bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of short-term complications of transcatheter aortic valve replacement on longer-term outcomes: results from the STS/ACC Transcatheter Valve Therapy Registry
Authors: Arnold Suzanne V , Manandhar Pratik , Vemulapalli Sreekanth , Kosinski Andrzej , Desai Nimesh D , Bavaria Joseph E , Carroll John D , Mack Michael J , Thourani Vinod H , Cohen David J
Published: January 2020

Aims

While complications of transcatheter aortic valve replacement (TAVR) have decreased, they still occur commonly and may negatively impact both short- and long-term outcomes. We sought to examine the association of complications after TAVR with survival and health status in a real-world cohort.

Methods and results

Among 45 884 TAVR patients from 513 US sites who survived 30 days, 21.4% had at least one major complication [stroke, bleed, vascular complication, new pacemaker, acute kidney injury (AKI), and moderate/severe paravalvular leak (PVL)]. In multivariable models, Stage 3 AKI [hazard ratio (HR) 3.43, 95% confidence interval (CI) 2.64–4.45], stroke (HR 2.62, 95% CI 2.06–3.32), and bleeding (HR 1.83, 95% CI 1.55–2.16) were independently associated with significantly increased risk of early death (<3 months) with slight attenuation in these hazards between 3 and 12 months. Moderate/severe PVL (HR 1.37, 95% CI 1.21–1.55) and new pacemaker (HR 1.15, 95% CI 1.05–1.25) were associated with more modest risk of excess mortality that was consistent through 12 months. Among surviving patients, stroke (−6.1 points, 95% CI −8.4 to −3.7), moderate/severe PVL (−3.2 points, 95% CI −4.9 to −1.6), and new pacemaker (−2.3 points, 95% CI −3.2 to −1.5) were associated with less improvement in 1-year health status, as assessed by the Kansas City Cardiomyopathy Questionnaire.

Conclusion

In this study of contemporary TAVR, we found that complications remain common within the first 30 days after TAVR and are associated with worse 1-year survival and health status among survivors. These findings support continued efforts to reduce major complications of TAVR and may also help define quality of care.
The 2018 AACC/SYCL PhD Clinical Chemist Compensation Survey
Authors: Bunch Dustin R , El-Khoury Joe M , Colby Jennifer , Colon-Franco Jessica , Hackenmueller Sarah A , Olson Kalen N , Cotten Steven W , Kampfrath Thomas , Chittiprol Seetharamaiah , Suh-Lailam Brenda , French Deborah , Isbell T Scott , Nerenz Robert D , Parnas M Laura , Tolan Nicole V
Published: January 2020

Background

Doctoral level board-certified clinical chemists play an invaluable role in many facets of laboratory medicine and healthcare. However, information concerning their total compensation is sparse.

Content

A confidential self-reported compensation survey was conducted by the American Association for Clinical Chemistry’s Society for Young Clinical Laboratorians (AACC SYCL) Core Committee from April 1 to April 17, 2018. Respondents provided information on geographic location, employment sector, gender, and years of experience to account for the influence of these variables on compensation. There were 199 respondents in total from the United States and Canada, however, only respondents employed in the United States with an earned doctoral degree and certification by the American Board of Clinical Chemistry (n = 133), were included in the full analysis. In comparison to compensation reported in AACC SYCL salary surveys conducted in 2010 and 2013, early career median salaries are trending upwards after correction for inflation.

This survey is the first to collect the gender of respondents, and identify a pay gap for some geographic groups. However, this gap could be due in part to a difference in the years of experience, since males were highly represented in the group with >20 years of experience (25 out of 35, 71%). Future studies on compensation trends within clinical chemistry that do not rely on self-report are needed to ensure accuracy and completeness of the dataset.
Heritability and genetic correlations of feed intake, body weight gain, residual gain, and residual feed intake of beef cattle as heifers and cows
Authors: Freetly Harvey C , Kuehn Larry A , Thallman Richard M , Snelling Warren M
Published: January 2020

The cow herd consumes approximately 70% of the annual feed resources. To date, most genetic evaluations of feed intake in beef cattle have been made in growing animals and little information is available for mature cows. Genetic evaluations in mature cows have predominately been confined to lactating dairy cows and the relationship between feed intake as growing heifers and mature cows has not been addressed. It was the purpose of this study to estimate the heritability of feed intake when measured as growing heifers and mature cows and determine the genetic correlation between these measurements. Individual feed intake and BW gain were measured on 687 heifers and 622 5-yr-old cows. The heritability of average daily DMI (ADDMI) estimated in heifers was 0.84 ± 0.12 and 0.53 ± 0.12 in cows. The heritability of ADG estimated in heifers was 0.53 ± 0.12 and 0.34 ± 0.11 in cows. The genetic correlation between heifer and cow ADDMI was 0.84 ± 0.09. The genetic correlation between heifer and cow ADG was 0.73 ± 019. Heritability of residual feed intake in heifers was 0.25 ± 0.11 and 0.16 ± 0.10 in cows. Heritability for residual gain in heifers was 0.21 ± 0.11 and 0.14 ± 0.10 in cows. Feed intake and ADG are heritable and genetically correlated between heifers and cows. Selection for decreased feed intake and ADG in growing animals will probably have the same directional effects on mature cows.
Redescription of Americlus rankini (Woodward, 1868) (Pancrustacea: Cyclida: Americlidae) and interpretation of its systematic placement, morphology, and paleoecology
Authors: Clark Neil D L , Feldmann Rodney M , Schram Frederick R , Schweitzer Carrie E
Published: January 2020

