bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of different interventions on animal models of ischemic stroke
Authors: Zhang Yan , Yu Hui-Jin , Shi Shu-Zhen , Wang Jian-Cheng
Published: April 2019

Background:

Ischemic stroke often leads to lifelong disability or death in stroke patients. It is one of the most common causes of death and disability worldwide, so it is a global health problem. The objective of this protocol is to provide the methods for using overview and network meta-analysis to identify the more effective intervention for infarct volume and neurobehavioral score in animal models of ischemic stroke.

Methods:

A systematic literature search will be conducted in PubMed and Embase to obtain relevant systematic reviews on December 11, 2018. Assessing the Methodological Quality of Systematic Reviews (AMSTAR2) and SYRCLE's risk of bias tool will be used to assess quality of the included reviews and risk of bias of randomized controlled trials (RCTs) for animal studies. Infarct volume and neurobehavioral score will be chosen as primary and secondary outcomes. The relative effect size of the treatment will be calculated using the standardized mean difference (SMD) and 95% confidence interval (CI). R 3.5.1 through the GEMTC package will be used to perform a network meta-analysis to synthesize direct and indirect evidence.

Results:

The results of this paper will be submitted to a peer-reviewed journal for publication.

Conclusion:

Our study can provide a reference for further clinical practice and can be compared with clinical trial results to obtain a more credible therapeutic effect of this intervention.

Ethics and communication:

Formal ethical approval is unnecessary, because this study is based on published researches.

PROSPERO registration number:

CRD42019126811
Scapula chondrosarcoma
Authors: Qiang Shuai , Ma Xin-Nan , Wang Hong-Wei , Lv Song-Cen
Published: April 2019

Rationale

Chondrosarcoma is a malignant mesenchymal tumor originating from cartilage. The pelvis, ribs, femur, and humerus are the most frequently affected sites, and scapula involvement is relatively rare. The aim of the present study was to report a case of chondrosarcoma in the scapula.

Patient concerns

A 42-year-old woman presented with a 3-month history of a painful mass in the right scapula.

Diagnoses and intervention

The patient underwent tumor resection. The post-operative pathological diagnosis was scapula chondrosarcoma.

Outcomes

Following resection, the patient continued to receive routine follow-up care. There was no recurrence or tumor metastasis at a follow-up of 5 years.

Conclusions

Surgery remains the primary therapy for chondrosarcoma. One of the greatest challenges in the management of chondrosarcoma is to accurately assess tumor grade before surgical intervention. Chemotherapy and radiotherapy have been applied without success. Chemo- and radioresistance have been examined beyond classic phenotypic properties to identify more efficient therapeutic strategies. Therefore, development of future novel therapies is contingent upon elucidating the molecular mechanisms of chondrosarcoma.
General anesthesia for patient with Fahr's syndrome
Authors: Park Suyong , Jee Dae-Lim , Kim Hyuckgoo
Published: April 2019

Rationale:

Fahr's syndrome (FS) is a rare neurological and psychiatric disorder characterized by bilateral brain calcifications when a secondary cause of the calcification is found.

Patient concerns:

A 53-year-old female patient diagnosed with FS for laminectomy because of ossification of posterior longitudinal ligament. She had a history of generalized tonic-clonic (GTC) seizure and medication with anticonvulsant drugs. She had gait disturbance, spasticity, bradykinesia, and diffuse calcifications in the basal ganglia, thalamus, cerebellum, and cerebral hemispheres on the brain computed tomography. On the preoperative examination, the serum and ionized calcium (Ca) were decreased to 3.7 and 2.22 mg/dL. Hypomagnesemia is combined with hypocalcemia. Furthermore, the level of parathyroid hormone was decreased to 2.18 pg/mL.

Diagnoses:

Due to the radiologic findings and laboratory test results, she was diagnosed with FS with primary hypoparathyroidism.

Interventions:

The Ca and magnesium (Mg) had been corrected before surgery but the electrolytes revealed low level at the intraoperative period. The 300 mg of calcium chloride was administered at 2 times and 1200 mg of it were infused for 1 hour during intraoperative periods. In addition, total 4 g of Mg sulfate intravenously administered. We used rocuronium as a neuromuscular block and checked neuromuscular function by train-of-four monitoring.

Outcomes:

Residual neuromuscular blockade was reversed with pyridostigmine and her muscle power completely recovered. The patient was extubated successfully and no unpredictable events occurred. On the day following transfer, serum electrolytes remained low, and although Ca was continuously supplied, serum Ca did not recover to a normal level. The patient was medicated with anticonvulsant drugs but experienced GTC seizure 2 weeks after surgery.

