bluuebunny/crossref_metadata_2025 huggingface dataset:
Low polyethylene glycol (PEG) concentration contributes to photoprotection in Chlamydomonas reinhardtii under highlight stress
Authors: Xavier Jerome , Yadav Ranay Mohan , Subramanyam Rajagopal
Published: September 2022

The highlight is one of the major problems encountered by all the autotrophs in the natural environment, as it affects the photosynthetic performance of these organisms, they were equipped themself with the diverse photoprotective mechanism. However, the drastic climate change in recent years had a more lethal effect on these organisms as it is beyond their threshold to withstand. In the past decade, scientists have unravelled many photoprotective mechanisms like qE, qZ, qT and qI (NPQ) used by autotrophs to combat highlight stress and the thirst for discovering such a new mechanism remains constant. In this regard, we studied the effect of mild osmotic stress (2%PEG) in alleviating high-light stress using Chlamydomonas (C) reinhardtii as a model system. The cells were grown in low Polyethylene glycol (PEG)-induced osmotic stress at varying light intensities; their response to these treatments had been examined via biochemical and biophysical approaches. The PEG-treated cells showed better growth and photosynthetic efficiency even at highlight than control, but their NPQ level is lesser than control, suggesting a unique or novel photoprotective mechanism is operating in PEG-treated samples. The Circular dichroism and ATG8 localization assay suggest that supercomplexes organization is not much disturbed in PEG-treated samples irrespective of light intensity. Also, the latter indicates that PEG-treated cells were healthier than the control at the highlight. This result is promising as we can improve the algal biomass under natural environmental conditions with fluctuating light intensity. As algal biomass has immense commercial importance in biofuel production, cosmetics and pharmaceutical application. This mechanism can be exploited to promote the socio-economic status of our nation.

Highlights

PEG application triggers ROS accumulations, stimulating signalling cascade and overcoming highlight-induced compromise in biomass.

Under highlight, the photosynthetic pigment (chlorophyll and carotenoid) constantly increased with PEG except for C-250. Specifically, the photoprotective pigment like violaxanthin and lutein has been increased.

PEG shielding stabilizes pigment-protein interaction, confirming that the supercomplex organization is in its native state.

PEG keeps low ATG8 accumulation, preventing cells and enabling it to combat highlights more effectively.

Graphical abstract
Chlamydia trachomatis effectors target the mitochondria and alter mitochondrial protein composition
Authors: Dimond Zoe , Bauler Laura D. , Zhang Yixiang , Carmody Aaron , Hackstadt Ted
Published: September 2022

Mitochondria are critical cellular organelles that perform a wide variety of functions including energy production and immune regulation. To perform these functions, mitochondria contain approximately 1,500 proteins, the majority of which are encoded in the nuclear genome, translated in the cytoplasm, and translocated to the mitochondria using distinct mitochondria targeting sequences (MTS). Bacterial proteins can also contain MTS and localize to the mitochondria. For the obligate intracellular human pathogen, Chlamydia trachomatis, interaction with various host cell organelles promotes intracellular replication. However, the extent and mechanisms through which Chlamydia interact directly with mitochondria remain unclear. We investigated the presence of MTS in the C. trachomatis genome and discovered 30 genes with around 70% or greater probability of mitochondrial localization. Five are translocated to the mitochondria upon ectopic expression in HeLa cells. Mass spectrometry of isolated mitochondria from infected cells revealed that two of these proteins localize to the mitochondria during infection. Comparison of mitochondria from infected and uninfected cells suggests that chlamydial infection affects mitochondrial protein composition. Around 125 host proteins were significantly decreased or absent in mitochondria from infected cells. Among these are pro-apoptotic factors and those related to mitochondrial fission/fusion dynamics. Conversely, 82 host proteins were increased in or specific to mitochondria of infected cells, many of which act as anti-apoptotic factors and upregulators of cellular metabolism. These data support the notion that C. trachomatis specifically targets host mitochondria to manipulate cell fate decisions and metabolic function to support pathogen survival and replication.

Importance

Obligate intracellular bacteria have evolved multiple means to promote their intracellular survival and replication within the otherwise harsh environment of the eukaryotic cell. Nutrient acquisition and avoidance of cellular defense mechanisms are critical to an intracellular lifestyle. Mitochondria are critical organelles that produce energy in the form of ATP and regulate programmed cell death responses to invasive pathogenic microbes. Cell death prior to completion of replication would be detrimental to the pathogen. C. trachomatis produces at least two and possibly more proteins that target the mitochondria. Collectively, C. trachomatis infection modulates mitochondrial protein composition favoring a profile suggestive of down-regulation of apoptosis.
A Novel Dry-Stabilized Whole Blood Microsampling and Protein Extraction Method for Testing of SARS-CoV-2 Antibody Titres
Authors: McCarthy Patrick , Pathakamuri Joseph A , Kuebler Daniel , Neves Jocelyn , Krohn Madison , Rohall Michael , Archibeque Isaac , Giese Heidi , Werner Martina , Thomann Ulrich
Published: September 2022

