bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokines and chemokines triggered by Chikungunya virus infection in human patients during the very early acute phase
Authors: Tanabe Ithallo S B , Santos Elane C , Tanabe Eloiza L L , Souza Stephannie J M , Santos Fabio E F , Taniele-Silva Jamile , Ferro Jean F G , Lima Magliones C , Moura Adriana A , Anderson Leticia , Bassi Ênio J
Published: June 2019

Background

The immune response against the Chikungunya virus (CHIKV) during the very early acute phase is not fully elucidated. Therefore we explored the cytokine and chemokine profile triggered by CHIKV in infected patients.

Methods

Cytokines, chemokines and C5a anaphylatoxin were analysed in serum from CHIKV-infected patients during the viraemic phase (mean 2.97±1.27 d after illness onset) compared with a healthy group.

Results

CHIKV-infected patients had a significant increase of interferon-α (IFN-α), interleukin-6 (IL-6), interleukin-8 (CXCL8/IL-8), interleukin-10 (IL-10), interferon-γ (IFN-γ), monokine induced by interferon-γ (CXCL9/MIG), monocyte chemoattractant protein-1 (CCL2/MCP-1), interferon-γ-induced protein-10 (CXCL10/IP-10) and complement C5a anaphylatoxin.

Conclusions

The very early acute immune response triggered against CHIKV leads to an increase in pro-inflammatory immune mediators such as IFN-γ and its induced chemokines, and a high level of C5a anaphylatoxin as a result of complement activation.
Association of Blood Component Ratios With 24-Hour Mortality in Injured Children Receiving Massive Transfusion
Authors: Butler Elissa K. , Mills Brianna M. , Arbabi Saman , Bulger Eileen M. , Vavilala Monica S. , Groner Jonathan I. , Stansbury Lynn G. , Hess John R. , Rivara Frederick P.
Published: June 2019

Objectives:

To determine if higher fresh frozen plasma and platelet to packed RBC ratios are associated with lower 24-hour mortality in bleeding pediatric trauma patients.

Design:

Retrospective cohort study using the Pediatric Trauma Quality Improvement Program Database from 2014 to 2016.

Setting:

Level I and II pediatric trauma centers participating in the Trauma Quality Improvement Program

Patients:

Injured children (≤ 14 yr old) who received massive transfusion (≥ 40 mL/kg total blood products in 24 hr). Of 123,836 patients, 590 underwent massive transfusion, of which 583 met inclusion criteria.

Interventions:

None.

Measurements and Main Results:

Ratios of fresh frozen plasma:packed RBC and platelet:packed RBC. Of the 583 patients, 60% were male and the median age was 5 years (interquartile range, 2–10 yr). Overall mortality was 19.7% (95% CI, 16.6–23.2%) at 24 hours. There was 51% (adjusted relative risk, 0.49; 95% CI, 0.27–0.87; p = 0.02) and 40% (adjusted relative risk, 0.60; 95% CI, 0.39–0.92; p = 0.02) lower risk of death at 24 hours for the high (≥ 1:1) and medium (≥ 1:2 and < 1:1) fresh frozen plasma:packed RBC ratio groups, respectively, compared with the low ratio group (< 1:2). Platelet:packed RBC ratio was not associated with mortality (adjusted relative risk, 0.94; 95% CI, 0.51–1.71; p = 0.83).

Conclusions:

Higher fresh frozen plasma ratios were associated with lower 24-hour mortality in massively transfused pediatric trauma patients. The platelet ratio was not associated with mortality. Although these findings represent the largest study evaluating blood product ratios in pediatric trauma patients, prospective studies are necessary to determine the optimum blood product ratios to minimize mortality in this population.
PREDICTIVE ACTIVATION BIOMARKERS OF TREATMENT-NAIVE ASYMPTOMATIC CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION
Authors: Serra Rita , Coscas Florence , Boulet Jean François , Cabral Diogo , Lupidi Marco , Coscas Gabriel J. , Souied Eric H.
Published: June 2019

Purpose:

To assess the long-term evolution of treatment-naive quiescent choroidal neovascularization (CNV), in age-related macular degeneration (AMD), to identify predictive activation biomarkers.

Methods:

Patients with quiescent CNV underwent a comprehensive ophthalmological examination, including fluorescein and indocyanine green angiographies, structural optical coherence tomography (OCT), and OCT angiography. Qualitative and quantitative analyses of structural OCT and OCT angiography images were performed during the study period. At the last follow-up evaluation, the enrolled eyes were divided into two groups: eyes with quiescent CNV converting to exudative AMD (eAMD) and those not progressing to eAMD.

Results:

Sixty-eight eyes of 68 patients were enrolled in the study. Mean follow-up duration was 40 ± 28 months using multimodal imaging and 22 ± 13 months using OCT angiography. On structural OCT, quiescent CNV not converting to eAMD showed a preferential growth of the pigment epithelium detachment greatest linear diameter (P = 0.009), whereas the eAMD group presented a preferential growth of the pigment epithelium detachment maximal height (P < 0.0001) during the study period. Quantitative analysis of choriocapillaris OCT angiograms confirmed the CNV area growth during follow-up (from 4.18 ± 4.77 mm2 at baseline to 5.10 ± 5.06 mm2 at the last follow-up visit; P = 0.02).

