bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic reconstruction of measles transmission clusters from routinely collected surveillance data
Authors: Robert Alexis , Kucharski Adam J. , Gastañaduy Paul A. , Paul Prabasaj , Funk Sebastian
Published: June 2020

Pockets of susceptibility resulting from spatial or social heterogeneity in vaccine coverage can drive measles outbreaks, as cases imported into such pockets are likely to cause further transmission and lead to large transmission clusters. Characterizing the dynamics of transmission is essential for identifying which individuals and regions might be most at risk. As data from detailed contact-tracing investigations are not available in many settings, we developed an R package called
o2geosocial
to reconstruct the transmission clusters and the importation status of the cases from their age, location, genotype and onset date. We compared our inferred cluster size distributions to 737 transmission clusters identified through detailed contact-tracing in the USA between 2001 and 2016. We were able to reconstruct the importation status of the cases and found good agreement between the inferred and reference clusters. The results were improved when the contact-tracing investigations were used to set the importation status before running the model. Spatial heterogeneity in vaccine coverage is difficult to measure directly. Our approach was able to highlight areas with potential for local transmission using a minimal number of variables and could be applied to assess the intensity of ongoing transmission in a region.
Fungi.guru: comparative genomic and transcriptomic database for the Fungi kingdom
Authors: Lim Jolyn Jia Jia , Koh Jace , Moo Jia Rong , Villanueva Erielle Marie Fajardo , Putri Dhira Anindya , Lim Yuen Shan , Seetoh Wei Song , Mulupuri Sriya , Ng Janice Wan Zhen , Nguyen Nhi Le Uyen , Reji Rinta , Zhao Margaret Xuan , Chan Tong Ling , Rodrigues Edbert Edric , Kairon Ryan , Chee Natasha Cassandra , Low Ann Don , Xin Zoe Chen Hui , Lim Shan Chun , Lunardi Vanessa , Choy Fong Tuck , Chua Cherlyn Xin’Er , Sween Kenny Koh Ting , Ng Jonathan Wei Xiong , Mutwil Marek
Published: June 2020

The fungi kingdom is composed of eukaryotic heterotrophs, which are responsible for balancing the ecosystem and play a major role as decomposers. They also produce a vast diversity of secondary metabolites, which have antibiotic or pharmacological properties. However, our lack of knowledge of gene function in fungi precludes us from tailoring them to our needs and tapping into their metabolic diversity. To remedy this, we gathered genomic and gene expression data of 19 most widely-researched fungi to build a database, fungi.guru, which contains tools for cross-species identification of conserved pathways, functional gene modules, and gene families. We exemplify how our database can elucidate the molecular function, biological process and cellular component of genes involved in various biological processes, by identifying a secondary metabolite pathway producing gliotoxin inAspergillus fumigatus, the catabolic pathway of cellulose inCoprinopsis cinereaand the conserved DNA replication pathway inFusarium graminearumandPyricularia oryzae. The database is available atwww.fungi.guru.
Mapping of DNA damage genome-wide at nucleotide resolution by circle-damage-sequencing
Authors: Jin Seung-Gi , Pettinga Dean , Johnson Jennifer , Pfeifer Gerd P.
Published: June 2020

To establish relationships between mutations, for example in cancer genomes, and possible mechanisms linked to DNA damage, it is necessary to know at what sequence positions of the genome the damage occurs. However, it has been challenging to specifically map DNA damage at the nucleotide level of resolution and genome-wide with high sensitivity. Here, we describe a new method, which we named circle damage sequencing (circle-damage-seq), to accomplish this goal. The method is based on circularization of DNA molecules and DNA damage-selective cleavage of the circularized DNA followed by adapter ligation and sequencing. Based on the design of this approach, only DNA damage-containing molecules are sequenced. We conducted proof-of-principle studies to show that mapping of ultraviolet B-induced cyclobutane pyrimidine dimers (CPDs) can easily be achieved and show a specific tetranucleotide sequence context for CPDs (5’PyPy<>PyT/A) with no further sequence enrichment outside of this context. Our approach shows strongly reduced levels of CPDs near transcription start sites and a spike of this damage near the transcription end sites of genes. We then show that 1,N6-etheno-deoxyadenosine DNA adducts formed after treatment of cells with the lipid peroxidation product 4-hydroxynonenal can be mapped genome-wide at adenine positions within a preferred sequence context of 5’TAC/G3’. The circle-damage-seq method can be adapted for a variety of DNA lesions for which specific excision enzymes are available.
Detection of Horizontal Gene Transfer in the Genome of the ChoanoflagellateSalpingoeca rosetta
Authors: Matriano Danielle M. , Alegado Rosanna A. , Conaco Cecilia
Published: June 2020