The best-preserved Scottish species of a cyclidan is reinterpreted, based upon recent advances in cyclidan paleobiology. Americlus rankini (Woodward, 1868) is one of the best-preserved members of this crustacean group, and its morphology suggests that it and related forms exhibited a unique and distinct morphology within Multicrustacea. Paleoecological evidence suggests that the animal was most likely free living, possibly as a scavenger, in a marginal marine environment. Americlus lived in Laurentia during the Middle Mississippian (Visean) to Middle Pennsylvanian (Moscovian).
Strategic Legitimation through Rhetorical Dissociation in International Relations
Authors: Sundaram Sasikumar S
Published: January 2020

What are the processes through which strategic political actors legitimize their preferred policy choice with multiple audiences in international politics? This article builds a conceptual framework of rhetorical dissociation where strategic actors present normative justifications hierarchically to gain acceptance among different audiences. Such hierarchizing works in three interconnected ways whereby strategic actors delineate audience types, create a rhetorical presence to resonate with sympathetic audiences, and establish a bounded dialogue in their legitimation politics to sideline the normative validity claims of other audiences. By engaging with International Relations (IR) theories of strategic legitimation, this article contributes to this field by showing how strategic actors use multiple audiences in the game to their advantage and wrestle a distinct normativity through rhetoric so that it fits their strategic goals. I illustrate the model by empirically examining India's strategic legitimation of intervention in the East Pakistan crisis in 1971. This article also sets the stage for further empirical examination of strategic legitimation, particularly in engaging with humanitarian crises abroad.
A Clinical Prediction Score Including Trial of Antibiotics and C-Reactive Protein to Improve the Diagnosis of Tuberculosis in Ambulatory People With HIV
Authors: Boyles Tom H , Nduna Matilda , Pitsi Thalitha , Scott Lesley , Fox Matthew P , Maartens Gary
Published: January 2020

Background

The use of a “trial of antibiotics” as empiric therapy for bacterial pneumonia as a diagnostic tool for tuberculosis in people with HIV (PWH) was removed from World Health Organization (WHO) recommendations in 2007, based on expert opinion. Current guidelines recommend antibiotics only after 2 Xpert MTB/RIF tests (if available), chest x-ray, and clinical assessment have suggested that tuberculosis is unlikely. Despite this, a “trial of antibiotics” remains common in algorithms in low-resource settings, but its value is uncertain. C-reactive protein (CRP), which has been proposed as a “rule-out” test for tuberculosis, may be an objective marker of response to antibiotics.

Methods

We performed a passive case-finding cohort study of adult PWH with a positive WHO symptom screen. All participants received antibiotics at first visit according to the local protocol and were reviewed to ascertain clinical response. Point-of-care CRP was measured at both visits. All patients had sputum tested with Xpert MTB/RIF Ultra (Ultra), and the reference standard was based on 2 sputum mycobacterial cultures. We explored multivariable prediction models (MPM) for tuberculosis based on 1 or 2 visits.

Results

Seventy-five of 207 patients (36%) had confirmed tuberculosis. Clinical response to antibiotics after 2 days was a good predictor of disease. An MPM based on 2 visits, without CRP, had acceptable discrimination (c-statistic, 0.75) and calibration (goodness-of-fit P = .07). Addition of CRP after antibiotics improved the model moderately (c-statistic, 0.78). CRP at first visit was not an independent predictor of tuberculosis.

Conclusions

In adult PWH seeking care for symptoms suggestive of tuberculosis, lack of response to antibiotics is a strong predictor of disease and is likely to be useful, particularly when access to Ultra is limited. CRP adds value when measured after antibiotics but is of limited value at first visit.
Spontaneous recovery of neuromuscular blockade is an independent risk factor for postoperative pulmonary complications after abdominal surgery
Authors: Garutti Ignacio , Errando Carlos L. , Mazzinari Guido , Bellón José M. , Díaz-Cambronero Oscar , Ferrando Carlos
Published: January 2020

BACKGROUND

In intermediate-to-high-risk patients, major abdominal surgery is associated with a high incidence of postoperative complications, mainly pulmonary. Neuromuscular blocking drugs have been suggested as a contributing factor, but this remains unproven.

OBJECTIVE

To define the relationship of neuromuscular blockade management (reversal) with postoperative pulmonary complications (PPCs).

DESIGN

The individualised PeRioperative Open-lung approach Versus standard protectivE ventilation in abdominal surgery study was a prospective, multicentre, four-arm, randomised controlled trial. This is a secondary analysis of the data.

SETTING

Twenty-one teaching hospitals in Spain. The study was conducted between 2 January 2015, and 18 May 2016.

