bluuebunny/crossref_metadata_2025 huggingface dataset:
Corneal cisterns as drainage aqueducts
Authors: Gupta Shikha , Joshi Shivani , Mahalingam Karthikeyan , Singh Abhishek , Arora Monika , Gupta Viney
Published: January 2022

Importance

Anterior chamber paracentesis (ACP) is a known method of rapid reduction of IOP. The mechanism of how corneal fluid clears after ACP is not well described.

Objective

To determine the mechanism of instantaneous corneal clearing of edema after ACP.

Design, setting, and participants

This case series includes consecutive patients with high IOP and associated corneal edema, who presented to the Glaucoma Services of our tertiary care center. Pre- and post-intervention (ACP) ASOCTs were analyzed.

Main outcome measures

Resolution of corneal edema (clinical picture) and imaging of peripheral cornea and iridocorneal angle area.

Results

Ten consecutive patients who underwent an ACP were included in this study. The mean IOP pre-intervention was 48.4 ± 8.2 mmHg. ASOCT showed ill-defined conventional pathways of aqueous outflow, which were blocked by peripheral anterior synechiae in 4 eyes. Immediately post ACP, the IOP was 16.3 ± 5.6 mmHg (p < 0.001) and corneal edema resolved immediately. We found on ASOCT, that the intrastromal hypolucency of the peripheral cornea, (corneal cistern) which was limited in extent and U shaped, showed a posterior extension into the corneo-limbal junction to form well-defined anastomoses with the conventional aqueous drainage channels demonstrating a direct conduit for intracorneal fluid to egress. In 2/10 eyes, Schlemm’s canal opened intracamerally as well, suggesting direct reflux of intra-corneal fluid into the anterior chamber.

Conclusion and Relevance

After an ACP, in eyes with corneal edema to relieve IOP, we observed that the intracorneal cisterns undergo peripheral extension to drain corneal fluid through the conventional distal outflow channels.
Extreme γ’ fibrinogen levels in COVID-19 patients
Authors: Farrell David H. , Hudkins Matthew , Hamilton Heather , Underwood Samantha J. , Dewey Elizabeth N. , Kazmierczak Diana E. , Kazmierczak Steven C. , Messer William B. , Khan Akram , Schreiber Martin A.
Published: January 2022

Background

COVID-19 progression can be accompanied by a “cytokine storm” that leads to secondary sequelae such as thrombosis and acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 progression, but have far too much daily intra-individual variability to be useful in tracking the course of the disease. In contrast, we have shown that the inflammatory biomarker γ’ fibrinogen (γ’ Fbg) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. Objectives: The aims of the study were to measure γ’ Fbg in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression.

Methods

COVID-19 patients at a tertiary care medical center were retrospectively enrolled between 3/16/2020 and 8/1/2020. γ’ Fbg was measured using a commercial ELISA. Results: Our results showed that nine out of the seventeen patients with COVID-19 had extremely high levels of γ’ Fbg. γ’ Fbg levels were significantly associated with the need for ECMO and with mortality.

Conclusions

We found that COVID-19 patients can develop extraordinarily high levels of γ’ Fbg. The previous highest γ’ Fbg level that we are aware of was 80.3 mg/dL found in a study of 10,601 participants in the ARIC study. These results have several important clinical implications. γ’ Fbg contains a high affinity binding site for thrombin that binds to anion-binding exosite II on thrombin and protects it from inactivation by heparin. High levels of γ’ Fbg therefore provide a reservoir of heparin-resistant clot-bound thrombin when the γ’ Fbg is clotted. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients and suggest that heparin prophylaxis may be less effective than using other anticoagulants, particularly direct thrombin inhibitors.
Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
Authors: Hassanin Emadeldin , Spier Isabel , Bobbili Dheeraj R. , Aldisi Rana , Klinkhammer Hannah , David Friederike , Dueñas Nuria , Hüneburg Robert , Perne Claudia , Brunet Joan , Capella Gabriel , Nöthen Markus M. , Forstner Andreas J. , Mayr Andreas , Krawitz Peter , May Patrick , Aretz Stefan , Maj Carlo
Published: January 2022

Background and aims

Summarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification.

Methods

To assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (<20%), intermediate (20-80%), or high PRS (>80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios (OR) and to compute the lifetime incidence, respectively.

Results

Depending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6% and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve (AUC) in risk prediction (0.704).

