVUM1 neurons target multiple neurons, including olfactory projection neurons (PNs), the inhibitory neuron APL, and a pair of extrinsic output neurons, but relatively few mushroom body intrinsic neurons, Kenyon cells. PN terminals carried the OA receptor Oamb, aDrosophilaα1-adrenergic receptor ortholog. Using an odor discrimination learning paradigm, we showed that optogenetic activation of OA neurons compromised discrimination of similar odors but not learning ability. Our results suggest that sVUM1 neurons modify odor representations via multiple extrinsic inputs at the sensory input area to the MB olfactory learning circuit.
Unique mapping of structural and functional connectivity on cognition
Authors: Zimmermann J. , Griffiths J.G. , McIntosh A.R.
Published: April 2018

The unique mapping of structural and functional brain connectivity (SC, FC) on cognition is currently not well understood. It is not clear whether cognition is mapped via a global connectome pattern or instead is underpinned by several sets of distributed connectivity patterns. Moreover, we also do not know whether the pattern of SC and of FC that underlie cognition are overlapping or distinct. Here, we study the relationship between SC and FC and an array of psychological tasks in 609 subjects from the Human Connectome Project (HCP). We identified several sets of connections that each uniquely map onto different aspects of cognitive function. We found a small number of distributed SC and a larger set of cortico-cortical and cortico-subcortical FC that express this association. Importantly, SC and FC each show unique and distinct patterns of variance across subjects and differential relationships to cognition. The results suggest that a complete understanding of connectome underpinnings of cognition calls for a combination of the two modalities.

Significance Statement

Structural connectivity (SC), the physical white-matter inter-regional pathways in the brain, and functional connectivity (FC), the temporal co-activations between activity of brain regions, have each been studied extensively. Little is known, however, about the distribution of variance in connections as they relate to cognition. Here, in a large sample of subjects (N = 609), we showed that two sets of brain-behavioural patterns capture the correlations between SC, and FC with a wide range of cognitive tasks, respectively. These brain-behavioural patterns reveal distinct sets of connections within the SC and the FC network and provide new evidence that SC and FC each provide unique information for cognition.
Chromosomally Encoded mcr-5 in Colistin Non-susceptible Pseudomonas aeruginosa
Authors: Snesrud Erik , Maybank Rosslyn , Kwak Yoon I. , Jones Anthony R. , Hinkle Mary K. , Gann Patrick Mc
Published: April 2018

Whole genome sequencing (WGS) of historical Pseudomonas aeruginosa clinical isolates identified a chromosomal copy of mcr-5 within a Tn3-like transposon in P. aeruginosa MRSN 12280. The isolate was non-susceptible to colistin by broth microdilution and genome analysis revealed no mutations known to confer colistin resistance. To the best of our knowledge this is the first report of mcr in colistin non-susceptible P. aeruginosa.
Congenital glaucoma with anterior segment dysgenesis in individuals with biallelicCPAMD8variants
Authors: Siggs Owen M , Souzeau Emmanuelle , Taranath Deepa A , Zhou Tiger , Dubowsky Andrew , Javadiyan Shari , Chappell Angela , Narita Andrew , Elder James E , Pater John , Ruddle Jonathan B , Smith James EH , Kearns Lisa S , Staffieri Sandra E , Hewitt Alex W , Mackey David A , Burdon Kathryn P , Craig Jamie E
Published: April 2018

Purpose

Congenital glaucoma is a significant cause of irreversible blindness. In some instances glaucoma is associated with developmental abnormalities of the ocular anterior segment, which can impair drainage of aqueous humor, leading to an increase in intraocular pressure.

Methods

Genome sequencing was performed on a parent-proband congenital glaucoma trio, with exome sequencing of 79 additional individuals with suspected primary congenital glaucoma.

