bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated blood pressure in childhood and hypertension risk in adulthood: a systematic review and meta-analysis
Authors: Yang Lili , Sun Jiahong , Zhao Min , Liang Yajun , Bovet Pascal , Xi Bo
Published: July 2020

Objective:

Several longitudinal studies have investigated the association between elevated blood pressure (BP) in childhood and hypertension in adulthood but the strength of the association has not been always consistent. This study aimed at quantitatively assessing the strength of the association between elevated BP in childhood and hypertension in adulthood based on both a meta-analysis and a systematic review.

Methods:

We identified eligible studies using PubMed and Embase databases up to 1 November, 2019 and by manually searching the reference lists of all identified studies. All longitudinal studies on the association between elevated BP in childhood and hypertension in adulthood were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model in this meta-analysis.

Results:

Eleven articles (N = 39 714) were included in our meta-analysis and five additional articles were used for systematic review (two providing ORs without 95% CIs, one not using standard cut-offs for elevated BP in childhood, and two not using standard criteria for adult hypertension). Elevated BP in childhood (3--18 years in the included studies) was significantly associated with hypertension in adulthood (18--57 years in the included studies), with a summary OR of 2.02 (95% CI 1.62--2.53). We also found that an increase of 1 standard deviation in systolic BP and diastolic BP, respectively, in childhood (3--19 years in the included studies) was associated with hypertension in adulthood (21--49 years in the included studies), with summary ORs of 1.71 (1.50–1.95) and 1.57 (1.37–1.81). Our systematic review of the five additional articles not eligible for meta-analysis also suggested a significant association between elevated BP in childhood and hypertension in adulthood.

Conclusion:

This meta-analysis and systematic review demonstrated a significant association between elevated BP in childhood and hypertension in adulthood. The findings support measures to promote healthy BP during childhood to reduce the risk of hypertension later in life.
Cataract surgery of eyes with previous vitrectomy: risks and benefits as reflected in the European Registry of Quality Outcomes for Cataract and Refractive Surgery
Authors: Lundström Mats , Dickman Mor , Henry Ype , Manning Sonia , Rosen Paul , Tassignon Marie-José , Young David , Stenevi Ulf
Published: July 2020

Purpose:

To explore the frequency and outcomes of cataract surgery in eyes with previous vitrectomy.

Setting:

Fifteen European countries.

Design:

Retrospective cross-sectional register-based study.

Methods:

The European Registry of Quality Outcomes of Cataract and Refractive Surgery (EUREQUO) contains data on baseline characteristics, surgery, and follow-up for cataract surgeries. Previous vitrectomy is included as a mandatory parameter in baseline characteristics. According to the protocol for EUREQUO, consecutive cases should be reported by participating units.

Results:

This study included data from units in 15 European countries from 2008 to 2018; 1 715 348 cataract extractions with follow-up data were reported to EUREQUO. Previous vitrectomy was reported in 19 416 eyes comprising 1.1% of all cases. This proportion was about the same for each study year. Most patients were men, and their mean age was 64.1 years compared with 73.7 years for the rest of the database. The preoperative visual acuity was modestly worse in postvitrectomy eyes compared with the opposite (corrected distance visual acuity [CDVA] 0.45 vs 0.25, respectively). A postoperative CDVA of 0.5 or better was achieved by 82.8% of the postvitrectomy eyes compared with 95.6% for the non-postvitrectomy eyes. The absolute mean biometry prediction error for the same groups was 0.52 diopters (D) vs 0.43 D, respectively.

Conclusions:

Patients undergoing cataract extraction after previous vitrectomy were younger and mostly men. Their visual and refractive outcomes were slightly inferior compared with the patients without vitrectomy.
Multiple locus variable number tandem repeat analysis of Acinetobacter baumannii strains isolated from human clinical and animal meat samples
Authors: Karimi Sepideh , Momtaz Hassan , Fazel Nazanin
Published: July 2020

The current research was done to study the prevalence rate and molecular typing of Acinetobacter baumannii strains isolated from human and animal samples. One-hundred and seventy-four animal meat and 128 human clinical samples were collected and subjected to bacterial culture. A. baumannii isolates were confirmed using the Loop-mediated isothermal amplification. Approved strains were subjected to molecular typing using the multiple-locus variable number tandem repeat analysis method. Forty-four out of 174 (25.28%) raw meat and 64 out of 128 (50%) human samples were positive for A. baumannii strains. Ovine meat (39.28%) and urine (56.06%) samples had the highest prevalence of A. baumannii strains. Eighteen human isolates were located in eight separate profiles, whereas 18 animal isolates were located in six separate profiles. The highest similarities were found between human-based A. baumannii isolates nos 6, 7 and 18 with isolates nos 5, 11, 13 and 15 (85.6% similarity). The highest similarities were found between animal-based A. baumannii isolates nos 10, 11 and 17 (99.8% similarity). From a total of 10 studied variable copy numbers of tandem repeats (VNTR) loci, 0845, 0826 and 3406 were detected in all animal-based A. baumannii isolates. Moreover, 3406 VNTR loci was only detected in all 18 human-based A. baumannii isolates. A. baumannii isolate no 17 (harbored all 10 VNTR loci) and A. baumannii isolates nos 6, 7 and 18 (harbored 9 VNTR loci) were the most pathogenic human and animal-based strains. Multiple-locus variable number tandem repeat analysis was considered as an accurate and practical method for molecular typing of A. baumannii strains.
Perceived Stress, Sexually Transmitted Infection, and Pelvic Inflammatory Disease: Examination of Differences in Associations Among Black and White Women
Authors: Scheidell Joy D. , Thorpe Lorna E. , Adimora Adaora A. , Caniglia Ellen C. , Lejuez Carl W. , Troxel Andrea B. , Khan Maria R.
Published: July 2020

Introduction

Perceived stress is linked to poor sexual and reproductive health, but its relationship with sexually transmitted infections (STIs) is less clear. The elevated burden of stress and STI among Black women suggests a need to examine racial differences in the associations on additive and multiplicative scales.

