bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Network Support and Decreased Risk of Seroconversion in Black MSM: Results of the BROTHERS (HPTN 061) Study
Authors: Hermanstyne Keith A. , Green Harold D. , Cook Ryan , Tieu Hong-Van , Dyer Typhanye V. , Hucks-Ortiz Christopher , Wilton Leo , Latkin Carl , Shoptaw Steven
Published: February 2018

Background and setting:

Black men who have sex with men (BMSM) in the United States have disproportionately high HIV infection rates. Social networks have been shown to influence HIV risk behavior; however, little is known about whether they affect the risk of HIV seroconversion. This study uses data from the BROTHERS (HPTN 061) study to test whether contextual factors related to social networks are associated with HIV seroconversion among BMSM.

Methods:

We analyzed data from the BROTHERS study (2009–2011), which examined a multicomponent intervention for BMSM in 6 US cities. We ran a series of Cox regression analyses to examine associations between time-dependent measures of network support (personal/emotional, financial, medical, and social participation) and time to HIV seroconversion. We ran unadjusted models followed by models adjusted for participant age at enrollment and study location.

Results:

A total of 1000 BMSM tested HIV negative at baseline and were followed at 6- and 12-month study visits. Twenty-eight men tested HIV positive. In adjusted hazard ratio models, study participants who remained HIV negative had higher proportions of social network members who provided personal/emotional {0.92 [95% confidence interval (CI): 0.85 to 0.99]}, medical [0.92 (95% CI: 0.85 to 0.99)], or social participation [0.91 (95% CI: 0.86 to 0.97)] support.

Conclusion:

Findings suggest that the increased presence of social network support can be protective against HIV acquisition. Future research should explore the processes that link social network support with sexual and other transmission risk behaviors as a basis to inform HIV prevention efforts.
Texture Analysis and Machine Learning for Detecting Myocardial Infarction in Noncontrast Low-Dose Computed Tomography
Authors: Mannil Manoj , von Spiczak Jochen , Manka Robert , Alkadhi Hatem
Published: February 2018

Objectives

The aim of this study was to test whether texture analysis and machine learning enable the detection of myocardial infarction (MI) on non–contrast-enhanced low radiation dose cardiac computed tomography (CCT) images.

Materials and Methods

In this institutional review board–approved retrospective study, we included non–contrast-enhanced electrocardiography-gated low radiation dose CCT image data (effective dose, 0.5 mSv) acquired for the purpose of calcium scoring of 27 patients with acute MI (9 female patients; mean age, 60 ± 12 years), 30 patients with chronic MI (8 female patients; mean age, 68 ± 13 years), and in 30 subjects (9 female patients; mean age, 44 ± 6 years) without cardiac abnormality, hereafter termed controls. Texture analysis of the left ventricle was performed using free-hand regions of interest, and texture features were classified twice (Model I: controls versus acute MI versus chronic MI; Model II: controls versus acute and chronic MI). For both classifications, 6 commonly used machine learning classifiers were used: decision tree C4.5 (J48), k-nearest neighbors, locally weighted learning, RandomForest, sequential minimal optimization, and an artificial neural network employing deep learning. In addition, 2 blinded, independent readers visually assessed noncontrast CCT images for the presence or absence of MI.

Results

In Model I, best classification results were obtained using the k-nearest neighbors classifier (sensitivity, 69%; specificity, 85%; false-positive rate, 0.15). In Model II, the best classification results were found with the locally weighted learning classification (sensitivity, 86%; specificity, 81%; false-positive rate, 0.19) with an area under the curve from receiver operating characteristics analysis of 0.78. In comparison, both readers were not able to identify MI in any of the noncontrast, low radiation dose CCT images.

Conclusions

This study indicates the ability of texture analysis and machine learning in detecting MI on noncontrast low radiation dose CCT images being not visible for the radiologists' eye.
Intravenous Calcium-/Zinc-Diethylene Triamine Penta-Acetic Acid in Patients With Presumed Gadolinium Deposition Disease
Authors: Semelka Richard C. , Ramalho Miguel , Jay Michael , Hickey Lisa , Hickey Joseph
Published: February 2018

Objectives

The aim of this study was to report the use of intravenous calcium (Ca)-/zinc (Zn)-diethylene triamine penta-acetic acid (DTPA) for the treatment of 25 symptomatic patients diagnosed with gadolinium deposition disease (GDD).

Materials and Methods

Written informed consent was obtained. Twenty-five patients (18 women; mean age, 46.8 ± 15.3 years) with a diagnosis of GDD were included. All patients had received at least 1 administration of a gadolinium (Gd)-based contrast agent. Patients received 3 treatment sessions with Ca-/Zn-DTPA, 15 with treatments spaced 1 month apart, and 10 with treatments spaced 1 week apart. In all cases, every treatment consisted of an application of Ca-DTPA and Zn-DTPA separated by 24 hours. Measurements of 24-hour urine Gd content before dosing and on the first and second days of therapy were performed. Symptomatic improvement of patients was determined by use of a 10-point scale of patient symptoms. Serum electrolytes were quantified.