Results

We describe a unique ocular anterior segment dysgenesis associated with congenital glaucoma in four individuals from three unrelated families. In each case, disease was associated with compound heterozygous variants inCPAMD8, a gene of unknown function recently associated with ocular anterior segment dysgenesis, myopia, and ectopia lentis.CPAMD8expression was highest in neural crest-derived tissues of the adult anterior segment, suggesting thatCPAMD8variation may cause malformation of key drainage structures and the development of high intraocular pressure and glaucoma.

Conclusions

This study reveals a unique genetic cause of childhood glaucoma, and expands the phenotypic spectrum ofCPAMD8-associated ocular disease.
Cancer modeling by Transgene Electroporation in Adult Zebrafish (TEAZ)
Authors: Callahan Scott J. , Tepan Stephanie , Zhang Yan M , Lindsay Helen , Burger Alexa , Campbell Nathaniel R. , Kim Isabella S. , Hollmann Travis J. , Studer Lorenz , Mosimann Christian , White Richard M.
Published: April 2018

Transgenic animals are invaluable for modeling cancer genomics, but often require complex crosses of multiple germline alleles to obtain the desired combinations. Zebrafish models have advantages in that transgenes can be rapidly tested by mosaic expression, but these typically lack spatial and temporal control of tumor onset, which limits their utility for the study of tumor progression and metastasis. To overcome these limitations, we have developed a method called Transgene Electroporation in Adult Zebrafish (TEAZ). TEAZ can deliver DNA constructs with promoter elements of interest to drive fluorophores, oncogenes, or CRISPR-Cas9-based mutagenic cassettes in specific cell types. Using TEAZ, we created a highly aggressive melanoma model by expression of BRAFV600Ein spatially constrained melanocytes in the context of p53 deficiency and Cas9-mediated inactivation of Rb1. Unlike prior models that take ~4 months to develop, we found that TEAZ leads to tumor onset in ~7 weeks and these develop in fully immunocompetent animals. As the resulting tumors initiated at highly defined locations, we could track their progression via fluorescence and documented deep invasion into tissues and metastatic deposits. TEAZ can be deployed to other tissues and cell types such as the heart with the use of suitable transgenic promoters. The versatility of TEAZ makes it widely accessible for rapid modeling of somatic gene alterations and cancer progression at a scale not achievable in other in vivo systems.
sFlt-1 commutes unfolded protein response into endoplasmic reticulum stress in trophoblast cells in preeclamptic pregnancies
Authors: Mochan Sankat , Dhingra Manoj Kumar , Gupta Sunil Kumar , saxena Shobhit , Arora Pallavi , Rani Neerja , Sharma Arundhati , Luthra Kalpana , Dwivedi Sadanand , Bhatla Neerja , Kumar Rani , Dhingra Renu
Published: April 2018

Preeclampsia (PE) and its subtypes (early and late onset) are serious concerns all across the globe affecting about 8% of total pregnancies and accounts for approximately 60,000 deaths annually with a predominance in developing under-developed and countries. The two-stage model in the progression of this disease, deficient spiral artery remodelling and an imbalance between angiogenic (VEGF) and anti-antigenic factor(s) (sFlt-1) are well established facts pertaining to this disease. The presence of increased sFlt-1, high oxidative stress and Endoplasmic reticulum stress (ER stress) have been proposed in preeclamptic pregnancies. Recently, the role of endoplasmic reticulum stress in the onset of the variant forms of PE highlighted a new window to explore further. In our previous studies, we demonstrated that sFlt-1 can induce apoptosis and oxidative stress in trophoblast cells. However the role of sFlt-1, in inducing ER stress is not known so far. In the present study, we for the first time demonstrated significant ER stress in the placental cells (BeWo Cells) (in vitro) when exposed to sera from preeclamptic pregnancies having increased concentration of sFlt-1. The expression of ER stress markers (GRP78, eIF2α, XBP1, ATF6 and CHOP) at both transcript and protein levels were compared (between preeclamptic and normotensive non-proteinuric women) at three different time points (8h, 14h and 24hrs), analyzed and found to be significant (p<0.05).

