bluuebunny/crossref_metadata_2025 huggingface dataset:
KIF2C regulates synaptic plasticity and cognition by mediating dynamic microtubule invasion of dendritic spines
Authors: Zheng Rui , Du Yong-Lan , Wang Xin-Tai , Liao Tai-Lin , Zhang Zhe , Wang Na , Li Xiu-Mao , Shen Ying , Shi Lei , Luo Jian-Hong , Xia Jun , Wang Ziyi , Xu Junyu
Published: August 2021

Dynamic microtubules play a critical role in cell structure and function. In nervous system, microtubules specially extend into and out of synapses to regulate synaptic development and plasticity. However, the detailed polymerization especially the depolymerization mechanism that regulates dynamic microtubules in synapses is still unclear. In this study, we find that KIF2C, a dynamic microtubule depolymerization protein without known function in the nervous system, plays a vital role in the structural and functional plasticity of synapses and regulates cognitive function. Using RNAi knockdown and conditional knockout approaches, we showed that KIF2C regulates spine morphology and synaptic membrane expression of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors. Moreover, KIF2C deficiency leads to impaired excitatory transmission, long-term potentiation, and altered cognitive behaviors in mice. Mechanistically, KIF2C regulates microtubule dynamics and microtubule invasion of spines in neurons by its microtubule depolymerization capability in a neuronal activity-dependent manner. This study explores a novel function of KIF2C in the nervous system and provides an important regulatory mechanism on how microtubule invasion of spines regulates synaptic plasticity and cognition behaviors.
Is the genomics ‘cart’ before the restoration ecology ‘horse’? Insights from qualitative interviews and trends from the literature
Authors: Mohr Jakki J. , Harrison Peter A. , Stanhope Jessica , Breed Martin F.
Published: August 2021

Harnessing new technologies is vital to achieve global imperatives to restore degraded ecosystems. We explored the potential of genomics as one such tool. We aimed to understand barriers hindering the uptake of genomics, and how to overcome them, via exploratory interviews with leading scholars in both restoration and its sister discipline of conservation – a discipline that has successfully leveraged genomics. We also conducted an examination of research trends to explore some insights that emerged from the interviews, including publication trends that have used genomics to address restoration and conservation questions. Our qualitative findings revealed varied perspectives in harnessing genomics. For example, scholars in restoration without genomics experience felt genomics was over-hyped. Scholars with genomics experience emphatically emphasised the need to proceed cautiously in using genomics in restoration. Both genomics-experienced and less-experienced scholars called for case studies to demonstrate the benefits of genomics in restoration. These qualitative data contrasted with our examination of research trends, which revealed 70 restoration genomics studies, particularly studies using environmental DNA as a monitoring tool. We provide a roadmap to facilitate the uptake of genomics into restoration, to help the restoration sector meet the monumental task of restoring huge areas to biodiverse and functional ecosystems.
Extracellular and intracellular components of the impedance of neural tissue
Authors: Bedard Claude , Piette Charlotte , Venance Laurent , Destexhe Alain
Published: August 2021

Electric phenomena in brain tissue can be measured using extracellular potentials, such as the local field potential, or the electro-encephalogram. The interpretation of these signals depend on the electric structure and properties of extracellular media, but the measurements of these electric properties are still debated. Some measurements point to a model where the extracellular medium is purely resistive, and thus parameters such as electric conductivity and permittivity should be independent of frequency. Other measurements point to a pronounced frequency dependence of these parameters, with scaling laws that are consistent with capacitive or diffusive effects. However, these experiments correspond to different preparations, and it is unclear how to correctly compare them. Here, we provide for the first time, impedance measurements (in the 1-10 KHz frequency range) using the same set-up in various preparations, from primary cell cultures to acute brain slices, with a comparison with similar measurements performed in artificial cerebrospinal fluid with no biological material. The measurements show that when the current flows across a cell membrane, the frequency dependence of the macroscopic impedance between intracellular and extracellular electrodes is significant, and cannot be captured by a model with resistive media. Fitting a mean-field model to the data shows that this frequency dependence could be explained by the ionic diffusion mainly associated to Debye layers surrounding the membranes. We conclude that neuronal membranes and their ionic environment induce strong deviations to resistivity, that should be taken into account to correctly interpret extracellular potentials generated by neurons.

Significance

The electro-encephalogram recorded at the scalp surface and local-field potentials recorded within neural tissue are generated by electric currents in neurons, and thus depend on the impedance of neural tissue. Different measured values were proposed, and it is currently unclear what is the real impedance of neural tissue. Here, we show that the impedance depends on the measurement technique. If the measurement is exclusively extracellular, the system appears as equivalent to a simple resistor. However, if the measurement includes an intracellular electrode, a more complex impedance is observed, because the current has to flow through the membrane, as happening in the brain. Thus, we provide an explanation for apparent disagreements, and indicate in which cases each impedance should be used.
Coordinated Cross-Talk Between the Myc and Mlx Networks in Liver Regeneration and Neoplasia
Authors: Wang Huabo , Lu Jie , Alencastro Frances , Roberts Alexander , Fiedor Julia , Carroll Patrick , Eisenman Robert N. , Ranganathan Sarangarajan , Torbenson Michael , Duncan Andrew W. , Prochownik Edward V.
Published: August 2021

