bluuebunny/crossref_metadata_2025 huggingface dataset:
Second-Stage Duration and Outcomes Among Women Who Labored After a Prior Cesarean Delivery
Authors: Hehir Mark P. , Rouse Dwight J. , Miller Russell S. , Ananth Cande V. , Wright Jason D. , Siddiq Zainab , D'Alton Mary E. , Friedman Alexander M.
Published: February 2018

OBJECTIVE:

To characterize probabilities of vaginal delivery based on second-stage duration along with maternal and neonatal risks for women undergoing labor after cesarean delivery.

METHODS:

This unplanned secondary analysis of the Maternal-Fetal Medicine Units Cesarean Registry, a prospective observational cohort, assessed outcomes in women with a prior uterine scar and included women with a previous cesarean delivery without prior vaginal delivery who reached the second stage of labor. The primary outcome was mode of delivery by second-stage duration. Secondary outcomes included assessment of individual adverse maternal (chorioamnionitis, atony, endometritis, hysterectomy, uterine rupture or dehiscence, and red cell transfusion) and neonatal (cord pH less than 7.10, Apgar score less than 6 at 5 minutes, neonatal intensive care unit admission, and ventilatory support) outcomes.

RESULTS:

Of 4,579 women with a previous cesarean delivery who reached the second stage of labor, 4,147 (90.6%) delivered vaginally. As second stage increased, successful vaginal delivery rates decreased: 97.3% at less than 1 hour (95% CI 96.6–97.9%), 91.5% at 1 to less than 2 hours (95% CI 89.8–93.1%), 78.5% at 2 to less than 3 hours (95% CI 74.5–82.1%), 62.3% at 3 to less than 4 hours (95% CI 55.2–69.1%), and 45.6% at 4 hours or greater (95% CI 37.7–53.7%). Risk of all adverse maternal outcomes increased with the length of the second stage. Specifically, risk of uterine rupture or dehiscence increased with second-stage length from less than 1 hour (0.7%), 1 to less than 2 hours (1.4%), 2 to less than 3 hours (1.5%), to 3 hours or greater (3.1%) (P<.001 for differential risk across the second stage). Risk of neonatal outcomes did not differ significantly by second-stage length.

CONCLUSION:

Although many women with a longer second stage (greater than 3 hours) will achieve successful vaginal delivery, these patients may be at increased risk for adverse maternal outcomes and should have close observation of fetal heart rate monitoring, maternal vital signs, and symptoms suggestive of uterine rupture or dehiscence.
Conjunctival Autograft Combined With Either Preoperative Mitomycin C Injection or Intraoperative Local Mitomycin C Over the Medial Rectus Muscle Tendon in Primary Pterygium Surgery
Authors: Lotfy Ayman , Gad Ahmed A. M. , Abdelrahman Ayman , Samir Ahmed , Abdulhalim Bahaa-Eldin Hasan
Published: February 2018

Purpose:

To evaluate and compare the recurrence rate and complications of conjunctival autograft (CAG) combined with preoperative mitomycin C (MMC) injection versus CAG with intraoperative local MMC over the medial rectus muscle tendon in primary pterygium.

Study Design:

Randomized prospective study.

Methods:

This study included 108 eyes of 108 patients with primary fleshy or growing pterygium. All patients were from rural areas and less than 50 years old. Fifty-three patients were treated with injection of 0.1 mL of 0.15 mg/mL MMC into the body of pterygium followed 1 day later by pterygium excision and CAG (group I), and 55 patients were treated with pterygium excision and local application of 0.2 mg/mL MMC for 2 min over the medial rectus tendon followed by CAG (group II). The minimum follow-up period was 18 months.

Results:

Two patients from group I and one patient from group II did not complete the follow-up period and were excluded. There were no statistically significant differences between the two groups regarding age, sex, laterality, or follow-up period. Recurrence occurred in 2 eyes in group I (3.92%) and 1 eye in group II (1.85%); (P=0.52). All recurrences occurred in male patients of less than 30 years of age. No significant complications were encountered in both groups.

Conclusions:

Both preoperative MMC injection followed 1 day later by pterygium excision with CAG, and pterygium excision and intraoperative local application of MMC on the medial rectus tendon are successful in treating primary pterygium with low recurrence rate and few complications.
High-Grade Conventional Osteosarcoma of the Mandible Associated With P53 Germline Mutation
Authors: Ginat Daniel , Schulte Jefree , Gooi Zhen , Cipriani Nicole
Published: February 2018

High-grade conventional osteosarcoma of the mandible is a rare entity that can manifest as a rapidly growing mass. The authors report the case of a young adult patient with right mandible pain and swelling and a history of humeral osteosarcoma treated over 1 decade earlier. Computed tomography and magnetic resonance imaging showed a mass arising from the right mandible that progressed despite induction chemotherapy and the patient underwent surgery. Histopathology revealed the presence of malignant osteoblasts and osteoid, which led to the diagnosis of high-grade conventional osteosarcoma. There were also regional lymph node metastases. Genetic testing revealed a p53 germline mutation. The presence of mandibular osteosarcoma in a young patient should raise the suspicion of an underlying p53 germline mutation. Ultimately, the recurrent tumor regressed with Etoposide and Ifosfamide.
Geomagnetic field influences upward movement of young Chinook salmon emerging from nests
Authors: Putman Nathan F. , Scanlan Michelle M. , Pollock Amanda M. , O'Neil Joseph P. , Couture Ryan B. , Stoner Joseph S. , Quinn Thomas P. , Lohmann Kenneth J. , Noakes David L. G.
Published: February 2018

