bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive Thermal Evaluation of Ventriculoperitoneal Shunt Patency and Cerebrospinal Fluid Flow Using a Flow Enhancing Device
Authors: Hameed Mustafa Q , Zurakowski David , Proctor Mark R , Stone Scellig S D , Warf Benjamin C , Smith Edward R , Goumnerova Liliana C , Swoboda Marek , Anor Tomer , Madsen Joseph R
Published: May 2018

BACKGROUND

While a noninvasive flow determination would be desirable in the diagnosis of cerebrospinal fluid shunt malfunction, existing studies have not yet defined a role for thermal flow detection.

OBJECTIVE

To evaluate a revised test protocol using a micropumper designed to transiently enhance flow during thermal testing to determine whether thermal detection of flow is associated with progression to shunt revision surgery.

METHODS

Eighty-two unique tests were performed in 71 shunts. The primary outcome, need for revision within 7 d of testing, was compared with results of micropumper-augmented thermal flow detection. Statistical analysis was based on blind interpretation of test results and raw temperature data recorded during testing.

RESULTS

The test was sensitive (73%) and specific (68%) in predicting need for revision, with 5.6-fold higher probability of revision when flow was not detected. Negative predictive value in our sample was 94.2%. The probability of not requiring revision increased with increasing total temperature drop. Analysis of various possible thresholds showed that the optimal temperature cutoff may be lower than suggested by the manufacturer (0.125°C vs 0.2°C).

CONCLUSION

This is the first study to report a strong association between thermal flow evaluation and a clinical impression that a shunt is not malfunctioning. The current recommended threshold may increase the false positive rate unnecessarily, and as clinicians gain experience with the method, they may find value in examining the temperature curves themselves. Multicenter studies are suggested to further define a role for this diagnostic test.
Initial Experience Using Intraoperative Magnetic Resonance Imaging During a Trans-Sulcal Tubular Retractor Approach for the Resection of Deep-Seated Brain Tumors: A Case Series
Authors: Akbari S Hassan A , Sylvester Peter T , Kulwin Charles , Shah Mitesh V , Somasundaram Aravind , Kamath Ashwin A , Beaumont Thomas L , Rich Keith M , Chicoine Michael R
Published: May 2018

BACKGROUND

Treatment of deep-seated subcortical intrinsic brain tumors remains challenging and may be improved with trans-sulcal tubular brain retraction techniques coupled with intraoperative magnetic resonance imaging (iMRI).

OBJECTIVE

To conduct a preliminary assessment of feasibility and efficacy of iMRI in tubular retractor-guided resections of intrinsic brain tumors.

METHODS

Assessment of this technique and impact upon outcomes were assessed in a preliminary series of brain tumor patients from 2 centers.

RESULTS

Ten patients underwent resection with a tubular retractor system and iMRI. Mean age was 53.2 ± 9.0 yr (range: 37-61 yr, 80% male). Lesions included 6 gliomas (3 glioblastomas, 1 recurrent anaplastic astrocytoma, and 2 low-grade gliomas) and 4 brain metastases (1 renal cell, 1 breast, 1 lung, and 1 melanoma). Mean maximal tumor diameter was 2.9 ± 0.95 cm (range 1.2-4.3 cm). The iMRI demonstrated subtotal resection (STR) in 6 of 10 cases (60%); additional resection was performed in 5 of 6 cases (83%), reducing STR rate to 2 of 10 cases (20%), with both having tumor encroaching on eloquent structures. Seven patients (70%) were stable or improved neurologically immediately postoperatively. Three patients (30%) had new postoperative neurological deficits, 2 of which were transient. Average hospital length of stay was 3.4 ± 2.0 d (range: 1-7 d).

CONCLUSION

Combining iMRI with tubular brain retraction techniques is feasible and may improve the extent of resection of deep-seated intrinsic brain tumors that are incompletely visualized with the smaller surgical exposure of tubular retractors.
Management of Cavernous Sinus Meningioma Presenting With Cerebrovascular Insufficiency Secondary to Cavernous Carotid Artery Occlusion: Report of 2 Cases
Authors: Alzhrani Gmaan , Derrico Nicholas , Abou-Al-Shaar Hussam , Couldwell William T
Published: May 2018

BACKGROUND

Surgical removal of cavernous sinus meningiomas is challenging and associated with high morbidities as a result of the anatomic location and the surrounding neurovascular structures that are often invaded or encased by the tumor. Advances in radiotherapy techniques have led to the adoption of more conservative approaches in the management of cavernous sinus meningioma. Internal carotid artery encasement and invasion has been documented in these cases; however, ischemic presentation secondary to internal carotid artery stenosis or occlusion by meningioma in the region of the cavernous sinus is rare, with only few cases reported in the literature.

OBJECTIVE

To report our surgical technique and experience with bypass grafting for cavernous sinus meningiomas that invade or narrow the internal carotid artery.

METHODS

We report 2 patients who presented with signs and symptoms attributed to cavernous carotid artery occlusion secondary to cavernous sinus meningioma in the last 5 yr. Both patients were treated with flow augmentation without surgical intervention for the cavernous sinus meningioma.

RESULTS

In both cases, the clinical and radiological signs of cerebrovascular insufficiency improved markedly, and the patients’ tumors are currently being monitored.

