bluuebunny/crossref_metadata_2025 huggingface dataset:
Avirulent ME49Δgra5Protecting Hosts AgainstToxoplasma gondiiInfection and Breast Tumors
Authors: Chen Min , Yang Pei , Xin Zixuan , Chen Jiating , Zou Weihao , Zhou Lijuan , Yang Lili , Peng Jiao , Peng Hongjuan
Published: February 2023

Toxoplasma gondiiis the causative agent of toxoplasmosis, a zoonotic disease that poses a threat to human health and a considerable loss to livestock farming. At present, clinical therapeutic drugs mainly targetT. gondiitachyzoites and fail to eradicate bradyzoites. Developing a safe and effective vaccine against toxoplasmosis is urgent and important.T. gondiipossesses dense granule organelles that secrete immunogenic dense granule proteins (GRAs). GRA5 localizes to the parasitophorous vacuole membrane (PVM) in the tachyzoite stage and to the cyst wall in the bradyzoite stage. Here we report thatgra5knockoutT. gondiistrain is avirulent and fails to form cysts, but stimulates sero-conversion in mice. We next investigated the protective efficacy of ME49Δgra5vaccination againstT. gondiiinfection. All the immunized mice survived the challenge infection with either wild-type RH, ME49, VEG tachyzoites or ME49 cysts. Remarkably, ME49Δgra5tachyzoites inoculationin situattenuated the growth of murine breast tumor (4T1) in mice and prevented 4T1’s lung metastasis. ME49Δgra5inoculation might upregulate the levels of Th1 cytokines and tumor-infiltrating T cells in tumor microenvironment (TME) and trigger anti-tumor responses by increasing the number of NK, B, T cells, macrophages, and dendritic cells (DCs) in spleen. Collectively, the results support the potential of ME49Δgra5as attenuated live vaccine againstT. gondiiinfection and breast cancer.

Author summary

The zoonotic toxoplasmosis poses a great disease burden to humans and big loss to livestock farming. At present, clinical therapeutic drugs mainly targetT. gondiitachyzoites but have no effect on bradyzoites. A safe and effective vaccine against toxoplasmosis is urgent and important. Dense granule proteins (GRAs) are a group of immunoactive proteins secreted byT. gondiidense granule organelles. GRA5 is located on the parasitophorous vacuole membrane (PVM) at the tachyzoite stage and on the cyst wall at the bradyzoite stage. We discovered that thegra5knockoutT. gondiistrain became avirulent and failed to form cysts in mice. ME49Δgra5immunized mice survived the challenge infection of wild-type RH, ME49, and VEG tachyzoites, and ME49 cysts. Meanwhile, ME49Δgra5tachyzoites inoculationin situremarkably attenuated the growth of murine breast tumor (4T1) in mice including the injected and distant tumors, as well as prevented 4T1’s lung metastasis. This results support the potential of ME49Δgra5as attenuated live vaccine againstT. gondiiinfection and breast cancer.
GLI1 facilitates rheumatoid arthritis by collaborative regulation of DNA methyltransferases
Authors: Ge Gaoran , Guo Qianping , Zhou Ying , Li Wenming , Zhang Wei , Bai Jiaxiang , Wang Qing , Tao Huaqiang , Wang Wei , Wang Zhen , Gan Minfeng , Xu Yaozeng , Yang Huilin , Li Bin , Geng Dechun
Published: February 2023

Rheumatoid arthritis (RA) is characterized by joint synovitis and bone destruction, the etiology of which remains to be explored. Overactivation of M1 macrophages and osteoclasts has been thought a direct cause of joint inflammation and bone destruction. Glioma-associated oncogene homolog 1 (GLI1) has been revealed to be closely linked to bone metabolism. In this study, GLI1-expression in synovial tissue of RA patients showed to be positively correlated with RA-related scores and was highly expressed in collagen-induced arthritis (CIA) mouse articular macrophage-like cells. The decreased expression and inhibition of nuclear transfer of GLI1 downregulated macrophage M1 polarization and osteoclast activation, the effect of which was achieved by modulation of DNA methyltransferases (DNMTs) via transcriptional regulation and protein interaction ways. By pharmacological inhibition of GLI1, the proportion of proinflammatory macrophages and the number of osteoclasts were significantly reduced, and the joint inflammatory response and bone destruction in CIA mice were alleviated. This study clarified the mechanism of GLI1 in macrophage phenotypic changes and activation of osteoclasts, suggesting potential applications of GLI1 inhibitor in the clinical treatment of RA.
Transcranial direct current stimulation elevates the baseline activity while sharpening the spatial tuning of the human visual cortex
Authors: Ahn Jeongyeol , Ryu Juhyoung , Lee Sangjun , Lee Chany , Im Chang-Hwan , Lee Sang-Hun
Published: February 2023

Background

Although transcranial direct current stimulation (tDCS) is widely used to affect various kinds of human cognition, behavioral studies on humans have produced highly inconsistent results. This requires a clear understanding of how tDCS impacts the system-level neural activity, a prerequisite for the principled application of tDCS to human cognition.

Objective

Here, we aim to gain such understanding by probing the spatial and temporal cortical activity of the human early visual cortex (EVC) in diverse aspects while controlling the polarity and presence of tDCS. We target EVC to capitalize on its well-established anatomical and functional architecture that is readily accessible with non-invasive quantitative neuroimaging methods.

