bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated analysis of PSMA-PET/CT studies using convolutional neural networks
Authors: Edenbrandt Lars , Borrelli Pablo , Ulén Johannes , Enqvist Olof , Trägårdh Elin
Published: March 2021

Purpose

Prostate-specific membrane antigen (PSMA) PET/CT has shown to be more sensitive and accurate than conventional imaging. Visual interpretation of the images causes both intra- and inter-reader disagreement and there is therefore a need for objective methods to analyze the images. The aim of this study was to develop an artificial intelligence (AI) tool for PSMA PET/CT and to evaluate the influence of the tool on inter-reader variability.

Approach

We have recently trained AI tools to automatically segment organs, detect tumors, and quantify volume and tracer uptake of tumors in PET/CT. The primary prostate gland tumor, bone metastases, and lymph nodes were analyzed in patients with prostate cancer. These studies were based on non-PSMA targeting PET tracers. In this study an AI tool for PSMA PET/CT was developed based on our previous AI tools. Letting three physicians analyze ten PSMA PET/CT studies first without support from the AI tool and at a second occasion with the support of the AI tool assessed the influence of the tool. A two-sided sign test was used to analyze the number of cases with increased and decreased variability with support of the AI tool.

Results

The range between the physicians in prostate tumor total lesion uptake (TLU) decreased for all ten patients with AI support (p=0.002) and decreased in bone metastases TLU for nine patients and increased in one patient (p=0.01). Regarding the number of detected lymph nodes the physicians agreed in on average 72% of the lesions without AI support and this number decreased to 65% with AI support.

Conclusions

Physicians supported by an AI tool for automated analysis of PSMA-PET/CT studies showed significantly less inter-reader variability in the quantification of primary prostate tumors and bone metastases than when performing a completely manual analysis. A similar effect was not found for lymph node lesions. The tool may facilitate comparisons of studies from different centers, pooling data within multicenter trials and performing meta-analysis. We invite researchers to apply and evaluate our AI tool for their PSMA PET/CT studies. The AI tool is therefore available upon reasonable request for research purposes atwww.recomia.org.
Disparities in outcomes among patients diagnosed with cancer associated with emergency department visits
Authors: Pettit Nicholas , Sarmiento Elisa , Kline Jeffrey
Published: March 2021

Importance

Diagnosis of cancer in the emergency department (ED) may be associated with poor outcomes, related to socioeconomic (SES) disparities, however data are limited.

Objective

To examine the morality and associated disparities for cancer diagnoses made less than six months after an ED visit.

Design

This study is case-control analysis of the Indiana State Department of Health Cancer Registry, and the Indiana Network for Patient Care. First time diagnoses of ICD-“cancer” appearing in the registry between January 2013 and December 2017 were included. Cases were patients who had an ED visit in the 6 months before their cancer diagnosis; controls had no recent ED visits.

Main Outcome(s) and Measure(s)

Primary outcome was mortality, comparing ED-associated mortality to non-ED-associated. Secondary outcomes include SES and demographic disparities.

Results

134,761 first-time cancer patients were identified, including 15,432 (11.5%) cases. In cases and controls, the mean age was same at 65 and the Charlson Comorbidity Index (CCI) was the same at 2.0 in both groups. More of the ED cohort were Black than the non-ED cohort (12.4% vs 7.4%, P<.0001, Chi Square) and more were low income (36.4%. vs 29.3%). The top 3 ED-associated cancer diagnoses were lung (18.4%), breast (8.9%), and colorectal cancer (8.9%), vs. the non-ED cohort were breast (17%), lung (14.9%), and prostate cancer (10.1%). Regardless of type, all ED-associated cancers had an over three-fold higher mortality, with cumulative death rate of 32.9% for cases vs 9.0% for controls (P<.0001) over the entire study period. Regression analysis predicting mortality, clustering by city, controlling for age, gender, race, SES, drug/alcohol/tobacco use, and CCI score, produced an odds ratio of 4.12 (95% CI 3.72-4.56 for ED associated cancers).

Conclusion and Relevance

This study found that an ED visit within 6 months prior to the first time of ICD-coded cancer is associated with Black race, low income and an overall three-fold increased risk of death. The mortality rates for ED-associated cancers are uniformly worse for all cancer types. These data suggest that additional work is needed in order to reduce disparities among ED-associated cancer diagnoses, including increased surveillance and improved transitions of care.

Key Points

Question

Do patients diagnosed with cancer, shortly after an emergency department (ED) visit have worsened outcomes than patients with diagnoses not associated with an ED visit.

Findings

In this retrospective, epidemiological assessment, 134,761 patients were diagnosed with cancer, 11.5% (15,432) were seen in the ED within 6 months prior to their diagnosis. They had increased mortality, associated with racial and socioeconomic disparities.

Meaning

These findings imply an urgent need for improved transitions of care for minority and low-income patients with suspected cancer in the ED.
Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers
Authors: Lundström Annika , Ziegler Louise , Havervall Sebastian , Rudberg Ann-Sofie , von Meijenfeldt Fien , Lisman Ton , Mackman Nigel , Sandén Per , Thålin Charlotte
Published: March 2021

Rationale

Angiotensin-converting enzyme 2 (ACE2) is the main entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how SARS-CoV-2 interactions with ACE2 influences the renin-angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) is unknown.