The COVID-19 pandemic has revealed a crucial need for rapid, straightforward collection and testing of biological samples. Serological antibody assays can analyse patient blood samples to confirm immune response following mRNA vaccine administration or to verify past exposure to the SARS-CoV-2 virus. While blood tests provide vital information for clinical analysis and epidemiology, sample collection is not uncomplicated. This process requires a visit to the doctor’s office, a professionally trained phlebotomist to draw several millilitres of blood, processing to yield plasma or serum, and necessitates appropriate cold chain storage to preserve the specimen. The Covaris truCOLLECT Whole Blood Collection Kit allows for a lancet-based, decentralised capillary blood collection of exactly metered low volumes and eliminates the need for refrigerated transport and storage through the process of active desiccation. Anti-SARS CoV-2 spike and nucleocapsid protein antibody titres in plasma samples collected via venepuncture were compared to antibody titres in whole blood extracts obtained by treating desiccated whole blood samples stored in truCOLLECT sampling devices with Covaris Adaptive-focused Acoustics (AFA). Pearson correlation coefficients of 0.98, 95% CI [0.96, 0.99] for anti-SARS-CoV spike protein antibodies and 0.97, 95% CI [0.94, 0.99] for anti-SARS-CoV-2 nucleocapsid protein antibodies were observed. These data suggest that serology testing using desiccated whole blood samples collected and stored in truCOLLECT devices can be a convenient and cost-effective alternative to conventionally collected plasma.
Analysis of Healthcare Seeking Behavior Among Patients Visiting Public Primary and Secondary Healthcare Facilities in an Urban Indian District
Authors: Fatma Najiya , Ramamohan Varun
Published: September 2022

In this work, we examined healthcare seeking behavior (HSB) of patients visiting public healthcare facilities in an urban context. We conducted a cross-sectional survey across twenty-two primary and secondary public healthcare facilities in the South-west Delhi district in India. The survey was designed to ascertain from patients at these facilities their HSB - i.e., on what basis patients decide the type of healthcare facility to visit, or which type of medical practitioner to consult. From each facility visited, we also collected operational information, such as the average number of patients visiting per day, and the medical services provided at each facility. Based on participant responses, we observed that factors such as wait time, prior experience with care providers, distance from the facility, and also socioeconomic and demographic factors such as annual income, educational qualification, and gender significantly influenced preferences of patients in choosing healthcare facilities. We used binomial and multinomial logistic regression to determine associations between HSB and socioeconomic and demographic attributes of patients at a 0.05 level of significance. Our statistical analyses revealed that patients in the lower income group preferred to seek treatment from public healthcare facilities (OR = 3.51, 95% CI = (1.65, 7.46)) irrespective of the perceived severity of their illness, while patients in the higher income group favored directly consulting specialized doctors (OR = 2.71, 95% CI = (1.34, 5.51)). Other factors such as having more than two children increased probability of seeking care from public facilities. This work contributes to the literature by providing quantitative evidence regarding overall patient HSB, especially at primary and secondary public healthcare facilities, regardless of their presenting illness, and operational information regarding healthcare delivery at these facilities. This work can inform policy designed to improve accessibility and quality of care at public primary and secondary healthcare facilities in India.
Single-strain behavior predicts responses to environmental pH and osmolality in the gut microbiota
Authors: Ng Katharine M. , Pannu Sagar , Liu Sijie , Burckhardt Juan C. , Hughes Thad , Van Treuren William , Nguyen Jen , Naqvi Kisa , Nguyen Bachviet , Clayton Charlotte A. , Pepin Deanna M. , Collins Samuel R. , Tropini Carolina
Published: September 2022

Changes to gut environmental factors such as pH and osmolality due to disease or drugs correlate with major shifts in microbiome composition; however, we currently cannot predict which species can tolerate such changes or how the community will be affected. Here, we assessed the growth of 92 representative human gut bacterial strains spanning 28 families across multiple pH values and osmolalities in vitro. The ability to grow in extreme pH or osmolality conditions correlated with the availability of known stress response genes in many cases, but not all, indicating that novel pathways may participate in protecting against acid or osmotic stresses. Machine learning analysis uncovered genes or subsystems that are predictive of differential tolerance in either acid or osmotic stress. For osmotic stress, we corroborated the increased abundance of these genes in vivo during osmotic perturbation. The growth of specific taxa in limiting conditions in isolation in vitro correlated with survival in complex communities in vitro and in an in vivo mouse model of diet-induced intestinal acidification. Our data show that in vitro stress tolerance results are generalizable and that physical parameters may supersede interspecies interactions in determining the relative abundance of community members. Importantly, we provide an extensive resource for predicting shifts in microbial composition and gene abundance in complex perturbations. Furthermore, this work highlights the physical environment as a major driver of bacterial composition and the importance of performing physical measurements in animal and clinical studies to elucidate the drivers of shifts in microbiota abundance.