Results

Gadolinium content increased in the urine, with an overall mean of 30.3-fold increase in the monthly regimen (P < 0.001) and 12.9-fold in the weekly regimen (P < 0.001). Eleven patients experienced transient worsening of at least some of their symptoms, termed a “flare-up” phenomenon, in most of whom symptoms improved or receded. Overall, symptoms improved in 13 patients, unchanged in 10, and worse in 2. Significant clinical improvement was present for headache, brain fog, and bone pain for the monthly regimen and arm pain and leg pain for the weekly regimen. There were no significant changes in major serum electrolytes.

Conclusions

Three courses of intravenous Ca-/Zn-DTPA therapy results in significantly increased urine content of Gd after treatment and moderate symptomatic improvement.
Occlusion-Fit Three-Dimensional–Printed Zygoma Repositioner
Authors: Cho Jinyong , Kwon Jae-Sung , Lee Ui-Lyong
Published: February 2018

Reduction malarplasty is utilized to reshape the facial form into an oval shape. However, complications and unfavorable results in reduction malarplasty have been reported. Reoperation of a nonunion malar complex is difficult relative to the achievement of a satisfactory outcome using the intraoral approach with a narrow surgical field because the normal anatomy has been destroyed, and previous surgery may have caused asymmetry. In this situation, computer-aided simulation surgery and surgical guides can serve as effective solutions to overcome the limitations of reoperative malarplasty using the intraoral approach.

In this report, the authors present a case with successful treatment outcomes for a nonunion malar complex using a three-dimensional-printed zygoma repositioner.
Surgical Treatment of Osteoma in the Basilar Region of the Mandible
Authors: Bartoli Manoela Moura De , Maciel Luis Felipe Oliveira , de Alencar Marília Gabriela Mendes , da Silva Thiago Coelho Gomes , Vasconcellos Ricardo José Holanda
Published: February 2018

Osteoma is an uncommon benign osteogenic tumor characterized by the proliferation of compact and cancellous bone. The objective of this study was to report a case of osteoma in the basilar region of the mandible. The patient reported no pain, but the affected area was tender to touch and there was esthetic concern because of the apparent swelling. The mass measured approximately 5 cm in diameter and extended to the lingual area of the mandible. A vestibular approach was used for surgical treatment. After infiltration of a local anesthetic and vasoconstrictor, to expose the mandibular ramus, an incision was made with an electric scalpel along the external oblique ridge through the mucosa, submucosa and muscle, fascia and periosteum until the lower second molar, 3 to 5 mm inferior to the mucogingival junction. A mucoperiosteal flap was raised until the base of the mandible to access the tumor. Osteotomy was performed and the tumor was removed. The patient shows no recurrence of the tumor after 1 year and 6 months of follow-up. Periodical clinical and radiographic follow-up are satisfactory since recurrence is rare.
Neurofibroma of the Nasal Ala: Pediatric Nasal Reconstruction
Authors: Gómez Oswaldo J. , Bernal Mónica , Martínez Diana Carolina
Published: February 2018

Benign tumors of the nasal cavity originating from a peripheral nerve sheath are rare. The authors present a case of a 3-month-old boy with a mass in the left nasal vestibule. The surgical resection was complicated by full-thickness necrosis of more than 50% of the nasal ala. The tumor was diagnosed histopathologically as a neurofibroma with glial heterotopia. The details of the nasal reconstruction with a paramedian forehead flap in 3 stages and postoperative results are provided with satisfactory cosmetic and functional results.
Esterification of phenyl acetic acid with
p
-cresol using metal cation exchanged montmorillonite nanoclay catalysts
Authors: Bhaskar M. , Surekha M. , Suma N.
Published: February 2018

The liquid phase esterification of phenyl acetic acid with
p
-cresol over different metal cation exchanged montmorillonite nanoclays yields
p
-cresyl phenyl acetate. Different metal cation exchanged montmorillonite nanoclays (M

n

+
 = Al
3+
, Zn
2+
, Mn
2+
, Fe
3+
, Cu
2+
) were prepared and the catalytic activity was studied. The esterification reaction was conducted by varying molar ratio of the reactants, reaction time and catalyst amount on the yield of the ester. Among the different metal cation exchanged catalysts used, Al
3+
-montmorillonite nanoclay was found to be more active. The characterization of the material used was studied under different techniques, namely X-ray diffraction, scanning electron microscopy and thermogravimetric analysis. The product obtained,
p
-cresyl phenyl acetate, was identified by thin-layer chromotography and confirmed by Fourier transform infrared,
1
H NMR and
13
C NMR. The regeneration activity of used catalyst was also investigated up to fourth generation.
Context-dependent signaling of coincident auditory and visual events in primary visual cortex
Authors: Deneux Thomas , Kempf Alexandre , Bathellier Brice
Published: February 2018

Detecting rapid coincident changes across sensory modalities is essential to recognize sudden threats and events. Using two-photon calcium imaging in identified cell types in awake mice, we show that auditory cortex (AC) neurons projecting to primary visual cortex (V1) preferentially encode the abrupt onsets of sounds. In V1, a sub-population of layer 1 interneurons gates this selective cross-modal information by a suppression specific to the absence of visual inputs. However, when large auditory onsets coincide with visual stimuli, visual responses are strongly boosted in V1. Thus, a dynamic asymmetric circuit across AC and V1 specifically identifies visual events starting simultaneously to sudden sounds, potentially catalyzing localization of new sound sources in the visual field.
Rationally-engineered reproductive barriers using CRISPR & CRISPRa: an evaluation of the synthetic species concept inDrosophila melanogaster
Authors: Waters Andrew J , Capriotti Paolo , Gaboriau David , Papathanos Philippos Aris , Windbichler Nikolai
Published: February 2018

