bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiological and cognitive consequences of a daily 26 h photoperiod in a primate:exploring the underlying mechanisms of the circadian resonance theory
Authors: Hozer Clara , Pifferi Fabien
Published: July 2020

The biological clock expresses circadian rhythms, whose endogenous period (tau) is close to 24 h. Daily resetting of the circadian clock to the 24 h natural photoperiod might induce marginal costs that would accumulate over time and forward affect fitness. It was proposed as the circadian resonance theory. For the first time, we aimed to evaluate these physiological and cognitive costs that would partially explain the mechanisms of the circadian resonance hypothesis. We evaluated the potential costs of imposing a 26 h photoperiodic regimen compared to the classical 24 h entrainment measuring several physiological and cognitive parameters (body temperature, energetic expenditure, oxidative stress, cognitive performances) in males of a non-human primate (Microcebus murinus), a nocturnal species whose endogenous period is about 23.5 h. We found significant higher resting body temperature and energy expenditure and lower cognitive performances when the photoperiodic cycle length was 26 h. Together these results suggest that a great deviation of external cycles from tau leads to daily greater energetic expenditure, and lower cognitive capacities. To our knowledge, this study is the first to highlight potential mechanisms of circadian resonance theory.
Age influences the thermal suitability of
Plasmodium falciparum
transmission in the Asian malaria vector
Anopheles stephensi
Authors: Miazgowicz K. L. , Shocket M. S. , Ryan S. J. , Villena O. C. , Hall R. J. , Owen J. , Adanlawo T. , Balaji K. , Johnson L. R. , Mordecai E. A. , Murdock C. C.
Published: July 2020

Models predicting disease transmission are vital tools for long-term planning of malaria reduction efforts, particularly for mitigating impacts of climate change. We compared temperature-dependent malaria transmission models when mosquito life-history traits were estimated from a truncated portion of the lifespan (a common practice) versus traits measured across the full lifespan. We conducted an experiment on adult female
Anopheles stephensi
, the Asian urban malaria mosquito, to generate daily per capita values for mortality, egg production and biting rate at six constant temperatures. Both temperature and age significantly affected trait values. Further, we found quantitative and qualitative differences between temperature–trait relationships estimated from truncated data versus observed lifetime values. Incorporating these temperature–trait relationships into an expression governing the thermal suitability of transmission, relative
R
0
(
T
), resulted in minor differences in the breadth of suitable temperatures for
Plasmodium falciparum
transmission between the two models constructed from only
An. stephensi
trait data. However, we found a substantial increase in thermal niche breadth compared with a previously published model consisting of trait data from multiple
Anopheles
mosquito species. Overall, this work highlights the importance of considering how mosquito trait values vary with mosquito age and mosquito species when generating temperature-based suitability predictions of transmission.
Perfect mimicry between
Heliconius
butterflies is constrained by genetics and development
Authors: Van Belleghem Steven M. , Alicea Roman Paola A. , Carbia Gutierrez Heriberto , Counterman Brian A. , Papa Riccardo
Published: July 2020

Müllerian mimicry strongly exemplifies the power of natural selection. However, the exact measure of such adaptive phenotypic convergence and the possible causes of its imperfection often remain unidentified. Here, we first quantify wing colour pattern differences in the forewing region of 14 co-mimetic colour pattern morphs of the butterfly species
Heliconius erato
and
Heliconius melpomene
and measure the extent to which mimicking colour pattern morphs are not perfectly identical. Next, using gene-editing CRISPR/Cas9 KO experiments of the gene
WntA
, which has been mapped to colour pattern diversity in these butterflies, we explore the exact areas of the wings in which
WntA
affects colour pattern formation differently in
H. erato
and
H. melpomene.
We find that, while the relative size of the forewing pattern is generally nearly identical between co-mimics, the CRISPR/Cas9 KO results highlight divergent boundaries in the wing that prevent the co-mimics from achieving perfect mimicry. We suggest that this mismatch may be explained by divergence in the gene regulatory network that defines wing colour patterning in both species, thus constraining morphological evolution even between closely related species.
Sphaerochaeta halotolerans sp. nov., a novel spherical halotolerant spirochete from a Russian heavy oil reservoir, emended description of the genus Sphaerochaeta, reclassification of Sphaerochaeta coccoides to a new genus Parasphaerochaeta gen. nov. as Parasphaerochaeta coccoides comb. nov. and proposal of Sphaerochaetaceae fam. nov.
Authors: Bidzhieva Salimat Kh. , Sokolova Diyana Sh. , Grouzdev Denis S. , Kostrikina Nadezhda A. , Poltaraus Andrey B. , Tourova Tatyana P. , Shcherbakova Viktoria A. , Troshina Olga Yu. , Nazina Tamara N.
Published: July 2020