Conclusion:

A close follow-up is recommended to early identify predictive activation biomarkers of treatment-naive quiescent CNV.
A Path Analysis of Effects of Patients’ Underlying Conditions, Treatment Satisfaction, and Adherence on Quality of Life Among Korea Glaucoma Patients
Authors: Kim Chan Yun , Park Ki Ho , Ahn Jaehong , Ahn Myung-Douk , Cha Soon Cheol , Kim Ho-Soong , Kim Joon Mo , Kim Moon Jung , Kim Tae-Woo , Kim Yong Yeon , Lee Ji Woong , Park Sang-Woo , Sohn Yong Ho , Sung Kyung Rim , Yoo Chungkwon , Cha Jin-Hye , Kim Young-Joo , Lee Junyoung , Choi Jimi
Published: June 2019

Précis:

This observed patient-specific features and treatment-driven conditions that were significantly associated with the impairment of health-related quality of life (HRQOL) among glaucoma patients. The results suggest that more systematic strategies should be implemented to improve an HRQOL.

Purpose:

To determine factors contributing to an HRQOL and assess total, direct and indirect, effects that may exist between the determinants using path analysis.

Materials and Methods:

Data were derived from previous Korea glaucoma outcomes research. A total of 847 glaucoma outpatients with ≤2 years of eye-drop use were included in the present study. Including factors and their hypothetical pathways to an HRQOL were based on the literature review and consultation with specialists. Age, sex, comorbidities, and education levels were included as underlying conditions and treatment patterns were defined by the number of daily instillations of prescribed eye-drops. Treatment satisfaction and adherence were estimated using a Treatment Satisfaction Questionnaire for Medication, which assessed side-effects, effectiveness, convenience, global satisfaction, and pill count. An HRQOL was assessed by EQ-5D and EQ-visual analogue scale (EQ-VAS).

Results:

In EQ-5D analysis, male individuals showed total effects (β=0.102,P=0.0026), including both direct (β=0.076,P=0.0095) and indirect effects (β=0.0253,P=0.0020), which were mediated by treatment satisfaction in the side effects and global satisfaction categories. Higher education (β=0.197,P=0.0020) and satisfaction in the side effect (β=0.095,P=0.0076) and global satisfaction (β=0.075,P=0.0414) categories were found to have direct effects on EQ-5D. For EQ-VAS, higher education levels had significant total effects (β=0.153,P=0.0020) accounting for direct effects (β=0.131,P=0.0030) and indirect effects (β=0.0223,P=0.0531) through global satisfaction. In addition, male individuals had indirect effects (β=0.274,P=0.0165), which was indirectly mediated by satisfaction in the global satisfaction category. Comorbidity (β=−0.096,P=0.0090) and satisfaction in the effectiveness (β=0.094,P=0.0302), convenience (β=0.076,P=0.0390), and global satisfaction (β =0.144,P=0.0020) categories showed indirect effect on EQ-VAS.

Conclusion:

Higher education and better treatment satisfaction had positive effects on HRQOL both in direct and indirect ways whereas comorbidities indirectly showed negative associations with HRQOL.
Argon Laser Iridoplasty For Plateau Iris Syndrome: Long-Term Outcomes of 48 Eyes
Authors: Romito Norman , Bluwol Elisa , Graber Martin , Le Pape Clémence , Lachkar Yves
Published: June 2019

Precis:

Argon laser peripheral iridoplasty (ALPI) was performed on 48 eyes with plateau iris syndrome (PIS). Indentation gonioscopy was used to monitor the opening of the iridocorneal angle. Mean intraocular pressure (IOP) at 5 years decreased from 15.9 to 14.4 mm Hg. None of the eyes required trabeculectomy.

Purpose:

The purpose of this article was to report the long-term outcomes of ALPI for PIS.

Materials and Methods:

A retrospective chart review was performed on all patients with PIS treated with ALPI from 2001 to 2012. The study included 48 eyes from 28 patients with PIS after peripheral iridotomy, with a follow-up of at least 5 years. Patients with advanced glaucoma requiring initial surgical treatment (pathologic discs and IOP above the target IOP despite medical treatment) were excluded. The primary outcomes were the effect on the number of IOP medications, and the need for complementary selective laser trabeculoplasty (SLT) or surgery (trabeculectomy and/or phacoemulsification). Secondary outcomes were optic nerve head changes and adverse events.

Results:

The mean IOP statistically decreased after ALPI (15.91±2.62 vs. 14.35±2.18 mm Hg, P>0.001). The mean number of IOP-lowering medications statistically increased after ALPI (0.81±0.94 vs. 1.2±1.04, P>0.001). Mean follow-up was 92.4±26.5 months. At the end of the follow-up, 12 (25%) eyes had no medications, 20 (42%) had 1 medication, 11 (23%) had 2 medications, 3 (6%) had 3 medications, and 2 (4%) had 4. Ten (21%) eyes underwent SLT, 6 (10%) underwent phacoemulsification, and no trabeculectomy was necessary during follow-up. The change in cup to disc ratio from pre-ALPI to latest follow-up was not statistically significant, and no adverse events were reported.

Conclusions:

ALPI is relatively effective and safe to prevent angle-closure glaucoma and avoid trabeculectomy in patients with PIS. This procedure often helps to control IOP, although SLT and additional medical treatments are frequently necessary to maintain the target IOP.
Influence of Ocular Dimensional Change on 24-Hour Intraocular Pressure Measurement With Contact Lens Sensor
Authors: Tojo Naoki , Hayashi Atsushi
Published: June 2019

Purpose:

We measured changes in the corneal morphology and intraocular pressure (IOP) before and after the use of contact lens sensor (CLS). Then, we investigated whether the ocular dimensional change affected the measured IOP value with CLS.