The ability to erect rationally-engineered reproductive barriers in animal or plant species promises to enable a number of biotechnological applications such as the creation of genetic firewalls, the containment of gene drives or novel population replacement and suppression strategies for genetic control. However, to date no experimental data exist that explores this concept in a multicellular organism. Here we examine the requirements for building artificial reproductive barriers in the metazoan modelDrosophila melanogasterby combining CRISPR-based genome editing and transcriptional transactivation (CRISPRa) of the same loci. We directed 13 single guide RNAs (sgRNAs) to the promoters of 7 evolutionary conserved genes and used 11 drivers to conduct a miss-activation screen. We identify dominant-lethal activators of theevelocus and find that they disrupt development by strongly activatingeveoutside its native spatio-temporal context. We employ the same set of sgRNAs to isolate, by genome editing, protective INDELs that render these loci resistant to transactivation without interfering with target gene function. When these sets of genetic components are combined we find that complete synthetic lethality, a prerequisite for most applications, is achievable using this approach. However, our results suggest a steep trade-off between the level and scope of dCas9 expression, the degree of genetic isolation achievable and the resulting impact on fly fitness. The genetic engineering strategy we present here allows the creation of single or multiple reproductive barriers and could be applied to other multicellular organisms such as disease vectors or transgenic organisms of economic importance.
Comprehensive and empirical evaluation of machine learning algorithms for LC retention time prediction
Authors: Bouwmeester Robbin , Martens Lennart , Degroeve Sven
Published: February 2018

Liquid chromatography is a core component of almost all mass spectrometric analyses of (bio)molecules. Because of the high-throughput nature of mass spectrometric analyses, the interpretation of these chromatographic data increasingly relies on informatics solutions that attempt to predict an analyte’s retention time. The key components of such predictive algorithms are the features these are supplies with, and the actual machine learning algorithm used to fit the model parameters.

We here therefore evaluate the performance of seven machine learning algorithms on 36 distinct metabolomics data sets, using two distinct feature sets. Interestingly, the results show that no single learning algorithm performs optimally for all data sets, with different algorithm types achieving top performance for different types of analytes or different protocols. Our results can thus be used to find an optimal retention time prediction algorithm for specific analytes or protocols. Importantly, however, our results also show that blending different types of models together decreases the error on outliers, indicating that the combination of several approaches holds substantial promise for the development of more generic, high-performing algorithms.
Loss of SDHB reprograms energy metabolisms and inhibits high fat diet induced metabolic syndromes
Authors: Mu Chenglong , Ma Biao , Zhang Chuanmei , Geng Guangfeng , Zhang Xinling , Chen Linbo , Wang Meng , Li Jie , Zhao Tian , Cheng Hongcheng , Zhang Qianping , Ma Kaili , Luo Qian , Chang Rui , Liu Qiangqiang , Wu Hao , Liu Lei , Wang Xiaohui , Wang Jun , Zhang Yong , Zhao Yungang , Wen Li , Chen Quan , Zhu Yushan
Published: February 2018

Mitochondrial respiratory complex II utilizes succinate, key substrate of the Krebs cycle, for oxidative phosphorylation, which is essential for glucose metabolism. Mutations of complex II cause cancers and mitochondrial diseases, raising a critical question of the (patho-)physiological functions. To address the fundamental role of complex II in systemic energy metabolism, we specifically knockout SDHB in mice liver, a key complex II subunit that tethers the catalytic SDHA subunit and transfers the electrons to ubiquinone, and found that SHDB deficiency abolishes the assembly of complex II without affecting other respiration complexes while largely retaining SDHA stability. SHDB ablation reprograms energy metabolism and hyperactivates the glycolysis, Krebs cycle and β-oxidation pathways, leading to catastrophic energy deficit and early death. Strikingly, sucrose supplementation or high fat diet resumes both glucose and lipid metabolism and prevent early death. Also, SDHB deficient mice are completely resistant to high fat diet induced obesity. Our findings reveal that the unanticipated role of complex II orchestrating both lipid and glucose metabolisms, and suggest that SDHB is an ideal therapeutic target for combating obesity.
CLIC4 is regulated by RhoA-mDia2 signaling through Profilin-1 binding to modulate filopodium length
Authors: Argenzio Elisabetta , Kedziora Katarzyna M. , Nahidiazar Leila , Isogai Tadamoto , Perrakis Anastassis , Jalink Kees , Moolenaar Wouter H. , Innocenti Metello
Published: February 2018