Background & Aims

The c-Myc (Myc) bHLH-ZIP transcription factor is deregulated in most cancers. In association with Max, Myc controls target genes that supervise metabolism, ribosome biogenesis, translation and proliferation. This “Myc Network” cross-talks with the “Mlx Network”, which consists of the Myc-like proteins MondoA and ChREBP and Max-like Mlx. Together, this “Extended Myc Network” regulates both common and distinct genes targets. Here we studied the consequence of Myc and/or Mlx ablation in the liver, particularly those pertaining to hepatocyte proliferation, metabolism and spontaneous tumorigenesis.

Methods

We examined the ability of hepatocytes lacking Mlx (MlxKO) or Myc+Mlx (double KO or DKO) to repopulate the liver over an extended period of time in a murine model of Type I tyrosinemia. We also compared this and other relevant behaviors, phenotypes and transcriptomes of the livers to those from previously characterized MycKO, ChrebpKO and MycKO x ChrebpKO mice.

Results

Hepatocyte regenerative potential deteriorated as the Extended Myc Network was progressively dismantled. Genes and pathways dysregulated in MlxKO and DKO hepatocytes included those pertaining to translation, mitochondrial function and non-alcoholic fatty liver disease (NAFLD). The Myc and Mlx Networks were shown to cross-talk, with the latter playing a disproportionate role in target gene regulation. All cohorts also developed NAFLD and molecular evidence of early steatohepatitis. Finally, MlxKO and DKO mice displayed extensive hepatic adenomatosis.

Conclusions

In addition to demonstrating cooperation between the Myc and Mlx Networks, this study revealed the latter to be more important in maintaining proliferative, metabolic and translational homeostasis, while concurrently serving as a suppressor of benign tumorigenesis.

Synopsis

The Myc and Mlx Networks exhibit extensive cross-talk and regulate distinct but overlapping sets of transcriptional targets. The current work demonstrates the cooperation between these two Networks in supporting the regenerative capabilities of normal hepatocytes while also revealing that the Mlx Network serves as a suppressor of spontaneous hepatic adenomatosis
Expression of soluble methane monooxygenase in Escherichia coli enables methane conversion
Authors: Bennett R. Kyle , Dzvova Nyaradzo , Dillon Michael , Jones Stephanie , Hestmark Kelley , Zhu Baolong , Helman Noah , Greenfield Derek , Clarke Elizabeth , Papoutsakis Eleftherios T.
Published: August 2021

Natural gas and biogas provide an opportunity to harness methane as an industrial feedstock. Bioconversion is a promising alternative to chemical catalysis, which requires extreme operating conditions and exhibits poor specificities. Though methanotrophs natively utilize methane, efforts have been focused on engineering platform organisms like Escherichia coli for synthetic methanotrophy. Here, a synthetic E. coli methanotroph was developed by engineering functional expression of the Methylococcus capsulatus soluble methane monooxygenase in vivo via expression of its cognate GroESL chaperone. Additional overexpression of E. coli GroESL further improved activity. Incorporation of an acetone formation pathway then enabled the conversion of methane to acetone in vivo, as validated via 13C tracing. This work provides the first reported demonstration of methane bioconversion to liquid chemicals in a synthetic methanotroph.
A single layer artificial neural network type architecture with molecular engineered bacteria for complex conventional and reversible computing
Authors: Sarkar Kathakali , Bonnerjee Deepro , Srivastava Rajkamal , Bagh Sangram
Published: August 2021

Here, we adapted the basic concept of artificial neural networks (ANN) and experimentally demonstrate a broadly applicable single layer ANN type architecture with molecular engineered bacteria to perform complex irreversible computing like multiplexing, de-multiplexing, encoding, decoding, majority functions, and reversible computing like Feynman and Fredkin gates. The encoder and majority functions and reversible computing were experimentally implemented within living cells for the first time. We created molecular-devices, which worked as artificial neuro-synapses in bacteria, where input chemical signals were linearly combined and processed through a non-linear activation function to produce fluorescent protein outputs. To create such molecular devices, we established a set of rules by corelating truth tables, mathematical equations of ANN, and molecular-device design, which unlike molecular computing, does not require circuit diagram and the equation directly correlates the design of the molecular-device. To our knowledge this is the first adaptation of ANN type architecture with engineered cells. This work may have significance in new platform for biomolecular computing, reversible computing and in transforming living cells as ANN-enabled hardware.
One Health or Three? Transmission modelling ofKlebsiellaisolates reveals ecological barriers to transmission between humans, animals and the environment
Authors: Thorpe Harry , Booton Ross , Kallonen Teemu , Gibbon Marjorie J. , Couto Natacha , Passet Virginie , Fernandez Juan Sebastian Lopez , Rodrigues Carla , Matthews Louise , Mitchell Sonia , Reeve Richard , David Sophia , Merla Cristina , Corbella Marta , Ferrari Carolina , Comandatore Francesco , Marone Piero , Brisse Sylvain , Sassera Davide , Corander Jukka , Feil Edward J.
Published: August 2021

