bluuebunny/crossref_metadata_2025 huggingface dataset:
Humoral Response to BNT162b2 mRNA Covid19 Vaccine in Peritoneal and Hemodialysis Patients: a Comparative Study
Authors: Duarte Rui , Roldão Marisa , Figueiredo Cátia , Ferrer Francisco , Gonçalves Hernâni , Luz Ivan , Sofia Flora , Lopes Karina
Published: June 2021

Introduction

Generalized immunization against COVID19 has become the cornerstone in prevention of severe acute respiratory syndrome associated with this pandemic. Maintenance dialysis patients (MDP) are at higher risk of both exposure and mortality from the disease. Efficacy and security of BNT162b2 vaccine is well documented for the general population, but not in MDP, particularly in peritoneal dialysis (PD) patients. This study aims to compare humoral response between hemodialysis (HD) and PD patients.

Materials and Methods

Observational prospective study including MDP on HD or PD program from a Portuguese middle-sized Nephrology Center, who received BNT162b2 vaccine. Specific anti-Spike IgG was measured as arbitrary units per milliliter (AU/mL) on two separate occasions: 3 weeks after the first dose and 3 weeks after the second. The two modality groups were compared both for absolute value and number of non-responders (NR) after both inoculations. Demographic data was also compared.

Results

Of 73 patients enrolled, 67 were eligible for the final study: 42 HD and 25 PD patients. PD group developed significantly higher antibody titers in both inoculations: first dose with Med 5.44 vs 0.99 (p<0.01) and second dose with Med 170.43 vs 65.81 (p<0.01). HD status was associated with NR after the first dose (Phi=0.383; p<0.01), but not after the second (p=0.08). Age, Charlson comorbidity index and dialysis vintage were lower in the PD group (p<0.01; p=0.02; p<0.01, respectively).

Conclusion

This study demonstrated a better humoral response to immunization with BNT162b2 in PD patients, when compared to HD patients, after each of the two recommended inoculations. Both groups showed substantial humoral response after just one dose of the vaccine. Older age and higher comorbidity burden may explain the relative immunogenicity deficit, probably in a superior degree comparing with age matched healthy population.

What is already known about this subject

Maintenance hemodialysis patients have lower humoral response to BNT162b2 mRNA COVID19 vaccine when compared to the general population;

Maintenance dialysis patients are at high risk of exposure to COVID19 in addition to a more severe course of the disease;

What this study adds

Maintenance peritoneal dialysis patients have better humoral response with BNT162b2 when compared to those on hemodialysis;

There is a substantial humoral response after a single dose of the vaccine for both hemodialysis (50%) and peritoneal dialysis (88%) patients.

What impact this may have on clinical practice or policy

Protocols for follow-up measures, including extra inoculations, might have to be considered for hemodialysis patients;

Peritoneal dialysis patients should be promptly immunized in all centers, rejecting constraints regarding lower effectiveness or yield.
EXTENDED ABSORPTION OF LIOTHYRONINE FROM POLY-ZINC-LIOTHYRONINE (PZL) IN HUMANS
Authors: Dumitrescu Alexandra M. , Hanlon Erin C. , Arosemena Marilyn , Duchon Olga , Ettleson Matthew , Giurcanu Mihai , Bianco Antonio C.
Published: June 2021

Background

Liothyronine (LT3) has been increasingly used in combination with levothyroxine (LT4) in the treatment of hypothyroidism. A metal coordinated form of LT3, known as poly-zinc-liothyronine (PZL), avoided in rats the typical T3 peak seen after oral administration of LT3.

Objectives

To evaluate in healthy volunteers (i) the pharmacokinetics of PZL-derived T3 after a single dose, (ii) the pharmacodynamics of PZL-derived T3, (iii) monitoring for the adverse events; (iv) exploratory analysis of the sleep patterns after LT3, PZL or placebo administration.

Methods

12 healthy volunteers 18 to 50 years of age were recruited for a Phase 1, double-blind, randomized, single-dose placebo-controlled, cross-over study to compare PZL against LT3 or placebo. Subjects were admitted three separate times to receive a randomly assigned capsule containing placebo, 50-mcg LT3, or 50-mcg-PZL, and were observed for 48h. A 2-week washout period separated each admission.

Results

LT3-derived serum T3 levels exhibited the expected profile, with a Tmax at 2h and return to basal levels by 24-36h. PZL-derived serum T3 levels exhibited a ∼30% lower Cmax that was 1 h delayed and extended into a plateau that lasted up to 6h. This was followed by a lower but much longer plateau; by 24 hours serum T3 levels still exceeded ½ of Cmax. TSH levels were similarly reduced indistinguishably in both groups.

Conclusion

PZL possesses the necessary properties to achieve a much improved T3 pharma-cokinetic. Drug product development of PZL should improve the delivery of T3 even further. PZL is on track to provide hypothyroid patients with stable levels of serum T3.
Exploration of Antibacterial Activities of Berberis royleana Fractions Extracts
Authors: Rafique Muhammad , Salman Muhammad
Published: June 2021

Objectives

Prepare various solvent extracts of Berberis royleana (areal part of plant) to determine the in vitro antibacterial potential of methanolic, ethyl acetate, chloroform, n-hexane and water extracts of B. royleana against various bacterial isolates and Compare the efficacy of outstanding antimicrobial extracts of B. royleana with commonly used antibiotics. Berberis species are medicinally important plants, produce various metabolites and used as treatment for multiple complications. Berberis royleana is a rare specie belongs to genus Berberis.