Conclusion

The findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups.
Interaction of surface topography and taper mismatch on head-stem modular junction contact mechanics during assembly in modern total hip replacement
Authors: Gustafson Jonathan A. , Mell Steven P. , Levine Brett , Pourzal Robin , Lundberg Hannah J.
Published: January 2022

Implant failure due to fretting corrosion at the head-stem modular junction is an increasing problem in modular total hip arthroplasty. The effect of varying microgroove topography on modular junction contact mechanics has not been well characterized. The aim of this work was to employ a novel, microgrooved finite element (FEA) model of the hip taper interface and assess the role of microgroove geometry and taper mismatch angle on the modular junction mechanics during assembly. A two-dimensional, axisymmetric FEA model was created using a modern 12/14 taper design of a CoCrMo femoral head taper and Ti6Al4V stem taper. Microgrooves were modelled at the contacting interface of the tapers and varied based on height and spacing measurements obtained from a repository of measured retrievals. Additionally, taper angular mismatch between the head and stem was varied to simulate proximal- and distal-locked engagement. Forty simulations were conducted to parametrically evaluate the effects of microgroove surface topography and angular mismatch on predicted contact area, contact pressure, and equivalent plastic strain. Multiple linear regression analysis was highly significant (p < 0.001; R2> 0.74) for all outcome variables. The regression analysis identified microgroove geometry on the head taper to have the greatest influence on modular junction contact mechanics. Additionally, there was a significant second order relationship between both peak contact pressure (p < 0.001) and plastic strain (p < 0.001) with taper mismatch angle. These modeling techniques will be used to identify the implant parameters that maximize taper interference strength via large in-silico parametric studies.
Additive genetic effects in interacting species jointly determine the outcome of caterpillar herbivory
Authors: Gompert Zachariah , Saley Tara , Philbin Casey , Yoon Su’ad A. , Perry Eva , Sneck Michelle E. , Harrison Joshua G. , Buerkle C. Alex , Fordyce James A. , Nice Chris C. , Dodson Craig , Lebeis Sarah L. , Lucas Lauren K. , Forister Matthew L.
Published: January 2022

Plant-insect interactions are common and important in basic and applied biology. Trait and genetic variation can affect the outcome and evolution of these interactions, but the relative contributions of plant and insect genetic variation and how these interact remain unclear and are rarely subject to assessment in the same experimental context. Here we address this knowledge gap using a recent host range expansion onto alfalfa by the Melissa blue butterfly. Common garden rearing experiments and genomic data show that caterpillar performance depends on plant and insect genetic variation, with insect genetics contributing to performance earlier in development and plant genetics later. Our models of performance based on caterpillar genetics retained predictive power when applied to a second common garden. Much of the plant genetic effect could be explained by heritable variation in plant phytochemicals, especially saponins, peptides, and phosphatidyl cholines, providing a mechanistic understanding of variation in the species interaction. We find evidence of polygenic, mostly additive effects within and between species, with consistent effects of plant genotype on growth and development across multiple butterfly species. Our results inform theories of plant-insect coevolution and the evolution of diet breadth in herbivorous insects and other host-specific parasites.

Teaser summary

The combined, additive effects of plant and insect genetic variation explain Melissa blue caterpillar growth and development on alfalfa plants.
A quantitative, genome-wide analysis inDrosophilareveals transposable elements’ influence on gene expression is species-specific
Authors: Fablet Marie , Salces-Ortiz Judit , Jacquet Angelo , Menezes Bianca F. , Dechaud Corentin , Veber Philippe , Rebollo Rita , Vieira Cristina
Published: January 2022

Transposable elements (TEs) are parasite DNA sequences that are able to move and multiply along the chromosomes of all genomes. They can be controlled by the host through the targeting of silencing epigenetic marks, which may affect the chromatin structure of neighboring sequences, including genes. In this study, we used transcriptomic and epigenomic high-throughput data produced from ovarian samples of severalDrosophila melanogasterandDrosophila simulanswild-type strains, in order to finely quantify the influence of TE insertions on gene RNA levels and histone marks (H3K9me3 and H3K4me3). Our results reveal a stronger epigenetic effect of TEs on ortholog genes inD. simulanscompared toD. melanogaster. At the same time, we uncover a larger contribution of TEs to gene H3K9me3 variance within genomes inD. melanogaster, which is evidenced by a stronger correlation of TE numbers around genes with the levels of this chromatin mark inD. melanogaster. Overall, this work contributes to the understanding of species-specific influence of TEs within genomes. It provides a new light on the considerable natural variability provided by TEs, which may be associated with contrasted adaptive and evolutionary potentials.

Significance Statement

Transposable elements (TEs) are parasitic DNA sequences that are widespread components of all genomes. In this study, we combined genomic, transcriptomic and epigenomic high-throughput data produced from ovarian samples ofDrosophila melanogasterandDrosophila simulanswild-type strains, in order to finely quantify the genome-wide influence of TE insertions on gene expression. Our results uncover contrasted patterns depending on the strain, which may have evolutionary impacts.
Organ Scaffold Characterizations Using Intravital Microscopy
Authors: Corridon Peter R , Khan Anousha
Published: January 2022