Methods

Using data from Black and White female participants from wave IV of the National Longitudinal Study of Adolescent to Adult Health (n = 4744), we examined the association of high stress (scores ≥6 on the Perceived Stress Scale-4) with self-reported past-year chlamydia diagnosis, combined curable STI, and lifetime pelvic inflammatory disease using modified Poisson regression with robust variance to estimate prevalence ratios and prevalence differences. Models included a race-stress product-interaction term and adjusted for sociodemographic variables, prior trauma and stressors, and mental health factors.

Results

In unadjusted analyses, stress was associated with STI among Black and White women. Adjusted associations were attenuated among White women; among Black women, stress remained associated with chlamydia (adjusted prevalence ratio, 2.22; 95% confidence interval, 1.30–3.79) and curable STI (adjusted prevalence ratio, 1.59; 95% confidence interval, 1.05–2.40), corresponding to approximately 5 excess cases of each. Among White women, poverty and personality traits were the strongest confounders; among Black women, poverty, trauma, and neurotic personality traits were the strongest confounders for chlamydia, although no factors seemed to confound the association with curable STI.

Conclusions

Stress is independently linked to STI, particularly among Black women. Additional research with longitudinal data is needed to understand the role of stress on STI and address a significant health disparity.
Sexual Health Knowledge, Attitudes, and Perceptions Among Men Who Have Sex With Men During Co-Occurring Sexually Transmitted Infection Epidemics in Toronto, Canada: A Qualitative Study
Authors: Gesink Dionne , Salway Travis , Kimura Lauren , Connell James
Published: July 2020

Background

Our objective was to explore the sexual health knowledge, attitudes, and perceptions of men who have sex with men (MSM).

Methods

In-depth interviews were conducted with 31 MSM who lived, worked, or socialized in Toronto in June and July 2016. Participants were asked about concepts of risky sex and knowledge of, and attitudes toward, sexually transmitted infections (STIs), especially syphilis, and potential interventions. Thematic analysis was used to analyze interview transcripts.

Results

The prevention of STI relied on HIV prevention strategies. No one used condoms for oral sex, nor did they intend to. Pre-exposure prophylaxis was perceived as both threatening and liberating. Concepts of risky sex included emotional risk. Conversations with partners about STI testing were easier than STI status. Stigma and concealment of sexual identity were barriers to sexual health care. None of the participants recommended sexual behavior or sexual health interventions. Instead, recommendations centered on social changes to reduce or eliminate shame, embarrassment, stigma, and discrimination around both STIs and sexual orientation.

Conclusion

Participants were thinking about sexual risk and using a variety of ways to prevent STI transmission, although most relied on HIV prevention strategies, possibly because they knew little about other STIs, and other STIs were perceived as curable, especially syphilis. Interventions promoting conversations about STI testing may be promising and will also reduce stigma as STI testing is normalized. Social and clinic interventions focused on creating psychologically safe spaces to disclose sexual identity and providing sexual orientation affirming health care may reduce STIs and improve sexual health for MSM.
Differences in Cytotoxicity of Lidocaine, Ropivacaine, and Bupivacaine on the Viability and Metabolic Activity of Human Adipose-Derived Mesenchymal Stem Cells
Authors: Kubrova Eva , Su Min , Galeano-Garces Catalina , Galvan M. Lizeth , Jerez Sofia , Dietz Allan B. , Smith Jay , Qu Wenchun , van Wijnen Andre J.
Published: July 2020

Purpose

We evaluated biological effects of distinct local anesthetics on human adipose-derived mesenchymal stem cells when applied to reduce periprocedural pain during mesenchymal stem cell injections.

Methods and Materials

Metabolic activity (MTS assay), viability (Live/Dead stain), and gene expression (quantitative real-time reverse-transcriptase polymerase chain reaction) were measured in mesenchymal stem cells incubated with various concentrations of lidocaine, ropivacaine, or bupivacaine during a 12-hr time course.

Results

Cell viability and metabolic activity decreased in a dose, time, and substance-specific manner after exposure to lidocaine, ropivacaine, and bupivacaine, with ropivacaine being the least cytotoxic. Cell viability decreases after brief exposure (<1.5 hrs) at clinically relevant concentrations (eg, 8 mg/ml of lidocaine, 2.5 mg/ml of ropivacaine or bupivacaine). Mesenchymal stem cells exposed to local anesthetics change their expression of mRNA biomarkers for stress response (EGR1, EGR2), proliferation (MKI67, HIST2H4A), ECM (COL1A1, COL3A1), and cell surface marker (CD105).