Material and Methods:

In this prospective study, we examined 112 eyes of glaucoma patients. We measured the IOP fluctuation using a Sensimed Triggerfish CLS. We measured the corneal morphology before and after making measurements using a CLS in anterior segment optic coherent optical coherence tomography and measured the IOP with a Goldmann applanation tonometer. We investigated the correlation between these ocular dimensional changes and the last IOP value with CLS.

Results:

Measurement with the CLS significantly increased the IOP (P=0.0305), made the corneal thickness (CT) significantly thicker (P<0.001), and increased the steeper meridian (P=0.0026). The last value of IOP-patterns recorded with CLS was significantly correlated with the IOP immediately after the measurement with Goldmann applanation tonometer (P=0.0134), was not significantly correlated with central and peripheral CT. The difference of steeper and flatter curvature between before and after measurement significantly correlated with the last value of IOP-patterns recorded with CLS.

Conclusions:

Measurement with a CLS affects the IOP, CT, and corneal steeper meridian. From the last value of IOP-related patterns recorded with CLS, CLS could perceive accurate IOP. The change of corneal curvature might affect CLS output values.
A Case of Murine Typhus Presenting With Hemophagocytic Lymphohistiocytosis
Authors: Poulos Samuel , Grundy Brain , Al Mouslmani Mohammed , Bellur Sunil , Goodgame Boone , Douglass Elizabeth , Mondy Kristin
Published: June 2019

Murine typhus, also known as endemic typhus, is a rickettsial illness transmitted by the flea Xenopsylla cheopis, usually in contact with rats. Symptoms of the illness can be nonspecific, and murine typhus has been considered an underrecognized entity as it is sometimes confused with viral illnesses. Although hemophagocytic lymphohistiocytosis (HLH), a rare inflammatory condition characterized by activation of macrophages and phagocytosis of hematopoietic cells in the bone marrow, liver, and spleen, has been reported to occur in other rickettsial illnesses, to our knowledge it has not been reported as a complication of murine typhus. We report the case of a 39-year-old man for whom murine typhus was diagnosed with serological evaluation and HLH was diagnosed via bone marrow biopsy and other studies. Although HLH has been previously described with scrub typhus, and iron overload has been described with murine typhus infection, our case represents the first report of HLH diagnosed concurrently with a murine typhus infection.
Zika and Flint Water Public Health Emergencies
Authors: Lavin Roberta P. , Veenema Tener G. , Langan Joanne C. , Charney Rachel L. , Zimmerman Rick S. , Bender Annah
Published: June 2019

Pregnant women and children and individuals suffering from chronic illness are disproportionally impacted by public health emergencies. To meet the healthcare needs of these populations, the nursing workforce must be capable of responding in a timely and appropriate manner. The goal of this project was to create interactive and engaging evidence-based educational tool kits to advance healthcare provider readiness in the management of population health in response to the Zika and Flint Water crises. A multipronged, mixed-methods approach was used to identify essential education needs and required core competencies. Data were synthesized from discussion with key informants, review of relevant documents, and surveys of schools of nursing, public health, and medicine. The ADDIE model was used to integrate results into the development of the online learning tool kits using the ThingLink software program. An innovative online educational program to prepare healthcare providers to rapidly identify, mitigate, and manage the impact of the Zika and Flint Water crises upon pregnant women and children was implemented by the Society for the Advancement of Disaster Nursing. Innovative online learning tool kits can advance healthcare provider readiness by increasing knowledge and understanding of key components of specific public health emergencies.
Electrocardiographic and Echocardiographic Findings in Black Athletes: A General Review
Authors: Pambo Prince , Scharhag Jürgen
Published: June 2019

Background:

Participation in regular physical activity produces electrophysiological and structural cardiac changes in electrocardiograms (ECGs) and echocardiographs (ECHOs) of athletes, and the term “athlete's heart” is used to describe these physiological cardiovascular adaptations. Extent and type of sporting discipline, age, sex, body dimensions, and ethnicity have an influence on cardiac remodeling.

Objective:

As the recent scientific literature increasingly reports on ethnicity-specific ECG and ECHO findings in black athletes, it is the aim of this review to provide an overview of ECG and ECHO findings among athletes of black African/Afro-Caribbean descent.

Data Sources:

A systematic search of PubMed and MEDLINE databases up to and including August 2017 was conducted using the following terms/phrases “black OR African OR Afro-Caribbean athlete heart,” “black OR African OR Afro-Caribbean athlete electrocardiogram,” and “black OR African OR Afro-Caribbean athlete echocardiogram.” The search generated a total of 130 papers, out of which 16 original articles fitted our criteria and were selected for this review.

Main Results:

The various studies reviewed revealed that about 10% to 30% of black African/Afro-Caribbean athletes had abnormal ECG. R/S voltage criteria exceeding hypertrophic indices were found in about 60% to 89% of black African/Afro-Caribbean athletes. ST-segment elevation (17%-90%) and T-wave inversions were also common findings among this ethnicity. About 10% to 12% of black African/Afro-Caribbean athletes had a left ventricular wall thickness ranging from 13 to 15 mm. Cavity dimensions ranged from 40 to 66 mm in black African/Afro-Caribbean athletes with a relative wall thickness >0.44.