CLIC4 is a cytosolic protein implicated in diverse actin-based processes, including integrin trafficking, cell adhesion and tubulogenesis. CLIC4 is rapidly recruited to the plasma membrane by G12/13-coupled receptor agonists and then partly co-localizes with β1 integrins. Receptor-mediated CLIC4 translocation depends on actin polymerization, but the mechanism and functional significance of CLIC4 trafficking are unknown. Here we show that RhoA activation by either LPA or EGF is necessary and sufficient for CLIC4 translocation, with a regulatory role for the RhoA effector mDia2, an inducer of actin polymerization. We find that CLIC4 directly interacts with the G-actin-binding protein Profilin-1 via conserved residues that are required for CLIC4 trafficking and lie in a concave surface. Consistently, silencing of Profilin-1 impaired CLIC4 trafficking induced by either LPA or EGF. CLIC4 knockdown promoted the formation of long integrin-dependent filopodia, a phenotype rescued by wild-type CLIC4 but not by trafficking-incompetent CLIC4(C35A). Our results establish CLIC4 as a Profilin-1-binding protein and suggest that CLIC4 translocation provides a feedback mechanism to modulate mDia2/Profilin-1-driven cortical actin assembly and membrane protrusion.
Apolipoprotein L1 Dynamics in Human Parietal Epithelial Cell Molecular Phenotype Kinetics
Authors: Kumar Vinod , Vashistha Himanshu , Lan Xiqian , Chandel Nirupama , Ayasolla Kamesh , Shoshtari Shadafarin Marashi , Aslam Rukhsana , Paliwal Nitpriya , Abbruscato Frank , Mikulak Joanna , Popik Waldemar , Malhotra Ashwani , Meyer-Schwesinger Catherine , Skorecki Karl , Singhal Pravin C
Published: February 2018

Human Parietal Epithelial cells (PECs) are considered as a source of progenitor cells to sustain podocyte (PD) homeostasis. We hypothesized that the absence of apolipoprotein (APO) L1 favors the PEC phenotype and that induction of APOL1 transitions to PD renewal. During PECs’ transition, APOL1 expression coincided with the expression of PD markers (PEC transition) along with down regulation of miR193a. The induction of APOL1 down regulated miR193a and induced PD markers in PECs/HEKs; whereas, the APOL1-silencing in transited (Tr)-PECs/HepG2s up regulated miR193a expression suggesting a reciprocally linked feedback loop relationship between APOL1 and miR193a. HIV, IFN-y, and vitamin D receptor agonist (VDA) induced APOL1 expression and PEC transition markers but down regulated miR193a in PECs/HEKs. Glomeruli in HIV patients and HIV: APOL1 transgenic mice displayed foci of PECs expressing synaptopodin, a PEC transition marker. Since APOL1 silencing in PECs partially attenuated HIV-, VDA-, and IFN-y-induced PECs transition, this would suggest that APOL1 is an important functional constituent of APOL1-miR193a axis.
Imposing a curfew on the use of screen electronic devices improves sleep and daytime vigilance in adolescents
Authors: Perrault Aurore A. , Bayer Laurence , Peuvrier Matthias , Afyouni Alia , Ghisletta Paolo , Brockmann Celine , Spiridon Mona , Vesely Sophie Hulo , Perrig Stephen , Schwartz Sophie , Sterpenich Virginie
Published: February 2018

The use of screen electronic devices (SED) in the evening negatively affects sleep. Yet, sleep is known to be essential for brain maturation and a key factor for good academic performance, and thus is particularly critical during childhood and adolescence. While previous studies reported correlations between SED use and sleep impairments, the causal relationship between SED use and sleep in adolescents remains unclear. Using actigraphy and daily questionnaires in a large sample of students (12 to 19 years old), we assessed SED use and sleep habits over one month, including a two-week baseline phase and a two-week interventional phase, where participants were asked to stop screen use after 9 pm during pre-school nights. During the interventional phase, we found that reduction in time spent on SED after 9 pm correlated with earlier sleep onset time and increased total sleep duration. The latter led to improved daytime vigilance. We also observed that the beneficial impact of the intervention on sleep was influenced by catechol-O-methyltransferase gene (COMT) Val158Met polymorphism, which is implicated in the dopaminergic modulation of human behaviors, including wake and sleep regulation. These findings provide evidence that restricting SED use in the evening represents a valid and promising approach for improving sleep duration in adolescents, with potential implications for daytime functioning and health.

STATEMENT OF SIGNIFICANCE

With the emergence of smartphones and other connected devices, adolescents spend a lot of time on screen electronic devices (SED), especially during the evening. We report that time spent on SED after 9 pm negatively correlates with sleep onset time, sleep duration as well as mood, body weight, and academic performance. Such observable correlations urge for educational strategies to address the chronic lack of sleep observed in today’s adolescent populations. Here we also show that limiting the use of SED after 9 pm improves sleep duration and daytime vigilance in most adolescents. This simple education recommendation pertaining to sleep hygiene can be implemented by every household, yielding direct positive effects on sleep, and presumed benefits for health and daytime functioning.
GSEA-InContext: Identifying novel and common patterns in expression experiments
Authors: Powers Rani K. , Goodspeed Andrew , Pielke-Lombardo Harrison , Tan Aik-Choon , Costello James C.
Published: February 2018

Motivation

Gene Set Enrichment Analysis (GSEA) is routinely used to analyze and interpret coordinate changes in transcriptomics experiments. For an experiment where less than seven samples per condition are compared, GSEA employs a competitive null hypothesis to test significance. A gene set enrichment score is tested against a null distribution of enrichment scores generated from permuted gene sets, where genes are randomly selected from the input experiment. Looking across a variety of biological conditions, however, genes are not randomly distributed with many showing consistent patterns of up- or down-regulation. As a result, common patterns of positively and negatively enriched gene sets are observed across experiments. Placing a single experiment into the context of a relevant set of background experiments allows us to identify both the common and experiment-specific patterns of gene set enrichment.