PATIENTS

Age more than 18 years with an intermediate-to-high risk for PPCs, scheduled for major abdominal surgery lasting more than 2 h. Exclusion criteria included pregnancy or breastfeeding, and moderate-to-severe organ diseases.

INTERVENTIONS

The mode of reversal of neuromuscular blockade determined two patient groups: pharmacological reversal versus spontaneous recovery.

MAIN OUTCOME MEASURES

The primary outcome was a composite of PPCs during the first 30 postoperative days. The association between categorical variables and PPCs within 30 days was studied. Univariate and multivariable logistic regression modelling and propensity score analyses were performed.

RESULTS

From the 923 patients included, 596 (64.6%) presented with PPCs within 30 days after surgery. Patients who developed these complications were older with a higher BMI, a lower pre-operative SpO2, a higher ASA physical status score and a higher incidence of arterial hypertension, diabetes mellitus or chronic obstructive pulmonary disease. Pharmacological neuromuscular blockade reversal was associated with a lower incidence of PPCs (odds ratio 0.62, 95% CI 0.47 to 0.82).

CONCLUSION

Spontaneous recovery of neuromuscular blockade was an independent risk factor for PPCs in patients with intermediate-to-high risk, undergoing abdominal surgery. We suggest this factor should be included in future studies on PPCs.

TRIAL REGISTRATION

clinicaltrials.gov identifier: NCT02158923.
The effect of pH on rates of reaction and hydrogen generation during serpentinization
Authors: McCollom Thomas M. , Klein Frieder , Solheid Peter , Moskowitz Bruce
Published: January 2020

A series of three laboratory experiments were conducted to investigate how pH affects reaction pathways and rates during serpentinization. Two experiments were conducted under strongly alkaline conditions using olivine as reactant at 200 and 230°C, and the results were compared with previous studies performed using the same reactants and methods at more neutral pH. For both experiments, higher pH resulted in more rapid serpentinization of the olivine and generation of larger amounts of H
2
for comparable reaction times. Proportionally greater amounts of Fe were partitioned into brucite and chrysotile and less into magnetite in the experiments conducted at higher pH. In a third experiment, alkaline fluids were injected into an ongoing experiment containing olivine and orthopyroxene to raise the pH from circumneutral to strongly alkaline conditions. Increasing the pH of the olivine-orthopyroxene experiment resulted in an immediate and steep increase in H
2
production, and led to far more extensive reaction of the primary minerals compared to a similar experiment conducted under more neutral conditions. The results suggest that the development of strongly alkaline conditions in actively serpentinizing systems promotes increased rates of reaction and H
2
production, enhancing the flux of H
2
available to support biological activity in these environments.

This article is part of a discussion meeting issue ‘Serpentinite in the Earth System’.
Prevalence of Mild Cognitive Impairment in Mexican Older Adults: Data from the Mexican Health and Aging Study (MHAS)
Authors: Rentería Miguel Arce , Manly Jennifer J. , Vonk Jet M. J. , Arango Silvia Mejia , Obregon Alejandra Michaels , Samper-Ternent Rafael , Wong Rebeca , Mayeux Richard , Barral Sandra , Tosto Giuseppe
Published: January 2020

INTRODUCTION

We estimated the prevalence and risk factors for mild cognitive impairment (MCI) and its subtypes in Mexican population using the cognitive aging ancillary study of the Mexican Health and Aging Study.

METHODS

Using a robust norms approach and comprehensive neuropsychological criteria, we determined MCI in a sample of adult Mexicans (N=1,807;55-97years). Additionally, we determined prevalence rates using traditional criteria.

RESULTS

Prevalence of amnestic MCI was 5.9%. Other MCI subtypes ranged 4.3% to 7.7%. MCI with and without memory impairment was associated with older age and rurality. Depression, diabetes and low educational attainment were associated with MCI without memory impairment. Using traditional criteria, prevalence of MCI was lower (2.2% amnestic MCI, other subtypes ranged 1.3%-2.4%).

DISCUSSION

Older age, depression, low education, diabetes, and rurality were associated with increased risk of MCI among older adults in Mexico. Our findings suggest that the causes of cognitive impairment are likely multifactorial and may vary by MCI subtype.

Research in Context

Systematic review

We reviewed the literature using Google Scholar and PubMed. Few studies have reported prevalence rates for mild cognitive impairment (MCI) in Mexican population. These studies have primarily relied on limited cognitive assessments, and diverse MCI criteria. Evaluating the prevalence of MCI with a robust neuropsychological approach can help understand the rates and risk factors associated with MCI across a large and representative sample of the aging Mexican population.

Interpretation

Various sociodemographic and health factors such as older age, depression, low education, diabetes, and rurality were significant correlates of MCI and differed by MCI subtype.

Future directions

Longitudinal studies will be needed to evaluate the diagnostic stability of MCI over time, and its association with incident dementia. Future work will evaluate the casual path of these sociodemographic and health factors on cognitive impairment to develop effective interventions.
Childhood vaccination coverage and equity impact in Ethiopia by socioeconomic, geographic, maternal and child characteristics
Authors: Geweniger Anne , Abbas Kaja M.
Published: January 2020

Background

Ethiopia is a priority country of Gavi, the Vaccine Alliance to improve vaccination coverage and equitable uptake. The Ethiopian National Expanded Programme on Immunisation (EPI) and the Global Vaccine Action Plan set coverage goals of 90% at national level and 80% at district level by 2020. This study aims to analyse basic vaccination coverage among children in Ethiopia and to estimate the equity impact by socioeconomic, geographic, maternal and child characteristics based on data from the Ethiopia Demographic and Health Survey 2016.