Objective

To measure circulating ACE2 and ACE levels in COVID-19 patients and investigate association with risk factors, outcome and inflammatory markers.

Methods and results

Soluble ACE2 (sACE2) and sACE concentrations were measured by ELISA in plasma samples from 114 hospital-treated COVID-19 patients and 10 healthy controls. Follow-up samples after four months were available for 58/114 patients. Von Willebrand factor (VWF), factor VIII (fVIII), D-dimer, interleukin 6 (IL-6), tumor necrosis factor α and plasminogen activator inhibitor 1 (PAI-1) had previously been determined. Levels of sACE2 were higher in COVID-19 patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < 0.0001. sACE2 was higher in men than women, but were not affected by other risk factors for severe COVID-19. sACE 2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < 0.0001, but remained higher than in healthy controls, p=0.012. Follow-up sACE2 levels were higher with increasing age, BMI, total number of comorbidities, for patients with diabetes and patients on RAS-inhibition. sACE was marginally lower during COVID-19 compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. Levels of sACE2 and sACE did not differ depending on survival or disease severity (care level, respiratory support). sACE2 during COVID-19 correlated with VWF, fVIII and D-dimer, while sACE correlated with IL-6, TNFα and PAI-1.

Conclusions

sACE2 was transiently elevated in COVID-19, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 differed distinctly in their correlations with markers of inflammation and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.
Factors associated with severe sepsis in diarrheal adults and their outcome at an urban hospital, Bangladesh: A retrospective analysis
Authors: Sarmin Monira , Begum Monjory , Islam Farhana , Afroze Farzana , Shahrin Lubaba , zaman Sharifuz , Alam Tahmina , Bin Shahid Abu Sadat Mohammad Sayeem , Ahmed Tahmeed , Chisti Mohammod Jobayer
Published: March 2021

Background

Clinical features of sepsis and severe diarrhea often overlap and create a dilemma among the clinicians. To describe factors associated with severe sepsis in diarrheal adults and their outcomes to understand their interplay as clinical features of sepsis and severe diarrhea often overlap.

Methods and results

We used this retrospective chart analysis employing a case-control design to study critically ill diarrheal adults aged ≥ 18 years treated in ICU Dhaka hospital, icddr,b between January 2011 to December 2015. Diarrheal adults with a diagnosis of severe sepsis were cases and an equal number of randomly selected non-septic patients were the controls. Of 8,863 in-patient adults, 350 fulfilled the criteria of cases. Cases died significantly more (9% vs 3%, p=0.002) than controls. 69% of the cases progressed to septic shock. In logistic regression analysis, steroid intake, ileus, acute kidney injury, metabolic acidosis, and hypocalcemia were significantly associated with severe sepsis in diarrheal adults (all, p<0.05). 12% of cases (40/335) had bacteremia. Streptococcus pneumoniae [9 (22.5%)] was the single most common pathogen and gram-negatives [27 (67.5%)] were prevailing as a group.

Conclusion

Diarrheal adults who had ileus, AKI, metabolic acidosis, hypocalcemia, and also took steroids were prone to have severe sepsis. Strikingly, gram-negatives were the predominant bacteria among the diarrheal adults having severe sepsis.
V3 Interneurons are Active and Recruit Spinal Motor Neurons DuringIn VivoFictive Swimming in Larval Zebrafish
Authors: Wiggin Timothy D. , Montgomery Jacob E. , Brunick Amanda J. , Peck Jack H. , Masino Mark A.
Published: March 2021

Survival for vertebrate animals is dependent on the ability to successfully find food, locate a mate, and avoid predation. Each of these behaviors requires motor control, which is set by a combination of kinematic properties. For example, the frequency and amplitude of motor output combine in a multiplicative manner to determine features of locomotion such as distance traveled, speed, force (thrust), and vigor. Although there is a good understanding of how different populations of excitatory spinal interneurons establish locomotor frequency, there is a less thorough mechanistic understanding for how locomotor amplitude is established. Recent evidence indicates that locomotor amplitude is regulated in part by a subset of functionally and morphologically distinct V2a excitatory spinal interneurons (type II, non-bursting) in larval and adult zebrafish. Here we provide direct evidence, for the first time, that most V3 interneurons (V3-INs), which are a developmentally and genetically defined population of ventromedial glutamatergic spinal neurons, are active during fictive swimming. We also show that elimination of the spinal V3-IN population reduces the proportion of active MNs during fictive swimming but does not alter the range of locomotor frequencies produced. These data are consistent with V3-INs providing excitatory drive to spinal motor neurons and contributing to the production of locomotor amplitude, but not frequency, during swimming in larval zebrafish.