Significance Statement

Changes in pH and particle concentration (osmolality) commonly result from gut disease or the ingestion of common drugs, causing changes in bacterial growth and microbiota composition within the intestine. Thus far, the effects of physical parameters on the growth of intestinal bacterial taxa have not been well documented in the context of predicting microbiota community composition. To address this gap, we examined the growth of 92 bacterial species under varying pH and osmolality conditions. We found that physical parameters are key predictors of bacterial abundance in individual-strain cultures and in complex bacterial communities. Moreover, our results identified specific genes and pathways that are predictive of growth in specific environments. Together, these findings can aid in determining the effectiveness of microbiota therapies in gut environments subjected to various perturbations.
The SARS-CoV-2 Spike S1 Protein Induces Global Proteomic Changes in ATII-Like Rat L2 Cells that are Attenuated by Hyaluronan
Authors: Mobley James A. , Molyvdas Adam , Kojima Kyoko , Jilling Tamas , Li Jian-Liang , Garantziotis Stavros , Matalon Sadis
Published: September 2022

The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants that have been characterized to date, COVID-19 has led to 571,198,904 confirmed cases, and 6,387,863 deaths worldwide (as of July 15th, 2022). Despite tremendous advances in our understanding of COVID19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics applications combined with systems biology analysis identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in an ATII-like Rat L2 cells that include three significant network hubs: E2F1, CREB1/ RelA, and ROCK2/ RhoA. Separately, we found that pre-treatment with High Molecular Weight Hyaluronan (HMW-HA), greatly attenuated the S1 effects. Immuno-targeted studies carried out on E2F1 and Rock2/ RhoA induction and kinase-mediated activation, in addition to cell cycle measurements, validated these observations. Taken as a whole, our discovery proteomics and systems analysis workflow, combined with standard immuno-targeted and cell cycle measurements revealed profound and novel biological changes that contribute to our current understanding of both Spike S1 and Hyaluronan biology. This data shows that the Spike S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV2 induced cell injury.
Comparative genomic and metagenomic investigations of the Corynebacterium tuberculostearicum species complex reveals potential mechanisms underlying associations to skin health and disease
Authors: Salamzade Rauf , Swaney Mary Hannah , Kalan Lindsay R.
Published: September 2022

Corynebacterium are a diverse genus and dominant member of the human skin microbiome. Recently, we reported that the most prevalent Corynebacterium species found on skin – including Corynebacterium tuberculostearicum and Corynebacterium kefirresidentii – comprise a narrow species complex despite the diversity of the genus. Here, we apply high-resolution phylogenomics and comparative genomics to describe the structure of the C. tuberculostearicum species complex. We find this species complex is missing a fatty acid biosynthesis gene family which is often found in multi-copy in approximately 99% of other Corynebacterium species. Conversely, this species complex is enriched for multiple genetic traits, including a gene encoding for a collagen-like peptide. Further, through metagenomic investigations, we find that one species within the complex, C. kefirresidentii, increases in relative abundance during atopic dermatitis flares and show that most members of this species possess a colocalized set of putative virulence genes.
Myoglobin promotes cardiomyocyte differentiation through oxidatively modulating the Hippo Kinase Pathway
Authors: Rao Krithika , Rochon Elizabeth , Singh Anuradha , Jagnnathan Rajaganapathi , Peng Zishan , Moulik Mousumi , Zhang Manling , Corti Paola , Shiva Sruti
Published: September 2022

Background

While cardiomyocytes undergo terminal differentiation postnatally and rarely re-enter the cell cycle, the endogenous mechanisms that propagate differentiation and prevent de-differentiation remain unclear. The monomeric heme protein myoglobin, which stores oxygen and regulates reactive oxygen/nitrogen species balance in the heart, increases in expression by over 50% during cardiomyocyte differentiation. Though myoglobin deletion without significant compensation is embryonic lethal in mice, a role for the protein in regulating cardiomyocyte differentiation has not been tested. We hypothesized that myoglobin expression is required for cardiomyocyte differentiation and the loss of myoglobin enables de-differentiation.

Methods

Myoglobin was genetically silenced in HL-1, H9C2 cells, and neonatal rat ventricular cardiomyocytes (NRVM) to examine myoglobin-dependent effects on differentiation, proliferation, and Hippo pathway signaling. A zebrafish model of Mb depletion was made using CRISPR-Cas9 to test the effect of myoglobin depletion on cardiac regeneration after apical resection injury in vivo.

Results

Myoglobin deletion in cultured cell lines and NRVM decreased the gene expression of cardiomyocyte differentiation markers (troponin, myosin light chain, and myosin heavy chain), upregulated markers of dedifferentiation (runx1 and dab2) and stimulated cell proliferation. Mechanistically, we show that the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, which activates the enzyme to phosphorylate the downstream Yes-associated protein (YAP) transcription factor, which prevents its transcriptional activity. Thus, the loss of myoglobin results in the de-phosphorylation and nuclear translocation of YAP, which propagates proliferation and fetal gene expression. In vivo, myoglobin-deficient zebrafish hearts recapitulated the increase in YAP signaling and showed accelerated regeneration at 20 days post apical injury.