CONCLUSION

Although the cerebrovascular insufficiency in this subset of patients is attributed to the occlusion of the cavernous carotid artery caused by the tumor, we propose treating those patients with flow augmentation first with or without radiation therapy when there is a clear imaging feature suggestive of meningioma in the absence of significant cranial nerve deficit.
Using Naturalistic Methods to Examine Real-World Driving Behavior in Individuals With TBI Upon Return to Driving
Authors: Hua Phuong , Charlton Judith L. , Ponsford Jennie L. , Gooden James R. , Ross Pamela E. , Bédard Michel , Marshall Shawn , Gagnon Sylvain , Stolwyk Renerus J.
Published: June 2018

Objectives:

To characterize the real-world driving habits of individuals with traumatic brain injury (TBI) using naturalistic methods and to demonstrate the feasibility of such methods in exploring return to driving after TBI.

Methods:

After passing an on-road driving assessment, 8 participants with TBI and 23 matched controls had an in-vehicle device installed to record information regarding their driving patterns (distance, duration, and start/end times) for 90 days.

Results:

The overall number of trips, distance and duration or percentage of trips during peak hour, above 15 km from home or on freeways/highways did not differ between groups. However, the TBI group drove significantly less at night, and more during the daytime, than controls. Exploratory analyses using geographic information system (GIS) also demonstrated significant within-group heterogeneity for the TBI group in terms of location of travel.

Conclusions:

The TBI and control groups were largely comparable in terms of driving exposure, except for when they drove, which may indicate small group differences in driving self-regulatory practices. However, the GIS evidence suggests driving patterns within the TBI group were heterogeneous. These findings provide evidence for the feasibility of employing noninvasive in-car recording devices to explore real-world driving behavior post-TBI.
Predictors of inadequate bowel preparation for colonoscopy: a systematic review and meta-analysis
Authors: Mahmood Sultan , Farooqui Samid M. , Madhoun Mohammad F.
Published: May 2018

The aim of this study was to investigate factors contributing to poor bowel preparation in patients undergoing colonoscopy procedures. We used a reproducible search strategy to identify studies, searching 10 medical databases, including PubMed, Ovid, Medline, and Cochrane Library Database for reports published between 2000 and 2016. Fully published studies, evaluating risk factors for inadequate bowel preparation, were included. Two reviewers independently scored the identified studies for methodology and abstracted pertinent data. Pooling was conducted with both fixed-effects and random-effects models; results were presented from the random effects model when heterogeneity was significant. Odds ratios (OR) estimates with 95% confidence interval were calculated. Heterogeneity was assessed by I
2 statistics. Twenty-four studies with a total of 49 868 patients met the inclusion criteria. Age (OR: −1.20), male sex (OR: 0.85), inpatient status (OR: 0.57), diabetes mellitus (OR: 0.58), hypertension (OR: 0.58), cirrhosis (OR: 0.49), narcotic use (OR: 0.59), constipation (OR: 0.61), stroke (OR; 0.51), and tricyclic antidepressant (TCA) use (0.51), were associated with inadequate bowel preparation. In our sensitivity analysis comparing Western and Asian countries, we found that diabetes, cirrhosis, male sex, history of stroke and TCA use were stronger risk factors for inadequate bowel preparation in Western countries than in Asian countries. We also found that history of stroke, TCA use, and race were risk factors for inadequate bowel preparation in patients receiving conventional bowel preparation compared with those receiving split-dose bowel preparation. Multiple risk factors affect the quality of bowel preparation and specific risk factors can be intervened upon, in different populations, to optimize preparation.
Endoscopic stenting for palliation of intra-abdominal gastrointestinal malignant obstruction: predictive factors for clinical success
Authors: Pais-Cunha Inês , Castro Rui , Libânio Diogo , Pita Inês , Bastos Rui P. , Silva Rui , Dinis-Ribeiro Mario , Pimentel-Nunes Pedro
Published: May 2018

Background

Endoscopic stenting proved to be a safe alternative to surgery for malignant intra-abdominal gastrointestinal obstruction. Although high technical success rates have been reported, some patients do not experience relief in symptoms.

Aim

This study aimed to analyse the factors predicting the effectiveness of stent placement in patients with gastrointestinal obstruction.

Patients and methods

A retrospective study was carried out including 160 patients who underwent palliative stenting for intra-abdominal obstruction in a tertiary centre from December 2012 to July 2017. Technical and clinical success, stent dysfunction and adverse events were analysed.

Results

The rate of technical success was 98%. The rate of early clinical success was 69 and 81% in upper and lower gastrointestinal obstructions, respectively (P=0.107). In the upper tract, obstruction caused by carcinomatosis was the only independent factor predicting early and late clinical failure [odds ratio (OR): 9.7, 95% confidence interval (CI): 2.5–38.4, P=0.001 and OR: 7.6, 95% CI: 1.8–31.9, P=0.006, respectively]. In the colon, Eastern Cooperative Oncology Group score of at least 3 was an independent factor for early clinical failure (OR: 29.8, 95% CI: 1.9–464.9, P=0.002) and obstruction caused by carcinomatosis was an independent factor for late clinical failure (OR: 14.4, 95% CI: 1.7–119.6, P=0.013). Perforation occurred in 4 patients (2.5%) and stent dysfunction occurred in 15% of patients (4% stent migration; 9% restenosis). Carcinomatosis was a risk factor for perforation (P=0.039) and migration was higher with shorter 6 cm stents (P=0.044).