This study contains intravital microscopy (IVM) data to characterize organ scaffolds created using decellularization. Decellularization creates cell-free collagen-based matrices from native organs, which can be used as scaffolds for regenerative medicine applications. This data set contains in vivo assays evaluating the effectiveness of decellularization and structural and functional integrity of the acellular nephron in the post-transplantation environment. Qualitative and quantitative assessments of scaffold DNA concentrations, tissue fluorescence signals, structural and functional integrities of various decellularized nephron segments, and velocity within the microcirculation were acquired and compared to the native (non-transplanted) organ. Cohorts of 2-3-month-old male Sprague Dawley rats were used: non-transplanted (n = 4), transplanted day 0 (n=4), transplanted day 1 (n = 4), transplanted day 2 (n = 4), and transplanted day 7 (n = 4). OIF formatted files illustrate IVM measurement processes and are made publicly available in a data repository. Such data is intended to support scientific reproducibility, complement future renal studies, and extend the use of this powerful imaging application to analyze other organ scaffold systems.
Parallels of quantum superposition in ecological models: from counterintuitive patterns to eco-evolutionary interpretations of cryptic species
Authors: Angeler David G. , Fried-Petersen Hannah B.
Published: January 2022

Superposition, i.e. the ability of a particle (electron, photon) to occur in different states or positions simultaneously, is a hallmark in the subatomic world of quantum mechanics but non-sensical from the perspective of macro-systems such as ecosystems and other complex systems of people and nature. Using time series and spatial analysis of bird, phytoplankton and benthic invertebrate communities, this paper shows that superposition can occur analogously in redundancy analysis (RDA), a form of canonical ordination frequently used by ecologists. Specifically, we used correlation analysis to show that species can be associated simultaneously with different orthogonal axes in RDA models, a pattern reminiscent of superposition. We discuss this counterintuitive result in relation to the statistical and mathematical features of RDA and the recognized limitations with current traditional species concepts based on vegetative morphology. We suggest that such “quantum weirdness” is reconcilable with classical ecosystems logic when the focus of research shifts from morphological species to cryptic species that consist of genetically and ecologically differentiated subpopulations. We support our argument with theoretical discussions of eco-evolutionary interpretations that should become testable once suitable data are available.
Metabolic resource overlap impacts on the competition of phyllosphere bacteria
Authors: Schlechter Rudolf O. , Kear Evan J. , Bernach Michał , Remus Daniela M. , Remus-Emsermann Mitja N. P.
Published: January 2022

The phyllosphere is densely colonised by rich microbial communities, despite sparse and heterogeneously distributed resources. The limitation of resources is expected to drive bacterial competition resulting in exclusion or coexistence based on fitness differences and resource overlap between individual colonisers. We studied the impact of resource competition by determining the effects of different bacterial colonisers on the growth of the model epiphytePantoea eucalypti299R (Pe299R). Resource overlap was predicted based on genome-scale metabolic modelling. By combining results of metabolic modelling and pairwise competitions in theArabidopsis thalianaphyllosphere andin vitro, we found that ten resources sufficed to explain fitness of Pe299R. An effect of both resource overlap and phylogenetic relationships was found on competition outcomesin vitroas well as in the phyllosphere. However, effects of resource competition were much weaker in the phyllosphere when compared toin vitroexperiments. When investigating growth dynamics and reproductive success at the single-cell resolution, resource overlap and phylogenetic relationships are only weakly correlated with epiphytic Pe299R reproductive success, indicating that the leaf’s spatial heterogeneity mitigates resource competition. Although the correlation is weak, the presence of competitors led to the development of Pe299R subpopulations that experienced different life histories and cell divisions. Surprisingly, in somein plantacompetitions, Pe299R benefitted from the presence of epiphytes despite high resource overlap to the competitor strain suggesting other factors having stronger effects than resource competition. This study provides fundamental insights into how bacterial communities are shaped in heterogeneous environments and provides a framework to predict competition outcomes.
Trophic ecology of deep-sea megafauna in the ultra-oligotrophic Southeastern Mediterranean Sea
Authors: Guy-Haim Tamar , Stern Nir , Sisma-Ventura Guy
Published: January 2022

The trophic ecology of fourteen species of bathybenthic and bathypelagic fishes and six species of bathybenthic decapod crustaceans from the continental slope and rise of the Southeastern Mediterranean Sea (SEMS) was examined using stable isotope analysis. Mean δ13C values among fish species varied by more than 4.0‰, from −20.85‰ (Macroramphosus scolopax) to −16.57‰ (Conger conger and Centrophorus granulosus), and increased as a function of depth (200 - 1400 m). Mean δ13C values of the crustaceans showed smaller variation, between −16.38‰ (Polycheles typhlops) and −18.50‰ (Aristeus antennatus). This suggests a shift from pelagic to regenerated benthic carbon sources with depth. Benthic carbon regeneration is further supported by the low benthic-pelagic POM-δ13C values, averaging −24.7 ± 1.2‰, and the mixing model results, presenting very low contribution of epipelagic POM to the bathyal fauna. Mean δ15N values of fish and crustacean species ranged 7.91 ± 0.36‰ to 11.36 ± 0.39‰ and 6.15 ± 0.31‰ to 7.69 ± 0.37‰, respectively, resulting in trophic position estimates, occupying the third and the fourth trophic levels. Thus, despite the proximity to the more productive areas of the shallow shelf, low number of trophic levels (TL~1.0) and narrow isotopic niche breadths (SEAc <1) were observed for bathybenthic crustaceans (TL = 3.62 ± 0.22) and bathypelagic fishes (TL = 4.33 ± 0.34) in the study area – probably due to the ultra-oligotrophic state of the SEMS resulting in limited carbon sources. Our results, which provide the first trophic description of deep-sea megafauna in the SEMS, offer insight into the carbon sources and food web structure of deep-sea ecosystems in oligotrophic marginal seas, and can be further used in ecological modeling and support the sustainable management of marine resources in the deep Levantine Sea.
A new demethylase gene OsDML4 involved in high temperature induced floury endosperm formation in rice (Oryza sativa L.)
Authors: Yan Yan , Li Chao , Liu Zhen , Zhuang Jun-Jie , Kong Jia-Rui , Yang Zhen-Kun , Yu Jie , Alam Mohammad Shah , Ruan Cheng-Cheng , Zhang Heng-Mu , Xu Jian-Hong
Published: January 2022

