bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure–function relationships of the 5‐oxoprolinase subunit A: Guiding biological sciences students down the path less traveled
Authors: Oke Muse , Oni Omobukola , Bello Ronke , Samuel‐Omoyajowo Kennedy , Senbadejo Tosin 
Published: September 2019

AbstractBioinformatics was recently introduced as a module for both undergraduate and postgraduate biological sciences students at our institution. Our experience shows that inquiry‐based hands‐on exercises provide the most efficient approach to bioinformatic straining. In this article, we report a structural bioinformatics project carried out by Master degree students to determine structure–function relationships of the uncharacterized prokaryotic 5‐oxoprolinase subunit A (PxpA). PxpA associates with the PxpBC complex to form a functional 5‐oxoprolinase enzyme for conversion of 5‐oxoproline to L‐glutamate. Although the exact role of PxpA is yet to be determined, it has been demonstrated that PxpBC catalyses the first step of the reaction, which is phosphorylation of 5‐oxoproline. Here, we provide evidence that PxpA is involved in the last two steps of the reaction:decyclization of the labile phosphorylated 5‐oxoproline to the equally labile γ‐glutamylphosphate, and subsequent dephosphorylation to L‐glutamate. Structural bioinformatics analysis of four putative PxpA structures revealed that PxpA adopts a non‐canonical TIM barrel fold with well‐characterized TIM barrel enzyme features. These include a C‐terminal groove comprising potentially essential conserved amino acid residues organized into putative motifs. Phylogenetic analysis suggests a relationship between taxonomic grouping and PxpA oligomerization. PxpA forms a tunnel upon ligand binding, thus suggesting that the PxpABC complex employs the mechanism of substrate channeling to protect labile intermediates. Ultimately, students were able to form a testable hypothesis on the function of PxpA, an achievement we consider encouraging other students to emulate. © 2019 International Union of Biochemistry and Molecular Biology, 47(6):620–631, 2019.
Subperiosteal Papilla Augmentation With a Non–Animal‐Derived Hyaluronic Acid Overlay Technique
Authors: Spano Stephen J. , Ghilzon Romanita , Lam David K. , Goldberg Michael B. , Tenenbaum Howard C. 
Published: September 2019

IntroductionLoss of the interdental papilla, leading to the formation of black triangular spaces just below the contact area of adjacent teeth, is one of the most challenging periodontal conditions to treat and often requires an interdisciplinary approach by the periodontist, restorative dentist, and orthodontist. Although these “black triangles” may appear quite small from a clinician's standpoint, they can have a significant impact on oral health satisfaction for patients. This case series illustrates a novel minimally invasive approach to restore interdental papilla deficiencies.Case PresentationFour interdental papilla defects were treated in three females. No patients were lost to follow‐up over 6 months. The surgery consisted of a horizontal incision placed apical to the area of papillary loss in the alveolar mucosa just beyond the mucogingival junction. An interdental subperiosteal tissue space was then created by tunneling toward and under the dental papilla. Once adequate release was achieved, dermal filler was administered into and underneath the deficient papilla. The papillary margins were then sealed with cyanoacrylate and additional dermal filler was injected as needed to achieve ideal papillary fill. Six months after treatment there was an improvement in patient‐satisfaction regarding papilla fill demonstrated by a mean increase in visual analogue scale (VAS) measurements of 62.46%. Mean papilla fill was 1.75 mm.ConclusionThis surgical technique demonstrates the restoration of deficient interdental papillae between teeth and implants, and perhaps as importantly, a considerable improvement in patient‐based outcomes quantified through VASs.
A novel de novo PDE4D gene mutation identified in a Chinese patient with acrodysostosis
Authors: Zhan Yongkun , Chen Weicheng , Feng Zhiyu , Tan Chaozhong , Li Mengru , Song Yangliu , Zhao Zhengshan , Sheng Wei , Huang Guoying 
Published: September 2019