TheKlebsiellagroup is highly diverse both genetically and ecologically, being commonly recovered from humans, livestock, plants, soil, water, and wild animals. Many species are opportunistic pathogens, and can harbour diverse classes of antimicrobial resistance (AMR) genes.K. pneumoniaeis responsible for a high public-health burden, due in part to the rapid spread of health-care associated clones that are non-susceptible to carbapenems.Klebsiellathus represents a highly pertinent taxon for assessing the risk to public health posed by animal and environmental reservoirs. Here we report an analysis of 6548 samples and 3,482 genome sequences representing 15Klebsiellaspecies sampled over a 15-month period from a wide range of clinical, community, animal and environmental settings in and around the city of Pavia, in the northern Italian region of Lombardy. Despite carbapenem-resistant clones circulating at a high frequency in the hospitals, we find no genotypic or phenotypic evidence for non-susceptibility to carbapenems outside of the clinical environment. The non-random distribution of species and strains across sources point to ecological barriers that are likely to limit AMR transmission. Although we find evidence for occasional transmission between settings, hierarchical modelling and intervention analysis suggests that direct transmission from the multiple non-human (animal and environmental) sources included in our sample accounts for less than 1% of hospital disease, with the vast majority of clinical cases originating from other humans.
Evolution of the folding landscape of effector caspases
Authors: Shrestha Suman , Clark A. Clay
Published: August 2021

Caspases are a family of cysteinyl proteases that control programmed cell death and maintain homeostasis in multicellular organisms. The caspase family is an excellent model to study protein evolution because all caspases are produced as zymogens (procaspases) that must be activated to gain full activity; the protein structures are conserved through hundreds of millions of years of evolution; and some allosteric features arose with the early ancestor while others are more recent evolutionary events. The apoptotic caspases evolved from a common ancestor into two distinct subfamilies: monomers (initiator caspases) or dimers (effector caspases). Differences in activation mechanisms of the two subfamilies, and their oligomeric forms, play a central role in the regulation of apoptosis. Here, we examine changes in the folding landscape by characterizing human effector caspases and their common ancestor. The results show that the effector caspases unfold by a minimum three-state equilibrium model at pH 7.5, where the native dimer is in equilibrium with a partially folded monomeric (procaspase-7, common ancestor) or dimeric (procaspase-6) intermediate. In comparison, the unfolding pathway of procaspase-3 contains both oligomeric forms of the intermediate. Overall, the data show that the folding landscape was first established with the common ancestor and was then retained for >650 million years. Partially folded monomeric or dimeric intermediates in the ancestral ensemble provide mechanisms for evolutionary changes that affect stability of extant caspases. The conserved folding landscape allows for the fine-tuning of enzyme stability in a species-dependent manner while retaining the overall caspase-hemoglobinase fold.
Integrating omics approaches to discover and prioritize candidate genes involved in oil biosynthesis in soybean
Authors: Turquetti-Moraes Dayana K. , Moharana Kanhu C. , Almeida-Silva Fabricio , Pedrosa-Silva Francisnei , Venancio Thiago M.
Published: August 2021

Soybean is one of the major sources of edible protein and oil. Oil content is a quantitative trait that is significantly determined by genetic and environmental factors. Over the past 30 years, a large volume of soybean genetic, genomic, and transcriptomic data have been accumulated. Nevertheless, integrative analyses of such data remain scarce, in spite of their importance for crop improvement. We hypothesized that the co-occurrence of genomic regions for oil-related traits in different studies may reveal more stable regions encompassing important genetic determinants of oil content and quality in soybean. We integrated publicly available data, obtained with distinct techniques, to discover and prioritize candidate genes involved in oil biosynthesis and regulation in soybean. We detected key fatty acid biosynthesis genes (e.g., BCCP and ACCase, FADs, KAS family proteins) and several transcripton factors, which are likely regulators of oil biosynthesis. In addition, we identified new candidates for seed oil accumulation and quality, such as Glyma.03G213300 and Glyma.19G160700, which encode a translocator protein and a histone acetyltransferase, respectively. Further, oil and protein genomic hotspots are strongly associated with breeding and not with domestication, suggesting that soybean domestication prioritized other traits. The genes identified here are promising targets for breeding programs and for the development of soybean lines with increased oil content and quality.
Structure of PINK1 reveals autophosphorylation dimer and provides insights into binding to the TOM complex
Authors: Rasool Shafqat , Veyron Simon , Soya Naoto , Eldeeb Mohamed , Lukacs Gergely L. , Fon Edward A. , Trempe Jean-François
Published: August 2021