Conclusion

Our results suggested that sFlt-1, released from placental cells in preeclampsia may be one of the various factors having potential to induce endoplasmic reticulum stress in BeWo cells.
Learning recurrent dynamics in spiking networks
Authors: Kim Christopher M. , Chow Carson C.
Published: April 2018

Spiking activity of neurons engaged in learning and performing a task show complex spatiotemporal dynamics. While the output of recurrent network models can learn to perform various tasks, the possible range of recurrent dynamics that emerge after learning remains unknown. Here we show that modifying the recurrent connectivity with a recursive least squares algorithm provides sufficient flexibility for synaptic and spiking rate dynamics of spiking networks to produce a wide range of spatiotemporal activity. We apply the training method to learn arbitrary firing patterns, stabilize irregular spiking activity of a balanced network, and reproduce the heterogeneous spiking rate patterns of cortical neurons engaged in motor planning and movement. We identify sufficient conditions for successful learning, characterize two types of learning errors, and assess the network capacity. Our findings show that synaptically-coupled recurrent spiking networks possess a vast computational capability that can support the diverse activity patterns in the brain.
Ecological assessment of the River Nile around Gizert El-Warrak by Phytoplankton and macroinvertebrates assemblages
Authors: Mahmoud Kadria M.A. , Sayed Sara S.M. , Habib Mohamed R.
Published: April 2018

Biological assessment is considered a useful tool for assessing the ecological status of the aquatic ecosystems. Therefore, the goal of the present study was to use phytoplankton and macroinvertebrates as biological tools for ecological assessment of the River Nile around Gizert El-Warrak. A total of 33 phytoplankton species identified in the studied stations; these include 16 species of Chlorophyta, 5 species of Cyanophyta and 12 species of Bacillariophyta. All investigated stations characterized by high organic pollution according to Palmer′s index. Trophic state index showed a hyper-eutrophic status in stations S1, S2, S4, S6 and S8 and an eutrophic status in stations S3, S5 and S7.Gastropoda and Oligochaeta were the most dominant of macroinvertebrates taxa recorded 50.8 and 24.6%, respectively. Diversity Index (H′) ranged (1.14 – 2) which indicated that the structure of macroinvertebrates habitat was poor. Also, Evenness Index (J) ranged (0.016 – 0.043) which indicated that individuals were not distributed equally. The values of biotic index depending on macroinvertebrates categories showed that the River Nile’s water quality is fairly poor with significant organic pollution.

Summary statement

Bioassessment based on non-taxonomic measurements of algae and biotic indices of macroinvertebrates may be considered as vital methods that reflect disturbances in aquatic systems for both short-term and long-term.
Typical visual-field locations facilitate access to awareness for everyday objects
Authors: Kaiser Daniel , Cichy Radoslaw M.
Published: April 2018

In real-world vision, humans are constantly confronted with complex environments that contain a multitude of objects. These environments are spatially structured, so that objects have different likelihoods of appearing in specific parts of the visual space. Our massive experience with such positional regularities prompts the hypothesis that the processing of individual objects varies in efficiency across the visual field: when objects are encountered in their typical locations (e.g., we are used to seeing lamps in the upper visual field and carpets in the lower visual field), they should be more efficiently perceived than when they are encountered in atypical locations (e.g., a lamp in the lower visual field and a carpet in the upper visual field). Here, we provide evidence for this hypothesis by showing that typical positioning facilitates an object’s access to awareness. In two continuous flash suppression experiments, objects more efficiently overcame inter-ocular suppression when they were presented in visual-field locations that matched their typical locations in the environment, as compared to non-typical locations. This finding suggests that through extensive experience the visual system has adapted to the statistics of the environment. This adaptation may be particularly useful for rapid object individuation in natural scenes.
Recombination rate variation shapes barriers to introgression across butterfly genomes
Authors: Martin Simon H. , Davey John W. , Salazar Camilo , Jiggins Chris D.
Published: April 2018