Results

We compiled a compendium of 442 small molecule transcriptomic experiments and used GSEA to characterize common patterns of positively and negatively enriched gene sets. To identify experiment-specific gene set enrichment, we developed the GSEA-InContext method that accounts for gene expression patterns within a user-defined background set of experiments to identify statistically significantly enriched gene sets. We evaluated GSEA-InContext on experiments using small molecules with known targets and show that it successfully prioritizes gene sets that are specific to each experiment, thus providing valuable insights that complement standard GSEA analysis.

Availability and Implementation

GSEA-InContext is implemented in Python. Code, the background expression compendium, and results are available at:https://github.com/CostelloLab/GSEA-InContext
Local Cortical Activity of Distant Brain Areas can Phase-Lock to the Respiratory Rhythm in the Freely Behaving Rat
Authors: Rojas-Líbano Daniel , del Solar Jonathan Wimmer , Aguilar Marcelo , Montefusco-Siegmund Rodrigo , Maldonado Pedro E.
Published: February 2018

An important unresolved question about neural processing is the mechanism by which distant brain areas coordinate their activities and relate their local processing to global neural events. A potential candidate for the local-global integration are slow rhythms such as respiration, which is also linked to sensory exploration. In this article, we asked if there are modulations of local cortical processing which are time-locked to (peripheral) sensory-motor exploratory rhythms. We studied rats freely behaving on an elevated platform where they would display exploratory and rest behaviors. Concurrent with behavior, we monitored orofacial sampling rhythms (whisking and sniffing) and local field potentials (LFP) from olfactory bulb, dorsal hippocampus, primary motor cortex, primary somatosensory cortex and primary visual cortex. We defined exploration as simultaneous whisking and sniffing above 5 Hz and found that this activity peaked at about 8 Hz. We considered rest as the absence of whisking and sniffing, and in this case, mean respiration occurred at about 3 Hz. We found a consistent shift across all areas toward these rhythm peaks accompanying behavioral state changes. We also found, across areas, that LFP gamma (70-100 Hz) amplitude could phase-lock to the animal’s respiratory rhythm, a finding indicative of respiration-locked changes in local processing. The respiratory rhythm, although occurring at the same frequencies of hippocampal theta, was not spectrally coherent with it, implying a different oscillator. Our results are consistent with the notion of respiration as a binder or integrator of activity between distant brain regions.
The Rate of Molecular Evolution When Mutation May Not Be Weak
Authors: de Koning A.P. Jason , De Sanctis Bianca D.
Published: February 2018

One of the most fundamental rules of molecular evolution is that the rate of neutral evolution equals the mutation rate and is independent of effective population size. This result lies at the heart of the Neutral Theory, and is the basis for numerous analytic approaches that are widely applied to infer the action of natural selection across the genome and through time, and for dating divergence events using the molecular clock. However, this result was derived under the assumption that evolution is strongly mutation-limited, and it has not been known whether it generalizes across the range of mutation pressures or the spectrum of mutation types observed in natural populations. Validated by both simulations and exact computational analyses, we present a direct and transparent theoretical analysis of the Wright-Fisher model of population genetics, which shows that some of the most important rules of molecular evolution are fundamentally changed by considering recurrent mutation’s full effect. Surprisingly, the rate of the neutral molecular clock is found to have population-size dependence and to not equal the mutation rate in general. This is because, for increasing values of the population mutation rate parameter (θ), the time spent waiting for mutations quickly becomes smaller than the cumulative time mutants spend segregating before a substitution, resulting in a net deceleration compared to classical theory that depends on the population mutation rate. Furthermore, selection exacerbates this effect such that more adaptive alleles experience a greater deceleration than less adaptive alleles, introducing systematic bias in a wide variety of methods for inferring the strength and direction of natural selection from across-species sequence comparisons. Critically, the classical weak mutation approximation performs well only whenθ<0.1, a threshold that many biological populations seem to exceed.
Variable training but not sleep improves consolidation of motor adaptation
Authors: Thürer Benjamin , Weber Frederik D. , Born Jan , Stein Thorsten
Published: February 2018