Mutations in PINK1 causes autosomal-recessive Parkinson’s disease. Mitochondrial damage results in PINK1 import arrest on the Translocase of the Outer Mitochondrial Membrane (TOM) complex, resulting in the activation of its ubiquitin kinase activity by autophosphorylation and initiation of Parkin-dependent mitochondrial clearance. Herein we report crystal structures of the entire cytosolic domain of insect PINK1. Our structures reveal a dimeric autophosphorylation complex targeting phosphorylation at the invariant Ser205 (human Ser228). The dimer interface requires insert 2, which is unique to PINK1. The structures also reveal how an N-terminal helix binds to the C-terminal extension and provide insights into stabilization of PINK1 on the core TOM complex.
Fat specific adipose triglyceride lipase is necessary for iron-mediated lipolysis and lipid mobilization in response to negative energy balance
Authors: Romero Alicia R. , Mu Andre , Ayres Janelle S.
Published: August 2021

Maintenance of energy balance is essential for the overall health of an organism. In mammals, both negative and positive energy balance are associated with disease states. To maintain their energy balance within a defined homeostatic setpoint, mammals have evolved complex regulatory mechanisms that control energy intake and expenditure. Traditionally, studies have focused on understanding the role of macronutrient physiology in energy balance. In the present study, we examined the role of the essential micronutrient iron in regulating energy balance. Using a dietary model, we found that a short course of excess dietary iron caused a negative energy balance resulting in a severe whole body wasting phenotype. This disruption in energy balance was due to an iron dependent increase in energy expenditure caused by a heightened basal metabolic rate and activity level. Using a transgenic mouse model lacking adipose triglyceride lipase (ATGL) specifically in fat tissue, we found that to meet the increased energetic demands, dietary iron caused increased lipid utilization that required fat specific ATGL-mediated lipid mobilization and wasting of subcutaneous white adipose tissue deposits. When fed dietary iron, mice lacking fat-specific ATGL activity were protected from fat wasting, and developed a severe cachectic response that is necessary to meet the increased energetic demands caused by the dietary regimen. Our work highlights the multi-faceted role of iron regulation of organismal metabolism and provides a novel in vivo mechanism for micronutrient control of lipolysis that is necessary for regulating mammalian energy balance.
Physiological Magnesium Concentrations Increase Fidelity of Diverse Reverse Transcriptases from HIV-1, HIV-2, and Foamy Virus, but not MuLV or AMV
Authors: Wang Ruofan , Belew Ashton T. , Achuthan Vasudevan , Sayed Najib El , DeStefano Jeffrey J.
Published: August 2021

Reverse transcriptases (RTs) are typically assayed in vitro using optimized Mg2+ concentrations (∼5-10 mM) several-fold higher than physiological cellular free Mg2+ (∼0.5 mM). Analysis of fidelity using lacZα-based α-complementation assays showed that tested HIV RTs, including HIV-1 from subtype B (HXB2-derived), HIV-2, subtype A/E, and several drug-resistant HXB2 derivatives all showed significantly higher fidelity using physiological Mg2+. This also occurred with prototype foamy virus (PFV) RT. In contrast, Moloney murine leukemia virus (MuLV) and avian myeloblastosis virus (AMV) RTs demonstrated equivalent fidelity in both low and high Mg2+. In 0.5 mM Mg2+, all RTs demonstrated ≈ equal fidelity, except for PFV RT which showed higher fidelity. A Next Generation Sequencing (NGS) approach that used barcoding to accurately determine mutation rates and profiles was used to examine the types of mutations made by HIV-1 (subtype B, wild type) in low (0.5 mM) and high (6 mM) Mg2+ with DNA or RNA that coded for lacZα. Unlike the α-complementation assay, which is dependent on LacZα activity, the NGS assay scores mutations at all positions and of every type. Consistent with α-complementation assays, a ∼4-fold increase in mutations was observed in high Mg2+. These findings help explain why HIV RT displays lower fidelity in vitro (with high Mg2+ concentrations) than other RTs (e.g., MuLV and AMV), yet cellular fidelity for these viruses is comparable. Establishing in vitro conditions that accurately represent RT’s activity in cells is pivotal to determining the contribution of RT and other factors to the mutation profile observed with HIV.
Design of Transmembrane Mimetic Structural Probes to Trap Different Stages of γ-Secretase-Substrate Interaction
Authors: Bhattarai Sanjay , Devkota Sujan , Wolfe Michael S.
Published: August 2021

The transmembrane domain (TMD) of the amyloid precursor protein of Alzheimer’s disease is processively cut by γ-secretase through endoproteolysis and tricarboxypeptidase “trimming”. We recently developed a prototype substrate TMD mimetic for structural analysis—composed of a helical peptide inhibitor linked to a transition-state analog—that simultaneously engages a substrate exosite and the active site and is pre-organized to trap the carboxypeptidase transition state. Here we developed variants of this prototype designed to allow visualization of transition states for endoproteolysis, TMD helix unwinding, and lateral gating of substrate, identifying potent inhibitors for each class. These TMD mimetics exhibited non-competitive inhibition and occupy both exosite and active site as demonstrated by inhibitor cross competition experiments and photoaffinity probe binding assays. The new probes should be important structural tools for trapping different stages of substrate recognition and processing via ongoing cryo-electron microscopy with γ-secretase, ultimately aiding rational drug design.
The orphan drug dichloroacetate reduces amyloid beta-peptide production whilst promoting non-amyloidogenic proteolysis of the amyloid precursor protein
Authors: Parkin Edward T. , Hammond Jessica E. , Hodges Matthew D.
Published: August 2021

