bluuebunny/crossref_metadata_2025 huggingface dataset:
A Prospective Study of Outcomes After Tubularized Incised Plate (TIP) Urethroplasty: a Multivariable Analysis of Prognostic Factors in Children 1-3 Years Old
Authors: Roshandel M. Reza , Rashed Fahimeh Kazemi , Badr Tannaz Aghaei , Salomon Samantha , Ferrer Fernando A.
Published: September 2020

Background

Tubularized incised plate (TIP) urethroplasty as the most common hypospadias repair method, aims to achieve normal functioning of the penis along with cosmetic reconstruction. However, there are remaining questions toward anatomical prognostic factors affecting the results of surgery. Lack of age-matched controls or controlling for meatal location, employment of several surgical techniques or multiple surgeons, or age heterogeneity of the study population are the problems affected the results of the current body of literature.

Objective

This prospective study aimed to evaluate the preoperative factors to predict future complications associated with hypospadias repair outcomes in males aged between 1-3 years and performed by a single surgeon with employing multivariable analysis.

Patients and methods

A prospective cohort of 101 males aging from 1 to 3 years with distal to mid-shaft hypospadias were consecutively selected for TIP repair. The urethral plate dimensions in erect and flaccid states, penile length, glans diameter, and chordee were evaluated individually before reconstruction. After surgery and during follow-up visits, the subsequent transient and persistent complications were recorded.

Results

Postoperatively, the acute transient events were observed in 42 cases (41.6%) and the persistent complications in 16 cases (15.8%). The uncomplicated group had a higher percentage of patients with distal meatal location than the complicated group (P = 0.01%). Furthermore, fistula formation was notably higher in the group with acute surgical site infection (P< 0.001). The analysis also showed the width of the urethral plate to be associated with the development of complications (P = 0.03).

Conclusion

By performing TIP by a single surgeon on a homogenous study population and eliminating the impact of severe chordee as a potential cofounding variable, this study prospectively found that out of the anatomical specifications, pre- and postoperative factors, the urethral meatus location was the only significant and independent predictor of the development of complications in young children with midshaft to distal hypospadias. Moreover we found that in young children the wider the plate was, the more complications happened. Consequently, we hypostatized that in young children who their anatomical dimensions are almost in same range of values, a combination of urethral width and depth should be considered in the investigation of prognostic factors for hypospadias repair outcomes. (figure 1)

Figure 1.

The inverse relationship between width and depth in hypospadias anomalies
Validated ICP-MS method for measurement of plasma and intracellular antimony concentrations applied to pharmacokinetics of meglumine antimoniate
Authors: Garay-Baquero Diana J. , Rebellon-Sánchez David E. , Prieto Miguel D. , Giraldo-Parra Lina , Navas Adriana , Atkinson Sheryl , McDougall Stuart , Gómez Maria Adelaida
Published: September 2020

Aim

A high-throughput method using inductively coupled plasma mass spectrometry (ICP-MS) was developed and validated for the quantitative analysis of antimony in human plasma and peripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis undergoing treatment with meglumine antimoniate.

Methods

For this study, antimony was digested in clinical samples with 1% TMAH / 1% EDTA and indium was used as internal standard. Calibration curves for antimony, over the range of 25 to 10000 ng/mL were fitted to a linear model using a weighting of 1/concentration2. Accuracy, precision and stability were evaluated.

Results

Taking the lower limit of quantitation (LLOQ) to be the lowest validation concentration with precision and accuracy within 20% (25% at the LLOQ), the current assay was successfully validated from 25 to 10000 ng/mL for antimony in human plasma and PBMCs. Dilution studies demonstrated that concentrations up to 100000 ng/mL of antimony in plasma were reliably analyzed when diluted into the calibration range.

Conclusion

This protocol will serve as a baseline for future analytical designs, aiming to provide a reference method to allow inter-study comparisons.

What is already known about this subject

Antimonial drugs are the mainstay treatment for cutaneous leishmaniasis of which systemically administered pentavalent antimonials (SbV) are widely used, however the pharmacokinetics (PK) of these drugs at the site of action is unknown.

A wide range of analytical strategies have been used to quantify antimony in biological samples and atomic absorption spectroscopy is the most employed technique, however, no standardized methods for determination of intracellular concentrations of antimony were available.

Relationships between plasma and intracellular drug concentrations remain unknown for most antiparasitic drugs, and PK studies rely on plasma drug concentrations assuming these act as surrogates of intracellular concentrations.

What this study adds

We have developed and validated a reproducible and accurate ICP-MS method for the quantification of total antimony in human plasma and peripheral blood mononuclear cells (PBMCs) in accordance with the European Bioanalysis Forum (EBF) recommendations.