Lessons:

We presume that the pathophysiology of FS was related to primary hypoparathyroidism and hypomagnesemia. FS raises concerns associated with neuromuscular problems, spasticity, and seizure, and concerns of hypotension, heart failure, cardiac arrhythmia, and cerebrovascular attack during perioperative periods, among anesthesiologists because of hypocalcemia and vessel calcification. During the perioperative period, Ca levels should be closely monitored, and titrated Ca replacement therapy is recommended. The simultaneous correction of hypomagnesemia is of considerable importance when correcting hypocalcemia.
Identifying the superior antibiotic prophylaxis strategy for breast surgery
Authors: Guo Tao , Chen Baiyang , Rao Fengying , Wu Ping , Liu Pengpeng , Liu Zhisu , Li Zhen
Published: April 2019

Background:

The clinical roles of different antibiotic prophylaxis strategies for breast surgery remains large unknowns. The aim of this study is to evaluate different antibiotic prophylaxis strategies based on a network meta-analysis.

Methods:

We initially retrieved literature from globally recognized databases, namely, MEDLINE, EMBASE and Cochrane Central, to address relative randomized controlled trials (RCTs) investigating the antibiotic prophylaxis strategies for breast surgery. Relative postoperative infection rates were quantitatively pooled and estimated based on the Bayesian theorem. Values of surface under the cumulative ranking curve (SUCRA) probabilities were calculated and ranked. Additional pairwise meta-analyses were performed to validate differences between the respective strategies at the statistical level for further explanations.

Results:

After a detailed review, a total of 14 RCTs containing 6 different strategies were included for the network meta-analysis. The results indicated that the application of antibiotics administered during pre- plus post- plus intraoperative periods possessed the highest possibility of having the best clinical effects (SUCRA, 0.40), followed by intraoperative administration alone (SUCRA, 0.35) and pre- plus intraoperative administrations (SUCRA, 0.20). Moreover, an additional pairwise meta-analysis determined that pre- and intraoperative-related strategies significantly reduced postoperative infections at a statistical level.

Conclusion:

Based on the current evidence, we concluded that application of antibiotics administered during pre- plus post- plus intraoperative periods seemed to reveal superior benefits. However, the essential roles of pure intraoperative and postoperative application were still need to be further validated.
Primary nasal diffuse large B-cell lymphoma with synchronous pulmonary involvement
Authors: Hao Shuhong , Sun Yan , Hu Chunmei , Zhi Yunhui , Xiao Han , Li Yarong
Published: April 2019

Rationale:

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring type of non-Hodgkin's lymphoma, which may be found at various extranodal sites. The nose is not a common site for DLBCL as compared with natural killer/T-cell lymphoma, and synchronous pulmonary involvement is even rarer. We report a case of primary nasal DLBCL who presented with a mass in the left lower lobe, mimicking primary lung carcinoma.

Patient concerns:

A 62-year-old Chinese female visited the Ear-Nose-Throat Department of our hospital with nasal congestion and rhinorrhea for 2 months.

Diagnosis:

Computed tomography scan revealed a mass with soft tissue density in the left vestibule and nasal cavity. Histopathological examination revealed a large number of lymphoma cells, and immunohistochemistry confirmed the diagnosis of DLBCL.

Interventions:

The patient was treated with 6 cycles of R-CHOP (cyclophosphamide, adriamycin, vincristine, prednisone, and rituximab).

Outcomes:

The treatment was well tolerated and led to complete remission for the patient. There was no sign of relapse over the 3-year close follow-up

Lessons:

DLBCL can be present at various extranodal sites and clinicians irrespective of their specialty must be vigilant for the synchronous mode of presentation of such lesions. Immunohistochemical techniques play a vital role in the diagnosis, because clinical characteristics may be misleading.
Plasmacytoma of the skull mimicking an epidural hematoma
Authors: Chen Zupeng , Li Xu
Published: April 2019

Rationale:

Plasmacytoma as the 1st presentation of skull tumors is a rare disorder. When it is combined with brain trauma or dramatic changes in intracranial pressure, patients are more prone to misdiagnosis.

Patient concerns:

A 67-year-old woman complaining of a headache presented with a history of head trauma for the past 1 hour. Emergency head computed tomography initially suggested an epidural hematoma.

Diagnosis:

Emergency surgery was performed to remove the intracranial hematoma, but a tumor-like mass was found during surgery, and pathologic assessment confirmed plasmacytoma. Surgery was difficult because of bleeding. The tumor was radically removed.

Interventions and outcomes:

The patient underwent whole-brain radiotherapy and chemotherapy. She died 40 months after the surgery.

Lessons:

Epidural lesions found after a head injury may be assumed to be an epidural hematoma, leading to unnecessary surgery. Diseases such as hematomas, meningiomas, eosinophilic granulomas, bone metastases, and osteosarcomas must be considered.
Craniosynostosis: A Reversible Pathology?
Authors: Säljö Karin , Maltese Giovanni , Tarnow Peter , Kölby Lars
Published: April 2019

The formation of the cranial sutures, in utero, occurs when the ossification of the skull bones reaches predestined positions around gestational week 15 to 20. Craniosynostosis, and the consequent skull shape deformities, is treated with surgery including osteotomies of the fused sutures. The occasional appearance of a new suture in the osteotomy lines has previously been described as sporadic events. In this retrospective study, a 4-year consecutive series of osteotomies combined with springs for craniosynostosis were systematically analysed regarding the appearance of neosutures. In total, 84 patients were included and in 16 patients (19%) a new radiologically normal suture appeared in a part of the suture that was completely closed preoperatively. Additionally, in 7 patients (8%) a new suture appeared in a part of the suture that had a discernible suture prior to surgery.