The amyloid cascade hypothesis proposes that excessive accumulation of amyloid beta-peptides is the initiating event in Alzheimer’s disease. These neurotoxic peptides are generated from the amyloid precursor protein via sequential cleavage by β- and γ-secretases in the ‘amyloidogenic’ proteolytic pathway. Alternatively, the amyloid precursor protein can be processed via the ‘non-amyloidogenic’ pathway which, through the action of the α-secretaseadisintegrinandmetalloproteinase (ADAM) 10, both precludes amyloid beta-peptide formation and has the additional benefit of generating a neuroprotective soluble amyloid precursor protein fragment, sAPPα. In the current study, we investigated whether the orphan drug, dichloroacetate, could alter amyloid precursor protein proteolysis. In SH-SY5Y neuroblastoma cells, dichloroacetate enhanced sAPPα generation whilst inhibiting β-secretase processing of endogenous amyloid precursor protein and the subsequent generation of amyloid beta-peptides. Over-expression of the amyloid precursor protein partly ablated the effect of dichloroacetate on amyloidogenic and non-amyloidogenic processing whilst over-expression of the β-secretase only ablated the effect on amyloidogenic processing. Similar enhancement of ADAM-mediated amyloid precursor protein processing by dichloroacetate was observed in unrelated cell lines and the effect was not exclusive to the amyloid precursor protein as an ADAM substrate, as indicated by dichloroacetate-enhanced proteolysis of the Notch ligand, Jagged1. Despite altering proteolysis of the amyloid precursor protein, dichloroacetate did not significantly affect the expression of α-, β- or γ-secretases. In conclusion, dichloroacetate can inhibit amyloidogenic and promote non-amyloidogenic proteolysis of the amyloid precursor protein. As the drug is already used for the treatment of lactic acidosis and is known to cross the blood-brain-barrier, it might represent a cheap and effective therapy for slowing the progression of Alzheimer’s disease.
Effects of enhanced insect feeding on the faecal microbiota and transcriptome of a family of captive common marmosets (Callithrix jacchus)
Authors: Yamazaki Yumiko , Moriya Shigeharu , Kawarai Shinpei , Morita Hidetoshi , Kikusui Takefumi , Iriki Atsushi
Published: August 2021

Common marmosets have been widely used in biomedical research for years. Nutritional control is an important factor in managing their health, and insect intake would be beneficial for that purpose because common marmosets frequently feed on insects in natural habitats. Here, we examined the effect of enhanced insect feeding on the gut by analysing the faecal microbiota and transcripts of captive marmosets. A family consisting of six marmosets was divided into two groups. During the seven-day intervention period, one group (the insect feeding group, or Group IF) was fed one cricket and one giant mealworm per marmoset per day, while the other (the control group, or Group C) was not fed these insects. RNA was extracted from faecal samples to evaluate the ecology and transcripts of the microbiota, which were then compared among time points before (Pre), immediately after (Post), and two weeks after intervention (After) by total RNA sequencing. The gut microbiota of marmosets showedFirmicutes,Actinobacteria,Bacteroidetes, andProteobacteriaas dominant phyla. Linear discriminant analysis showed differential characteristics of microbiota with and without insect feeding treatment. Further analysis of differentially expressed genes revealed increases and decreases inBacteroidetesandFirmicutes, respectively, corresponding to the availability of insects under both Post and After conditions. Significant changes specific to insect feeding were also detected within the transcriptome, some of which were synchronized with the fluctuations in the microbiota, suggesting a functional correlation or interaction between the two. The rapid changes in the microbiota and transcripts may be deeply connected to the original microbiota community shaped by marmoset feeding ecology in the wild. The results were informative for identifying the physiological impact of insect feeding to produce a better food regimen and for detecting transcripts that are currently unidentifiable.
The pink salmon genome: uncovering the genomic consequences of a strict two-year life-cycle
Authors: Christensen Kris A. , Rondeau Eric B. , Sakhrani Dionne , Biagi Carlo A. , Johnson Hollie , Joshi Jay , Flores Anne-Marie , Leelakumari Sreeja , Moore Richard , Pandoh Pawan K. , Withler Ruth E. , Beacham Terry D. , Leggatt Rosalind A. , Tarpey Carolyn M. , Seeb Lisa W. , Seeb James E. , Jones Steven J.M. , Devlin Robert H. , Koop Ben F.
Published: August 2021

Pink salmon (Oncorhynchus gorbuscha) adults are the smallest of the five Pacific salmon native to the western Pacific Ocean. Pink salmon are also the most abundant of these species and account for a large proportion of the commercial value of the salmon fishery worldwide. A strict two-year life-history of most pink salmon generates temporally isolated populations that spawn either in even-years or odd-years. To uncover the influence of this genetic isolation, reference genome assemblies were generated for each year-class and whole genome re-sequencing data was collected from salmon of both year-classes. The salmon were sampled from six Canadian rivers and one Japanese river. At multiple centromeres we identified peaks of Fst between year-classes that were millions of base-pairs long. The largest Fst peak was also associated with a million base-pair chromosomal polymorphism found in the odd-year genome near a centromere. These Fst peaks may be the result of centromere drive or a combination or reduced recombination and genetic drift, and they could influence speciation. Other regions of the genome influenced by odd-year and even-year temporal isolation and tentatively under selection were mostly associated with genes related to immune function, organ development/maintenance, and behaviour.
Conjugates for use in peptide therapeutics: a systematic review and meta-analysis
Authors: Wijesinghe Ashan , Kumari Sarika , Booth Valerie
Published: August 2021

