bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral Oxygenation as a Monitoring Parameter for Mortality During Venoarterial Extracorporeal Membrane Oxygenation
Authors: Kim Hyoung Soo , Ha Sang Ook , Yu Kyung-Ho , Oh Mi Sun , Park Sunghoon , Lee Sun Hee , Han Sang Jin , Kim Hyun-Sook , Chang In Bok , Ahn Jun Hyong
Published: May 2018

There are no recommended guidelines for monitoring parameters during venoarterial extracorporeal membrane oxygenation (V-A ECMO). We evaluated whether regional cerebral oxygen saturation (rScO2) could be a monitoring parameter for mortality during V-A ECMO. We retrospectively searched our database for adult patients who underwent V-A ECMO between April 2015 and October 2016 and identified 21 patients with rScO2 data. Their baseline and clinical characteristics during the first 7 days (vital signs, arterial blood gas results, ECMO variables, rScO2, Swan-Ganz catheter parameters, transthoracic echocardiography parameters, and outcomes) were collected and evaluated for associations with 28 day mortality. The survivor group (12 patients, 57.1%) had higher rScO2 values and lower lactate levels, compared with the nonsurvivor group (nine cases, 42.9%) during the first 7 days. The areas under the receiver operating characteristics curves were 0.87 for right rScO2 (p < 0.001) and 0.86 for left rScO2 (p < 0.001). The optimal cutoff values for right and left rScO2 were 58% (sensitivity: 78.7%, specificity: 83.3%) and 57% (sensitivity: 80.0%, specificity: 70.8%), respectively. Kaplan–Meier analysis revealed that the risks of 28 day mortality were higher among patients with a right rScO2 of <58% and a left rScO2 of <57%, compared with patients with a right rScO2 of ≥58% and a left rScO2 of ≥57% (both, p < 0.001). We suggest that rScO2 may be used as a monitoring parameter for 28 day mortality among patients undergoing V-A ECMO.
Impact of Provider Participation in ACO Programs on Preventive Care Services, Patient Experiences, and Health Care Expenditures in US Adults Aged 18–64
Authors: Hong Young-Rock , Sonawane Kalyani , Larson Samantha , Mainous Arch G. , Marlow Nicole M.
Published: May 2018

Background:

Little is known about the impact of accountable care organization (ACO) on US adults aged 18–64.

Objectives:

To examine whether having a usual source of care (USC) provider participating in an ACO affects receipt of preventive care services, patient experiences, and health care expenditures among nonelderly Americans.

Research Design:

A cross-sectional analysis of the 2015 Medical Organizations Survey linked with the Medical Expenditure Panel Survey.

Subjects:

Survey respondents aged 18–64 with an identified USC and continuous health insurance coverage during 2015.

Measures:

Preventative care services (routine checkup, flu vaccination, and cancer screening), patient experiences with health care (access to care, interaction quality with providers, and global satisfaction), and health care expenditures (total and out-of-pocket expenditures) for respondents with USC by ACO and non-ACO provider groups.

Results:

Among 1563, nonelderly Americans having a USC, we found that nearly 62.7% [95% confidence interval (CI), 58.6%–66.7%; representing 15,722,208 Americans] were cared for by ACO providers. Our analysis showed no significant differences in preventive care services or patient experiences between ACO and non-ACO groups. Adjusted mean total health expenditures were slightly higher for the ACO than non-ACO group [$7016 (95% CI, $4949–$9914) vs. $6796 (95% CI, $4724–$9892)]; however, this difference was not statistically significant (P=0.250).

Conclusions:

Our findings suggest that having a USC provider participating in an ACO is not associated with preventive care services use, patient experiences, or health care expenditures among a nonelderly population.
Seasonality of Common Pediatric Infectious Diseases
Authors: Lipsett Susan C. , Monuteaux Michael C. , Fine Andrew M.
Published: May 2018

Background/Objective

Traditional sources cite seasonal patterns for common infectious diseases, often based on microbiologic data, but little is known about cyclical trends in clinically diagnosed infectious conditions in the emergency department (ED). We leveraged the publicly available Nationwide Emergency Department Sample database to measure the seasonality of the most common pediatric infectious diseases diagnosed in US EDs.

Methods

We searched the Nationwide Emergency Department Sample database to identify infectious diagnoses comprising at least 1% of all diagnosis codes ascribed to patients 21 years and younger in US EDs from 2009 to 2013. We used Fourier regression to examine seasonal trends in disease and calculated the peak-to-nadir ratio for each infectious condition.

Results

Over 20% of pediatric visits during the study period were for infectious conditions. Upper respiratory infection, otitis media, gastroenteritis, urinary tract infection/pyelonephritis, cellulitis/abscess, and pneumonia showed a seasonal pattern that matched trends found in prior regional or microbiologic-based studies. The strongest seasonal trend as measured by goodness of model fit was found in pneumonia (peak-to-nadir incidence ratio of 2.7), followed by otitis media (2.0), cellulitis/abscess (2.0), gastroenteritis (1.6), upper respiratory infection (3.2), and urinary tract infection/pyelonephritis (1.4). Pharyngitis did not show a strong seasonal trend.