Methods

Basic vaccination coverage (1-dose BCG, 3-doses DPT-HepB-Hib, 3-doses polio, 1-dose measles vaccine) of 2,004 children aged 12-23 months was analysed. Mean coverage was disaggregated by socioeconomic (household wealth, religion, ethnicity), geographic (area of residence, region), maternal (maternal age at birth, maternal education, maternal marital status, sex of household head) and child (sex of child, birth order) characteristics. Concentration indices assessed wealth and education-related inequalities. Multiple logistic regression estimated associations between basic vaccination coverage and socioeconomic, maternal and child characteristics.

Results

National coverage for basic vaccinations was 39.7% in 2016. Single vaccination coverage ranged between between 53.2% (DTP3) and 69.2% (BCG). Wealth and maternal education related inequities were present for all vaccines. Children from richer households, urban regions, primary maternal education and male headed households were associated with higher vaccination coverage. The Ethiopia Mini Demographic and Health Survey 2019 reports national coverage for basic vaccinations at 43.3% with single vaccination coverage ranging between 57.8% (measles) and 74.2% (BCG).

Conclusions

Vaccination coverage has improved from 2016 to 2019, but remains below the coverage goals of the EPI. Low vaccination coverage is associated with poorer households, rural regions of Afar and Somali, no maternal education and female headed households. Targeted approaches are necessary to improve vaccination coverage among these population subgroups and equitable uptake of vaccines in Ethiopia.
What matters to patients?: a timely question for Value Based Care
Authors: Hirpa Meron , Woreta Tinsay , Addis Hilena , Kebede Sosena
Published: January 2020

Background

Our healthcare system is moving towards patient-centered and value-based care models that prioritize health outcomes that matter to patients. However, little is known about what aspects of care patients would prioritize when presented with choices of desirable attributes and whether these patient priorities differ based on certain demographics.

Objective

To assess patients’ priorities for a range of attributes in ambulatory care consultations across five key health service delivery domains and determine potential associations between patient priorities and certain demographic profiles.

Methods

Using aWhat Matters to Yousurvey patients ranked in order of importance various choices related to five health service domains (patient-physician relationship, personal responsibility, tests/procedures, medications and cost). Subjects were selected from two Johns Hopkins affiliated primary care clinics and a third gastroenterology subspecialty clinic over a period of 11 months. We calculated the percentage of respondents who selected each quality as their top 1-3 choice. Univariate and multivariate analyses determined demographic characteristics associated with patient priorities.

Results

Humanistic qualities of physicians, leading a healthy lifestyle, shared decision making (SDM) for medications and tests/procedures and knowledge about insurance coverage were the most frequently ranked choices. Privately insured and more educated patients were less likely to rank humanistic qualities highly. Those with younger age, higher educational attainment and private insurance had higher odds of ranking healthy lifestyle as a top choice. Those with more education had higher odds of ranking SDM as a top choice.

Conclusions

Identifying what matters most to patients is useful as we move towards patient-centered and value based care models. Our findings suggest that patients have priorities on qualities they value across key health service domains. Multiple factors including patient demographics can be predictors of these priorities. Elucidating these preferences is a challenging but a valuable step in the right direction.
Simultaneous Discovery of Positive and Negative Interactions Among Root Microbiome Bacteria Using Microwell Recovery Arrays
Authors: Barua Niloy , Herken Ashlee M. , Stern Kyle R. , Reese Sean , Powers Roger L. , Morrell-Falvey Jennifer L. , Platt Thomas G. , Hansen Ryan R.
Published: January 2020

Understanding the consequences of microbe-microbe interactions is critical in efforts to predict the function of microbiomes and to manipulate or construct communities to achieve desired outcomes. The investigation of these interactions poses a significant challenge - in part due to the lack of suitable experimental tools. We present the Microwell Recovery Array, a high throughput approach designed to rapidly screen interactions across a microbiome and uncover higher-order combinations of strains that either inhibit or promote the function of a GFP-producing focal species. One experiment generates 104unique microbial communities that contain a focal species combined with a unique combination of previously uncharacterized cells from plant rhizosphere. Cells are then sequentially extracted from individual co-culture wells that display highest or lowest levels of focal species function using a novel high-resolution photopolymer extraction system. Microbes present are subsequently identified and the putative interactions are validated. Using this approach, we screen thePopulus trichocarparhizosphere for bacterial strains affecting the survival and growth ofPantoeasp. YR343, a plant growth promoting strain isolated from theP. trichocarparhizosphere. We were able to simultaneously isolate and validate multipleStenotrophomonasstrains that antagonize strain YR343 growth and a set ofEnterobacterstrains that promote strain YR343 growth. The latter demonstrates the unique ability of the platform to uncover multi-membered consortia that generate emergent phenotypes. This knowledge will inform the development of beneficial consortia that promote the production ofPopulusbiofuel feedstock, while the platform is adaptable to screening higher-order interactions in any microbiome of interest.