SummaryAcrodysostosis is an extremely rare disorder at birth, that is, characterized by skeletal dysplasia with short stature and midfacial hypoplasia, which has been reported to be caused by PDE4D and PRKAR1A gene mutations. Here, a Chinese boy with acrodysostosis, ventricular septal defect, and pulmonary hypertension was recruited for our study, and his clinical and biochemical characteristics were analyzed. A novel de novo heterozygous missense mutation (NM_001104631: c.2030A>C, p.Tyr677Ser) of the PDE4D gene was detected by whole exome sequencing and confirmed by Sanger sequencing. The c.2030A>C (p.Tyr677Ser) variant was located in exon 15 of the PDE4D gene, predicted to be damaging by a functional prediction program and shown to be highly conserved among many species. Further functional analysis showed that the p.Tyr677Ser substitution changes the function of the PDE4D protein, affects its subcellular localization in transfected cells, increases PDE4 activity in the regulation of cAMP signaling and affects cell proliferation. Our study identified a novel de novo PDE4D mutation in acrodysostosis of Chinese origin that not only contributes a deeper appreciation of the phenotypic characteristics of patients with PDE4D mutations but also expands the spectrum of PDE4D mutations.
Foraging ecology drives social information reliance in an avian eavesdropping community
Authors: Jones Harrison H. , Sieving Kathryn E. 
Published: September 2019

AbstractVertebrates obtain social information about predation risk by eavesdropping on the alarm calls of sympatric species. In the Holarctic, birds in the family Paridae function as sentinel species; however, factors shaping eavesdroppers' reliance on their alarm calls are unknown. We compared three hypothesized drivers of eavesdropper reliance: (a) foraging ecology, (b) degree of sociality, and (c) call relevance (caller‐to‐eavesdropper body‐size difference). In a rigorous causal‐comparative design, we presented Tufted Titmouse (Baeolophus bicolor) alarm calls to 242 individuals of 31 ecologically diverse bird species in Florida forests and recorded presence/absence and type (diving for cover or freezing in place) of response. Playback response was near universal, as individuals responded to 87% of presentations (N = 211). As an exception to this trend, the sit‐and‐wait flycatcher Eastern Phoebe (Sayornis phoebe) represented 48% of the nonresponses. We tested 12 predictor variables representing measures relevant to the three hypothesized drivers, distance to playback speaker, and vulnerability at time of playback (eavesdropper's microhabitat when alarm call is detected). Using model‐averaged generalized linear models, we determined that foraging ecology best predicted playback response, with aerial foragers responding less often. Foraging ecology (distance from trunk) and microhabitat occupied during playback (distance to escape cover) best predicted escape behavior type. We encountered a sparsity of sit‐and‐wait flycatchers (3 spp.), yet their contrasting responses relative to other foraging behaviors clearly identified foraging ecology as a driver of species‐specific antipredator escape behavior. Our findings align well with known links between the exceptional visual acuity and other phenotypic traits of flycatchers that allow them to rely more heavily on personal rather than social information while foraging. Our results suggest that foraging ecology drives species‐specific antipredator behavior based on the availability and type of escape cover.
Development of a CE‐MS method for the study of riociguat and metabolite M1 in pharmaceutical analysis
Authors: Štícha Martin , Hložek Tomáš , Bursová Miroslava , Čabala Radomír , Jelínek Ivan 
Published: September 2019

AbstractRiociguat is a novel antihypertensive drug for the treatment of pulmonary hypertension. We present electrophoretic characterization, i.e. migration behavior of riociguat and metabolite M1 as support for optimized CZE/MS assay. Fundamental separation parameters, such as peak width, symmetry, and resolution are studied in a series of ammonium formate buffers within pH range 2.60–5.61. The narrow region of peak symmetry lies close to pH 4.0 for both analytes. Accordingly, the value of resolution maximizes in a background electrolyte adjusted to pH 4.10. Basic calibration parameters estimated from CZE experiments with absorption photometric and mass spectrometric detection of riociguat and metabolite M1 were evaluated. More than three orders lower LOD was achieved with high resolution mass spectrometric detection. The observed difference in the sensitivity of both detection techniques gives priority to the utilization of CZE/MS in practice. The values of dissociation constants of riociguat and metabolite M1, pKBH, were determined from CZE measurements in lithium formate and lithium acetate background electrolytes with constant ionic strength. The value of pKBH = 4.30 ± 0.02 for riociguat corresponds well to the value already presented in the literature. According to our observation, metabolite M1 behaves like a slightly stronger base with estimated pKBH = 4.40 ± 0.02.
Determinants and outcome of repeat continuous electroencephalogram monitoring—A case‐control study
Authors: Punia Vineet , Zawar Ifrah , Briskin Isaac , Burgess Richard , Newey Christopher R. , Hantus Stephen 
Published: September 2019