Methods

To create an electric field in EVC precisely and effectively, we tailored high-definition stimulation montages for 15 individual brains by running electric field simulations. We then conducted an fMRI (functional magnetic neuroimaging)-tDCS experiment on each brain with a sham-controlled crossover design over multiple days. We quantified tDCS effects with eight measures, tested their significance with mixed ANOVA, and further validated their robustness to across-voxel and across-subject variability.

Results

The anodal application of tDCS gradually elevated EVC’s baseline BOLD activity and sharpened its spatial tuning by augmenting surround suppression without affecting its evoked activity.

Conclusions

Comparisons of our and previous findings suggest the fundamental differences in tDCS effects between the visual and motor cortices, inhibitory and excitatory effects predominant in the former and latter, respectively. This calls for considering the differences in the excitatory-inhibitory recurrent network between brain regions in predicting or interpreting tDCS effects.
Rapid, activity-dependent intrinsic plasticity in the developing zebra finch auditory cortex
Authors: Lu Yao , Sciaccotta Francesca , Kiely Leah , Bellanger Benjamin , Erisir Alev , Meliza C Daniel
Published: February 2023

The acoustic environment an animal experiences early in life shapes the structure and function of its auditory system. This process of experience-dependent development is thought to be primarily orchestrated by potentiation and depression of synapses, but plasticity of intrinsic voltage dynamics may also contribute. Here we show that at the peak of the critical period for song memorization, neurons in the zebra finch caudal mesopallium, a cortical-level auditory area, can rapidly change their firing dynamics. This plasticity was only observed in birds that were reared in a complex acoustic and social environment, which also caused increased expression of the low-threshold potassium channel Kv1.1 in the plasma membrane and endoplasmic reticulum. Intrinsic plasticity depended on activity, was reversed by blocking low-threshold potassium currents, and was prevented by blocking intracellular calcium signaling. Taken together, these results suggest that Kv1.1 is rapidly mobilized to the plasma membrane by activity-dependent elevation of intracellular calcium. This produces a shift in the excitability and temporal integration of CM neurons that may be permissive for auditory learning in complex acoustic environments during a crucial period for the development of vocal perception and production.
LIM-HD transcription factors are required for regeneration of neuronal and intestinal cell subtypes in planarians
Authors: Molina M. Dolores , Abduljabbar Dema , Fraguas Susanna , Cebrià Francesc
Published: February 2023

Adult planarians can regenerate the gut, eyes, and even a functional brain in just a few days after injury. Proper regeneration of these complex structures requires that signals guide and restrict the commitment of their adult stem cells and ensure the identity and patterning of the newly formed structures. During embryogenesis of both vertebrates and invertebrates, LIM Homeodomain (LIM-HD) transcription factors act in a combinatorial ‘LIM code’ that controls crucial aspects of cell fate determination and cell differentiation, including specification of neuronal cell type identity and axonal guidance. So far, however, our understanding about the role these genes may play during regeneration is limited. Here, we report the identification and functional characterization of the full repertoire of LIM-HD genes inSchmidtea mediterranea. We found that theselim homeobox genes(lhx) appear mainly expressed in complementary patterns along the cephalic ganglia and digestive system of the planarian. By functional RNAi based analysis we have identified that severalSmed-lhxgenes (islet1,lhx1/5-1,lhx2/9-3,lhx6/8,lmx1a/b-2andlmx1a/b-3) are essential to pattern and size the planarian brain as well as for correct regeneration of specific subpopulations of dopaminergic, serotonergic, GABAergic and cholinergic neurons, while others (Smed-lhx1/5.2andSmed-lhx2/9.2) are required for the proper expression of diverse intestinal cell type markers, specifically the goblet subtype. LIM-HD are also involved in the control of axonal pathfinding (lhx6/8), axial patterning (islet1andlmx1a/b-3), head/body proportions (islet2) and stem cell proliferation (lhx3/4,lhx2/9-3,lmx1a/b-2andlmx1a/b-3) in planarians. Altogether, our results suggest that planarian LIM-HD could provide a combinatorial LIM code to control axial patterning, axonal growing as well as to specify distinct neuronal and intestinal cell identities during regeneration.
Subdural CMOS optical probe (SCOPe) for bidirectional neural interfacing
Authors: Pollmann Eric H. , Yin Heyu , Uguz Ilke , Dubey Agrita , Wingel Katie Elizabeth , Choi John S , Moazeni Sajjad , Gilhotra Yatin , Pavlovsky Victoria A. , Banees Adam , Boominathan Vivek , Robinson Jacob , Veeraraghavan Ashok , Pieribone Vincent A. , Pesaran Bijan , Shepard Kenneth L.
Published: February 2023

Optical neurotechnologies use light to interface with neurons and can monitor and manipulate neural activity with high spatial-temporal precision over large cortical extents. While there has been significant progress in miniaturizing microscope for head-mounted configurations, these existing devices are still very bulky and could never be fully implanted. Any viable translation of these technologies to human use will require a much more noninvasive, fully implantable form factor. Here, we leverage advances in microelectronics and heterogeneous optoelectronic packaging to develop a transformative, ultrathin, miniaturized device for bidirectional optical stimulation and recording: the subdural CMOS Optical Probe (SCOPe). By being thin enough to lie entirely within the subdural space of the primate brain, SCOPe defines a path for the eventual human translation of a new generation of brain-machine interfaces based on light.
MGAdeletion leads to Richter’s transformation via modulation of mitochondrial OXPHOS
Authors: Iyer Prajish , Zhang Bo , Liu Tingting , Jin Meiling , Hart Kevyn , Zhang Jibin , Song Joo , Chan Wing C. , Siddiqi Tanya , Rosen Steven T. , Danilov Alexey , Wang Lili
Published: February 2023