Hybridisation and introgression can dramatically alter the relationships among groups of species, leading to phylogenetic discordance across the genome and between populations. Introgression can also erode species differences over time, but selection against introgression at certain loci acts to maintain post-mating species barriers. Theory predicts that species barriers made up of many loci throughout the genome should lead to a broad correlation between introgression and recombination rate, which determines the extent to which selection on deleterious foreign alleles will affect neutral alleles at physically linked loci. Here we describe the variation in genealogical relationships across the genome among three species ofHeliconiusbutterflies:H. melpomene,H. cydnoandH. timareta, using whole genomes of 92 individuals, and ask whether this variation can be explained by heterogeneous barriers to introgression. We find that species relationships vary predictably at the chromosomal scale. By quantifying recombination rate and admixture proportions, we then show that rates of introgression are predicted by variation in recombination rate. This implies that species barriers are highly polygenic, with selection acting against introgressed alleles across most of the genome. In addition, long chromosomes, which have lower recombination rates, produce stronger barriers on average than short chromosomes. Finally, we find a consistent difference between two species pairs on either side of the Andes, which suggests differences in the architecture of the species barriers. Our findings illustrate how the combined effects of hybridisation, recombination and natural selection, acting at multitudes of loci over long periods, can dramatically sculpt the phylogenetic relationships among species.
Travelling waves in somitogenesis: collective cellular properties emerge from time-delayed juxtacrine oscillation coupling
Authors: Tomka Tomas , Iber Dagmar , Boareto Marcelo
Published: April 2018

The sculpturing of the vertebrate body plan into segments begins with the sequential formation of somites in the presomitic mesoderm (PSM). The rhythmicity of this process is controlled by travelling waves of gene expression. These kinetic waves emerge from coupled cellular oscillators and sweep across the PSM. In zebrafish, the oscillations are driven by autorepression ofhergenes and are synchronized via Notch signalling. Mathematical modelling has played an important role in explaining how collective properties emerge from the molecular interactions. Increasingly more quantitative experimental data permits the validation of those mathematical models, yet leads to increasingly more complex model formulations that hamper an intuitive understanding of the underlying mechanisms. Here, we review previous efforts, and design a mechanistic model of theher1oscillator, which represents the experimentally viableher7;hes6double mutant. This genetically simplified system is ideally suited to conceptually recapitulate oscillatory entrainment and travelling wave formation, and to highlight open questions. It shows that three key parameters, the autorepression delay, the juxtacrine coupling delay, and the coupling strength, are sufficient to understand the emergence of the collective period, the collective amplitude, and the synchronization of neighbouring Her1 oscillators. Moreover, two spatiotemporal time delay gradients, in the autorepression and in the juxtacrine signalling, are required to explain the collective oscillatory dynamics and synchrony of PSM cells. The highlighted developmental principles likely apply more generally to other developmental processes, including neurogenesis and angiogenesis.
TheDrosophilamitochondrial citrate carrier regulates L-2-hydroxyglutarate accumulation by coupling the tricarboxylic acid cycle with glycolysis
Authors: Li Hongde , Hurlburt Alexander J. , Tennessen Jason M.
Published: April 2018

The oncometabolites D- and L-2-hydroxyglutarate (2HG) broadly interfere with cellular metabolism, physiology, and gene expression. A key regulator of 2HG metabolism is the mitochondrial citrate carrier (CIC), which, when mutated, promotes excess D-/L-2HG accumulation. The mechanism by which CIC influences 2HG levels, however, remains unknown. Here we studied theDrosophilagenescheggia(sea), which encodes the fly CIC homolog, to explore the mechanisms linking mitochondrial citrate efflux to L-2HG metabolism. Our findings demonstrate that decreasedDrosophilaCIC activity results in elevated glucose catabolism and increased lactate production, thereby creating a metabolic environment that inhibits L-2HG degradation.
Whole-brain white matter organization, intelligence, and educational attainment
Authors: Bathelt J. , Scerif G. , Nobre K. , Astle D.E.
Published: April 2018