Horizontal gene transfer (HGT), the movement of heritable materials between distantly related organisms, is crucial in eukaryotic evolution. However, the scale of HGT in choanoflagellates, the closest unicellular relatives of metazoans, and its possible roles in the evolution of animal multicellularity remains unexplored. We identified 703 potential HGTs in theS. rosettagenome using sequence-based tests. The majority of which were orthologous to bacterial lineages, yet displayed genomic features consistent with the rest of theS. rosettagenome – evidence of ancient acquisition events. Putative functions include enzymes involved in amino acid and carbohydrate metabolism, cell signaling, the synthesis of extracellular matrix components, and the detection of bacterial compounds. Functions of candidate HGTs may have contributed to the ability of choanoflagellates to assimilate novel metabolites, thereby supporting adaptation, survival in diverse ecological niches, and response to external cues that are possibly critical in the evolution of multicellularity in choanoflagellates.
Apoptotic endometrial caspase-3 mediated phospholipase a2 activation, a critical component in programing uterine receptivity
Authors: Garvin Sicily E. , Kyathanahalli Chandrashekara , Simpson Arren E. , Condon Jennifer C. , Jeyasuria Pancharatnam
Published: June 2020

The objective of this study was to determine the consequence of uterine apoptotic caspase-3 activation on day 1 post coitus (dpc) in the pregnant mouse. We previously demonstrated that during pregnancy uterine caspase-3 activation isolated to the myometrial compartment is largely non-apoptotic and controls uterine quiescence. In this study we determined that uterine caspase-3 activation on 1 dpc may play a critical role in regulating endometrial PGE2 synthesis though iPLA2 activation. These analyses provide novel insight into the molecular mechanisms that regulate previously reported increases in endometrial PGE2 synthesis in very early pregnancy, that act to enhance uterine receptivity.

We have identified the site and impact of that uterine apoptotic caspase-3 activation utilizing uteri isolated from non-pregnant control animals at estrous and diestrous and from control pregnant mice at 1-19 dpc. In addition, uteri were isolated from non-ligated controls (GD), unilateral (UL) and bilateral ligated (BL) uterine horn mouse models at 1, 3 and 6 dpc. Uteri were examined for apoptotic indices, such as caspase-3 activation and TUNEL staining. Immunohistochemical analysis was performed to identify the site of apoptotic caspase-3 activation. The presence of the truncated form of phospholipase A2 (tiPLA2) was examined as a measure of apoptotic caspase-3 mediated iPLA2 activation.

Our analysis determined that apoptotic caspase-3 and iPLA2 activation were limited to the endometrial compartments of the control and unilateral uteri on 1dpc and were not found in the bilateral ligated uterine horn on 3 or 6 dpc. Our data indicates that the presence of a conceptus on 1 dpc triggers an increase in endometrial apoptotic caspase-3 mediated iPLA2 activation. iPLA2 when activated causes the hydrolysis of fatty acids resulting in arachidonic acid release and production of PGE2, which in early pregnancy has been demonstrated to act in a leutoprotective manner, prolonging progesterone synthesis and promoting uterine receptivity.
Effect of hydrogen inhalation on IL-40 and SIgA in a Rat Model of Pulmonary Mucosal Immunity
Authors: Ma Yiping , Li Zhu , Zhao Yalei , Sun Mo , Sun Wuzhuang , Wang Jiechao
Published: June 2020

Background

Recently, some researchers have reported that PIgR expression is down-regulated in Chronic Obstructive Pulmonary Disease (COPD) and SIgA deficiency correlates with severity of airflow obstruction. What’ s more, some studies have demonstrated that 2 percent of hydrogen or hydrogen water is effective in treating and preventing various diseases.

Objectives

The aim of this study was to observe the effect of hydrogen on the expression of SIgA, PIgR, IL-4, IL-5, TGF-β1 and IL-40 in lung tissue of COPD rats, to study the relationship between lung pathology parameter and SIgA, PIgR, therefore we can understand the effect of hydrogen on the development of COPD by changing SIgA expression of airway mucosal in COPD rats.

Methods

A rat model of COPD was established by cigarette smoke exposure, and different concentrations of hydrogen were inhaled as intervention measures. After 4 months of cigarette smoke exposure, pathologic changes and airway wall remodeling of the lung were assessed by optical microscope. The protein expressions of SIgA, PIgR, IL-4, IL-5, TGF-β1 as well as IL-40 in the lung tissues were observed by immunohistochemistry or Western blot. The correlation between lung pathology parameter and the expression of SIgA, PIgR was analyzed. The correlation between SIgA and the expression of IL-4, IL-5, TGF-β1 and IL-40 was analyzed.

Results

The results showed that hydrogen inhalation significantly ameliorated lung pathology and airway wall remodeling, increased the protein expression of SIgA, PIgR, IL-4, IL-5, and IL-40, and reduced the protein expression of TGF-β1.

Conclusions

Inhalation of 22% and 41.6% hydrogen showed a better effect than inhalation of 2% hydrogen. Hydrogen inhalation can significantly improve the expression of SIgA on the mucosal surface of COPD rats, which may be one of the mechanisms which hydrogen works on COPD pathogenesis.
Exploring the Free Energy Landscape and Thermodynamics of Protein-Protein Association: HIV-1 Integrase Multimerization Induced by an Allosteric Inhibitor
Authors: Tse C. , Wickstrom L. , Kvaratskhelia M. , Gallicchio E. , Levy R. , Deng N.
Published: June 2020