This method was successfully used to compare pharmacokinetic curves of antimony in plasma and intracellular compartments, in samples collected from patients undergoing treatment for cutaneous leishmaniasis with meglumine antimoniate.
Clinical Thrombosis Rate was not Increased in a Cohort of Cancer Patients with COVID-19
Authors: Zavras Phaedon D. , Kabarriti Rafi , Mehta Vikas , Goel Sanjay , Billett Henny H.
Published: September 2020

Increased rates of thromboembolic events (TE) have been reported in patients with coronavirus disease (COVID-19), even without prior predisposition to thrombosis. D-dimer levels have been shown to positively correlate with disease severity and mortality, leading to adoption of new empiric anticoagulation protocols by many centers.

We aimed to assess whether COVID-19 further increased the risk of TE events in a cancer population who tested positive for COVID-19 at Montefiore Medical Center, Bronx, NY.

The electronic medical records of 218 cancer patients were retrospectively reviewed up to April 10th, 2020. Work-up of thrombosis was done by the primary team upon clinical or laboratory suspicion. All imaging studies’ reports, within 20 days of COVID-19 positive test, were reviewed for presence of new arterial or venous thrombosis. Mortality was assessed up to one month since positive COVID-19 test result.

Twelve patients (5.5%) were found to have new arterial (N=6, 50%) or venous (N=6, 50%) thrombosis. Five patients (41.7%) had history of prior TE events. Incidence of deep venous thrombosis and pulmonary embolism was 1.8% and 0.5%, respectively. Arterial events occurred in the brain (66.7%), aorta (16.7%) and coronary arteries (16.7%). Median time from COVID test was 8 days (IQR, 1.5 - 11.3). Five patients (41.7%) had received either prophylactic or therapeutic anticoagulation for a median 2 days (IQR, 1 - 5). Median peak D-dimer within 36 hours of the TE event was 9.8 mcg/mL (N=4 patients, IQR, 1.7 - 18.3). Mortality did not differ significantly between the patients with new TE events vs those without; mortality 41.7% vs 37.4%, respectively, p=0.77. Empiric anticoagulation did not improve mortality.

Fifty percent of all TE events were arterial. The overall TE rate of 5.5% in the cancer population was not higher than the risk of general population. Our findings support the need for larger studies in the COVID-19+ cancer population.
Extreme Fuzzy Association of an Intrinsically Disordered Protein with Acidic Membranes
Authors: Hicks Alan , Escobar Cristian A. , Cross Timothy A. , Zhou Huan-Xiang
Published: September 2020

Many physiological and pathophysiological processes, including Mycobacterium tuberculosis (Mtb) cell division, may involve fuzzy membrane association by proteins via intrinsically disordered regions. The fuzziness is extreme when the conformation and pose of the bound protein and the composition of the proximal lipids are all highly dynamic. Here we tackled the challenge in characterizing the extreme fuzzy membrane association of the disordered, cytoplasmic N-terminal region (NT) of ChiZ, an Mtb divisome protein, by combining solution and solid-state NMR spectroscopy and molecular dynamics simulations. In a typical pose, NT is anchored to acidic membranes by Arg residues in the midsection. Competition for Arg interactions between lipids and acidic residues, all in the first half of NT, makes the second half more prominent in membrane association. This asymmetry is accentuated by membrane tethering of the downstream transmembrane helix. These insights into sequence-interaction relations may serve as a paradigm for understanding fuzzy membrane association.
Topographic Guidance in Melt-Electrowritten Tubular Scaffolds Enhances Engineered Kidney Tubule Performance
Authors: van Genderen Anne Metje , Jansen Katja , Kristen Marleen , van Duijn Joost , Li Yang , Schuurmans Carl C.L. , Malda Jos , Vermonden Tina , Jansen Jitske , Masereeuw Rosalinde , Castilho Miguel
Published: September 2020

To advance the engineering of kidney tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported kidney proximal tubules with enhanced properties. A custom-built MEW device was used to fabricate tubular fibrous scaffolds with small diameter sizes (Ø = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Tubular scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 0.5 mm and pore sizes of 0.2 mm were achieved. CiPTEC formed tight monolayers in all scaffold microarchitectures tested, but well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). To conclude, we present smaller diameter engineered kidney tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
Optimal carbon partitioning reconciles the apparent divergence between optimal and observed canopy profiles of photosynthetic capacity
Authors: Buckley Thomas N.
Published: September 2020

Research conducted

Photosynthetic capacity per unit irradiance is greater, and the marginal carbon revenue of water (∂A/∂E) is smaller, in shaded leaves than sunlit leaves, apparently contradicting optimization theory. I tested the hypothesis that these patterns arise from optimal carbon partitioning subject to biophysical constraints on leaf water potential.

Methods

In a whole plant model with two canopy modules, I adjusted carbon partitioning, nitrogen partitioning and leaf water potential to maximize carbon profit or canopy photosynthesis, and recorded how gas exchange parameters compared between shaded and sunlit modules in the optimum.

Key results

The model predicted that photosynthetic capacity per unit irradiance should be larger, and ∂A/∂Esmaller, in shaded modules compared to sunlit modules. This was attributable partly to radiation-driven differences in evaporative demand, and partly to differences in hydraulic conductance arising from the need to balance marginal returns on stem carbon investment between modules. The model verified, however, that invariance in the marginal carbon revenue of N (∂A/∂N) is in fact optimal.