SIGNIFICANCE STATEMENT

Currently, there is a limited understanding about the cellular and spinal network properties that produce locomotor amplitude, defined as limb displacement in limbed animals or tail-bend in non-limbed animals during locomotion. Here we show, directly for the first time in a vertebrate, that V3 interneurons (V3-INs) in zebrafish larvae are active duringin vivofictive locomotion, and that targeted ablation of the spinal V3-IN population reduces the proportion of active motoneurons during fictive swimming. Importantly, ablation of V3-INs does not affect locomotor frequency (speed), which clarifies their role in motor control rather than rhythm generation. Thus, we propose that the V3-IN population is a source of excitation in the vertebrate locomotor neural circuitry that regulates locomotor amplitude independently of speed.
Pro-inflammatory alveolar macrophages associated with allograft dysfunction after lung transplantation
Authors: Moshkelgosha Sajad , Wilson Gavin , Duong Allen , Andrews Tallulah , Berra Gregory , Renaud-Picard Benjamin , Keshavjee Shaf , Martinu Tereza , MacParland Sonya , Yeung Jonathan , Juvet Stephen
Published: March 2021

Purpose

Lung transplant (LT) recipients experience episodes of immune-mediated acute lung allograft dysfunction (ALAD). We have applied single-cell RNA sequencing (scRNAseq) to bronchoalveolar lavage (BAL) cells of stable and ALAD patients to determine key cellular elements in dysfunctional lung allografts. Our particular focus here is on studying alveolar macrophages (AMs) as scRNAseq enables us to elucidate their heterogeneity and possible association with ALAD where our knowledge from cytometry-based assays is very limited.

Methods

Fresh bronchoalveolar lavage (BAL) cells from 6 LT patients, 3 with stable lung function (3044 ± 1519 cells) and 3 undergoing an episode of ALAD (2593 ± 904 cells) were used for scRNAseq. R Bioconductor and Seurat were used to perform QC, dimensionality reduction, annotation, pathway analysis, and trajectory. Donor and recipient deconvolution was performed using single nucleotide variations.

Results

Our data revealed that AMs are highly heterogeneous (12 transcriptionally distinct subsets in stable). We identified two AM subsets uniquely represented in ALAD. Based on pathway analysis and the top differentially expressed genes in BAL we annotated them as pro-inflammatory interferon-stimulated genes (ISG) and metallothioneins-mediated inflammatory (MT). Pseudotime analysis suggested that ISG AMs represent an earlier stage of differentiation which may suggest them as monocyte drive macrophages. Our functional analysis on an independent set of BAL samples shows that ALAD samples have significantly higher expression of CXCL10, a marker of ISG AM, as we as higher secretion of pro-inflammatory cytokines. Single nucleotide variation calling algorithm has allowed us to identify macrophages of donor origin and demonstrated that donor AMs are lost with time post-transplant.

Conclusion

Using scRNAseq, we observed AMs heterogeneity and identified specific subsets that may be associated with allograft dysfunction. Further exploration with scRNAseq will shed light on LT immunobiology and the role of AMs in allograft injury and dysfunction.
In situ community dynamics influences the temperature- and light- dependent succession of seasonal phytoplankton
Authors: Tragin Margot , Lambert Stefan , Lozano Jean-Claude , Bouget François-Yves
Published: March 2021

Temperature and light play a crucial role in regulating phytoplankton blooms in the Ocean. To assess the importance of these two parameters experimentally, microcosms were conducted on seven picoplankton communities (<3 μm) sampled in December, March, June and September 2015 and 2016 in the North Western Mediterranean Sea. Each community was exposed to 4 realistic seasonal conditions (December, March, June and September). Metabarcoding was used to investigate the eukaryotic diversity in the 56 microcosms experiments in parallel to high-frequency monitoring of environmental diversity in the sea. The three major lineages identified were the Stramenopiles, Alveolata and Archaeplastida. Overall, the five-day incubations were not sufficient to reshape the initial microbial communities completely. The microcosm outcome was strongly influenced by the dynamics of phytoplankton starting communities. In pre-bloom conditions, phytoplanktonic species were the most sensitive to temperature and light conditions. During a bloom, species belonging to diatoms or Chlorodendrophyceae usually did not respond to light and temperature in microcosms and continued to bloom independently of the applied seasonal condition. Together, these results suggest that light and temperature seasonal conditions play a crucial role in regulating phytoplankton dynamics in pre-bloom conditions and biotic interactions may be preponderant in bloom and post-bloom conditions.
Towards a standardization of non-symbolic numerical experiments: GeNEsIS, a flexible and user-friendly tool to generate controlled stimuli
Authors: Zanon Mirko , Potrich Davide , Bortot Maria , Vallortigara Giorgio
Published: March 2021

Several studies have suggested that vertebrate and invertebrate species may possess anumber sense, i.e. an ability to process in a non-symbolic and non-verbal way the numerousness of a set of items. However, this hypothesis has been challenged by the presence of other non-numerical continuous physical variables, that vary along with numerosity (e.g. any change in the number of visual physical elements in a set naturally involves a related change in visual features such as area, density, contour length and convex hull of the stimulus). It is therefore necessary to control and manipulate the continuous physical information when investigating the ability of humans and other animals to perceive numerousness. During decades of research, different methods have been implemented in order to address this issue, which has implications for experiments replicability and inter-species comparisons, since no general standardized procedure is currently being used. Here we present the “Generation of Numerical Elements Images Software” (GeNEsIS) for the creation of non-symbolic numerical arrays in a standardized and user-friendly environment. The main aim of this tool would be to provide researchers in the field of numerical cognition with a manageable and precise instrument to produce visual numerical arrays controlled for all the continuous variables; additionally, we implemented the possibility to actively guide stimuli presentation during habituation/dishabituation and dual-choice comparison tasks used in human and comparative research.
PyADM1: a Python implementation of Anaerobic Digestion Model No. 1
Authors: Sadrimajd P. , Mannion P. , Howley E. , Lens P. N. L.
Published: March 2021