In conclusion, in this consecutive and well-defined patient cohort operated for craniosynostosis, the formation of a neosuture is not a rare, and speculatively not a random, event. The appearance of a new suture long after the normal time period for suture formation in utero indicates that the craniosynostosis may just as well be caused by disturbed formation of the suture as actual premature closure.
Potential Patient Education of YouTube Videos Related to Wisdom Tooth Surgical Removal
Authors: Özdal Zincir Özge , Bozkurt Aylin Paşaoğlu , Gaş Selin
Published: April 2019

This present study aimed to evaluate the education of YouTube videos about wisdom tooth surgical removal for viewers. In this study, the term “wisdom tooth surgical removal” was searched on YouTube. After excluding duplicates, irrelevant videos, non-English-language videos; 92 relevant videos in English were independently examined by 3 reviewers. The videos were categorized as ‘poor’, ‘moderate’ and ‘excellent’ by scoring 9 points in order to evaluate the information they provided to the audience. Chi-square test was performed for categorical variables and differences between groups were compared with ANOVA-Kruskal Wallis. Correlations were analyzed using Pearson and Spearman test. Statistical significance was set P < 0.05. Majority of the videos (63%, n = 58) were uploaded by layperson for sharing personal experience, 19.6%, (n = 18) healthcare professionals (dentist, orthodontist, surgeon). There were 64 (69.6%) not useful videos, 19 (20.7%) moderately useful videos, and 9 (9.8%) very useful videos. There is no significant correlation between efficiency ratio and source of upload (P > 0.05). There is a significant relationship between efficiency ratio and interaction index (P = 0.019 < 0.05). Interaction indexes of poor useful videos are more than others. There is a significant relationship between the type of video and video demographics (all data’ significant values < 0.05). Mean values of patient's experience are more than others. Healthcare professionals should be aware of the accuracy of information on the internet in order to guide patients.
Single-Cell Analysis Reveals Regional Reprogramming during Adaptation to Massive Small Bowel Resection in Mice
Authors: Seiler Kristen M. , Waye Sarah E. , Kong Wenjun , Kamimoto Kenji , Bajinting Adam , Goo William H. , Onufer Emily J. , Courtney Cathleen , Guo Jun , Warner Brad W. , Morris Samantha A.
Published: April 2019

Background & Aims

The small intestine (SI) displays regionality in nutrient and immunological function. Following SI tissue loss (as occurs in short gut syndrome, or SGS), remaining SI must compensate, or ‘adapt’; the capacity of SI epithelium to reprogram its regional identity has not been described. Here, we apply single-cell resolution analyses to characterize molecular changes underpinning adaptation to SGS.

Methods

Single-cell RNA-sequencing was performed on epithelial cells isolated from distal SI of mice following 50% proximal small bowel resection (SBR) vs. sham surgery. Single-cell profiles were clustered based on transcriptional similarity, reconstructing differentiation events from intestinal stem cells (ISCs) through to mature enterocytes. An unsupervised computational approach to score cell identity was used to quantify changes in regional (proximal vs distal) SI identity, validated using immunofluorescence, immunohistochemistry, qPCR, western blotting, and RNA-FISH.

Results

Uniform Manifold Approximation and Projection-based clustering and visualization revealed differentiation trajectories from ISCs to mature enterocytes in sham and SBR. Cell identity scoring demonstrated segregation of enterocytes by regional SI identity: SBR enterocytes assumed more mature proximal identities. This was associated with significant upregulation of lipid metabolism and oxidative stress gene expression, which was validated via orthogonal analyses. Observed upstream transcriptional changes suggest retinoid metabolism and proximal transcription factorCreb3l3drive proximalization of cell identity in response to SBR.

Conclusions

Adaptation to proximal SBR involves regional reprogramming of ileal enterocytes toward a proximal identity. Interventions bolstering the endogenous reprogramming capacity of SI enterocytes—conceivably by engaging the retinoid metabolism pathway—merit further investigation, as they may increase enteral feeding tolerance, and obviate intestinal failure, in SGS.