Anaerobic, fermentative, halotolerant bacteria, strains 4-11Tand 585, were isolated from production water of two low-temperature petroleum reservoirs (Russia) and were characterized by using a polyphasic approach. Cells of the strains were spherical, non-motile and 0.30–2.5 µm in diameter. Strain 4-11Tgrew optimally at 35 °C, pH 6.0 and 1.0–2.0% (w/v) NaCl. Both strains grew chemoorganotrophically with mono-, di- and trisaccharides. The major cellular fatty acids of both strains were C14:0, C16:0, C16:1ω9 and C18:03-OH. Major polar lipids were glycolipids and phospholipids. The 16S rRNA gene sequences of the strains 4-11Tand 585 had 99.9% similarity and were most closely related to the sequence ofSphaerochaeta associataGLS2T(96.9, and 97.0% similarity, respectively). The G+C content of the genomic DNA of strains 4-11Tand 585 were 46.8 and 46.9%, respectively. The average nucleotide identity and digital DNA–DNA hybridization values between the genomes of strain 4-11TandS. associataGLS2Twere 73.0 and 16.9%, respectively. Results of phylogenomic metrics analysis of the genomes and 120 core proteins of strains 4-11Tand 585 and their physiological and biochemical characteristics confirmed that the strains represented a novel species of the genusSphaerochaeta, for which the nameSphaerochaeta halotoleranssp. nov. is proposed, with the type strain 4-11T(=VKM B-3269T=KCTC 15833T). Based on the results of phylogenetic analysis,Sphaerochaeta coccoideswas reclassified as member of a new genusParasphaerochaetagen. nov.,Parasphaerochaeta coccoidescomb. nov. The generaSphaerochaetaandParasphaerochaetaform a separate clade, for which a novel family,Sphaerochaetaceaefam. nov., is proposed.
Circulating Microparticles are increased amongst people presenting with HIV and advanced immune suppression in Malawi and correlate closely with arterial stiffness
Authors: Kelly C , Gurung R , Tinago W , Kamngona R , Sheha I , Chammudzi M , Jambo K , Mallewa J , Rapala A , Heyderman RS , Mallon PWG , Mwandumba H , Khoo S , Klein N
Published: July 2020

Objectives

We aim to investigate whether circulating microparticle (CMPs) subsets were raised amongst people presenting with HIV and advanced immune suppression in Malawi, and whether they associated with arterial stiffness.

Methods

ART-naïve adults with a new HIV diagnosis and CD4 <100 cells/µL had microparticle characterisation and carotid femoral Pulse Wave Velocity (cfPWV) at 2 weeks post ART initiation. HIV uninfected controls were matched on age, systolic BP and diastolic BP in a 1:1 ratio. Circulating microparticles were identified from platelet poor plasma and stained for endothelial, leucocyte, monocyte and platelet markers.

Results

The median (IQ) total CMP count was 1 log higher in participants with HIV compared to those without (p<0.0001) and was associated with arterial stiffness (spearman rho 0.47, p<0.001). In adjusted analysis, every log increase in circulating particles showed a 20% increase in cfPWV (95% CI 4 – 40%, p=0.02).

In terms of subsets, endothelial and platelet derived microparticles were most strongly associated with HIV. Endothelial derived E-selectin+ CMPs were 1.3log-fold higher and platelet derived CD42a+ CMPs were 1.4log-fold higher (both p<0.0001). Endothelial and platelet derived CMPs also correlated most closely with arterial stiffness [spearman rho: E-selectin+ 0.57 and CD42a 0.56, both p<0.0001).

Conclusions

Circulating microparticles associate strongly with arterial stiffness among PLWH in Malawi. Endothelial damage and platelet activation are of particular importance and future translational studies should consider prioritising this pathway.
Assessing the relative contributions of healthcare protocols for epidemic control: an example with network transmission model for COVID-19
Authors: Tenório Baumgartner Matheus , Lansac-Tôha Fernando Miranda
Published: July 2020

The increasing number of COVID-19 cases threatens human life and requires retainment actions that control the spread of the virus in the absence of effective medical therapy or a reliable vaccine. There is a general consensus that the most efficient health protocol in the actual state is to disrupt the infection chain through social distancing, although economic interests stand against closing non-essential activities and poses a debatable tradeoff. In this study, we used an individual-based age-structured network model to assess the effective roles of different healthcare protocols such as the use of personal protection equipment and social distancing at neighbor- and city-level scales. Using as much as empirical data available in the literature, we calibrated a city model and simulated low, medium, and high parameters representing these protocols. Our results revealed that the model was more sensitive to changes in the parameter representing the rate of contact among people from different neighborhoods, which defends the social distancing at the city-level as the most effective protocol for the control of the disease outbreak. Another important identified parameter represented the use of individual equipment such as masks, face shields, and hand sanitizers like alcohol-based solutions and antiseptic products. Interestingly, our simulations suggest that some periodical activities such as going to the supermarket, gas station, and pharmacy would have little contribution to the SARS-CoV-2 spread once performed within the same neighborhood. As we can see nowadays, there is an inevitable context-dependency and economic pressure on the level of social distancing recommendations, and we reinforce that every decision must be a welfare-oriented science-based decision.
HIV coinfection is associated with low fitnessrpoBvariants in rifampicin-resistantMycobacterium tuberculosis
Authors: Loiseau Chloé , Brites Daniela , Reinhard Miriam , Zürcher Kathrin , Borrell Sonia , Ballif Marie , Fenner Lukas , Cox Helen , Rutaihwa Liliana K. , Wilkinson Robert J. , Yotebieng Marcel , Carter E Jane , Abimiku Alash’le , Marcy Olivier , Gotuzzo Eduardo , Avihingsanon Anchalee , Zetola Nicola , Doulla Basra , Böttger Erik C. , Egger Matthias , Gagneux Sebastien
Published: July 2020