Richter’s transformation (RT) is a progression of chronic lymphocytic leukemia (CLL) to aggressive lymphoma.MGA(Max gene associated), a functional MYC suppressor, is mutated at 3% in CLL and 36% in RT. However, genetic models and molecular mechanisms ofMGAdeletion driving CLL to RT remain elusive. We established a novel RT mouse model by knockout ofMgain theSf3b1/MdrCLL model via CRISPR-Cas9 to determine the role ofMgain RT. Murine RT cells exhibit mitochondrial aberrations with elevated oxidative phosphorylation (OXPHOS). We identifiedNme1(Nucleoside diphosphate kinase) as aMgatarget through RNA sequencing and functional characterization, which drives RT by modulating OXPHOS. AsNME1is also a known MYC target without targetable compounds, we found that concurrent inhibition of MYC and ETC complex II significantly prolongs the survival of RT micein vivo. Our results suggest thatMga-Nme1axis drives murine CLL-to-RT transition via modulating OXPHOS, highlighting a novel therapeutic avenue for RT.

Statement of Significance

We established a murine RT model through knockout ofMgain an existing CLL model based on co-expression ofSf3b1-K700E anddel(13q). We determined that theMGA/NME1regulatory axis is essential to the CLL-to-RT transition via modulation of mitochondrial OXPHOS, highlighting this pathway as a novel target for RT treatment.
mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy
Authors: Riedmayr Lisa Maria , Hinrichsmeyer Klara Sonnie , Thalhammer Stefan Bernhard , Karguth Nina , Böhm Sybille , Mittas David Manuel , Weber Valentin Johannes , Otify Dina , Splith Victoria , Brümmer Manuela , Boon Nanda , Wijnholds Jan , Mehlfeld Verena , Michalakis Stylianos , Fenske Stefanie , Biel Martin , Becirovic Elvir
Published: February 2023

Large genes including several CRISPR-Cas modules, such as gene activators (CRISPRa), require dual adeno-associated viral (AAV) vectors for an efficientin vivodelivery and expression. Current dual AAV vector approaches have important limitations, e.g., low reconstitution efficiency, production of alien proteins, or low flexibility in split site selection. Here, we present a dual AAV vector technology based onreconstitutionvia mRNA trans-splicing (REVeRT). REVeRT is flexible in split site selection and can efficiently reconstitute different split genes in numerousin vitromodels, in human organoids, andin vivo. Furthermore, REVeRT can functionally reconstitute a CRISPRa module targeting genes in various mouse tissues and organs in single or multiplexed approaches upon different routes of administration. Finally, intravitreal supplementation ofABCA4via REVeRT improves retinal degeneration and function in a mouse model of Stargardt disease. Due to its flexibility and efficiency REVeRT harbors great potential for basic research and clinical applications.
Detection of Activated Receptor Tyrosine Kinases in Human Lung Squamous Cell Carcinoma
Authors: Kendrick Nancy , Hoelter Matt , Koll Andrew , Darie Costel C. , Johansen Jon
Published: February 2023

Lung squamous cell carcinoma (LSCC) has a high mutational burden and poor prognosis, even with immunotherapy. In the Lux-Lung 8 trial, afatinib, an epidermal growth factor receptor (EGFR) inhibitor, showed a long-term benefit in 5.3% of patients with LSCC. Because activating mutations of EGFR are rare in LSCC, the response was likely due to wild-type EGFR being activated by an unknown mechanism. All receptor tyrosine kinase (RTK) proteins, both wild-type and mutated, are activated by phosphorylation of specific tyrosines which serve as binding sites for various SH2 proteins. The aim of this feasibility study was to determine whether enhanced chemiluminescent western blotting (WB) with a phosphotyrosine (pTyr) antibody is sufficiently sensitive to detect pTyr-RTK proteins in human LSCC tissues. We performed WB analysis on 25 resected human lung tissue samples, including 12 LSCC, two adenocarcinomas (LADC), and 11 control (non-tumor) lung samples. The analysis showed ∼220 kDa pTyr-protein bands in two LSCC samples that were much more abundant than the corresponding bands in controls or LADC samples. To identify pTyr-RTKs, pTyr WB patterns of the two samples were compared to those of five RTK candidates: EGFR, platelet-derived growth factor receptor beta (PDGFRB), vascular endothelial growth factor receptor, anaplastic lymphoma receptor, and mesenchymal-epithelial transition factor. The strong pTyr signal in one sample matched EGFR, whereas the other matched a combination of EGFR and PDGFRB. We conclude that pTyr WB is sufficiently sensitive to detect pTyr-RTK drivers in flash-frozen tumor tissues and might identify LSCC patient subsets responsive to RTK inhibitors.
Genome-wide mapping of theEscherichia coliPhoB regulon reveals many transcriptionally inert, intragenic binding sites
Authors: Fitzgerald Devon , Stringer Anne , Smith Carol , Lapierre Pascal , Wade Joseph T.
Published: February 2023