Synopsis

Here, single-cell RNA sequencing reveals interactions between the retinoid metabolism pathway and ‘regional reprogramming’ of distal small intestinal epithelium to a proximal identity following proximal small bowel resection. This provides novel insight into physiological adaptation to short gut syndrome.
A lipophilicity-based energy function for membrane-protein modelling and design
Authors: Weinstein Jonathan Yaacov , Elazar Assaf , Fleishman Sarel Jacob
Published: April 2019

Membrane-protein design is an exciting and increasingly successful research area which has led to landmarks including the design of stable and accurate membrane-integral proteins based on coiled-coil motifs. Design of topologically more complex proteins, such as most receptors, channels, and transporters, however, demands an energy function that balances contributions from intra-protein contacts and protein-membrane interactions. Recent advances in water-soluble all-atom energy functions have increased the accuracy in structure-prediction benchmarks. The plasma membrane, however, imposes different physical constraints on protein solvation. To understand these constraints, we recently developed a high-throughput experimental screen, called dsTβL, and inferred apparent insertion energies for each amino acid at dozens of positions across the bacterial plasma membrane. Here, we express these profiles as lipophilicity energy terms in Rosetta and demonstrate that the new energy function outperforms previous ones in modelling and design benchmarks. Rosetta ab initio simulations starting from an extended chain recapitulate two-thirds of the experimentally determined structures of membrane-spanning homo-oligomers with <2.5 Å root-mean-square deviation within the top-predicted five models. Furthermore, in two sequence-design benchmarks, the energy function improves discrimination of stabilizing point mutations and recapitulates natural membrane-protein sequences of known structure, thereby recommending this new energy function for membrane-protein modelling and design.
Predictability of salient distractor increases top-down control in healthy younger and older adults
Authors: Haupt Marleen , Napiórkowski Natan , Sorg Christian , Müller Hermann J. , Finke Kathrin
Published: April 2019

Younger adults are able to shield attentional selection against distractors when they have preknowledge about the upcoming distractor location. For older adults, who suffer from an overall decrease in attentional capacity and who are, in addition, particularly prone to attentional capture, such an adaptive shielding ability would be of particular importance. However, it is an open question whether healthy older adults can utilise the predictability of distractor locations to improve top-down controlled selection to the same degree as younger adults. The theory of visual attention (TVA) framework provides a systematic way to measure an individual’s efficiency of top-down control. The present study combined a TVA-based partial-report paradigm with abrupt-onset cues rendering the indicated location highly salient in a bottom-up fashion. Experiment 1, in which (on cued trials) the cue was invariably followed by a distractor at the cued location, showed that the cueing increased the weight of the distractor in the competition for selection compared to uncued distractors (on trials without a cue). In Experiment 2, the probability with which the abrupt-onset cue indicated the upcoming distractor location (1/3 vs. 2/3 of trials) was manipulated between experimental blocks. Participants were able to learn these statistical contingencies and exert top-down control more efficiently in blocks with highly valid distractor location cues, as compared to low-validity blocks. This finding suggests that, even though abrupt-onset spatial cues increase the attentional weights of distractors, participants can acquire and use pre-knowledge about the likelihood that a distractor will appear at an indicated location to down-weight the bottom-up attentional-capture signal. This ability turned out to be comparable across age groups, suggesting that efficient use of predictive information to shield against distracting information is preserved in normal ageing.
Conditions for synaptic specificity during the maintenance phase of synaptic plasticity
Authors: Huertas Marco A. , Sacktor Todd Charlton , Shouval Harel Z.
Published: April 2019

Activity-dependent modifications of synaptic efficacies are a cellular substrate of learning and memory. Experimental evidence shows that these modifications are synapse-specific and that the long-lasting effects are associated with the sustained increase in concentration of specific proteins like PKMζ. However, such proteins are likely to diffuse away from their initial synaptic location and spread out to neighboring synapses, potentially compromising synapse-specificity. In this paper we address the issue of synapse-specificity during memory maintenance. Assuming that the long-term maintenance of synaptic plasticity is accomplished by a molecular switch we perform simulations using the reaction-diffusion package in NEURON and analytical calculations to determine the limits of synaptic-specificity during maintenance. Moreover, we explore the effects of the diffusion and degradation rates of proteins and of the geometrical characteristics of dendritic spines on synapse specificty. We conclude that the necessary conditions for synaptic specificity during maintenance require that protein synthesis occurs in dendritic spines and that the activated dendritic spines exhibit small neck diameters.
The histone demethylase KDM5 controls developmental timing inDrosophilaby promoting prothoracic gland endocycles
Authors: Drelon Coralie , Belalcazar Helen M. , Secombe Julie
Published: April 2019

InDrosophila, the larval prothoracic gland integrates nutritional status with developmental signals to regulate growth and maturation through the secretion of the steroid hormone ecdysone. While the nutritional signals and cellular pathways that regulate prothoracic gland function are relatively well studied, the transcriptional regulators that orchestrate the activity of this tissue remain largely unknown. Here we show thatlysine demethylase 5 (KDM5) is essential for prothoracic gland function. Indeed, restoringkdm5expression only in the prothoracic gland in an otherwisekdm5mutant animal is sufficient to rescue both the larval developmental delay and the pupal lethality caused by loss of KDM5. Molecularly, our studies show that KDM5 functions by promoting the endoreplication of prothoracic gland cells, a process that increases ploidy and is rate-limiting for the expression of ecdysone biosynthetic genes. This occurs through KDM5-mediated regulation of the receptor tyrosine kinasetorso, which in in turn promotes polyploidization and growth through activation of the MAPK signaling pathway. Taken together, our studies provide key insights into the biological processes regulated by KDM5 and the molecular mechanisms that govern the transcriptional regulation of animal development.
Neighbor predation linked to natural competence fosters the transfer of large genomic regions inVibrio cholerae
Authors: Matthey Noémie , Stutzmann Sandrine , Stoudmann Candice , Guex Nicolas , Iseli Christian , Blokesch Melanie
Published: April 2019