Conclusion

We a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation, and a regulator of the Hippo pathway. These findings suggest myoglobin as a potential target for strategies to enhance cardiac development and improve cardiac repair and regeneration.
Effective root responses to salinity stress include maintained cell expansion and carbon allocation
Authors: Li Hongfei , Duijts Kilian , Pasini Carlo , van Santen Joyce E , Wang Nan , Zeeman Samuel C. , Santelia Diana , Zhang Yanxia , Testerink Christa
Published: September 2022

Acclimation of root growth is vital for plants to survive salt stress. Halophytes are great examples of plants that thrive under high salt concentrations but their salt tolerance mechanisms, especially those mediated by root responses, are still largely unknown. We compared root growth responses of the halophyteSchrenkiella parvulawith its glycophytic relative speciesArabidopsis thalianaunder salt stress, and performed root transcriptomic analysis to identify differences in gene regulatory networks underlying their physiological responses. Primary root growth ofS. parvulais less sensitive to salt compared with Arabidopsis. The root transcriptomic analysis ofS. parvularevealed the induction of sugar transporters and genes regulating cell expansion and suberization under salt stress.14C-labelled carbon partitioning analyses consistently showed thatS. parvulahad a higher incorporation rate of soluble sugars in roots under salt stress compared to Arabidopsis. Further physiological investigation revealed thatS. parvularoots do not show a halotropic response and maintain root cell expansion and enhanced suberization even under severe salt stress. In summary, our study demonstrates that roots ofS. parvuladeploy multiple physiological and developmental adjustments under salt stress to maintain growth, providing new avenues to improve salt tolerance of plants using root-specific strategies.
Determining the Insemination Status of Aedes Mosquitoes
Authors: Parsana Dhwani , Nanfack-Minkeu Ferdinand , Sirot Laura K.
Published: September 2022

Within the genus Aedes, the reproductive biology of two species has been most thoroughly studied: Aedes aegypti and Aedes albopictus. In these species, females tend to copulate with one or more males once sexually mature. Within a few hours after an initial insemination, most females become refractory to insemination for the rest of their lives. Aedes females store sperm in three sclerotized spherical structures called spermathecae, where they can remain viable for >3 mo after copulation. This protocol outlines a quick (∼3–5 min per female once you are practiced in dissection) and effective method for dissecting the female spermathecae from Ae. aegypti and Ae. albopictus mosquitoes and scoring them for the presence or absence of sperm in cases in which the researcher does not need the female for further studies.
Can MSMEs in tourism survive the COVID-19 storm? A MSME view of their stakeholders
Authors: John Lijo
Published: September 2022

Purpose

This paper explores the challenges faced by the micro, small and medium enterprises (MSMEs) in the tourism industry in building capabilities toward being resilient in the wake of crises through a stakeholder perspective.

Design/methodology/approach

This study identifies the barriers to building resilience through detailed literature review and expert interviews. A total of 13 barriers were identified and were classified into into three main categories, namely economic barriers, organizational barriers, and stakeholder barriers. Subsequently, primary data were collected to emperically validate the nature and strength of interactions between these barriers and to quantitatively identify their impact.

Findings

The study identifies that in long run, stakeholder barriers are the most significant in building capabilities toward being resilient in the wake of crisis. However, for initial recovery, economic barriers need to be focused. Subsequently, organizational capabilities needs to be developed through stakeholder support.

Practical implications

The study provides actionable insights to help MSMEs in the tourism industry to recover economically and to help them build lasting capabilities through organizational capability development and stakeholder support.

Originality/value

This study is novel on two aspects. First, the study investigates role of MSMEs in the tourism industry and how MSMEs are pivotal in helping the industry recover from a crisis by being resilient. Second, the role of stakeholders in the MSMEs sector in tourism is underexplored area and this study adds value to this nascent literature.
Verbal elder abuse in India: a descriptive phenomenological study
Authors: Patel Avanish Bhai
Published: September 2022

Purpose

Verbal abuse of the aged people in later life is a matter of grave concern in contemporary times. Aged people are abused by family members, relatives and neighbors in the form of yelling, taunting, swearing and threats, among other things. These abusive behaviors have the greatest influence on their social standing and well-being, and they cause society and families to dismantle their social networks as a result. This study aims to understand the nature of verbal elder abuse as a social phenomenon under the theoretical framework of sociocultural paradigm and examines the causes.

Design/methodology/approach

The descriptive phenomenology method has been applied in this study. The study has been conducted on a sample of 60 elderly living in Kanpur district of Uttar Pradesh. The concern of using descriptive phenomenology in the present study is to understand the nature of verbal abuse against the elderly systematically by exploring cultural, situational and social aspects of verbal abuse in Indian society. This method analyzes the reality behind the verbal elder abuse as a social phenomenon and relationship between elderly and their abusers.

Findings

The study finds an increase in verbal elder abuse in Indian families, which can range from psychological torture to physical torture, and includes insults, humiliation and neglecting the needs of the elderly for food, clothing, shelter and medical attention. The study also points out that reduction in attachment is as a responsible factor for verbal abuse with the elderly in modern times.