Conclusions:

Updated ethnic-specific guidelines are required to discriminate physiological from pathologic hypertrophy and repolarization changes. Future studies should focus on homogeneous cohorts of African athletes.
Switching to Bortezomib may Improve Recovery From Severe Vincristine Neuropathy in Pediatric Acute Lymphoblastic Leukemia
Authors: Joshi Jaitri , Tanner Lynn , Gilchrist Laura , Bostrom Bruce
Published: June 2019

Purpose:

The purpose of this study was to evaluate the impact of switching patients being treated for acute lymphoblastic leukemia (ALL) from vincristine to bortezomib.

Patients and Methods:

A total of 20 patients with ALL were switched from vincristine to bortezomib (1.3 mg/m2/dose) because of worsening neuropathy despite physical therapy interventions (n=18) or at increased risk of neuropathy (n=2). Relapse rates were compared with 56 vincristine-only patients matched by prognostic factors. Maintenance blood counts in bortezomib patients were compared with cooperative group data using vincristine during maintenance. In addition, 6 evaluable patients were assessed for neuropathy using the pediatric-modified total neuropathy score. Neuropathy scores were collected during treatment with vincristine and after switching to bortezomib.

Results:

After a median follow-up of 3.5 years the relapse rate in patients switched to bortezomib was nonsignificantly different than those remaining on vincristine. Patients on monthly bortezomib had statistically significantly lower platelet counts that did not require transfusions or dose adjustment. Total neuropathy for all 6 cases decreased significantly when switched to bortezomib from vincristine (P=0.015), with motor neuropathy declines in 5 of 6 subjects.

Conclusions:

Bortezomib substitution for vincristine in ALL treatment is a potential strategy to mitigate severe vincristine neuropathy. These findings should be confirmed in a randomized clinical trial to further assess benefits and risks of this approach.
Obesity is associated with postinjury hypercoagulability
Authors: Samuels Jason M. , Moore Ernest E. , Coleman Julia R. , Sumislawski Joshua J. , Cohen Mitchell J. , Silliman Christopher C. , Banerjee Anirban , Ghasabyan Arsen , Chandler James , Sauaia Angela
Published: June 2019

BACKGROUND

Obesity is linked to hypercoagulability with an increased risk of venous thromboembolic events (VTE) in the uninjured population. Therefore, we hypothesize that obesity (body mass index [BMI] ≥30 kg/m2 [BMI30]) is associated with a hypercoagulable state postinjury characterized by increased clot strength and resistance to fibrinolysis.

METHODS

Our prospective Trauma Activation Protocol database includes all trauma activations patients for whom a rapid thrombelastography is obtained within 60 minutes postinjury prior to any transfusions. The data set was then stratified by BMI and subjects with BMI30 were compared with those with BMI less than 30 kg/m2). The following thrombelastography measurements were obtained: activated clotting time, clot formation rate (angle), maximum clot strength (MA), and % clot lysis 30 minutes after MA (LY30, %). Fibrinolysis shutdown (SD) was defined as LY30 < 0.6% and hyperfibrinolysis (HF) as LY30 greater than 7.6%. Continuous variables are expressed as median (interquartile range).

RESULTS

Overall, 687 patients were included of whom 161 (23%) had BMI30. The BMI30 group was older, had a lower proportion of males and of blunt trauma, and was less severely injured. After adjustment for confounders, BMI30 was independently associated with lower odds of MA less than 55 mm (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.13–0.60) and of HF (OR, 0.31; 95% CI, 0.10–0.97) and higher odds of SD (OR, 1.82; 95% CI, 1.09–3.05). No independent association was observed with angle less than 65° (OR 0.57 95% CI 0.30–1.05). While VTEs were more frequent among BMI30 patients (5.0 vs. 3.3%), this did not reach significance after confounding adjustment (p = 0.11).

CONCLUSION

Obesity was protective against diminished clot strength and hyperfibrinolysis, and obesity was associated with an increased risk of fibrinolytic SD in severely injured patients. These findings suggest a relative hypercoagulability. Although no difference in VTEs was noted in this study, these findings may explain the higher rate of VTEs reported in other studies.

LEVEL OF EVIDENCE

Prognostic and Epidemiological, level III.
Redlisting the redlist: a global analysis of species distributions and biodiversity
Authors: Hughes Alice C.
Published: June 2019

Global conservation and research has come to rely on the IUCN species range-maps to direct research, allocate funding and define and design protected areas. However, IUCN species range-maps may be created on the basis of little actual data. Though the IUCN methods may be suitable for well known species, they may be liable unreliable for lesser known species or areas. In such cases, human biases may limit the usefulness of the output maps and potentially misdirect conservation funding and protection. Possible errors in these IUCN maps has global implications for the preservation of biodiversity, as flawed data leads to flawed decisions, which are of critical importance to the protection of the biodiversity of this planet. Ultimately we show that the current IUCN “expert-assessment based” range-maps may hinder rather than assist global conservation, as errors ranged from tens to thousands of kilometres (between recorded distributions and IUCN-maps), and for some taxa under 50% of records fell within their mapped-ranges. IUCN maps are being used globally to evaluate global conservation and protection, yet up to 85.4% of IUCN species-range boundaries follow political-boundaries, making using IUCN maps to evaluate the protected-area system and it’s efficacy impossible. The current availability of data, methods and computer-power has relegated these maps in the wake of more empirically based methods, and better use of available data provides the ability to make better conservation decisions, especially for highly threatened species and regions.
TGAC Browser: An open-source genome browser for non-model organisms
Authors: Thanki Anil S. , Bian Xingdong , Davey Robert P.
Published: June 2019

Genome browsers play a vital role to provide visualisation for genomic data. It is often the case that bespoke genome browser customisations are required between different research groups, with an obvious necessity to update, upgrade and tailor tracks and features on a potentially frequent basis. However, most of the current genome browsers require highly curated data held in public repositories. Besides, these genome browsers often rely on particular dependencies, where writing plug-in or modifying existing code can be troublesome and resource expensive.