How motor memory consolidates still remains elusive. Motor tasks’ consolidation were shown to depend on periods of sleep, whereas pure non-hippocampal dependent tasks, like motor adaptation, might not. Some research suggests that the mode of training might affect the sleep dependency of motor adaptation tasks. Here we investigated whether sleep differentially impacts memory consolidation dependent on the variability during training. Healthy men were trained with their dominant, right hand on a force field adaptation task and re-tested after an 11-h consolidation period either involving overnight sleep (Sleep) or daytime wakefulness (Wake). Retesting also included a transfer to the non-dominant hand. Half of the subjects in each group adapted to different force field magnitudes with low inter-trial variability (Sleep-Blocked; Wake-Blocked), the other half with high variability (Sleep-Random; Wake-Random). EEG was recorded during task execution and overnight polysomnography. Motor adaptation was comparable between Wake and Sleep groups, although performance changes over sleep correlated with sleep spindles nesting in slow wave upstates. Higher training variability improved retest, including transfer learning, and these improvements correlated with higher alpha power in contralateral parietal areas. Enhanced consolidation after training might foster the ability to correct ongoing movements by responsive feedback rather than their pre-execution prediction.
Conbase: a software for unsupervised discovery of clonal somatic mutations in single cells through read phasing
Authors: Hård Joanna , Håkim Ezeddin Al , Kindblom Marie , Björklund Åsa K. , Demirci Ilke , Paterlini Marta , Reu Pedro , Sennblad Bengt , Borgström Erik , Ståhl Patrik L. , Michaelsson Jakob , Mold Jeff E. , Frisén Jonas
Published: February 2018

Here we report the development of Conbase, a software application for the identification of somatic mutations in single cell DNA sequencing data with high rates of allelic dropout and at low read depth. Conbase leverages data from multiple samples in a dataset and utilizes read phasing to call somatic single nucleotide variants and to accurately predict genotypes in whole genome amplified single cells in somatic variant loci. We demonstrate the accuracy of Conbase on simulated datasets, in vitro expanded fibroblasts and clonally in vivo expanded lymphocyte populations isolated directly from a healthy human donor.
Smartphone Application with Wireless Cardiac Monitoring Device to Analyze Real-Time ECG Using Modified Pan Tompkins Algorithm
Authors: Pervaiz Usama , Khawaldeh Saed , Aleef Tajwar Abrar , Minh Vu Hoang
Published: February 2018

Heart patients are constantly at risk of a heart failure, therefore, it is crucial to track their vitals. There is also a dire need to make a single platform which has patients and doctors on board, provides health-care assistance remotely, and have a low-cost and accessible solution that would cater large masses, both in terms of its buying accessibility as well as its ease of use. We are bringing a one stop solution, with a wearable device which monitors Electrocardiogram (ECG) and consequently measure heart rate. The wearable wireless device have an application compatibility on Smartphone which allows real time monitoring of ECG as well as it gives various post processing options, in which heart rate would be measured using modified Pan-Tompkins Algorithm and kept overtime for maintaining health history of the patient.
Evidence for the coupling of substrate recognition with transporter opening in MOP-family flippases
Authors: Sham Lok To , Zheng Sanduo , Kruse Andrew C. , Bernhardt Thomas G.
Published: February 2018

Bacteria produce a variety of surface-exposed polysaccharides important for cell integrity, biofilm formation, and evasion of the host immune response. Synthesis of these polymers often involves the assembly of monomer oligosaccharide units on the lipid carrier undecaprenyl-phosphate at the inner face of the cytoplasmic membrane. For many polymers, including cell wall peptidoglycan, the lipid-linked precursors must be transported across the membrane by flippases to facilitate polymerization at the membrane surface. Flippase activity for this class of polysaccharides is most often attributed to MOP (Multidrug/Oligosaccharidyllipid/Polysaccharide) family proteins. Little is known about how this ubiquitous class of transporters identifies and translocates its cognate precursor over the many different types of lipid-linked oligosaccharides produced by a given bacterial cell. To investigate the specificity determinants of MOP proteins, we selected for variants of the WzxC flippase involved in Escherichia coli capsule (colanic acid) synthesis that can substitute for the essential MurJ MOP-family protein and promote transport of cell wall peptidoglycan precursors. Variants with substitutions predicted to destabilize the inward-open conformation of WzxC lost substrate specificity and supported both capsule and peptidoglycan synthesis. Our results thus suggest that specific substrate recognition by a MOP transporter normally destabilizes the inward-open state, promoting transition to the outward-open conformation and concomitant substrate translocation. Furthermore, the ability of WzxC variants to suppress MurJ inactivation provides strong support for the designation of MurJ as the flippase for peptidoglycan precursors, the identity of which has been controversial.

SIGNIFICANCE

From cell walls in bacteria to protein glycosylation in eukaryotes, surface exposed polysaccharides are built on polyprenol-phosphate lipid carriers. Monomer units are typically assembled at the cytoplasmic face of the membrane and require translocation to the cell surface for polymerization/assembly. MOP-family proteins are a major class of transporters associated with this flippase activity. Despite their ubiquity and importance for cell surface biology, little is known about their transport mechanism. Here, we investigated substrate recognition by MOP transporters in bacteria. We present evidence that transport proceeds via destabilization of the inward-open state of the transporter by specific substrate binding thereby promoting a transition to the outward-open state and substrate release on the opposite face of the membrane.
Temporally unconstrained decoding reveals consistent but time-varying stages of stimulus processing
Authors: Vidaurre Diego , Myers Nicholas E. , Stokes Mark , Nobre Anna C. , Woolrich Mark W.
Published: February 2018