Originality/value

This is an original paper. This paper talks about the most concerning issue of verbal abuse which is faced by aged people in their family and society. Basically, this paper has applied the descriptive phenomenological method for the analysis of verbal elder abuse as a social phenomenon in the sociocultural context of Indian society.
The Oxford Cognitive Screen for use with Australian people after stroke (OCS‐AU): The adaptation process and determining cut scores for cognitive impairment using a cross‐sectional normative study
Authors: Sanctuary Colette , Hewitt Luisa , Demeyere Nele , Kankkunen Kirsti , Oxenham D. Vincent , Simpson Dawn B. , Stolwyk Renerus J. , Synn Artemis , Webb Sam S. , Marsden Dianne L.
Published: September 2022

Introduction

Two parallel versions (A and B) of the Oxford Cognitive Screen (OCS) were developed in the United Kingdom (UK) as a stroke‐specific screen of five key cognitive domains commonly affected post‐stroke. We aimed to develop the Australian versions A and B (OCS‐AU), including Australian cut‐scores indicative of impairment. We hypothesised there to be no difference in performance between the UK and Australian normative data cohorts.

Methods

Our multidisciplinary expert panel used the UK pre‐defined process to develop the OCS‐AU versions A and B. We then conducted a cross‐sectional normative study. We purposively recruited community‐dwelling, Australian‐born, and educated adults; with no known cognitive impairment; representative of age, sex, education level, and living location; at seven sites (four metropolitan, three regional) across four Australian states. Participants completed one or both OCS‐AU versions in a randomised order. Australian cohorts were compared with the corresponding UK cohorts for demographics using Pearson's chi‐squared test for sex and education, and Welch two‐sample t test for age. For the cut‐scores indicating cognitive impairment, the fifth (95th) percentiles and group mean performance score for each scored item were compared using Welch two‐sample t tests. The pre‐defined criteria for retaining OCS cut‐scores had no statistically significant difference in either percentile or group mean scores for each scored item.

Results

Participants (n = 83) were recruited: fifty‐eight completed version A [age (years) mean = 61,SD = 15; 62% female], 60 completed version B [age (years) mean = 62,SD = 13, 53% female], and 35 completed both [age (years) mean = 64,SD = 11, 54% female]. Education was different between the cohorts for version B (12 years, p = 0.002). Cut‐scores for all 16 scored items for the OCS‐AU version B and 15/16 for version A met our pre‐defined criteria for retaining the OCS cut scores.

Conclusions

The OCS‐AU provides clinicians with an Australian‐specific, first‐line cognitive screening tool for people after stroke. Early screening can guide treatment and management.
Incorporating parameter variability into Monod models of nutrient‐limited growth of non‐diazotrophic and diazotrophic cyanobacteria
Authors: Wang Jingyu , James Scott C. , Back Jeffery A. , Scott J. Thad
Published: September 2022

Models are widely used tools in aquatic science to understand the mechanism of phytoplankton growth and anticipate the occurrence of harmful algal blooms. However, model parameterization remains challenging and issues that may introduce prediction uncertainty exist. Many models use the Monod equation to predict cyanobacteria growth rate based on ambient nutrient concentrations. The half‐saturation concentrations in the Monod equation varies greatly among different studies and depends on environmental conditions. In this study, we estimated the growth rate due to nutrient limitations for two cyanobacteria species (Microcystis aeruginosa and Dolichospermum flos‐aquae) using a modified Monod model which allows the half‐saturation concentration to vary according to initial nitrogen (N) conditions. The model is calibrated against observations from laboratory experiment where cyanobacteria growth and ambient nutrient concentrations were measured simultaneously, which is rarely done in the literature. Our results show this modified model produce better predictions on growth rate and biomass, indicating many commonly used mechanistic models may need improvement regarding phytoplankton growth representation. Furthermore, our study quantifies the flexibility in cyanobacteria growth parameter across a wide range of environmental N in eutrophic lakes thus provides important information for large‐scale modelling applications.
Finland: Political Developments and Data in 2021
Authors: PALONEN EMILIA
Published: September 2022

In 2021, Finland implemented the long‐planned health, social and rescue services reform under the new regional governance framework. The Covid‐19 vaccinations were issued and the pandemic governance debated as the minister responsible wanted to maintain tighter control. Pandemic fatigue was emerging and measures were lifted in October, only to be restored in December due to the Omicron variant of Covid‐19. A new populist‐splinter party emerged, speeded by contestation of the pandemic measures. As Finland made a large‐scale investment in US‐based fighter jets, NATO collaboration and Russian security concerns were discussed at the end of the year. Women remained strong in Finnish political leadership, and there were also some related changes in ministerial positions. The Finnish municipalities chose their councils for the last time independent of the regional elections. The municipal elections, delayed due to the pandemic to June, indicated the status of party competition at the time.
Do risk exposures explain accounting anomalies? A new testing method
Authors: Peng Zihang
Published: September 2022