Significance Statement

Achieving a fundamental understanding of microbe-microbe interactions that occur within microbial communities is a grand challenge in microbiology due to the limited experimental tools available. In this report, we describe a new tool that enables one to screen microbial interactions across thousands of compositionally unique communities to discover collections of bacteria that antagonize or promote the survival and growth of bacteria with important functions. This approach has the unique ability to uncover higher-order combinations of bacteria that generate emergent phenotypes, information useful for development of biofertilizer, biocontrol, or probiotic consortia, as well as in the design of communities for biosynthetic compound production.
Engineering Cell-Permeable Proteins through Insertion of Cell-Penetrating Motifs into Surface Loops
Authors: Chen Kuangyu , Pei Dehua
Published: January 2020

Effective delivery of proteins into the cytosol and nucleus of mammalian cells would open the door to a wide range of applications including treatment of many currently intractable diseases. However, despite great efforts from numerous investigators and the development of a variety of innovative methods, effective protein delivery in a clinical setting is yet to be accomplished. Herein we report a potentially general approach to engineering cell-permeable proteins by genetically grafting a short cell-penetrating peptide to an exposed loop region of a protein of interest. The grafted peptide is conformationally constrained by the protein structure, sharing the structural features of cyclic cell-penetrating peptides and exhibiting enhanced proteolytic stability and cellular entry efficiency. Insertion of an amphipathic motif, Arg-Arg-Arg-Arg-Trp-Trp-Trp, into the loop regions of enhanced green fluorescent protein (EGFP), protein-tyrosine phosphatase 1B (PTP1B), and purine nucleoside phosphorylase (PNP) rendered all three proteins cell-permeable and biologically active in cellular assays. When added into growth medium, the engineered PTP1B dose-dependently reduced the phosphotyrosine levels of intracellular proteins, while the modified PNP protected PNP-deficient mouse T lymphocytes (NSU-1) against toxic levels of deoxyguanosine, providing a potential enzyme replacement therapy for a rare genetic disease.
Bioethanol from Sago Waste Fermented by Baker’s and Tapai Yeast as a Renewable Energy Source
Authors: Rijal Muhammad
Published: January 2020

Renewable energy is collected through sustainable natural processes. One of the examples of renewable energy is a biofuel. A biofuel is produced from organic materials, such as plants with high sugar content. Sago starch extracted from sago pith contains starch and fiber that can be converted into glucose by hydrolysis. Sago starch and fiber can be processed into bioethanol as the main ingredient of renewable energy source. In this study, bioethanol production from sago waste fermented by baker’s yeast and tapai underwent the following stages: delignification, hydrolysis, fermentation, and distillation. The highest bioethanol content was obtained from the BRT treatment where wet solid sago waste was fermented by baker’s yeast (45.7021%), while the lowest was found in the BTP treatment (0.9504%). Two or more than two peaks were shown by the ART, ATP, BTP, and KTP treatments, whereas only one peak was indicated by the BRT and KRT treatments suggesting that there was only one compound that can be identified as ethanol.
Capturing volumetric dynamics at high speed in the brain by confocal light field microscopy
Authors: Zhang Zhenkun , Bai Lu , Cong Lin , Yu Peng , Zhang Tianlei , Shi Wanzhuo , Li Funing , Du Jiulin , Wang Kai
Published: January 2020

Neural network performs complex computations through coordinating collective neural dynamics that are fast and in three-dimensions. Meanwhile, its proper function relies on its 3D supporting environment, including the highly dynamic vascular system that drives energy and material flow. Better understanding of these processes requires methods to capture fast volumetric dynamics in thick tissue. This becomes challenging due to the trade-off between speed and optical sectioning capability in conventional imaging techniques. Here we present a new imaging method, confocal light field microscopy, to enable fast volumetric imaging deep into brain. We demonstrated the power of this method by recording whole brain calcium transients in freely swimming larval zebrafish and observed behaviorally correlated activities on single neurons during its prey capture. Furthermore, we captured neural activities and circulating blood cells over a volume ⌀ 800 μm × 150 μm at 70 Hz and up to 600 μm deep in the mice brain.
Cyano-assassins: Widespread cyanogenic production from cyanobacteria
Authors: Panou Manthos , Gkelis Spyros
Published: January 2020