In this paper, we propose a method to track trial-specific neural dynamics of stimulus processing and decision making with high temporal precision. By applying this novel method to a perceptual template-matching task, we tracked representational brain states associated with the cascade of neural processing, from early sensory areas to higher-order areas that are involved in integration and decision-making. We address a major limitation of the traditional decoding approach: that it relies on consistent timing of these processes over trials. Using a temporally unconstrained decoding analysis approach, we found that the timing of the cognitive processes involved in perceptual judgements can vary considerably over trials. This revealed that the sequence of processing states was consistent for all subjects and trials, even when the timing of these states varied. Furthermore, we found that the specific timing of states on each trial was related to the quality of performance over trials.
Flexible sensorimotor computations through rapid reconfiguration of cortical dynamics
Authors: Remington Evan D. , Narain Devika , Hosseini Eghbal A. , Jazayeri Mehrdad
Published: February 2018

Sensorimotor computations can be flexibly adjusted according to internal states and contextual inputs. The mechanisms supporting this flexibility are not understood. Here, we tested the utility of a dynamical system perspective to approach this problem. In a dynamical system whose state is determined by interactions among neurons, computations can be rapidly and flexibly reconfigured by controlling the system‘s inputs and initial conditions. To investigate whether the brain employs such control strategies, we recorded from the dorsomedial frontal cortex (DMFC) of monkeys trained to measure time intervals and subsequently produce timed motor responses according to multiple context-specific stimulus-response rules. Analysis of the geometry of neural states revealed a control mechanism that relied on the system‘s inputs and initial conditions. A tonic input specified by the behavioral context adjusted firing rates throughout each trial, while the dynamics in the measurement epoch allowed the system to establish initial conditions for the ensuing production epoch. This initial condition in turn set the speed of neural dynamics in the production epoch allowing the animal to aim for the target interval. These results provide evidence that the language of dynamical systems can be used to parsimoniously link brain activity to sensorimotor computations.
Mutation in DsbA signal sequence hampers the SRP mechanism: A new strategy to combat virulence factor
Authors: Durrani Faiza Gul , Gul Roquyya , Mirza Muhammad Usman , Kaderbhai Naheed Nazly , Saleem Mahjabeen , Akhter Muhammad Waheed
Published: February 2018

Disulphide bond (Dsb) protein, characterized as an important virulence factor in gram negative bacteria. In this study, amino acid mutations in DsbA signal sequence (ss) and its effect on translocation of recombinant Ovine growth hormone (rOGH) was observed. Eight constructs were designed on the basis of increased hydrophobicity and showed that hydrophobicity and specificity of amino acid plays a crucial role in translocation of rOGH. Two DsbAss with the same hydropathy (1.539), one had alteration at -13 and second at -11 position; alanine (Ala) to isoleucine respectively were designed. The former DsbAss translocated rOGH from membrane to cytoplasmic fraction in E. coli as confirmed by SDS-PAGE, Western blot and molecular modelling analysis. MD simulations and binding free energy calculations evidenced that, altering Ala changed the orientation of signal peptide in the Ffh-M domain binding groove and hampered the process of translocation while change at position -11 pointed it outward. We hypothesize, amino acid and position of mutations in DsbAss can hinder the translocation process of signal recognition particle system, thus affecting the virulence of bacteria.
ATP-dependent force generation and membrane scission by ESCRT-III and Vps4
Authors: Schöneberg Johannes , Yan Shannon , Righini Maurizio , Pavlin Mark Remec , Lee Il-Hyung , Carlson Lars-Anders , Bahrami Amir Houshang , Goldman Daniel H. , Ren Xuefeng , Hummer Gerhard , Bustamante Carlos , Hurley James H.
Published: February 2018

The ESCRTs catalyze reverse-topology scission from the inner face of membrane necks in HIV budding, multivesicular endosome biogenesis, cytokinesis, and other pathways. We encapsulated a minimal ESCRT module consisting of ESCRT-III subunits Snf7, Vps24, and Vps2, and the AAA+ ATPase Vps4 such that membrane nanotubes reflecting the correct topology of scission could be pulled from giant vesicles. Upon ATP release by photo-uncaging, this system was capable of generating forces within the nanotubes in a manner dependent upon Vps4 catalytic activity, Vps4 coupling to the ESCRT-III proteins, and membrane insertion by Snf7. At physiological concentrations, single scission events were observed that correlated with forces of ~6 pN, verifying predictions that ESCRTs are capable of exerting forces on membranes. Imaging of scission with subsecond resolution revealed Snf7 puncta at the sites of membrane cutting, directly verifying longstanding predictions for the ESCRT scission mechanism.

One Sentence Summary

ESCRT-III and Vps4 were reconstituted from within the interior of nanotubes pulled from giant vesicles, revealing that this machinery couples ATP-dependent force production for membrane scission.
2-Amino-4-(4-methoxyphenyl)-1-(4-methylphenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carbonitrile
Authors: Tamam Asmaa H. A. , Kaur Manpreet , Akkurt Mehmet , Mohamed Shaaban K. , Jasinski Jerry P. , Hussain Faiq H. S.
Published: February 2018

In the title compound, C24H23N3O2, the cyclohexene and 1,4-dihydropyridine rings of the 1,4,5,6,7,8-hexahydroquinoline ring system each adopt a twisted-boat conformation. The dihedral angle between the benzene rings is 13.89 (10)°. In the crystal, molecules are linked through pairs of amino–nitrile N—H...N hydrogen bonds, forming inversion dimers. Weak C—H...O and C—H...π interactions connect the dimers, forming a three-dimensional network.
(Z)-1-(1,3-Diphenyl-1H-pyrazol-4-yl)-N-phenylmethanimineN-oxide
Authors: Mohamed Shaaban K. , Mague Joel T. , Akkurt Mehmet , Said Awad I. , Hawaiz Farouq E. , Elgarhy Sahar M. I.
Published: February 2018