Anaerobic Digestion (AD) is a waste treatment technology widely used for wastewater and solid waste treatment, with the advantage of being a source of renewable energy in the form of biogas. Anaerobic digestion model number 1 (ADM1) is the most common mathematical model available for AD modelling. Commercial software implementations of ADM1 are available but have limited flexibility and availability due to the closed sources and licensing fees. Python is the fastest growing programming language and is open source freely available. Python implementation of ADM1 makes this AD model available to the mass user base of the Python ecosystem and it’s libraries. The open easy to use implementation in PyADM1 makes it more accessible and provides possibilities for flexible direct use of the model linked to other software, e.g. machine learning libraries or Linux operating system on embedded hardware.
LncRNA analyses reveal increased levels of non-coding centromeric transcripts in hepatocellular carcinoma
Authors: Necsulea Anamaria , Veber Philippe , Boldanova Tuyana , Ng Charlotte K Y , Wieland Stefan , Heim Markus H
Published: March 2021

The search for new biomarkers and drug targets for hepatocellular carcinoma (HCC) has spurred an interest in long non-coding RNAs (lncRNAs), often proposed as oncogenes or tumor suppressors. Furthermore, lncRNA expression patterns can bring insights into the global de-regulation of cellular machineries in tumors. Here, we examine lncRNAs in a large HCC cohort, comprising RNA-seq data from paired tumor and adjacent tissue biopsies from 114 patients. We find that numerous lncRNAs are differentially expressed between tumors and adjacent tissues and between tumor progression stages. Although we find strong differential expression for most lncRNAs previously associated with HCC, the expression patterns of several prominent HCC-associated lncRNAs disagree with their previously proposed roles. We examine the genomic characteristics of HCC-expressed lncRNAs and reveal an enrichment for repetitive elements among the lncRNAs with the strongest expression increases in advanced-stage tumors. This enrichment is particularly striking for lncRNAs that overlap with satellite repeats, a major component of centromeres. Consistently, we find increased non-coding RNA transcription from centromeres in tumors, in the majority of patients, suggesting that aberrant centromere activation takes place in HCC.
Experimental tests of functional molecular regeneration via a standard framework for coordinating synthetic cell building
Authors: Wei Eric , Endy Drew
Published: March 2021

The construction of synthetic cells from lifeless ensembles of molecules is expected to require integration of hundreds of genetically-encoded functions whose collective capacities enable self-reproduction in simple environments. To date the regenerative capacities of various life-essential functions tend to be evaluated on an ad hoc basis, with only a handful of functions tested at once and only successful results typically reported. Here, we develop a framework for systematically evaluating the capacity of a system to remake itself. Using the cell-free Protein synthesis Using Recombinant Elements (PURE) as a model system we apply our framework to evaluate the capacity of PURE, whose composition is completely known, to remake 36 life-essential functions. We find that only 23 of the components can be well tested and that only 19 of the 23 can be remade by the system itself; translation release factors remade by PURE are not fully functional. From both a qualitative and quantitative perspective PURE alone cannot remake PURE. We represent our findings via a standard visual form we call the Pureiodic Table that serves as a tool for tracking which life-essential functions can work together in remaking one another and what functions remain to be remade. We curate and represent all available data to create an expanded Pureiodic Table in support of collective coordination among ongoing but independent synthetic cell building efforts. The history of science and technology teaches us that how we organize ourselves will impact how we organize our cells, and vice versa.
Modulation of tactile feedback for the execution of dexterous movement
Authors: Conner James M. , Bohannon Andrew , Igarashi Masakazu , Taniguchi James , Baltar Nicholas , Azim Eiman
Published: March 2021

While dexterity relies on the constant transmission of sensory information, unchecked feedback can be disruptive to behavior. Yet how somatosensory feedback from the hands is regulated as it first enters the brain, and whether this modulation exerts any influence on movement, remain unclear. Leveraging molecular-genetic access in mice, we find that tactile afferents from the hand recruit neurons in the brainstem cuneate nucleus whose activity is modulated by distinct classes of local inhibitory neurons. Selective manipulation of these inhibitory circuits can suppress or enhance the transmission of tactile information, affecting behaviors that rely on movement of the hands. Investigating whether these local circuits are subject to top-down control, we identify distinct descending cortical pathways that innervate cuneate in a complementary pattern. Somatosensory cortical neurons target the core tactile region of cuneate, while a large rostral cortical population drives feed-forward inhibition of tactile transmission through an inhibitory shell. These findings identify a circuit basis for tactile feedback modulation, enabling the effective execution of dexterous movement.
Detection of ESKAPE pathogens andClostridioides difficilein Simulated Skin Transmission Events with Metagenomic and Metatranscriptomic Sequencing
Authors: Ternus Krista L. , Keplinger Nicolette C. , Kappell Anthony D. , Godbold Gene D. , Palsikar Veena , Acevedo Carlos A. , Weber Katharina L. , LeSassier Danielle S. , Schulte Kathleen Q. , Westfall Nicole M. , Hewitt F. Curtis
Published: March 2021

1

Background

Antimicrobial resistance is a significant global threat, posing major public health risks and economic costs to healthcare systems. Bacterial cultures are typically used to diagnose healthcare-acquired infections (HAI); however, culture-dependent methods provide limited presence/absence information and are not applicable to all pathogens. Next generation sequencing (NGS) has the capacity to detect a wide variety of pathogens, virulence elements, and antimicrobial resistance (AMR) signatures in healthcare settings without the need for culturing, but few research studies have explored how NGS could be used to detect viable human pathogen transmission events under different HAI-relevant scenarios.