Organisms use a variety of environmental cues to orient their movements in three-dimensional space. Here, we show that the upward movement of young Chinook salmon (
Oncorhynchus tshawytscha
) emerging from gravel nests is influenced by the geomagnetic field. Fish in the ambient geomagnetic field travelled farther upwards through substrate than did fish tested in a field with the vertical component inverted. This suggests that the magnetic field is one of several factors that influences emergence from the gravel, possibly by serving as an orientation cue that helps fish determine which way is up. Moreover, our work indicates that the
Oncorhynchus
species are sensitive to the magnetic field throughout their life cycles, and that it guides their movements across a range of spatial scales and habitats.
Analysing the structure and glass transition behaviour of silks for archaeology and conservation
Authors: Wang Jianlan , Guan Juan , Hawkins Nicholas , Vollrath Fritz
Published: February 2018

Silk is an iconic material in many cultures. Silk archaeology and conservation is affected by silk production technology as well as subsequent environmental effects such as humidity, temperature, UV radiation and ageing
.
The complex interactions and various effects on silk materials affect the practical use of silk, for example, in the conservation of ancient manuscripts. This study examines the various influences of silk provenance and processing, adhesive coatings and chemical treatments as well as natural and artificial ageing of the silk material. We use infrared spectroscopy (FTIR) and dynamic mechanical thermal analysis to investigate the glass transition behaviours in a range of archaeological and control silk samples. This allows us to establish structural differences in century-old museum silks and predict the effects of silk ageing and degradation.
Small cities face greater impact from automation
Authors: Frank Morgan R. , Sun Lijun , Cebrian Manuel , Youn Hyejin , Rahwan Iyad
Published: February 2018

The city has proved to be the most successful form of human agglomeration and provides wide employment opportunities for its dwellers. As advances in robotics and artificial intelligence revive concerns about the impact of automation on jobs, a question looms: how will automation affect employment in cities? Here, we provide a comparative picture of the impact of automation across US urban areas. Small cities will undertake greater adjustments, such as worker displacement and job content substitutions. We demonstrate that large cities exhibit increased occupational and skill specialization due to increased abundance of managerial and technical professions. These occupations are not easily automatable, and, thus, reduce the potential impact of automation in large cities. Our results pass several robustness checks including potential errors in the estimation of occupational automation and subsampling of occupations. Our study provides the first empirical law connecting two societal forces: urban agglomeration and automation's impact on employment.
Modification of wheat gluten for improvement of binding capacity with keratin in hair
Authors: Wang Shukun , Meng Danyang , Wang Sisi , Zhang Zhong , Yang Ruijin , Zhao Wei
Published: February 2018

In this study, enzymatic hydrolysis and cationization with epoxypropyldodecyldimethylammonium chloride of wheat protein, an economic protein complex containing great amount of disulfide bonds, were conducted to improve properties such as solubility and disassociation behaviour for recovery of damaged hair when used in shampoo. The optimal conditions for enzymatic hydrolysis were pH 8.2, 55°C with Alcalase for 60 min. After the selected hydrolysis, the degree of hydrolysis, nitrogen solubility index, foaming capacity index, foam stability index, emulsifying activity index and emulsion stability index of hydrolysate with 58.71% of short-chain peptides (less than 1000 Da) were 8.81%, 39.07%, 225%, 56.67%, 9.62 m
2
 g
−1
and 49.08, respectively. The cationization was followed to raise the isoelectric point of wheat protein hydrolysate from 7.0 to 10.0, which could facilitate the quaternized protein hydrolysate to adhere to the surface of hair at the range of pH 5–6 of hair care products to form more disulfide bonds. The results show that a shampoo with quaternized wheat proteins hydrolysate possesses excellent properties in recovering damaged hair, making the surface of hair smooth and compact.
Porous metallosilicates for heterogeneous, liquid-phase catalysis: perspectives and pertaining challenges
Authors: Hammond Ceri , Padovan Daniele , Tarantino Giulia
Published: February 2018

Porous silicates containing dilute amounts of tri-, tetra- and penta-valent metal sites, such as TS-1, Sn-β and Fe-ZSM-5, have recently emerged as state of the art catalysts for a variety of sustainable chemical transformations. In contrast with their aluminosilicate cousins, which are widely employed throughout the refinery industry for gas-phase catalytic transformations, such metallosilicates have exhibited unprecedented levels of performance for a variety of liquid-phase catalytic processes, including the conversion of biomass to chemicals, and sustainable oxidation technologies with H
2
O
2
. However, despite their unique levels of performance for these new types of chemical transformations, increased utilization of these promising materials is complicated by several factors. For example, their utilization in a liquid, and often polar, medium hinders process intensification (scale-up, catalyst deactivation). Moreover, such materials do not generally exhibit the active-site homogeneity of conventional aluminosilicates, and they typically possess a wide variety of active-site ensembles, only some of which may be directly involved in the catalytic chemistry of interest. Consequently, mechanistic understanding of these catalysts remains relatively low, and competitive reactions are commonly observed. Accordingly, unified approaches towards developing more active, selective and stable porous metallosilicates have not yet been achieved. Drawing on some of the most recent literature in the field, the purpose of this mini review is both to highlight the breakthroughs made with regard to the use of porous metallosilicates as heterogeneous catalysts for liquid-phase processing, and to highlight the pertaining challenges that we, and others, aim to overcome during the forthcoming years.
Evolutionary time drives global tetrapod diversity
Authors: Marin Julie , Rapacciuolo Giovanni , Costa Gabriel C. , Graham Catherine H. , Brooks Thomas M. , Young Bruce E. , Radeloff Volker C. , Behm Jocelyn E. , Helmus Matthew R. , Hedges S. Blair
Published: February 2018