We present TGAC Browser, a new open-source web-based genome browser designed to overcome shortcomings in available approaches. It uses a locally installed Ensembl Core Database schema and is also able to visualise data from well-known NGS data formats. We also added simple analysis functionality to perform BLAST searches within TGAC Browser. TGAC Browser also allows uploading your genomic data. TGAC Browser is an open-source, easy to set up, and user-friendly genome browser with minimal, lightweight configuration details.
Human and mouse essentiality screens as a resource for disease gene discovery
Authors: Cacheiro Pilar , Muñoz-Fuentes Violeta , Murray Stephen A. , Dickinson Mary E. , Bucan Maja , Nutter Lauryl M.J. , Peterson Kevin A. , Haselimashhadi Hamed , Flenniken Ann M. , Morgan Hugh , Westerberg Henrik , Konopka Tomasz , Hsu Chih-Wei , Christiansen Audrey , Lanza Denise G. , Beaudet Arthur L. , Heaney Jason D. , Fuchs Helmut , Gailus-Durner Valerie , Sorg Tania , Prochazka Jan , Novosadova Vendula , Lelliott Christopher J. , Wardle-Jones Hannah , Wells Sara , Teboul Lydia , Cater Heather , Stewart Michelle , Hough Tertius , Wurst Wolfgang , Sedlacek Radislav , Adams David J. , Seavitt John R. , Tocchini-Valentini Glauco , Mammano Fabio , Braun Robert E. , McKerlie Colin , Herault Yann , de Angelis Martin Hrabě , Mallon Ann-Marie , Lloyd K.C. Kent , Brown Steve D.M. , Parkinson Helen , Meehan Terrence F. , Smedley Damian ,   on behalf of the Genomics England Research Consortium and the International Mouse Phenotyping Consortium
Published: June 2019

Although genomic sequencing has been transformative in the study of rare genetic diseases, identifying causal variants remains a considerable challenge that can be addressed in part by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from the comprehensive viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and from human cell line essentiality screens. We propose a novel, cross-species gene classification across theFullSpectrum of Intolerance toLoss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing characteristics in the biological processes they regulate, tissue expression levels and human mutation rates. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented in the developmental lethal category, representing genes not essential for cell survival but required for organism development. Exploiting this finding, we have screened developmental disorder cases from three independent disease sequencing consortia and identified potentially pathogenic,de novovariants shared in different patients for several developmental lethal genes that have not previously been associated with rare disease. We therefore propose FUSIL as an efficient resource for disease gene discovery.
Assessment of the gene expression profiles of leukocytes from different isolations
Authors: Xing Yanru , Yang Xi , Chen Haixiao , Zhu Sujun , Xu Jinjin , Chen Yuan , Zeng Juan , Chen Fang , Jiang Hui , Wang Wen-Jing
Published: June 2019

BACKGROUND

Research on peripheral leukocyte gene expression in human health and disease is growing rapidly. However, how to process sample efficiently, simply and stably, and how to reflect human physiological state preferably remains critical issues in large cohort studies.

METHODS

We used RNA-seq to explore the differences of gene expression profiles among whole blood (WB) and three groups of leukocytes from buffy coat (BC) extraction, red blood cell (RBC) lysis and peripheral blood mononuclear cell (PBMC) isolation.

RESULTS

The residual globin mRNA in leukocytes from RBC lysis (1.00% ±1.23%) and PBMC isolation (0.06% ± 0.03%) was much less than that in leukocytes from BC extraction (17.48% ± 6.95%) and WB (24.46% ± 6.43%), resulting in higher transcriptome mapping rates and larger numbers of detected genes. The expression of 616 genes associated with leukocyte function was slightly higher in leukocytes from RBC lysis than that from BC extraction and WB, but barely detected in leukocytes from PBMC isolation.

CONCLUSIONS

We suggest that sample processing based on RBC lysis could allow better applications of gene expression profiling of peripheral leukocytes in large cohort studies.
TulsiPIN: an interologous protein interactome ofOcimum tenuiflorum
Authors: Singh Vikram , Singh Gagandeep , Singh Vikram
Published: June 2019

Ocimum tenuiflorum, commonly known as holy basil or tulsi, is globally recognized for its multitude of medicinal properties. However, a comprehensive study revealing the complex interplay among its constituent proteins at subcellular level is still lacking. To bridge this gap, a genome scale interologous protein-protein interaction (PPI) network, TulsiPIN, is developed using 49 template plants. The reported network consists of 13, 660 nodes and 327, 409 binary interactions. A high confidence PPI network consisting of 7, 719 nodes having 95, 532 interactions was inferred using domain-domain interaction information along with interolog based statistics, and its reliability was further assessed using functional homogeneity and protein colocalization. 1, 625 vital proteins are predicted by statistically evaluating this high confidence TulsiPIN with two ensembles of corresponding random networks, each consisting of 10, 000 realizations of Erdős-Rényi and Barabási-Albert models. Topological features of TulsiPIN including small-world, scale-free and modular architecture are inspected and found to resemble with other plant PPI networks. Finally, numerous regulatory proteins like transcription factors, transcription regulators and protein kinases are profiled in TulsiPIN and a sub-network of proteins participating in 10 secondary metabolite biosynthetic pathways is studied. We believe, the methodology developed and insights imparted would be useful in understanding regulatory mechanisms in various plant species.
Understanding the functional and structural differences across excitatory and inhibitory neurons
Authors: Minni Sun , Ji-An Li , Moskovitz Theodore , Lindsay Grace , Miller Kenneth , Dipoppa Mario , Yang Guangyu Robert
Published: June 2019