We report the free energy landscape and thermodynamics of the protein-protein association responsible for the drug-induced multimerization of HIV-1 integrase (IN). Allosteric HIV-1 integrase inhibitors (ALLINIs) promote aberrant IN multimerization by bridging IN-IN intermolecular interactions. However, the thermodynamic driving forces and kinetics of the multimerization remain largely unknown. Here we explore the early steps in the IN multimerization by using umbrella sampling and unbiased molecular dynamics simulations in explicit solvent. In direct simulations, the two initially separated dimers spontaneously associate to form near-native complexes that resemble the crystal structure of the aberrant tetramer. Most strikingly, the effective interaction of the protein-protein association is very short-ranged: the two dimers associate rapidly within tens of nanoseconds when their binding surfaces are separated by d ≤ 4.3 Å (less than two water diameters). Beyond this distance, the oligomerization kinetics appears to be diffusion controlled with a much longer association time. The free energy profile also captured the crucial role of ALLINI in promoting multimerization, and explained why several CTD mutations are remarkably resistant to the drug-induced multimerization. The results also show that at small separation the protein-protein binding process contains two consecutive phases with distinct thermodynamic signatures. First, inter-protein water molecules are expelled to the bulk resulting in a small increase in entropy, as the solvent entropy gain from the water release is nearly cancelled by the loss of side chain entropies as the two proteins approach each other. At shorter distances, the two dry binding surfaces adapt to each other to optimize their interaction energy at the expense of further protein configurational entropy loss. While the binding interfaces feature clusters of hydrophobic residues, overall, the protein-protein association in this system is driven by enthalpy and opposed by entropy.

Statement of Significance

Elucidating the energetics and thermodynamic aspects of protein-protein association is important for understanding this fundamental biophysical process. This study provided a more complete physical picture of the protein-protein association responsible for the drug-induced HIV-1 integrase multimerization. The results captured the critical role of the inhibitor, and accounted for the effects of mutations on the protein association. Remarkably, the effective range of the protein-protein attractive funnel is found to be very short, at less than two layers of water, despite the fact that the two binding partners carry opposite net charges. Lastly, entropy/enthalpy decomposition shows that the solvent release from the inter-protein region into the bulk is more than offset by the loss of the solute configurational entropy due to complexation.
Generation of clonal male and female mice through CRISPR/Cas9-mediated Y chromosome deletion in embryonic stem cells
Authors: Qin Yiren , Wong Bokey , Geng Fuqiang , Zhong Liangwen , Parada Luis F. , Wen Duancheng
Published: June 2020

Mice derived entirely from embryonic stem (ES) cells can be generated in one step through tetraploid complementation. Although XY male ES cell lines are commonly used in this system, occasionally, monosomic XO female all-ES mice are produced through spontaneous Y chromosome loss. Here, we describe an efficient method to obtain monosomic XO ES cells by CRISPR/Cas9-mediated deletion of the Y chromosome allowing generation of clonal male and female mice by tetraploid complementation. The monosomic XO female mice are viable and are able to produce normal male and female offspring. Direct generation of clonal male and female mice from the same mutant ES cells significantly accelerates the production of complex genetically modified mouse models by circumventing multiple rounds of outbreeding.
Effect of ligands on HP-induced unfolding and oligomerization of β-lactoglobulin
Authors: Minić S. , Annighöfer B. , Hélary A. , Hamdane D. , Hoa G. Hui Bon , Loupiac C. , Brûlet A. , Combet S.
Published: June 2020

To probe intermediate states during unfolding and oligomerization of proteins remains a major challenge. High pressure (HP) is a powerful tool for studying these problems, revealing subtle structural changes in proteins not accessible by other means of denaturation. Bovine β-lactoglobulin (BLG), the main whey protein, has a strong propensity to bind various bioactive molecules, such as retinol and resveratrol, two ligands with different affinity and binding sites. By combiningin situHP-small-angle neutron scattering (SANS) and HP-UV/visible absorption spectroscopy, we report the specific effects of these ligands on 3D conformational and local changes in BLG induced by HP. Depending on BLG concentration, two different unfolding mechanisms are observedin situunder pressures up to ~300 MPa, mediated by the formation of disulfide bonds: either a complete protein unfolding, from native dimers to Gaussian chains, or a partial unfolding with oligomerization in tetramers. Retinol, which has a high affinity for BLG hydrophobic cavity, significantly stabilizes BLG both in 3D and local environments, by shifting the onset of protein unfolding by ~100 MPa. Increasing temperature from 30 to 37°C enhances the hydrophobic stabilization effects of retinol. In contrast, resveratrol, which has a low binding affinity for site(s) on the surface of the BLG, does not induce any significant effect on the structural changes of BLG due to pressure. HP treatment back and forth up to ~300 MPa causes irreversible covalent oligomerization of BLG.Ab initiomodeling of SANS shows that the oligomers formed from BLG/retinol complex are smaller and more elongated compared to BLG without ligand or in the presence of resveratrol. By combining HP-SANS and HP-UV/vis absorption spectroscopy, our strategy highlights the crucial role of BLG hydrophobic cavity and opens up new possibilities for the structural determination of HP-induced protein folding intermediates and irreversible oligomerization.