Global variation in species richness is widely recognized, but the explanation for what drives it continues to be debated. Previous efforts have focused on a subset of potential drivers, including evolutionary rate, evolutionary time (maximum clade age of species restricted to a region), dispersal (migration from one region to another), ecological factors and climatic stability. However, no study has evaluated these competing hypotheses simultaneously at a broad spatial scale. Here, we examine their relative contribution in determining the richness of the most comprehensive dataset of tetrapods to our knowledge (84% of the described species), distinguishing between the direct influences of evolutionary rate, evolutionary time and dispersal, and the indirect influences of ecological factors and climatic stability through their effect on direct factors. We found that evolutionary time exerted a primary influence on species richness, with evolutionary rate being of secondary importance. By contrast, dispersal did not significantly affect richness patterns. Ecological and climatic stability factors influenced species richness indirectly by modifying evolutionary time (i.e. persistence time) and rate. Overall, our findings suggest that global heterogeneity in tetrapod richness is explained primarily by the length of time species have had to diversify.
Foraging and fasting can influence contaminant concentrations in animals: an example with mercury contamination in a free-ranging marine mammal
Authors: Peterson Sarah H. , Ackerman Joshua T. , Crocker Daniel E. , Costa Daniel P.
Published: February 2018

Large fluctuations in animal body mass in relation to life-history events can influence contaminant concentrations and toxicological risk. We quantified mercury concentrations in adult northern elephant seals (
Mirounga angustirostris
) before and after lengthy at sea foraging trips (
n
= 89) or fasting periods on land (
n
= 27), and showed that mercury concentrations in blood and muscle changed in response to these events. The highest blood mercury concentrations were observed after the breeding fast, whereas the highest muscle mercury concentrations were observed when seals returned to land to moult. Mean female blood mercury concentrations decreased by 30% across each of the two annual foraging trips, demonstrating a foraging-associated dilution of mercury concentrations as seals gained mass. Blood mercury concentrations increased by 103% and 24% across the breeding and moulting fasts, respectively, demonstrating a fasting-associated concentration of mercury as seals lost mass. In contrast to blood, mercury concentrations in female's muscle increased by 19% during the post-breeding foraging trip and did not change during the post-moulting foraging trip. While fasting, female muscle mercury concentrations increased 26% during breeding, but decreased 14% during moulting. Consequently, regardless of exposure, an animal's contaminant concentration can be markedly influenced by their annual life-history events.
Physiological motion of the carotid atherosclerotic plaque quantified using ultrasound B-Mode image analysis
Authors: Kanber Baris , Hartshorne Timothy C. , Garrard James W. , Naylor A. Ross , Robinson Thompson G. , Ramnarine Kumar V.
Published: February 2018

Background

Physical motion throughout the cardiac cycle may contribute to the rupture of the atherosclerotic carotid plaque, resulting in ischaemic stroke. The purpose of this study was to quantify the physiological motion of the atherosclerotic carotid plaque and to investigate any relationship between the quantified motion parameters and the degree of stenosis, greyscale plaque characteristics, and the presence of cerebrovascular symptoms.

Methods

Displacement, velocity and acceleration of 81 plaques (51% symptomatic, stenosis range 10%-95%) from 51 patients were measured using an automated system employing a block matching algorithm relative to the ultrasound probe and relative to the periadventitial tissues, over a mean duration of 5 cardiac cycles.

Results

Averaged across all plaques, the displacement amplitude was 1.2 mm relative to the probe, and 0.35 mm relative to the periadventitial tissues. Maximum and mean plaque velocities were 4.7 and 1.3 mm/s relative to the ultrasound probe, and 2.4 and 0.70 mm/s relative to the periadventitial tissues. The corresponding acceleration magnitudes were 69 and 22 mm/s2 relative to the probe, and 57 and 18 mm/s2 relative to the periadventitial tissues. There were no significant differences in any of the motion parameters, with respect to the presence of cerebrovascular symptoms, and none of the parameters showed a statistically significant relationship to the degree of stenosis, and the greyscale plaque characteristics (p≤0.05). The technique used was able to detect plaque motion amplitudes above 50μm.