I quantitatively evaluate how much of the cross‐sectional return predictive ability of a range of accounting anomalies can be attributed to firm‐specific stock return covariances with market risk factors. Using a novel two‐step regression‐based testing method, I find robust evidence that the risk factor exposures do not explain a meaningful fraction of the time‐series variations in the return predictive coefficients of the anomaly variables. Out‐of‐sample tests further confirm that it is the mispricing component of the accounting anomalies that is mainly responsible for the return predictability.
How does economic policy uncertainty affect the relationship between household debt and consumption?
Authors: Jin Xuejun , Zhou Xue , Yang Xiaolan
Published: September 2022

This paper investigates the effect of economic policy uncertainty on the consumption response to household debt using household‐level data from China. Our results suggest that there is a positive relationship between household debt and consumption. However, a higher level of economic policy uncertainty not only weakens this positive relationship but also inhibits the effect of household debt on the consumption structure. In addition, the negative impacts of policy uncertainty are stronger among households that are more liquidity constrained, whose heads have lower cognitive abilities and financial literacy, and that are located in provinces with lower levels of digital financial inclusion.
Comparison of noninvasive prenatal screening with combined first‐trimester screening as a frontline screening approach for common trisomies in a public hospital in Australia
Authors: Battese Ellis Katie , Sathasivam Nalayin , Bonifacio Michael , Benzie Ronald
Published: September 2022

Background

Combined first‐trimester screening (cFTS) for fetal anomalies involves maternal serum screening for biochemical markers and measurement of the nuchal translucency (NT) by ultrasound. Noninvasive prenatal screening (NIPS) analyses cell‐free DNA present in a maternal blood sample for presence of fetal chromosomal aneuploidies.

Aims

To compare NIPS with cFTS as frontline screening in a public hospital in Australia.

Materials and methods

Women were offered NIPS in addition to the usual cFTS routinely offered to all women at a public hospital in NSW, Australia. The cFTS sample was collected at ten weeks' gestation and the NIPS sample at 12 weeks' gestation at the ultrasound appointment.

Results

In a low‐risk population of 997 women, frontline NIPS had a screen‐positive rate of 0.5% (5/997) vs 4.2% (42/997) with cFTS. cFTS correctly identified one trisomy 21 case and one trisomy 18 case; however, there were two trisomy 18 false negatives. Of five positive NIPS calls, four were correctly identified as trisomy 21 (one) and trisomy 18 (three); there were no NIPS false negatives. Overall, the false‐positive rate with NIPS was 0.1% vs 4.0% by cFTS.

Conclusions

The lower screen‐positive rate with NIPS for common trisomies was a result of the significantly lower false‐positive rate with NIPS. Consequently, NIPS as first‐line screening, even if funded by the hospital, may provide cost savings. We believe NIPS should be used from ten weeks' gestation in conjunction with morphology ultrasound for routine first‐trimester prenatal management.
Comparison of macro‐molluscan assemblages in a protected and a non‐protected tropical seagrass ecosystem
Authors: Paramasivam K. , Venkataraman K.
Published: September 2022

Humans benefit from a variety of ecosystem services provided by seagrass meadows. However, seagrass conservation efforts appear to be insufficient, as evidenced by its low representation in marine protected areas around the world. Protecting seagrasses benefits not just the seagrass itself, but also the macro‐benthic invertebrate assemblages that dwell beside it and contribute indirectly to the various environmental services through their functions. Studies comparing seagrass‐associated invertebrate assemblages and functional trait composition within and outside marine protected areas are uncommon, so the current study compares invertebrate assemblages and functional trait composition from a marine protected area (Gulf of Mannar Marine National Park) and an adjacent non‐marine protected area (Palk Bay) along the southeast coast of India. The species richness (meanS = 83.3) and density (meanD = 6276.6) of seagrass‐associated macro‐molluscs were higher in marine protected areas than in non‐marine protected areas (meanS = 54.6, meanD = 5264.0), but not the species diversity (meanH′ = 2.1 for marine protected areas; meanH′ = 2.0 for non‐marine protected areas). Protected seagrass ecosystems, on the contrary, exhibited much higher species richness within functional groups (i.e., deposit feeders [meanS = 5.5], micro‐/macro‐grazers [21.7], predators [34.8], ectoparasites [2.1], and suspension feeders [19.3]), suggesting that the protection status supports functional redundancy. The study's findings reveal the importance of protection status in enhancing macro‐mollusc assemblages in seagrass ecosystems, which improves the ecosystem's resilience and function.
Pancreatic ductal adenocarcinoma cells regulated the gemcitabine‐resistance function of CAFs by LINC00460
Authors: Zhu Xiao‐Xu , Li Jian‐Hui , Ni Xuhao , Wu Xiao , Hou Xun , Li Ya‐Xiong , Li Shi‐Jin , Zhao Wei , Yin Xiao‐Yu
Published: September 2022