General cognitive ability, sometimes referred to as intelligence, is associated with educational attainment throughout childhood. Most studies that have explored the neural correlates of intelligence in childhood focus on individual brain regions. This analytical approach is designed to identify restricted sets of voxels that overlap across participants. By contrast, we explored the relationship between white matter connectome organization, intelligence, and education. In both a sample of typically-developing children (N=63) and a sample of struggling learners (N=139), the white matter connectome efficiency was strongly associated with intelligence and educational attainment. Further, intelligence mediated the relationship between connectome efficiency and educational attainment. In contrast, a canonical voxel-wise analysis failed to identify any significant relationships. The results emphasize the importance of distributed brain network properties for cognitive or educational ability in childhood. Our findings are interpreted in the context of a developmental theory, which emphasizes the interaction between different subsystems over developmental time.
A novel emotional and cognitive approach to welfare phenotyping in rainbow trout exposed to poor water quality
Authors: Colson V , Mure A , Valotaire C , Calvez JM Le , Goardon L , Labbé L , Leguen I , Prunet P
Published: April 2018

Recent scientific evidence for fish sentience has stressed the need for novel sentience-based detection tools of fish welfare impairment in commercial farms. In order to mimic a well-characterised stress situation, rainbow trout (Oncorhynchus mykiss) were exposed to poor water quality (hypoxia combined with high ammonia level) for three weeks (stressed group, S) and compared to a non-stressed control group (NS). After a return to water quality standard, emotional responses were assessed in fish subjected to two potentially threatening situations: (i) social isolation in a novel environment and (ii) human presence. In addition, we used an appetitive-conditioning paradigm to determine whether previous chronic deterioration of water quality disturbs cognitive abilities in fish. Spontaneous behaviour in the tanks was also recorded during the environmental challenge as a reference for fish activity. We observed that in S fish, plasma cortisol levels were increased before and after social isolation in a novel environment compared to the plasma cortisol levels in the NS group, despite the absence of a behavioural difference between the two groups. Under deteriorated water quality, fish locomotor activity was globally reduced and this reduction was correlated to increased shoaling behaviour. Farmers can use these first behavioural modifications as a sentinel detector for fish welfare impairment. More importantly, we demonstrated that reactivity to a human presence in a home-environment and food-anticipatory behaviour were both inhibited in the S group. We consider that these two sentience-based tests are highly relevant for fish welfare assessment at the group level and are easy to use in the aquaculture industry.
Dynamic Extreme Aneuploidy (DEA) in the vegetable pathogen Phytophthora capsici sheds light on instant evolution and intractability
Authors: Hu Jian , Shrestha Sandesh , Zhou Yuxin , Liu Xili , Lamour Kurt
Published: April 2018

summary

Oomycete plant pathogens are notoriously difficult to control, and individual isolates are highly unstable; making routine research challenging. Sequencing reveals extreme aneuploidy for single-spore progeny of the vegetable pathogen Phytophthora capsici; a phenomenon dubbed Dynamic Extreme Aneuploidy (DEA). Although extreme, the aneuploidy appears to be moderately stable. A single sporulating plant lesion may produce an armada of genetically unique individuals and helps explain the rapid increase of advantageous alleles (e.g. drug resistance), mating type switches to allow sex and the widely observed phenomenon, loss of heterozygosity (LOH). Investigation of other oomycetes indicate this phenomenon is not unique to P. capsici.
The histone demethylase KDM5 is essential for larval growth inDrosophila
Authors: Drelon Coralie , Belalcazar Helen M. , Secombe Julie
Published: April 2018