Conclusions

Many of the most common pediatric infectious diseases diagnosed in US EDs exhibited seasonal patterns. Large administrative databases can be used to track seasonal disease patterns, with the advantage that they reflect clinician diagnosis beyond microbiologic confirmation. This methodology could aid in resource planning, infection control, and public health educational initiatives.
Comparison Between Ultrasonography and Galactography in Detecting Lesions in Patients With Pathologic Nipple Discharge
Authors: Jung Hyun Kyung , Park Young Mi , Baek Hye Jin , Choo Hye Jung , Kim Eun-Kyung , Kim Dong Wook , Lee Sun Joo , Lee Jin Hwa
Published: May 2018

Purpose

This study aimed to compare the diagnostic performance of breast ultrasonography (US) with that of galactography in the detection of lesions in patients with pathologic nipple discharge.

Methods

We included 46 cases from 39 patients (all women; mean age, 44.0 years; range, 22–68 years) who had pathologic nipple discharge and underwent US and galactography between March 2004 and December 2012. Two radiologists retrospectively reviewed and compared the detectability of lesions on US and galactography images. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of US and galactography, and the area under the curve was compared between the 2 imaging modalities.

Results

A total of 35 cases were pathologically diagnosed. Out of 11 cases that completed a follow-up, none developed malignancies during the follow-up period (mean: 63.5 months; range: 34.8–125.7 months). The sensitivity, specificity, and positive and negative predictive values of US with respect to detectability of lesions were 75%, 42.9%, 11.1%, and 94.7%, respectively, and those of galactography were 100%, 38.1%, 13.3%, and 100%, respectively.

Conclusions

Galactography is more sensitive than US in the detection of lesions in patients with pathologic nipple discharge.
Ultrasound, Computed Tomography, and Magnetic Resonance Imaging in a Patient With Medullary Cystic Kidney Disease
Authors: Whang Gilbert , Tchelepi Hisham
Published: May 2018

Among the renal cystic diseases that result in end-stage renal disease, an important hereditary cause is medullary cystic kidney disease, which affects adults in an autosomal dominant pattern. It is characterized by progressive renal failure, tubulointerstitial fibrosis, and formation of small cysts in the renal medulla and corticomedullary junction. While the appearance of medullary/corticomedullary cysts may not be pathognomonic for medullary cystic kidney disease, encountering a patient with renal failure and medullary/corticomedullary cysts should prompt further investigation, given the implication of having the disease. Genetic testing can be used to identify potential renal donors as well as identify affected individuals in order to control risk factors for chronic renal disease that may mitigate the progression of the disease process. The treatment of choice is renal transplantation.
Mechanistic models versus machine learning, a fight worth fighting for the biological community?
Authors: Baker Ruth E. , Peña Jose-Maria , Jayamohan Jayaratnam , Jérusalem Antoine
Published: May 2018

Ninety per cent of the world's data have been generated in the last 5 years (
Machine learning: the power and promise of computers that learn by example
. Report no. DES4702. Issued April 2017. Royal Society). A small fraction of these data is collected with the aim of validating specific hypotheses. These studies are led by the development of mechanistic models focused on the causality of input–output relationships. However, the vast majority is aimed at supporting statistical or correlation studies that bypass the need for causality and focus exclusively on prediction. Along these lines, there has been a vast increase in the use of machine learning models, in particular in the biomedical and clinical sciences, to try and keep pace with the rate of data generation. Recent successes now beg the question of whether mechanistic models are still relevant in this area. Said otherwise, why should we try to understand the mechanisms of disease progression when we can use machine learning tools to directly predict disease outcome?
The grazing gait, and implications of toppling table geometry for primate footfall sequences
Authors: Usherwood James R. , Smith Benjamin J. H.
Published: May 2018

Many medium and large herbivores locomote forwards very slowly and intermittently when grazing. While the footfall order during grazing is the same as for walking, the relative fore–hind timing—phasing—is quite different. Extended periods of static stability are clearly required during grazing; however, stability requirements are insufficient to account for the timing. Aspects of relatively rapid rolling and pitching—toppling due to the resistance of the back to bending and twisting—can be included in a simplifying geometric model to explain the observation that, in grazing livestock, a step forward with a forefoot is consistently and immediately followed by a step forward from the hind; but not vice versa. The same principles and geometry, but applied to the footfall pattern of walking primates, show that toppling would occur at a different point in the gait cycle. This provides a potential account for the distinctive diagonal-sequence footfall pattern of primates, as it prevents the instant of toppling from being at forefoot placement. Careful and controlled hand positioning would thus be facilitated, presumably beneficial to walking on top of branches, despite a slight energetic cost compared with the usual lateral sequence pattern of horses.
Cell geometry across the ring structure of Sitka spruce
Authors: Reynolds T. P. S. , Burridge H. C. , Johnston R. , Wu G. , Shah D. U. , Scherman O. A. , Linden P. F. , Ramage M. H.
Published: May 2018