One of the most fundamental organizational principles of the brain is the separation of excitatory (E) and inhibitory (I) neurons. In addition to their opposing effects on post-synaptic neurons, E and I cells tend to differ in their selectivity and connectivity. Although many such differences have been characterized experimentally, it is not clear why they exist in the first place. We studied this question in an artificial neural network equipped with multiple E and I cell types. We found that a deep convolutional recurrent network trained to perform an object classification task was able to capture salient distinctions between E and I neurons. We explored the necessary conditions for the network to develop distinct selectivity and connectivity across cell types. We found that neurons that project to higher-order areas will have greater stimulus selectivity, regardless of whether they are excitatory or not. Sparser connectivity is required for higher selectivity, but only when the recurrent connections are excitatory. These findings demonstrate that the differences observed across E and I neurons are not independent, and can be explained using a smaller number of factors.
The anaerobic digestion microbiome: a collection of 1600 metagenome-assembled genomes shows high species diversity related to methane production
Authors: Campanaro Stefano , Treu Laura , Rodriguez-R Luis M , Kovalovszki Adam , Ziels Ryan M , Maus Irena , Zhu Xinyu , Kougias Panagiotis G. , Basile Arianna , Luo Gang , Schlüter Andreas , Konstantinidis Konstantinos T. , Angelidaki Irini
Published: June 2019

Background

Microorganisms in biogas reactors are essential for degradation of organic matter and methane production through anaerobic digestion process. However, a comprehensive genome-centric comparison, including relevant metadata for each sample, is still needed to identify the globally distributed biogas community members and serve as a reliable repository.

Results

Here, 134 publicly available datasets derived from different biogas reactors were used to recover 1,635 metagenome-assembled genomes (MAGs) representing different bacterial and archaeal species. All genomes were estimated to be >50% complete and nearly half were ≥90% complete with ≤5% contamination. In most samples, specialized microbial communities were established, while only a few taxa were widespread among the different reactor systems. Metabolic reconstruction of the MAGs enabled the prediction of functional traits related to biomass degradation and methane production from waste biomass. An extensive evaluation of the replication index provided an estimation of the growth rate for microbes involved in different steps of the food chain. The recovery of many MAGs belonging to Candidate Phyla Radiation and other underexplored taxa suggests their specific involvement in the anaerobic degradation of organic matter.

Conclusions

The outcome of this study highlights a high flexibility of the biogas microbiome. The dynamic composition and adaptability to the environmental conditions, including temperatures and a wide range of substrates, were demonstrated. Our findings enhance the mechanistic understanding of anaerobic digestion microbiome and substantially extend the existing repository of genomes. The established database represents a relevant resource for future studies related to this engineered ecosystem.
PEGylated surfaces for the study of DNA-protein interactions by atomic force microscopy
Authors: Akpinar Bernice , Bell Nicholas A. W. , Pyne Alice L.B. , Hoogenboom Bart W.
Published: June 2019

DNA-protein interactions are vital to cellular function, with key roles in the regulation of gene expression and genome maintenance. Atomic force microscopy (AFM) offers the ability to visualize DNA-protein interactions at nanometre resolution in near-physiological buffers, but it requires that the DNA be adhered to the surface of a solid substrate. This presents a problem when working at biologically relevant protein concentrations, where protein may be present at large excess in solution; much of the biophysically relevant information can therefore be occluded by non-specific protein binding to the underlying substrate. Here we explore the use of PLLx-b-PEGyblock copolymers to achieve selective adsorption of DNA on a mica surface. Through varying both the number of lysine and ethylene glycol residues in the block copolymers, we show selective adsorption of DNA on mica that is functionalized with a PLL10-b-PEG113/ PLL1000-2000mixture as viewed by AFM imaging in a solution containing high concentrations of streptavidin. We show that this selective adsorption extends to DNA-protein complexes, through the use of biotinylated DNA and streptavidin, and demonstrate that DNA-bound streptavidin can be unambiguously distinguished by in-liquid AFM in spite of an excess of unbound streptavidin in solution.
The full-length transcriptome of Spartina alterniflora reveals the complexity of high salt tolerance in monocotyledonous halophyte
Authors: Ye Wenbin , Wang Taotao , Wei Wei , Lou Shuaitong , Lan Faxiu , Zhu Sheng , Li Qinzhen , Ji Guoli , Lin Chentao , Wu Xiaohui , Ma Liuyin
Published: June 2019