Methods

In the current study the areal parts of the plant were isolated to explore antibacterial activities. Antibacterial activities were done using standard procedures. The antibacterial activities of different fractions were tested by 100 μg methanolic, ethyl acetate, chloroform, n-hexane and water fractions of B. royleana against bacterial isolates Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella Typhi and Proteus spp. The ciprofloxacin (5μg) was used as a positive control and DMSO as a negative control.

Results

All fractions showed zone of inhibition against the growth of tested bacterial isolates. Methanolic fractions have maximum ZI against S. aureus and K. pneumoniae (25.7±1.5 mm), S. aureus (23±2.7), Salmonella Typhi (25±1), water fraction have Klebsiella pneumoniae (24.4 ±2.5), Salmonella Typhi (23 ±1 mm), S. aureus (21±2.8 mm) and the n-hexane fraction exhibits ZI against K. pneumoniae (24.7±1.5), Salmonella Typhi (24±2) S. aureus, ethyl acetate maximum zone against E. coli (16.6±3.1) and chloroform fraction showed maximum ZI against S. Typhi (21.6±3.3).

Conclusion

From current report it may be concluded that B. royleana extracts have medicinally effective potentials against drugs resistant bacteria.
Antibody response after a single dose of ChAdOx1-nCOV (Covishield™®) vaccine in subjects with prior SARS-CoV2 infection: Is a single dose sufficient?
Authors: Borkakoty Biswajyoti , Sarmah Mandakini Das , Bhattacharjee Chandra Kanta , Bali Nargis , Gogoi Gayatri
Published: June 2021

It is crucial to know whether a single dose of vaccine against SARS-CoV-2 is sufficient to elicit immune response in previously infected people in India. A total of 121 participants (baseline seropositive 46 and seronegative 75) were included to study the immune response to ChAdOx1-nCOV (Covishield) vaccine in previously infected or uninfected people. IgG antibodies were estimated at three different time intervals, i.e. pre-vaccination, 25-35 days post 1st vaccination and 25-35 days post 2nd vaccination. The IgG antibody titre was significantly high among previous seropositive subjects with single dose of vaccine compared to seronegative group with both doses of vaccine respectively (4.59±1.04 vs 3.08±1.22, p-value: <0.0001).

In conclusion, a single dose of Covishield™® vaccine might be sufficient to induce an effective immune responsein subjects with prior SARS-CoV2 infection. Stratifying vacinees based on their SARS-CoV2 IgG antibody titre before vaccination would help in meeting the increasing vaccine demand and could be effective to circumvent further wave of the pandemic in India.
β-Catenin Limits Osteogenesis on Regenerative Materials in a Stiffness-Dependent Manner
Authors: Zhou Qi , Ren Xiaoyan , Oberoi Michelle K. , Caprini Rachel M. , Dewey Marley J. , Kolliopoulos Vasiliki , Yamaguchi Dean T. , Harley Brendan A.C. , Lee Justine C.
Published: June 2021

Targeted refinement of regenerative materials requires mechanistic understanding of cell-material interactions. The nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffold is a porous biomaterial that promotes regenerative healing of calvaria defects in vivo without addition of exogenous growth factors or progenitor cells, suggesting its potential as an off-the-shelf implant for reconstructing skull defects. In this work, we evaluate the relationship between material stiffness, a tunable MC-GAG property, and activation of the canonical Wnt (cWnt) signaling pathway. Primary human bone marrow-derived mesenchymal stem cells (hMSCs) were differentiated on two MC-GAG scaffolds varying by stiffness (non- crosslinked, NX-MC, 0.3 kPa vs. conventionally crosslinked, MC, 3.9 kPa). hMSCs exhibited increased expression of activated β-catenin, the major cWnt intracellular mediator, and the mechanosensitive YAP protein with near complete subcellular colocalization in stiffer MC scaffolds. Small molecule Wnt pathway inhibitors reduced activated β-catenin and YAP protein quantities and colocalization, osteogenic differentiation, and mineralization on MC, with no effects on NX-MC. Concomitantly, Wnt inhibitors increased BMP4 and phosphorylated Smad1/5 (p-Smad1/5) expression on MC, but not NX-MC. Unlike non-specific Wnt pathway downregulation, isolated canonical Wnt inhibition with β-catenin knockdown increased osteogenic gene expression and mineralization specifically on the stiffer MC. β-catenin knockdown also increased p-Smad1/5, Runx2, and BMP4 expression only on the stiffer MC material. Our data indicates stiffness-induced activation of the Wnt and mechanotransduction pathways promotes osteogenesis in MC-GAG scaffolds. However, activated β-catenin is a limiting agent and may serve as a useful target or readout for optimal modulation of stiffness in skeletal regenerative materials.