For wood to be used to its full potential as an engineering material, it is necessary to quantify links between its cell geometry and the properties it exhibits at bulk scale. Doing so will make it possible to predict timber properties crucial to engineering, such as mechanical strength and stiffness, and the resistance to fluid flow, and to inform strategies to improve those properties as required, as well as to measure the effects of interventions such as genetic manipulation and chemical modification. Strength, stiffness and permeability of timber all derive from the geometry of its cells, and yet current practice is to predict them based on properties, such as bulk density, that do not directly describe the cell structure. This work explores links between micro-computed tomography data for structural-size pieces of wood, which show the variation of porosity across the wood's ring structure, and high-resolution tomography showing the geometry of the cells, from which we measure cell length, lumen area, porosity, cell wall thickness and the number density of cells. High-resolution scans, while informative, are time-consuming and expensive to run on a large number of samples at the scale of building components. By scanning the same volume of timber at both low and high resolutions (high-resolution scans over a near-continuous volume of timber of approx. 20 mm
3
at 15 μm
3
per voxel), we are able to demonstrate correlations between the measurements at the two different resolutions, reveal the physical basis for these correlations, and demonstrate that the data from the low-resolution scan can be used to estimate the variation in (small-scale) cell geometry throughout a structural-size piece of wood.
Lead acid battery recycling for the twenty-first century
Authors: Ballantyne Andrew D. , Hallett Jason P. , Riley D. Jason , Shah Nilay , Payne David J.
Published: May 2018

There is a growing need to develop novel processes to recover lead from end-of-life lead-acid batteries, due to increasing energy costs of pyrometallurgical lead recovery, the resulting CO
2
emissions and the catastrophic health implications of lead exposure from lead-to-air emissions. To address these issues, we are developing an iono-metallurgical process, aiming to displace the pyrometallurgical process that has dominated lead production for millennia. The proposed process involves the dissolution of Pb salts into the deep eutectic solvent (DES) Ethaline 200, a liquid formed when a 1 : 2 molar ratio of choline chloride and ethylene glycol are mixed together. Once dissolved, the Pb can be recovered through electrodeposition and the liquid can then be recycled for further Pb recycling. Firstly, DESs are being used to dissolve the lead compounds (PbCO
3
, PbO, PbO
2
and PbSO
4
) involved and their solubilities measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The resulting Pb
2+
species are then reduced and electrodeposited as elemental lead at the cathode of an electrochemical cell; cyclic voltammetry and chronoamperometry are being used to determine the electrodeposition behaviour and mechanism. The electrodeposited films were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). We discuss the implications and opportunities of such processes.
Acceptor range of endo-β-
N
-acetylglucosaminidase mutant endo-CC N180H: from monosaccharide to antibody
Authors: Manabe Shino , Yamaguchi Yoshiki , Abe Junpei , Matsumoto Kana , Ito Yukishige
Published: May 2018

The endo-β-
N
-acetylglucosaminidase mutant endo-CC N180H transfers glycan from sialylglycopeptide (SGP) to various acceptors. The scope and limitations of low-molecular-weight acceptors were investigated. Several homogeneous glycan-containing compounds, especially those with potentially useful labels or functional moieties, and possible reagents in glycoscience were synthesized. The 1,3-diol structure is important in acceptor molecules in glycan transfer reactions mediated by endo-CC N180H as well as by endo-M-N175Q. Glycan remodelling of antibodies was explored using core-fucose-deficient anti-CCR4 antibody with SGP and endo-CC N180H. Homogeneity of the glycan in the antibody was confirmed by mass spectrometry without glycan cleavage.
Synthesis of 4-substituted ethers of benzophenone and their antileishmanial activities
Authors:   Arshia, Ahad Faiza , Ghouri Nida ,   Kanwal, Khan Khalid Mohammed , Perveen Shahnaz , Choudhary M. Iqbal
Published: May 2018

Leishmaniasis is a vector-borne protozoan disease; it mainly originates from the bite of sandfly and initiated when parasite is transmitted to human at metacyclic flagellated promastigote form. In the current study, a synthesis of a series of 4-substituted benzophenone ethers1–20was carried out in good yields and theirin vitroantileishmanial activities were also screened. Among synthetic derivatives, 15 compounds1,3,5–12,15and17–20showed antileishmanial activities against promastigotes ofLeishmania majorwith IC50values in the range of 1.19–82.30 µg ml−1, and the values were compared with those of the standard pentamidine (IC50 = 5.09 ± 0.09 µg ml−1). Our study identified a series of new antileishmanial molecules as potential leads. Structures of these synthetic compounds were deduced by different spectroscopic techniques, such as1H and13C nuclear magnetic resonance, electron impact and high-resolution electron impact mass spectrometry and IR.
The physical and qualitative analysis of fluctuations in air and vapour concentrations in a porous medium
Authors: Poorun Y. , Dauhoo M. Z. , Bessafi M. , Elahee M. K. , Gopaul A. , Khoodaruth A.
Published: May 2018