Methods

The objective of this project was to assess the capability of NGS-based methods to detect the direct and indirect transmission of high priority healthcare-related pathogens. DNA was extracted and sequenced from a previously published study exploring pathogen transfer with simulated skin containing background microorganisms, which allowed for complementary culture and metagenomic analysis comparisons. RNA was also isolated from an additional set of samples to evaluate metatranscriptomic analysis methods at different concentrations.

Results

Using various analysis methods and custom reference databases, both pathogenic and non-pathogenic members of the microbial community were taxonomically identified. Virulence and AMR genes known to reside within the community were also routinely detected. Ultimately, pathogen abundance within the overall microbial community played the largest role in successful taxonomic classification and gene identification.

Conclusions

These results illustrate the utility of metagenomic analysis in clinical settings or for epidemiological studies, but also highlight the limits associated with the detection and characterization of pathogens at low abundance in a microbial community.
A vesicle microrheometer for high-throughput viscosity measurements of lipid and polymer membranes
Authors: Faizi Hammad A. , Dimova Rumiana , Vlahovska Petia
Published: March 2021

Viscosity is a key property of cell membranes that controls mobility of embedded proteins and membrane remodeling. Measuring it is challenging because existing approaches involve complex experimental designs and/or models, and the applicability of some is limited to speciﬁc systems and membrane compositions. As a result there is scarcity of data and the reported values for membrane viscosity vary by orders of magnitude for the same system. Here, we show how viscosity of bilayer membranes can be obtained from the transient deformation of giant unilamellar vesicles. The approach enables a non-invasive, probe-independent and high-throughput measurement of the viscosity of bilayers made of lipids or polymers with a wide range of compositions and phase state. Pure lipid and single-phase mixed bilayers are found to behave as Newtonian ﬂuids with strain-rate independent viscosity, while phase-separated and diblock-copolymers systems exhibit shear-thinning in the explored range of strain rates 1-2000 s−1. The results also reveal that electrically polarized bilayers can be signiﬁcantly more viscous than charge-neutral bilayers. These ﬁndings suggest that biomembrane viscosity is a dynamic property that can be actively modulated not only by composition but also by membrane polarization, e.g., as in action potentials.
Identification and characterization of novel plasma proteins in drug resistant HIV/AIDS patients by SWATH-MS
Authors: Barik Sushanta Kumar , Tripathy Srikanth Prasad , Bisht Deepa , Singh Praveen , Chakraborty Rahul , Chadar Monu Kumar , Patil Shripad A , Singh Tej Pal , Tandon Rekha , Jena Srikanta , Mohanty Keshar Kunja
Published: March 2021

Background and Objectives

Acquired immunodeficiency syndrome is one of the most important diseases caused by human immunodeficiency virus. Understanding its molecular pathogenesis is essential to manage the disease at the population level. In this study, a quantitative analysis of plasma proteins was carried out in drug resistant and drug respondent patients using the SWATH-MS.

Methods

Sequential window acquisition of all theoretical mass spectra (SWATH-MS) is a prime technique to seek the key plasma proteins involved in virus replication and drug metabolism during therapy.

Results

In total, 204 proteins were identified and quantified, 57 proteins were differentially expressed, 25 proteins were down regulated and 32 proteins were upregulated in drug resistant patients. Six proteins such as complement C4-A, immunoglobulin heavy variable 1-2, carboxylic ester hydrolase, fibulin-1, immunoglobulin lambda constant 7, secreted phosphoprotein 24 were statistically expressed in drug resistant patients compared to the drug respondent patients. Gene ontology study and protein-protein interaction networks were established in six statistically significant differentially expressed proteins of the drug resistant patients.

Interpretation and Conclusion

Our findings high lights the novel proteins that were differentially expressed in drug resistant patients. A label-free quantitative proteomics method for depleted human plasma samples by SWATH-MS that can be useful in plasma proteomics research in any biological system.
Canopy Volume as a Tool for Early Detection of Plant Drought and Fertilization Stress: Banana plant fine-phenotype
Authors: Brook Anna , Tal Yasmin , Markovich Oshry , Rybnikova Nataliya
Published: March 2021