We analysed 312 drug-resistant genomes ofMycobacterium tuberculosis (Mtb)collected from HIV coinfected and HIV negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistantMtbstrains isolated from HIV coinfected patients carried disproportionally more resistance-conferring mutations inrpoBthat are associated with a low fitness in the absence of the drug, suggesting these low fitnessrpoBvariants can thrive in the context of reduced host immunity.
Berberine Alleviates Adiposity and Cardiac Dysfunction in Offspring Exposed to Gestational Diabetes Mellitus
Authors: Cole Laura K. , Chen Li , Sparagna Genevieve C. , Vandel Marilyne , Xiang Bo , Dolinsky Vernon W. , Hatch Grant M.
Published: July 2020

The most robust risk factor for type 2 diabetes in childhood is prior exposure to diabetes during gestation. Currently, there are few evidence-based strategies to attenuate the of risk of metabolic syndrome in offspring exposed to gestational diabetes mellitus (GDM). Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese herbs and exhibits glucose lowering properties. It has been used safely for centuries in humans. Our objective was to determine whether BBR treatment improves health outcomes in the mouse offspring of GDM dams. Dams were fed either a lean low-fat diet (Lean, LF,10% kcal fat) or a GDM-inducing high-fat/high sucrose diet (GDM, HF, 45% kcal fat) prior to breeding and throughout pregnancy. The resulting Lean and GDM-exposed offspring were randomly assigned a LF, HF or HF diet containing BBR (160 mg/kg/d) for 12 weeks. We determined that BBR treatment significantly reduced body weight (∼20%), % body fat (∼40%) and gonadal fat pad mass (∼60%) compared to HF-fed GDM offspring. Furthermore, BBR treatment of HF-fed GDM offspring normalized insulin levels in the plasma and isolated pancreatic islets. Differences in food consumption did not contribute to altered body composition in BBR treated mice, as levels remained similar between experimental groups. Alternatively, BBR-treatment was associated with increased whole-body oxygen consumption (VO2), activity and heat production. Additionally, we determined that HF-fed GDM offspring developed a cardiomyopathy, characterized by increased isovolumetric contraction (∼150%, IVCT), relaxation time (∼70%, IVRT), elevated cardiac triglyceride (∼120%) and reduced mitochondrial function (30%, spare capacity) compared to LF fed Lean controls. BBR treatment normalized heart function, reduced triglyceride levels and maintained mitochondrial function. Our data supports BBR as a potential pharmacotherapeutic approach to improve health outcomes in individuals exposed to GDM.

Key Points Summary

Gestational diabetes mellitus is a common metabolic complication of pregnancy which is increasing worldwide due to the prevalence of obesity.

It is known that individuals exposed to gestational diabetes have elevated risk of developing metabolic syndrome however there are few evidence-based strategies which provide protection.

Berberine is a natural compound found in Chinese herbs which has been safely used for centuries to treat type 2 diabetes mellitus.

We determined that berberine treatment of offspring exposed to gestational diabetes attenuated weight gain, reduced insulin levels and normalized both heart and pancreatic function.

Our data supports berberine as a potential pharmacotherapeutic approach to improve health outcomes in individuals exposed to gestational diabetes.
MicrobeAnnotator: a user-friendly, comprehensive microbial genome annotation pipeline
Authors: Ruiz-Perez Carlos A. , Conrad Roth E. , Konstantinidis Konstantinos T.
Published: July 2020

High-throughput sequencing has increased the number of microbial genomes from isolates, single cells, and metagenomes available. To analyze and compare these genomes, fast and comprehensive annotation pipelines are needed. Although several approaches exist for genome annotation, these are typically not designed for easy incorporation into analysis pipelines, do not combine results from several annotation databases or offer easy-to-use summaries of metabolic reconstructions in a high-throughput mode. Here, we introduce MicrobeAnnotator, a fully automated pipeline for the comprehensive annotation of microbial genomes that combines results from several reference protein databases to reliably summarize the metabolic potential of the genomes based on KEGG modules.

Availability

MicrobeAnnotator is implemented in Python and is freely available under an open source Artistic Licence 2.0 fromhttps://github.com/cruizperez/MicrobeAnnotator

Contact

cruizperez3@gatech.edu;kostas@ce.gatech.edu
Accel-Align: A Fast Sequence Mapper and Aligner Based on the Seed–Embed–Extend Method
Authors: Yan Yiqing , Chaturvedi Nimisha , Appuswamy Raja
Published: July 2020

Background

Improvements in sequencing technology continue to drive sequencing cost towards $100 per genome. However, mapping sequenced data to a reference genome remains a computationally-intensive task due to the dependence on edit distance for dealing with indels and mismatches introduced by sequencing. All modern aligners use seed–filter–extend (SFE) methodology and rely on filtration heuristics to reduce the overhead of edit distance computation. However, filtering has inherent performance–accuracy trade-offs that limits its effectiveness.