One Sentence Summary

β-Catenin limits stiffness-induced osteogenenic differentiation on nanoparticulate mineralized collagen glycosaminoglycan materials
Ehrlichia ruminantiumuses its transmembrane protein Ape to adhere to host bovine aortic endothelial cells
Authors: Pinarello Valérie , Bencurova Elena , Marcelino Isabel , Gros Olivier , Puech Carinne , Bhide Mangesh , Vachiery Nathalie , Meyer Damien F.
Published: June 2021

Abstract

Ehrlichia ruminantiumis an obligate intracellular bacterium, transmitted by ticks of the genusAmblyommaand responsible for heartwater, a disease of domestic and wild ruminants. High genetic diversity ofE. ruminantiumstrains hampers the development of an effective vaccine against all strains present in the field. In order to develop strategies for the control of heartwater through both vaccine and alternative therapeutic approaches, it is important to first gain a better understanding of the early interaction ofE. ruminantiumand its host cell. Particularly, the mechanisms associated with bacterial adhesion remain to be elucidated. Herein, we studied the role ofE. ruminantiummembrane protein ERGA_CDS_01230 (UniProt Q5FFA9), a probable iron transporter, in the adhesion process to host bovine aortic endothelial cells (BAEC). The recombinant version of the protein ERGA_CDS_01230, successfully produced in theLeishmania tarentolaesystem, is O-glycosylated. Followingin vitroculture ofE. ruminantiumin BAEC, the expression of CDS ERGA_CDS_01230 peaks at the extracellular infectious elementary body stages. This result suggest the likely involvement of ERGA_CDS_01230, named hereafter Ape for Adhesion protein ofEhrlichia, in the early interaction ofE. ruminantiumwith its host cells. We showed using flow cytometry and scanning electron microscopy that beads coated with recombinant ERGA_CDS_01230 (rApe) adheres to BAEC. In addition, we also observed that rApe interacts with proteins of the cell lysate, membrane and organelle fractions. Additionally, enzymatic treatment degrading dermatan and chondroitin sulfates on the surface of BAEC is associated with a 50% reduction in the number of bacteria in the host cell after a developmental cycle, indicating that glycosaminoglycans seem to play a role in the adhesion ofE. ruminantiumto the host cell. Finally, Ape induces a humoral response in vaccinated animals. Globally, our work identifying the role of Ape inE. ruminantiumadhesion to host cells makes it a gold vaccine candidate and represents a first step toward the understanding of the mechanisms of cell invasion byE. ruminantium.
Coexistence patterns and diversity in a trait-based metacommunity on an environmental gradient
Authors: Mohammed Mozzamil , Blasius Bernd , Ryabov Alexey
Published: June 2021

The dynamics of trait-based metacommunities have attracted much attention, but not much is known about how dispersal and spatial environmental variability mutually interact with each other to drive coexistence patterns and diversity. Here, we present a spatially-explicit model of resource competition in a metacommunity on a one-dimensional environmental gradient. We find that both the strength of dispersal and the range of spatial environmental variability affect coexistence patterns, spatial structure, trait distribution and local and regional diversity. Without dispersal, species are sorted according to their optimal growth conditions on the gradient. With the onset of dispersal source-sink effects are initiated, which increases the effects of environmental filtering and interspecific competition and generates trait lumping, so that only a few species from an environment-defined trait range can survive. Interestingly, for very large dispersal rates the system becomes spatially homogeneous, but nevertheless two species at the extreme ends of the trait-off curve can coexist for large environmental variability. Local species richness follows a classic hump-shaped dependence on dispersal rate, while local and regional diversity exhibit a pronounced peak for intermediate values of the environmental variability. Our findings provide important insights into the factors that shape the structure of trait-based metacommunities.
Whole-brain studies of spontaneous behavior in head-fixed rats enabled by zero echo time MB-SWIFT fMRI
Authors: Paasonen Jaakko , Stenroos Petteri , Laakso Hanne , Pirttimäki Tiina , Paasonen Ekaterina , Salo Raimo A. , Tanila Heikki , Idiyatullin Djaudat , Garwood Michael , Michaeli Shalom , Mangia Silvia , Gröhn Olli
Published: June 2021

Understanding the link between the brain activity and behavior is a key challenge in modern neuroscience. Behavioral neuroscience, however, lacks tools to record whole-brain activity in complex behavioral settings. Here we demonstrate that a novel Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) functional magnetic resonance imaging (fMRI) approach enables whole-brain studies in spontaneously behaving head-fixed rats. First, we show anatomically relevant functional parcellation. Second, we show sensory, motor, exploration, and stress-related brain activity in relevant networks during corresponding spontaneous behavior. Third, we show odor-induced activation of olfactory system with high correlation between the fMRI and behavioral responses. We conclude that the applied methodology enables novel behavioral study designs in rodents focusing on tasks, cognition, emotions, physical exercise, and social interaction. Importantly, novel zero echo time and large bandwidth approaches, such as MB-SWIFT, can be applied for human behavioral studies, allowing more freedom as body movement is dramatically less restricting factor.
Reference-free cell-type deconvolution of multi-cellular pixel-resolution spatially resolved transcriptomics data
Authors: Miller Brendan F. , Huang Feiyang , Atta Lyla , Sahoo Arpan , Fan Jean
Published: June 2021