Conclusions

Local anesthetics are cytotoxic to clinical-grade human mesenchymal stem cells in a dose-, time-, and agent-dependent manner and change expression of ECM, proliferation, and cell surface markers. Lidocaine and bupivacaine are more cytotoxic than ropivacaine. Single-dose injections of local anesthetics may affect the biological properties of mesenchymal stem cells in vitro but may not affect the effective dose of MSCs in a clinical setting.
Accelerated T2 Mapping of the Lumbar Intervertebral Disc
Authors: Raudner Marcus , Schreiner Markus , Hilbert Tom , Kober Tobias , Weber Michael , Windhager Reinhard , Trattnig Siegfried , Juras Vladimir
Published: July 2020

Objectives

T2 mapping of the intervertebral disc (IVD) can depict quantitative changes reflecting biochemical change due to loss of glycosaminoglycan content. Conventional T2 mapping is usually performed using a 2-dimensional multi-echo-spin echo sequence (2D-MESE) with long acquisition times that are generally not compatible with clinical routine. This study investigates the applicability of GRAPPATINI, a T2 mapping sequence combining undersampling, model-based reconstruction, and parallel imaging, to offer clinically feasible acquisition times in T2 mapping of the lumbar IVD.

Materials and Methods

Fifty-eight individuals (26 female; mean age, 23.3 ± 8.1 years) were prospectively studied at 3 T. GRAPPATINI was conducted with the same parameters as the 2D-MESE while shortening the acquisition time from 13:18 to 2:27 minutes. The setup was also validated in a phantom experiment using a 6.48-hour-long single echo-spin echo sequence as reference. The IVDs were manually segmented on 4 central slices.

Results

The median nucleus pulposus showed a strong Pearson correlation coefficient between T2GRAPPATINI and T2MESE (r
p = 0.919; P < 0.001). There was also a significant correlation for the ventral (r
p = 0.241; P < 0.001) and posterior (r
p = 0.418; P < 0.001) annular regions.

In the single spin-echo phantom experiment, the most accurate T2 estimation was achieved using T2GRAPPATINI with a median absolute deviation of 15.3 milliseconds as compared with T2MESE with 26.5 milliseconds.

Conclusions

GRAPPATINI facilitates precise T2 mapping at 3 T in accordance with clinical standards and reference methods using the same parameters while shortening acquisition times from 13:18 to 2:27 minutes with the same parameters.
Ulcerated Infantile Hemangioma of the Hard Palate: Diagnostic Treatment With Oral Propranolol
Authors: Ishikawa Kosuke , Fujita Munezumi , Takeda Tomohiro , Mitamura Shintaro , Nishio Takuya , Funayama Emi , Hayashi Toshihiko , Osawa Masayuki , Maeda Taku , Yamamoto Yuhei , Sasaki Satoru
Published: July 2020

Infantile hemangiomas arising in the palate are rare. The authors describe a case of ulcerated infantile hemangioma of the hard palate with feeding difficulty. To our knowledge, this is the first reported case of immunohistochemically diagnosed palatal infantile hemangioma successfully treated using oral propranolol.
Autogenous Dental Transplantation in a Patient Undergoing Class III Dento-Facial Deformity
Authors: Quirino Lilian Caldas , Carvalho Pedro Henrique de Azambuja , Rocha Audrey Foster Lefort , Gabrieli Marisa Aparecida Cabrini , Pereira-Filho Valfrido Antonio
Published: July 2020

Dental transplantation is an alternative for rehabilitation with a high success rate. This article presents a clinical case of autogenous dental transplantation in a 17-year-old male patient undergoing treatment for Class III dento-facial deformity. After 32 months followup, low-cost rehabilitation was possible, and without prejudice to ortho-surgical treatment.
Modified V-Y Myocutaneous Flap With Vascular Pedicle for the Repair of Maxillofacial Skin Defects
Authors: Lu Ruohuang , Xiao Zhiqiang , Li Zan , Guo Xincheng
Published: July 2020

Objective:

It is challenging to repair postoperative defect caused by skin tumor resection on the maxillofacial, which not only affects appearance but also impairs functions. To better repair skin defect on the maxillofacial, the application value of V-Y vascular myocutaneous flap was introduced in our study.

Methods:

Between June 2011 and December 2018, 16 patients with maxillofacial skin tumors who received extensive resection were enrolled in our study. The defect on the maxillofacial was repaired by V-Y vascular myocutaneous flap. The follow-up period lasted for 12 to 24 months.

Results:

All 16 cases of myocutaneous flaps survived with 1 case of partial venous congestion and 1 case of partial distal necrosis. No recurrence occurred during follow-up. The color and texture of myocutaneous flaps like those of the surrounding skin.

Conclusion:

Featured with better freeness, larger repair range and aesthetic effect of “kite” flaps, V-Y vascular myocutaneous flap can repair the superior border of zygomatic arch pedicled with facial artery and repair 1.5 cm above the superior border of zygomatic arch pedicled with transverse facial artery for elderly patients in Asia.
Short-Term Efficacy and Safety of Different Mechanical Hemodynamic Support Devices for Cardiogenic Shock or High-Risk Pci: a Network Meta-Analysis of Thirty-Seven Trials
Authors: Duan Jingwei , Shi Yuanchao , Luo Gongming , Peng Yu , Duan Baomin , Zhang Zheng
Published: July 2020

Background:

With more advanced mechanical hemodynamic support for patients with cardiogenic shock (CS) or high-risk percutaneous coronary intervention (HS-PCI), the morality rate is now significantly lower than before. While previous studies showed that intra-aortic balloon pumping (IABP) did not reduce the risk of mortality in patients with CS compared to conservative treatment, the efficacy in other mechanical circulatory support (MCS) trials was inconsistent.