High temperature (HT) can affect the accumulation of seed storage materials and cause adverse effects on the yield and quality in rice. DNA methylation plays an important role in plant growth and development. However, the temperature and DNA methylation interaction on rice seed development has not been studied yet. Here, we identified a new demethylase gene OsDML4 and discovered its function on cytosine demethylation to affect the endosperm formation during the grain filling. Knockout of OsDML4 induced floury endosperm only under HT, which resulted from dramatically reduced the transcription and accumulation of glutelins and 16-kDa prolamin. The expression of two important transcription factors RISBZ1 and RPBF was significantly declined in the osdml4 mutants. The absence of OsDML4 also caused adverse effects on the formation of protein bodies (PBs), the number of PB-II was greatly decreased and incomplete PB-II with empty space and abnormally shaped PB-II were observed in the osdml4 mutants. Whole-genome bisulfite sequencing analysis of seeds at 15 days after pollination revealed much higher global methylation levels of CG, CHG and CHH contexts in the osdml4 mutants compared to wild type (WT). Moreover, the methylation status of RISBZ1 promoter was hypermethylated but RPBF promoter was nearly unchanged. No significant difference was detected between WT and the osdml4 mutants under room temperature. In conclusion, our study demonstrates a novel OsDML4-mediated epigenetic regulatory mechanism involving in the formation of floury endosperm, which will provide a new perspective in regulating endosperm development and the accumulation of SSPs in rice.
Using Survey Data to Estimate the Impact of the Omicron Variant on Vaccine Efficacy against COVID-19 Infection
Authors: Rufino Jesús , Baquero Carlos , Frey Davide , Glorioso Christin A. , Ortega Antonio , Reščič Nina , Roberts Julian Charles , Lillo Rosa E. , Menezes Raquel , Champati Jaya Prakash , Anta Antonio Fernádez
Published: January 2022

Data collected in the Global COVID-19 Trends and Impact Surveys (UMD Global CTIS), and data on variants sequencing from GISAID, are used to evaluate the impact of the Omicron variant (in South Africa and other countries) on the prevalence of COVID-19 among unvaccinated and vaccinated population, in general and discriminating by the number of doses. In South Africa, we observe that the prevalence of COVID-19 in December (with strong presence of Omicron) among the unvaccinated population is comparable to the prevalence during the previous wave (in August-September), in which Delta was the variant with the largest presence. However, among vaccinated, the prevalence of COVID-19 in December is much higher than in the previous wave. In fact, a significant reduction of the vaccine efficacy is observed from August-September to December. For instance, the efficacy drops from 0.81 to 0.30 for those vaccinated with 2 doses, and from 0.51 to 0.09 for those vaccinated with one dose. The study is then extended to other countries in which Omicron has been detected, comparing the situation in October (before Omicron) with that of December. While the reduction measured is smaller than in South Africa, we still found, for instance, an average drop in vaccine efficacy from 0.53 to 0.45 among those vaccinated with two doses. Moreover, we found a significant negative (Pearson) correlation of around −0.6 between the measured prevalence of Omicron and the vaccine efficacy.
Reconstitution of an active human CENP-E motor
Authors: Craske Benjamin , Legal Thibault , Welburn Julie P.I.
Published: January 2022

CENP-E is a large kinesin motor protein which plays pivotal roles in mitosis by facilitating chromosome capture, alignment and promoting microtubule flux in the spindle. So far, it has not been possible to obtain active human CENP-E to study its molecular properties. Xenopus CENP-E motor has been characterised in vitro and is used as a model motor, however its protein sequence differs significantly from human CENP-E. Here, we characterise human CENP-E motility in vitro. Full-length CENP-E exhibits an increase in run length and longer residency times on microtubules when compared to CENP-E motor truncations, indicating that the C-terminal microtubule binding site enhances the processivity when the full-length motor is active. In contrast to constitutively active human CENP-E truncations, full-length human CENP-E has a reduced microtubule landing rate in vitro, suggesting that the non-motor coiled coil regions self-regulate motor activity. Together, we demonstrate that human CENP-E is a processive motor, providing a useful tool to study the mechanistic basis for how human CENP-E drives chromosome congression and spindle organisation during human cell division.
CRISPR-Cas systems in Fusobacterium: An untapped genetic frontier
Authors: Umaña Ariana , Slade Daniel J.
Published: January 2022