Conclusion

Stents are effective and safe for palliation of intra-abdominal obstruction. Carcinomatosis predicts an unfavourable clinical outcome. Palliative stenting as an option should be weighed carefully in these patients.
Dietary and developmental shifts in butterfly-associated bacterial communities
Authors: Phalnikar Kruttika , Kunte Krushnamegh , Agashe Deepa
Published: May 2018

Bacterial communities associated with insects can substantially influence host ecology, evolution and behaviour. Host diet is a key factor that shapes bacterial communities, but the impact of dietary transitions across insect development is poorly understood. We analysed bacterial communities of 12 butterfly species across different developmental stages, using amplicon sequencing of the 16S rRNA gene. Butterfly larvae typically consume leaves of a single host plant, whereas adults are more generalist nectar feeders. Thus, we expected bacterial communities to vary substantially across butterfly development. Surprisingly, only few species showed significant dietary and developmental transitions in bacterial communities, suggesting weak impacts of dietary transitions across butterfly development. On the other hand, bacterial communities were strongly influenced by butterfly species and family identity, potentially due to dietary and physiological variation across the host phylogeny. Larvae of most butterfly species largely mirrored bacterial community composition of their diets, suggesting passive acquisition rather than active selection. Overall, our results suggest that although butterflies harbour distinct microbiomes across taxonomic groups and dietary guilds, the dramatic dietary shifts that occur during development do not impose strong selection to maintain distinct bacterial communities across all butterfly hosts.
Optimization of parameters in cylindrical and surface grinding for improved surface finish
Authors: Kumar Patel Dinesh , Goyal Deepam , Pabla B. S.
Published: May 2018

Surface integrity has attracted the attention of researchers for improving the functional performance of engineering products. Improvement in surface finish, one of the important parameters in surface integrity, has been attempted by researchers through different processes. Grinding has been widely used for final machining of components requiring smooth surfaces coupled with precise tolerances. Proper selection of grinding wheel material and grade with grinding parameters can result in an improved surface finish and improved surface characteristics. The present work reports the study of the effect of grinding parameters on surface finish of EN8 steel. Experiments were performed on surface grinding and cylindrical grinding for optimization of grinding process parameters for improved surface finish. Grinding wheel speed, depth of cut, table feed, grinding wheel material and table travel speed for surface grinding operation, and work speed for cylindrical grinding operation were taken as the input parameters with four types of grinding wheels (Al
2
O
3
of grades K and L, and white alumina of grades J and K). The surface roughness was taken as an output parameter for experimentation. The grinding wheel material and grade have been observed to be the most significant variables for both cylindrical grinding and surface grinding. Surface roughness in the case of surface grinding is better compared to that of cylindrical grinding, which can be attributed to vibrations produced in the cylindrical grinding attachment. Surface roughness (
R
a
) values of 0.757 µm in cylindrical grinding and 0.66 µm in surface grinding have been achieved.
What are we missing? Advantages of more than one viewpoint to estimate fish assemblages using baited video
Authors: Whitmarsh Sasha K. , Huveneers Charlie , Fairweather Peter G.
Published: May 2018

Counting errors can bias assessments of species abundance and richness, which can affect assessments of stock structure, population structure and monitoring programmes. Many methods for studying ecology use fixed viewpoints (e.g. camera traps, underwater video), but there is little known about how this biases the data obtained. In the marine realm, most studies using baited underwater video, a common method for monitoring fish and nekton, have previously only assessed fishes using a single bait-facing viewpoint. To investigate the biases stemming from using fixed viewpoints, we added cameras to cover 360° views around the units. We found similar species richness for all observed viewpoints but the bait-facing viewpoint recorded the highest fish abundance. Sightings of infrequently seen and shy species increased with the additional cameras and the extra viewpoints allowed the abundance estimates of highly abundant schooling species to be up to 60% higher. We specifically recommend the use of additional cameras for studies focusing on shyer species or those particularly interested in increasing the sensitivity of the method by avoiding saturation in highly abundant species. Studies may also benefit from using additional cameras to focus observation on the downstream viewpoint.
Metabolic profiles of Cuibi-1 and Zhongyan-100 flue-cured tobacco leaves in different growing regions by gas chromatography/mass spectrometry
Authors: Sun Bo , Zheng Ai-Hong , Zhang Fen , Wei Ke-Su , Chen Qing , Luo Ya , Zhang Yong , Wang Xiao-Rong , Lin Fu-Cheng , Yang Jun , Tang Hao-Ru
Published: May 2018

The metabolic profiles of tobacco leaves of two differential Chinese cultivars from different growing regions were analysed using gas chromatography–mass spectrometry (GC–MS). The results of principal component analysis, partial least-squares discriminant analysis and hierarchical cluster analysis showed significant differences in metabolome among three groups, identified 24 differential metabolites, and analysed the metabolic pathway in which the metabolites were involved. Among them, 13 metabolites were associated with geographical regions, including seven organic and fatty acids, four carbohydrates and two secondary metabolites. Four amino acids and two monosaccharides were associated with cultivars and the remaining five metabolites were associated with both. The relationships among the differential metabolites and the distinct characteristics of environment and cultivar were further discussed. In addition, correlation analysis indicated that most of the differential carbohydrates were negatively correlated with the differential amino acids and organic acids. Taken together, this study demonstrates the metabolite differences between two cultivars in different regions, and highlights the effect of environment and cultivar on tobacco leaf metabolism.
Zeolitic-imidazolate frameworks derived Pt-free counter electrodes for high-performance quantum dot-sensitized solar cells
Authors: Xu Wenjiao , Sun Yuxiu , Ding Bin , Zhang Jingbo
Published: May 2018