Results

Motivated by algorithmic advances in randomized low-distortion embedding, we introduceseed– embed–extend(SEE), a new methodology for developing sequence mappers and aligners. While SFE focuses on eliminating sub-optimal candidates, SEE focuses instead on identifying optimal candidates. To do so, SEE transforms the read and reference strings from edit distance regime to the Hamming regime by embedding them using a randomized algorithm, and uses Hamming distance over the embedded set to identify optimal candidates. To show that SEE performs well in practice, we present Accel-Align, an SEE-based short-read sequence mapper and aligner that is 3-12×faster than state-of-the-art aligners on commodity CPUs, without any special-purpose hardware, while providing comparable accuracy.

Conclusions

As sequencing technologies continue to increase read length while improving throughput and accuracy, we believe that randomized embeddings open up new avenues for optimization that cannot be achieved by using edit distance. Thus, the techniques presented in this paper have a much broader scope as they can be used for other applications like graph alignment, multiple sequence alignment, and sequence assembly.

Availability

https://github.com/raja-appuswamy/accel-align-release
Spatio-temporal patterns of population responses in the visual cortex under Isoflurane: from wakefulness to loss of consciousness
Authors: Margalit Shany Nivinsky , Golomb Neta Gery , Tsur Omer , Raz Aeyal , Slovin Hamutal
Published: July 2020

Anesthetic drugs are widely used in medicine and research to mediate loss of consciousness (LOC). Despite the vast use of anesthesia, how LOC affects cortical sensory processing and the underlying neural circuitry, is not well understood. We measured neuronal population activity in the visual cortices of awake and isoflurane anesthetized mice and compared the visually evoked responses under different levels of consciousness. We used voltage-sensitive dye imaging (VSDI) to characterize the temporal and spatial properties of cortical responses to visual stimuli over a range of states from wakefulness to deep anesthesia. VSDI enabled measuring the neuronal population responses at high spatial (meso-scale) and temporal resolution from several visual regions (V1, extrastiate-lateral (ESL) and extrastiate-medial (ESM)) simultaneously. We found that isoflurane has multiple effects on the population evoked response that augmented with anesthetic depth, where the largest changes occurred at LOC. Isoflurane reduced the response amplitude and prolonged the latency of response in all areas. In addition, the intra-areal spatial spread of the visually evoked activity decreased. During visual stimulation, intra-areal and inter-areal correlation between neuronal populations decreased with increasing doses of isoflurane. Finally, while in V1 the majority of changes occurred at higher doses of isoflurane, higher visual areas showed marked changes at lower doses of isoflurane. In conclusion, our results demonstrate a reverse hierarchy shutdown of the visual cortices regions: low-dose isoflurane diminishes the visually evoked activity in higher visual areas before lower order areas and cause a reduction in inter-areal connectivity leading to a disconnected network.
Direct Photon-by-photon Analysis of Time-Resolved Pulsed Excitation Data using Bayesian Nonparametrics
Authors: Tavakoli Meysam , Jazani Sina , Sgouralis Ioannis , Heo Wooseok , Ishii Kunihiko , Tahara Tahei , Pressé Steve
Published: July 2020

Lifetimes of chemical species are typically estimated, across each illuminated spot of a sample, by either fitting time correlated single photon counting (TCSPC) decay histograms or, more recently, through phasor analysis from time-resolved photon arrivals. While both methods yield lifetimes in a computationally efficient manner, the performance of both methods is limited by the choices made when fitting a TCSPC histogram. In addition, phasor analysis also requires setting the number of chemical species by hand before lifetimes can be determined. Yet the number of species itself is encoded in the photon arrival times collected for each illuminated spot and need not be set by handa priori. Here we propose a direct photo-by-photon analysis of data drawn from pulsed excitation experiments to infer, simultaneously and self-consistently, the number of species and their associated lifetimes from as little as a few thousand photons for two species. We do so by leveraging new mathematical tools within the Bayesian nonparametric (BNP) paradigm that we have previously exploited in the analysis of single photon arrivals from single spot confocal microscopy. We benchmark our method on simulated as well as experimental data for one, two, three, and four species with data sets from both immobilized and freely diffusing molecules at the level of one illuminated spot.

Photon arrivals obtained from fluorescence experiments encode not only the lifetimes of chemical species but also the number of chemical species involved in the experiment. Traditional methods of analysis, such as phasor methods and methods relying on maximum likelihood or (parametric) Bayesian analysis of photon arrivals or photon arrival histograms of TCSPC data, must first ascertain the number of chemical species separately and, once specified, determine their associated lifetimes. Here we develop a method to learn the number of fluorescence species and their associated lifetimes simultaneously. We achieve this by exploiting Bayesian nonparametrics. We benchmark our approach on both simulated and experimental data for one species and mixtures of two to four species.
Basolateral amygdala to nucleus accumbens projections differentially mediate flexibility of sign- and goal-tracking rats
Authors: Kochli Daniel E. , Keefer Sara E. , Gyawali Utsav , Calu Donna J
Published: July 2020