Irrigation and fertilization stress in plants are limitations for securing global food production. Sustainable agriculture is at the heart of global goals because threats of a rapidly growing population and climate changes are affecting agricultural productivity. Plant phenotyping is defined as evaluating plant traits. Traditionally, this measurement is performed manually but with advanced technology and analysis, these traits can be observed automatically and nondestructively. A high correlation between plant traits, growth, biomass, and final yield has been found. From the early stages of plant development, lack of irrigation and fertilization directly influence developing stages, thus the final crop yield is significantly reduced. In order to evaluate drought and fertilization stress, plant height, as a morphological trait, is the most common one used in precision-agriculture research. The present study shows that three-dimension volumetric approaches are more representative markers for alerting growers to the early stages of stress in young banana plants’ for fine-scale phenotyping. This research demonstrates two different group conditions: 1) Normal conditions; and 2) zero irrigation and zero fertilization. The statistical analysis results show a successfully distinguished early stress with the volumetric traits providing new insights on identifying the key phenotypes and growth stages influenced by drought stress.
Three PilZ domain proteins, PlpA, PixA and PixB, have distinct functions in regulation of motility and development inMyxococcus xanthus
Authors: Kuzmich Sofya , Skotnicka Dorota , Szadkowski Dobromir , Klos Philipp , Pérez-Burgos María , Schander Eugenia , Schumacher Dominik , Søgaard-Andersen Lotte
Published: March 2021

In bacteria, the nucleotide-based second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) binds to effectors to generate outputs in response to changes in the environment. InMyxococcus xanthus, c-di-GMP regulates type IV pili-dependent motility and the starvation-induced developmental program that results in the formation of spore-filled fruiting bodies; however, little is known about the effectors that bind c-di-GMP. Here, we systematically inactivated all 24 genes encoding PilZ domain-containing proteins, which are among the most common c-di-GMP receptors. We confirm that PlpA, a stand-alone PilZ-domain protein, is specifically important for motility and that Pkn1, which is composed of a Ser/Thr domain and a PilZ domain, is specifically important for development. Moreover, we identify two PilZ-domain proteins that have distinct functions in regulating motility and development. PixB, which is composed of two PilZ domains and an acetyltransferase domain, binds c-di-GMPin vitroand regulates type IV pili-dependent and gliding motility upstream of the Frz chemosensory system as well as development. The acetyltransferase domain is required and sufficient for function during growth while all three domains and c-di-GMP binding are essential for PixB function during development. PixA is a response regulator composed of a PilZ domain and a receiver domain, binds c-di-GMPin vitro, and regulates motility downstream of the Frz chemosensory system by setting up the polarity of the two motility systems. Our results support a model whereby the three proteins PlpA, PixA and PixB act in parallel pathways and have distinct functions to regulation of motility.

Importance

c-di-GMP signaling controls bacterial motility in many bacterial species by binding to downstream effector proteins. Here, we identify two PilZ domain-containing proteins inMyxococcus xanthusthat bind c-di-GMP. We show that PixB, which contains two PilZ domains and an acetyltransferase domain, acts upstream of the Frz chemosensory system to regulate motility via the acetyltransferase domain while the intact protein and c-di-GMP binding are essential for PixB to support development. By contrast, PixA acts downstream of the Frz system to regulate motility. Together with previous observations, we conclude that PilZ-domain proteins and c-di-GMP act in multiple parallel pathways to regulate motility and development inM. xanthus.
TRAIT2D: a Software for Quantitative Analysis of Single Particle Diffusion Data
Authors: Reina Francesco , Wigg John M. A. , Dmitrieva Mariia , Lefebvre Joёl , Rittscher Jens , Eggeling Christian
Published: March 2021

Single Particle Tracking (SPT) is one of the most widespread techniques to evaluate particle mobility in a variety of situations, such as in cellular and model membrane dynamics. The proposed TRAIT2D Python library is developed to provide object tracking, trajectory analysis and produce simulated datasets with graphical user interface. The tool allows advanced users to customise the analysis to their requirements.

Availability and implementation: the software has been coded in Python, and can be accessed from:https://github.com/Eggeling-Lab-Microscope-Software/TRAIT2D, or the pypi and condaforge repositories.

A comprehensive user guide is provided athttps://eggeling-lab-microscope-software.github.io/TRAIT2D/.
Ex vivomass cytometry analysis reveals a profound myeloid proinflammatory signature in psoriatic arthritis synovial fluid
Authors: Yager Nicole , Cole Suzanne , Lara Alicia Lledo , Maroof Ash , Penkava Frank , Knight Julian , Bowness Paul , Al-Mossawi Hussein
Published: March 2021

Objectives

A number of immune populations have been implicated in psoriatic arthritis (PsA) pathogenesis. This study used mass cytometry (CyTOF) combined with transcriptomic analysis to generate a high-dimensional dataset of matched PsA synovial fluid (SF) and blood leucocytes, with the aim of identifying cytokine productionex vivoin unstimulated lymphoid and myeloid cells.

Methods

Fresh SF and paired blood were either fixed or incubated with protein transport inhibitors for 6 h. Samples were stained with two CyTOF panels: a phenotyping panel and an intracellular panel, including antibodies to both T cell and myeloid cell secreted proteins. Transcriptomic analysis by gene array of key expanded cell populations and single-cell RNA-seq, and ELISA and LEGENDplex analysis of PsA SF were also performed.

Results

We observed marked changes in the myeloid compartment of PsA SF relative to blood, with expansion of intermediate monocytes, macrophages and dendritic cell populations. Classical monocytes, intermediate monocytes and macrophages spontaneously produced significant levels of the proinflammatory mediators osteopontin and CCL2 in the absence of anyin vitrostimulation. By contrast minimal spontaneous cytokine production by T cells was detected. Gene expression analysis showed the genes for osteopontin and CCL2 to be amongst those most highly upregulated by PsA monocytes/macrophages; and both proteins were elevated in PsA SF.