Natural competence for transformation is a primary mode of horizontal gene transfer (HGT). Competent bacteria are able to absorb free DNA from their surroundings and exchange this DNA against pieces of their own genome when sufficiently homologous. And while it is known that transformation contributes to evolution and pathogen emergence in bacteria, there are still questions regarding the general prevalence of non-degraded DNA with sufficient coding capacity. In this context, we previously showed that the naturally competent bacteriumVibrio choleraeuses its type VI secretion system (T6SS) to actively acquire DNA from non-kin neighbors under chitin-colonizing conditions. We therefore sought to further explore the role of the T6SS in acquiring DNA, the condition of the DNA released through T6SS-mediated killing versus passive cell lysis, and the extent of the transfers that occur due to these conditions. To do this, we herein measured the frequency and the extent of genetic exchanges in bacterial co-cultures on competence-inducing chitin under various DNA-acquisition conditions. We show that competentV. choleraestrains acquire DNA fragments with an average and maximum length exceeding 50 kbp and 150 kbp, respectively, and that the T6SS is of prime importance for such HGT events. Collectively, our data support the notion that the environmental lifestyle ofV. choleraefosters HGT and that the coding capacity of the exchanged genetic material is sufficient to significantly accelerate bacterial evolution.

Significance Statement

DNA shuffled from one organism to another in an inheritable manner is a common feature of prokaryotes. It is a significant mechanism by which bacteria acquire new phenotypes, for example by first absorbing foreign DNA and then recombining it into their genome. In this study, we show the remarkable extent of the exchanged genetic material, frequently exceeding 150 genes in a seemingly single transfer event, inVibrio cholerae. We also show that to best preserve its length and quality, bacteria mainly acquire this DNA by killing adjacent, healthy neighbors then immediately absorbing the released DNA before it can be degraded. These new insights into this prey-killing DNA acquisition process shed light on how bacterial species evolve in the wild.
Gene-Specific Methylation Profiles for Integrative Methylation-Expression Analysis in Cancer Research
Authors: Liu Yusha , Baggerly Keith A. , Orouji Elias , Manyam Ganiraju , Chen Huiqin , Lam Michael , Davis Jennifer S. , Lee Michael S. , Broom Bradley M. , Menter David G. , Rai Kunal , Kopetz Scott , Morris Jeffrey S.
Published: April 2019

DNA methylation is a key epigenetic factor regulating gene expression. While promoter-associated methylation has been extensively studied, recent publications have revealed that functionally important methylation also occurs in intergenic and distal regions, and varies across genes and tissue types. Given the growing importance of inter-platform integrative genomic analyses, there is an urgent need to develop methods to construct gene-level methylation summaries that account for the potentially complex relationships between methylation and expression. We introduce a novel sequential penalized regression approach to construct gene-specific methylation profiles (GSMPs) which find for each gene and tissue type a sparse set of CpGs best explaining gene expression and weights indicating direction and strength of association. Using TCGA and MD Anderson colorectal cohorts to build and validate our models, we demonstrate our strategy better explains expression variability than standard approaches and produces gene-level scores showing key methylation differences across recently discovered colorectal cancer subtypes. We share an R Shiny app that presents GSMP results for colorectal, breast, and pancreatic cancer with plans to extend it to all TCGA cancer types. Our approach yields tissue-specific, gene-specific sparse lists of functionally important CpGs that can be used to construct gene-level methylation scores that are maximally correlated with gene expression for use in integrative models, and produce a tissue-specific summary of which genes appear to be strongly regulated by methylation. Our results introduce an important resource to the biomedical community for integrative genomics analyses involving DNA methylation.
Disrupted basal ganglia—thalamocortical loops in focal to bilateral tonic-clonic seizures
Authors: He Xiaosong , Chaitanya Ganne , Asma Burcu , Caciagli Lorenzo , Bassett Danielle S. , Tracy Joseph I. , Sperling Michael R.
Published: April 2019

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, as well as unfavorable treatment outcomes. Achieving greater understanding of its underlying circuitry offers better opportunity to control these particularly serious seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and the cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia—thalamus network with resting-state functional magnetic resonance imaging in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for over one year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of “disconnection” simulations, we showed that these changes in interactive profiles of the basal ganglia—thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between the basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.
Identification of neuronal lineages in theDrosophilaperipheral nervous system with a novel multi-spectral lineage tracing system
Authors: Veling Macy W. , Li Ye , Veling Mike T. , Litts Christopher , Michki Nigel , Liu Hao , Cai Dawen , Ye Bing
Published: April 2019