STATEMENT OF SIGNIFICANCE

High pressure (HP) is a powerful probe to access the intermediate states of proteins through subtle structural changes not accessible by other means of denaturation. Bovine β-lactoglobulin (BLG), the main whey protein, is able to bind various bioactive molecules, such as retinol and resveratrol, exhibiting different affinity and binding sites. By combining HP-small-angle neutron scattering and HP-UV/visible absorption spectroscopy, we highlight two different mechanisms during the unfolding and oligomerization of BLG depending on protein concentration. Above all, we show that retinol significantly prevents the unfolding and oligomerization of BLG, unlike resveratrol, emphasizing the crucial role of the hydrophobic cavity in BLG stabilization. Our strategy opens up new possibilities for the structural determination of protein intermediates and oligomers using HP.
Inhibition of fibrosis with multi-agent therapy in pulmonary fibrosis: Results of a drug library screening
Authors: Braun Cassandra Batzlaff , Girtman Megan , Jenson Paige , Bourne Michael H , Chae JuneMee , Kottom Theodore , Limper Andrew
Published: June 2020

Aims

Successful management of IPF will likely require multi-drug therapy as its pathogenesis is thought to be both driven by both pro-inflammatory and pro-fibrotic pathways. We hypothesized that the available anti-fibrotic agents, pirfenidone and nintedanib, may exhibit synergy in suppressing lung fibroblast extracellular matrix protein generation when administered in combination with other orally active agents.

Materials and Methods

A fibroblastic cell line (AKR-2B) was stimulated with TGF-β1 and used to screen a library of over 1500 FDA approved drugs. Extracellular matrix protein generation was assessed via fibronectin ELISA assay and maintenance of cell viability confirmed with XTT assay.

Results

The screening revealed sixty-two drugs from the repurposed drug-screening library that were shown to significantly suppress fibronectin expression and not result in cell death. Specifically drugs within the category of NSAIDs, steroids, azole antifungal agents, and antipyrine were associated with significant suppression of fibronectin on ELISA analysis. Surprisingly, we observed anti-fibrotic activity across a number of the azole antifungal compounds. We next assessed whether combination of azoles would exhibit synergy when combined with current anti-fibrotic therapies in the stimulated fibroblasts. As proof of concept, we demonstratedin vitrosynergy between oxiconazole and nintedanib in suppressing fibroblast generation of extracellular matrix fibronectin.

Conclusions

These results suggest an approach to identify potential combinations of therapy that may improve patient outcomes by reducing cost and potential toxicities during treatment.
Mapping the Multiscale Organisation of Escherichia Coli Chromosome in a Hi-C-integrated Model
Authors: Wasim Abdul , Gupta Ankit , Mondal Jagannath
Published: June 2020

The chromosome of Escherichia Coli (E. coli) is riddled with multi-faceted complexity and its nature of organization is slowly getting recognised. The emergence of chromosome conformation capture techniques and super-resolution microscopy are providing newer ways to explore chromosome organization, and dynamics and its effect on gene expression. Here we combine a beads-on-a-spring polymer-based framework with recently reported high-resolution Hi-C data of E. coli chromosome to develop a comprehensive model of E. coli chromosome at 5 kilo base-pair resolution. The model captures a self-organised chromosome composed of linearly organised genetic loci, and segregated macrodomains within a ring-like helicoid architecture, with no net chirality. Additionally, a genome-wide map identifies multiple chromosomal interaction domains (CIDs) and corroborates well with a transcription-centric model of the E. coli chromosome. The investigation further demonstrates that while only a small fraction of the Hi-C contacts is dictating the underlying chromosomal organization, a random-walk polymer chain devoid of Hi-C encoded contact information would fail to map the key genomic interactions unique to E. coli. Collectively, the present work, integrated with Hi-C interaction, elucidates the organization of bacterial chromosome at multiple scales, ranging from identifying a helical, macro-domain-segregated morphology at coarse-grained scale to a manifestation of CIDs at a fine-grained scale.
Site-specific Crosslinking Coupled with Mass Spectrometry as a Structural Tool in Studies of the Human α1Glycine Receptor
Authors: Veeramachaneni Rathna J. , Donelan Chelsee A. , Tomcho Kayce A. , Aggarwal Shaili , Lapinsky David J. , Cascio Michael
Published: June 2020

Recent advances in mass spectrometry coupled with chemical crosslinking (CX-MS) can be applied for the structural interrogation of macromolecular complexes to identify statedependent distance constraints and provides a powerful complementary technique to other structural methods. In this study, we develop a CX-MS approach to identify the sites of crosslinking from a single targeted location within the human glycine receptor (GlyR) in a single apo/resting state. The GlyR belongs to the family of pentameric ligand-gated ion channel receptors that function in fast neuronal transmission. A single cysteine residue was re-introduced intoCys nullGlyR construct at position 41 within the extracellular domain of an overexpressed human a1 homomeric GlyR. After purification and reconstitution into vesicles, a methanethiosulfonate benzophenone heterobifunctional crosslinker was attached via formation of a disulfide bond, and the resting receptor is subsequently photocrosslinked. Monomeric and oligomeric bands from SDS-PAGE gels were then trypsinized and analyzed by tandem MS in bottom-up studies. Dozens of intra- and inter-subunit sites of crosslinking were differentiated and identified from single gel bands (pmols of purified GlyR), showing the utility of this approach to identify a diverse array of distance constraints of GlyR in its resting state. These studies highlight the potential of CX-MS as an experimental approach to identify state-dependent crosslinks of full length integral membrane protein assemblies in a native-like lipid environment.
Secondary single-cell transcriptomic analysis reveals common molecular signatures of cerebrovascular injury between traumatic brain injury and aging
Authors: Guo Xinying , Zhang Bangyan , Gomez-Pinilla Fernando , Gao Fan , Zhao Zhen
Published: June 2020