Conclusions

This study provides quantitative data on the physiological motion of the atherosclerotic carotid plaque in-vivo. No significant relationship was found between the measured motion parameters and the presence of cerebrovascular symptoms, the degree of stenosis, and the greyscale plaque characteristics.
Ultrastructure of viruliferous Javesella pellucida transmitting Festuca leaf streak virus (genus Cytorhabdovirus)
Authors: Lundsgaard Thorben
Published: February 2018

The ultrastructure of cells in the head and thorax from viruliferous Javesella pellucida transmitting Festuca leaf streak virus was studied. Aggregates of nonenveloped nucleocapsid particles were observed at the periphery of viroplasms located in cytoplasm of salivary gland cells, fat cells, and nerve cell bodies. Aggregates of nucleocapsid particles, not associated with viroplasms, were seen within a distance of about 1 μm from the basal lamina of salivary glands. Enveloped virions, singly or aggregated, were observed in nerve cell axons and/or dendrites.
Investigation of Gluthatione S-Transferase Variants in a Healht Population in Goiânia-Go
Authors: Pereira Lucas Carlos Gomes , Bérgamo Nádia Aparecida , da Silva Reis Angela Adamski , Anunciação Carlos Eduardo , de Paula Silveira-Lacerda Elisangela
Published: February 2018

Genetic polymorphisms in glutathione S-transferases (GSTs) genes might influence the detoxification activities of the enzymes predisposing individuals to a lot of disiases. Owing to the presence of these genetic variants, inter-individual and ethnic differences in GSTs detoxification capacity have been observed in various populations. Therefore, the present study was performed to determine the prevalenceGSTM1*0/*0, GSTT1*0/*0andGSTP1Ile105Val polymorphisms in 100 healthy individuals from Goiânia - GO.GSTM1andGSTT1polymorphisms were analyzed by a Multiplex-PCR approach, whereasGSTP1polymorphisms were examined by PCR-RFLP. The frequencies ofGSTM1andGSTT1 *0/*0genotypes are 49% and 31%, respectively. The frequencies ofGSTP1Ile/Ile, Ile/Val, and Val/Val genotypes were 40%, 53%, and 7%, respectively. The wild-type (Ile) and variant (Val) allele frequencies were 66.5% and 33.5%, respectively. The combined genotypes distribution ofGSTM1, GSTT1andGSTP1polymorphisms showed 12 possible genotypes present in our population; seven of them have a frequency greater than 5%. The effect of combined genotypes of theseGSTspolymorphisms is still unknown. These findings in healthy population, give us such more information for the future epidemiological and clinical studies. Using to examine the effect of these combinations in drugs metabolism and cancer predisposition, further largest group would be needed, since their frequencies are quite low. To our ofGSTspolymorfisms, this is the first study indicating the frequencies of genetic polimorphisms of GST superfamily in a health population in a Goiania population.
De novo acetate production is coupled to central carbon metabolism in mammals
Authors: Liu Xiaojing , Cooper Daniel E. , Cluntun Ahmad A. , Warmoes Marc O. , Zhao Steven , Reid Michael A. , Liu Juan , Wellen Kathryn E. , Kirsch David G. , Locasale Jason W.
Published: February 2018

In cases of nutritional excess, there is incomplete catabolism of a nutritional source and secretion of a waste product (overflow metabolism), such as the conversion of glucose to lactate (the Warburg Effect) in tumors. Here we report that excess glucose metabolism generates acetate, a key nutrient whose source has been unclear. Conversion of pyruvate, the product of glycolysis, to acetate occurs through two mechanisms: 1) coupling to reactive oxygen species (ROS), and 2) a neomorphic enzyme activity from keto acid dehydrogenases that enable it to function as a pyruvate decarboxylase. Furthermore, we demonstrate that glucose-derived acetate is sufficient to maintain acetyl-coenzyme A (Ac-CoA) pools and cell proliferation in certain limited metabolic environments such as during mitochondrial dysfunction or ATP citrate lyase (ACLY) deficiency. Thus, de novo acetate production is coupled to the activity of central carbon metabolism providing possible regulatory mechanisms and links to pathophysiology.
The interplay of immune components and ECM in oral cancer
Authors: Kwak Yigang , Alsaihati Burair , Zhang Chi , Xu Ying , Cao Sha
Published: February 2018

We report that in Oral Squamous Cell Carcinoma (OSCC), extracellular matrix (ECM) plays a vitally important role in defining the characteristics of cancer vs. normal, as it is a compartment with significant enrichment of known OSCC biomarkers, and the number of genes constituting ECM are more prominently upregulated in OSCC than almost all the rest of the cancer types. This is probably due to the constant exposure of oral cavity to external stimuli, resulting in the ECM remodeling, which further is a key player in tumor invasion. While we showed ECM molecules alone could well distinguish oral cancer from normal tissue samples, a significant portion of these predictive ECM molecules, share the same transcriptional regulator, NFKB1, a master regulator of immune response. We further studied the level of involvement of the immune system in OSCC, and found that the immune composition in OSCC is distinctly different from the other cancer types. OSCC has a higher level of infiltration of adaptive immune cells, including B cell, T cell and neutrophil, compared with other cancer types, while a lower level of infiltration of innate immune, including macrophage and monocyte. Previous studies have revealed the roles of ECM and immune system in OSCC development, and our study showed that ECM plays a very prominent role in OSCC, subject to the complex microenvironment in oral cavity, particularly the immune system profile, and our association analysis revealed it is likely the interactions between ECM and immune cells that define the highly invasive property of OSCC.
Spatiotemporal dynamics of river viruses, bacteria and microeukaryotes
Authors: Rossum Thea Van , Uyaguari-Diaz Miguel I. , Vlok Marli , Peabody Michael A. , Tian Alvin , Cronin Kirby I. , Chan Michael , Croxen Matthew A. , Hsiao William W.L. , Isaac-Renton Judith , Tang Patrick K.C. , Prystajecky Natalie A. , Suttle Curtis A. , Brinkman Fiona S.L.
Published: February 2018