Fusobacterium nucleatum has recently received significant attention for its strong connection with the acceleration and gravity of multiple cancers (e.g., colorectal, pancreatic, esophageal). However, our understanding of the molecular mechanisms that drive infection by this ‘oncomicrobe’ have been hindered by a lack of universal genetic tools. Herein we report a global bioinformatic identification and characterization of multiple Fusobacterium CRISPR-Cas adaptive immune systems including Cas13c, and detailed report of the proteins, spacer/repeat loci, trans- activating CRISPR RNA (tracrRNA), and CRISPR RNA (cRNA) from a Type II-A CRISPR-Cas9 system. Since most Fusobacterium are currently genetically intractable, this CRISPR-Cas bioinformatic roadmap could be used to build new genome editing and transcriptional tuning tools to characterize an increasingly important genus of human opportunistic-pathogens connected to the onset, progression, and severity of cancer.
Structural basis for Parkinson’s Disease-linked LRRK2’s binding to microtubules
Authors: Snead David M. , Matyszewski Mariusz , Dickey Andrea M. , Lin Yu Xuan , Leschziner Andres E. , Reck-Peterson Samara L.
Published: January 2022

Leucine Rich Repeat Kinase 2 (LRRK2) is one of the most commonly mutated genes in familial Parkinson’s Disease (PD). Under some circumstances, LRRK2 co-localizes with microtubules in cells, an association enhanced by PD mutations. We report a cryo-electron microscopy structure of the catalytic half of LRRK2, containing its kinase, which is in a closed conformation, and GTPase domains, bound to microtubules. We also report a structure of the catalytic half of LRRK1, which is closely related to LRRK2, but is not linked to PD. LRRK1’s structure is similar to LRRK2, but LRRK1 does not interact with microtubules. Guided by these structures, we identify amino acids in LRRK2’s GTPase domain that mediate microtubule binding; mutating them disrupts microtubule binding in vitro and in cells, without affecting LRRK2’s kinase activity. Our results have implications for the design of therapeutic LRRK2 kinase inhibitors.
Genomes of the extinct Sicilian wolf reveal a complex history of isolation and admixture with ancient dogs
Authors: Ciucani Marta Maria , Ramos-Madrigal Jazmín , Hernández-Alonso Germán , Carmagnini Alberto , Aninta Sabhrina Gita , Scharff-Olsen Camilla Hjorth , Lanigan Liam Thomas , Fracasso Ilaria , Clausen Cecilie G. , Aspi Jouni , Kojola Ilpo , Baltrūnaitė Laima , Balčiauskas Linas , Moore Jane , Åkesson Mikael , Saarma Urmas , Hindrikson Maris , Hulva Pavel , Bolfíková Barbora Černá , Nowak Carsten , Godinho Raquel , Smith Steve , Paule Ladislav , Nowak Sabina , Mysłajek Robert W. , Brutto Sabrina Lo , Ciucci Paolo , Boitani Luigi , Vernesi Cristiano , Stenøien Hans K. , Smith Oliver , Frantz Laurent , Rossi Lorenzo , Angelici Francesco Maria , Cilli Elisabetta , Sinding Mikkel-Holger S. , Gilbert M. Thomas P. , Gopalakrishnan Shyam
Published: January 2022

The Sicilian wolf represented the only population of wolves living on a Mediterranean island until the first half of the twentieth century (1930s-1960s)1–7. Previous studies hypothesised that they remained isolated from mainland wolves from the end of the Last Glacial Maximum (LGM)8,9, until human persecutions led them to extinction1–7.

There are only seven known Sicilian wolf specimens from the 19th and 20th century preserved in museums in Italy and recent morphometric analyses assigned them to the new subspeciesCanis lupus cristaldii10. To better understand the origins of the Sicilian wolf, and its relationship to other wolf populations, we sequenced four whole genomes (3.8×-11.6×) and five mitogenomes. We investigated the relationship between Sicilian wolves and other modern breeds to identify potential admixture. Furthermore, considering that the last land-bridge between Sicily and Italy disappeared after the LGM11, around 17 kya, we explored the possibility that the Sicilian wolf retained ancestry from ancient wolf and dog lineages. Additionally, we explored whether the long-term isolation might have affected the genomic diversity, inbreeding levels and genetic load of the Sicilian wolf.