Objective:

We conducted this network meta-analysis to assess the short-term efficacy and safety of different intervention measures for patients with CS or who underwent HS-PCI.

Methods:

Four online databases were searched. From the initial 1,550 articles, we screened 38 studies (an extra 14 studies from references) into this analysis, including a total of 11,270 patients from five interventions (pharmacotherapy, IABP, pMCS, ECMO alone, and ECMO+IABP).

Result:

The short-term efficacy was determined by 30-day or in-hospital mortality. ECMO+IABP significantly reduced mortality compared with pMCS and ECMO alone (OR = 1.85, 95% CrI [1.03–3.26]; OR = 1.89, 95% CrI [1.19–3.01], respectively). ECMO+IABP did not show reduced mortality when compared with pharmacotherapy and IABP (OR = 1.73, 95% CrI [0.97–3.82]; OR = 1.67, 95% CrI [0.98–2.89], respectively). The rank probability, however, supported that ECMO+IABP might be a more suitable intervention in improving mortality for patients with CS or who underwent HS-PCI. Regarding bleeding, compared with other invasive intervention measures, IABP showed a trend of reduced bleeding (with pMCS OR = 3.86, 95% CrI [1.53–10.66]; with ECMO alone OR = 3.74, 95% CrI [1.13–13.78]; with ECMO+IABP OR = 4.80, 95% CrI [1.61–18.53]). No difference was found in stroke, myocardial infarction, limb ischemia, and hemolysis among the invasive therapies evaluated.

Conclusion:

Following this analysis, ECMO+IABP might be a more suitable intervention measure in improving short-term mortality for patients with CS and who underwent HS-PCI. However, the result was limited by the lack of sufficient direct comparisons and evidence from randomized controlled trials. Moreover, bleeding and other device-related complications should be considered in clinical applications.
A Novel Staging System for De Novo Metastatic Breast Cancer Refines Prognostic Estimates
Authors: Plichta Jennifer K. , Thomas Samantha M. , Sergesketter Amanda R. , Greenup Rachel A. , Rosenberger Laura H. , Fayanju Oluwadamilola M. , Kimmick Gretchen , Force Jeremy , Hyslop Terry , Hwang E. Shelley
Published: July 2020

Objective:

We aim to identify prognostic groups within a de novo metastatic cohort, incorporating both anatomic and biologic factors.

Background:

Staging for breast cancer now includes anatomic and biologic factors, although the guidelines for stage IV disease do not account for how these factors may influence outcomes.

Methods:

Adults with de novo metastatic breast cancer were selected from the National Cancer DataBase (2010–2013). Recursive partitioning analysis was used to group patients with similar overall survival (OS) based on clinical T/N stage, tumor grade, ER, PR, HER2, number of metastatic sites, and presence of bone-only metastases. Categories were created by amalgamating homogeneous groups based on 3-year OS rates (stage IVA: >50%, stage IVB: 30%–50%, stage IVC: <30%).

Results:

16,187 patients were identified; median follow-up was 32 months. 65.2% had 1 site of distant metastasis, and 42.9% had bone-only metastases. Recursive partitioning analysis identified the number of metastatic sites (1 vs >1) as the first stratification point, and ER status as the second stratification point for both resulting groups. Additional divisions were made based on HER2 status, PR status, cT stage, tumor grade, and presence of bone-only metastases. After bootstrapping, significant differences in 3-year OS were noted between the 3 groups [stage IVB vs IVA: HR 1.58 (95% confidence interval 1.50–1.67), stage IVC vs IVA: HR 3.54 (95% confidence interval 3.33–3.77)].

Conclusions:

Both anatomic and biologic factors yielded reliable and reproducible prognostic estimates among patients with metastatic disease. These findings support formal stratification of de novo stage IV breast cancer into 3 distinct prognosis groups.
Predictors of retained hemothorax in trauma: Results of an Eastern Association for the Surgery of Trauma multi-institutional trial
Authors: Prakash Priya S. , Moore Sarah A. , Rezende-Neto Joao B. , Trpcic Sandy , Dunn Julie A. , Smoot Brittany , Jenkins Donald H. , Cardenas Tatiana , Mukherjee Kaushik , Farnsworth Joshua , Wild Jeffrey , Young Katelyn , Schroeppel Thomas J. , Coimbra Raul , Lee Jeanne , Skarupa David J. , Sabra Michel J. , Carrick Matthew M. , Moore Forrest O. , Ward Jeanette , Geng Thomas , Lapham David , Piccinini Alice , Inaba Kenji , Dodgion Christopher , Gooley Brian , Schwartz Tim , Shraga Sarrina , Haan James M. , Lightwine Kelly , Burris Jennifer , Agrawal Vaidehi , Seamon Mark J. , Cannon Jeremy W.
Published: July 2020

BACKGROUND

The natural history of traumatic hemothorax (HTX) remains unclear. We aimed to describe outcomes of HTX following tube thoracostomy drainage and to delineate factors that predict progression to a retained hemothorax (RH). We hypothesized that initial large-volume HTX predicts the development of an RH.

METHODS

We conducted a prospective, observational, multi-institutional study of adult trauma patients diagnosed with an HTX identified on computed tomography (CT) scan with volumes calculated at time of diagnosis. All patients were managed with tube thoracostomy drainage within 24 hours of presentation. Retained hemothorax was defined as blood-density fluid identified on follow-up CT scan or need for additional intervention after initial tube thoracostomy placement for HTX.