Genome-scale analyses have revealed many transcription factor binding sites within, rather than upstream of genes, raising questions as to the function of these binding sites. Here, we use complementary approaches to map the regulon of theEscherichia colitranscription factor PhoB, a response regulator that controls transcription of genes involved in phosphate homeostasis. Strikingly, the majority of PhoB binding sites are located within genes, but these intragenic sites are not associated with detectable transcription regulation and are not evolutionarily conserved. Many intragenic PhoB sites are located in regions bound by H-NS, likely due to shared sequence preferences of PhoB and H-NS. However, these PhoB binding sites are not associated with transcription regulation even in the absence of H-NS. We propose that for many transcription factors, including PhoB, binding sites not associated with promoter sequences are transcriptionally inert, and hence are tolerated as genomic “noise”.

IMPORTANCE

Recent studies have revealed large numbers of transcription factor binding sites within the genes of bacteria. The function, if any, of the vast majority of these binding sites has not been investigated. Here, we map the binding of the transcription factor PhoB across theEscherichia coligenome, revealing that the majority of PhoB binding sites are within genes. We show that PhoB binding sites within genes are not associated with regulation of the overlapping genes. Indeed, our data suggest that bacteria tolerate the presence of large numbers of non-regulatory, intragenic binding sites for transcription factors, and that these binding sites are not under selective pressure.
Peer’s Presence Reverses Escalated Cocaine Intake in Rats
Authors: Vielle Cassandre , Tiran-Cappello Alix , Vignal Lucie , Maurice Nicolas , Degoulet Mickael , Brocard Cécile , Pelletier Florence , Pelloux Yann , Baunez Christelle
Published: February 2023

The immediate social context at the time of drug consumption is critical at modulating it. The neurobiological substrate of such an influence is however poorly documented. The presence of a stranger peer, naïve to the drug, has been shown to reduce recreational cocaine intake in rats with similar results in human cocaine users. Here we assessed its influence in rats having previously lost their control over drug consumption. The subthalamic nucleus (STN) has been shown to play a critical role in cocaine motivation, escalation and re-escalation, as well as compulsive drug seeking. We show here that after escalation of cocaine intake, the presence of a stranger peer drastically reduced cocaine intake. The same effect was observed after both optogenetic inhibition and high-frequency stimulation of the STN in absence of a peer. We further show that the beneficial influence of social presence is mediated via the STN.

One Sentence Summary

The presence of a stranger peer drastically decreases cocaine intake after drug escalation, as does a subthalamic optogenetic modulation.
Pathogen-driven CRISPR screens identify TREX1 as a regulator of DNA self-sensing during influenza virus infection
Authors: King Cason R. , Liu Yiping , Amato Katherine A. , Schaack Grace A. , Hu Tony , Smith Judith A , Mehle Andrew
Published: February 2023

Intracellular pathogens interact with host factors, exploiting those that enhance replication while countering those that suppress it. Genetic screens have begun to define the host:pathogen interface and establish a mechanistic basis for host-directed therapies. Yet, limitations of current approaches leave large regions of this interface unexplored. To uncover host factors with pro-pathogen functions, we developed a novel fitness-based screen that queries factors important during the middle-to-late stages of infection. This was achieved by engineering influenza virus to direct the screen by programing dCas9 to modulate host gene expression. A genome-wide screen identified the cytoplasmic DNA exonuclease TREX1 as a potent pro-viral factor. TREX1 normally degrades cytoplasmic DNA to prevent inappropriate innate immune activation by self DNA. Our mechanistic studies revealed that this same process functions during influenza virus infection to enhance replication. Infection triggered release of mitochondrial DNA into the cytoplasm, activating antiviral signaling via cGAS and STING. TREX1 metabolized the mitochondrial DNA preventing its sensing. Collectively, these data show that self-DNA is deployed to amplify host innate sensing during RNA virus infection, a process tempered by TREX1. Moreover, they demonstrate the power and generality of pathogen driven fitness-based screens to pinpoint key host regulators of intracellular pathogens.
Genotypic and phenotypic evidence indicates the introduction of two distinct forms of a non-native species (Gekko gecko) to Florida, USA
Authors: Fieldsend Thomas W. , Rösler Herbert , Krysko Kenneth L. , Harman Madison E.A. , Mahony Stephen , Collins Timothy M.
Published: February 2023

The red-spotted tokay geckoGekko gecko(Linnaeus, 1758) is a widely distributed Asian gecko that has established outside of its native range in Florida, USA. This study used genotypic and phenotypic data to determine whether multiple, distinct forms of red-spotted tokay gecko are present in Florida, specifically the morphologically distinct “G. g. gecko” and “Form B”. Two discrete mitochondrial clades (ND2) were identified in Florida tokay geckos, the native range distributions of which were found to correspond closely with the native ranges ofG. g. gecko(the Malay Archipelago) and Form B (mainland Asia), respectively. Furthermore, each mitochondrial clade was non-randomly associated with a separate nuclear (RAG-1) clade, supporting the existence of two discrete genotypic lineages, representative ofG. g. geckoand Form B. Both lineages were detected in Florida, and population-level morphological structure was non-randomly associated with genotype, confirming a genotype-phenotype link. Multiple lines of evidence thus indicate the introduction of both forms of tokay gecko to Florida, where hybridisation likely also occurs. The link between morphological Form B and a unique genotypic lineage also indicates the existence of a tokay gecko taxon distinct from the recognised subspeciesG. g. azhariMertens, 1955 andG. g. gecko(Linnaeus, 1758).
HOPS-dependent lysosomal fusion controls Rab19 availability for ciliogenesis in polarized epithelial cells
Authors: Hoffman Huxley K. , Prekeris Rytis
Published: February 2023