This work presents the development and physical analysis of a sweat transport model that couples the fluctuations in air and vapour concentrations, and temperature, in a one-dimensional porous clothing assembly. The clothing is exposed to inherent time-varying conditions due to variations in the body temperature and ambient conditions. These fluctuations are governed by a coupled system of nonlinear relaxation–transport–diffusion PDEs of Petrovskii parabolic type. A condition for the well-posedness of the resulting system of equations is derived. It is shown that the energy of the diffusion part of the system is exponentially decreasing. The boundedness and stability of the system of equations is thus confirmed. The variational formulation of the system is derived, and the existence and uniqueness of a weak solution is demonstrated analytically. This system is shown to conserve positivity. The difficulty of obtaining an analytical solution due to the complexity of the problem, urges for a numerical approach. A comparison of three cases is made using the Crank–Nicolson finite difference method (FDM). Numerical experiments show the existence of singular coefficient matrices at the site of phase change. Furthermore, the steady-state profiles of temperature, air and vapour concentrations influence the attenuation of fluctuations. Numerical results verify the analytical findings of this work.
Elucidation of immunological response and its regulatory network by P-TUFT-ALT-2: a promising fusion protein vaccine for human lymphatic filariasis
Authors: Paul Rajkumar , Jaiswal Sandeep , Mahalakshmi Natarajan , Kaliraj Perumal
Published: May 2018

Human lymphatic filariasis, a mosquito-borne neglected tropical parasitic disease, needs an early development of prophylactic agents such as a vaccine for its successful elimination. Our earlier study suggested the enhanced immunological response by fusion protein (P-TUFT-ALT-2) of Tuftsin and ALT-2 in a mice model. We cultured human peripheral blood mononuclear cells (PBMCs) and treated cells withEscherichia coli-expressed ALT-2 (E-ALT-2) and P-TUFT-ALT-2. Real-time polymerase chain reaction was performed to identify the mRNA copy number of various cytokine and transcription factor genes. The recombinant vaccine candidate was also validated for humans by immunoreactivity with human sera samples of natural infection. In this study, P-TUFT-ALT-2 stimulated 12% higher PBMC proliferation in endemic normal (EN) individuals than E-ALT-2 alone. There was enhanced production of IFNγ, IL-2, IL-5 and IL-12, indicating a balanced Th1/Th2 response. However, higher expression of IL-5 and lower IL-4 validate the humoral response through an IL-5-dependent manner. Also, high level of IL-17 indicates a strong Th/Treg regulation over T-cell activation. The upregulated T-bet might have enhanced IFN-γ production, whereas GATA-3 was supposed to enhance IL-5 expression. The fusion protein also exhibited 15–16% higher reactivity with EN clinical sera, exposing the upregulation of IgG1 and IgM in natural infection. The higher reactivity of P-TUFT-ALT-2 with sera of natural infection (EN) was validated indirectly by B-cell activation through various cytokines and regulatory genes produced from different T cells. Thus, these findings endorse P-TUFT-ALT-2 as a potential vaccine candidate for human lymphatic filariasis.
Perovskite solar cells in N-I-P structure with four slot-die-coated layers
Authors: Burkitt Daniel , Searle Justin , Watson Trystan
Published: May 2018

The fabrication of perovskite solar cells in an N-I-P structure with compact titanium dioxide blocking, mesoporous titanium dioxide scaffold, single-step perovskite and hole-transport layers deposited using the slot-die coating technique is reported. Devices on fluorine-doped tin oxide-coated glass substrates with evaporated gold top contacts and four slot-die-coated layers are demonstrated, and best cells reach stabilized power conversion efficiencies of 7%. This work demonstrates the suitability of slot-die coating for the production of layers within this perovskite solar cell stack and the potential to transfer to large area and roll-to-roll manufacturing processes.
Geometric models to explore mechanisms of dynamic shape change in skeletal muscle
Authors: Dick Taylor J. M. , Wakeling James M.
Published: May 2018

Skeletal muscle bulges when it contracts. These three-dimensional (3D) dynamic shape changes play an important role in muscle performance by altering the range of fascicle velocities over which a muscle operates. However traditional muscle models are one-dimensional (1D) and cannot fully explain
in vivo
shape changes. In this study we compared medial gastrocnemius behaviour during human cycling (fascicle length changes and rotations) predicted by a traditional 1D Hill-type model and by models that incorporate two-dimensional (2D) and 3D geometric constraints to
in vivo
measurements from B-mode ultrasound during a range of mechanical conditions ranging from 14 to 44 N m and 80 to 140 r.p.m. We found that a 1D model predicted fascicle lengths and pennation angles similar to a 2D model that allowed the aponeurosis to stretch, and to a 3D model that allowed for aponeurosis stretch and variable shape changes to occur. This suggests that if the intent of a model is to predict fascicle behaviour alone, then the traditional 1D Hill-type model may be sufficient. Yet, we also caution that 1D models are limited in their ability to infer the mechanisms by which shape changes influence muscle mechanics. To elucidate the mechanisms governing muscle shape change, future efforts should aim to develop imaging techniques able to characterize whole muscle 3D geometry
in vivo
during active contractions.
Synthesis and photocatalytic activity of mesoporous g-C
3
N
4
/MoS
2
hybrid catalysts
Authors: Qi Yirong , Liang Qinghua , Lv Ruitao , Shen Wanci , Kang Feiyu , Huang Zheng-Hong
Published: May 2018