Recent technological advancements have enabled spatially resolved transcriptomic profiling but at multi-cellular pixel resolution, thereby hindering the identification of cell-type-specific spatial patterns and gene expression variation. To address this challenge, we developed STdeconvolve as a reference-free approach to deconvolve underlying cell-types comprising such multi-cellular pixel resolution spatial transcriptomics (ST) datasets. Using simulated as well as real ST datasets from diverse spatial transcriptomics technologies comprising a variety of spatial resolutions such as Spatial Transcriptomics, 10X Visium, DBiT-seq, and Slide-seq, we show that STdeconvolve can effectively recover cell-type transcriptional profiles and their proportional representation within pixels without reliance on external single-cell transcriptomics references. STdeconvolve provides comparable performance to existing reference-based methods when suitable single-cell references are available, as well as potentially superior performance when suitable single-cell references are not available. STdeconvolve is available as an open-source R software package with the source code available at https://github.com/JEFworks-Lab/STdeconvolve.
Yanocomp: robust prediction of m6A modifications in individual nanopore direct RNA reads
Authors: Parker Matthew T. , Barton Geoffrey J. , Simpson Gordon G.
Published: June 2021

Yanocomp is a tool for predicting the positions and stoichiometries of RNA modifications in Nanopore direct RNA sequencing data. It uses general mixture models to identify differentially modified sites between two conditions, with good support for replicates. Yanocomp models across adjacent kmers and uses a uniform component to account for outliers, improving the accuracy of single molecule predictions. Consequently, Yanocomp can be used to measure modification stoichiometry, and correlate modifications with other RNA processing events.

Availability

Yanocomp is available under an MIT license at www.github.com/bartongroup/yanocomp.
Attrition Rate in Infant fNIRS Research: A Meta-Analysis
Authors: Baek Sori , Marques Sabrina , Casey Kennedy , Testerman Meghan , McGill Felicia , Emberson Lauren
Published: June 2021

Understanding the trends and predictors of attrition rate, or the proportion of collected data that is excluded from the final analyses, is important for accurate research planning, assessing data integrity, and ensuring generalizability. In this pre-registered meta-analysis, we reviewed 182 publications in infant (0-24 months) functional near-infrared spectroscopy (fNIRS) research published from 1998 to April 9, 2020 and investigated the trends and predictors of attrition. The average attrition rate was 34.23% among 272 experiments across all 182 publications. Among a subset of 136 experiments which reported the specific reasons of subject exclusion, 21.50% of the attrition were infant-driven while 14.21% were signal-driven. Subject characteristics (e.g., age) and study design (e.g., fNIRS cap configuration, block/trial design, and stimulus type) predicted the total and subject-driven attrition rates, suggesting that modifying the recruitment pool or the study design can meaningfully reduce the attrition rate in infant fNIRS research. Based on the findings, we established guidelines on reporting the attrition rate for scientific transparency and made recommendations to minimize the attrition rates. We also launched an attrition rate calculator (LINK) to aid with research planning. This research can facilitate developmental cognitive neuroscientists in their quest toward increasingly rigorous and representative research.

Highlights

Average attrition rate in infant fNIRS research is 34.23%

21.50% of the attrition are infant-driven (e.g., inattentiveness) while 14.21% are signal-driven (e.g., poor optical contact)

Subject characteristics (e.g., age) and study design (e.g., fNIRS cap configuration, block/trial design, and stimulus type) predict the total and infant-driven attrition rates

Modifying the recruitment pool or the study design can meaningfully reduce the attrition rate in infant fNIRS research
Members of the ELMOD protein family specify formation of distinct aperture domains on the Arabidopsis pollen surface
Authors: Zhou Yuan , Amom Prativa , Reeder Sarah H. , Lee Byung Ha , Helton Adam , Dobritsa Anna A.
Published: June 2021

Pollen apertures, the characteristic gaps in pollen wall exine, have emerged as a model for studying the formation of distinct plasma-membrane domains. In each species, aperture number, position, and morphology are typically fixed; across species they vary widely. During pollen development certain plasma-membrane domains attract specific proteins and lipids and become protected from exine deposition, developing into apertures. However, how these aperture domains are selected is unknown. Here, we demonstrate that patterns of aperture domains in Arabidopsis are controlled by the members of the ancient ELMOD protein family, which, although important in animals, has not been studied in plants. We show that two members of this family, MACARON (MCR) and ELMOD_A, act upstream of the previously discovered aperture proteins and that their expression levels influence the number of aperture domains that form on the surface of developing pollen grains. We also show that a third ELMOD family member, ELMOD_E, can interfere with MCR and ELMOD_A activities, changing aperture morphology and producing new aperture patterns. Our findings reveal key players controlling early steps in aperture domain formation, identify residues important for their function, and open new avenues for investigating how diversity of aperture patterns in nature is achieved.
Inhibitory and Stimulatory Micropeptides Preferentially Bind to Different Conformations of the Cardiac Calcium Pump
Authors: Cleary Sean R. , Fang Xuan , Cho Ellen E. , Pribadi Marsha P. , Seflova Jaroslava , Beach Jordan R. , Kekenes-Huskey Peter , Robia Seth L.
Published: June 2021