Spartina alterniflora (Spartina) is the only halophyte in the salt marsh. However, the molecular basis of its high salt tolerance remains elusive. In this study, we used PacBio full-length single molecule long-read sequencing and RNA-seq to elucidate the transcriptome dynamics of high salt tolerance in Spartina by salt-gradient experiments (0, 350, 500 and 800 mM NaCl). We systematically analyzed the gene expression diversity and deciphered possible roles of ion transporters, protein kinases and photosynthesis in salt tolerance. Moreover, the co-expression network analysis revealed several hub genes in salt stress regulatory networks, including protein kinases such as SaOST1, SaCIPK10 and three SaLRRs. Furthermore, high salt stress affected the gene expression of photosynthesis through down-regulation at the transcription level and alternative splicing at the post-transcriptional level. In addition, overexpression of two Spartina salt-tolerant genes SaHSP70-I and SaAF2 in Arabidopsis significantly promoted the salt tolerance of transgenic lines. Finally, we built the SAPacBio website for visualizing the full-length transcriptome sequences, transcription factors, ncRNAs, salt-tolerant genes, and alternative splicing events in Spartina. Overall, this study sheds light on the high salt tolerance mechanisms of monocotyledonous-halophyte and demonstrates the potential of Spartina genes for engineering salt-tolerant plants.
Organotypic slice culture model demonstrates interneuronal spreading of alpha-synuclein aggregates
Authors: Elfarrash Sara , Jensen Nanna Møller , Ferreira Nelson , Betzer Cristine , Thevathasan Jervis Vermal , Diekmann Robin , Adel Mohamed , Omar Nisreen Mansour , Boraie Mohamed Z. , Gad Sabry , Ries Jonas , Kirik Deniz , Nabavi Sadegh , Jensen Poul Henning
Published: June 2019

Here we describe the use of an organotypic hippocampal slice model for studying α-synuclein aggregation and inter-neuronal spreading initiated by injection of preformed α-synuclein filaments (PFFs). PFF injection at dentate gyrus templates the endogenous α-synuclein to form aggregates in axons and cell bodies that spread to CA3 and CA1 regions. Aggregates were insoluble and phosphorylated at serine 129, recapitulating Lewy pathology features found in Parkinson’s disease and other synucleinopathies. The spreading of the aggregates were favoring the anterograde direction in the slice model. The model allowed development of slices expressing only serine-129 phosphorylation-deficient human α-synuclein (S129G) using adeno-associated viral (AAV) vector in α-synuclein knockout slices. Processes of aggregation and spreading of α-synuclein were thereby shown to be independent of phosphorylation at serine 129. We provide methods and highlight crucial steps for PFF microinjection and characterization of aggregate formation and spreading. Slices derived from genetically engineered mice or manipulated by using viral vectors allow testing of hypotheses on mechanisms involved in formation of α-synuclein aggregates and their prion-like spreading.
Extreme tolerance of Paramecium to acute injury induced by γ rays
Authors: Wang Ye , Duan Xiaopeng , Hu Yiping
Published: June 2019

Due to the wide use of nuclear energy, nuclear radiation threat is increasing day by day. However, methods for protection against nuclear radiation are limited and not effective. Therefore, it is necessary to develop an effective method for protection and therapy against injury caused by radiation. According to the law of biological evolution, one of the most primitive eukaryotes, Paramecium, could be tolerant to ionizing radiations, in a way similar to or better than Ramazzottius varieornatus and Bdelloids rotifer. Therefore, in the present study, the anti-radiation effects of Paramecium were explored, which could be applicable to human beings. Paramecium was found to be tolerant to 60Co γ rays, and its half lethal dose (LD50) was approximately 3000 Gy, which is 60 times more than that of human beings. The GSPATT00021409001 and GSPATT00016349001 genes were significantly up-regulated, which might play a role in DNA binding and nuclear transport, and thus, could function in DNA protection or repair. The biological function of the two genes and their effects in humans need to be explored in future studies.
Connecting gene regulatory relationships to neurobiological mechanisms of brain disorders
Authors: Sey Nancy Y. A , Fauni Harper , Ma Won , Won Hyejung
Published: June 2019

Despite being clinically distinguishable, many neuropsychiatric disorders display a remarked level of genetic correlation and overlapping symptoms. Deciphering neurobiological mechanisms underlying potential shared genetic etiology is challenging because (1) most common risk variants reside in the non-coding region of the genome, and (2) a genome-wide framework is required to compare genome-wide association studies (GWAS) having different power. To address these challenges, we developed a platform, Hi-C coupled MAGMA (H-MAGMA), that converts SNP-level summary statistics into gene-level association statistics by assigning non-coding SNPs to their cognate genes based on chromatin interactions. We applied H-MAGMA to five psychiatric disorders and four neurodegenerative disorders to interrogate biological pathways, developmental windows, and cell types implicated for each disorder. We found that neuropsychiatric disorder-associated genes coalesce at the level of developmental windows (mid-gestation) and cell-type specificity (excitatory neurons). On the contrary, neurodegenerative disorder-associated genes show more diverse cell type specific, and increasing expression over time, consistent with the age-associated elevated risk of developing neurodegenerative disorders. Genes associated with Alzheimer’s disease were not only highly expressed in microglia, but also subject to microglia and oligodendrocyte-specific dysregulation, highlighting the importance of understanding the cellular context in which risk variants exert their effects. We also obtained a set of pleiotropic genes that are shared across multiple psychiatric disorders and may form the basis for common neurobiological susceptibility. Pleiotropic genes are associated with neural activity and gene regulation, with selective expression in corticothalamic projection neurons. These results show how H-MAGMA adds to existing frameworks to help identify the neurobiological basis of shared and distinct genetic architecture of brain disorders.
Topographic specificity of alpha power during auditory spatial attention
Authors: Deng Yuqi , Choi Inyong , Shinn-Cunningham Barbara
Published: June 2019