The key to solving environmental and energy issues through photocatalytic technology requires highly efficient, stable and eco-friendly photocatalysts. Graphitic carbon nitride (g-C
3
N
4
) is one of the most promising candidates except for its limited photoactivity. In this work, a facile and scalable one-step method is developed to fabricate an efficient heterostructural g-C
3
N
4
photocatalyst
in situ
coupled with MoS
2
. The strong coupling effect between the MoS
2
nanosheets and g-C
3
N
4
scaffold, numerous mesopores and enlarged specific surface area helped form an effective heterojunction. As such, the photocatalytic activity of the g-C
3
N
4
/MoS
2
is more than three times higher than that of the pure g-C
3
N
4
in the degradation of RhB under visible light irradiation. Improvement of g-C
3
N
4
/MoS
2
photocatalytic performance is mainly ascribed to the effective suppression of the recombination of charge carriers.
Crystalline modification of a rare earth nucleating agent for isotactic polypropylene based on its self-assembly
Authors: Zhang Yuanming , Sun Tingting , Jiang Wei , Han Guangting
Published: May 2018

In this paper, the crystalline modification of a rare earth nucleating agent (WBG) for isotactic polypropylene (PP) based on its supramolecular self-assembly was investigated by differential scanning calorimetry, wide-angle X-ray diffraction and polarized optical microscopy. In addition, the relationship between the self-assembly structure of the nucleating agent and the crystalline structure, as well as the possible reason for the self-assembly behaviour, was further studied. The structure evolution of WBG showed that the self-assembly structure changed from a needle-like structure to a dendritic structure with increase in the content of WBG. When the content of WBG exceeded a critical value (0.4 wt%), it self-assembled into a strip structure. This revealed that the structure evolution of WBG contributed to the
K
β
and the crystallization morphology of PP with different content of WBG. In addition, further studies implied that the behaviour of self-assembly was a liquid–solid transformation of WBG, followed by a liquid–liquid phase separation of molten isotactic PP and WBG. The formation of the self-assembly structure was based on the free molecules by hydrogen bond dissociation while being heated, followed by aggregation into another structure by hydrogen bond association while being cooled. Furthermore, self-assembly behaviour depends largely on the interaction between WBG themselves.
Ecology of sleeping: the microbial and arthropod associates of chimpanzee beds
Authors: Thoemmes Megan S. , Stewart Fiona A. , Hernandez-Aguilar R. Adriana , Bertone Matthew A. , Baltzegar David A.  , Borski Russell J. , Cohen Naomi , Coyle Kaitlin P. , Piel Alexander K. , Dunn Robert R.
Published: May 2018

The indoor environment created by the construction of homes and other buildings is often considered to be uniquely different from other environments. It is composed of organisms that are less diverse than those of the outdoors and strongly sourced by, or dependent upon, human bodies. Yet, no one has ever compared the composition of species found in contemporary human homes to that of other structures built by mammals, including those of non-human primates. Here we consider the microbes and arthropods found in chimpanzee beds, relative to the surrounding environment (n = 41 and 15 beds, respectively). Based on the study of human homes, we hypothesized that the microbes found in chimpanzee beds would be less diverse than those on nearby branches and leaves and that their beds would be primarily composed of body-associated organisms. However, we found that differences between wet and dry seasons and elevation above sea level explained nearly all of the observed variation in microbial diversity and community structure. While we can identify the presence of a chimpanzee based on the assemblage of bacteria, the dominant signal is that of environmental microbes. We found just four ectoparasitic arthropod specimens, none of which appears to be specialized on chimpanzees or their structures. These results suggest that the life to which chimpanzees are exposed while in their beds is predominately the same as that of the surrounding environment.
scVAE: Variational auto-encoders for single-cell gene expression data
Authors: Grønbech Christopher Heje , Vording Maximillian Fornitz , Timshel Pascal , Sønderby Casper Kaae , Pers Tune Hannes , Winther Ole
Published: May 2018

Motivation

Models for analysing and making relevant biological inferences from massive amounts of complex single-cell transcriptomic data typically require several individual data-processing steps, each with their own set of hyperparameter choices. With deep generative models one can work directly with count data, make likelihood-based model comparison, learn a latent representation of the cells and capture more of the variability in different cell populations.

Results

We propose a novel method based on variational auto-encoders (VAEs) for analysis of single-cell RNA sequencing (scRNA-seq) data. It avoids data preprocessing by using raw count data as input and can robustly estimate the expected gene expression levels and a latent representation for each cell. We tested several count likelihood functions and a variant of the VAE that has a priori clustering in the latent space. We show for several scRNA-seq data sets that our method outperforms recently proposed scRNA-seq methods in clustering cells and that the resulting clusters reflect cell types.

Availability and implementation

Our method, called scVAE, is implemented in Python using the TensorFlow machine-learning library, and it is freely available at https://github.com/scvae/scvae.
Entrainment of circadian rhythms depends on firing rates and neuropeptide release of VIP SCN neurons
Authors: Mazuski Cristina , Abel John H. , Chen Samantha P. , Hermanstyne Tracey O. , Jones Jeff R. , Simon Tatiana , Doyle Francis J. , Herzog Erik D.
Published: May 2018

The mammalian suprachiasmatic nucleus (SCN) functions as a master circadian pacemaker, integrating environmental input to align physiological and behavioral rhythms to local time cues. Approximately 10% of SCN neurons express vasoactive intestinal polypeptide (VIP); however, it is unknown how firing activity of VIP neurons releases VIP to entrain circadian rhythms. To identify physiologically relevant firing patterns, we optically tagged VIP neurons and characterized spontaneous firing over three days. VIP neurons had circadian rhythms in firing rate and exhibited two classes of instantaneous firing activity. We next tested whether physiologically relevant firing affected circadian rhythms through VIP release. We found that VIP neuron stimulation with high, but not low, frequencies shifted gene expression rhythms in vitro through VIP signaling. In vivo, high frequency VIP neuron activation rapidly entrained circadian locomotor rhythms. Thus, increases in VIP neuronal firing frequency release VIP and entrain molecular and behavioral circadian rhythms.