Elucidating cell lineages provides crucial understanding of development. Recently developed sequencing-based techniques enhance the scale of lineage tracing but eliminate the spatial information offered by conventional approaches. Multispectral labeling techniques, such asBrainbow, have the potential to identify lineage-related cellsin situ. Here, we reportLineage Tracker Bitbow, a “digital” version ofBrainbowthat greatly expands the color diversity, and a suite of statistical methods for quantifying the lineage relationship of any two cells. Applying these tools toDrosophilaperipheral nervous system, we determined lineage relationship between all neuronal pairs. Based on the refined lineage map, we explored whether distinctcis-regulatory elements are used in controlling the expression of a terminal selector gene in distinct lineage patterns. This study demonstratesLT-Bitbowas an efficient tool forin-situlineage mapping and its potential in studying molecular mechanisms in the lineage context.
Differential Expression Gene Explorer (DrEdGE): A tool for generating interactive online data visualizations for exploration of quantitative transcript abundance datasets
Authors: Tintori Sophia C. , Golden Patrick , Goldstein Bob
Published: April 2019

As the scientific community becomes increasingly interested in data sharing, there is a growing need for tools that facilitate the querying of public data. Mining of RNA-seq datasets, for example, has value to many biomedical researchers, yet is often effectively inaccessible to non-genomicist experts, even when the raw data are available. Here we present DrEdGE (dredge.bio.unc.edu), a free Web-based tool that facilitates data sharing between genomicists and their colleagues. The DrEdGE software guides genomicists through easily creating interactive online data visualizations, which colleagues can then explore and query according to their own conditions to discover genes, samples, or patterns of interest. We demonstrate DrEdGE’s features with three example websites we generated from publicly available datasets—human neuronal tissue, mouse embryonic tissue, and a C. elegans embryonic series. DrEdGE increases the utility of large genomics datasets by removing the technical obstacles that prevent interested parties from exploring the data independently.
The structural basis for RNA selectivity by the IMP family of RNA binding proteins
Authors: Biswas Jeetayu , Patel Vivek L. , Bhaskar Varun , Chao Jeffrey A. , Singer Robert H. , Eliscovich Carolina
Published: April 2019

The Igf2 mRNA binding proteins (ZBP1/IMP1, IMP2, IMP3) are highly conserved post-transcriptional regulators of RNA stability, localization and translation. They play important roles in cell migration, neural development, metabolism and cancer cell survival. The knockout phenotypes of individual IMP proteins suggest that each family member regulates a unique pool of RNAs, yet evidence and an underlying mechanism for this is lacking. Here, we combine SELEX and NMR spectroscopy to demonstrate that the major RNA binding domains of the two most distantly related IMPs (ZBP1 and IMP2) bind to different consensus sequences and regulate targets consistent with their knockout phenotypes and roles in disease. We find that the targeting specificity of each IMP is determined by few amino acids in their variable loops. As variable loops often differ amongst KH domain paralogs, we hypothesize that this is a general mechanism for evolving specificity and regulation of the transcriptome.
Thermophilic PHB depolymerase ofStenotrophomonassp., an isolate from the plastic contaminated site is best purified on Octyl-Sepharose CL-4B
Authors: Sayyed R Z , Wani S J , Shaikh S S , Al-Harthi Helal F. , Syed Asad , El-Enshasy Hesham Ali
Published: April 2019

There are numerous reports on PHB depolymerases produced by a wide variety of microorganisms isolated from various habitats, however, reports on PHB depolymerase isolated from plastic contaminated sites are scares. Thermophilic PHB polymerase produced by isolates obtained from plastic contaminated sites is expected to have better relevance for its application in plastic/ bioplastic degradation. Although PHB has attracted commercial significance, the inefficient production and recovery methods, inefficient purification of PHB depolymerase and lack of ample knowledge on PHB degradation by PHB depolymerase have hampered its large scale commercialization. Therefore, to ensure the biodegradability of biopolymers, it becomes imperative to study the purification of the biodegrading enzyme system. We report the production, purification, and characterization of extracellular PHB depolymerase fromStenotrophomonassp. RZS 7 isolated from a plastic contaminated site. The isolate produced extracellular poly-β-hydroxybutyrate (PHB) depolymerase in the mineral salt medium at 30oC during 4 days of incubation under shake flask condition. Purification of the enzyme was carried out by three different methods using PHB as a substrate. Purification of PHB depolymerase by ammonium salt precipitation, column chromatography, and solvent purification method was successfully carried out. Among the purification method tested, the enzyme was best purified by column chromatography on Octyl-Sepharose CL-4B column with maximum (0.7993 U/mg/ml) purification yield. The molecular weight of purified PHB depolymerase (40 kDa) closely resembled with PHB depolymerase ofAureobacterium saperdae.
Force-dependent facilitated dissociation can generate protein-DNA catch bonds
Authors: Dahlke K. , Zhao J. , Sing C.E. , Banigan E. J.
Published: April 2019