Zeolitic-imidazole frameworks (ZIFs), as novel porous materials, are attracting much attention in several fields due to their special advantages such as large specific surface area, versatile porosity and well-connected networks. Here, we develop a porous ZIF-derived catalytic thin film, which was coated on the conducting glass as a counter electrode (CE) to substitute costly platinum for quantum dot-sensitized solar cells (QDSSCs). A ZIF layer is first prepared by coating ZIF-67 powders on the conducting glass, followed by the careful calcination treatments in sulfur vapour (sulfuration) or nitrogen gas (carbonization). The structure and morphologies of the derived porous film are characterized by the measurements of XRD, SEM and BET, and the electrochemical properties in the polysulfide solution are evaluated by the measurements of Tafel curves and electrochemical impedance spectroscopies. The derived porous film is used as a CE to fabricate QDSSC with CdSe quantum dot-sensitized TiO
2
nanocrystalline thin film and the polysulfide solution. Compared with the photovoltaic performance of CdSe QDSSCs based on the CE prepared by the different sulfuration conditions, QDSSC based on the CE derived by the sulfuration for 30 min shows an excellent light-to-electric conversion efficiency of 3.77%, it is even higher than that of QDSSC based on Pt CE (2.98%). This work will open a new avenue to design a facile, low-cost and renewable CE for QDSSC.
An investigation into the origins and history of pandemic small ruminant lentivirus infection
Authors: Carrozza Maria-Luisa , Niewiadomska Anna-Maria , Mazzei Maurizio , Abi-Said Mounir R. , Hué Stéphane , Singer Joshua B. , Hughes Joseph , Gifford Robert J.
Published: May 2018

Small ruminant lentiviruses (SRLVs) cause chronic, persistent infections in populations of domestic sheep and goats throughout the world. In this study, we use genomic data to investigate the origins and history of the SRLV pandemic. To explore the hypothesis that SRLV infection disseminated during Neolithic times, we performed a serology and DNA sequencing-based investigation of SRLVs diversity in the Fertile Crescent region, where domestication of sheep and goats is thought to have originally occurred. While we found an elevated level of viral genetic diversity compared to other regions of the world, we did not find unambiguous evidence that the Fertile Crescent region was the centre of the contemporary SRLV pandemic. We therefore examined historical reports to investigate the relationship between contemporary SRLV distribution and diversity and the emergence of SRLV-associated disease. Historical data suggested that the emergence of SRLV-associated disease might be associated with the long-distance export of exotic small ruminant breeds - in particular, karakul sheep from Central Asia - during the late 19thand early 20thcenturies. Phylogeographic analysis could neither confirm nor refute this hypothesis. However, we anticipate that future accumulation of genomic data from SRLV strains found throughout the world may allow for a more definitive assessment. The openly available data and resources assembled in this study will facilitate future investigations in this area.

Importance

Viruses that cause chronic, persistent infections have circulated in animals for millions of years. However, many have only emerged as pathogens within the far shorter timeframe of recorded human history. It is important to understand the history of chronic viral infections in domestic animals, so that more effective control and eradication programs can be developed.
Genetic Modifiers of Pathogenic LRRK2 G2019S Neurodegeneration in Drosophila
Authors: Lavoy Sierra , Chittoor-Vinod Vinita G. , Chow Clement Y. , Martin Ian
Published: May 2018

Disease phenotypes can be highly variable among individuals with the same pathogenic mutation. There is increasing evidence that background genetic variation is a strong driver of disease variability in addition to the influence of environment. To understand the genotype-phenotype relationship that determines the expressivity of a pathogenic mutation, a large number of backgrounds must be studied. This can be efficiently achieved using model organism collections such as the Drosophila Genetic Reference Panel (DGRP). Here, we used the DGRP to assess the variability of locomotor dysfunction in a LRRK2 G2019S Drosophila melanogaster model of Parkinson’s disease. We find substantial variability in the LRRK2 G2019S locomotor phenotype in different DGRP backgrounds. A genome-wide association study for candidate genetic modifiers reveals 177 genes that drive wide phenotypic variation, including 19 top association genes. Genes involved in the outgrowth and regulation of neuronal projections are enriched in these candidate modifiers. RNAi functional testing of the top association and neuronal projection-related genes reveals that pros, pbl, ct and CG33506 significantly modify age-related dopamine neuron loss and associated locomotor dysfunction in the Drosophila LRRK2 G2019S model. These results demonstrate how natural genetic variation can be used as a powerful tool to identify genes that modify disease-related phenotypes. We report novel candidate modifier genes for LRRK2 G2019S that may be used to interrogate the link between LRRK2, neurite regulation and neuronal degeneration in Parkinson’s disease.
Flux Balance Analysis Identifies Distinct NADPH Production Strategies Across NCI 60 Cancer Cell Lines
Authors: Ahmad Zaid
Published: May 2018