Freshwater is an essential resource of increasing value, as clean water sources diminish. Microorganisms in rivers, a major source of renewable freshwater, are significant due to their role in drinking water safety, signalling environmental contamination1, and driving global nutrient cycles2,3. However, a foundational understanding of microbial communities in rivers is lacking4, especially temporally and for viruses5‒7. No studies to date have examined the composition of the free-floating river virome over time, and explanations of the underlying causes of spatial and temporal changes in riverine microbial composition, especially for viruses, remain unexplored. Here, we report relationships among riverine microbial communities and their environment across time, space, and superkingdoms (viruses, bacteria, and microeukaryotes), using metagenomics and marker-based microbiome analysis methods. We found that many superkingdom pairs were synchronous and had consistent shifts with sudden environmental change. However, synchrony strength, and relationships with environmental conditions, varied across space and superkingdoms. Variable relationships were observed with seasonal indicators and chemical conditions previously found to be predictive of bacterial community composition4,8‒10, emphasizing the complexity of riverine ecosystems and raising questions around the generalisability of single-site and bacteria-only studies. In this first study of riverine viromes over time, DNA viral communities were stably distinct between sites, suggesting the similarity in riverine bacteria across significant geographic distances10‒12does not extend to viruses, and synchrony was surprisingly observed between DNA and RNA viromes. This work provides foundational data for riverine microbial dynamics in the context of environmental and chemical conditions and illustrates how a bacteria-only or single-site approach would lead to an incorrect description of microbial dynamics. We show how more holistic microbial community analysis, including viruses, is necessary to gain a more accurate and deeper understanding of microbial community dynamics.
The N-terminus of Sec61p plays key roles in ER protein import and ERAD
Authors: Elia Francesco , Tretter Thomas , Römisch Karin
Published: February 2018

Sec61p is the channel-forming subunit of the heterotrimeric Sec61 complex that mediates co-translational protein import into the endoplasmic reticulum (ER). In yeast, proteins can also be post-translationally translocated by the hetero-heptameric Sec complex, composed of the Sec61 and the Sec63 complexes. The Sec61 channel is also a candidate for the dislocation channel for misfolded proteins from the ER to the cytosol during ER-associated degradation (ERAD). The structure of the Sec61 complex is highly conserved, but the roles of its N-terminal acetylation and its amphipathic N-terminal helix are unknown so far. To gain insight into the function of the Sec61p N-terminus, we mutated its N-acetylation site, deleted its amphipathic helix, or both the helix and the N-acetylation site. Mutation of the N-acetylation site on its own had no effect on protein import into the ER in intact cells, but resulted in an ERAD defect. Yeast expressing sec61 without the N-terminal amphipathic helix displayed severe growth defects and had profound defects in post-translational protein import into the ER. Nevertheless the formation of the hetero-heptameric Sec complex was not affected. Instead, the lack of the N-terminal amphipathic helix compromised the integrity of the heterotrimeric Sec61 complex. We conclude that the N-terminal helix of Sec61p is required for post-translational protein import into the ER and Sec61 complex stability, whereas N-terminal acetylation of Sec61p plays a role in ERAD.
Enhanced translation expands the endo-lysosome size and promotes antigen presentation during phagocyte activation
Authors: Hipolito Victoria E. B. , Diaz Jacqueline A. , Tandoc Kristofferson V. , Oertlin Christian , Ristau Johannes , Chauhan Neha , Saric Amra , Mclaughlan Shannon , Larsson Ola , Topisirovic Ivan , Botelho Roberto J.
Published: February 2018

The mechanisms that govern organelle adaptation and remodeling remain poorly defined. The endo-lysosomal system degrades cargo from various routes including endocytosis, phagocytosis and autophagy. For phagocytes, endosomes and lysosomes (endo-lysosomes) are kingpin organelles since they are essential to kill pathogens and process and present antigens. During phagocyte activation, endo-lysosomes undergo a morphological transformation, going from a collection of dozens of globular structures to a tubular network in a process that requires the phosphatidylinositol-3-kinase-AKT-mTOR signalling pathway. Here, we show that the endo-lysosomal system undergoes an expansion in volume and holding capacity during phagocyte activation within 2 h of LPS stimulation. Endo-lysosomal expansion was paralleled by an increase in lysosomal protein levels, but this was unexpectedly largely independent of TFEB and TFE3 transcription factors, known to scale up lysosome biogenesis. Instead, we demonstrate a hitherto unappreciated mechanism of acute organelle expansion via mTORC1-dependent increase in translation, which appears to be mediated by both, S6Ks and 4E-BPs. Moreover, we show that stimulation of RAW cells with LPS alters translation of a subset but not all of mRNAs encoding endo-lysosomal proteins, thereby suggesting that endo-lysosome expansion is accompanied by functional remodelling. Importantly, mTORC1-dependent increase in translation activity was necessary for efficient and rapid antigen presentation by dendritic cells. Collectively, we identified a previously unknown and functionally relevant mechanism for endo-lysosome expansion that relies on mTORC1-dependent translation to stimulate endo-lysosome biogenesis in response to an infection signal.
Cognition and behaviour in learning difficulties and ADHD: A dimensional approach
Authors: Gathercole Susan E. , Astle Duncan A. , Manly Tom ,   the CALM Team, Holmes Joni
Published: February 2018

Background

Academic underachievement often accompanies the symptoms of inattention and hyperactivity/ impulsivity associated with ADHD. The aim of the present study is to establish whether learning difficulties have the same cognitive origins in this comorbid condition as in children who do not have ADHD.