Cerebrovascular injury is a common pathological feature of a spectrum of neurological disorders including traumatic brain injury (TBI), stroke, Alzheimer’s disease (AD), as well as aging. Vascular manifestations among these conditions are similar indeed, including the breakdown of the blood-brain barrier (BBB). However, whether there is a common molecular mechanism underlying the vascular changes among these conditions remains elusive. Here, we report secondary transcriptomic analysis on cerebrovascular cells based single-cell RNA-seq datasets of mouse models of mild TBI and aging, with a focus on endothelial cells and pericytes. We identify several molecular signatures commonly found between mTBI and aging vasculature, includingAdamts1, Rpl23a, Tmem252, Car4, Serpine2, andNdnfin endothelial cells, andRps29andSepp1in pericytes. These markers may represent the shared endophenotype of microvascular injury and be considered as cerebrovascular injury responsive genes. Additionally, pathway analysis on differentially expressed genes demonstrated alterations in common pathways between mTBI and aging, including vascular development and extracellular matrix pathways in endothelial cells. Hence, our analysis suggests that cerebrovascular injury triggered by different neurological conditions may share common molecular signatures, which may only be detected at the single-cell transcriptome level.
Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants
Authors: Leitsalu Liis , Palover Marili , Tõnis Sikka Timo , Reigo Anu , Kals Mart , Pärn Kalle , Nikopensius Tiit , Esko Tõnu , Metspalu Andres , Padrik Peeter , Tõnisson Neeme
Published: June 2020

Genotype-first approach allows to systematically identify carriers of pathogenic variants in BRCA1/2 genes conferring a high risk of familial breast and ovarian cancer. Participants of the Estonian biobank have expressed support for the disclosure of clinically significant findings. With an Estonian biobank cohort, we applied a genotype-first approach, contacted carriers and offered return of results with genetic counseling. We evaluated participants’ responses to and the clinical utility of the reporting of actionable genetic findings. Twenty-two of 40 contacted carriers of 17 pathogenic BRCA1/2 variants responded and chose to receive results. Eight of these 22 participants qualified for high-risk assessment based on National Comprehensive Cancer Network criteria. Twenty of 21 counseled participants appreciated being contacted. Relatives of 10 participants underwent cascade screening. Five of 16 eligible female BRCA1/2 variant carriers chose to undergo risk-reducing surgery, and 10 adhered to surveillance recommendations over the 30-month follow-up period. We recommend the return of results to population-based biobank participants; this approach could be viewed as a model for population-wide genetic testing. The genotype-first approach permits the identification of individuals at high risk who would not be identified by application of an approach based on personal and family histories only.
Dairy-free imitation cheese: is further development required?
Authors: Nicolás Saraco Maximiliano , Blaxland James
Published: June 2020

Purpose

The aim of this study was to compare the organoleptic attributes and meltability of selected, commercial dairy-free imitation cheeses (DFICs) with those of their dairy counterparts to thus determine whether commercial DFIC needs to be further developed.

Design/methodology/approach

Market research was conducted to determine the availability of DFICs in the United Kingdom (UK) and thus select the varieties to assess. Mild cheddar was chosen for its popularity wide availability in the United Kingdom and Italian-style hard cheese for its complex organoleptic profile. The organoleptic attributes and melting properties of the chosen DFIC products were assessed by using descriptive sensory evaluation and their meltability was assessed using the Arnott test, respectively.

Findings

109 different DFICs were found; most of them (74%) presented coconut oil as their primary ingredient. None of the assessed DFICs assessed could mimic the organoleptic attributes of their dairy counterparts accurately; however, one of the non-dairy mild cheddar samples was regarded as potentially acceptable by the assessors of the sensory evaluation assessors. Nonetheless, the meltability of this sample was significantly lower than that of mild cheddar cheese.

Practical implications

The findings indicate that, to obtain products that can mimic the organoleptic attributes and meltability of cheese more accurately, further development is required for the DFIC varieties assessed.

Originality/value

No academic publications have explored and investigated commercial DFICs with similar ingredients to those found in commercial DFICs; the commercial importance of these products may augment in the short term owing to the reported growth in the number of vegan individuals in the UK and in Europe.
A simple model of time zone differences, virtual trade and informality
Authors: Mandal Biswajit , Prasad Alaka Shree
Published: June 2020

Purpose

This paper aims to strive to model virtual trade resulting from time zone differences in an otherwise Heckscher–Ohlin set up which is absent in the literature. So, the paper adds some value to the existing literature on time zones (TZ) and trade.

Design/methodology/approach

A competitive general equilibrium model is developed first to capture the effect of TZ differences on virtual trade. Then the authors examine, in brief, if distance can be accommodated in such framework. Finally, the authors extend the model to incorporate informality.