Flux Balance Analysis is a linear mathematical procedure which determines the set of reaction fluxes to produce a maximum flux of a reaction of interest. In this study, a core cancer model developed by Zielinski et al. 2017 is constrained by a set of 59 cancer cell type specific uptake and secretion rates. Optimizing for cell type specific biomass objective reactions and examining serine flux distributions reveals variability in production of NADPH. In many cell lines, production of NADPH is correlated to biosynthetic demand, however, outliers exist that produce excess NADPH beyond that of biomass demand. These outliers are first characterized by their NADPH production strategy (pentose phosphate pathway or a combination of One Folate Cycle and Malic Enzyme) and then the factors responsible for the different NADPH production strategies are identified. Results indicate that pentose phosphate pathway (PPP) producing NADPH cell lines had reprogrammed tricarboxylic acid cycle metabolism to meet the demand for decreased flux through glycolytic enzymes, while one folate cycle and malic enzyme (OFC + ME) producing NADPH cell lines had higher threonine, tyrosine and serine uptake.
De novo computational RNA modeling into cryoEM maps of large ribonucleoprotein complexes
Authors: Kappel Kalli , Liu Shiheng , Larsen Kevin P. , Skiniotis Georgios , Puglisi Elisabetta Viani , Puglisi Joseph D. , Zhou Z. Hong , Zhao Rui , Das Rhiju
Published: May 2018

RNA-protein assemblies carry out many critical biological functions including translation, RNA splicing, and telomere extension. Increasingly, cryo-electron microscopy (cryoEM) is used to determine the structures of these complexes, but nearly all maps determined with this method have regions in which the local resolution does not permit manual coordinate tracing. Because RNA coordinates typically cannot be determined by docking crystal structures of separate components and existing structure prediction algorithms cannot yet model RNA-protein complexes, RNA coordinates are frequently omitted from final models despite their biological importance. To address these omissions, we have developed a new framework for De novo Ribonucleoprotein modeling in Real-space through Assembly of Fragments Together with Electron density in Rosetta (DRRAFTER). We show that DRRAFTER recovers near-native models for a diverse benchmark set of small RNA-protein complexes, as well as for large RNA-protein machines, including the spliceosome, mitochondrial ribosome, and CRISPR-Cas9-sgRNA complexes where the availability of both high and low resolution maps enable rigorous tests. Blind tests on yeast U1 snRNP and spliceosomal P complex maps demonstrate that the method can successfully build RNA coordinates in real-world modeling scenarios. Additionally, to aid in final model interpretation, we present a method for reliable in situ estimation of DRRAFTER model accuracy. Finally, we apply this method to recently determined maps of telomerase, the HIV-1 reverse transcriptase initiation complex, and the packaged MS2 genome, demonstrating that DRRAFTER can be used to accelerate accurate model building in challenging cases.
Variation at the TRIM11 locus modifies Progressive Supranuclear Palsy phenotype
Authors: Jabbari E , Woodside J , Tan MMX , Shoai M , Pittman A , Ferrari R , Mok KY , Zhang D , Reynolds RH , de Silva R , Grimm MJ , Respondek G , Müller U , Al-Sarraj S , Gentleman SM , Lees AJ , Warner TT , Hardy J , Revesz T ,   PROSPECT-UK consortium, Höglinger GU , Holton JL , Ryten M , Morris HR ,   PROSPECT-UK consortium
Published: May 2018

Objective

The basis for clinical variation related to underlying Progressive Supranuclear Palsy (PSP) pathology is unknown. We performed a genome wide association study (GWAS) to identify genetic determinants of PSP phenotype.

Methods

Two independent pathological and clinically diagnosed PSP cohorts were genotyped and phenotyped to create Richardson’s syndrome (RS) and non-RS groups. We carried out separate logistic regression GWAS to compare RS and non-RS groups and then combined datasets to carry out a whole cohort analysis (RS=367, non-RS=130). We validated our findings in a third cohort by referring to data from 100 deeply phenotyped cases from a recent GWAS. We assessed the expression/co-expression patterns of our identified genes and used our data to carry out gene-based association testing.

Results

Our lead single nucleotide polymorphism (SNP), rs564309, showed an association signal in both cohorts, reaching genome wide significance in our whole cohort analysis – OR 5.5 (3.2-10.0), p-value 1.7×10−9. rs564309 is an intronic variant of the tripartite motif-containing protein 11 (TRIM11) gene, a component of the ubiquitin proteasome system (UPS). In our third cohort, minor allele frequencies of surrogate SNPs in high linkage disequilibrium with rs564309 replicated our findings. Gene based association testing confirmed an association signal at TRIM11. We found that TRIM11 is predominantly expressed neuronally, in the cerebellum and basal ganglia.