Highlights

Mazuski et al. identified three classes of circadian SCN neurons based on their distinct firing patterns consistent over multiple days

There are two distinct classes (tonic and irregular firing) of VIP SCN neurons.

Stimulation of VIP SCN neurons at physiologically relevant frequencies phase shifts whole-SCN circadian rhythms in gene expression through VIP release. These effects are blocked with VIP antagonists.

Firing of VIP SCN neurons entrains circadian rhythms in locomotor behavior in a frequency and time-of-day dependent manner.
Autolysin-Independent DNA Release inStreptococcus pneumoniae in vitroBiofilms
Authors: Domenech Mirian , García Ernesto
Published: May 2018

Biofilms are defined as layers of cells of microorganisms adhered to the surface of a substrate and embedded in an extracellular matrix and provide an appropriate environment for increased genetic exchange. Extracellular DNA (eDNA) is an essential component of the extracellular matrix of microbial biofilms, but the pathway(s) responsible for DNA release are largely unknown. Autolysis (either spontaneous or phage-induced) has been proposed the major event leading to the appearance of eDNA. The ‘suicidal tendency’ ofStreptococcus pneumoniaeis well-known, with lysis mainly caused by the triggering of LytA, the major autolytic amidase. However, the LytC lysozyme and CbpD (a possible murein hydrolase) have also been shown involved. The present work examines the relationship between eDNA, autolysins, and the formation and maintenance ofin vitropneumococcal biofilms, via fluorescent labelling combined with confocal laser scanning microscopy, plus genetic transformation experiments. Bacterial DNA release mechanisms other than those entailing lytic enzymes were shown to be involved by demonstrating that horizontal gene transfer in biofilms takes place even in the absence of detectable autolytic activity. It had been previously suggested that the quorum sensing systems ComABCDE and LuxS/AI-2 are involved in the production of eDNA as a response to the accumulation of quorum sensing signals, although our immunofluorescence results do not support this hypothesis. Evidence that the release of DNA is somehow linked to the production of extracellular vesicles byS. pneumoniaeis provided.
Using High Throughput DNA Sequencing to Evaluate the Accuracy of Serial Dilution Based Tests of Microbial Activities in Oil Pipelines
Authors: Khanipov K. , Golovko G. , Rojas M. , Pimenova M. , Albayrak L. , Chumakov S. , Duarte R. , Widger W.R. , Pickthall T. , Fofanov Y.
Published: May 2018

Microbial activities have detrimental effects on industrial infrastructure. If not controlled, microbial presence can result in corrosion, biofilm formation, and product degradation. Serial dilution tests are routinely used for evaluating presence and abundance of microorganisms by diluting samples and culturing microbes in specific media designed to support microorganisms with particular properties, such as sulfate reduction.

A high-throughput sequencing approach was used to evaluate changes in microbial composition during four standard serial dilution tests. Analysis of 159 isolates revealed significant differences in the microbial compositions of sequential serial dilution titers and identified several cases where: (a) bacteria known to have a detrimental metabolic function (such as acid production) were lost in the serial dilution medium designed to test for this function; (b) bacteria virtually absent in the original sample became dominant in the serial dilution medium. These observations raise concerns regarding the accuracy and overall usefulness of serial dilution tests.
Quasi-periodic patterns contribute to functional connectivity in the brain
Authors: Abbas Anzar , Belloy Michaël , Kashyap Amrit , Billings Jacob , Nezafati Maysam , Schumacher Eric , Keilholz Shella
Published: May 2018

Functional connectivity is widely used to study the coordination of activity between brain regions over time. Functional connectivity in the default mode and task positive networks is particularly important for normal brain function. However, the processes that give rise to functional connectivity in the brain are not fully understood. It has been postulated that low-frequency neural activity plays a key role in establishing the functional architecture of the brain. Quasi-periodic patterns (QPPs) are a reliably observable form of low-frequency neural activity that involve the default mode and task positive networks. Here, QPPs from resting-state and working memory task-performing individuals were acquired. The spatiotemporal pattern, strength, and frequency of the QPPs between the two groups were compared and the contribution of QPPs to functional connectivity in the brain was measured. In task-performing individuals, the spatiotemporal pattern of the QPP changes, particularly in task-relevant regions, and the QPP tends to occur with greater strength and frequency. Differences in the QPPs between the two groups could partially account for the variance in functional connectivity between resting-state and task-performing individuals. The QPPs contribute strongly to connectivity in the default mode and task positive networks and to the strength of anti-correlation seen between the two networks. Many of the connections affected by QPPs are also disrupted during several neurological disorders. These findings contribute to understanding the dynamic neural processes that give rise to functional connectivity in the brain and how they may be disrupted during disease.