RESULTS

A total of 369 patients who presented with an HTX initially managed with tube thoracostomy drainage were enrolled from 17 trauma centers. Retained hemothorax was identified in 106 patients (28.7%). Patients with RH had a larger median (interquartile range) HTX volume on initial CT compared with no RH (191 [48–431] mL vs. 88 [35–245] mL, p = 0.013) and were more likely to be older with a higher burden of thoracic injury. After controlling for significant differences between groups, RH was independently associated with a larger HTX on presentation, with a 15% increase in risk of RH for each additional 100 mL of HTX on initial CT imaging (odds ratio, 1.15; 95% confidence interval, 1.08–1.21; p < 0.001). Patients with an RH also had higher rates of pneumonia and longer hospital length of stay than those with successful initial management. Retained hemothorax was also associated with worse functional outcomes at discharge and first outpatient follow-up.

CONCLUSION

Larger initial HTX volumes are independently associated with RH, and unsuccessful initial management with tube thoracostomy is associated with worse patient outcomes. Future studies should use this experience to assess a range of options for reducing the risk of unsuccessful initial management.

LEVEL OF EVIDENCE

Therapeutic/care management study, level III.
Performance characteristics of a high throughput automated transcription mediated amplification test for SARS-CoV-2 detection
Authors: Pham Jimmykim , Meyer Sarah , Nguyen Catherine , Williams Analee , Hunsicker Melissa , McHardy Ian , Gendlina Inessa , Goldstein D. Yitzchak , Fox Amy S. , Hudson Angela , Darby Paul , Hovey Paul , Morales Jose , Mitchell James , Harrington Karen , Majlessi Mehrdad , Moberly Joshua , Shah Ankur , Worlock Andrew , Walcher Marion , Eaton Barbara , Getman Damon , Clark Craig
Published: July 2020

The COVID-19 pandemic caused by the new SARS-CoV-2 coronavirus has imposed severe challenges on laboratories in their effort to achieve sufficient diagnostic testing capability for identifying infected individuals. In this study we report the analytical and clinical performance characteristics of a new, high-throughput, fully automated nucleic acid amplification test system for the detection of SARS-CoV-2. The assay utilizes target capture, transcription mediated amplification, and acridinium ester-labeled probe chemistry on the automated Panther System to directly amplify and detect two separate target sequences in the ORF1ab region of the SARS-CoV-2 RNA genome. The probit 95% limit of detection of the assay was determined to be 0.004 TCID50/ml using inactivated virus, and 25 c/ml using synthetic in vitro transcript RNA targets. Analytical sensitivity (100% detection) was confirmed to be 83 – 194 c/ml using three commercially available SARS-CoV-2 nucleic acid controls. No cross reactivity or interference was observed with testing six related human coronaviruses, as well as 24 other viral, fungal, and bacterial pathogens, at high titer. Clinical nasopharyngeal swab specimen testing (N=140) showed 100%, 98.7%, and 99.3% positive, negative, and overall agreement, respectively, with a validated reverse transcription PCR NAAT for SARS-CoV-2 RNA. These results provide validation evidence for a sensitive and specific method for pandemic-scale automated molecular diagnostic testing for SARS-CoV-2.
Synthetic promoter based azide biosensor toolkit to advance chemical-biology
Authors: Bandi Chandra Kanth , Skalenko Kyle S. , Agrawal Ayushi , Sivaneri Neelan , Thiry Margaux , Chundawat Shishir P.S.
Published: July 2020

Real-time azide or azido-functionalized molecular detection inside living cells using bioorthogonal chemistry-based approaches has been revolutionary to advancing chemical-biology. These methods have enabled diverse applications ranging from understanding the role of cellular glycosylation pathways, identifying diseased cells, and targeting delivery of azido-based therapeutic drugs. However, while classical techniques were applicable only toin-vitrodetection of such functional groups, even recent bioorthogonal based-detection methods require expensive sensing reagents and also cannot selectively identify inorganic azide. Here, we report anin-vivosynthetic promoter based azide biosensor toolkit to selectively detect azide anions. A promiscuous cyanate-specific promoter was engineered to detect azide and rapidly induce expression of green fluorescent protein (GFP) inEscherichia coli. Our synthetic azide operon allows highly-tunable GFP expression, outperforming the classiclac-operon, and also offers an alternative low-cost protein expression system. Finally, we showcase the utility of this toolkit forin-vivobioorthogonal reaction biosensing and glycoengineering based applications.
RefPlantNLR: a comprehensive collection of experimentally validated plant NLRs
Authors: Kourelis Jiorgos , Sakai Toshiyuki , Adachi Hiroaki , Kamoun Sophien
Published: July 2020