While peptides can be excellent therapeutics for several conditions, their limited in vivo half-lives have been a major bottleneck in the development of therapeutic peptides. Conjugating the peptide to an inert chemical moiety is a strategy that has repeatedly proven to be successful in extending the half-life of some therapeutics. This systematic review and meta-analysis was conducted to examine the available literature and assess it in an unbiased manner to determine which conjugates, both biological and synthetic, provide the greatest increase in therapeutic peptide half-life. Systematic searches run on PubMed, Scopus and SciFinder databases resulted in 845 studies pertaining to the topic, 16 of these were included in this review after assessment against pre-specified inclusion criteria registered on PROSPERO (#CRD42020222579). The most common reasons for exclusion were non-IV administration and large peptide size. Of the 16 studies that were included, a diverse suite of conjugates that increased half-life from 0.1 h to 33.57 h was identified. Amongst these peptides, the largest increase in half-life was seen when conjugated with glycosaminoglycans. A meta-analysis of studies that contained fatty acid conjugates indicated that acylation contributed to a statistically significant extension of half-life. Additionally, another meta-analysis followed by a sensitivity analysis suggested that conjugation with specifically engineered recombinant peptides might contribute to a more efficient extension of peptide half-life as compared to PEGylation. Moreover, we confirmed that while polyethylene glycol is a good synthetic conjugate, its chain length likely has an impact on its effectiveness in extending half-life. Furthermore, we found that most animal studies do not include as much detail when reporting findings as compared to human studies. Inclusion of additional experimental detail on aspects such as independent assessment and randomization may be an easily accomplished strategy to drive more conjugated peptides towards clinical studies.
Small-molecule ligands can inhibit −1 programmed ribosomal frameshifting in a broad spectrum of coronaviruses
Authors: Munshi Sneha , Neupane Krishna , Ileperuma Sandaru M. , Halma Matthew T.J. , Kelly Jamie A. , Halpern Clarissa F. , Dinman Jonathan D. , Loerch Sarah , Woodside Michael T.
Published: August 2021

Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases since 2000 have high-lighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use −1 programmed ribosomal frameshifting (−1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates −1 PRF provides a promising potential target for such therapeutics. To test the viability of this strategy, we explored a group of 6 small-molecule ligands, evaluating their activity against the frameshift signals from a panel of representative bat CoVs—the most likely source of future zoonoses—as well as SARS-CoV-2 and MERS-CoV. We found that whereas some ligands had notable activity against only a few of the frameshift signals, the serine protease inhibitor nafamostat suppressed −1 PRF significantly in several of them, while having limited to no effect on −1 PRF caused by frameshift signals from other viruses used as negative controls. These results suggest it is possible to find small-molecule ligands that inhibit −1 PRF specifically in a broad spectrum of CoVs, establishing the frameshift signal as a viable target for developing pan-coronaviral therapeutics.
Crystal structure of (C9H17N2)3[Bi2I9]
Authors: James Zoe , Cai Yunhe , Vaqueiro Paz
Published: August 2021

Single crystals of tris(2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepin-1-ium) tri-μ2-iodido-bis[triiodidobismuth(III)], (C9H17N2)3[Bi2I9], were prepared by a solvothermal method, heating a mixture of BiI3, KI, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and ethanol at 443 K for six days. The asymmetric unit of the title compound, which crystallizes in the monoclinic space group P21/c, contains one [Bi2I9]3− anion and three protonated DBUH+ moieties. The dinuclear [Bi2I9]3− anions, which are composed of face-sharing BiI6
3− octahedra, are packed in columns parallel to the [010] direction, and separated by protonated DBUH+ moieties. The optical band gap of (C9H7N2)3Bi2I9 is 2.1 eV.
Crystal structure of 2-(2,6-diisopropylphenyl)-N,N-diethyl-3,3-dimethyl-2-azaspiro[4.5]decan-1-amine: a diethylamine adduct of a cyclic(alkyl)(amino)carbene (CAAC)
Authors: Naumann Roxanne A. , Ziller Joseph W. , Liberman-Martin Allegra L.
Published: August 2021

The structure of the title compound, C27H46N2, at 93 K has monoclinic (P21/n) symmetry. The title compound was prepared by treatment of 2-(2,6-diisopropylphenyl)-3,3-dimethyl-2-azaspiro[4.5]dec-1-en-2-ium hydrogen dichloride with two equivalents of lithium diethylamide. Characterization of the title compound by single-crystal X-ray diffraction and 1H and 13C NMR spectroscopy is presented. Formation of the diethylamine adduct of the cyclic(alkyl)(amino)carbene (CAAC) was unexpected, as deprotonation using lithium diisopropylamide results in free CAAC formation.
Does institutional fragility affect innovation investment?
Authors: Li Xinli , Cheng Jun , Wan Shouyi , Zhao Zhenyang
Published: August 2021

Purpose

This study aims to investigate the impact of institutional fragility on the innovation investments of enterprises by analyzing the moderating effect of government subsidies and the integration of industry and finance.