Conclusions

Using multiomic analyses we have generated a comprehensive cellular map of PsA SF and blood to reveal key expanded myeloid proinflammatory modules in PsA of potential pathogenic and therapeutic importance.
Long runs of homozygosity are correlated with marriage preferences across global population samples
Authors: Sahoo Samali Anova , Zaidi Arslan A. , Anagol Santosh , Mathieson Iain
Published: March 2021

Children of consanguineous unions carry long runs of homozygosity (ROH) in their genomes, due to their parents’ recent shared ancestry. This increases the burden of recessive disease in populations with high levels of consanguinity and has been heavily studied in some groups. However, there has been little investigation of the broader effect of consanguinity on patterns of genetic variation on a global scale. Here, we collect published genetic data and information about marriage practices from 396 worldwide populations and show that preference for cousin marriage has a detectable effect on the distribution of long ROH in these samples, increasing the expected number of ROH longer than 10Mb by a factor of 1.5 (P=2.3 × 10−4). Variation in marriage practice and consequent rates of consanguinity is therefore an important aspect of demographic history for the purposes of modeling human genetic variation. However, marriage practices explain a relatively small proportion of the variation in ROH distribution and consequently the ability to predict marriage practices from population genetic samples (for example of ancient populations) is limited.
Projecting climate-driven shifts in demersal fish habitat in Iceland’s waters
Authors: Mason Julia G. , Woods Pamela J. , Thorlacius Magnús , Guðnason Kristinn , Saba Vincent S. , Sullivan Patrick J. , Kleisner Kristin M.
Published: March 2021

As climate change shifts marine species distribution and abundance worldwide, projecting local changes over decadal scales may be a valuable adaptive strategy for managers and industry. In Iceland, one of the top fish-producing nations in the world, long-term monitoring enables model simulations of groundfish species habitat distribution. We used generalized additive models to characterize suitable thermal habitat for 47 fish species in Iceland’s waters. We then projected changes in thermal habitat by midcentury with an ensemble of five general circulation models from the Coupled Model Intercomparison Program 6 (CMIP6) and NOAA (CM2.6) and two scenarios (SSP 5-8.5 and SSP 2-4.5). We find a general northward shift in centroids of habitat distribution, with variable regional dynamics among species. Species thermal affinity was the most significant predictor of future habitat change, with warmer-water species more likely to see projected increases in suitable habitat. We present spatially explicit habitat change projections for commercially and culturally important species. These projections might serve as guideposts to inform long-term management decisions about regional and species-specific suitability for Iceland’s fisheries, infrastructure investment, and risk evaluation under climate change.
Diffusion barriers and adaptive carbon uptake strategies enhance the modeled performance of the algal CO2-concentrating mechanism
Authors: Fei Chenyi , Wilson Alexandra T. , Mangan Niall M. , Wingreen Ned S. , Jonikas Martin C.
Published: March 2021

Many photosynthetic organisms enhance the performance of their CO2-fixing enzyme Rubisco by operating a CO2-concentrating mechanism (CCM). Most CCMs in eukaryotic algae supply concentrated CO2to Rubisco in an organelle called the pyrenoid. Ongoing efforts seek to engineer an algal CCM into crops that lack a CCM to increase yields. To advance our basic understanding of the algal CCM, we develop a chloroplast-scale reaction-diffusion model to analyze the efficacy and the energy efficiency of the CCM in the green algaChlamydomonas reinhardtii. We show that achieving an effective and energetically efficient CCM requires a physical barrier such as thylakoid stacks or a starch sheath to reduce CO2leakage out of the pyrenoid matrix. Our model provides insights into the relative performance of two distinct inorganic carbon uptake strategies: at air-level CO2, a CCM can operate effectively by taking up passively diffusing external CO2and catalyzing its conversion to HCO3−, which is then trapped in the chloroplast; however, at lower external CO2levels, effective CO2concentration requires active import of HCO3−. We also find that proper localization of carbonic anhydrases can reduce futile carbon cycling between CO2and HCO3−, thus enhancing CCM performance. We propose a four-step engineering path that increases predicted CO2saturation of Rubisco up to seven-fold at a theoretical cost of only 1.5 ATP per CO2fixed. Our system-level analysis establishes biophysical principles underlying the CCM that are broadly applicable to other algae and provides a framework to guide efforts to engineer an algal CCM into land plants.