Reference datasets are critical in computational biology. They help define canonical biological features and are essential for benchmarking studies. Here, we describe a comprehensive reference dataset of experimentally validated plant NLR immune receptors. RefPlantNLR consists of 442 NLRs from 31 genera belonging to 11 orders of flowering plants. This reference dataset has several applications. We used RefPlantNLR to determine the canonical features of functionally validated plant NLRs and to benchmark the five most popular NLR annotation tools. This revealed that although NLR annotation tools tend to retrieve the majority of NLRs, they frequently produce domain architectures that are inconsistent with the RefPlantNLR annotation. Guided by this analysis, we developed a new pipeline, NLRtracker, which extracts and annotates NLRs based on the core features found in the RefPlantNLR dataset. The RefPlantNLR dataset should also prove useful for guiding comparative analyses of NLRs across the wide spectrum of plant diversity and identifying under-studied taxa. We hope that the RefPlantNLR resource will contribute to moving the field beyond a uniform view of NLR structure and function.
Several geranylgeranyl diphosphate synthase isoforms supply metabolic substrates for carotenoid biosynthesis in tomato
Authors: Barja M. Victoria , Ezquerro Miguel , Diretto Gianfranco , Florez-Sarasa Igor , Feixes Elisenda , Fiore Alessia , Karlova Rumyana , Fernie Alisdair R. , Beekwilder Jules , Rodriguez-Concepcion Manuel
Published: July 2020

Geranylgeranyl diphosphate (GGPP) produced by GGPP synthase (GGPPS) serves as a precursor for many plastidial isoprenoids, including carotenoids. Here we show that five different GGPPS isoforms exist in tomato (Solanum lycopersicum). From these, SlGGPPS1, 2 and 3 (or SlG1-3 in short) produce GGPP in plastids and exhibit similar kinetic parameters. Phytoene synthase (PSY) converts GGPP into phytoene, the first committed intermediate of the carotenoid pathway. Gene expression and co-expression network analyses showed a preferential association of individual GGPPS and PSY isoforms in processes linked to carotenoid biosynthesis such as root mycorrhization, seedling deetiolation and fruit ripening. Co-immunoprecipitation experiments showed that SlG2, but not SlG3, physically interacts with PSY proteins. By contrast, CRISPR-Cas9 mutants defective in SlG3 showed a stronger impact on carotenoid levels and derived metabolic, physiological and developmental phenotypes that those impaired in SlG2. Double mutants with a simultaneous knockout of both genes could not be found. Our work demonstrates that the bulk of GGPP production in tomato chloroplasts and chromoplasts relies on two cooperating GGPPS paralogs, unlike other plant species such asArabidopsis thaliana, rice or pepper, which produce their essential plastidial isoprenoids using a single GGPPS isoform.
Are populations of economically important bonefish and queen conch ‘open’ or ‘closed’ in the northern Caribbean Basin?
Authors: Douglas Marlis R. , Chafin Tyler K. , Claussen Julie E. , Philipp David P. , Douglas Michael E.
Published: July 2020

Demographics of co-occurring species can often be diagnosed through population genomic analyses of single nucleotide polymorphisms (SNPs). These data can define population structure, gene flow, and candidate regions in the genome that potentially reflect local adaptations. They can also gauge if populations are demographically ‘open’ or ‘closed’ (i.e., with global or local recruitment). We derived SNPs from double-digest restriction-site associated DNA (ddRAD) to test the demographics of commercially important bonefishAlbula vulpes(N=117) and queen conchLobatus gigas(N=60) from two northeast Caribbean Basin islands (Grand Bahama to the north and Eleuthera to the south). Specifically, we tested the hypothesis that the strong west-to-east current in the Great Bahama Canyon is a vicariant barrier separating the two islands. We conducted Bayesian assignment tests on putatively neutral (A. vulpes=36,206 SNPs;L. gigas=64,863) and highly-differentiated outlier datasets (A. vulpes=123 and 79 SNPs;L. gigas=88 and 51, respectively). For bonefish, results diagnosed asymmetrical gene flow and north-south differentiation, as potentially driven by adult mobility and easterly currents. However, both analyses indicated genetic structure in conch, substantiating the vicariant hypothesis. These results provide templates for future research endeavors with these impacted species. Outlier loci, for example, can potentially place populations of each within a demographic continuum, rather than within a dichotomous ‘open/closed’ framework, as well as diagnose ‘source’ and ‘sink’ populations, as herein. These methodologies can then be applied to co-distributed species with similar but less well understood ecologies so as to evaluate basin-wide trends in connectivity and local adaptation.
Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2
Authors: Nielsen Sandra C. A. , Yang Fan , Jackson Katherine J. L. , Hoh Ramona A. , Röltgen Katharina , Stevens Bryan , Lee Ji-Yeun , Rustagi Arjun , Rogers Angela J. , Powell Abigail E. , Najeeb Javaria , Otrelo-Cardoso Ana R. , Yost Kathryn E. , Daniel Bence , Chang Howard Y. , Satpathy Ansuman T. , Jardetzky Theodore S. , Kim Peter S. , Wang Taia T. , Pinsky Benjamin A. , Blish Catherine A. , Boyd Scott D.
Published: July 2020

During virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.
Astrocytic modulation of information processing by layer 5 pyramidal neurons of the mouse visual cortex
Authors: Ryczko Dimitri , Hanini-Daoud Maroua , Condamine Steven , Bréant Benjamin J. B. , Fougère Maxime , Araya Roberto , Kolta Arlette
Published: July 2020

Abstract

The most complex cerebral functions are performed by the cortex which most important output is carried out by its layer 5 pyramidal neurons. Their firing reflects integration of sensory and contextual information that they receive. There is evidence that astrocytes influence cortical neurons firing through the release of gliotransmitters such as ATP, glutamate or GABA. These effects were described at the network and at the synaptic levels, but it is still unclear how astrocytes influence neurons input-output transfer function at the cellular level. Here, we used optogenetic tools coupled with electrophysiological, imaging and anatomical approaches to test whether and how astrocytic activation affected processing and integration of distal inputs to layer 5 pyramidal neurons (L5PN). We show that optogenetic activation of astrocytes near L5PN cell body prolonged firing induced by distal inputs to L5PN and potentiated their ability to trigger spikes. The observed astrocytic effects on L5PN firing involved glutamatergic transmission to some extent but relied on release of S100β, an astrocytic Ca2+-binding protein that decreases extracellular Ca2+once released. This astrocyte-evoked decrease of extracellular Ca2+elicited firing mediated by activation of Nav1.6 channels. Our findings suggest that astrocytes contribute to the cortical fundamental computational operations by controlling the extracellular ionic environment.