Conclusion

The Cowan-Farquhar optimality solution (invariance of ∂A/∂E) does not apply to spatial variation within a canopy. The resulting variation in carbon-water economy explains differences in capacity per unit irradiance, reconciling optimization theory with observations.
Single cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis
Authors: Bais Abha S. , Cerqueira Débora M. , Clugston Andrew , Ho Jacqueline , Kostka Dennis
Published: September 2020

The kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only be treated by transplant or dialysis. A better understanding of molecular mechanisms that drive kidney development is important for designing strategies to enhance renal repair and regeneration. In this study, we profiled gene expression in the developing mouse kidney at embryonic day 14.5 at single cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney. Cell cycle activity distinguishes between the “primed” and “self-renewing” sub-populations of nephron progenitors, with increased expression of the cell cycle related genesBirc5, Cdca3, Smc2andSmc4in “primed” nephron progenitors. AugmentedBirc5expression was also detected in immature distal tubules and a sub-set of ureteric bud cells, suggesting thatBirc5might be a novel key molecule required for early events of nephron patterning and tubular fusion between the distal nephron and the collecting duct epithelia.
Short Peptides as Predictors for the Structure of Polyarginine Sequences in Disordered Proteins
Authors: Milorey B. , Schweitzer-Stenner R. , Andrews B. , Schwalbe H. , Urbanc B.
Published: September 2020

Intrinsically disordered proteins (IDPs) and regions (IDRs) are frequently enriched in charged amino acids. IDRs are regularly involved in important biological processes, where one or more charged residues is the driving force behind a protein-biomolecule interaction. Several lines of experimental and computational evidence suggest that polypeptides and proteins that carry high net charges have a high preference for extended conformations with average end to end distances exceeding expectations for self-avoiding random coils. Here, we show that charged arginine (R) residues in even short glycine (G) capped model peptides (GRRG and GRRRG) significantly affect the conformational propensities of each other when compared to the intrinsic propensities of a mostly unperturbed arginine in the tripeptide GRG. A conformational analysis based on experimentally determined J-coupling constants from heteronuclear NMR spectroscopy and amide I’ band profiles from polarized Raman spectroscopy reveals that nearest neighbor interactions stabilize extended β-strand conformations at the expense of polyproline II and turn conformations. The results from MD simulations with an CHARMM36m force field and TIP3P water reproduce our results only to a limited extent. The use of the Ramachandran distribution of the central residue of GRRRG in a calculation of end-to-end distances of polyarginines of different length yielded the expected power law behavior. The scaling coefficient of 0.66 suggests that such peptides would be more extended than predicted by a self-avoiding random walk. Our findings thus support in principle theoretical predictions of Mao et al. (Proc. Natl. Acad. Sci. USA, 107, 8183-8188, 2010).

Significance

Intrinsically disordered proteins are rich in charged and deficient in hydrophobic residues. High net charges of disordered protein segments favor statistical coil ensembles which are more extended than a self-avoiding random coil. It is unclear whether the chain extension solely reflects the avoidance of non-local interactions or also local nearest neighbor interactions provide significant contributions. The relevance of nearest neighbor interactions, which are neglected in random coil models, has been emphasized in the literature, but only sporadically considered in molecular modellings of disordered proteins and peptides. We determined the Ramachandran distributions of protonated arginine in GRRG and GRRRG peptides. Our results reveal the contribution of nearest neighbor interactions to the extended conformations reported for a variety of poly-arginine protein segments.
Transcriptional and morpho-physiological responses of Marchantia polymorpha upon phosphate starvation
Authors: Rico-Reséndiz Felix , Cervantes-Pérez Sergio Alan , Espinal-Centeno Annie , Dipp-Álvarez Melissa , Oropeza-Aburto Araceli , Hurtado-Bautista Enrique , Cruz-Hernández Andres , Bowman John L. , Ishizaki Kimitsune , Arteaga-Vázquez Mario A. , Herrera-Estrella Luis , Cruz-Ramírez Alfredo
Published: September 2020

Phosphate (Pi) is a pivotal nutrient that constraints plant development and productivity in natural ecosystems. Land colonization by plants, more than 470 million years ago, evolved adaptive mechanisms to conquer Pi-scarce environments. However, little is known about the molecular basis underlying such adaptations at early branches of plant phylogeny. To shed light on how early divergent plants respond to Pi limitation, we analyzed the morpho-physiological and transcriptional dynamics of Marchantia polymorpha upon Pi starvation. Our phylogenomic analysis highlights some gene networks present since the Chlorophytes and others established in the Streptophytes (eg. PHR1-SPX1 and STOP1-ALMT1, respectively). At the morpho-physiological level, the response is characterized by the induction of phosphatase activity, media acidification, accumulation of auronidins, reduction of internal Pi concentration and developmental modifications of rhizoids. The transcriptional response involves the induction of MpPHR1, Pi transporters, lipid turnover enzymes and MpMYB14, an essential transcription factor for auronidins biosynthesis. MpSTOP2 up-regulation correlates with expression changes in genes related to organic acid biosynthesis and transport, suggesting preference for citrate exudation. Analysis of MpPHR1 binding sequences (P1BS) shows enrichment of this cis regulatory element in differentially expressed genes. Our study unravels the strategies, at diverse levels of organization, exerted by M. polymorpha to cope with low Pi availability.