The ATP-dependent ion pump SERCA sequesters Ca2+ in the endoplasmic reticulum to establish a reservoir for cell signaling. Because of its central importance in physiology, this transporter is tightly controlled by physical interactions with tissue-specific regulatory micropeptides that tune SERCA function to match changing physiological conditions. In the heart, phospholamban (PLB) inhibits SERCA, while dwarf open reading frame (DWORF) stimulates SERCA. These competing interactions determine cardiac performance by modulating the amplitude of Ca2+ signals that drive the contraction/relaxation cycle. The distinct functions of these peptides may relate to their reciprocal preferences for SERCA binding. While SERCA binds PLB more avidly at low cytoplasmic Ca2+, it binds DWORF better at high Ca2+. In the present study, we determined that this opposing Ca2+ sensitivity is due to preferential binding of DWORF and PLB to different intermediate conformations that the pump samples during the Ca2+ transport cycle. The results suggest a mechanistic basis for inhibitory and stimulatory micropeptide function. In addition, fluorescence resonance energy transfer (FRET) measurements revealed dynamic shifts in SERCA-micropeptide binding equilibria during cellular Ca2+ elevations. The data suggest Ca2+-dependent dynamic exchange of inhibitory and stimulatory micropeptides from SERCA during the cardiac cycle. Together, these mechanisms provide beat-to-beat modulation of cardiac Ca2+ handling and contribute to the heart's adaptation to the increased physiological demands of exercise.
The Oncoprotein BCL6 Enables Cancer Cells to Evade Genotoxic Stress
Authors: Liu Yanan , Feng Juanjuan , Yuan Kun , Lu Yue , Li Kun , Guo Jiawei , Ma Chengbin , Chen Jing , Pang Xiufeng
Published: June 2021

Genotoxic agents remain the mainstay of cancer treatment. Unfortunately, the clinical benefits are often countered by a rapid tumor adaptive response. Here, we report that the oncoprotein B cell lymphoma 6 (BCL6) is a core component that confers tumor adaptive resistance to genotoxic stress. Multiple genotoxic agents promoted BCL6 transactivation, which was positively correlated with a weakened therapeutic efficacy and a worse clinical outcome. Mechanistically, we discovered that treatment with the genotoxic agent etoposide led to the transcriptional reprogramming of multiple pro-inflammatory cytokines, among which the interferon-α and interferon-γ responses were selectively and substantially enriched in resistant cells. Our results further revealed that the activation of interferon/signal transducer and activator of transcription 1 axis directly upregulated BCL6 expression. The increased expression of BCL6 further repressed the tumor suppressor PTEN and consequently enabled resistant cancer cell survival. Accordingly, targeted inhibition of BCL6 remarkably enhanced etoposide-triggered DNA damage and apoptosis both in vitro and in vivo. Our findings highlight the importance of BCL6 signaling in conquering tumor tolerance to genotoxic stress, further establishing a rationale for a combined approach with genotoxic agents and BCL6-targeted therapy.
Incorporating evolutionary and threat processes into crop wild relatives conservation
Authors: Tobón-Niedfeldt Wolke , Mastretta-Yanes Alicia , Urquiza-Haas Tania , Goettsch Bárbara , Cuervo-Robayo Angela P. , Urquiza-Haas Esmeralda , Orjuela-R. M. Andrea , Acevedo Gasman Francisca , Oliveros-Galindo Oswaldo , Burgeff Caroline , Rivera-Rodríguez Diana , de Jesús Sánchez González José , Alarcón-Guerrero Jesús , Sarukhán José , Koleff Patricia
Published: June 2021

Biodiversity conservation calls for spatial explicit approaches to maximize the representation and persistence of genetic diversity given species’ idiosyncratic threats in mosaic landscapes, but conservation planning methodologies seldom account for this. Here, we introduce a novel approach that uses proxies of genetic diversity to identify conservation areas, applying systematic conservation planning tools to produce hierarchical prioritizations of the landscape. It accounts for: (i) evolutionary processes, including historical and environmental drivers of genetic diversity, and (ii) threat processes, considering taxa specific tolerance to human-modified habitats and their extinction risk status. We illustrate our approach with crop wild relatives (CWR) because their intra- and interspecific diversity is important for crop breeding and food security. Although we focus on Mesoamerican CWR within Mexico, our methodology offers new opportunities to effectively guide conservation and monitoring strategies to safeguard the evolutionary resilience of any taxa, including in regions of complex evolutionary histories and mosaic landscapes.
Dietary palmitic acid induces innate immune memory via ceramide production that enhances severity of acute septic shock and clearance of infection
Authors: Seufert AL , Hickman JW , Traxler SK , Peterson RM , Lashley SJ , Shulzhenko N , Napier RJ , Napier BA
Published: June 2021

Trained immunity is an innate immune memory response that is induced by primary microbial or sterile stimuli that sensitizes monocytes and macrophages to a secondary pathogenic challenge, reprogramming the host response to infection and inflammatory disease. Nutritional components, such as dietary fatty acids, can act as inflammatory stimuli, but it is unknown if they can act as the primary stimuli in the context of innate immune memory. Here we find mice fed diets enriched in saturated fatty acids (SFAs) confer a hyper-inflammatory response to systemic lipopolysaccharide (LPS) and increased mortality, independent of diet-induced microbiome and glycemic modulation. Ex vivo, we show monocytes and splenocytes from mice fed enriched SFAs do not have altered baseline inflammation, but enhanced responses to a secondary inflammatory challenge. Lipidomics identified enhanced free palmitic acid (PA) and PA-associated lipids in SFA-fed mice serum. We found pre-treatment with physiologically relevant concentrations of PA alone reprograms macrophages to induce a hyper-inflammatory response to secondary challenge with LPS. This response was found to be dependent on the synthesis of ceramide, and reversible when treated with oleic acid, a mono-unsaturated FA that depletes intracellular ceramide. In vivo, we found systemic PA confers enhanced inflammation and mortality during an acute septic response to systemic LPS, which was not reversible for up to 7 days post-PA-exposure. While PA-treatment is harmful for acute septic shock outcome, we find PA exposure enhanced clearance of Candida albicans in RAG-/- mice. These are the first data to implicate enriched dietary SFAs, and specifically PA, in the induction of long-lived innate immune memory that is detrimental during an acute septic response, but beneficial for clearance of pathogens.
Vision is required for the formation of binocular neurons prior to the classical critical period
Authors: Tan Liming , Ringach Dario L. , Zipursky S. Lawrence , Trachtenberg Joshua T.
Published: June 2021