AbstractObjectiveA retrospective, single‐center study to analyze the determinants of a repeat continuous EEG (cEEG) monitoring during hospitalization and its outcomes using a matched case‐control study design.MethodsAdults with a repeat cEEG session (cases) were matched by age (±3 years), gender, and mental status to patients with a single cEEG (controls) during hospitalization. Several clinical and EEG characteristics were analyzed to identify predictors of repeat cEEG. Repeat cEEG outcomes were analyzed based on its yield of electrographic seizure. We investigated the predictors of finding increased epileptic potential (degree of association with electrographic seizures) on the repeat cEEG, a marker for possible anti‐epileptic drugs (AEDs) management change.ResultsA total of 213 (8.6% of all unique cEEG patients) cases were included. A multivariable conditional logistic regression model comparing cases and controls showed that the presence of acute brain insult [odds ratio (OR) = 3.36, 95% CI = 1.26‐8.94, P = .015], longer hospital admission (OR = 1.11, 95% CI = 1.07‐1.15, P < .001) and being on AEDs at the end of index cEEG (OR = 4.0, 95% CI = 1.8‐8.87, P < .001) was determinants of a repeat cEEG. Among cases, 17 (8%) had electrographic seizures on repeat cEEG. Increased epileptic potential on repeat cEEG was noted in 34 (16%) cases. The latter is associated with change in etiology after the index cEEG (P = .03) and duration of repeat cEEG (P = .003) based on multivariable logistic regression model. AEDs were changed in 46 (21.6%) patients based on repeat cEEG findings.SignificanceRepeat cEEG is not an uncommon practice. It leads to the diagnosis of electrographic seizures in a significant percentage of patients. With the potential of impacting AED management in 16%‐21% patients, it should be considered in high‐risk patients suffering acute brain insults undergoing prolonged hospitalization.
Indium‐rich InGaN/GaN solar cells with improved performance due to plasmonic and dielectric nanogratings
Authors: Kumawat Uttam K. , Kumar Kamal , Bhardwaj Priyanka , Dhawan Anuj 
Published: September 2019

AbstractIn this study, we propose an indium‐rich InGaN/GaN p‐i‐n thin‐film solar cell which incorporates a dual nanograting (NG) structure: Ag nanogratings (Ag‐NGs) on the backside of the solar cell and gallium nitride nanogratings (GaN‐NGs) on the frontside. Finite‐difference time‐domain (FDTD) simulation results show that the dual NG structure couples the incident sunlight to the plasmonic and photonic modes, thereby increasing the absorption of the solar cell in a broad spectral range. It is observed that the solar cells having the dual nanograting structures have a significant enhancement in light absorption as compared to cells having either no nanogratings or having only the frontside nanogratings or only the backside nanogratings. Analysis of light absorption in solar cells containing the dual NG structures showed that the absorption enhancement of longer wavelengths is mostly due to the Ag‐NGs on the backside and of shorter wavelengths is mostly due to the GaN‐NGs on frontside of the solar cell. The Jsc and power conversion efficiency (PCE) are calculated under AM1.5G solar illumination and are observed to be significantly enhanced due to the presence of optimized dual NG structures. While there is an increase in Jsc from 17.88 to 23.19 mA/cm2 (~30% enhancement), there is an increase in PCE from 15.49% to 20.24% (~31% enhancement) under unpolarized light (average of TM and TE). Moreover, the study of oblique light incidence shows significantly larger Jsc of the dual nanograting solar cells compared to the cells with no nanogratings.
Population‐wide copy number variation calling using variant call format files from 6,898 individuals
Authors: Png Grace , Suveges Daniel , Park Young‐Chan , Walter Klaudia , Kundu Kousik , Ntalla Ioanna , Tsafantakis Emmanouil , Karaleftheri Maria , Dedoussis George , Zeggini Eleftheria , Gilly Arthur 
Published: September 2019