Findings

It is seen that exploitation of time zone difference benefits skilled labor and hurts capital under reasonable assumption. In what follows, time zone difference exploiting sector expands, whereas the other sector contracts. Then, the model has been extended to examine how distance may also lead to similar outcomes. In addition, the model is further modified to explore the effect of virtual trade in an informality and associated extortion ridden economy. Interestingly, virtual trade turns out to be beneficial to unskilled workers as well, and leads to a fall in the number of extortionists, though informal production is augmented.

Research limitations/implications

This model is a competitive model that may not clearly reflect the realistic world. However, interestingly this may form the basis of looking into some other appealing dimensions of the real world.

Originality/value

TZ and related communication-cost-driven trade arguments are relatively less explored theoretically. Therefore, the work adds some value to the theoretical understanding of outsourcing in service trade that uses day-night differences across the globe.
Las Cruces housing price fluctuations
Authors: Fullerton Steven L. , Holcomb James H. , Fullerton Jr Thomas M.
Published: June 2020

Purpose

This paper aims to analyze the median price for existing single-family housing units in Las Cruces, New Mexico. The proposed theoretical model accounts for the interplay between supply and demand sides of a metropolitan housing market.

Design/methodology/approach

This study analyzes the median price for existing single-family housing units in Las Cruces, New Mexico. The proposed theoretical model accounts for the interplay between supply and demand sides of a metropolitan housing market. Explanatory variables used in the analysis are real per capita income, the housing stock, real mortgage rates, real apartment rents and the median real price of single-family units in the USA. Annual frequency data are collected for a 1971–2017 sample period. Parameter estimation is completed using two-stage generalized least squares. Empirical results confirm several, but not all, of the hypotheses associated with the underlying analytical model. In particular, Las Cruces housing prices are found to be reliably correlated with local income and national housing prices.

Findings

Empirical results confirm several of the hypotheses associated with the underlying analytical model. In particular, Las Cruces housing prices are found to be reliably correlated with local income and national housing prices.

Research limitations/implications

Results obtained support only a subset of the hypothetical relationships associated with the theoretical model. Additional testing for other small and/or medium sized is required to clarify whether these outcomes are unique to Las Cruces.

Practical implications

Local income fluctuations and national housing price fluctuations appear to be reliably related to housing price fluctuations for this metropolitan economy.

Originality/value

Comparatively little housing market research has been conducted for small and medium size urban economies. There is no guarantee that results obtained for large metropolitan housing markets are representative of smaller regional housing markets. The model developed has fairly moderate data requirements and may be applicable to other small and medium size economies such as Las Cruces.
Mark Johnson: “Future-back” strategizing for beyond-the-core growth
Authors: Leavy Brian
Published: June 2020

Purpose

Interview with Mark W. Johnson, Innosight co-founder and former consultant at Booz Allen Hamilton,an authority on the application of disruption theory. ]His latest book, Lead From the Future: How to Turn Visionary Thinking into Breakthrough Growth, co-authored with Innosight partner Josh Suskewicz, addresses the challenge of how to strategize for the beyond-the-core breakthrough initiatives which will be key to sustaining future growth.

Design/methodology/approach

His interviewer is Brian Leavy, emeritus professor of strategy at Dublin City University Business School and a Strategy & Leadership contributing editor. The interview focuses on Future-back thinking and a set of allied processes that can help leaders think further out than the three to five years that most set as their planning horizons. Then they can identify the threats and opportunities that await them and envision their best path forward.

Findings

Future-back thinking and planning begins with exploring and envisioning–actively, intensively and imaginatively immersing yourself in your organization’s likely future and then determining what you must do to not only fit into that environment but to actively shape your enterprise to thrive in it.

Practical implications

Future-back thinking is geared to discovery, so it iswhat you use when you need to develop a market-creating innovation or new business model to fill a projected gap–to explore, envision and then chart out a new path.

Originality/value

The lesson for leaders: when programming a breakthrough strategy, you need to formalize the roles and responsibilities of the senior leadership team as its champions and overseers, set up an organizational model that will protect those teams from the countervailing influences of the core and ensure that the initiative is managed with an explore, envision and discover approach.
Frequent brain metastases during treatment with BRAF/MEK inhibitors: A retrospective single institutional study
Authors: Nakamura Yoshiyuki , Ishitsuka Yosuke , Tanaka Ryota , Okiyama Naoko , Watanabe Rei , Saito Akimasa , Furuta Junichi , Fujisawa Yasuhiro
Published: June 2020