Significance Statement

This study unravels the transcriptional and morphophysiological mechanisms executed by the non-vascular, and rootless, plant Marchantia polymorpha upon phosphate starvation conditions. The findings in this study shed light on the mechanisms that early land plants may have developed for the conquest of substrates poor in available phosphate, some of which are still conserved by current-day plants. Moreover, our results open several working hypotheses and novel perspectives for the study of Pi-starvation responses along plant evolution.
Slipped strand mispairing in the gene encoding sialidase NanH3 inGardnerellaspp
Authors: Kurukulasuriya Shakya P. , Patterson Mo H. , Hill Janet E.
Published: September 2020

Cell wall proteins with sialidase activity are involved in carbohydrate assimilation, adhesion to mucosal surfaces, and biofilm formation.Gardnerellaspp. inhabit the human vaginal microbiome and encode up to three sialidase enzymes, two of which are suspected to be cell wall associated. Here we demonstrate that the gene encoding extracellular sialidase NanH3 is found almost exclusively inG. piotiiand closely relatedGardnerellagenome sp. 3, and its presence correlates with sialidase positive phenotype in a collection of 112Gardnerellaisolates. ThenanH3gene sequence includes a homopolymeric repeat of cytosines that varies in length within cell populations, indicating that this gene is subject to slipped-strand mispairing, a mechanisms of phase variation in bacteria. Variation in the length of the homopolymer sequence results in encoding of either the full length sialidase protein or truncated peptides lacking the sialidase domain due to introduction of reading-frame shifts and premature stop codons. Phase variation in NanH3 may be involved in immune evasion or modulation of adhesion to host epithelial cells, and formation of biofilms characteristic of the vaginal dysbiosis known as bacterial vaginosis.
Modulation of fungal virulence through CRZ1 regulated F-BAR-dependent actin remodeling and endocytosis in chickpea infecting phytopathogenAscochyta rabiei
Authors: Sinha Manisha , Shree Ankita , Singh Kunal , Kumar Kamal , Kumar Vimlesh , Verma Praveen Kumar
Published: September 2020

Polarized hyphal growth of filamentous pathogenic fungi is an essential event for host penetration and colonization. The long-range early endosomal trafficking during the hyphal growth is crucial for nutrient uptake, sensing of host-specific cues, and regulation of effector production. Bin1/Amphiphysin/Rvs167 (BAR) domain-containing proteins mediate fundamental cellular processes, including membrane remodeling and endocytosis. Here, we identified an F-BAR domain protein (ArF-BAR) in the necrotrophic fungusAscochyta rabieiand demonstrate its involvement in endosome-dependent fungal virulence on the host plant,Cicer arietinum. We show that ArF-BAR regulates endocytosis at the hyphal tip, localizes to the early endosomes, and is involved in actin dynamics. Functional studies involving gene knockout and complementation experiments reveal that ArF-BAR is essential for virulence. The loss-of-function of ArF-BAR results in delayed formation of first septa from the hyphal tip, crucial for host penetration and proliferation. ArF-BAR was induced in response to oxidative stress and infection and localized to endocytic vesicles within the fungal hyphae. We also show that ArF-BAR is able to tubulate synthetic liposomes, suggesting the functional role of F-BAR domain in membrane tubule formationin vivo. Further, our studies identified a stress-induced transcription factor, ArCRZ1 (Calcineurin-responsive zinc finger 1) as key regulator for transcriptional reprogramming of ArF-BAR. We propose a model in which ArCRZ1 functions upstream of ArF-BAR to regulate fungal pathogenesis through a mechanism that involves membrane remodeling and actin cytoskeleton regulation.

Author summary

BAR-domain superfamily is known to mold amorphous lipid bilayer into defined tubular shapes and critical for endosome formation and trafficking. Although these processes are studied earlier in the context of their structural and biochemical properties, there is limited evidence on the direct role of F-BAR domain proteins in the pathophysiological development of other economically important fungi. Our study assumes functional significance for plant infection as we identified an F-BAR domain-containing protein that is regulated by a distinct transcriptional network. We characterized F-BAR in a necrotrophic fungal pathogen,Ascochyta rabieithat causes the Ascochyta blight (AB) disease in chickpea plants. Additionally, we have also identified a calcium-regulated CRZ1 transcription factor that regulates the transcription ofArF-BAR. Our study will help to understand the complex interplay underlying the endosome formation required for fungal virulence.
Fixed single-cell RNA sequencing for understanding virus infection and host response
Authors: Van Phan Hoang , van Gent Michiel , Drayman Nir , Basu Anindita , Gack Michaela U. , Tay Savaş
Published: September 2020