Primary cilia are sensory cellular organelles crucial for organ development and homeostasis. Ciliogenesis in polarized epithelial cells requires Rab19-mediated clearing of apical cortical actin to allow the cilium to grow from the apically-docked basal body into the extracellular space. Loss of the lysosomal membrane-tethering HOPS complex disrupts this actin-clearing and ciliogenesis, but it remains unclear how ciliary function of HOPS relates to its canonical function in regulating late endosome-lysosome fusion. Here, we show that disruption of HOPS-dependent lysosomal fusion indirectly impairs actin-clearing and ciliogenesis by disrupting the targeting of Rab19 to the basal body. We also find that Rab19 functions in endolysosomal cargo trafficking apart from its previously-identified role in ciliogenesis. In summary, we show that inhibition of lysosomal fusion abnormally accumulates Rab19 on late endosomes, thus depleting Rab19 from the basal body and thereby disrupting Rab19-mediated actin-clearing and ciliogenesis.

Summary statement

Loss of HOPS-mediated lysosomal fusion indirectly blocks apical actin clearing and ciliogenesis in polarized epithelia by trapping Rab19 on late endosomes and depleting Rab19 from the basal body.
Lack of neutralizing antibodies against the current circulating influenza viruses during the Omicron outbreak in Hong Kong
Authors: Liang Weiwen , Lv Huibin , Chen Chunke , Sun Yuanxin , Hui David S , Pun Mok Chris Ka
Published: February 2023

We report the seroprevalence to the circulating influenza A H1N1 and H3N2 viruses from plasma samples collected from 479 adults between 2021 and 2022. Our results show that there is lack of neutralizing antibodies to these viruses and highlight the importance of promoting influenza vaccination during the emerging of COVID-19.
Attentional capture by fearful faces requires consciousness and is modulated by task-relevancy: a dot-probe EEG study
Authors: Qiu Zeguo , Jiang Jiaqin , Becker Stefanie I. , Pegna Alan J.
Published: February 2023

In the current EEG study, we used a dot-probe task in conjunction with backward masking to examine the neural activity underlying awareness and spatial processing of fearful faces and the neural processes for subsequent cued spatial targets. We presented face images under different viewing conditions (subliminal and supraliminal) and manipulated the relation between a fearful face in the pair and a subsequent target. Through both mass univariate analysis and multivariate pattern analysis, we found that fearful faces can be processed to an extent where they attract spatial attention only when they are presented supraliminally and when they are task-relevant. The spatial attention capture by fearful faces also modulated the processing of subsequent lateralised targets that were spatially congruent with the fearful face, in both behavioural and neural data. There was no evidence for nonconscious processing of the fearful faces in the current paradigm. We conclude that spatial attentional capture by fearful faces requires visual awareness and it is modulated by top-down task demands.
Decoupling cell size homeostasis in diatoms from the geometrical constraints of the silica cell-wall
Authors: de Haan Diede , Ramos Nahuel-Hernan , Gal Assaf
Published: February 2023

Unicellular organisms are known to exert tight control over their cell size. In the case of diatoms, abundant eukaryotic microalgae, the layout of the rigid silica cell wall imposes geometrical restrictions on cell size. A generally accepted theory states that the need to fit any new silica element into a previously formed structure causes a reduction in size with each vegetative division cycle, until cell size restoration is achieved by a switch to another life-cycle stage. Nevertheless, several reported exceptions cast doubt on the generality of this theory.

Here, we monitored clonal cultures of the diatomStephanopyxis turrisfor up to two years, recording the sizes of thousands of cells, in order to follow the distribution of cell sizes in the population.

Our results show that allS. turriscultures above a certain size threshold undergo a gradual size reduction, in accordance with the postulated geometrical driving force. However, once the cell size reaches a lower threshold, a constant size range is maintained by different cellular strategies.

These observations suggest two distinct mechanisms to regulate the cell size of diatoms, reduction and homeostasis. The interplay between these mechanisms can explain the behavior of different diatoms species in various environments.
Micro- to nano-scale investigation of Precambrian metasediments: biogenicity and preservation in the 3.22 Ga Moodies Group (Barberton Greenstone Belt, S. Africa) and the 2.46 Ga Brockman Iron Formation (Hamersley Basin, W. Australia)
Authors: Bellon Hervé , Gieraltowski Jacek , Michaud François , Simon Gaëlle , Cerantola Stéphane , Homann Martin , Foster Ian , Ballet Pascal , Lalonde Stefan V.
Published: February 2023