KeyPointsSummary

Integration of inputs along the dendritic tree of layer 5 pyramidal neurons is an essential operation as these cells represent the most important output carrier of the cerebral cortex. However, the contribution of astrocytes, a type of glial cell to these operations is poorly documented.

Here we found that optogenetic activation of astrocytes in the vicinity of layer 5 in the mouse primary visual cortex induce spiking in local pyramidal neurons through Nav1.6 ion channels and prolongs the responses elicited in these neurons by stimulation of their distal inputs in cortical layer 1.

This effect partially involved glutamatergic signalling but relied mostly on the astrocytic calcium-binding protein S100β, which regulates the concentration of calcium in the extracellular space around neurons.

These findings show that astrocytes contribute to the fundamental computational operations of the cortex by acting on the ionic environment of neurons.
Sensitive and reproducible determination of clinical HDL proteotypes
Authors: Goetze Sandra , Frey Kathrin , Rohrer Lucia , Radosavljevic Silvija , Krützfeldt Jan , Landmesser Ulf , Bueter Marco , Pedrioli Patrick G. A. , von Eckardstein Arnold , Wollscheid Bernd
Published: July 2020

Background

High-density lipoprotein (HDL) is a heterogenous mixture of blood-circulating multimolecular particles containing many different proteins, lipids, and RNAs. Recent advancements in mass spectrometry-based proteotype analysis strategies enable the sensitive and reproducible quantification of proteins across large patient cohorts.

Methods

HDL particles were isolated from plasma of more than 300 healthy individuals or patients with a multiplicity of physiological HDL states. From these, peptides were extracted and HDL proteome spectral libraries were generated. This is a prerequisite for using data-independent acquisition (DIA) strategies to analyze HDL particles from clinical cohorts using mass spectrometry.

Results

The resulting HDL proteome spectral libraries consist of 296 protein groups and 341 peptidoforms of potential biological significance identified with high confidence. We used the HDL proteome libraries to evaluate HDL proteotype differences in between healthy individuals and patients suffering from diabetes mellitus type 2 (T2DM) and/or coronary heart disease (CHD). Bioinformatic interrogation of the data revealed significant quantitative differences in the HDL proteotypes including a significant depletion of phosphatidylinositol-glycan-specific phospholipase D (PHLD) from disease-derived HDL particles.

Conclusion

The DIA-based HDL proteotyping strategy enabled sensitive and reproducible digitization of HDL proteotypes derived from patient cohorts and provides new insights into the composition of HDL particles as a rational basis to decode structure-function-disease relationships of HDL.

List of human genes and protein names discussed in the paper

- APOA1 (Apolipoprotein A-I)

- APOA2 (Apolipoprotein A-II)

- APOE (Apolipoprotein E)

- APOC3 (Apolipoprotein C3)

- CLUS (Clusterin)

- PHLD (Phosphatidylinositol-glycan-specific phospholipase D)

- PON1 (Serum paraoxonase/arylesterase 1)

- PON3 (Serum paraoxonase/lactonase 3)

- PSPB (Pulmonary surfactant-associated protein B)

- RAB1B (Ras-related protein Rab-1B)

- RAB6A (Ras-related protein Rab-6A)

- RB11A/B (Ras-related protein Rab-11A/B)

- RP1BL (Ras-related protein Rap-1b-like protein)

- RAB10 (Ras-related protein Rab-10)

- SAA1 (Serum amyloid A-1 protein)

- SAA2 (Serum amyloid A-2 protein)

- SAA4 (Serum amyloid A-4 protein)

- SCRB1 (Scavenger receptor class B member 1)
Activation of STING due to COPI-deficiency
Authors: Steiner Annemarie , Schaale Katja Hrovat , Prigione Ignazia , De Nardo Dominic , Dagley Laura F. , Yu Chien-Hsiung , Laohamonthonkul Pawat , Harapas Cassandra R. , Gantier Michael P. , Gattorno Marco , Volpi Stefano , Davidson Sophia , Masters Seth L.
Published: July 2020

COPA syndrome is caused by loss-of-function mutations in the COP-α subunit of coatomer protein complex I (COPI), which participates in retrograde vesicular trafficking of proteins from the Golgi to the endoplasmic reticulum (ER). Disease manifests early in life with arthritis, lung pathology, kidney dysfunction and systemic inflammation associated with NF-κB activation and type I interferon (IFNαβ) production. Here, we generatedin vitromodels for COPA syndrome and interrogated inflammatory signalling pathways via a range of biochemical and molecular biological techniques. Results were confirmed with cell lines in which mutant COPA was overexpressed and with COPA syndrome patient PBMCs. We identified Stimulator of Interferon Genes (STING), as a driver of inflammation in COPA syndrome. Furthermore, we found that genetic deletion of COPG1, another COPI subunit protein, induced NF-κB and type I IFN pathways similar to COPA-deficiency. Finally, we demonstrate thatin vitro, inflammation due to COPA syndrome mutations was ameliorated by treatment with the small molecule STING inhibitor H-151. Therefore, inflammation induced by deletion of COPI subunits in general suggests a link between retrograde trafficking and STING regulation, and this innate immune sensor represents a novel therapeutic target in COPA syndrome.
Exceptional aggregation propensity of amino acids in polyglutamine amino-acid-homopolymer
Authors: Mishra Rahul , Thakur Ashwani K.
Published: July 2020