Interpretation

Our study suggests that the TRIM11 locus is a genetic modifier of PSP phenotype and potentially adds further evidence for the UPS having a key role in tau pathology, therefore representing a target for disease modifying therapies.
The role of dendritic brain-derived neurotrophic factor transcripts on altered inhibitory circuitry in depression
Authors: Oh Hyunjung , Piantadosi Sean C. , Rocco Brad R. , Lewis David A. , Watkins Simon C. , Sibille Etienne
Published: May 2018

Background

A parallel downregulation of brain-derived neurotrophic factor (BDNF) and somatostatin (SST), a marker of inhibitory γ-amino-butyric acid (GABA) interneurons which target pyramidal cell dendrites, has been reported in several brain areas of subjects with major depressive disorder (MDD), and rodent genetic studies suggests they are linked and both contribute to the illness. However, the mechanism by which they contribute to the pathophysiology of the illness has remained elusive.

Methods

With qPCR, we determined the expression level of BDNF transcript variants and synaptic markers in the prefrontal cortex (PFC) of MDD patients and matched controls (n=19/group) and of C57BL/6J mice exposed to chronic stress or control conditions (n=12/group). We next suppressed BDNF transcripts with long 3’ untranslated region (L-3’-UTR) using small hairpin RNA (shRNA) and investigated changes in cell morphology, gene expression and behavior.

Results

L-3’-UTR containing BDNF mRNAs, which migrate to distal dendrites of pyramidal neurons, are selectively reduced and highly correlated with SST expression in the PFC of MDD subjects. A similar downregulation occurs in mice submitted to chronic stress. We next show that Bdnf L-3’-UTR knockdown is sufficient to induce (i) dendritic shrinkage in cortical neurons, (ii) cell-specific MDD-like gene changes (including Sst downregulation), and (iii) depressive-/anxiety-like behaviors. The translational validity of the Bdnf L-3’-UTR shRNA-treated mice was confirmed by significant cross-species correlation of changes in MDD-associated gene expression.

Conclusion

These findings provide evidence for a novel MDD-related pathological mechanism linking local neurotrophic support, pyramidal cell structure, dendritic inhibition and mood regulation.
Extreme and rapid bursts of functional adaptations shape bite force in amniotes
Authors: Sakamoto Manabu , Ruta Marcello , Venditti Chris
Published: May 2018

Adaptation is the fundamental driver of functional and biomechanical evolution and can be linked to rates of phenotypic trait evolution. Significant shifts in evolutionary rates are seen as instances of exceptional adaptation. However, whether or not signatures of exceptional adaptations (elevated rates) can be distinguished from general adaptations (background rate) in biomechanical traits remains to be tested in a robust statistical framework. Here, we apply a recently developed phylogenetic statistical approach for detecting exceptional adaptations in bite force, in a large group of terrestrial vertebrates, the amniotes. Our results show that bite force in amniotes evolved through multiple bursts of exceptional changes, whereby whole groups – including Darwin′;s finches, maniraptoran dinosaurs (group of non-avian dinosaurs including birds), anthropoids and hominins (the group of species including modern humans) – experienced significant rate increases compared to the background rate. However, in most parts of the amniote tree of life we find no exceptional rate increases, indicating that coevolution with body size was primarily responsible for the patterns observed in bite force. Our approach represents a template for future studies in functional morphology and biomechanics, where exceptional functional adaptations can be quantified and potentially linked to specific ecological factors underpinning major evolutionary radiations.
TheNeurospora crassastandard Oak Ridge background exhibits an atypically efficient meiotic silencing by unpaired DNA
Authors: Giri Dev Ashish , Pankajam Ajith V. , Nishant Koodali T. , Kasbekar Durgadas P.
Published: May 2018

Meiotic silencing by unpaired DNA (MSUD) was discovered in crosses made in the standard Oak Ridge (OR) genetic background ofNeurospora crassa. However, MSUD often was decidedly less efficient when the OR-derived MSUD tester strains were crossed with wild-isolated strains (W), which suggested either that sequence heterozygosity intesterx W crosses suppresses MSUD, or that OR represents the MSUD-conducive extreme in the range of genetic variation in MSUD efficiency. Our results support the latter model. MSUD was much less efficient in near-isogenic crosses made in a novelN. crassaB/S1 and theN. tetrasperma85 genetic backgrounds. Possibly, regulatory cues that in other genetic backgrounds calibrate the MSUD response are missing from OR. The OR versus B/S1 difference appears to be determined by loci on chromosomes 1, 2, and 5. OR crosses heterozygous for a duplicated chromosome segment (Dp) have for long been known to exhibit an MSUD-dependent barren phenotype. However, inefficient MSUD inN. tetrasperma85 madeDp-heterozygous crosses non-barren. This is germane to our earlier demonstration thatDps can act as dominant suppressors of repeat-induced point mutation (RIP). Occasionally, during ascospore partitioning rare asci contained >8 nuclei, and round ascospores dispersed less efficiently than spindle-shaped ones.