Single-cell transcriptomic studies that require intracellular protein staining, rare cell sorting, or inactivation of infectious pathogens are severely limited because current high-throughput RNA sequencing methods are incompatible with paraformaldehyde treatment, a common tissue and cell fixation and preservation technique. Here we present FD-seq, a high-throughput method for droplet-based RNA sequencing of paraformaldehyde-fixed, stained and sorted single-cells. We show that FD-seq preserves the mRNA integrity and relative abundances during fixation and subsequent cell retrieval. Furthermore, FD-seq detects a higher number of genes and transcripts than methanol fixation. We applied FD-seq to investigate two important questions in Virology. First, by analyzing a rare population of cells supporting lytic reactivation of the human tumor virus KSHV, we identifiedTMEM119as a host factor that mediates viral reactivation. Second, we found that upon infection with the betacoronavirus OC43, which causes the common cold and is a close relative of SARS-CoV-2, pro-inflammatory pathways are primarily upregulated in lowly-infected cells that are exposed to the virus but fail to express high levels of viral genes. FD-seq thus enables integrating phenotypic with transcriptomic information in rare cell populations, and preserving and inactivating pathogenic samples that cannot be handled under regular biosafety measures.
Chemical Stabilization of the HIV-1 Capsid Results in Efficient HIV-1 Reverse Transcriptionin vitro
Authors: Jennings Jordan , Shi Jiong , Varadarajan Janani , Jamieson Parker J. , Aiken Christopher
Published: September 2020

A defining activity of retroviruses is reverse transcription, the process during which the viral genomic RNA is converted into the double strand DNA required for virus replication. Reverse transcriptase (RT), the viral enzyme responsible for this process, was identified in 1970 by assaying permeabilized retrovirus particles for DNA synthesisin vitro. Such reactions are inefficient with only a small fraction of viral genomes being converted to full-length double strand DNA molecules, possibly owing to disruption of the structure of the viral core. Here we show that reverse transcription in purified HIV-1 cores is enhanced by the addition of the capsid-binding host cell metabolite inositol hexakisphosphate (IP6). IP6 potently enhanced full-length minus strand synthesis, as did hexacarboxybenzene (HCB) which also stabilizes the HIV-1 capsid. Both IP6 and HCB stabilized the association of the viral CA and RT proteins with HIV-1 cores. In contrast to the wild type, cores isolated from mutant HIV-1 particles containing intrinsically hyperstable capsids exhibited efficient reverse transcription in the absence of IP6, further indicating that the compound promotes reverse transcription by stabilizing the viral capsid. Our results show that stabilization of the HIV-1 capsid permits efficient reverse transcription in HIV-1 cores, providing a sensitive experimental system for analyzing the functions of viral and host cell molecules and the role of capsid disassembly (uncoating) in the process.

IMPORTANCE

HIV-1 infection requires reverse transcription of the viral genome. While much is known about the biochemistry of reverse transcription from simplified biochemical reactions, reverse transcription during infection takes place within a viral core. However, endogenous reverse transcription reactions using permeabilized virions or purified viral cores have been inefficient. Using viral cores purified from infectious HIV-1 particles, we show that efficient reverse transcription is achievedin vitroby addition of the capsid-stabilizing metabolite inositol hexakisphosphate. Enhancement of reverse transcription was linked to the capsid-stabilizing effect of the compound, consistent with the known requirement for an intact or semi-intact viral capsid for HIV-1 infection. Our results establish a biologically relevant system for dissecting the function of the viral capsid and its disassembly during reverse transcription. The system may also prove useful for mechanistic studies of emerging capsid-targeting antiviral drugs.
Topography, spike dynamics and nanomechanics of individual native SARS-CoV-2 virions
Authors: Kiss Bálint , Kis Zoltán , Pályi Bernadett , Kellermayer Miklós S.Z.
Published: September 2020

SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, displays a corona-shaped layer of spikes which play fundamental role in the infection process. Recent structural data suggest that the spikes possess orientational freedom and the ribonucleoproteins segregate into basketlike structures. How these structural features regulate the dynamic and mechanical behavior of the native virion, however, remain unknown. By imaging and mechanically manipulating individual, native SARS-CoV-2 virions with atomic force microscopy, here we show that their surface displays a dynamic brush owing to the flexibility and rapid motion of the spikes. The virions are highly compliant and able to recover from drastic mechanical perturbations. Their global structure is remarkably temperature resistant, but the virion surface becomes progressively denuded of spikes upon thermal exposure. Thus, both the infectivity and thermal sensitivity of SARS-CoV-2 rely on the dynamics and the mechanics of the virus.