Our findings show that the Sicilian wolves shared most ancestry with the modern Italian wolf population but are better modelled as admixed with European dog breeds, and shared traces of Eneolithic and Bronze age European dogs. We also find signatures of severe inbreeding and low genomic diversity at population and individual levels due to long-term isolation and drift, suggesting also low effective population size.
Virus-assisted directed evolution of enhanced suppressor tRNAs in mammalian cells
Authors: Kelemen Rachel E. , Jewel Delilah , Huang Rachel L. , Zhu Zeyu , Cao Xiaofu , Pasha Muhammad , Anthony Jon , van Opijnen Tim , Chatterjee Abhishek
Published: January 2022

Site-specific incorporation of unnatural amino acids (Uaas) in living cells relies on engineered aminoacyl-tRNA synthetase/tRNA pairs borrowed from a distant domain of life. Such heterologous suppressor tRNAs often show poor intrinsic activity, presumably due to the failure to optimally interact with a non-native translation system. This limitation can be addressed in E. coli using directed evolution. However, no suitable selection system is currently available to do the same in mammalian cells. Here we report virus-assisted directed evolution of tRNAs (VADER) in mammalian cells, which employs a double-sieve selection scheme to facilitate single-step enrichment of active-yet-orthogonal tRNA mutants from naïve libraries. Using VADER, we developed improved mutants of M. mazei pyrrolysyl-tRNA, the most popular Uaa mutagenesis platform in eukaryotes. We also show that the higher activity of the most efficient mutants is specific for mammalian cells, alluding to an improved interaction with the unique mammalian translation system.
Credit constraints and the survival and growth of beginning farms
Authors: Key Nigel
Published: January 2022

Purpose

Credit may help farmers survive and grow by helping farm households cope with farm or off-farm income variation and by allowing farmers to adopt more efficient production technologies and take advantage of scale economies. This study estimates how credit constraints affect the survival and growth of beginning farms and explores how this effect varies depending on the age of the farm operator.

Design/methodology/approach

Farms businesses are classified as credit constrained using a measure of repayment capacity: the interest expense ratio (interest expenses relative to gross income). Linked data from consecutive Agricultural Censuses are used to track individual farms over time.

Findings

Results show that beginning farms with a high interest expense ratio take on less new debt over the subsequent five years. These credit-constrained farms were found to have lower five-year survival and growth rates than similar unconstrained farms. The negative effect of being constrained on growth is greater for farms with operators younger than 40 years old.

Practical implications

The finding that credit constraints impede the growth and survival of beginning farms supports a rationale for targeted loan programs designed to help beginning farmers. Results suggest that some of the benefits from these programs will be greater for farms with younger operators.

Originality/value

This study is the first to estimate the effect of credit constraints on the survival and growth of farm businesses. The expansive farm-level panel dataset, which includes almost all beginning farmers in the US, allows for precise coefficient estimates while controlling for numerous farm and operator characteristics.
Supply chain finance in enhancing supply-oriented and demand-oriented performance capabilities – moderating role of perceived partner opportunism
Authors: Rajaguru Rajesh , Matanda Margaret Jekanyika , Zhang Wenqing
Published: January 2022

Purpose

While supply chain scholars concur on the need to integrate supply chain finance (SCF) processes to meet ever-changing customer demands, it is unclear how SCF influences business performance in the presence of perceived opportunistic behavior. Therefore, the study aims to investigate the moderating role of perceived partner opportunism in the supply chain.

Design/methodology/approach

Drawing on the dynamic capability theory (DCT), this study investigates how perceived supply chain partner opportunism moderates the mediating role of supply- and demand-oriented performances on the link between SCF and business performance, from the retail industry perspective. Data was collected from Australian retailing firms. In all, 293 completed surveys were received. Moderated mediation analysis was conducted.

Findings

The results of this study indicate that supply- and demand-oriented performances serially mediate the relationship between SCF and business performance. The study also found that the effect of SCF on performance was higher when perceived partner opportunism was lower.

Practical implications

To respond to changes in consumer preferences and demand effectively, supply chain and marketing managers need to understand the complex interaction between supply- and demand-oriented performances and the key role of SCF in developing such capabilities.

Originality/value

The current study theorizes and demonstrates the effects of supply- and demand-oriented performances that can facilitate the effects of SCF on business performance. Also, the study reveals the effect of each dimension of SCF (accounts payable, accounts receivable and inventory finance) on supply- and demand-oriented performances. Additionally, the study shows the key role of perceived partner opportunism in supply chain management.
Engaging luxury brand consumers on social media
Authors: Kumar Vikas , Khan Imran , Fatma Mobin , Singh Amrinder
Published: January 2022

Purpose

Although the consumption of luxury brands is significantly on the rise in emerging markets, a significant impetus is needed to boost their growth to achieve desired revenues and profitability. This paper aims to consider social media marketing activities and consumer-brand engagement as key constructs to realize these desired objectives.

Design/methodology/approach

The empirical relationships among social media marketing activities, consumer-brand engagement and consumer response have been examined with a sample of 465 respondents.

Findings

Social media marketing activities foster engagement among luxury brand consumers, translating into a favorable response. Besides this, informational marketer generated content (MGC) moderates the relationship between social media marketing activities and consumer-brand engagement.

Practical implications

Marketers can use the outcomes of this study to better engage consumers of luxury brands on social media platforms to engender a favorable response.