Methods

Participants were 163 school-aged children with learning difficulties. Over a third also had a diagnosis of ADHD. Cognition, behaviour and learning attainments were assessed.

Results

The sample was distinguished by three cognitive and three behavioural dimensions. Learning was equivalently related to cognitive dimensions for children with and without ADHD. A diagnosis of ADHD was associated only with elevated levels of ADHD symptoms and problems with emotional control.

Conclusions

Distinct dimensions underpin academic learning and the control of impulsive and emotional behaviour impaired in ADHD. Phonological deficits are associated with learning problems in literacy and maths, and impairments in nonverbal and executive abilities with mathematical learning difficulties. The comorbid condition of ADHD combined with learning difficulties reflects independent deficits in the cognitive dimensions critical for learning and in the control of impulsive and emotional behaviour.
A transcript-wide association study in physical activity intervention implicates molecular pathways in chronic disease
Authors: Claypool Kajal , Patel Chirag J
Published: February 2018

Background

Physical activity is associated with decreased risk for several chronic and acute conditions including obesity, diabetes, cardiovascular disease, mental health and aging. However, the biological mechanisms associated with this decreased risk are elusive. One way to ascertain biological changes influenced by physical activity is by monitoring changes in how genes are expressed. In this investigation, we conducted a transcriptome-wide association study of physical activity, meta-analyzing 20 independent studies to increase power for discovery of genes expressed before and after physical activity. Further, we hypothesize that genes identified in physical activity are expressed in obesity, inflammation, major depressive disorder and healthy aging.

Results

Our analysis identified thirty (30) transcripts induced by physical activity (PA signature), at an FDR < 0.05. Twenty (20) of these transcripts, including COL4A3, CAMKD1, SLC4A5, EPS15L1, RBM33, and CACNG1, are up-regulated and ten (10) transcripts including CRY1, ZNF346, SDF4, ANXA1 and YWHAZ are down-regulated. We find that several of these physical activity transcripts are associated and biologically concordant in direction with body mass index, white blood cell count, and healthy aging.

Conclusions

powerful approach, we found thirty genes that were putatively influenced by physical activity, eight of which are inversely associated with body mass index, thirteen inversely associated with white blood cell count, and three associated and concordant with healthy aging. One gene was significant and concordant with major depressive disorder. These results highlight the potential molecular basis for the protective benefit of physical activity for a broad set of chronic conditions.
Reprogramming protein abundance fluctuations in single cells by degradation
Authors: Matalon O , Steinberg A , Sass E , Hausser J , Levy ED
Published: February 2018

Isogenic cells living in the same environment show a natural heterogeneity associated with fluctuations in gene expression. When these fluctuations propagate through cellular regulatory networks, they can give rise to noise regulons, whereby multiple genes fluctuate in a coordinated fashion in single cells. The propagation of these fluctuations has been extensively characterized at the transcriptional level. For example, variations in transcription factor concentration induce correlated fluctuations in the abundance of target gene products. Here, we find that such noise regulons can also stem from protein degradation. We expressed pairs of yellow and red fluorescent proteins, subjected them to differential translation or degradation, and analyzed their fluctuations in single cells. While differential translation had little impact on fluctuations, protein degradation was found to be a dominant contributor. A mathematical model to decompose fluctuations arising from multiple sources of regulation revealed that cells with higher protein production capacity also exhibited higher protein degradation capacity. This association uncouples fluctuations in protein abundance from fluctuations in production rate, and can generate orthogonal noise regulons even for proteins relying on the same transcriptional program.
MSIGNET: a Metropolis sampling-based method for global optimal significant network identification
Authors: Chen Xi , Xuan Jianhua
Published: February 2018

In this paper, we propose a novel approach namely MSIGNET to identify subnetworks with significantly expressed genes by integrating context specific gene expression and protein-protein interaction (PPI) data. Specifically, we integrate differential expression of each gene and mutual information of gene pairs in a Bayesian framework and use Metropolis sampling to identify functional interactions. During the sampling process, a conditional probability is calculated given a randomly selected gene to control the network state transition. Our method provides global statistics of all genes and their interactions, and finally achieves a global optimal sub-network. We apply MSIGNET to simulated data and have demonstrated its superior performance over comparable network identification tools. Using a validated Parkinson data set we show that the network identified using MSIGNET is consistent to previously reported results but provides more biology meaningful interpretation of Parkinson’s disease. Finally, to study networks related to ovarian cancer recurrence, we investigate two patient data sets. Identified networks from independent data sets show functional consistence. And those common genes and interactions are well supported by current biological knowledge.
Inference of population structure from ancient DNA
Authors: Joseph Tyler A. , Pe’er Itsik
Published: February 2018

Methods for inferring population structure from genetic information traditionally assume samples are contemporary. Yet, the increasing availability of ancient DNA sequences begs revision of this paradigm. We present Dystruct (Dynamic Structure), a framework and toolbox for inference of shared ancestry from data that include ancient DNA. By explicitly modeling population history and genetic drift as a time-series, Dystruct more accurately and realistically discovers shared ancestry from ancient and contemporary samples. Formally, we use a normal approximation of drift, which allows a novel, efficient algorithm for optimizing model parameters using stochastic variational inference. We show that Dystruct outperforms the state of the art when individuals are sampled over time, as is common in ancient DNA datasets. We further demonstrate the utility of our method on a dataset of 92 ancient samples alongside 1941 modern ones genotyped at 222755 loci. Our model tends to present modern samples as the mixtures of ancestral populations they really are, rather than the artifactual converse of presenting ancestral samples as mixtures of contemporary groups.