Cyanobacteria have been linked with hydrogen cyanide, based on their ability to catabolize it by the nitrogenase enzyme, as a part of nitrogen fixation. Nitrogenase can also use hydrogen cyanide instead of its normal substrate, dinitrogen and convert it to methane and ammonia. In this study, we tested whether cyanobacteria are able, not only to reduce, but also to produce HCN. The production of HCN was examined in 78 cyanobacteria strains from all five principal sections of cyanobacteria, both non-heterocytous and heterocytous, representing a variety of lifestyles and habitats. Twenty-eight (28) strains were found positive for HCN production, with universal representation amongst 22 cyanobacterial planktic and epilithic genera inhabiting freshwater, brackish, marine (including sponges), and terrestrial (including anchialine) habitats. The HCN production could be linked with nitrogen fixation, as all of HCN producing strains are considered capable of fixing nitrogen. Epilithic lifestyle, where cyanobacteria are more vulnerable to a number of grazers and accumulate more glycine, had the largest percentage (75%) of HCN-producing cyanobacteria compared to strains from aquatic ecosystems. Further, we demonstrate the isolation and characterisation of taxa likeGeitleria calcareaandKovacikia muscicola, for which no strain existed andChlorogloeasp. TAU-MAC 0618 which is, to the best of our knowledge, the first bacterium isolate from anchialine ecosystems. Our results highlight the complexity of cyanobacteria secondary metabolism, as well as the diversity of cyanobacteria in underexplored habitats, providing a missing study material for this type of environments.
The G-protein coupled receptor SRX-97 is required for concentration dependent sensing of Benzaldehyde inCaenorhabditis elegans
Authors: Kadam Nagesh Y. , Behera Sukanta , Kumar Sandeep , Ghosh-Roy Anindya , Babu Kavita
Published: January 2020

The G-protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors in the olfactory system function to sense the surroundings and respond to various odorants. The genes encoding for the olfactory receptors inC. elegansare larger in number in comparison to those in mammals, suggesting complexity in the receptor– odorant relationships. Recent studies have shown that the same odorant in different concentration could act on multiple receptors in different neurons to induce attractive or repulsive responses. The ASH neuron is known to be responsible for responding to high concentrations of volatile odorants. Here we characterize a new GPCR, SRX-97. We found that thesrx-97promoter shows expression specifically in the head ASH and tail PHB chemosensory neurons ofC. elegans. Further, the SRX-97 protein localizes to the ciliary ends of the ASH neurons. Analysis of CRISPR/based deletion mutants of thesrx-97gene suggest that this gene is involved in the recognition of high concentrations of benzaldehyde. This was further confirmed through rescue and neuronal ablation experiments. Our work gives insight into concentration dependent receptor function in the olfactory system and provides details of an additional molecule that could help the animal navigate its surroundings.
A Length Penalized Probabilistic Principal Curve Algorithm With Applications To Handwritten Digits And Pharmacologic Colon Imaging
Authors: Chen Huan , Weld Ethel , Hendrix Craig , Caffo Brian
Published: January 2020

The classical Principal Curve algorithm was developed as a nonlinear version of principal component analysis to model curves. However, existing principal curve algorithms with classical penalties, such as smoothness or ridge penalties, lack the ability to deal with complex curve shapes. In this manuscript, we introduce a robust and stable length penalty which solves issues of unnecessary curve complexity, such as the self-looping, that arise widely in principal curve algorithms. A novel probabilistic mixture regression model is formulated. A modified penalized EM(Expectation Maximization) Algorithm was applied to the model to obtain the penalized MLE. Two applications of the algorithm were performed. In the first, the algorithm was applied to the MNIST dataset of handwritten digits to find the centerline, not unlike defining a TrueType font. We demonstrate that the centerline can be recovered with this algorithm. In the second application, the algorithm was applied to construct a three dimensional centerline through single photon emission computed tomography images of the colon arising from the study of pre-exposure prophylaxis for HIV. The centerline in this application is crucial for understanding the distribution of the antiviral agents in the colon for HIV prevention. The new algorithms improves on previous applications of principal curves to this data.
Derived ecological niches of indoor microbes are crucial for asthma symptoms in university dormitories
Authors: Fu Xi , Li Yanling , Meng Yi , Yuan Qianqian , Zhang Zefei , Norbäck Dan , Deng Yiqun , Zhang Xin , Sun Yu
Published: January 2020

Increasing evidences from home environment indicate that microbiome community is associated with asthma. However, indoor microbiome composition can be highly diverse and dynamic, and thus current studies fail to produce consistent association. Chinese university dormitories are special high-density dwellings with a standard built environment and personal characteristics for occupants, which can be used to disentangle the complex interactions between microbes, environmental characteristics and asthma.

Settled air dust and floor dust was collected from 87 dormitory rooms in Shanxi University. Bacterial community was characterized by 16S rRNA amplicon sequencing. Students (n = 357) were surveyed for asthma symptoms.

Asthma symptoms were not associated with the overall bacterial richness, but associated with different phylogenetic classes. Taxa richness and abundance in Clostridia and Bacteroidia were positively associated with asthma (p < 0.05), and these taxa were mainly derived from human gut. Taxa richness (p < 0.1) and abundance (p < 0.05) in Alphaproteobacteria and Actinobacteria were protectively associated with asthma, and these taxa were mainly derived from outdoor environment. Building age, floor and curtain cleaning frequency shaped the overall bacterial community of air dust (p < 0.05). Frequent curtain cleaning increased the relative abundance of 10 protective genera (p < 0.05), and old buildings had mix effects to protective genera (p < 0.05).