Originality/value

This paper highlights how consumers of luxury brands are engaged through different marketing activities in the social media context. Also, the moderating role of MGC has been explored.
The diagnostic accuracy of temporal artery ultrasound and temporal artery biopsy in giant cell arteritis: A single center Australian experience over 10 years
Authors: He Jianna , Williamson Luke , Ng Beverly , Wang Jeremy , Manolios Nicholas , Angelides Socrates , Farlow David , Wong Peter K. K.
Published: January 2022

Aim

To assess the diagnostic accuracy of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis in patients with suspected giant cell arteritis (GCA) over 10 years in an Australian center.

Method

Patients presenting to Westmead Hospital with possible GCA from March 2011 to December 2020 were retrospectively identified. The following parameters were obtained from the medical record: clinical presentation, inflammatory markers, temporal artery ultrasound findings, and temporal artery biopsy report. Data were assembled in a 2 × 2 table; sensitivity and specificity of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis were calculated.

Results

Over the 10‐year study period, 65 temporal artery ultrasounds were performed in 63 patients (n = 65; 61.9% female) with a mean ± standard deviation age of 69.6 ± 12.3 years. Thirteen out of 65 (20%) temporal artery ultrasounds had findings suggestive of GCA. Twenty patients (31.7%) had a clinical diagnosis of GCA irrespective of sonographic or biopsy findings. Compared with temporal artery biopsy, temporal artery ultrasound had a sensitivity of 71.4% and specificity of 93.3%. Compared with clinical diagnosis made by the treating rheumatologist, temporal artery ultrasound had a sensitivity of 55% and specificity of 95.3%.

Conclusion

Temporal artery ultrasound is a useful non‐invasive investigation in the assessment of suspected GCA. If positive in the setting of a suggestive clinical presentation, a temporal artery ultrasound probably avoids the need for a temporal artery biopsy. Temporal artery ultrasound could be more widely used in the clinical management of GCA.
Auditors' Professional Identities: Review and Future Directions*
Authors: Stack Ryan , Malsch Bertrand
Published: January 2022

Drawing on qualitative field studies, this literature review synthesizes research on the formation of professional identities. This journey is organized based on employee level, from the pre‐exposure phase of recruitment, up the hierarchy to staff‐, manager‐, and partner‐level work at auditing firms, to the level of those who leave professional service firms to pursue other work. Our analysis highlights the importance of acquiring soft skills over technical training in identity building, including the ability to incorporate unwritten rules and norms of professionalism that persist throughout professional careers. Our review reveals a scarcity of studies on the identity formation of managers. We also question the relevance of the literature on the socialization of staff auditors and partners and the impact on their identity. Critically, prior literature on auditor professional identity has emphasized one type of practitioner and setting—Western, urban, and Big 4 oriented—to the exclusion of other sites and perspectives. This emphasis has led to a disconnect between the extant research and the diversity of the realities in which auditing practices and auditors evolve. Thus, this review recognizes a need for new research directions and calls for research on professional services firms outside the Big 4 and in new and emerging markets. In addition, it advocates a greater focus on individuals and groups that have been excluded from prior research as the face of the profession changes.
Prediction models for severe manifestations and mortality due to COVID‐19: A systematic review
Authors: Miller Jamie L. , Tada Masafumi , Goto Michihiko , Chen Hao , Dang Elizabeth , Mohr Nicholas M. , Lee Sangil
Published: January 2022

Background

Throughout 2020, the coronavirus disease 2019 (COVID‐19) has become a threat to public health on national and global level. There has been an immediate need for research to understand the clinical signs and symptoms of COVID‐19 that can help predict deterioration including mechanical ventilation, organ support, and death. Studies thus far have addressed the epidemiology of the disease, common presentations, and susceptibility to acquisition and transmission of the virus; however, an accurate prognostic model for severe manifestations of COVID‐19 is still needed because of the limited healthcare resources available.

Objective

This systematic review aims to evaluate published reports of prediction models for severe illnesses caused COVID‐19.

Methods

Searches were developed by the primary author and a medical librarian using an iterative process of gathering and evaluating terms. Comprehensive strategies, including both index and keyword methods, were devised for PubMed and EMBASE. The data of confirmed COVID‐19 patients from randomized control studies, cohort studies, and case–control studies published between January 2020 and May 2021 were retrieved. Studies were independently assessed for risk of bias and applicability using the Prediction Model Risk Of Bias Assessment Tool (PROBAST). We collected study type, setting, sample size, type of validation, and outcome including intubation, ventilation, any other type of organ support, or death. The combination of the prediction model, scoring system, performance of predictive models, and geographic locations were summarized.

Results

A primary review found 445 articles relevant based on title and abstract. After further review, 366 were excluded based on the defined inclusion and exclusion criteria. Seventy‐nine articles were included in the qualitative analysis. Inter observer agreement on inclusion 0.84 (95%CI 0.78–0.89). When the PROBAST tool was applied, 70 of the 79 articles were identified to have high or unclear risk of bias, or high or unclear concern for applicability. Nine studies reported prediction models that were rated as low risk of bias and low concerns for applicability.