AbstractCopy number variants (CNVs) play an important role in a number of human diseases, but the accurate calling of CNVs remains challenging. Most current approaches to CNV detection use raw read alignments, which are computationally intensive to process. We use a regression tree‐based approach to call germline CNVs from whole‐genome sequencing (WGS, >18x) variant call sets in 6,898 samples across four European cohorts, and describe a rich large variation landscape comprising 1,320 CNVs. Eighty‐one percent of detected events have been previously reported in the Database of Genomic Variants. Twenty‐three percent of high‐quality deletions affect entire genes, and we recapitulate known events such as the GSTM1 and RHD gene deletions. We test for association between the detected deletions and 275 protein levels in 1,457 individuals to assess the potential clinical impact of the detected CNVs. We describe complex CNV patterns underlying an association with levels of the CCL3 protein (MAF = 0.15, p = 3.6x10−12) at the CCL3L3 locus, and a novel cis‐association between a low‐frequency NOMO1 deletion and NOMO1 protein levels (MAF = 0.02, p = 2.2x10−7). This study demonstrates that existing population‐wide WGS call sets can be mined for germline CNVs with minimal computational overhead, delivering insight into a less well‐studied, yet potentially impactful class of genetic variant.
Combining sequence data from multiple studies: Impact of analysis strategies on rare variant calling and association results
Authors: Chen Zhongsheng , Boehnke Michael , Fuchsberger Christian 
Published: September 2019

AbstractIndividual sequencing studies often have limited sample sizes and so limited power to detect trait associations with rare variants. A common strategy is to aggregate data from multiple studies. For studying rare variants, jointly calling all samples together is the gold standard strategy but can be difficult to implement due to privacy restrictions and computational burden. Here, we compare joint calling to the alternative of single‐study calling in terms of variant detection sensitivity and genotype accuracy as a function of sequencing coverage and assess their impact on downstream association analysis. To do so, we analyze deep‐coverage (~82×) exome and low‐coverage (~5×) genome sequence data on 2,250 individuals from the Genetics of Type 2 Diabetes study jointly and separately within five geographic cohorts.For rare single nucleotide variants (SNVs): (a) ≥97% of discovered SNVs are found by both calling strategies; (b) nonreference concordance with a set of highly accurate genotypes is ≥99% for both calling strategies; (c) meta‐analysis has similar power to joint analysis in deep‐coverage sequence data but can be less powerful in low‐coverage sequence data. Given similar data processing and quality control steps, we recommend single‐study calling as a viable alternative to joint calling for analyzing SNVs of all minor allele frequency in deep‐coverage data.
P2Y13 receptors regulate microglial morphology, surveillance, and resting levels of interleukin 1β release
Authors: Kyrargyri Vasiliki , Madry Christian , Rifat Ali , Arancibia‐Carcamo I. Lorena , Jones Steffan P. , Chan Victor T. T. , Xu Yajing , Robaye Bernard , Attwell David 
Published: September 2019

AbstractMicroglia sense their environment using an array of membrane receptors. While P2Y12 receptors are known to play a key role in targeting directed motility of microglial processes to sites of damage where ATP/ADP is released, little is known about the role of P2Y13, which transcriptome data suggest is the second most expressed neurotransmitter receptor in microglia. We show that, in patch‐clamp recordings in acute brain slices from mice lacking P2Y13 receptors, the THIK‐1 K+ current density evoked by ADP activating P2Y12 receptors was increased by ~50%. This increase suggested that the P2Y12‐dependent chemotaxis response should be potentiated; however, the time needed for P2Y12‐mediated convergence of microglial processes onto an ADP‐filled pipette or to a laser ablation was longer in the P2Y13 KO. Anatomical analysis showed that the density of microglia was unchanged, but that they were less ramified with a shorter process length in the P2Y13 KO. Thus, chemotactic processes had to grow further and so arrived later at the target, and brain surveillance was reduced by ~30% in the knock‐out. Blocking P2Y12 receptors in brain slices from P2Y13 KO mice did not affect surveillance, demonstrating that tonic activation of these high‐affinity receptors is not needed for surveillance. Strikingly, baseline interleukin‐1β release was increased fivefold while release evoked by LPS and ATP was not affected in the P2Y13 KO, and microglia in intact P2Y13 KO brains were not detectably activated. Thus, P2Y13 receptors play a role different from that of their close relative P2Y12 in regulating microglial morphology and function.
Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer's disease and mild cognitive impairment
Authors: Chandra Avinash , Valkimadi Polytimi‐Eleni , Pagano Gennaro , Cousins Oliver , Dervenoulas George , Politis Marios ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: September 2019