Depth perception emerges from the development of binocular neurons in primary visual cortex. Vision is required for these neurons to acquire their mature responses to visual stimuli. The prevailing view is that vision does not influence binocular circuitry until the onset of the critical period, about a week after eye opening, and that plasticity of visual responses is triggered by increased inhibition. Here, we show that vision is required to form binocular neurons and to improve binocular tuning and matching from eye opening until critical period closure. Enhancing inhibition does not accelerate this process. Vision soon after eye opening improves the tuning properties of binocular neurons by strengthening and sharpening ipsilateral-eye cortical responses. This progressively changes the population of neurons in the binocular pool and this plasticity is sensitive to interocular differences prior to critical period onset. Thus, vision establishes binocular circuitry and guides binocular plasticity from eye opening.
Lipid nanodiscs facilitate the identification of a fragment compound inhibiting the enzymatic activity of the bacterial membrane protein MsbA
Authors: Fujimoto Kaoru , Senoo Akinobu , Nagatoishi Satoru , Takahashi Daisuke , Ueda Tadashi , Tsumoto Kouhei , Caaveiro Jose M.M.
Published: June 2021

Membrane proteins are critical elements of numerous therapeutic approaches ranging from cancer to bacterial infections. MsbA is a bacterial membrane protein that has received increasing attention as an antibacterial target for its role in the processing of Lipid A, a key precursor of lipopolysaccharide that is essential for bacterial growth. When employing nanodiscs it is possible to stabilize MsbA by providing a membrane-like environment that enhances its enzymatic activity. Taking advantage of this property we have carried out a fragment screening using the biophysical method of surface plasmon resonance. This approach identified several compounds that bind specifically to MsbA. In particular, one of these fragment molecules not only binds to the target, but also inhibits the ATPase activity of the MsbA protein. The similarity of this fragment to the adenine moiety of ATP points at a route to generate stronger and more potent inhibitors for MsbA and even other proteins of its family of ABC transporters. Collectively, our study reveals biophysical approaches that facilitate the identification of fragment candidates inhibiting the activity of membrane proteins.
Genomic epidemiology of SARS-CoV-2 in Mauritius reveals a new wave of infections dominated by the B.1.1.318, a variant under investigation
Authors: Tegally Houriiyah , Ramuth Magalutcheemee , Amoaka Daniel , Scheepers Cathrine , Wilkinson Eduan , Giovanetti Marta , Lessells Richard J , Giandhari Jennifer , Ismail Arshad , Martin Darren , San Emmanuel James , Crawford Margaret , Daniels Rodney S , Harvey Ruth , Bahadoor Somduthsingh , Sonoo Janaki , Timol Myriam , Veerapa-Mangroo Lovena , Gottberg Anne von , Bhiman Jinal N. , de Oliveira Tulio , Manraj Shyam
Published: June 2021

Mauritius, a small island in the Indian Ocean, has had a unique experience of the SARS-CoV-2 pandemic. In March 2020, Mauritius endured a small first wave and quickly implemented control measures which allowed elimination of local transmission of SARS-CoV-2. When borders to the island reopened, it was accompanied by mandatory quarantine and testing of incoming passengers to avoid reintroduction of the virus into the community. As variants of concern (VOCs) emerged elsewhere in the world, Mauritius began using genomic surveillance to keep track of quarantined cases of these variants. In March 2021, another local outbreak occurred, and sequencing was used to investigate this new wave of local infections. Here, we analyze 154 SARS-CoV-2 viral genomes from Mauritius, which represent 12% of all the infections seem in Mauritius, these were both from specimens of incoming passengers before March 2021 and those of cases during the second wave. Our findings indicate that despite the presence of known VOCs Beta (B.1.351) and Alpha (B.1.1.7) among quarantined passengers, the second wave of local SARS-CoV-2 infections in Mauritius was caused by a single introduction and dominant circulation of the B.1.1.318 virus. The B.1.1.318 variant is characterized by fourteen non-synonymous mutations in the S-gene, with five encoded amino acid substitutions (T95I, E484K, D614G, P681H, D796H) and one deletion (Y144del) in the Spike glycoprotein. This variant seems to be increasing in prevalence and it is now present in 34 countries. This study highlights that despite having stopped the introduction of more transmissible VOCs by travel quarantines, a single undetected introduction of a B.1.1.318 lineage virus was enough to initiate a large local outbreak in Mauritius and demonstrated the need for continuous genomic surveillance to fully inform public health decisions.
Epigenetic Conditioning Induces Intergenerational Resilience to Dementia in a Mouse Model of Vascular Cognitive Impairment
Authors: Belmonte Krystal Courtney D. , Holmgren Eleanor B. , Wills Tiffany A. , Gidday Jeff M.
Published: June 2021

Background

Vascular cognitive impairment and dementia (VCID), which occurs immediately or in delayed fashion in 25-30% of stroke survivors, or secondary to chronic cerebral hypoperfusion, is the second leading cause of dementia following Alzheimer’s disease. To date, efficacious therapies are unavailable. We have shown previously in mice that repetitive hypoxic preconditioning (RHC) induces a long-lasting resilience to acute stroke (Stowe et al., 2011). More recently, we documented that untreated, first-generation adult progeny of mice exposed to RHC prior to mating are protected from retinal ischemic injury (Harman et al., 2020), consistent with accumulating evidence supporting the concept that long-lasting phenotypes induced epigenetically by intermittent stressors may be heritable. We undertook the present study to test the hypothesis that RHC will induce resilience to VCID, and that such RHC-induced resilience can also be inherited.