Recent clinical trials revealed that both immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors significantly prolonged survival in melanoma patients when used for both advanced stage disease and postoperative adjuvant therapy. Although BRAF/MEK inhibitors are associated with a higher objective response rate than ICI, most patients relapse during treatment. However, progression patterns during treatment with BRAF/MEK inhibitors have not been extensively investigated. Here, we retrospectively collected the data of melanoma patients initially treated with BRAF/MEK inhibitors or anti‐programmed death 1 (PD‐1) antibody monotherapy at the University of Tsukuba Hospital and compared their results. The χ2‐test revealed that frequency of brain metastasis (BM) development was significantly higher in cases treated with BRAF/MEK inhibitors compared with those with anti‐PD‐1 antibody monotherapy. In addition, BM‐free survival in cases treated with BRAF/MEK inhibitors was significantly shorter than those treated with anti‐PD‐1 antibody monotherapy. Our results indicate that BM development during treatment with BRAF/MEK inhibitors may be more frequent than anti‐PD‐1 antibody monotherapy, even though the extracranial metastases are well controlled. Therefore, we recommend frequent brain examinations during treatment with BRAF/MEK inhibitors to detect BM at an early stage and to promptly administrate ICI with local radiation therapy.
The Government Deference Dimension of Judicial Decision Making: Evidence from the Supreme Court of Norway
Authors: Skiple Jon Kåre , Littleré Bentsen Henrik , Hanretty Chris
Published: June 2020

Past research has revealed conflicting findings regarding the degree to which judges on European apex courts enact their policy preferences or instead disagree on the basis of divergent legal views. We investigate disagreement between judges on the Norwegian Supreme Court between 1996 and 2016. During this period, the court dealt with a greater volume of policy‐relevant cases than previously. The method of appointment to the court was also changed to a judicial appointments commission. We analyse non‐unanimous cases using item response theory models. We find that judges are not divided along left–right lines but instead disagree about the appropriate degree of deference to give to public authorities. There is no significant association between the appointing government and judges' ideal points either before or after the reform to appointments. Judges who were formerly academics are however much less deferential than career judges or judges who were previously lawyers in private practice.
Bovine skin gelatin hydrolysates as potential substitutes for polyphosphates: The role of degree of hydrolysis and pH on water‐holding capacity
Authors: Nuñez Suleivys M. , Cárdenas Constanza , Pinto Marlene , Valencia Pedro , Cataldo Patricio , Guzmán Fanny , Almonacid Sergio
Published: June 2020

The effects of adding bovine skin gelatin hydrolysate obtained with subtilisin, on water‐holding capacity (WHC), in a thermally processed chicken meat model, were investigated. Hydrolysates with different degrees of hydrolysis (DH) (6.57%, 13.14%, and 26.28%) were prepared. The results showed that all the tested hydrolysates improved water retention in the meat matrix. The hydrolysate with 26.28% DH showed similar behavior throughout the full range of concentrations [0% to 5% w/w] compared to that of the positive control (sodium tripolyphosphate [STPP]). In addition, the other hydrolysates [6.57% DH and 13.14% DH at 3% and 2.5% w/w concentrations, respectively] showed behaviors that coincided with that of STPP at its maximum limit allowed. A correlation was observed between the WHC and the pH of the meat samples treated with each hydrolysate or STPP. In addition, it was found that the WHC of the hydrolysates was due to increases in pH and the specific effects of the hydrolysate beyond the typical effects of pH and ionic strength in meat systems. The solubility of all hydrolysates was high (>90%). In conclusion, bovine skin gelatin hydrolysates could serve as an alternative to polyphosphates to improve water retention and the functional properties of thermally processed meat products.

Practical Application

This study investigated the effects of adding bovine skin gelatin hydrolysate obtained with subtilisin on water‐holding capacity (WHC) in a thermally processed chicken meat model. It was found that the hydrolysis of bovine skin gelatin with subtilisin can replace chemical products harmful to health, such as STPP, in terms of water‐holding capacity. Therefore, bovine skin gelatin hydrolysate can be used as an ingredient in the formulation of thermally processed meat products.
Customize and get the most out of your reduced‐representation sequencing experiment with the new simulation software RADinitio
Authors: Choquet Marvin
Published: June 2020

Whole‐genome sequencing is still often a difficult, costly and time‐consuming task. The emergence of various genome reduced‐representation sequencing (RRS) protocols such as restriction site‐associated DNA sequencing (RADseq) has facilitated the access to genome‐wide information, without the need for whole‐genome sequencing. Reaching the full potential of RRS protocols though requires adjustments and tailoring to the species under investigation. To that end, simulation software has been developed to guide researchers in the customization of their RADseq experiment, but the extent to which these tools mimic the behaviour of a protocol in generating sequencing data is limited. In this current issue of Molecular Ecology Resources, Rivera‐Colón et al. (2020) introduce RADinitio, a new software for simulating RADseq data designed to perform simulations at the highest level of representativeness. By taking into account the effects of library preparation and sequencing parameters on the resulting sequences, RADinitio allows the precise identification of the sources of failure when designing a RADseq experiment. This new software represents a considerable advance in RADseq data simulation and will likely lead to increased success in RADseq experiments.
The rise and ruin of a medieval port town: A reconsideration of the development of Julfar
Authors: Carter Robert Andrew , Zhao Bing , Lane Kevin , Velde Christian
Published: June 2020