Similar aggregation and β-sheet propensity of amino acids in globular proteins and amyloids, suggests comparable principles of their formation. Here we show that during the process of aggregation into amyloid-like fibers, these rules are not the same in an amino-acid-homopolymer (AAHP) polyglutamine (PolyGln). An aggregation kinetic analysis on nine-point mutants of a forty-six long PolyGln peptide was carried in physiological conditions. At the dynamic equilibrium state of aggregation, critical-concentration derived free-energy differences, signifying aggregation propensity of incorporated amino acids were obtained. None of the obtained propensities correlated with existing conventional aggregation and β-sheet propensities of the amino acids in proteins and amyloids. Further, the differential aggregation behavior of all the peptides only correlated with van der Waals volume of the incorporated amino acid and not with any other physicochemical characteristic of amino acids. The new rules obtained from PolyGln AAHP provide an opportunity to explore physiological relevance of a mutation within AAHP in human proteome. Additionally, this study opens up new avenues for protein model design exploring folding and aggregation behavior of other amino-acid-homopolymer (AAHP) existing in the human proteome.

Significance

Mutational analysis within PolyGln sequences adds to the knowledge of unique aggregation propensities of amino acids within PolyGln AAHP. This study highlights the importance of van der Waals volume in dictating stability-instability of an aggregation fold and in turn aggregation kinetics and thermodynamic stability of aggregates. The analysis signifies the role of Gln-Gln interlocking system within PolyGln folding motif and extent of disruption caused by van der Waals volume of an amino acid. The results can be taken as a starting point to evaluate the possible impact of amino acid insertions in PolyGln stretches of other proteins. It also opens opportunities to study the structural and functional relationship of other AAHPS for their unique folding and aggregation behavior. Learning outcome can be utilized as a bottom–up approach to design amyloid biomaterial with different strengths for biomedical applications.
Thalamic inputs determine functionally distinct gamma bands in mouse primary visual cortex
Authors: Meneghetti Nicolò , Cerri Chiara , Tantillo Elena , Vannini Eleonora , Caleo Matteo , Mazzoni Alberto
Published: July 2020

Gamma band is known to be involved in the encoding of visual features in the primary visual cortex (V1). Recent results in rodents V1 highlighted the presence, within a broad gamma band (BB) increasing with contrast, of a narrow gamma band (NB) peaking at ∼60 Hz suppressed by contrast and enhanced by luminance. However, the processing of visual information by the two channels still lacks a proper characterization. Here, by combining experimental analysis and modeling, we prove that the two bands are sensitive to specific thalamic inputs associated with complementary contrast ranges. We recorded local field potentials from V1 of awake mice during the presentation of gratings and observed that NB power progressively decreased from low to intermediate levels of contrast. Conversely, BB power was insensitive to low levels of contrast but it progressively increased going from intermediate to high levels of contrast. Moreover, BB response was stronger immediately after contrast reversal, while the opposite held for NB. All the aforementioned dynamics were accurately reproduced by a recurrent excitatory-inhibitory leaky integrate-and-fire network, mimicking layer IV of mouse V1, provided that the sustained and periodic component of the thalamic input were modulated over complementary contrast ranges. These results shed new light on the origin and function of the two V1 gamma bands. In addition, here we propose a simple and effective model of response to visual contrast that might help in reconstructing network dysfunction underlying pathological alterations of visual information processing.

Significance Statement

Gamma band is a ubiquitous hallmark of cortical processing of sensory stimuli. Experimental evidence shows that in the mouse visual cortex two types of gamma activity are differentially modulated by contrast: a narrow band (NB), that seems to be rodent specific, and a standard broad band (BB), observed also in other animal models.

We found that narrow band correlates and broad band anticorrelates with visual contrast in two complementary contrast ranges (low and high respectively). Moreover, BB displayed an earlier response than NB. A thalamocortical spiking neuron network model reproduced the aforementioned results, suggesting they might be due to the presence of two complementary but distinct components of the thalamic input into visual cortical circuitry.
Pili allow dominant marine cyanobacteria to avoid sinking and evade predation
Authors: del Mar Aguilo-Ferretjans Maria , Bosch Rafael , Puxty Richard J. , Latva Mira , Zadjelovic Vinko , Chhun Audam , Sousoni Despoina , Polin Marco , Scanlan David J. , Christie-Oleza Joseph A.
Published: July 2020

How oligotrophic marine cyanobacteria position themselves in the water column is currently unknown. The current paradigm is that these organisms avoid sinking due to their reduced size and passive drift within currents. Here, we show that one in four picocyanobacteria encode a type IV pilus which allows these organisms to increase drag and remain suspended at optimal positions in the water column, as well as evade predation by grazers. The evolution of this sophisticated floatation mechanism in these purely planktonic streamlined microorganisms has profound implications for our current understanding of microbial distribution in the oceans, predator-prey interactions and, ultimately, will influence future models of carbon flux dynamics in the oceans.