General abstract

In crosses made in the standard OR genetic background ofNeurospora crassa, an RNAi-mediated process called MSUD efficiently silences any gene not properly paired with its homologue during meiosis. We found that MSUD was not as efficient in comparable crosses made in theN. crassaB/S1 andN. tetrasperma85 backgrounds, suggesting that efficient MSUD is not necessarily the norm in Neurospora. Indeed, using OR strains for genetic studies probably fortuitously facilitated the discovery of MSUD and its suppressors. As few as three unlinked loci appear to underlie the OR versus B/S1 difference in MSUD.
Development of Optically-Controlled “Living Electrodes” with Long-Projecting Axon Tracts for a Synaptic Brain-Machine Interface
Authors: Adewole Dayo O. , Struzyna Laura A. , Harris James P. , Nemes Ashley D. , Burrell Justin C. , Petrov Dmitriy , Kraft Reuben H. , Chen H. Isaac , Serruya Mijail D. , Wolf John A. , Cullen D. Kacy
Published: May 2018

Achievements in intracortical neural interfaces are compromised by limitations in specificity and long-term performance. A biological intermediary between devices and the brain may offer improved specificity and longevity through natural synaptic integration with deep neural circuitry, while being accessible on the brain surface for optical read-out/control. Accordingly, we have developed the first “living electrodes” comprised of implantable axonal tracts protected within soft hydrogel cylinders for the biologically-mediated monitoring/modulation of brain activity. Here we demonstrate the controlled fabrication, rapid axonal outgrowth, reproducible cytoarchitecture, and simultaneous optical stimulation and recording of neuronal activity within these engineered constructs in vitro. We also present their transplantation, survival, integration, and optical recording in rat cortex in vivo as a proof-of-concept for this neural interface paradigm. The creation and functional validation of these preformed, axon-based “living electrodes” is a critical step towards developing a new class of biohybrid neural interfaces to probe and modulate native circuitry.
An electrochemical biosensor for rapid detection of anti-dsDNA antibodies in absolute scale
Authors: Fagúndez Pablo , Brañas Gustavo , Laíz Justo , Tosar Juan Pablo
Published: May 2018

Autoimmune diseases are chronic inflammatory pathologies that are characterized by the presence of antibodies against own epitopes in serum (autoantibodies). Systemic lupus erythematosus (SLE) is a common autoimmune pathology, characterized by the presence of antinuclear antibodies (ANAs). These include anti-dsDNA (α-dsDNA) antibodies, which are widely used for diagnosis and disease monitoring. Their determination is carried out by traditional techniques such as Indirect Immunofluorescence (IFI) or Enzyme Linked Immunosorbent Assay (ELISA), which are time consuming, require qualified technicians, and are not compatible with decentralized analysis outside a laboratory facility. Here, we show a sandwich-format electrochemical biosensor-based method for α-dsDNA determination in a rapid and simple manner. Total assay time is only 30 minutes and the sensor is capable of detecting 16 ng (8 μg / mL) of α-dsDNA antibodies. Using the current derived from the detection limit of the method as a cut-off, we could discriminate positive from negative serum samples with 90% sensitivity and 100% specificity. By using monoclonal antibodies for calibration curves, our results are presented in absolute scale (i.e., concentration instead of serum title) what will help to perform comparisons between methods and further improvements of this protocol. In an effort to render the sensor compatible with automation, we minimized manipulation steps without compromise of the analytical performance, even in complex samples such as serum.
Characterization of Oral Tactile Sensitivity and Chewing Efficiency Across Adulthood
Authors: Shupe Grace E. , Resmondo Zoe N. , Luckett Curtis R.
Published: May 2018

Texture perception is one of the most important factors in food acceptance, yet population-wide differences in texture sensations are not well understood. The variation in texture perception across populations is thought to depend on oral tactile sensitivity and oral processing behaviors. To address this hypothesis, we aimed to measure tactile acuity with a battery of tests and quantitate the relationship to oral processing. The study was performed on 98 participants, in 3 age groups (20-25, 35-45, or over 62). Two main measures of oral sensitivity were performed: to assess bite force, subjects were asked to discriminate between foam samples of varying hardness. Secondly, to assess lingual sensitivity the subjects were asked to identify 3D printed shapes, ranging from 3mm to 8mm, using their tongue, as well as identify confectionary letters. Additionally, chewing efficiency was measured through assessing each participants ability to mix two-colored chewing gum. In general, we found that sensitivity and chewing efficiency in the younger age groups was superior to that of older adults (p<0.0001). We also found a positive linear trend between bite force sensitivity and chewing efficiency with younger participants, a trend not found in older participants. We found no significant relationship between age groups for bite force and chewing efficiency, suggesting that age-related declines in bite force sensitivity are not a significant cause of altered oral processing ability. These results help bolster evidence that sensitivity and oral processing are related, as well previously reported declines in both as people age.
GWAS meta-analysis highlights the hypothalamic-pituitary-gonadal axis (HPG axis) in the genetic regulation of menstrual cycle length
Authors: Laisk Triin , Kukuškina Viktorija , Palmer Duncan , Laber Samantha , Chen Chia-Yen , Ferreira Teresa , Rahmioglu Nilufer , Zondervan Krina , Becker Christian , Smoller Jordan W. , Lippincott Margaret , Salumets Andres , Granne Ingrid , Seminara Stephanie , Neale Benjamin , Mägi Reedik , Lindgren Cecilia M.
Published: May 2018

The normal menstrual cycle requires a delicate interplay between the hypothalamus, pituitary, and ovary. Therefore, its length is an important indicator of female reproductive health. Menstrual cycle length has been shown to be partially controlled by genetic factors, especially in the follicle stimulating hormone beta-subunit (FSHB) locus. GWAS meta-analysis of menstrual cycle length in 44,871 women of European ancestry confirmed the previously observed association with the FSHB locus and identified four additional novel signals in, or near, the GNRH1, PGR, NR5A2 and INS-IGF2 genes. These findings confirm the role of the hypothalamic-pituitary-gonadal axis in the genetic regulation of menstrual cycle length, but also highlight potential novel local regulatory mechanisms, such as those mediated by IGF2.
WNT4 and WNT3A activate cell autonomous Wnt signaling independent of PORCN or secretion
Authors: Rao Deviyani M. , Bordeaux Evelyn K. , Yamamoto Tomomi M. , Bitler Benjamin G. , Sikora Matthew J.
Published: May 2018