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with extremely poor prognosis. Gemcitabine resistance is a major challenge in the treatment of PDAC. Here, we showed that LINC00460 was associated with the response to gemcitabine both in PDAC patients and PDAC‐PDX. After knocking down LINC00460 in PDAC tumor cells, results of RNA sequencing followed by gene ontology analysis indicated that LINC00460 influenced the activity of growth factors and modified the extracellular matrix. FISH showed that LINC00460 is mostly located in the cytoplasm. Results of RNA pull‐down, LC–MS/MS, RIP, and immunoblotting confirmed that LINC00460 could directly bind to PDAP1. Furthermore, we demonstrated that LINC00460 mediated the cellular communication of PDAC tumor cells and CAFs by PDAP1/PDGFA/PDGFR signaling pathway and regulated the gemcitabine‐resistance function of CAFs, which could be reversed by treatment with a PDGFR inhibitor (crenolanib). PDAC‐PDX tumors with lower expression of LINC00460 showed a better response to gemcitabine plus crenolanib treatment. Our finding supported the application of LINC00460 in precision medicine that uses gemcitabine plus crenolanib to treat PDAC with low expression of LINC00460.
SAR1A regulates the RhoA/YAP and autophagy signaling pathways to influence osteosarcoma invasion and metastasis
Authors: Zhan Fangbiao , Deng Qianrong , Chen Zhiyu , Xie Chaozheng , Xiang Shuang , Qiu Sheng , Tian Lin , Wu Chunrong , Ou Yunsheng , Chen Jian , Xu Lixin
Published: September 2022

Osteosarcoma is the most prevalent form of primary bone malignancy affecting adolescents. Secretion‐associated Ras‐related GTPase 1A (SAR1A) is a key regulator of endoplasmic reticulum (ER) homeostasis, but its role as a regulator of osteosarcoma metastasis has yet to be clarified. Bioinformatics analyses revealed SAR1A and RHOA to be upregulated in osteosarcoma patients, with the upregulation of these genes being associated with poor 5‐year metastasis‐free survival rates. In addition, the upregulation of SAR1A and RHOA in osteosarcoma was highly positively correlated. Immunohistochemical analyses additionally revealed that SAR1A levels were increased in osteosarcoma pulmonary metastases. In vitro wound healing and Transwell assays indicated that knocking down SAR1A or RHOA impaired the invasive and migratory activity of osteosarcoma cells, whereas RHOA overexpression had the opposite effect. Western blotting and immunofluorescent staining revealed the inhibition of osteosarcoma cell epithelial–mesenchymal transition following SAR1A or RHOA knockdown; RHOA overexpression had the opposite effect. Following SAR1A knockdown, phalloidin staining indicated that osteosarcoma cells showed reduced lamellipodia formation. Endoplasmic reticulum stress levels and reactive oxygen species production were enhanced following the knockdown of SAR1A, as was autophagic activity, with lung metastases being reduced in vivo after such knockdown. Knocking down SAR1A suppresses osteosarcoma cell metastasis through the RhoA/YAP, ER stress, and autophagic pathways, offering new insights into the regulation of autophagic activity in the context of osteosarcoma cell metastasis and suggesting that these pathways could be amenable to therapeutic intervention.
Rapid, recurring, structured survey versus bioblitz for generating biodiversity data and analysis with a multispecies abundance model
Authors: Gigliotti Franco N. , Franzem Thomas P. , Ferguson Paige F. B.
Published: September 2022

A bioblitz inexpensively and quickly generates biodiversity data, but bioblitzes are often conducted with haphazard, unreplicated sampling. Results tend to be taxonomically, geographically, or temporally biased, lack metadata, and consist of lists of observed taxa that do not enable further analyses or correction for imperfect detection. A rapid, recurring, structured survey (RRSS) uses a structured sampling design and temporal and spatial replication to survey randomly selected sites on a conservation property. We participated in a loosely structured bioblitz and a subsequent RRSS at Big Canoe Creek Nature Preserve in Springville (St. Clair County), Alabama (USA) to compare observed richness derived from the 2 survey approaches. The RRSS data structure enabled us to fit models that accounted for imperfect detection to estimate abundances, occupancy probabilities, and habitat associations. The loosely structured bioblitz data could not be used in such models. We present a new integrated multispecies abundance model that we applied to avian RRSS data. Our model extension enables estimation for the community, employs data augmentation to estimate the number of undetected species, and incorporates covariates. The RRSS generated a more comprehensive and less biased list of observed taxonomic richness than the loosely structured bioblitz (e.g., 73 vs. 45 bird species and 104 vs. 63 insect families from the RRSS vs. loosely structured bioblitz, respectively). Models fit to the RRSS data identified seasonal patterns in avian community composition and allowed for estimation of habitat–occupancy relationships for insect taxa. The RRSS protocol has potential for broad transferability as a standardized, quick, and inexpensive way to inventory biodiversity and estimate ecological parameters while providing an outreach opportunity.
Prevalence of alcohol consumption in emergency presentations: Novel approach using two biomarkers, ethanol and phosphatidylethanol
Authors: Cameron Cate M. , Vuong Kim , McWhinney Brett , Zournazi Anna , Manzanero Silvia , Warren Jacelle , Mitchell Gary , McCreanor Victoria , Vallmuur Kirsten , Howell Tegwen , Ungerer Jacobus P. J.
Published: September 2022

Introduction

The aim was to determine the prevalence of alcohol‐related presentations to an emergency department (ED) in a major Australian hospital, through a novel surveillance approach using two biomarkers, blood ethanol and phosphatidylethanol (PEth).