Rats rely on communication between basolateral amygdala (BLA) and nucleus accumbens (NAc) to express lever directed approach in a Pavlovian lever autoshaping (PLA) task that distinguishes sign- and goal-tracking rats. While sign-tracking rats inflexibly respond to cues even after the associated outcome is devalued, goal-tracking rats flexibly suppress conditioned responding during outcome devaluation. Here, we sought to determine whether BLA-NAc communication in sign-trackers drives rigid appetitive approach that is insensitive to manipulations of outcome value. Using a contralateral chemogenetic inactivation design, we injected contralateral BLA and NAc core with inhibitory DREADD (hm4D-mcherry) or control (mcherry) constructs. To determine sign- and goal-tracking groups, we trained rats in five PLA sessions in which brief lever insertion predicts food pellet delivery. We sated rats on training pellets (devalued condition) or chow (valued condition) prior to systemic clozapine injections (0.1 mg/kg) to inactivate BLA and contralateral NAc during two outcome devaluation probe tests, in which we measured lever and foodcup approach. Contralateral BLA-NAc chemogenetic inactivation promoted flexible lever approach in sign-tracking rats, but disrupted flexible food-cup approach in goal-tracking rats. Consistent with a prior BLA-NAc disconnection lesion study, we find contralateral chemogenetic inactivation of BLA and NAc core reduces lever, but not foodcup approach in PLA. Together these findings suggest rigid appetitive associative encoding in BLA-NAc of sign-tracking rats hinders the expression of flexible behavior when outcome value changes.
Single cell RNA sequencing of blood antigen-presenting cells in severe Covid-19 reveals multi-process defects in antiviral immunity
Authors: Saichi Melissa , Ladjemi Maha Zohra , Korniotis Sarantis , Rousseau Christophe , Ait-Hamou Zakaria , Massenet Lucile , Amblard Elise , Noel Floriane , Marie Yannick , Bouteiller Delphine , Medvedovic Jasna , Pène Frédéric , Soumelis Vassili
Published: July 2020

COVID-19 can lead to life-threatening acute respiratory failure, characterized by simultaneous increase in inflammatory mediators and viral load. The underlying cellular and molecular mechanisms remain unclear. We performed single-cell RNA-sequencing to establish an exhaustive high-resolution map of blood antigen-presenting cells (APC) in 7 COVID-19 patients with moderate or severe pneumonia, at day-1 and day-4 post-admission, and two healthy donors. We generated a unique dataset of 31,513 high quality APC, including monocytes and rare dendritic cell (DC) subsets. We uncovered multiprocess and previously unrecognized defects in anti-viral immune defense in specific APC compartments from severe patients: i) increase of pro-apoptotic genes exclusively in pDC, which are key effectors of antiviral immunity, ii) sharp decrease of innate sensing receptors, TLR7 and DHX9, in pDC and cDC1, respectively, iii) down-regulation of antiviral effector molecules, including Interferon stimulated genes (ISG) in all monocyte subsets, and iv) decrease of MHC class II-related genes, and MHC class II transactivator (CIITA) activity in cDC2, suggesting a viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore defective immune defense.
Impact of COVID-19 on Public Research Recruitment
Authors: Hsieh Yichuan Grace , Parker Holly , Estey Greg , Lorenz Stephen , Wylie Mark , Zhang Xiaofeng , Lopiccolo Joseph , Clarke Lloyd , Chung Jeanhee
Published: July 2020

The coronavirus disease 2019 (COVID-19) pandemic created a major challenge for clinical trials recruitment as early attention was focused on matters of public health and clinical care, and research--outside of COVID-19-- essentially shut down. Rally with Partners (rally.partners.org), an Internet-based portal for clinical research volunteer recruitment, continued to support studies that continued their recruitment during this period and additionally, implemented several measures to support COVID-19 research. In this paper, we summarize our experiences and preliminary results.
Invasive pulmonary aspergillosis in critically ill patients with severe COVID-19 pneumonia: results from the prospective AspCOVID-19 study
Authors: Lahmer Tobias , Kriescher Silja , Herner Alexander , Rothe Kathrin , Spinner Christoph D. , Schneider Jochen , Mayer Ulrich , Neuenhahn Michael , Hoffmann Dieter , Geisler Fabian , Heim Markus , Schneider Gerhard , Schmid Roland M , Huber Wolfgang , Rasch Sebastian
Published: July 2020

Background

Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia.

Methods

We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from bronchial aspirates. We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls.

Findings

CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort.

In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p=0.340) and days of mechanical ventilation (20 versus 15 days; p=0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA.

Interpretation

CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.