Precambrian metasediments provide a unique archive for understanding Earth’s earliest biosphere, however traces of microbial life preserved in ancient rocks are often controversial. In this study we leveraged several micro- to nano-scale techniques to study filamentous structures previously reported in clastic sediments of the 3.22 Ga Moodies Group, Barberton Greenstone Belt, S. Africa. We performed petrographic, mineralogical, electron microprobe, confocal fluorescence and electron microscopy analyses of these structures in order to evaluate their biogenicity and syngenecity. We also examined drill core samples of deep-water iron formations from the 2.46 Ga Joffre member of the Brockman Iron Formation (Hamersley Basin, W. Australia) to better understand their potential biogenicity. In both cases, we aimed to resolve primary vs. secondary mineral assemblages and their relation to filamentous or sedimentary structures. In the Moodies Group samples, filamentous structures were resolved by confocal imaging and revealed to be crosscut by later metamorphic phases, highlighting their syngenetic nature. Three-dimensional imaging reveals that while the filamentous structures are not necessarily associated with grain boundaries (e.g., as organic coatings), they form both sheets and filaments, complicating their interpretation but not ruling out a biological origin. No organic microstructures appeared to be preserved in our Dales Gorge samples. We also examined the possible application of electron paramagnetic resonance spectroscopy (EPR) to carbonaceous matter in ancient silica-rich matrices, similar to Bourbin et al. (2013), using samples from the Brockman iron formation. While resonance associated with organic matter was largely unresolvable in the Brockman iron formation samples due to their low organic matter contents, large effects on the EPR spectra were apparent stemming from the presence of magnetic iron minerals, highlighting the need to carefully consider sample composition in EPR analyses targeting ancient organic matter. Collectively, this study highlights the added value of micro- to nano-scale techniques as applied to Precambrian metasediments containing traces of ancient life, for example in revealing the pre-metamorphic emplacement and three-dimensional structure of filaments in the Moodies Group, but also the potential drawbacks and pitfalls, such as the case of strong magnetic mineral interference in EPR analysis of organic matter in trace abundance in the Dales Gorge.
Ev-OSMOSE: An eco-genetic marine ecosystem model
Authors: Morell Alaia , Shin Yunne-Jai , Barrier Nicolas , Travers-Trolet Morgane , Ernande Bruno
Published: February 2023

In the last decade, marine ecosystem models have been increasingly used to project interspecific biodiversity under various global change and management scenarios, considering ecological dynamics only. However, fish populations may also adapt to climate and fishing pressures, via evolutionary changes, leading to modifications in their life-history that could either mitigate or worsen, or even make irreversible, the impacts of these pressures. Building on the multispecies individual-based model Bioen-OSMOSE, an eco-evolutionary fish community model, Ev-Osmose, has been developed to account for evolutionary dynamics together with physiological and ecological dynamics in fish diversity projections. A gametic inheritance module describing the individuals’ genetic structure has been implemented. The genetic structure is defined by finite numbers of loci and alleles per locus that determine the genetic variability of growth, maturation and reproductive effort. Climate change and fishing activities will generate selection pressures on fish life-history traits that will respond through microevolution. This paper is an overview of the Ev-OSMOSE model. To illustrate the ability of the Ev-OSMOSE model to represent realistic fish community dynamics, genotypic and phenotypic traits’ mean and variance and consistent evolutionary patterns, we applied the model to the North Sea ecosystem. The simulated outputs are confronted to observed data of commercial catch, maturity ogives and length at age and to estimates of biomass for each modeled species. In addition to the evaluation of their mean value, the emerging traits’ variability is confronted to length-at-age and maturity data. To ensure the consistency of genetic inheritance and the resulting evolutionary patterns, we assessed the transmission of traits’ genotypic value across cohorts. Overall, the state of the modelled ecosystem was convincing at all these different biological levels. These results open perspectives for using Ev-OSMOSE in different marine regions to project the eco-evolutionary impact of various global change and management scenarios on different biological levels.
Regional assessment of male murine bone exposes spatial heterogeneity in osteocyte lacunar volume associated with intracortical canals and regulation by VEGF
Authors: Trend Jacob , Sharma Alisha , Michels Lysanne , Goggin Patricia , Schneider Philipp , Deinhardt Katrin , Clarkin Claire E
Published: February 2023

The porous bone cortex comprises an interconnected network of intracortical vascular canals and osteocyte lacunae, embedded within the bone mineral. Increases in cortical porosity reduce bone strength and increase fracture risk. To date, our understanding of mechanisms coupling the arrangements of the vascular: lacunar network in the bone cortex is poorly understood yet it could be key in establishing regulation of cortical porosity evident with age. Using synchrotron radiation-based computed tomography we develop automated tools to characterise the 3D spatial organisation and morphology of osteocyte lacunae, and the bone vasculature at the tibiofibular junction (TFJ), defining posterior, medial, lateral, and anterior regions in male C57BL/6 mice (n = 3). We also investigate the role of osteoblast-derived VEGF in regulating the 3D spatial arrangement by conditional disruption of VEGF in osteocalcin-expressing cells (OcnVEGFKO versus WT, n = 3). Regional lacunar phenotypes were assessed by 3D distance mapping of lacunar organisation surrounding the vascular compartments, including endosteal and periosteal surfaces, or intracortical canals. Surface-associated lacunae were indistinct in size across posterior, medial, lateral and anterior regions. However, lacunae associated with intracortical canals were significantly larger exclusively within the posterior region. In the absence of VEGF, the increased lacunar volume associated with posterior intracortical canals was lost. Our results suggest that the influence of intracortical canals on lacunar volumes is spatially regulated and sensitive to locally produced growth factors such as osteoblast-derived VEGF.
Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function
Authors: Roka-Moiia Yana , Ammann Kaitlyn , Miller-Gutierrez Samuel , Sheriff Jawaad , Bluestein Danny , Italiano Joseph E. , Flaumenhaft Robert C. , Slepian Marvin J.
Published: February 2023