Highlights

Quasi-periodic patterns (QPPs) of low-frequency activity contribute to functional connectivity

The spatiotemporal pattern of QPPs differs between resting-state and task-performing individuals

QPPs account for significant functional connectivity in the DMN and TPN during rest and task performance

Changes in functional connectivity in these networks may reflect differences in QPPs
Hyd ubiquitinates the NF-κB co-factor Akirin to activate an effective immune response in Drosophila
Authors: Cammarata-Mouchtouris Alexandre , Nguyen Xuan-Hung , Bonnay François , Goto Akira , Orian Amir , Fauvarque Marie-Odile , Boutros Michael , Reichhart Jean-Marc , Matt Nicolas
Published: May 2018

One Sentence Summary

Upon microbial infection in Drosophila, the E3-ubiquitin ligase Hyd ubiquitinylates the NF-κB co-factor Akirin for its efficient binding to the NF-κB factor Relish and subsequent activation of immune effectors genes.

The Drosophila IMD pathway is activated upon microbial challenge with Gramnegative bacteria to trigger the innate immune response. In order to decipher this NF-κB signaling pathway, we undertook an ex-vivo RNAi screen targeting specifically E3 ubiquitin ligases and identified the HECT E3 ubiquitin ligase Hyperplastic Discs “Hyd” as a new actor of the IMD pathway. We showed that Hyd targets the NF-κB cofactor of Akirin. The K63-polyubiquitination chains deposited by Hyd decorate Akirin for its efficient binding to the NF-κB transcription factor Relish. We showed that this Hyd-mediated interaction is critical to activate immune-induced genes that depend on both Relish and Akirin, but is dispensable for those that depend solely on Relish. Therefore Hyd is key in operating a NF-κB transcriptional selectivity downstream of the IMD pathway. Drosophila depleted for Hyd or Akirin failed to express the full set of immune-induced anti-microbial peptide coding genes and succumbed to immune challenges. We showed further that Ubr5, the mammalian homolog of Hyd, is also required downstream of the NF-κB pathway for the IL1β-mediated IL6 activation. This study links the action of a E3-ubiquitin ligase to the activation of immune effector genes, deepening our understanding of the involvement of ubiquitination in inflammation and identifying a potential target for the control of inflammatory diseases.
Organized spatial patterns of activated β2integrins in arresting neutrophils
Authors: Fan Zhichao , Kiosses William Bill , Zajonc Dirk M. , Arnaout M. Amin , Gutierrez Edgar , Groisman Alex , Ley Klaus
Published: May 2018

The transition from leukocyte rolling to firm adhesion is called arrest. β2integrins are required for neutrophil arrest1. Chemokines can trigger neutrophil arrest in vivo2and in vitro3. Resting integrins4exist in a “bent-closed” conformation, i.e., not extended (E−) and not high affinity (H−), unable to bind ligand. Electron microscopic images of isolated β2integrins in “open” and “closed” conformations5inspired the switchblade model of integrin activation from E−H−to E+H−to E+H+67. Recently8, we discovered an alternative pathway of integrin activation from E−H−to E−H+to E+H+. Spatial patterning of activated integrins is thought to be required for effective arrest, but so far only diffraction-limited localization maps of activated integrins exist8. Here, we combine superresolution microscopy with molecular modeling to identify the molecular patterns of H+E−, H−E+, and H+E+activated integrins on primary human neutrophils. At the time of neutrophil arrest, E+H+integrins form oriented (non-random) nanoclusters that contain a total of 4,625±369 E+H+β2integrin molecules.
Parasite intensity is driven by temperature in a wild bird
Authors: Mennerat Adèle , Charmantier Anne , Perret Philippe , Hurtrez-Boussès Sylvie , Lambrechts Marcel M.
Published: May 2018

Increasing awareness that parasitism is an essential component of nearly all aspects of ecosystem functioning, as well as a driver of biodiversity, has led to rising interest in the consequences of climate change in terms of parasitism and disease spread. Yet empirical knowledge on the extent and ways in which climatic factors affect parasite prevalence and intensities remains scarce. In an 18-year, multi-site, correlative study we investigated the contributions of weather variables and other factors to spatio-temporal variation in infestation by blowfly parasitic larvae (Protocalliphoraspp.) in nests of Corsican blue tits (Cyanistes caeruleus). We found that ambient temperature during the nestling stage is strongly and positively related to parasite load (number of parasites per chick), both across broods when controlling for year, and across years. In addition, annual mean parasite load also increased with minimal spring temperature, and decreased with increasing average temperature in the previous summer. There was no indication of a dependence of parasite dynamics on host dynamics in this system, likely due in part to the wide host range of blowflies that do not solely rely on blue tit hosts. This suggests a major effect of temperature during the blowfly life cycle, with potential implications for blowfly – host interactions across their geographical range as climate keeps warming up. Finally, given that ambient temperature increases throughout the breeding season and that blowflies negatively affect survival and recruitment of blue tits, these results also mean that parasites, along with caterpillar availability, can drive selection for breeding date in this system.
Genome-Scale CRISPR Screening Identifies Novel Human Pluripotent Gene Networks
Authors: Ihry Robert J. , Salick Max R. , Ho Daniel J. , Sondey Marie , Kommineni Sravya , Paula Steven , Raymond Joe , Frias Elizabeth , Worringer Kathleen A. , Russ Carsten , Reece-Hoyes John , Altshuler Bob , Randhawa Ranjit , Yang Zinger , McAllister Gregory , Hoffman Gregory R. , Dolmetsch Ricardo , Kaykas Ajamete
Published: May 2018