Availability

Dystruct is implemented in C++, open-source, and available at https://github.com/tyjo/dystruct.
Focal adhesion kinase regulates early steps of myofibrillogenesis in cardiomyocytes
Authors: Taneja Nilay , Neininger Abigail C. , Bersi Matthew R. , Merryman W. David , Burnette Dylan T.
Published: February 2018

Forces generated by myofibrils within cardiomyocytes must be balanced by adhesion to the substrate and to other cardiomyocytes for proper heart function. Loss of this force balance results in cardiomyopathies that ultimately cause heart failure. How this force balance is first established during the assembly of myofibrils is poorly understood. Using human induced pluripotent stem cell derived cardiomyocytes, we show coupling of focal adhesions to myofibrils during early steps ofde novomyofibrillogenesis is essential for myofibril maturation. We also establish a key role for Focal adhesion kinase (FAK), a known regulator of adhesion dynamics in non-muscle cells, in regulating focal adhesion dynamics in cardiomyocytes. Specifically, FAK inhibition increased the stability of vinculin in focal adhesions, allowing greater substrate coupling of assembling myofibrils. Furthermore, this coupling is critical for regulating myofibril tension and viscosity. Taken together, our findings uncover a fundamental mechanism regulating the maturation of myofibrils in human cardiomyocytes.
Neural signatures of the processing of temporal patterns in sound
Authors: Herrmann Björn , Johnsrude Ingrid S.
Published: February 2018

The ability to detect regularities in sound (i.e., recurring structure) is critical for effective perception, enabling, for example, change detection and prediction. Two seemingly unconnected lines of research concern the neural operations involved in processing regularities: one investigates how neural activity synchronizes with temporal regularities (e.g., frequency modulation; FM) in sounds, whereas the other focuses on increases in sustained activity during stimulation with repeating tone-frequency patterns. In three electroencephalography studies with male and female human participants, we investigated whether neural synchronization and sustained neural activity are dissociable, or whether they are functionally interdependent. Experiment I demonstrated that neural activity synchronizes with temporal regularity (FM) in sounds, and that sustained activity increases concomitantly. In Experiment II, phase coherence of FM in sounds was parametrically varied. Although neural synchronization was more sensitive to changes in FM coherence, such changes led to a systematic modulation of both neural synchronization and sustained activity, with magnitude increasing as coherence increased. In Experiment III, participants either performed a duration categorization task on the sounds, or a visual object tracking task to distract attention. Neural synchronization was observed irrespective of task, whereas the sustained response was observed only when attention was on the auditory task, not under (visual) distraction. The results suggest that neural synchronization and sustained activity levels are functionally linked: both are sensitive to regularities in sounds. However, neural synchronization might reflect a more sensory-driven response to regularity, compared with sustained activity which may be influenced by attentional, contextual, or other experiential factors.

Significance statement

Optimal perception requires that the auditory system detects regularities in sounds. Synchronized neural activity and increases in sustained neural activity both appear to index the detection of a regularity, but the functional interrelation of these two neural signatures is unknown. In three electroencephalography experiments, we measured both signatures concomitantly while listeners were presented with sounds containing frequency modulations that differed in their regularity. We observed that both neural signatures are sensitive to temporal regularity in sounds, although they functionally decouple when a listener is distracted by a demanding visual task. Our data suggest that neural synchronization reflects a more automatic response to regularity, compared with sustained activity which may be influenced by attentional, contextual, or other experiential factors.
Prediction of the secundary structure at the tRNASer (UCN) ofLutzomyia longipalpis(Diptera: Psychodidae)
Authors: Hoyos-Lopez Richard
Published: February 2018

Lutzomyia longipalpisis the main vector ofLeishmania infantum, the etiological agent of visceral leishmaniasis in America and Colombia. Taxonomically belongs to the subgenusLutzomyia, which includes other vector species that exhibit high morphological similarity to the female species difficult to identify vectors in leishmaniasis foci and suggesting the search for molecular markers that facilitate this task, further researchs with mitochondrial genes, chromosome banding, reproductive isolation and pheromones evidence the existence of species complex. The aim of this study was to predict the secondary structure of mitochondrial transfer RNA serine (tRNASer) for UCN codon ofLutzomyia longipalpisas molecular marker for identify of this species. Sequences recorded in Genbank ofL. longipalpissequences were aligned with tRNA′s from previously described species and then tRNASer secondary structure was inferred by software tRNAscan-SE 1.21. The length of tRNASer was 67 base pairs (bp). Two haplotypes were detected in the five sequences analyzed. TheL. longipalpistRNASer showed 7 intrachain pairing in the acceptor arm, 3 in the DHU arm, 4 in the anticodon arm and 5 in the TψC. The size of the loops corresponded to 5 nucleotides in the DHU, 7 in the anticodon, 4 in the variable and 7 in the TψC.L. longipalpisis distinguished from other species at subgeneraLutzomyiaby the secondary structure and substitutions inferred tRNASer evidenced in the primary sequence.
Liquid co-substrates repower sewage microbiomes
Authors: Hardegen Justus , Latorre-Pérez Adriel , Vilanova Cristina , Günther Thomas , Simeonov Claudia , Porcar Manuel , Luschnig Olaf , Abendroth Christian
Published: February 2018