Regulated gene expression is necessary for developmental and homeostatic processes. The KDM5 family of proteins are histone H3 lysine 4 demethylases that can regulate transcription through both demethylase-dependent and independent mechanisms. While loss and overexpression of KDM5 proteins are linked to intellectual disability and cancer, respectively, their normal developmental functions remain less characterized.Drosophila melanogasterprovides an ideal system to investigate KDM5 function, as it encodes a single ortholog in contrast to the four paralogs found in mammalian cells. To examine the consequences of complete loss of KDM5, we generated a null allele ofDrosophila kdm5, also known aslittle imaginal discs(lid), and show that it is essential for development. Animals lacking KDM5 die during late pupal development but show a dramatically delayed larval development that coincides with decreased proliferation and increased cell death in imaginal discs. Interestingly, this developmental delay is independent of the well-characterized Jumonji C (JmjC) domain-encoded histone demethylase activity and plant homedomain (PHD) motif-mediated chromatin binding activities of KDM5, suggesting key functions for less characterized domains. Consistent with the phenotypes observed, transcriptome analyses ofkdm5null mutant wing imaginal discs revealed the dysregulation of genes involved in several cellular processes, including cell cycle progression and DNA repair. Together, our data provide the first description of complete loss of KDM5 function in a metazoan and offer an invaluable tool for defining the biological activities of KDM5 family proteins.
C. elegansRAP-1 reinforces LET-60/Ras induction of cell fate
Authors: Rasmussen Neal R. , Dickinson Daniel J. , Reiner David J.
Published: April 2018

The notoriety of the small GTPase Ras as the most mutated oncoprotein has led to a well-characterized signaling network largely conserved across metazoans. Yet the role of its close relative Rap1 (Ras Proximal), which shares 100% identity between their core effector binding sequences, remains unclear. A long-standing controversy in the field is whether Rap1 also functions to activate the canonical Ras effector, the S/T kinase Raf. We used the developmentally simplerCaenorhabditis elegans, which lacks the extensive paralog redundancy of vertebrates, to examine the role of RAP-1 in two distinct LET-60/Ras-dependent cell fate patterning events: induction of 1˚ vulval precursor cell (VPC) fate and of the excretory duct cell. Fluorescently tagged endogenous RAP-1 is localized to plasma membranes and is expressed ubiquitously, with even expression levels across the VPCs. RAP-1 and its activating GEF PXF-1 function cell autonomously and are necessary for maximal induction of 1˚ VPCs. Critically, mutationally activated endogenous RAP-1 is sufficient both to induce ectopic 1˚s and duplicate excretory duct cells. Like endogenous RAP-1, before induction GFP expression from thepxf-1promoter is uniform across VPCs. However, unlike endogenous RAP-1, after induction GFP expression is increased in presumptive 1˚s and decreased in presumptive 2˚s. We conclude that RAP-1 is a positive regulator that promotes Ras-dependent inductive fate decisions. We hypothesize that PXF-1 activation of RAP-1 serves as a minor parallel input into the major LET-60/Ras signal through LIN-45/Raf.
Specific miRNA-GPCR networks regulate Sox9a/Sox9b activities to promote gonadal renewal in zebrafish
Authors: Du Xinlu , Guo Huiping , Zhang Ying , Wu Jiacheng , Li Minyou , Hua Xianxian , Yan Jizhou
Published: April 2018