Our data shows that taxa from different phylogenetic classes and ecological niches have different health effects, indicating the importance of incorporating evolutionary and ecological concepts in revealing general patterns in the microbiome asthma association analysis.
Variation in the expression of a transmembrane protein influences cell growth inArabidopsis thalianapetals by altering auxin availability
Authors: Miller Charlotte N. , Dumenil Jack , Smith Caroline , Lu Fu Hao , McKenzie Neil , Chapman Volodymyr , Ball Joshua , Box Mathew , Bevan Michael
Published: January 2020

Background

The same species of plant can exhibit highly diverse sizes and shapes of organs that are genetically determined. Defining genetic variation underlying this morphological diversity is an important objective in evolutionary studies and it also helps identify the functions of genes influencing plant growth and development. Extensive screens of mutagenised Arabidopsis populations have identified multiple genes and mechanisms affecting organ size and shape, but relatively few studies have exploited the rich diversity of natural populations to identify genes involved in growth control.

Results

We screened a relatively well characterised collection ofArabidopsis thalianaecotypes for variation in petal size. Association analyses identified sequence and gene expression variation on chromosome 4 that made a substantial contribution to differences in petal area. Variation in expression of At4g16850 (named asKSK), encoding a hypothetical protein, had a substantial role on variation in organ size by influencing cell size. Over-expression ofKSKled to larger petals with larger cells and promoted the formation of stamenoid features. The expression of auxin-responsive genes known to limit cell growth was reduced in response toKSKover-expression. ANT expression was also reduced inKSKover-expression lines, consistent with altered floral identities. Auxin availability was reduced inKSKover-expressing cells, consistent with changes in auxin-responsive gene expression.KSKmay therefore influence auxin availability during petal development.

Conclusions

Understanding how genetic variation influences plant growth is important for both evolutionary and mechanistic studies. We used natural populations ofArabidopsis thalianato identify sequence variation in a promoter region of Arabidopsis ecotypes that mediated differences in the expression of a previously uncharacterised membrane protein. This variation contributed to altered auxin availability and cell size during petal growth.
Different forms of variability could explain a difference between human and rat decision making
Authors: Nguyen Quynh Nhu , Reinagel Pamela
Published: January 2020

When observers make rapid, difficult perceptual decisions, their response time is highly variable from trial to trial. In a visual motion discrimination task, it has been reported that human accuracy declines with increasing response time, whereas rat accuracy increases with response time. This is of interest because different mathematical theories of decision-making differ in their predictions regarding the correlation of accuracy with response time. On the premise that perceptual decision-making mechanisms are likely to be conserved among mammals, we seek to unify the rodent and primate results in a common theoretical framework. We show that a bounded drift diffusion model (DDM) can explain both effects with variable parameters: trial-to-trial variability in the starting point of the diffusion process produces the pattern typically observed in rats, whereas variability in the drift rate produces the pattern typically observed in humans. We further show that the same effects can be produced by deterministic biases, even in the absence of parameter stochasticity or parameter change within a trial.
Coupling of translation quality control and mRNA targeting to stress granules
Authors: Moon Stephanie L. , Morisaki Tatsuya , Stasevich Timothy J. , Parker Roy
Published: January 2020

Stress granules (SGs) are dynamic assemblies of non-translating RNAs and proteins that form with translation inhibition1. Stress granules are similar to neuronal and germ cell granules, play a role in survival during stress, and aberrant, cytotoxic SGs are implicated in neurodegeneration2–4. Perturbations in the ubiquitin-proteasome (UPS) system also cause neurodegeneration5–10, and alter the dynamicity and kinetics of SGs11–14. Using single mRNA imaging in live cells15, 16, we took an unbiased approach to determine if defects in the UPS perturb mRNA translation and partitioning into SGs during acute stress. We observe ribosomes stall on mRNAs during arsenite stress, and the release of transcripts from stalled ribosomes for their partitioning into SGs requires the activities of valosin-containing protein (VCP) and the proteasome, which is in contrast to previous work showing VCP primarily affected SG disassembly11, 13, 14, 17. Moreover, members of a specialized complex in the UPS that targets aberrant nascent proteins for decay upon ribosome stalling, referred to as ribosome-associated quality control complex (RQC)18, are also required for mRNA release from ribosomes and partitioning into SGs. VCP alleles that increase segregase activity and cause neurodegeneration and inclusion body myopathies5, 6, 19, 20increase mRNA recruitment to SGs, suggesting aberrant mRNA localization to SGs in disease contexts. This work identifies a new type of stress-activated RQC (saRQC) distinct from canonical RQC pathways in mRNA substrates, cellular context and mRNA fate.
Calpain-2 regulates hypoxia/HIF-induced amoeboid reprogramming and metastasis
Authors: te Boekhorst Veronika , Jiang Liying , Mählen Marius , Meerlo Maaike , Dunkel Gina , Durst Franziska C. , Yang Yanjun , Levine Herbert , Burgering Boudewijn M. T. , Friedl Peter
Published: January 2020