Cellular structures are continually subjected to forces, which may serve as mechanical signals for cells through their effects on biomolecule interaction kinetics. Typically, molecular complexes interact via “slip bonds,” so applied forces accelerate off rates by reducing transition energy barriers. However, biomolecules with multiple dissociation pathways may have considerably more complicated force dependencies. This is the case for DNA-binding proteins that undergo “facilitated dissociation,” in which competitor biomolecules from solution enhance molecular dissociation in a concentration-dependent manner. Using simulations and theory, we develop a generic model that shows that proteins undergoing facilitated dissociation can form an alternative type of molecular bond, known as a “catch bond,” for which applied forces suppress protein dissociation. This occurs because the binding by protein competitors responsible for the facilitated dissociation pathway can be inhibited by applied forces. Within the model, we explore how the force dependence of dissociation is regulated by intrinsic factors, including molecular sensitivity to force and binding geometry, and the extrinsic factor of competitor protein concentration. We find that catch bonds generically emerge when the force dependence of the facilitated unbinding pathway is stronger than that of the spontaneous unbinding pathway. The sharpness of the transition between slip- and catch-bond kinetics depends on the degree to which the protein bends its DNA substrate. These force-dependent kinetics are broadly regulated by the concentration of competitor biomolecules in solution. Thus, the observed catch bond is mechanistically distinct from other known physiological catch bonds because it requires an extrinsic factor – competitor proteins – rather than a specific intrinsic molecular structure. We hypothesize that this mechanism for regulating force-dependent protein dissociation may be used by cells to modulate protein exchange, regulate transcription, and facilitate diffusive search processes.

Statement of significance

Mechanotransduction regulates chromatin structure and gene transcription. Forces may be transduced via biomolecular interaction kinetics, particularly, how molecular complexes dissociate under stress. Typically, molecules form “slip bonds” that dissociate more rapidly under tension, but some form “catch bonds” that dissociate more slowly under tension due to their internal structure. We develop a model for a distinct type of catch bond that emerges via an extrinsic factor: protein concentration in solution. Underlying this extrinsic catch bond is “facilitated dissociation,” whereby competing proteins from solution accelerate protein-DNA unbinding by invading the DNA binding site. Forces may suppress invasion, inhibiting dissociation, as for catch bonds. Force-dependent facilitated dissociation can thus govern the kinetics of proteins sensitive to local DNA conformation and mechanical state.
Crystal structures of 4-{(E)-3-[(imino-λ5-azanylidene)amino]prop-1-enyl}-N,N-dimethylimidazole-1-sulfonamide and 2-[(imino-λ5-azanylidene)amino]-4-{(E)-3-[(imino-λ5-azanylidene)amino]prop-1-enyl}-N,N-dimethylimidazole-1-sulfonamide
Authors: Cruz Lorenzo M. , Moore Raakiyah Y. , Gutierrez Marcela Torres , Herath Apsara K. , Lovely Carl J. , Yousufuddin Muhammed
Published: April 2019

The structures of two azide containing imidazole derivatives are reported. Allylic azides are fairly reactive making them attractive starting compounds to convert into amides. The first, C8H12N6O2S, contains one azide group with an Nα—Nβ distance of 1.229 (2) Å and an Nβ—Nγ distance of 1.128 (2) Å. The second, C8H11N9O2S, contains two azide groups with an average Nα—Nβ distance of 1.249 (2) Å and an average Nβ—Nγ distance of 1.132 (2) Å. Each compound contains a bulky protecting group (dimethylaminosulfonyl) which can be easily removed under mildly acidic conditions.
The e-government paradox in post-Soviet countries
Authors: Knox Colin , Janenova Saltanat
Published: April 2019

Purpose

The purpose of this paper is to investigate the emergence of e-government in post-Soviet countries using Kazakhstan as a case study. Extant research on e-government in developing countries highlights significant benefits including improved public services, reduced corruption, and more open and inclusive government. The paper asserts the presence of an e-government paradox which limits its potential to improve public services.

Design/methodology/approach

Primary data were collected from a number of sources: 6 focus groups with central government agencies, local authorities and civil society organisations; 25 structured and semi-structured interviews; and participant observation.

Findings

The research finds evidence of an e-government paradox in five forms: an emphasis on technological development; transactional services are faster but have displaced attention from core public services; petty corruption has been reduced but grand corruption remains; isomorphic mimicry; and greater participation by citizens has been limited.

Research limitations/implications

The focus of the research is Kazakhstan. Applying the lessons learned to other post-Soviet countries has limitations given their different stages of development since independence.

Practical implications

The key practical implication of this research is that countries can become absorbed by e-government technology without questioning the fundamental business model which underpins how public services are delivered. Ultimately, this impacts on the social value of e-government.