A range of parameters are known to shape the methanogenic communities of biogas-producing digesters and to strongly influence the amount of biogas produced. In this work, liquid and solid fractions of grass biomass were used separately for semicontinuous batch methanation using sewage sludge as seed sludge. During 6 months of incubation, the amount of input COD was increased gradually, and the underlying methanogenic microbiome was assessed by means of microscopy-based automated cell counting and full-length 16S rRNA high-throughput sequencing. In this sense, we prove for the first time the suitability of the ONT™MinION platform as a monitoring tool for anaerobic digestion systems. According to our results, solid-fed batches were highly unstable at higher COD input concentrations, and kept Methanosaeta spp. typically associated to sewage sludge-as the majoritary methanogenic archaea. In contrast, liquid-fed batches developed a more stable microbiome, proved enriched in Methanosarcina spp, and resulted in higher methanogenic yield. This work demonstrates the high repowering potential of microbiomes from sewage sludge digesters, and highlight the effectiveness of liquefied substrates for increasing biogas productivity in anaerobic digestions.
TreeCluster: Massively scalable transmission clustering using phylogenetic trees
Authors: Moshiri Niema
Published: February 2018

Background

The ability to infer transmission clusters from molecular data is critical to designing and evaluating viral control strategies. Viral sequencing datasets are growing rapidly, but standard methods of transmission cluster inference do not scale well beyond thousands of sequences.

Results

I present TreeCluster, a cross-platform tool that performs transmission cluster inference on a given phylogenetic tree orders of magnitude faster than existing inference methods and supports multiple clustering optimization functions.

Conclusions

TreeCluster is a freely-available cross-platform open source Python 3 tool for inferring transmission clusters from phylogenetic trees. Code, usage information, and in-depth descriptions of the implemented clustering modes are available publicly at the following repository:

https://github.com/niemasd/TreeCluster
Cell type-specific variation of somatotopic precision across corticostriatal projections
Authors: Hooks Bryan M. , Papale Andrew E. , Paletzki Ronald , Feroze Muhammad , Eastwood Brian S. , Couey Jonathan J. , Winnubst Johan , Chandrashekar Jayaram , Gerfen Charles R.
Published: February 2018

The striatum shows general topographic organization and regional differences in behavioral functions. How corticostriatal topography differs across cortical areas and cell types to support these distinct functions is unclear. This study contrasted corticostriatal projections from two layer 5 cell types, intratelencephalic (IT-type) and pyramidal tract (PT-type) neurons, using viral vectors expressing fluorescent reporters in Cre-driver mice. Long-range corticostriatal projections from sensory and motor cortex are somatotopic, with a decreasing somatotopic specificity as injections move from sensory to motor and frontal areas. Somatotopic organization differs between IT-type and PT-type neurons, including injections in the same site, with IT-type neurons having higher somatotopic stereotypy than PT-type neurons. Furthermore, IT-type projections from interconnected cortical areas have stronger correlations in corticostriatal targeting than PT-type projections do. Thus, as predicted by a long-standing basal ganglia model, corticostriatal projections of interconnected cortical areas form parallel circuits in basal ganglia-thalamus-cortex loops.
Myosin Heavy Chain-embryonic is a crucial regulator of skeletal muscle development and differentiation
Authors: Sharma Akashi , Agarwal Megha , Kumar Amit , Kumar Pankaj , Saini Masum , Kardon Gabrielle , Mathew Sam J.
Published: February 2018

Myosin heavy chains (MyHCs) are contractile proteins that are part of the thick filaments of the functional unit of the skeletal muscle, the sarcomere. In addition to MyHCs that are part of the adult muscle contractile network, two MyHCs - MyHC-embryonic and -perinatal are expressed during muscle development and are only transiently expressed in the adult during regeneration. The functions performed by these MyHCs has been a long-standing question and using a targeted mouse allele, we have characterized the role of MyHC-embryonic. Analysis of loss-of-function mice reveals that lack of MyHC-embryonic leads to mis-regulation of other MyHCs, alterations in fiber size, fiber number and fiber type at neonatal stages. We also find that loss of MyHC-embryonic leads to mis-regulation of genes involved in muscle differentiation. A broad theme from these studies is that loss of MyHC-embryonic has distinct effects on different muscles, possibly reflecting the unique fiber type composition of different muscles. Most significantly, our results indicate that MyHC-embryonic is required during embryonic and fetal myogenesis to regulate myogenic progenitor and myoblast differentiation in a non-cell autonomous manner via Mitogen Activated Protein Kinase (MAPKinase) and Fibroblast Growth Factor (FGF) signaling. Thus, our results signify that MyHC-embryonic is a key regulator of myogenic differentiation during embryonic, fetal and neonatal myogenesis.