Design/methodology/approach

Multiple regression analysis was used on 10,838 samples of 2,356 listed companies in China for the period 2007–2017, to empirically test the influence of institutional fragility on innovation investment. Moreover, Heckman’s two-stage approach was used for the robustness of the regression results.

Findings

The results show that the relationship between institutional fragility and innovation investment is an inverted U-shaped; government subsidies negatively moderate the relationship between institutional fragility and innovation investment, while the integration of industry and finance positively moderates them. Further analysis shows that the relationship between institutional fragility and innovation investment is more significant for high-tech enterprises. Similarly, the relationship between institutional fragility and innovation output also presents an inverted U-shape, which mainly affects enterprises’ breakthrough innovation output, but has no substantial impact on the incremental innovation output.

Originality/value

The conclusions provide new ideas for guiding the government’s reform, promoting the integration of industry and finance and promoting enterprise innovation.
Bibliometric analysis and critical review of the research on big data in the construction industry
Authors: Lu Yusheng , Zhang Jiantong
Published: August 2021

Purpose

The digital revolution and the use of big data (BD) in particular has important applications in the construction industry. In construction, massive amounts of heterogeneous data need to be analyzed to improve onsite efficiency. This article presents a systematic review and identifies future research directions, presenting valuable conclusions derived from rigorous bibliometric tools. The results of this study may provide guidelines for construction engineering and global policymaking to change the current low-efficiency of construction sites.

Design/methodology/approach

This study identifies research trends from 1,253 peer-reviewed papers, using general statistics, keyword co-occurrence analysis, critical review, and qualitative-bibliometric techniques in two rounds of search.

Findings

The number of studies in this area rapidly increased from 2012 to 2020. A significant number of publications originated in the UK, China, the US, and Australia, and the smallest number from one of these countries is more than twice the largest number in the remaining countries. Keyword co-occurrence is divided into three clusters: BD application scenarios, emerging technology in BD, and BD management. Currently developing approaches in BD analytics include machine learning, data mining, and heuristic-optimization algorithms such as graph convolutional, recurrent neural networks and natural language processes (NLP). Studies have focused on safety management, energy reduction, and cost prediction. Blockchain integrated with BD is a promising means of managing construction contracts.

Research limitations/implications

The study of BD is in a stage of rapid development, and this bibliometric analysis is only a part of the necessary practical analysis.

Practical implications

National policies, temporal and spatial distribution, BD flow are interpreted, and the results of this may provide guidelines for policymakers. Overall, this work may develop the body of knowledge, producing a reference point and identifying future development.

Originality/value

To our knowledge, this is the first bibliometric review of BD in the construction industry. This study can also benefit construction practitioners by providing them a focused perspective of BD for emerging practices in the construction industry.
Risk response incorporating risk preferences in international construction projects
Authors: Yan Peng , Liu Junying , Zhao Xianbo , Skitmore Martin
Published: August 2021

Purpose

The objective of this research is to develop a decision method that can generate appropriate risk response strategies for international construction project managers (PMs) and allow these strategies to reflect their different risk preferences.

Design/methodology/approach

The optimal model approach is adopted. A credibility-based fuzzy chance constrained programming (CFCCP) model is developed, which simultaneously minimizes the expected losses of risk events and total costs of risk response. To solve this multi-objective model, a fuzzy interactive solution method is used. Moreover, the model performance is demonstrated by a real international industrial plant project. In addition, a sensitivity analysis of the model is conducted.

Findings

The result of the sensitivity analysis indicates that PMs with a greater risk aversion can lead to a higher mitigation ratio of expected losses of risk events and a higher total cost of risk response.

Practical implications

This research provides contractors with an effective decision-making model to develop a project risk response plan, and it will assist contractors to minimize risk losses and enhance the project performance in the international construction market.

Originality/value

Previous studies overlook the risk preference, which is an important behavioral factor influencing decisions in risk response strategy selection. This research proposed a novel risk response strategy selection decision method that considers different attitudes toward risk among decision makers.
The impact of general data protection regulation on software engineering practices
Authors: Leite Luís , dos Santos Daniel Rodrigues , Almeida Fernando
Published: August 2021

Purpose

This paper aims to explore the changes imposed by the general data protection regulation (GDPR) on software engineering practices. The fundamental objective is to have a perception of the practices and phases that have experienced the greatest changes. Additionally, it aims to identify a set of good practices that can be adopted by software engineering companies.

Design/methodology/approach

This study uses a qualitative methodology through four case studies involving Portuguese software engineering companies. Two of these companies are small and medium enterprises (SMEs) while the other remaining two are micro-companies. The thematic analysis is adopted to identify patterns in the performed interviews.