Hypoxia, through hypoxia inducible factor (HIF), drives cancer cell invasion and metastatic progression in various cancer types, leading to poor prognosis. In epithelial cancer, hypoxia further induces the transition to amoeboid cancer cell dissemination, yet the molecular mechanisms, relevance for metastasis, and effective interventions to combat hypoxia-induced amoeboid reprogramming remain unclear. Here, we identify calpain-2 as key regulator and anti-metastasis target of hypoxia-induced transition from collective to amoeboid dissemination of breast and head and neck (HN) carcinoma cells. Hypoxia-induced amoeboid dissemination occurred through low ECM-adhesive, bleb-based amoeboid movement, which effectively invaded into 3D collagen with low-oxidative and -glycolytic energy metabolism, revealing an microenvironmentally-induced, energy-conserving dissemination route in epithelial cancers. Hypoxia-induced calpain-2 mediated amoeboid conversion by de-activating beta1 integrins, through enzymatic cleavage of the focal adhesion adaptor protein talin-1. Consequently, targeted downregulation of calpain-2 or pharmacological intervention restored talin-1 integrity, beta1 integrin engagement and reverted blebbing-amoeboid to elongated phenotypes under hypoxia. Calpain-2 activity was required for hypoxia-induced blebbing-amoeboid conversion in the orthotopic mouse dermis, and upregulated in invasive HN tumor xenografts in vivo, and attenuation of calpain activity prevented hypoxia-induced metastasis to the lungs. This identifies the calpain-2/talin-1/beta1 integrin axis as mechanosignaling program and promising intervention target of plasticity of cancer cell invasion and metastasis formation in epithelial cancers under hypoxia.
Assessing the Quality of Cotranscriptional Folding Simulations
Authors: Kühnl Felix , Stadler Peter F. , Findeiß Sven
Published: January 2020

Structural changes in RNAs are an important contributor to controlling gene expression not only at the post-transcriptional stage but also during transcription. A subclass of riboswitches and RNA thermometers located in the 5’ region of the primary transcript regulates the downstream functional unit – usually an ORF – through premature termination of transcription. Such elements not only occur naturally but they are also attractive devices in synthetic biology. The possibility to design such riboswitches or RNA thermometers is thus of considerable practical interest. Since these functional RNA elements act already during transcription, it is important to model and understand the dynamics of folding and, in particular, the formation of intermediate structures concurrently with transcription. Cotranscriptional folding simulations are therefore an important step to verify the functionality of design constructs before conducting expensive and labour-intensive wet lab experiments. For RNAs, full-fledged molecular dynamics simulations are far beyond practical reach both because of the size of the molecules and the time scales of interest. Even at the simplified level of secondary structures further approximations are necessary. The BarMap approach is based on representing the secondary structure landscape for each individual transcription step by a coarse-grained representation that only retains a small set of low-energy local minima and the energy barriers between them. The folding dynamics between two transcriptional elongation steps is modeled as a Markov process on this representation. Maps between pairs of consecutive coarse-grained landscapes make it possible to follow the folding process as it changes in response to transcription elongation.

In its original implementation, the BarMap software provides a general framework to investigate RNA folding dynamics on temporally changing landscapes. It is, however, difficult to use in particular for specific scenarios such as cotranscriptional folding. To overcome this limitation, we developed the user-friendly BarMap-QA pipeline described in detail in this contribution. It is illustrated here by an elaborate example that emphasizes the careful monitoring of several quality measures. Using an iterative workflow, a reliable and complete kinetics simulation of a synthetic, transcription regulating riboswitch is obtained using minimal computational resources. All programs and scripts used in this contribution are free software and available for download as a source distribution for Linux®, or as a platform-independent Docker®image including support for Apple macOS®and Microsoft Windows®.
Material-Driven Fibronectin Assembly Rescues Matrix Defects due to Mutations in Collagen IV in Fibroblasts
Authors: Mpoyi Elie Ngandu , Cantini Marco , Sin Yuan Yan , Fleming Lauren , Zhou Dennis W. , Costell Mercedes , Lu Yinhui , Kadler Karl , García Andrés J. , Van Agtmael Tom , Salmeron-Sanchez Manuel
Published: January 2020

Basement membranes (BMs) provide structural support to tissues and influence cell signaling. Mutations in COL4A1/COL4A2, a major BM component, cause eye, kidney and cerebrovascular disease, including stroke. Common variants in these genes are risk factors for intracerebral hemorrhage in the general population. However, the contribution of the matrix to the disease mechanism(s) and its effects on the biology of cells harboring a collagen IV mutation remain poorly understood. To shed light on this, we engineered controlled microenvironments using polymer biointerfaces coated with ECM proteins laminin or fibronectin (FN), to investigate the cellular phenotype of primary fibroblasts harboring aCOL4A2+/G702Dmutation. FN nanonetworks assembled on poly(ethyl acrylate) (PEA) induced increased deposition and assembly of collagen IV inCOL4A2+/G702Dcells, which was associated with reduced ER size and enhanced levels of protein chaperones such as BIP, suggesting increased protein folding capacity of cells. FN nanonetworks on PEA also partially rescued the reduced stiffness of the deposited matrix and cells, and enhanced cell adhesion through β1-mediated signaling and actin-myosin contractility, effectively rescuing some of the cellular phenotypes associated withCOL4A1/4A2mutations. Collectively, these results suggest that biomaterials are able to shape the matrix and cellular phenotype of theCOL4A2+/G702Dmutation in patient-derived cells.