Julfar was a major port town of the Persian Gulf during the fourteenth and fifteenth centuries AD. A possession of the Hormuzi empire, it was a lucrative source of taxes and pearls, and a port of trade for northern Oman, tapping into maritime trading networks connecting the Middle East with Africa, India, Southeast Asia and China. The site is found north of modern Ras Al‐Khaimah, UAE. Julfar Al‐Nudud was previously considered to be a late suburb of an urban core, Julfar Al‐Mataf, and is located on a creek opposite the latter. However, excavations in 2010 indicated that Al‐Nudud was part of the original urban core, which had grown up on either side of the creek. Moreover, re‐examination of previous work in Al‐Mataf, where a large mosque and fortification were excavated (by British and French teams), shows that the two areas followed different trajectories. Significant occupation in Al‐Nudud and southern Al‐Mataf (revealed by previous Japanese excavations) ended before the start of the sixteenth century, while use of the mosque and fort in central Al‐Mataf continued into the seventeenth century, albeit discontinuously. A revised concordance of the phases derived from the work of various archaeological teams is therefore proposed.
Fama's Ratio and the Effect of Operating Leverage on the Cost of Capital Under CAPM
Authors: Johnstone David
Published: June 2020

The firm's operating leverage is its ratio of fixed to variable costs. It is widely understood that production settings with higher fixed costs and lower variable costs are high risk. Well‐rehearsed CAPM arguments show how the firm's beta and cost of capital is higher when its proportion of fixed costs is higher. Importantly, that generalization holds under CAPM if expected total costs are constant and merely re‐apportioned between fixed and variable, but does not hold if expected total costs change. In actual business contexts, higher fixed costs are intended to bring lower unit variable costs and often lower expected total costs. Allowing for such efficiency gains, the firm's risk‐adjusted cost of capital might typically fall despite the higher operating leverage. Formal proof follows directly from the payoffs or ‘certainty equivalent’ expression of CAPM. The CAPM insights and new CAPM equations brought to light in this proof are surprising and useful.
High expression of Matrix Gla Protein in Schnyder corneal dystrophy patients points to an active role of vitamin K in corneal health
Authors: Sarosiak Anna , Oziębło Dominika , Udziela Monika , Vermeer Cees , Malejczyk Jacek , Szaflik Jacek P. , Ołdak Monika
Published: June 2020

Purpose

Schnyder corneal dystrophy (SCD) is a rare autosomal dominant disorder characterized by corneal lipid accumulation and caused by UBIAD1 pathogenic variants. UBIAD1 encodes a vitamin K (VK) biosynthetic enzyme. To assess the corneal and vascular VK status in SCD patients, we focused on matrix Gla protein (MGP), a VK‐dependent protein.

Methods

Conformation‐specific immunostainings of different MGP maturation forms were performed on corneal sections and primary keratocytes from corneal buttons of two SCD patients with UBIAD1 p.Asp112Asn and p.Asn102Ser pathogenic variants and unrelated donors. Native or UBIAD1‐transfected keratocytes were used for gene expression analysis. Plasma samples from SCD patients (n = 12) and control individuals (n = 117) were subjected for inactive desphospho‐uncarboxylated MGP level measurements with an ELISA assay.

Results

Substantial amounts of MGP were identified in human cornea and most of it in its fully matured and active form. The level of mature MGP did not differ between SCD and control corneas. In primary keratocytes from SCD patients, a highly increased MGP expression and presence of immature MGP forms were detected. Significantly elevated plasma concentration of inactive MGP was found in SCD patients.

Conclusion

High amount of MGP and the predominance of mature MGP forms in human cornea indicate that VK metabolism is active in the visual system. Availability of MGP seems of vital importance for a healthy cornea and may be related to protection against corneal calcification. Systemic MGP findings reveal a poor vascular VK status in SCD patients and indicate that SCD may lead to cardiovascular consequences.
How the other half lives: A reflection on Tivers (1978) from a physical geographer's point of view
Authors: Hart Jane K.
Published: June 2020

This is a reflection on Tivers' (1978) paper from a physical geography point of view. I discuss four elements of the original paper: the increase in women in the field of geography, fieldwork, family role, and “everyday sexism.” Alongside this, I provide a reflection of my own experience as a UK physical geographer over the last 40 years and discuss the major changes over that time.
Pilot experience of simultaneous robotic‐assisted partial nephrectomy for bilateral renal tumors–single center analysis
Authors: Otoshi Taiyo , Yamasaki Takeshi , Hirayama Yukiyoshi , Uchida Junji
Published: June 2020

Introduction

Bilateral renal tumors accounts for approximately 3% of renal tumors. However, surgical treatment methods for bilateral renal tumors have not yet been established. It is imperative to balance the need for curative surgery with the goal of maximal functional preservation in patients with bilateral synchronous renal tumors. Therefore, partial nephrectomy may be the optimal surgical treatment for bilateral synchronous renal tumors.

Methods

We conducted a retrospective, observational study to analyze the clinical outcome of simultaneous robotic‐assisted partial nephrectomy (RAPN) for bilateral renal tumors at our institution between 2016 and 2019. A total of eight patients were enrolled and the number of renal masses in the 16 kidneys was 18.

Results

There was no positive surgical margin after RAPN in our case series and no local recurrence or metastasis during the follow‐up period. The only complication of simultaneous RAPN in the present case series was that one patient experienced acute kidney injury after operation without need for dialysis therapy.

Conclusion

Our study suggests that simultaneous RAPN for bilateral renal tumors might be feasible both for the preservation of renal function and for oncological outcome such as negative surgical margin.