Conclusion

Several prognostic models for COVID‐19 were identified, with varying clinical score performance. Nine studies that had a low risk of bias and low concern for applicability, one from a general public population and hospital setting. The most promising and well‐validated scores include Clift et al.,15 and Knight et al.,18 which seem to have accurate prediction models that clinicians can use in the public health and emergency department setting.
Recruitment to higher specialty training in anaesthesia in the UK during the COVID‐19 pandemic: a national survey
Authors: Subramaniam J. , Durrant F. , Edwardson S. , El‐Ghazali S. , Holt C. , McCrossan R. , Pramanik I. , Wong D. J. N.
Published: January 2022

There were more applications for higher specialty training posts in anaesthesia in the UK starting in August 2021 than in previous years, with approximately two‐thirds being unsuccessful. We surveyed applicants to investigate their experience of the recruitment process (response rate 536/1056; 51%). Approximately 61% of respondents were not offered ST3 posts (n = 326). We enquired about their career plans for the next 12–24 months. Most respondents (79%) intended to take up a post equivalent to a third year of core training or a clinical fellow post from August 2021. Other options considered included: pursuing work abroad (17%); embarking on career breaks (16%); taking up higher training posts in intensive care medicine (15%); and permanently leaving medicine (9%). Nine per cent of respondents also expressed plans to pursue training in another medical specialty. Some expressed an intention to pursue further education or research (10%). A large proportion (42%) expressed a lack of confidence in being able to achieve the training requirements to later apply for a higher training post. The majority reported not feeling confident in achieving specialist registration in anaesthesia in the future without a training number (75%), and noted disruption to their wider life plans from the impending time out of training (78%). Sentiment analysis of free‐text responses indicated generally negative sentiment about the recruitment process. Themes elicited included: feeling the recruitment process was unfair; burnout and negative impact on well‐being; difficulties in making life plans; and feeling undervalued and abandoned. These results suggest that junior anaesthetic doctors in the UK negatively perceived postgraduate training structures and changes to the postgraduate curriculum and experienced difficulties in securing higher training.
Disadvantage, discrimination, and despair: Parental experiences of caring for children with disability in Bangladesh
Authors: Hussain Muhammed Muazzam , Raihan Mohammad Mojammel Hussain
Published: January 2022

This paper explored parental experiences of caring for children with disability (CWD) living in the Sylhet city corporation area of Bangladesh. This study applied a qualitative research approach. The purposive snowball sampling method was employed to recruit study participants. Twenty‐one in‐depth interviews and two focus group discussions with parents of children with physical, hearing, vision, and intellectual disabilities were conducted to learn more about their experiences and identify the difficulties and challenges they confront in their everyday lives. The results showed that respondents experience various disadvantages, for example, treatment‐related challenges, financial incapacity, housing, and transportation issues. The study also indicates that parents are subjected to discrimination, experience stress, and tension, and become depressed when they consider the future distressing condition of CWD after their death. Poverty, the societal stigma associated with disability, and a lack of social supports exacerbate parents' mental anguish and limit their ability to care for CWD patients. Therefore, it is recommended to develop new services delivery strategy, including home care, respite care, and monetary transfers for CWD caregivers, as well as community mobilization and inter‐professional collaboration, to enhance their current situation and overall well‐being.
Smooth muscle Rac1 contributes to pulmonary hypertension
Authors: Dilasser Florian , Rio Marc , Rose Lindsay , Tesse Angela , Guignabert Christophe , Loirand Gervaise , Sauzeau Vincent
Published: January 2022

Background and Purpose

Pulmonary hypertension (PH) is a multifactorial chronic disease characterized by an increase in pulmonary artery (PA) resistance leading to right ventricle (RV) failure. Endothelial dysfunction and alteration of NO/cGMP signalling in PA plays a major role in PH. We recently described the involvement of the Rho protein Rac1 in the control of systemic blood pressure through its involvement in NO‐mediated relaxation of arterial smooth muscle cell (SMC). The aim of this study was to analyse the role of SMC Rac1 in PH.

Experimental Approach

PH is induced by exposure of control and SMC Rac1‐deficient (SM‐Rac1‐KO) mice to chronic hypoxia (10% O2, 4 weeks). PH is assessed by the measurement of RV systolic pressure and hypertrophy. PA reactivity is analysed by isometric tension measurements. PA remodelling is quantified by immunofluorescence in lung sections and ROS are detected using the dihydroethidium probe and electronic paramagnetic resonance analysis. Rac1 activity is determined by immunofluorescence.

Key Results

Rac1 activation in PA of hypoxic mice and patients with idiopathic PH. Hypoxia‐induced rise in RV systolic pressure, RV hypertrophy and loss of endothelium‐dependent relaxation were significantly decreased in SM‐Rac1‐KO mice compared to control mice. SMC Rac1 deletion also limited hypoxia‐induced PA remodelling and ROS production in pulmonary artery smooth muscle cells (PASMCs).

Conclusion and Implications

Our results provide evidence for a protective effect of SM Rac1 deletion against hypoxic PH. Rac1 activity in PASMCs plays a causal role in PH by favouring ROS‐dependent PA remodelling and endothelial dysfunction induced by chronic hypoxia.