Funding

None
Characterization ofPlasmodium falciparumNEDD8 and identification of cullins as its substrates
Authors: Bhattacharjee Manish , Adhikari Navin , Sudhakar Renu , Rizvi Zeba , Das Divya , Palanimurugan R , Sijwali Puran Singh
Published: July 2020

A variety of post-translational modifications ofPlasmodium falciparumproteins, including phosphorylation and ubiquitination, are shown to have key regulatory roles. The neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) is a ubiquitin-like modifier of cullin-RING E3 ubiquitin ligases, which regulate diverse cellular processes, including the cell-cycle. Although neddylation pathway is conserved in eukaryotes, it is yet to be characterized in Plasmodium and related apicomplexan parasites. Towards studying the neddylation pathway in malaria parasites, we characterizedP. falciparumNEDD8 (PfNEDD8) and identified cullins as its physiological substrates. PfNEDD8 is a 76 amino acid residue protein without the C-terminal tail, indicating that it can be readily conjugated. The wild type and mutant (Gly75Gly76 mutated to Ala75Ala76) PfNEDD8 were expressed inP. falciparum. Western blot of wild type PfNEDD8-expressing parasites indicated multiple high molecular weight conjugates, which were absent in the parasites expressing the mutant, indicating conjugation of NEDD8 to proteins through Gly76. Immunoprecipitation followed by mass spectrometry of wild type PfNEDD8-expressing parasites identified several proteins, including two putative cullins. Furthermore, we expressed PfNEDD8 in mutantS. cerevisiaestrains that lacked endogenous NEDD8 (Δrub1) or NEDD8 conjugating E2 enzyme (ΔUbc12). The western blot of complemented strains and mass spectrometry of PfNEDD8 immunoprecipitate showed conjugation of PfNEDD8 toS. cerevisiaecullin cdc53, demonstrating functional conservation and cullins as the physiological substrates of PfNEDD8. The characterization of PfNEDD8 and identification of cullins as its substrates make ground for investigation of specific roles and drug target potential of neddylation pathway in malaria parasites.
Plasma microRNAs as predictive biomarkers of liver fibrosis and cirrhosis in patients with HBV-associated disease
Authors: Wang Tie-Zheng , Lin Dong-Dong , Zhang Yong-Hong , Zhang Yue-Wei , Li Ning
Published: July 2020

Both pathogenesis and detection of liver fibrosis and early cirrhosis are elusive. Our study focused on role of microRNAs (miRNAs) as predictive biomarkers of liver fibrosis and early cirrhosis. Methods: We recruited patients with chronic hepatitis B background and divided them into three subgroups according to the pathological staging results: no liver fibrosis group (CHB 11, 12.0%), liver fibrosis group but without liver cirrhosis (LF 41, 44.6%), and early liver cirrhosis group (LC 40, 43.4%). Results: Levels of miR-122 in the CHB and LF group were significantly elevated compared with the LC group. Meanwhile, upregulation levels of miR-146a-5p, miR-29c-3p, miR-223 were seen in the CHB group versus LC. MiR-122-5p was best able to differentiate between patients with LC and without LC (area under the curve (AUC) 0.734). It can also distinguish patients with LF from those without LF (AUC 0.681). Panel including miR-122-5p miR-29c-3p and miR-381-3p resulted in an AUC of 0.700 in detection of LF. Meanwhile panel including miR-122-5p, miR-29c-3p, MiR-223 turned out to be good predictors, resulted in an AUC of 0.752 to discriminate LC in HBV-associated disease. HBV load, ALT and AST showed significant positive correlation with miR-122-5p and miR-381-3p. Conclusions: Our study explored changes of plasm miRNA levels in HBV-associated disease patients, constructed diagnostic miRNAs panel to predict liver fibrosis and early cirrhosis. Meanwhile In the process of liver fibrosis and cirrhosis, there are involving not only common pathway molecules, but also its specific pathway molecules.
Can the creation of new freshwater habitat demographically offset losses of Pacific salmon from chronic anthropogenic mortality?
Authors: Gibeau Pascale , Bradford Michael J. , Palen Wendy J.
Published: July 2020

Over 1 billion USD are devoted annually to rehabilitating freshwater habitats to improve survival for the recovery of endangered salmon populations. Mitigation often requires the creation of new habitat (e.g. habitat compensation) to offset population losses from human activities, however compensation schemes are rarely evaluated. Anadromous Pacific salmon are ecologically, culturally, and economically important in the US and Canada, and face numerous threats from climate change, over-harvesting, and degradation of freshwater habitats. Here we used a matrix population model of coho salmon(Oncorhynchus kisutch)to determine the amount of habitat compensation needed to offset mortality (2-20% per year) caused by a range of development activities. We simulated chronic mortality to three different life stages (egg, parr, smolt/adult), individually and in combination, to mimic impacts from development, and evaluated if the number of smolts produced from constructed side-channels demographically offset losses. We show that under ideal conditions, the typical size of a constructed side-channel in the Pacific Northwest (PNW) (3405 m2) is sufficient to compensate for only relatively low levels of chronic mortality to either the parr or smolt/adult stages (2-7% per year), but populations do not recover if mortality is >10% per year. When we assumed lower productivity (e.g.; 25thpercentile), or imposed mortality at multiple life stages, we found that constructed channels would need to be larger (0.2-4.5 times) than if we assumed mean productivity or as compared to the typical size built in the PNW, respectively, to maintain population sizes.. We conclude that habitat compensation has the potential to mitigate chronic mortality to early life stages, but that current practices are likely not sufficient when we incorporate more realistic assumptions about productivity of constructed side-channels and cumulative effects of anthropogenic disturbances on multiple life stages.
Structural determination ofStreptococcus pyogenesM1 protein interactions with human immunoglobulin G using integrative structural biology
Authors: Khakzad Hamed , Happonen Lotta , Karami Yasaman , Nilges Michael , Van Nhieu Guy Tran , Malmström Johan , Malmström Lars
Published: July 2020