Human pluripotent stem cells (hPSCs) generate a wide variety of disease-relevant cells that can be used to improve the translation of preclinical research. Despite the potential of hPSCs, their use for genetic screening has been limited because of technical challenges. We developed a renewable Cas9/sgRNA-hPSC library where loss-of-function mutations can be induced at will. Our inducible-mutant hPSC library can be used for an unlimited number of genome-wide screens. We screened for novel genes involved in 3 of the fundamental properties of hPSCs: Their ability to self-renew/survive, their capacity to differentiate into somatic cells, and their inability to survive as single-cell clones. We identified a plethora of novel genes with unidentified roles in hPSCs. These results are available as a resource for the community to increase the understanding of both human development and genetics. In the future, our stem cell library approach will be a powerful tool to identify disease-modifying genes.

VISUAL ABSTRACT
Integration of cell cycle signals by multi-PAS domain kinases
Authors: Mann Thomas H. , Shapiro Lucy
Published: May 2018

Spatial control of intracellular signaling relies on signaling proteins sensing their subcellular environment. In many cases, a large number of upstream signals are funneled to a master regulator of cellular behavior, but it remains unclear how individual proteins can rapidly integrate a complex array of signals within the appropriate spatial niche within the cell. As a model for how subcellular spatial information can control signaling activity, we have reconstituted the cell pole-specific control of the master regulator kinase/phosphatase CckA from the asymmetrically dividing bacterium Caulobacter crescentus. CckA is active as a kinase only when it accumulates within a microdomain at the new cell pole, where it co-localizes with the pseudokinase DivL. Both proteins contain multiple PAS domains, a multifunctional class of sensory domains present across the kingdoms of life. Here, we show that CckA uses its PAS domains to integrate information from DivL and on its own oligomerization state to control the balance of its kinase and phosphatase activities. We reconstituted the DivL-CckA complex on liposomes in vitro and found that DivL directly controls the CckA kinase-phosphatase switch, and that stimulation of either CckA catalytic activity depends on the second of its two PAS domains. We further show that CckA oligomerizes through a multi-domain interaction that is critical for stimulation of kinase activity by DivL, while DivL stimulation of CckA phosphatase activity is independent of CckA homo-oligomerization. Our results broadly demonstrate how signaling factors can leverage information from their subcellular niche to drive spatiotemporal control of cell signaling.

Significance

Cells must constantly make decisions involving many pieces of information at a molecular level. Kinases containing multiple PAS sensory domains detect multiple signals to determine their signaling outputs. In the asymmetrically dividing bacterium Caulobacter crescentus, the multi-sensor proteins DivL and CckA promote different cell types depending upon their subcellular location. We reconstituted the DivL-CckA interaction in vitro and showed that specific PAS domains of each protein function to switch CckA between kinase and phosphatase activities, which reflects their functions in vivo. Within the context of the cell, our reconstitution illustrates how multi-sensor proteins can use their subcellular location to regulate their signaling functions.
Cryptsim: Modeling the evolutionary dynamics of the progression of Barrett’s esophagus to esophageal adenocarcinoma
Authors: Mallo Diego , Kostadinov Rumen , Cisneros Luis , Kuhner Mary K. , Maley Carlo C.
Published: May 2018

To alleviate the over-diagnosis and overtreatment of premalignant conditions we need to predict their progression to cancer, and therefore, the dynamics of an evolutionary process. However, monitoring evolutionary processes in vivo is extremely challenging. Computer simulations constitute an attractive alternative, allowing us to study these dynamics based on a set of evolutionary parameters.

We introduce CryptSim, a simulator of crypt evolution inspired by Barrett’s esophagus. We detail the most relevant computational strategies it implements, and perform a simulation study showing that the interaction between neighboring crypts may play a crucial role in carcinogenesis.
In vitro neural networks minimise variational free energy
Authors: Isomura Takuya , Friston Karl
Published: May 2018

In this work, we address the neuronal encoding problem from a Bayesian perspective. Specifically, we ask whether neuronal responses in anin vitroneuronal network are consistent with ideal Bayesian observer responses under the free energy principle. In brief, we stimulated anin vitrocortical cell culture with stimulus trains that had a known statistical structure. We then asked whether recorded neuronal responses were consistent with variational message passing (i.e., belief propagation) based upon free energy minimisation (i.e., evidence maximisation). Effectively, this required us to solve two problems: first, we had to formulate the Bayes-optimal encoding of the causes or sources of sensory stimulation, and then show that these idealised responses could account for observed electrophysiological responses. We describe a simulation of an optimal neural network (i.e., the ideal Bayesian neural code) and then consider the mapping from idealisedin silicoresponses to recordedin vitroresponses. Our objective was to find evidence for functional specialisation and segregation in thein vitroneural network that reproducedin silicolearning via free energy minimisation. Finally, we combined thein vitroandin silicoresults to characterise learning in terms of trajectories in a variational information plane of accuracy and complexity.