Methods

Observational study using secondary testing of blood samples collected during routine clinical care of ED patients presenting to the Royal Brisbane and Women's Hospital in Queensland, Australia, between 22 January and 2 February 2021. Data were collected from 1160 patients during the 10‐day study period. The main outcomes were the prevalence of acute alcohol intake, as determined by blood ethanol, and recent use over 2–4 weeks, as determined by PEth concentrations, for all ED presentations and different diagnostic groups.

Results

The overall prevalence for blood ethanol was 9.3% (95% confidence interval [CI] 7.8%, 11.1%), 5.3% for general medical presentations, increasing four‐fold to 22.2% for injury presentations. The overall prevalence of PEth positive samples was 32.5% (95% CI 29.9%, 35.3%) and 41.4% for injury presentations. There were 263 (25.3%) cases that tested negative for acute blood ethanol but positive for PEth concentrations indicative of significant to heavy medium‐term alcohol consumption.

Discussion and Conclusions

This novel surveillance approach demonstrates that using blood ethanol tests in isolation significantly underestimates the prevalence of medium‐term alcohol consumption in ED presentations. Prevalence of alcohol use was higher for key diagnostic groups such as injury presentations. Performing periodic measurement of both acute and medium‐term alcohol consumption accurately and objectively in ED presentations, would be valuable for informing targeted public health prevention and control strategies.
Standard histological techniques systematically under‐estimate the size fish start spawning
Authors: Prince Jeremy , Harford William J. , Taylor Brett M. , Lindfield Steven J.
Published: September 2022

Beverton & Holt's (1957) functional definition of maturity in fish (L50), as being the size class in which 50% of individuals begin producing gametes in some proportion to body weight, is widely used in assessment models to estimate spawning stock biomass, and manage the minimum size of capture. Standardized histological techniques for estimating L50 apply physiological definitions that identify cellular or hormonal markers indicating individuals are capable of producing gametes. Few studies have examined how those phases of gonadal development correlate with reproductive behaviour or reproductive output. We compare histological estimates of L50 for 10 species of reef fish from Palau, with the size composition of catches, surveys and spawning aggregations, and interpret those comparisons with simulation modelling. Our study shows that the histological L50 estimates coincide with the size species begin ontogenetically shifting between juvenile and adult habitat, and with the size the smallest individuals join spawning aggregations, but are ~15% smaller than the length at which we infer 50% of individuals begin joining spawning aggregations. This highlights a mismatch between the functional definition of L50 assumed for assessment and management, and the physiological definitions developed for histological studies, which identify the beginning of a sub‐adult adolescent phase, rather than the end, when functional adulthood starts. This definitional mismatch could be causing stock assessments to systematically over‐estimate the reproductive output of fisheries. By considering fish behaviour, we hope to better align estimates of physiological maturation with the estimation of functional reproductive potential required for assessment and management.
Identification and characterization of mercaptopyrimidine‐based small molecules as inhibitors of nonhomologous DNA end joining
Authors: Ray Ujjayinee , Gopinatha Vindya K. , Sharma Shivangi , Goyary Laijau , Choudhary Bibha , Mantelingu Kempegowda , Rangappa Kanchugarakoppal S. , Raghavan Sathees C.
Published: September 2022

Mercaptopyrimidine derivatives are heterocyclic compounds with potent biological activities including antiproliferative, antibacterial, and anti‐inflammatory properties. The present study describes the synthesis and characterization of several mercaptopyrimidine derivatives through condensation of 5,6‐diamino‐2‐mercaptopyrimidin‐4‐ol with various heterocyclic and aromatic aldehydes. Previous studies have shown that SCR7, synthesized from 5,6‐diamino‐2‐mercaptopyrimidin‐4‐ol, induced cytotoxicity by targeting cancer cells by primarily inhibiting DNA Ligase IV involved in nonhomologous end joining, one of the major DNA double‐strand break repair pathways. Inhibition of DNA repair pathways is considered as an important strategy for cancer therapy. Due to limitations of SCR7 in terms of IC50 in cancer cells, here we have designed, synthesized, and characterized potent derivatives of SCR7 using 5,6‐diamino‐2‐mercaptopyrimidin‐4‐ol as the starting material. Several synthesized imine compounds exhibited significant improvement in inhibition of end joining and cytotoxicity up to 27‐fold lower concentrations than SCR7. Among these, two compounds, SCR116 and SCR132, showed increased cancer cell death in a Ligase IV‐dependent manner. Treatment with the compounds also led to reduction in V(D)J recombination efficiency, cell cycle arrest at G2/M phase, accumulation of double‐strand breaks inside cells, and improved anti‐cancer potential when combined with γ‐radiation and radiomimetic drugs. Thus, we describe novel inhibitors of NHEJ with higher efficacy and potential, which can be developed as cancer therapeutics.