Findings

The findings indicate that significant changes have occurred at all stages of software development. In particular, the initial stages of identifying requirements and modeling processes were the stages that experienced the greatest changes. On the opposite, the technical development phase has not noticeably changed but, nevertheless, it is necessary to look at the importance of training software developers for GDPR rules and practices.

Research limitations/implications

Two relevant limitations were identified as follows: only four case studies involving micro-companies and SMEs were considered, and only the traditional software development methodology was considered. The use of agile methodologies was not explored in this study and the findings can only be mainly applied to the waterfall model.

Originality/value

This study offers mainly practical contributions by identifying a set of challenges that are posed to software engineering companies by the implementation of GDPR. Through their knowledge, it is expected to help these companies to better prepare themselves and anticipate the challenges they will necessarily face.
A wearable technology solution and research agenda for housekeeper safety and health
Authors: Mejia Cynthia , Ciarlante Katherine , Chheda Kinjal
Published: August 2021

Purpose

Adopting an interdisciplinary perspective, the purpose of this paper was to posit an industry-wide technological intervention for hotel housekeeper safety and health through the advancement of wearable technology.

Design/methodology/approach

Using the task-technology fit (TTF) model and examples of successful safety and health applications of wearable technologies in the health-care and construction management industries, interventions and future research directions are presented to address workplace hazards experienced by hotel housekeepers.

Findings

The fit between a variety of hotel housekeeper user requirements, task demands and wearable functions are explored with justification for the use of wearable devices to improve safety and health-related outcomes.

Research limitations/implications

A research agenda is proposed for the adoption and use of wearables in the hospitality industry with the intention to generate meaningful interventions beyond corporate wellness, and the mitigation of employee privacy concerns to enhance wearable adoption.

Practical implications

Given the importance of consumer safety and health assurance in a post-pandemic business environment, hospitality and tourism organizations should place greater emphasis on protecting front line employees who will be essential in regaining economic viability.

Social implications

Theoretical and practical foci should move beyond a simplistic view of hospitality and tourism worker safety and health that generally centers on wellness initiatives and other baseline strategies, toward a more holistic view benefitting the hospitality industry.

Originality/value

Extant concerns about hotel housekeeper safety and health, in addition to new concerns and threats in a post-pandemic work environment, are largely understudied and worthy of investigation.
Employee perceptions of hotel CSR activities during the COVID-19 pandemic
Authors: Choi Miju , Choi Youngjoon
Published: August 2021

Purpose

This study aims to adopt Carroll’s corporate social responsibility (CSR) pyramid framework as a theoretical lens for examining employee perspectives on South Korean hotels operating as quarantine facilities during the COVID-19 pandemic.

Design/methodology/approach

The study adopted a qualitative approach consisting of the following components: in-depth interviews with employees and stakeholders of quarantine hotels, including frontline staff, government officials and medical staff, field observations and data from one researcher’s direct experience in a quarantined hotel.

Findings

Six themes regarding the experience of operating quarantine hotels emerged from the in-depth interviews and field observations. The findings also showed an interplay between the hotel employees’ perspectives, the four components of the CSR pyramid and the benefits and costs to hotels operating as quarantine facilities.

Research limitations/implications

This study focusses on the particular case of quarantine hotels in South Korea, and therefore caution is required in generalising the findings.

Practical implications

The findings suggest that strategic partnerships can help to protect local communities whilst alleviating the hotel industry’s financial difficulties. They also explore an opportunity for business revitalisation in the midst of a global pandemic.

Originality/value

This study finds that the voluntary decision of hotels to operate as coronavirus quarantine facilities is aligned with CSR because its ultimate aim is to protect the community from the risk of coronavirus from overseas arrivals. This study broadens the CSR literature in the fields of COVID-19 and hospitality.
Unleashing analytics to reduce electricity consumption using incremental clustering algorithm
Authors: Chaudhari Archana Yashodip , Mulay Preeti
Published: August 2021

Purpose

To reduce the electricity consumption in our homes, a first step is to make the user aware of it. Reading a meter once in a month is not enough, instead, it requires real-time meter reading. Smart electricity meter (SEM) is capable of providing a quick and exact meter reading in real-time at regular time intervals. SEM generates a considerable amount of household electricity consumption data in an incremental manner. However, such data has embedded load patterns and hidden information to extract and learn consumer behavior. The extracted load patterns from data clustering should be updated because consumer behaviors may be changed over time. The purpose of this study is to update the new clustering results based on the old data rather than to re-cluster all of the data from scratch.

Design/methodology/approach

This paper proposes an incremental clustering with nearness factor (ICNF) algorithm to update load patterns without overall daily load curve clustering.

Findings

Extensive experiments are implemented on real-world SEM data of Irish Social Science Data Archive (Ireland) data set. The results are evaluated by both accuracy measures and clustering validity indices, which indicate that proposed method is useful for using the enormous amount of smart meter data to understand customers’ electricity consumption behaviors.

Originality/value

ICNF can provide an efficient response for electricity consumption patterns analysis to end consumers via SEMs.