In the title nitrone, C22H17N3O, the dihedral angles between the central pyrazole ring and pendant N-bound, C-bound and nitrone-bound phenyl rings are 20.93 (6), 41.27 (6), and 32.57 (6)°, respectively. In the crystal, (101) layers are generated by C—H...O hydrogen bonds coupled with C—H...π(ring) and offset π–π stacking interactions.
Are female leaders more efficient in family firms than in non-family firms?
Authors: Bjuggren Per-Olof , Nordström Louise , Palmberg Johanna
Published: February 2018

Purpose

The aim of this study is to investigate whether female leaders are more efficient in family firms than in non-family firms.

Design/methodology/approach

This paper uses a unique database of ownership and leadership in private Swedish firms that makes it possible to analyze differences in firm performance due to female leadership in family and non-family firms. The analysis is based on survey data merged with micro-level data on Swedish firms. Only firms with five or more employees are included in the analysis. The sample contains more than 1,000 firms.

Findings

The descriptive statistics show that there are many more male than female corporate leaders. However, the regression analysis indicates that female leadership has a much more positive impact on the performance of family firms than on that for non-family firms, where the effect is ambiguous.

Originality/value

Comparative studies examining the impact of female leadership on firm-level performance in family and non-family firms are rare, and those that exist are most often either qualitative or focused on large, listed firms. By investigating the role of female directors in family and non-family firms, the study adds to the literature on management, corporate governance and family firms.
When two worlds collide: critical reflection on co-production
Authors: Clayson Amanda , Webb Lucy , Cox Nigel
Published: February 2018

Purpose

The purpose of this paper is to report the findings from reflexive data collection on the evolving co-production research relationship between the two “worlds” of community and academia: people with lived experience and their community intermediaries and academic researchers. It reports analysis of reflections on experience as the different partners explore and evaluate their own experiences of co-productive research within the context of substance use recovery co-production research.

Design/methodology/approach

The research uses reflexive data from perspectives of an intermediary community partner, academic partners, and community researchers on experiences of a series of co-productive research projects. The aim is to identify thematic features of the co-productive experiences from different positions and through the process of adaptation to a co-productive relationship.

Findings

This paper outlines what has been learnt from the experience of co-production and what has “worked” for community and academic partners; around the nature of co-production, barriers to performance, and its value to participants and the wider recovery research agenda.

Originality/value

This paper reports a unique perspective on a developing methodology in health and social care, contributing to a growing body of knowledge pertaining to experiences of co-production research.
An international telecom acquisition: lost in translation when Ya'alla met Boben Yang
Authors: Swierczek Benjamin Morgan , Swierczek Fredric William
Published: February 2018

Purpose

This study aims to consider the transition that took place between two major telecom multinational companies (MNCs) during an acquisition in an emerging market, Laos. The differences in the orientation of top management, corporate culture and cultural distance led to the ineffective performance of the acquired telecom company.

Design/methodology/approach

Content analysis is used to identify the key factors in the case. The sources of data are annual reports, past interviews, market reports, and participant observation.

Findings

The ineffective performance of the acquisition was related to the lack of cultural compatibility of the new top management, a corporate culture that emphasized costs over customer satisfaction and the failure to close the cultural gap between the Middle Eastern cultural values and the Lao values.

Research limitations/implications

The data are mostly secondary data with some interviews of key managers. The case study would benefit with more extensive primary data, but the company was reluctant to respond.

Practical implications

The match between the top management leadership style, the complementarity of the new corporate culture with the existing one, and the reduction in the gap in national cultures are all critical in the continuing successful performance of an acquisition. A strategy of localization increasing the competencies of the local managers and professionals and the adaptation of the organization processes and practices to the local context are more effective in achieving positive performance.

Social implications

The change in corporate cultures from the collaborative/customer satisfaction emphasis of Tigo to a competitive/cost culture of Beeline led to a significant conflict with other telecom providers in Laos. This had performance consequences for Beeline and also the telecom sector.

Originality/value

This study is a unique demonstration of what happens in an acquisition of a telecom company in an emerging market. It is an interesting interplay of two major telecom companies with similar strategic choices but very different corporate culture orientations.
Looking to manage change successfully? It is dependent on alignment at every level
Authors: Lyman R. Kendall , Daloisio Tony C.
Published: February 2018

Purpose

To become a great agent of change, you need to diagnose impediments and create remedies. However, to implement change successfully, you must take an inside-out and outside-in approach and focus on and align individual behavior, the functions of teams, and the organization as a whole.

Design/methodology/approach

The paper draws from 10 years of research and work with individuals, teams, and organizations.

Findings

Accelerating change in an organization requires leaders to define and align those activities that set the organization apart and give it a competitive advantage at the individual, team, and organizational levels.

Originality/value

As change leaders or L&D/OD professionals, this paper helps you recognize the need to develop your capabilities in five key roles: focus, align, engage, lead, and sustain.