One sentence summary

The native coronavirus 2 displays a dynamic surface layer of spikes, a large mechanical compliance and unique self-healing capacity.
Insight into glycosphingolipid crypticity: Crystal structure of the anti-tumor antibody 14F7 and recognition of NeuGc GM3 ganglioside
Authors: Bjerregaard-Andersen Kaare , Johannesen Hedda , Abraha Fana , Šakanović Aleksandra , Groβer Daniel , Coskun Ünal , Anderluh Gregor , Oscarson Stefan , Moreno Ernesto , Grzybek Michal , Krengel Ute
Published: September 2020

Tumor-associated glycolipids such as NeuGc GM3 are auspicious molecular targets in antineoplastic therapies and vaccine strategies. 14F7 is an anti-tumor antibody with high clinical potential, which has extraordinary specificity for NeuGc GM3, but does not recognize the very similar, ubiquitous NeuAc GM3. Here we present the 2.3 Å crystal structure of the 14F7 binding domain (14F7 scFv) in complex with the NeuGc GM3 trisaccharide. Intriguingly, a water molecule appears to shape the specificity of 14F7. Using model membrane systems, we show that 14F7 recognizes NeuGc GM3 only above lipid concentrations that are likely to form glycolipid-rich domains. This “all-or-nothing” effect was exacerbated in giant unilamellar vesicles and multilamellar vesicles, whereas no binding was observed to 100 nm liposomes, emphasizing that the 14F7–NeuGc GM3 interaction is additionally modulated by membrane curvature. Unexpectedly, adding NeuAc GM3 strongly increased binding affinity to NeuGc GM3-containing liposomes. This effect may be important for tumor recognition, where the ubiquitous NeuAc GM3 may enhance 14F7 binding to NeuGc GM3-expressing cancer cells.
Detecting adaptive introgression in human evolution using convolutional neural networks
Authors: Gower Graham , Picazo Pablo Iáñez , Fumagalli Matteo , Racimo Fernando
Published: September 2020

Studies in a variety of species have shown evidence for positively selected variants introduced into one population via introgression from another, distantly related population—a process known as adaptive introgression. However, there are few explicit frameworks for jointly modelling introgression and positive selection, in order to detect these variants using genomic sequence data. Here, we develop an approach based on convolutional neural networks (CNNs). CNNs do not require the specification of an analytical model of allele frequency dynamics, and have outperformed alternative methods for classification and parameter estimation tasks in various areas of population genetics. Thus, they are potentially well suited to the identification of adaptive introgression. Using simulations, we trained CNNs on genotype matrices derived from genomes sampled from the donor population, the recipient population and a related non-introgressed population, in order to distinguish regions of the genome evolving under adaptive introgression from those evolving neutrally or experiencing selective sweeps. Our CNN architecture exhibits 95% accuracy on simulated data, even when the genomes are unphased, and accuracy decreases only moderately in the presence of heterosis. As a proof of concept, we applied our trained CNNs to human genomic datasets—both phased and unphased—to detect candidates for adaptive introgression that shaped our evolutionary history.
V(DD)J recombination is an important and evolutionarily conserved mechanism for generating antibodies with unusually long CDR3s
Authors: Safonova Yana , Pevzner Pavel A.
Published: September 2020

The V(DD)J recombination is currently viewed as an aberrant and inconsequential variant of the canonical V(D)J recombination. Moreover, since the classical 12/23 rule for the V(D)J recombination fails to explain the V(DD)J recombination, the molecular mechanism of tandem D-D fusions has remained unknown since they were discovered three decades ago. Revealing this mechanism is a biomedically important goal since tandem fusions contribute to broadly neutralizing antibodies with ultralong CDR3s. We reveal previously overlooked cryptic nonamers in the recombination signal sequences of human IGHD genes and demonstrate that these nonamers explain the vast majority of tandem fusions in human repertoires. We further reveal large clonal lineages formed by tandem fusions in antigen-stimulated immunosequencing data sets, suggesting that such data sets contain many more tandem fusions than previously thought and that about a quarter of large clonal lineages with unusually long CDR3s are generated through tandem fusions. Finally, we developed the SEARCH-D algorithm for identifying D genes in mammalian genomes and applied it to the recently completed Vertebrate Genomes Project assemblies, nearly doubling the number of mammalian species with known D genes. Our analysis revealed cryptic nonamers in RSSs of many mammalian genomes, thus demonstrating that the V(DD)J recombination is not a “bug” but an important feature preserved throughout mammalian evolution.
Methyl 5-chloro-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate: structure and Hirshfeld surface analysis
Authors: Shishkina Svitlana V. , Petrushova Lidiya A. , Burian Kateryna O. , Fedosov Andrii I. , Ukrainets Igor V.
Published: September 2020

The title compound, C10H8ClNO5S, which has potential analgesic activity, crystallizes in space group P21/n. The benzothiazine ring system adopts an intermediate form between sofa and twist-boat conformations. The coplanarity of the ester substituent to the bicyclic fragment is stabilized by an O—H...O intramolecular hydrogen bond. In the crystal, hydrogen bonds of type N—H...O(SO2) link the molecules into zigzag chains extending along the b-axis direction. Neighbouring chains are linked by both O—H...Cl and C—H...Cl interactions. A Hirshfeld surface analysis was used to compare different types of intermolecular interactions, giving contributions of O...H/H...O = 42.0%, C...H/H...C = 17.3%, Cl...H/H...Cl = 14.2%, H...H = 11.1%.
A risk-adjusted decoupled-net-present-value model to determine the optimal concession period of BOT projects
Authors: Nguyen Nhat , Almarri Khalid , Boussabaine Halim
Published: September 2020

Purpose

The net-present-value (NPV) method is well-known for its drawbacks. To overcome some of these NPV weaknesses this paper aims to provide a methodology to determine an optimal concession period that treats risk and time separately. The purpose of this paper is to apply the notion of risk-adjusted decoupled net present value (risk-adjusted DNPV) to determine a conception period taken into consideration synthetic insurance premiums as compensation for risks.