AbstractAlzheimer's disease (AD) is a devastating and progressive neurodegenerative disease for which there is no cure. Mild cognitive impairment (MCI) is considered a prodromal stage of the disease. Molecular imaging with positron emission tomography (PET) allows for the in vivo visualisation and tracking of pathophysiological changes in AD and MCI. PET is a very promising methodology for differential diagnosis and novel targets of PET imaging might also serve as biomarkers for disease‐modifying therapeutic interventions. This review provides an overview of the current status and applications of in vivo molecular imaging of AD pathology, specifically amyloid, tau, and microglial activation. PET imaging studies were included and evaluated as potential biomarkers and for monitoring disease progression. Although the majority of radiotracers showed the ability to discriminate AD and MCI patients from healthy controls, they had various limitations that prevent the recommendation of a single technique or tracer as an optimal biomarker. Newer research examining amyloid, tau, and microglial PET imaging in combination suggest an alternative approach in studying the disease process.
The importance of different learning stages for motor sequence learning after stroke
Authors: Dahms Christiane , Brodoehl Stefan , Witte Otto W. , Klingner Carsten M. 
Published: September 2019

AbstractThe task of learning predefined sequences of interrelated motor actions is of everyday importance and has also strong clinical importance for regaining motor function after brain lesions. A solid understanding of sequence learning in stroke patients can help clinicians to optimize and individualize rehabilitation strategies. Moreover, to investigate the impact of a focal lesion on the ability to successfully perform motor sequence learning can enhance our comprehension of the underlying physiological principles of motor sequence learning. In this article, we will first provide an overview of current concepts related to motor sequence learning in healthy subjects with focus on the involved brain areas and their assumed functions according to the temporal stage model. Subsequently, we will consider the question of what we can learn from studies investigating motor sequence learning in stroke patients. We will first focus on the implications of lesion location. Then, we will analyze whether distinct lesion locations affect specific learning stages. Finally, we will discuss the implications for clinical rehabilitation and suggest directions for further research.
Positron emission tomography visualized stimulation of the vestibular organ is localized in Heschl's gyrus
Authors: Devantier Louise , Hansen Allan K. , Mølby‐Henriksen Jens‐Jacob , Christensen Christian B. , Pedersen Michael , Hansen Kim V. , Magnusson Måns , Ovesen Therese , Borghammer Per 
Published: September 2019

AbstractThe existence of a human primary vestibular cortex is still debated. Current knowledge mainly derives from functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) acquisitions during artificial vestibular stimulation. This may be problematic as artificial vestibular stimulation entails coactivation of other sensory receptors. The use of fMRI is challenging as the strong magnetic field and loud noise during MRI may both stimulate the vestibular organ. This study aimed to characterize the cortical activity during natural stimulation of the human vestibular organ. Two fluorodeoxyglucose (FDG)‐PET scans were obtained after natural vestibular stimulation in a self‐propelled chair. Two types of stimuli were applied: (a) rotation (horizontal semicircular canal) and (b) linear sideways movement (utriculus). A comparable baseline FDG‐PET scan was obtained after sitting motion‐less in the chair. In both stimulation paradigms, significantly increased FDG uptake was measured bilaterally in the medial part of Heschl's gyrus, with some overlap into the posterior insula. This is the first neuroimaging study to visualize cortical processing of natural vestibular stimuli. FDG uptake was demonstrated in the medial‐most part of Heschl's gyrus, normally associated with the primary auditory cortex. This anatomical localization seems plausible, considering that the labyrinth contains both the vestibular organ and the cochlea.