Visual and somatosensory spatial attention both induce parietal alpha (7-14 Hz) oscillations whose topographical distribution depends on the direction of spatial attentional focus. In the auditory domain, contrasts of parietal alpha power for leftward and rightward attention reveal a qualitatively similar lateralization; however, it is not clear whether alpha lateralization changes monotonically with the direction of auditory attention as it does for visual spatial attention. In addition, most previous studies of alpha oscillation did not consider subject-specific differences in alpha frequency, but simply analyzed power in a fixed spectral band. Here, we recorded electroencephalography in human subjects when they directed attention to one of five azimuthal locations. After a cue indicating the direction of an upcoming target sequence of spoken syllables (yet before the target began), alpha power changed in a task specific manner. Subject-specific peak alpha frequencies differed consistently between frontocentral electrodes and parieto-occipital electrodes, suggesting multiple neural generators of task-related alpha. Parieto-occipital alpha increased over the hemisphere ipsilateral to attentional focus compared to the contralateral hemisphere, and changed systematically as the direction of attention shifted from far left to far right. These results showing that parietal alpha lateralization changes smoothly with the direction of auditory attention as in visual spatial attention provide further support to the growing evidence that the frontoparietal attention network is supramodal.
Exploring the role of the various methionine residues in the Escherichia coli CusB adapter protein
Authors: Meir Aviv , Walke Gulshan , Schwerdtfeger Fabian , Gevorkyan-Airapetov Lada , Ruthstein Sharon
Published: June 2019

The dissemination of resistant pathogenic microbes has become one of the most challenging problems that modern medicine has faced. Developing novel drugs based on new molecular targets that previously were not targeted, is therefore the highest priority in antibiotics research. One approach that has been recently suggested is to inhibit copper transporters in prokaryotic systems. Copper is required for many biological pathways, but sometimes it can harm the cell. Pathogenic systems have a highly sophisticated copper-regulation network; therefore, a better understanding of how this network operates at the molecular level should assist in developing the next generation of antibiotics. The CusB protein is part of the CusCBA periplasmic Cu(I) efflux system in Gram-negative bacteria, and it was recently reported to play a key role in the functioning of the whole CusCBA system, in which conformational changes as well as the assembly/disassembly process control the opening of the transporter. More knowledge of the underlying mechanism is needed to attain a full understanding of CusB functioning, which is associated with targeting specific and crucial residues in CusB. Here, we combine in-vitro structural measurements, which used EPR spectroscopy and UV-Vis measurements, with cell experiments to explore the role of the various methionine residues in CusB. We targeted two methionine residues (M227 and M241) that are essential for the proper function of CusB.
Degradation of miR-466d-3p by JEV NS3 facilitates viral replication and IL-1β expression
Authors: Jiang Hui , Zhao Caiquan , Bai Zhuofang , Meng Yanqing , Qin Tian , Wang Xiao , Wang Guojun , Cui Min , Ye Jing , Cao Shengbo , Li Guangpeng , Yang Yang
Published: June 2019

Previous studies revealed that Japanese encephalitis virus (JEV) infection alters the expression of miRNA in central nervous system (CNS). However, the mechanism of JEV infection contributes to the regulation of miRNAs in CNS remain obscure. Here, we found that a global degradation of mature miRNA in mouse brain and neuroblastoma cells after JEV infection. In additional, the integrative analysis of miRNAs and mRNAs suggests that those down-regulated miRNAs are primarily targeted inflammation genes and the miR-466d-3p target the IL-1β which in the middle of those inflammation genes. Transfection of miR-466d-3p decreased the IL-1β expression and inhibited the JEV replication in NA cells. Interestingly, the miR-466d-3p level increased after JEV infection in the presence of cycloheximide, which indicated that viral protein expression reduces miR-466d-3p. Therefore, we generated all the JEV coding protein and demonstrated that NS3 is a potent miRNA suppressor. Furthermore, the NS3 of ZIKA virus, WNV, DENV1 and DENV2 also decreased the expression of miR-466d-3p. The in vitro unwinding assay demonstrated that the NS3 could unwind the pre-miR-466d and induce the disfunction of miRNA. Using computational models and RNA immunoprecipitation assay, we found that arginine-rich domains of NS3 are critical for pre-miRNA binding and the degradation of host miRNAs. Importantly, site-directed mutagenesis of conserved residues revealed that R226G and R202W significantly reduced the binding affinity and degradation of pre-miR-466d. Together, these results extend the helicase of Flavivirus function beyond unwinding duplex RNA to the decay of pre-miRNAs, which provides a new mechanism of NS3 in regulating miRNA pathways and promoting the neuroinflammation.

Author Summary

Host miRNAs had been reported to regulate JEV induced inflammation in central nervous system. We found that the NS3 of JEV can reduce most of host miRNA expression. The helicase region of the NS3 specifically binds to precursors of miRNA and lead to incorrect unwinding of precursors of miRNAs which inhibits the function of miRNAs. This observation leads to two major findings. First, we identified the miR-466d-3p targets to the host IL-1β and E protein of JEV, and NS3 degrades the miR-466d-3p to promote the brain inflammation and viral replication. Second, we proved that the arginine on the helicase of NS3 is the main miRNA binding sites, and the miRNA degradation by NS3 was abolished when the R226 and R202 were mutated on the NS3. These findings were also confirmed with NS3 of ZIKA virus, WNV and DENV which could decrease the expression level of miR-466d-3p to enhance the inflammation. Our study provides new insights into the molecular mechanism of encephalitis caused by JEV, and reveals several amino acid sites to further attenuate the JEV vaccine.