Design/methodology/approach

This paper conducts theoretical and empirical analysis and provides an integrated model for deriving concession periods of any PPP projects. The model is able to capture several contractual issues such risks costing and other contractual scenarios. Methodologically, the paper addressees both the issues of risk-based cost–benefit analysis and cash flow analysis bearing an emphasis of risk-adjusted DNPV to compute an optimum concession period.

Findings

The results show that using DNPV will produce a shorter concession period comparatively to NPV. The consequence of this is that the public sector will gain financially from an earlier transfer of the concession.

Research limitations/implications

This paper contributes to the PPP literature by combing DNPV and risk to determine the PPP concession period for the mutual benefits both the private and public sectors. The decoupling of risk from traditional NPV computation will allow for risk pricing and tradability through insurance and allocation.

Originality/value

The attempt to decouple time and risk in the computation of NPV is the added value to the body of knowledge.
Supply chain workforce training: addressing the digital skills gap
Authors: Foroughi Abbas
Published: September 2020

Purpose

The purpose of this research was to address the critical need for supply chain workforce training to empower employees to use new digital technologies and to identify and evaluate current sources of supply chain training.

Design/methodology/approach

An online search was performed to locate training that is available for supply chain employees. Training providers who met the online delivery criterion were identified and evaluated on: (1) amount of supply chain content and/or digital technology content, (2) flexibility, (3) customizable and (4) credentials offered.

Findings

Several sources of supply chain training were identified—supply chain professional organizations, consultants, MOOC courses and MicroMasters programs at colleges and universities.

Research limitations/implications

The results of this study are limited by the fact that the number of supply chain training providers identified is not exhaustive and because the study examined training opportunities available at a particular point in time. Course offerings will change over time; certification requirements will be updated, and new providers will appear.

Practical implications

By identifying sources of supply chain training that are currently available to help bridge this serious skill shortage, the results can serve as a guide to enterprises moving toward supply chain digitalization.

Social implications

To succeed in the current environment of digital transformation, employees need opportunities to build digital skills that are demanded by corporations around the world. This is especially important at a time when unemployment is at an alarming rate.

Originality/value

An earlier version of the paper was presented at the 2019 Meeting of the Decision Sciences Institute, November 23–25, 2019, in New Orleans, LA.
Auditing in times of social distancing: the effect of COVID-19 on auditing quality
Authors: Albitar Khaldoon , Gerged Ali Meftah , Kikhia Hassan , Hussainey Khaled
Published: September 2020

Purpose

This paper aims to discuss the theoretical impact of COVID-19 social distancing outbreak on audit quality.

Design/methodology/approach

This paper uses a desk study method to explore the possible impact of COVID-19 crisis on five key considerations for audit quality during the pandemic. These include audit fees, going concern assessment, auditor human capital, audit procedures and audit personnel salaries.

Findings

As many believe that the COVID-19 outbreak is as yet not a financial crisis, the authors, on the contrary, believe that the effects of the COVID-19 pandemic would be the toughest challenge for auditors and their clients since the 2007–2008 global financial crisis. Specifically, the authors believe that the COVID-19 social distancing can largely affect audit fees, going concern assessment, audit human capital, audit procedures, audit personnel salaries and audit effort, which ultimately can pose a severe impact on audit quality.

Practical implications

Due to the implementations of work-from-home strategy, audit firms are highly recommended to invest more in digital programs, including artificial intelligence, blockchain, network security and data function development. This can help them to be more adaptable to working from home experience, which is ultimately expected to enhance the effectiveness and the flexibility of communication between auditors and their clients. Also, the authors recommend stock markets and other governmental bodies to provide temporary relaxations in compliance requirements to corporations. This procedure is expected to help firms that apply work-from-home strategy to report better earnings figures, which is appeared to be positively associated with audit quality.

Originality/value

To date, to the best of the authors’ knowledge, there is no academic study that explores the potential impact of the COVID-19 outbreak on audit quality. This paper, therefore, fills an important research gap in the auditing literature. In addition, this paper can be used as a base to construct a research instrument (e.g. questionnaire or interviews) to provide empirical evidence on the potential impact of COVID-19 on audit quality.
The neoliberal reality of higher education in Australia: how accountingisation is corporatising knowledge
Authors: Martin-Sardesai Ann , Guthrie AM James , Parker Lee
Published: September 2020

Purpose

As accounting academics, the authors know that performance measurement is well-trodden ground in the literature. Yet rarely have they turned their gaze inwards to examine the performance controls which they are subject to in the own everyday working life. Over the past 40 years, the rise of the New Public Management paradigm and neoliberalism has intensified changes in the way universities, disciplines and individual academics justify the quality of their work. This paper aims to explore the impact of accountingisation on the field and the Australian public sector higher education sector.