Methods

Chronic cerebral hypoperfusion (CCH) was induced in C57BL/6J mice secondary to bilateral carotid artery stenosis with microcoils in both the parental (F0) generation, and in their untreated first-generation (F1) offspring. Cohorts of F0 mice were directly exposed to either 8 wks of RHC (1 h of systemic hypoxia [11% oxygen] 3x/week) or normoxia prior to CCH. Cohorts of F1 mice were derived from F0 mice treated with RHC prior to mating, and untreated, normoxic controls that were age-matched at the time of stenosis induction. Demyelination in the corpus callosum of F0 mice was assessed following 3 months of CCH by immunohistochemistry. Mice from both generations were assessed for short-term recognition memoryin vivoby novel object preference (NOP) testing following 3 months of CCH, and a month thereafter,ex vivomeasurements of CA1 hippocampal long-term potentiation (LTP) were recorded from the same animals as a metric of long-lasting changes in synaptic plasticity.

Results

Three months of CCH caused demyelination and concomitant impairments in recognition memory in control mice from both generations. However, these CCH-induced memory impairments were prevented in F0 animals directly treated with RHC, as well as in their untreated adult F1 progeny. Similarly, hippocampal LTP was preserved in the 4-month CCH cohorts of mice directly treated with RHC, and in their untreated offspring with CCH.

Conclusions

Our findings demonstrate that RHC or other repetitively-presented, epigenetic-based therapeutics may hold promise for inducing a long-lasting resilience to VCID in treated individuals, and in their first-generation adult progeny.
A quasi-Monte Carlo statistical three-dimensional tolerance analysis method of products based on edge sampling
Authors: Zhou Chuanyuan , Liu Zhenyu , Qiu Chan , Tan Jianrong
Published: June 2021

Purpose

The conventional statistical method of three-dimensional tolerance analysis requires numerous pseudo-random numbers and consumes enormous computations to increase the calculation accuracy, such as the Monte Carlo simulation. The purpose of this paper is to propose a novel method to overcome the problems.

Design/methodology/approach

With the combination of the quasi-Monte Carlo method and the unified Jacobian-torsor model, this paper proposes a three-dimensional tolerance analysis method based on edge sampling. By setting reasonable evaluation criteria, the sequence numbers representing relatively smaller deviations are excluded and the remaining numbers are selected and kept which represent deviations approximate to and still comply with the tolerance requirements.

Findings

The case study illustrates the effectiveness and superiority of the proposed method in that it can reduce the sample size, diminish the computations, predict wider tolerance ranges and improve the accuracy of three-dimensional tolerance of precision assembly simultaneously.

Research limitations/implications

The proposed method may be applied only when the dimensional and geometric tolerances are interpreted in the three-dimensional tolerance representation model.

Practical implications

The proposed tolerance analysis method can evaluate the impact of manufacturing errors on the product structure quantitatively and provide a theoretical basis for structural design, process planning and manufacture inspection.

Originality/value

The paper is original in proposing edge sampling as a sampling strategy to generating deviation numbers in tolerance analysis.
Enhance corrosion behavior of AZ31 magnesium alloy by tailoring the anodic oxidation time followed by heat treatment in simulated body fluid
Authors: Rahimi Mohammadreza , Mehdinavaz Aghdam Rouhollah , Heydarzadeh Sohi Mahmoud , Rezayan Ali Hossein , Ettelaei Maryam
Published: June 2021

Purpose

This paper aims to investigate the impact of anodizing time and heat treatment on morphology, phase and corrosion resistance of formed coating. To characterize the anodic oxide layer, X-ray diffraction (XRD) patterns and scanning electron microscopy (SEM) that was equipped with energy dispersive spectroscopy (EDS) was hired. The corrosion behavior of oxide-coated samples was estimated by electrochemical polarization test in simulated body fluid (SBF).

Design/methodology/approach

Anodic oxidation method is applied to reinforce the corrosion and biological properties of biomaterials in the biomedical industry. In this paper, the alkaline NaOH (1 M) electrolyte was used for AZ31 magnesium alloy anodizing accompanied by heat treatment in the air.

Findings

It can be concluded that the best corrosion resistance belongs to the 10 min anodic oxidized sample and among the heat-treated samples the 30 min anodized sample represented the lowest corrosion rate.