Streptococcus pyogenes(Group A streptococcus; GAS) is an important human pathogen responsible for mild to severe, life-threatening infections. GAS expresses a wide range of virulence factors, including the M family proteins. The M proteins allow the bacteria to evade parts of the human immune defenses by triggering the formation of a dense coat of plasma proteins surrounding the bacteria, including IgGs. However, the molecular level details of the M1-IgG interaction have remained unclear. Here, we characterized the structure and dynamics of this interaction interface in human plasma on the surface of live bacteria using integrative structural biology, combining cross-linking mass spectrometry and molecular dynamics (MD) simulations. We show that the primary interaction is formed between the S-domain of M1 and the conserved IgG Fc-domain. In addition, we show evidence for a so far uncharacterized interaction between the A-domain and the IgG Fc-domain. Both these interactions mimic the protein G-IgG interface of group C and G streptococcus. These findings underline a conserved scavenging mechanism used by GAS surface proteins that block the IgG-receptor (FcγR) to inhibit phagocytic killing. We additionally show that we can capture Fab-bound IgGs in a complex background and identify the specific M1 epitopes targeted on live bacteria. Our results elucidate the M1-IgG interaction network involved in inhibition of phagocytosis and reveal important M1 peptides that can be further investigated as future vaccine targets.
Hello From the Other Side: Robust Contralateral Interference in Tactile Detection
Authors: Kusnir Flor , Pesin Slav , Landau Ayelet N.
Published: July 2020

Our sense of touch is unique in that our tactile receptors are spread across our body surface and constantly receive different inputs at the same time. These inputs vary in relevance according to our current goals, but there is little research on how simultaneous stimulation to different body sites affects the perception of touch. In this series of studies, we characterised how irrelevant tactile sensations across the body-midline affect tactile detection in a constantly-attended body site. Participants had to detect a target on their dominant index finger, while receiving irrelevant stimulation to another body site (homologous and non-homologous fingers, and the contralateral ankle). We document robust interference effects on all measured body-sites. Its impact on detection-performance was unaffected by body posture, exacerbated by the intensity of the irrelevant stimulation, and ameliorated by embedding a target-like signal in the irrelevant stimulation. In addition, we generalise our findings beyond the target stimulus (i.e., a vibration intensity decrement) and report similar effects when employing a target-increment. In light of our findings, we propose that tactile inputs may be pooled together early in the hierarchy of somatosensory processing, resulting in an integrated percept. The rules for integration across body sides are likely not described by a simple summation, but rather may be governed by more complex interactions between fingers and according to the corresponding perceived, as well as actual, intensities of the stimulation.

Highlights

Irrelevant stimulation to a contralateral body site hinders tactile detection.

We show robust and early integration of sensory inputs from across body sides.

The amount of interference varies by the signal-to-noise in the irrelevant stimulation.

Interference may result from cortical integration of bilateral tactile sensations.
Independent evolution of transcript abundance and gene regulatory dynamics
Authors: Krieger Gat , Lupo Offir , Levy Avraham A. , Barkai Naama
Published: July 2020

Changes in gene expression drive novel phenotypes, raising interest in how gene expression evolves. In contrast to the static genome, cells modulate gene expression in response to changing environments. Previous comparative studies focused on specific conditions, describing interspecies variation in expression levels, but providing limited information about variation across different conditions. To close this gap, we profiled mRNA levels of two related yeast species in hundreds of conditions and used coexpression analysis to distinguish variation in the dynamic pattern of gene expression from variation in expression levels. The majority of genes whose expression varied between the species maintained a conserved dynamic pattern. Cases of diverged dynamic pattern correspond to genes that were induced under distinct subsets of conditions in the two species. Profiling the interspecific hybrid allowed us to distinguish between genes with predominantly cis- or trans-regulatory variation. We find that trans-varying alleles are dominantly inherited, and that cis-variations are often complemented by variations in trans. Based on these results, we suggest that gene expression diverges primarily through changes in expression levels, but does not alter the pattern by which these levels are dynamically regulated.
Kanpur Confectioneries Private Limited (A)
Authors: Dixit Mukund , Dixit Vandana
Published: July 2020

This case describes the experience of Kanpur Confectioneries Private Limited (KCPL), a family managed company, in being a contract manufacturer for A–One Confectioneries Private Limited. The alliance had worked to the advantage of KCPL. It had prospered as a profitable contract manufacturer. It had used the surplus to diversify into unrelated businesses. The family members, however had doubts regarding the employment opportunities provided by the move. They were not sure whether the progress was sustainable. Alok Kumar Gupta, Chairman and Managing Director of KCPL, along with his brothers and son, is required to review the strategy and performance of his company and develop a course of action for the future.
Traditional Way of Learning Ayurveda and Practising It
Authors: Dixit Mukund R. , Verma Sanjay
Published: July 2020