Design/methodology/approach

The perceptions of accounting academics in Australia’s 37 business faculties and schools were collected via an online survey. Additionally, a document analysis of annual reports, internal reports, strategy documents and other confidential material were also used.

Findings

The changes have included the use of corporate and individual research metrics aimed at increasing institutional status, brand reputation and revenue generation. These changes have transformed business schools and universities into commercial enterprises and commoditised education. What this analysis demonstrates is the apparent relationship between various government agendas, the commercialisation of universities and the distortion of the research activities by individual academics. For increased profits and efficiencies, individual scholars have paid the highest price.

Practical implications

If the accounting discipline is to be sustainable in the long term, business schools in Australia must reconfigure their performance measurement systems.

Originality/value

To date, research on “accountingisation” has previously been primarily conducted in the health and social services sectors. This research raises rarely heard voices to expose the actual social and human costs of accountingisation in Australia’s higher education sector.
Examining the importance of gamification, social interaction and perceived enjoyment among young female online buyers in India
Authors: Raman Prashant
Published: September 2020

Purpose

The current research has dual motives. Firstly, this study aims to evaluate the effect of gamification on the behavioural intention (BI) of the young female consumers to use online websites for making purchases. Secondly, it examines the role of social interaction and perceived enjoyment (PE) – two antecedents that are considered to have an impact on the female buying behaviour in e-commerce.

Design/methodology/approach

A model is developed based on the technology acceptance model. The conceptual framework is augmented with additional constructs such as gamification, PE and social interaction. Data from a survey of 898 female respondents from India was collected to assess the proposed framework. The study uses partial least squares structural equation modelling technique to empirically validate the model.

Findings

Gamification exhibits a favourable influence on BI of young female consumers. Gamification also has a favourable and an indirect influence on BI through social interaction and PE. Although, gamification has a significant influence on perceived usefulness, the latter has no impact on the BI. The BI of using an online shopping website is directly associated with the buying intention. The online retailers need to offer an enjoyable and interactive experience to the female consumers so that the influence of gamification is sustainable.

Originality/value

The current research enlarges the ambit of gamification in the e-commerce segment, an area where empirical research is sparse. It highlights the significance of social interaction and PE as mediators. To the best of the author’s knowledge, gamification’s influence on female online buying behaviour has never been analysed before and hence different segmentation and marketing strategies are required to cater to their unique needs.
Changing the terminology from kidney replacement therapy to kidney support therapy
Authors: Raina Rupesh , Joshi Hirva , Chakraborty Ronith
Published: September 2020

Kidney replacement therapy (KRT) is a common supportive treatment for renal dysfunction, especially acute kidney injury. However, critically ill or immunosuppressed patients with renal dysfunction often have dysfunction in other organs as well. To improve patient outcomes, clinicians began to initiate kidney replacement therapy in situations where nonrenal conditions may lead to acute kidney injury, such as septic shock, hematopoietic stem cell transplantation, veno‐occlusive renal disease, cardiopulmonary bypass, chemotherapy, tumor lysis syndrome, hyperammonemia, and various others. In this review, we discuss the use of various modes of kidney replacement therapy in treating renal and nonrenal complications to illustrate why kidney support therapy is a more appropriate terminology than kidney replacement therapy.
Pea starch exhibits good expansion characteristics under relatively lower temperatures during extrusion cooking
Authors: Rangira Irene , Gu Bon‐Jae , Ek Pichmony , Ganjyal Girish M.
Published: September 2020

Extrusion processing characteristics of pea starch were studied as impacted by various extrusion cooking processing variables, including, moisture content (15%, 17.5%, and 20% w.b.), temperature (120, 135, and 150 °C), and screw speed (150, 200, and 250 rpm), in a co‐rotating twin‐screw extruder. Physicochemical properties such as radial expansion ratio (ER), unit density (UD), water absorption index (WAI), and water solubility index (WSI) were measured. ER of the extrudates ranged between 2.52 and 3.63. These values of ER were significantly high, although relatively lower compared to the highest values reported in the literature for corn and rice extrudates. The UD values for all the extrudates ranged from 0.12 to 0.35 g/cm3, WAI, and WSI values ranged from 10.98 to 12.10 g/g and from 0.12% to 7.73%, respectively. Both screw speed and moisture content had significant impacts on the ER (P < 0.01). The highest ER was observed for the extrusion cooking conditions of the lowest moisture content level (15%), lowest barrel temperature (120 °C), and lowest screw speed (150 rpm). The cross‐sectional microstructure of the extrudates showed that the samples with a high ER had thick and elongated pores. The results of this study indicate that pea starch is a viable ingredient for making puffed extruded products.

Practical Application

The food industry can utilize the information generated from this study in the development of extruded expanded food products with pea starch. The specific information related to process conditions can assist the food industry in determining the ideal conditions for extrusion cooking in the production.