Objective

Implantable cardiovascular therapeutic devices (CTD) including stents, percutaneous heart valves and ventricular assist devices, while lifesaving, impart supraphysiologic shear stress to platelets resulting in thrombotic and bleeding device-related coagulopathy. We previously demonstrated that shear-mediated platelet dysfunction is associated with downregulation of platelet GPIb-IX-V and αIIbβ3 receptors via generation of platelet-derived microparticles (PDMPs). Here, we test the hypothesis that shear-generated PDMPs manifest phenotypical heterogeneity of their morphology and surface expression of platelet receptors, and modulate platelet hemostatic function.

Approach and Results

Human gel-filtered platelets were exposed to continuous shear stress and sonication. Alterations of platelet morphology were visualized using transmission electron microscopy. Surface expression of platelet receptors and PDMP generation were quantified by flow cytometry. Thrombin generation was quantified spectrophotometrically, and platelet aggregation in plasma was measured by optical aggregometry. We demonstrate that platelet exposure to shear stress promotes notable alterations in platelet morphology and ejection of several distinctive types of PDMPs. Shear-mediated microvesiculation is associated with the differential remodeling of platelet receptors with PDMPs expressing significantly higher levels of both adhesion (αIIbβ3, GPIX, PECAM-1, P-selectin, and PSGL-1) and agonist-evoked receptors (P2Y12& PAR1). Shear-mediated PDMPs have a bidirectional effect on platelet hemostatic function, promoting thrombin generation and inhibiting platelet aggregation induced by collagen and ADP.

Conclusions

Shear-generated PDMPs demonstrate phenotypic heterogeneity as to morphologic features and defined patterns of surface receptor alteration, and impose a bidirectional effect on platelet hemostatic function. PDMP heterogeneity suggests that a range of mechanisms are operative in the microvesiculation process, contributing to CTD coagulopathy and posing opportunities for therapeutic manipulation.
Expression, purification and crystallization of N-acetyl-(R)-β-phenylalanine acylases derived from Burkholderia sp. AJ110349 and Variovorax sp. AJ110348 and structure determination of the Burkholderia enzyme
Authors: Kato Yuki , Kawasaki Hisashi , Nakamatsu Tsuyoshi , Matsuda Namio , Natsume Ryo
Published: February 2023

N-Acetyl-(R)-β-phenylalanine acylase is an enzyme that hydrolyzes the amide bond of N-acetyl-(R)-β-phenylalanine to produce enantiopure (R)-β-phenylalanine. In previous studies, Burkholderia sp. AJ110349 and Variovorax sp. AJ110348 were isolated as (R)-enantiomer-specific N-acetyl-(R)-β-phenylalanine acylase-producing organisms and the properties of the native enzyme from Burkholderia sp. AJ110349 were characterized. In this study, structural analyses were carried out in order to investigate the structure–function relationships of the enzymes derived from both organisms. The recombinant N-acetyl-(R)-β-phenylalanine acylases were crystallized by the hanging-drop vapor-diffusion method under multiple crystallization solution conditions. The crystals of the Burkholderia enzyme belonged to space group P41212, with unit-cell parameters a = b = 112.70–112.97, c = 341.50–343.32 Å, and were likely to contain two subunits in the asymmetric unit. The crystal structure was solved by the Se-SAD method, suggesting that two subunits in the asymmetric unit form a dimer. Each subunit was composed of three domains, and they showed structural similarity to the corresponding domains of the large subunit of N,N-dimethylformamidase from Paracoccus sp. strain DMF. The crystals of the Variovorax enzyme grew as twinned crystals and were not suitable for structure determination. Using size-exclusion chromatography with online static light-scattering analysis, the N-acetyl-(R)-β-phenylalanine acylases were clarified to be dimeric in solution.
A review on developing optimization techniques in civil engineering
Authors: Zaheer Qasim , Manzoor Mir Majaid , Ahamad Muhammad Jawad
Published: February 2023

Purpose

The purpose of this article is to analyze the optimization process in depth, elaborating on the components of the entire process and the techniques used. Researchers have been drawn to the expanding trend of optimization since the turn of the century. The rate of research can be used to measure the progress and increase of this optimization procedure. This study is phenomenal to understand the optimization process and different algorithms in addition to their application by keeping in mind the current computational power that has increased the implementation for several engineering applications.

Design/methodology/approach

Two-dimensional analysis has been carried out for the optimization process and its approaches to addressing optimization problems, i.e. computational power has increased the implementation. The first section focuses on a thorough examination of the optimization process, its objectives and the development of processes. Second, techniques of the optimization process have been evaluated, as well as some new ones that have emerged to overcome the above-mentioned problems.

Findings

This paper provided detailed knowledge of optimization, several approaches and their applications in civil engineering, i.e. structural, geotechnical, hydraulic, transportation and many more. This research provided tremendous emerging techniques, where the lack of exploratory studies is to be approached soon.