Originality/value

While existing research has examined how e-government has been implemented in developing countries, this paper focusses on Kazakhstan as an authoritarian state with wider implications for post-Soviet countries.
Interorganizational knowledge sharing in a science and technology park: the use of knowledge sharing mechanisms
Authors: Balle Andrea Raymundo , Steffen Mário Oscar , Curado Carla , Oliveira Mírian
Published: April 2019

Purpose

This paper aims to uncover the combinations of knowledge sharing mechanisms that organizations in a science and technology park in Brazil use to share managerial and technical knowledge.

Design/methodology/approach

This research adopts a qualitative approach that uses a fuzzy set qualitative comparative analysis to analyze data that are gathered from 51 managers of organizations in a science and technology park.

Findings

The results show that knowledge sharing happens regardless of the type of knowledge. There are more alternative paths that lead to knowledge sharing than to its absence. Regarding the type of knowledge shared, there are more alternative configurations that lead to managerial knowledge sharing than to technical knowledge sharing. Only the older organizations in the science and technology park abstain from knowledge sharing.

Research limitations/implications

Due to the qualitative nature of the study, no generalization is possible. Additionally, the study’s limitation is that it involves organizations from a single science and technology park.

Practical implications

The results offer managers of organizations in science and technology parks to choose from alternative combinations of mechanisms to either boost their knowledge sharing or to promote knowledge protection.

Originality/value

The paper provides an original contribution by identifying the combinations of mechanisms that organizations in a science and technology park use that leads to the sharing of specific knowledge types. The findings also identify the combination of mechanisms that older organizations use that prevents them from sharing knowledge.
Politically exposed entities: how to tailor PEP requirements to PEP owned legal entities
Authors: Canestri Daniele
Published: April 2019

Purpose

This paper aims to address the money laundering risk posed by politically exposed person’s (PEP’s) controlled legal entities. International standards and national legislation require enhanced due diligence of political office holders but no specific requirements exist on entities controlled by PEPs. While regulators expect the stringent AML risk mitigation regarding this type of entities, financial institutions have no guidelines to follow. This gap produces inconsistent due diligence measures applied to entities with significant PEPs’ connection.

Design/methodology/approach

The paper uses comparative analysis to identify discrepancies between legal requirements and their interpretation. Moreover, an empirical approach results in a standardised solution to address these discrepancies.

Findings

The paper defines the concept of politically exposed entities and the applicable due diligence framework. Anticipating legislative measures, it proposes to introduce this concept via best practices of financial institutions and private banking initiatives such as the Wolfsberg Group.

Research limitations/implications

The research addresses the topic from a legal point of view. However, the implementation of proposed ideas depends on decisions which are political by nature and are not within the scope of this paper.

Practical implications

The paper aims at stimulating a debate in both the private and public sector to form a consistent approach to AML due diligence of legal entities associated to PEPs.

Originality/value

This paper responds to an identified need to study how legal entities connected to PEPs should be defined and monitored.
Outcomes of patients on dual antiplatelet therapy post‐coronary stenting following emergency noncardiac surgery
Authors: Irie Hiromasa , Kawai Keiko , Otake Takanao , Shinjo Yasutaka , Kuriyama Akira , Yamashita Shigeki
Published: April 2019

Background

The outcomes of patients on dual antiplatelet therapy (DAPT) post‐coronary stenting following emergency noncardiac surgery remain unclear.

Methods

This retrospective cohort study included patients on DAPT post‐coronary stenting who underwent emergency noncardiac surgery within 24 hours of diagnosis from April 2007 to March 2018 where DAPT was discontinued within <5 days for aspirin and 7 days for P2Y12 inhibitors. Our primary outcome was 180‐day mortality in these patients. We investigated factors associated with bleeding within 180 days after surgery as our secondary outcome and exploratorily examined factors affecting 180‐day mortality.

Results

Of 62,528 patients who underwent any surgery under general anaesthesia during the 11‐year study period, 133 patients (0.22% of all and 1.41% of emergency surgical patients) were analysed. Among the eligible patients, 180‐day mortality was 9.8% (13/133). Eighteen patients (13.5%) developed bleeding within 180 days after surgery, which was the most common post‐operative complication. Restarting antiplatelet agents <2 days post‐operatively (OR, 4.51; 95% CI, 1.56‐13.0; P = 0.005) and stent implantation at bifurcation lesions before surgery (OR, 3.28; 95% CI, 1.07‐10.1; P = 0.04) were associated with post‐operative bleeding. Patients on haemodialysis had the worse prognosis (hazard ratio, 5.73; 95% CI, 1.87‐17.5; P = 0.002) in terms of 180‐day mortality.

Conclusion

The 180‐day mortality following emergency noncardiac surgery was approximately 10% in patients on DAPT post‐coronary stenting. Restarting antiplatelet agents earlier than 2 days post‐operatively and coronary stenting at bifurcation lesions were associated with bleeding within 180 days after surgery.