Fertility and endocrine function rely on a tightly regulated synchronicity within the hypothalamic-pituitary gonadal (HPG) axis. FSH/cAMP/MAPK/ Sox9 axis signaling and its regulated specific miRNAs are thought to regulate vertebrate gonadal development and sex differentiation, and yet the regulatory networks are largely unknown. Here we construct small RNA and mRNA libraries from sexually matured ovary and testis of zebrafish to identify specific miRNA-target pairs. Integration of Targetscan prediction and in vivo induced gene expression highlight four specific miRNAs that conditionally target three G protein–coupled receptor (GPCR) x-Sox9 signaling genes, and implicate two regulatory circuits of miR430a-Sox9a in the testis and miR218a-Sox9b in the ovary. Co-injected Sox9a-miR430a mixture increases the proportion of spermatogonia but degenerates primary oocyte, while Sox9b-miR218a mixture induces renewal of ovarian follicles. Co-immunoprecipitation and mass-spectrometry analyses further reveal that miR430a and Sox9a synergistically activate testicular PKC/Rock1 signals while miR218a and Sox9b constrict ovary PKC/PI3K/Rock1 signaling. These results clarify specific miRNAs-GPCR regulatory networks of Sox9a/Sox9b switch, and also provide mechanistic insight into gonadal rejuvenation and plasticity.
Interferon Alpha and Kinase Inhibitor Nilotinib Increase Cell Adhesion and Tunneling Nanotubes in CML
Authors: Omsland Maria , Andresen Vibeke , Ayuda-Durán Pilar , Gullaksen Stein-Erik , Hovland Randi , Enserink Jorrit , Gjertsen Bjørn Tore
Published: April 2018

Summary statement

This study describes the effects of tyrosine kinase inhibitors on tunneling nanotube formation via increased adhesion through β-integrin in chronic myeloid leukemia cells.

The actin-containing cell-to-cell communicator tunneling nanotube (TNT) is involved in regulation of cell death threshold of leukemic cells, while the mechanism of TNT regulation is mostly unknown. We have investigated TNT formation and its response to treatment in chronic myeloid leukemia (CML) cells with the pathognomonic chimeric fusion kinase BCR-ABL1 after treatment with the tyrosine kinase inhibitor nilotinib and interferon-α. Bone marrow cells of chronic phase CML patients and the CML cell line Kcl-22 formed few or no TNTs. Nilotinib and interferon-α treatment induced TNT formation in Kcl-22 cells and were found to be linked to increased adherence to fibronectin coated surfaces by restoration of β1-integrin function. This suggests modulation of TNT cell-cell communication in CML as a novel mechanism in kinase inhibitor therapy of CML.
Heteromeric RNP assembly at LINEs controls lineage-specific RNA processing
Authors: Attig Jan , Agostini Federico , Gooding Clare , Singh Aarti , Chakrabarti Anob M , Haberman Nejc , Emmett Warren , Smith Christopher WJ , Luscombe Nicholas M , Ule Jernej
Published: April 2018

It is challenging for RNA processing machineries to select exons within long intronic regions. We find that intronic LINE repeat sequences (LINEs) contribute to this selection by recruiting dozens of RNA-binding proteins (RBPs). This includes MATR3, which promotes binding of PTBP1 to multivalent binding sites in LINEs. Both RBPs repress splicing and 3’ end processing within and around LINEs, as demonstrated in cultured human cells and mouse brain. Notably, repressive RBPs preferentially bind to evolutionarily young LINEs, which are confined to deep intronic regions. These RBPs insulate both LINEs and surrounding regions from RNA processing. Upon evolutionary divergence, gradual loss of insulation diversifies the roles of LINEs. Older LINEs are located closer to exons, are a common source of tissue-specific exons, and increasingly bind to RBPs that enhance RNA processing. Thus, LINEs are hubs for assembly of repressive RBPs, and contribute to evolution of new, lineage-specific transcripts in mammals.
Time-Periodically Driven Brownian Motion of Rigid Rod in one dimensional space
Authors: Shahzad M. A.
Published: April 2018

In this paper we discuss a simple theoretical approach, taken from the theory of stochastic processes to understand the basic phenomenology of protein translocation through a flickering pore. In this theoretical approach we investigate the dynamics of Brownian particle driven by a periodically driving force. This toy model is further extended by considering the Langevin equation with constants drift and time dependent variance. Using the first passage time theory we derived the formalism for probability density function to comprehend the translocation process occurring in the presence of fluctuating environment.