Originality/value

Optimization processes have been studied for a very long time, in engineering, but the current computational power has increased the implementation for several engineering applications. Besides that, different techniques and their prediction modes often require high computational strength, such parameters can be mitigated with the use of different techniques to reduce computational cost and increase accuracy.
Key influence factors on the evacuation route selection for fire emergencies in urban underground complexes
Authors: Li Xiaojuan , Chang Ching-Ter , Zhu Yue-Yue , Li Lu-Lu
Published: February 2023

Purpose

The development of urban underground complexes (UUCs) has great positive significance for improving urban safety. Therefore, it is necessary to identify the key factors of the people's behavior of evacuation route selection (BERS) for fire emergencies and UUCs’ development. This study aims to find out the factors affecting people's BERS in the evacuation process of UUCs.

Design/methodology/approach

This study aims to find out the factors affecting people's BERS in the evacuation process of UUCs. To achieve this goal, the authors conducted a field experiment in F City. Furthermore, the people's BERS are obtained by using a structural equation model and compared with the field test results.

Findings

The authors found that the key factors for people's BERS are lighting conditions, route distance, flow direction guidance and indication. The results of this study contribute to the safety field by providing key factors for fire emergencies. It can also be used to improve fire safety management, evacuation strategies and assist in the development of intelligent evacuation systems.

Originality/value

The results of this study contribute to the safety field by providing key factors for fire emergencies. It can also be used to improve fire safety management, evacuation strategies and assist in the development of intelligent evacuation systems.
Energy analysis at the interface of piezo/thermoelastic half spaces
Authors: Gupta Vipin , Kumar Rajesh , Kumar Rajneesh , Barak M.S.
Published: February 2023

Purpose

This paper aims to study the energy ratios of plane waves on an interface of nonlocal thermoelastic halfspace (NTS) and nonlocal orthotropic piezothermoelastic half-space (NOPS).

Design/methodology/approach

The memory-dependent derivatives (MDDs) approach with a hyperbolic two-temperature (HTT), three-phase lag theory is used here to study how the energy ratios change at the interface with the angle of incidence.

Findings

Plane waves that travel through NTS and hit the interface as a longitudinal wave, a thermal wave, or a transversal wave send four waves into the NOPS medium and three waves back into the NTS medium. The amplitude ratios of the different waves that are reflected and transmitted are used to calculate the energy ratios of the waves. It is observed that these ratios are affected by the HTT, nonlocal and MDD parameters.

Research limitations/implications

The energy ratios correspond to four distinct models; nonlocal HTT with memory, nonlocal HTT without memory, local HTT with memory and nonlocal classical-two-temperature with memory concerning the angle of incidence from 0 degree to 90 degree.

Practical implications

This model applies to several fields, including earthquake engineering, soil dynamics, high-energy particle physics, nuclear fusion, aeronautics and other fields where nonlocality, MDD and conductive temperature play an important role.

Originality/value

The authors produced the submitted document entirely on their initiative, with equal contributions from all of them.
Risk homeostasis and security fatigue: a case study of data specialists
Authors: Bhana Anusha , Ophoff Jacques
Published: February 2023

Purpose

Organisations use a variety of technical, formal and informal security controls but also rely on employees to safeguard information assets. This relies heavily on compliance and constantly challenges employees to manage security-related risks. The purpose of this research is to explore the homeostatic mechanism proposed by risk homeostasis theory (RHT), as well as security fatigue, in an organisational context.

Design/methodology/approach

A case study approach was used to investigate the topic, focusing on data specialists who regularly work with sensitive information assets. Primary data was collected through semi-structured interviews with 12 data specialists in a large financial services company.

Findings

A thematic analysis of the data revealed risk perceptions, behavioural adjustments and indicators of security fatigue. The findings provide examples of how these concepts manifest in practice and confirm the relevance of RHT in the security domain.

Originality/value

This research illuminates homeostatic mechanisms in an organisational security context. It also illustrates links with security fatigue and how this could further impact risk. Examples and indicators of security fatigue can assist organisations with risk management, creating “employee-friendly” policies and procedures, choosing appropriate technical security solutions and tailoring security education, training and awareness activities.
The role of social media engagement in building relationship quality and brand performance in higher education marketing
Authors: Song Bee Lian , Lee Kim Lian , Liew Chee Yoong , Subramaniam Muthaloo
Published: February 2023

Purpose

Social media engagement is widely used by the higher education institutions (HEIs) to improve brand performance through brand image and brand loyalty. This study focusses on the effect of social media engagement on relationship quality and brand performance in the higher education marketing (HEM) context. Social media engagement dimensions comprising social interaction, sharing of information, surveillance and information quantity are tested as antecedents to relationship quality. Relationship quality is examined as antecedents to brand image and brand loyalty.

Design/methodology/approach

Data are obtained through survey questionnaire from 410 undergraduate and postgraduate students from six HEIs in Malaysia. Structural equation modelling was applied for data analysis.

Findings

The findings of this study reveal that social interaction, sharing of information, surveillance and information quantity have positive effect on relationship quality. Relationship quality has significant positive influence on brand image and brand loyalty, respectively.

Originality/value

The study contributes to the extension of social exchange theory through the development of an integrative framework of social media engagement (exchange) needed for improving relationship quality (relational responses) and brand performance (behavioural outcomes) in the HEM.