Significance Statement

Eukaryotic algae mediate approximately one-third of CO2fixation in the global carbon cycle. Many algae enhance their CO2-fixing ability by operating a CO2-concentrating mechanism (CCM). Our model of the algal CCM lays a solid biophysical groundwork for understanding its operation. The model’s consistency with experimental observations supports existing hypotheses about the operating principles of the algal CCM and the functions of its component proteins. We provide a quantitative estimate of the CCM’s energy efficiency and compare the performance of two distinct CO2assimilation strategies under varied conditions. The model offers a quantitative framework to guide the engineering of an algal CCM into land plants and supports the feasibility of this endeavor.
An in-frame deletion mutation in the degron tail of auxin co-receptorIAA2confers resistance to the herbicide 2,4-D inSisymbrium orientale
Authors: de Figueiredo Marcelo R. A. , Küpper Anita , Malone Jenna M. , Petrovic Tijana , de Figueiredo Ana Beatriz T. B. , Campagnola Grace , Peersen Olve B. , Prasad Kasavajhala V.S.K. , Patterson Eric L. , Reddy Anireddy S.N. , Kubeš Martin F. , Napier Richard , Preston Christopher , Gaines Todd A.
Published: March 2021

The natural auxin indole-3-acetic acid (IAA) is a key regulator of many aspects of plant growth and development. Synthetic auxin herbicides mimic the effects of IAA by inducing strong auxinic signaling responses in plants. Synthetic auxins are crucial herbicides in agriculture, made more important by the recent introduction of transgenic synthetic auxin resistant soybean and cotton. Currently, 41 weed species have evolved resistance to synthetic auxin herbicides and, in all but one case, the molecular basis of these resistance mechanisms is unknown. To determine the mechanism of 2,4-D resistance in aSisymbrium orientale(Indian hedge mustard) weed population, we performed a transcriptome analysis of 2,4-D-resistant (R) and-susceptible (S) genotypes that revealed an in-frame 27-nucleotide deletion removing 9 amino acids in the degron tail (DT) of the auxin co-receptor Aux/IAA2(SoIAA2).The deletion allele co-segregated with 2,4-D resistance in recombinant inbred lines. Further, this deletion was also detected in several 2,4-D resistant field populations of this species. Arabidopsis transgenic lines expressing theSoIAA2mutant allele were resistant to 2,4-D and dicamba. The IAA2-DT deletion reduced binding to TIR1in vitrowith both natural and synthetic auxins, causing reduced association and increased dissociation rates. This novel mechanism of synthetic auxin herbicide resistance assigns a newin plantafunction to the DT region of this Aux/IAA co-receptor for its role in synthetic auxin binding kinetics and reveals a potential biotechnological approach to produce synthetic auxin resistant crops using gene editing.
Characterization of theChlamydomonas reinhardtiiphycosphere reveals conserved features of the plant microbiota
Authors: Durán Paloma , Flores-Uribe José , Wippel Kathrin , Zhang Pengfan , Guan Rui , Garrido-Oter Ruben
Published: March 2021

Microscopic algae release organic compounds to the region immediately surrounding their cells, known as the phycosphere, constituting a niche for colonization by heterotrophic bacteria. These bacteria take up algal photoassimilates and provide beneficial functions to their host, in a process that resembles the establishment of microbial communities associated with the roots and rhizospheres of land plants. Here, we characterize the microbiota of the model algaChlamydomonas reinhardtiiand reveal extensive taxonomic and functional overlap with the root microbiota of land plants. Reconstitution experiments using synthetic communities derived fromC. reinhardtiiandArabidopsis thalianashow that phycosphere and root bacteria assemble into taxonomically equivalent communities on either host. We show that provision of diffusible metabolites is not sufficient for phycosphere community establishment, which additionally requires physical proximity to the host. Our data suggests that the microbiota of photosynthetic organisms, including green algae and flowering plants, assembles according to core ecological principles.
Elevation of TRPV1 expression on T cells during experimental immunosuppression
Authors: Kumar P Sanjai , Mukherjee Tathagata , Khamaru Somlata , Radhakrishnan Anukrishna , Kishore Dalai Jupiter Nanda , Chawla Saurabh , Sahoo Subhransu Sekhar , Chattopadhyay Subhasis
Published: March 2021

An intracellular rise in calcium (Ca2+) is an essential requisite underlying T cell activation and its associated pro-inflammatory cytokine production. Transient receptor potential vanilloid channel (TRPV1) is a thermo-sensitive, polymodal gated and permeable to cations such as Ca2+. It has been reported that TRPV1 expression increases during T cell activation. However, the possible involvement of TRPV1 during immunosuppression of T cells has not been studied yet. Here, we investigated the possible role of TRPV1 in FK506 or B16F10-culture supernatant (B16F10-CS) driven experimental immunosuppression in T cells. Intriguingly, it was found that TRPV1 expression is further elevated during immunosuppression compared to ConA or TCR activated T cells. Similarly, in B16F10 tumor-bearing mice, the TRPV1 expression was upregulated in T cells as compared to control mice,in vivo. Moreover, we observed an immediate rise in intracellular Ca2+levels in FK506 and B16F10-CS treated T cells as compared to ConA or TCR treated T cells. Likewise, in B16F10 tumor-bearing mice, the basal intracellular calcium level was upregulated in T cells as compared to control mice,in vivo. To further investigate the possible mechanism of such rise in intracellular Ca2+levels, TRPV1 specific functional inhibitor, 5 -iodoresiniferatoxin (5 -IRTX) was used in calcium influx studies. It was observed that the total intracellular Ca2+levels decreased significantly in presence of 5 -IRTX for either the FK506 or B16F10-CS as well as with ConA or TCR stimulated T cells, indicating the functional role of TRPV1 channels in FK506 or B16F10-CS mediated increase in intracellular Ca2+levels. The current findings highlight an essential role of the TRPV1 channel in upregulating intracellular calcium levels during both immune-activation and immunosuppression. This study might also have broad implications in the context of other immune-suppressive diseases as well.