The enzyme PORCN is considered essential for Wnt secretion and signaling, however, we observed PORCN inhibition did not phenocopy the effects of WNT4 knockdown in WNT4-dependent breast cancer cells. This suggests a unique relationship between PORCN and WNT4 signaling. To examine the role of PORCN in WNT4 signaling, WNT4 or WNT3A were over-expressed in breast and ovarian cancer, and fibrosarcoma cell lines. Conditioned medium from these lines, and co-culture systems, were used to assess the dependence of Wnt secretion and activity on critical Wnt secretion proteins PORCN and WLS. We observed that WLS was universally required for Wnt secretion and paracrine signaling. In contrast, the dependence of WNT3A secretion and activity on PORCN varied across cell lines, and WNT4 secretion was PORCN-independent in all models. Surprisingly, WNT4 did not present paracrine activity in any tested context. Absent the expected paracrine activity of secreted WNT4, we identified cell autonomous Wnt signaling activation by WNT4 and WNT3A, independent of PORCN or secretion. The PORCN-independent, cell-autonomous Wnt signaling demonstrated herein may be critical in WNT4-driven cellular contexts, or those that are otherwise considered to have dysfunctional Wnt signaling.

Summary Statement

Wnt proteins can mediate an atypical mode of cell-autonomous signaling, distinct from paracrine signaling, that is independent of both palmitoylation by PORCN and Wnt secretion.
SciReader: A Cloud-based Recommender System for Biomedical Literature
Authors: Desai Priya , Telis Natalie , Lehmann Ben , Bettinger Keith , Pritchard Jonathan K. , Datta Somalee
Published: May 2018

With the growing number of biomedical papers published each year, keeping up with relevant literature has become increasingly important, and yet more challenging. SciReader (www.scireader.com) is a cloud-based personalized recommender system that specifically aims to assist biomedical researchers and clinicians identify publications of interest to them. SciReader uses topic modeling and other machine learning algorithms to provide users with recommendations that are recent, relevant, and of high quality1.
The hotspots in primate cortical brain evolution support supramodal cognitive flexibility
Authors: Sneve Markus H. , Grydeland Håkon , Rosa Marcello G. P. , Paus Tomáš , Chaplin Tristan , Walhovd Kristine , Fjell Anders M.
Published: May 2018

Primate cortical evolution has been characterized by massive and disproportionate expansion of a set of specific regions in the neocortex. The associated increase in neocortical neurons comes with a high metabolic cost, thus the functions served by these regions must have conferred significant evolutionary advantage. Here, across a series of experiments, we show that the evolutionary high-expanding ‘hotspots’ – as estimated from patterns of evolutionary expansion from several primate species – share functional connections with different brain networks in a context-dependent manner. This capacity of the hotspots to connect flexibly with various specialized brain networks depending on particular cognitive requirements suggests that their selective growth and sustainment in evolution has been linked to their involvement in supramodal cognition. In accordance with an evolutionary-developmental view, we find that this ability to flexibly modulate functional connections as a function of cognitive state emerges gradually through childhood, with a prolonged developmental trajectory plateauing in young adulthood.
Wealth-relative effects in cooperation games
Authors: Shuler Robert L.
Published: May 2018

This paper investigates conditions under which game agents benefit from considering wealth relative to decision payoff, presents simulation analysis of these effects, and explains why they often do not show up but it is realistic that they should. We extend the known categories of games reported to exhibit wealth relative effects (chicken games) to many others (including Prisoner’s Dilemma) while clarifying that the poor must avoid survival risk, regardless of whether this is associated with cooperation or defection. A simulation of iterated Prisoner’s Dilemma with wealth accumulation and a survival threshold (which we call the Farmer’s Game) is used to evaluate tit-for-tat and four variants, including Subsist, Thief, Exploit and Middle (even lower risk than Subsist). Equilibrium payoffs are used to keep the game scaled to social relevance, with a fraction of all payoffs externalized as a turn cost parameter. Findings include poor performance of tit-for-tat near the survival threshold, superior performance of Subsist and Middle for both poor and wealthy players, dependence of survival of the poor near the threshold on tit-for-tat forgiveness, unexpected optimization of forgiveness without encountering a social dilemma, improved performance of a diverse mix of strategies, and a more abrupt threshold of social catastrophe for the better performing mix. Additionally we find that experimental results which appear to be at odds with conventional findings of cooperation vs. network size can be reconciled with theory and simulation via wealth-relative weighting, which opens the door to practical application of cooperation theory.

Significance Statement

Enabling comparison of theoretical and simulated game cooperation theory results to controlled experiments with live subjects and in-situ data from field surveys will enable application of scientifically verified results to societal and policy problems, and will generate new and unexpected insights through clearer interpretation of data. Extension of wealth-relative effects to a broader range of games also allows analysis of real life situations with greater confidence.