Originality/value

In this study, to the best of the authors’ knowledge for the first time, this paper describes the effect of anodizing process time on NaOH (1 M) electrolyte at 3 V on corrosion behavior of magnesium AZ31 alloy with an alternate method to change the phase composition of the formed oxide layer. The morphology and composition of the obtained anodic oxide layer were investigated under the results of SEM, EDS and XRD. The corrosion behavior of the oxide coatings layer fabricated on the magnesium-based substrate was studied by the potentiodynamic polarization test in the SBF solution.
Teaching entrepreneurship in China: culture matters
Authors: Lyu Jiejie , Shepherd Deborah M. , Lee Kerry
Published: June 2021

Purpose

The primary purpose of this research is to explore how the cultural context, in this case, China, influences the teaching of entrepreneurship that seeks to cultivate student entrepreneurs during their university experience.

Design/methodology/approach

A qualitative case study approach is adopted to explore how the cultural environment affects the delivery and application of entrepreneurship education to university students in a Chinese context. Seventeen student entrepreneurs and three lecturing staff members in three Chinese universities were interviewed using a semi-structured interview approach.

Findings

The findings suggest that while Chinese universities have been importing teaching models and methods of entrepreneurship education from the United States and other countries, both students and educators are starting to recognise the need for teaching methods to be contextualised and designed based on national conditions and cultural characteristics. Findings from this study highlight cultural fusion and collision in the process of importing and implementing entrepreneurial teaching methods. For example, teaching students how to write a business plan appears to offer limited value for students' start-up activities and their venture development. The didactic teaching method centred on teachers without entrepreneurial experience works for the teaching “about” entrepreneurship but is paradoxical to the goal of teaching “for” entrepreneurship.

Originality/value

Little theoretical or empirical attention has been paid to the complexity of the cultural environment of teaching approaches to entrepreneurship education. This paper provides novel empirical insight into why the cultural environment plays a critical role in teaching approaches to entrepreneurship education and how these teaching approaches can be culturally nuanced to better meet the needs of nascent student entrepreneurs in various cultural contexts.
Financing renewable energy projects in the Dominican Republic: an empirical study
Authors: Donastorg Angelines Daihana , Renukappa Suresh , Suresh Subashini
Published: June 2021

Purpose

Currently, renewable energy (RE) sources represent a crucial pillar in obtaining sustainable development, one of the global goals for all countries. However, this presents a unique challenge for emerging and developing countries. As the technical and financial issues remain a significant barrier in implementing RE projects, several mechanisms are available to aid the financial aspect of investing and implementing clean energy projects. This paper aims to discuss new and traditional trends in the financial area of renewable investment, focusing on the Dominican Republic (DR), identifying the gaps in the financial area regarding RE.

Design/methodology/approach

An empirical study was conducted in the DR. This country is located at the heart of the Caribbean. Given the complexity of RE and developing countries issues and the scarcity of comparable research in the area, an interpretivist research paradigm along with the qualitative methodology was adopted. Primary data was collected through semi-structured interviews. The study sample includes: directors, chief executive officers and managers responsible for the implementation of RE strategies in their respective departments/organisations. NVivo software was used for data management and the collected data was analysed using content analysis.

Findings

The research highlighted several severe financial handicaps regarding RE in the DR: The lack of RE assets recognition; lack of RE investment loans; perceived RE risk; and lack of financial guarantor. After extensive interviews with critical actors in the RE sector in the DR, the possible solutions and recommendations for avoiding locking the energy and economic sector in fossil fuel debt are: (a) diversification of RE technology assets recognition, (b) implementation of government RE fund, (c) RE education on all actors and (d) introduction and adoption of new financial trends such as green bonds, bank pooling, cooperatives and more.

Originality/value

This paper provides information and knowledge related to financial tools and policies that are available for the RE projects in the DR. The results have a socio-economic impact. This research provides a better understanding of the key financial tools to be explored by RE project developers in the developing countries. This study shows the gaps that exist between the knowledge that the stakeholders should possess and the actual knowledge that exists in the country regarding the financial aspect of an RE project.
The impact of high performance work system on employee service performance: the role of organizational support and organizational identification
Authors: Conteh Salamatu Bellah , Yuan Yijun
Published: June 2021

Purpose

An important objective of human resource (HR) research is to understand how HR practices can influence employee attitudes and behaviors in order to help achieve organizational goals via employee performance. The paper studies the relationship between High Performance Work System (HPWS) and employee service performance (ESP) via organizational support (OS) and organizational identification (OI). On one hand, this may help understand the “black box” between HPWS practices and ESP. On the other hand, while OS refers to employees' evaluations of favorable treatment from the organization and HPWS represent a significant channel the organization uses to communicate its support to employees, OS and OI literatures have not comprehensively examined the effect of HPWS practices on employee OS and OI beliefs.

Design/methodology/approach

This study takes a quantitative approach and employs hierarchical regression from a sample of 467 employees in 10 commercial banks in Sierra Leone.

Findings

The results show a positive relationship between HPWS practices and ESP and at the same time OS and OI partially mediate the relationship, suggesting that employees draw inferences from the HPWS-related treatment they receive in assessing the supportiveness of the organization.

Research limitations/implications

In this study, the authors put forth an innovative conceptual model of performance management by testing the relationships which have not been tested before, especially in a new context of banking industry in Sierra Leone. By implementing HPWS practices that demonstrate the organization cares about the employees' well-being and values their contribution, organizations are likely to be perceived as offering high levels of support for the employees.

Originality/value

The results of this study add to our knowledge about the antecedents of OS and OI. Moreover, while OS and OI research has been largely rooted in the organizational behavior literature, this study bridges the human resource literature and the organizational behavior literature, by combining HPWS, OS, OI and ESP.