This case describes the teaching and learning processes in Ayurveda, the ancient Indian system of medicine as explained by Vaidya Hardikar. He practised the system of diagnosis through ‘Nadi Nidan’, pulse reading and treated patients according to the principles of Ayurveda, the ancient Indian system of Medicine. The transfer of knowledge happened through formal and informal processes where he assisted his father and other practitioners in preparing medicines, interrogating the patients and pronouncing diagnosis. The participants can identify and analyze the various processes in the transfer of tacit and explicit knowledge.
UCO Bank - Strategic Renewal
Authors: Maheshwari Sunil Kumar , Bhat Ramesh
Published: July 2020

There have been plans to merge UCO Bank with larger banks owing to its poor performance for many years. There were leaders in the history who had not been committed. The inadequate governance of the bank has been responsible for some of the major lapses. Mr. Arun Kaul took strategic initiatives and systematically strengthened the functioning of the board. It enabled the bank to turnaround and report profits in challenging economic conditions. The Bank is not yet completely safe and probably need strengthening of its competencies to emerging challenges.
A cultural-economic examination of public relations measurement in the 1920s and its implications for contemporary practice
Authors: Anderson William
Published: July 2020

Purpose

What gets measured gets done” goes the cliché. Therefore, it is imperative for corporate communicators to understand the measurement of persuasive communication, starting with its antecedents. This paper will highlight the link between audience awareness/behavior and persuasive communication through an examination of how 1920s practitioners studied the effect their communications materials (specifically film and print brochures) had on key audiences.

Design/methodology/approach

The author used the cultural-economic model (CEM) of public relations (PR) as a framework to examine the various socio-cultural organizational factors that affected the production and the consumption of communication materials and messages.

Findings

The intent and techniques of PR measurement have not changed much in 100 years. A contemporary practitioner might conduct a study of communications materials in a similar manner as the 1920s social hygienists, and this study adds the concept of human agency to the discussion of PR measurement. This is not to engage in historical presentism and judge past practitioners on current standards. Instead, it is a call for contemporary practitioners to take a deeper look at the moment of consumption and all the variables that go into meaning making.

Originality/value

Most of the field's historical case studies focus on the production of communication messages and materials, while this paper examines those facets as well as audience consumption. Implications for contemporary practitioners are discussed.
Culture, productivity and competitiveness: disentangling the concepts
Authors: Chen Stephen , Lin Nidthida
Published: July 2020

Purpose

Culture has been identified as one of the main drivers of the “competitive productivity” (CP) of nations. However, research studies examining the relationships between culture, competition and productivity are highly fragmented across different streams of literature, leaving researchers with a lack of a holistic view of the topic. This study reviews research studies that examined the relationships between culture and productivity and between culture and competitiveness, as well as the joint relationships between culture, productivity and competitiveness in leading economic, business and management journals in the period 2009–2018 in order to identify research gaps and opportunities for future research.

Design/methodology/approach

The authors used a combination of bibliometric analysis using VOSviewer, text analysis using Leximancer and systematic review by expert reviewers to analyze 293 articles that consider culture, productivity and competitiveness published in leading business, management and economics journals in the period 2009–2018.

Findings

The findings indicate that, although productivity and competitiveness are often discussed jointly in some policy circles, research studies on the roles of culture on productivity and on competitiveness take place in quite different streams of academic literature, drawing on different sets of concepts and theoretical frameworks. The concept of innovation appears prominently in both sets of the literature as an antecedent of both productivity improvement and international competitiveness.

Research limitations/implications

The findings highlight the need for more research studies which jointly examine culture, productivity and competitiveness and the relationships between them.

Originality/value

To the best of the authors’ knowledge, this study is among the first attempts to systematically analyze the literature on the relationship between culture and CP.
Deep learning-based approach for segmentation of glioma sub-regions in MRI
Authors: Chaudhary Jiten , Rani Rajneesh , Kamboj Aman
Published: July 2020

Purpose

Brain tumor is one of the most dangerous and life-threatening disease. In order to decide the type of tumor, devising a treatment plan and estimating the overall survival time of the patient, accurate segmentation of tumor region from images is extremely important. The process of manual segmentation is very time-consuming and prone to errors; therefore, this paper aims to provide a deep learning based method, that automatically segment the tumor region from MR images.

Design/methodology/approach

In this paper, the authors propose a deep neural network for automatic brain tumor (Glioma) segmentation. Intensity normalization and data augmentation have been incorporated as pre-processing steps for the images. The proposed model is trained on multichannel magnetic resonance imaging (MRI) images. The model outputs high-resolution segmentations of brain tumor regions in the input images.

Findings

The proposed model is evaluated on benchmark BRATS 2013 dataset. To evaluate the performance, the authors have used Dice score, sensitivity and positive predictive value (PPV). The superior performance of the proposed model is validated by training very popular UNet model in the similar conditions. The results indicate that proposed model has obtained promising results and is effective for segmentation of Glioma regions in MRI at a clinical level.

Practical implications

The model can be used by doctors to identify the exact location of the tumorous region.

Originality/value

The proposed model is an improvement to the UNet model. The model has fewer layers and a smaller number of parameters in comparison to the UNet model. This helps the network to train over databases with fewer images and gives superior results. Moreover, the information of bottleneck feature learned by the network has been fused with skip connection path to enrich the feature map.