bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Corneal Endothelial Cell Density and Morphology With Optisol-GS and Life4C Storage Media in the Eye Bank: A 5-Year Retrospective Analysis
Authors: Petithomme Rubens , Karmakar Ranit , Lohmeier John , Terrin Staci , Koo Ellen H. , Eghrari Allen O.
Published: December 2023

Purpose:

Optisol-GS and Life4C are corneal storage media used by eye banks worldwide. We sought to determine whether either solution was associated with superior corneal endothelial cell density (ECD) or morphology in a large cohort of donor corneas.

Methods:

From January 2016 to December 2020, 10,316 corneas from 5624 unique donors were acquired and analyzed at Rocky Mountain Lions Eye Bank. In April 2019, Life4C replaced Optisol-GS as the sole storage medium. We compared ECD and morphology before and after April 2019 and excluded corneas processed within the transition period. Univariable and multivariable regression analyses accounted for age, sex, tobacco use, heavy alcohol use, and diabetes. Only right corneas were analyzed to account for the correlation between eyes.

Results:

Of 5042 right corneas analyzed, 3486 were stored in Optisol-GS and 1556 in Life4C. There was no significant difference in ECD across groups (2794 vs. 2793 cells/mm2 in Optisol-GS and Life4C, P = 0.88). In multivariate analyses, there was no significant difference in corneal ECD (0.6 cells/mm2 higher with Life4C, P = 0.96) or hexagonality (0.22% higher with Life4C, P = 0.31). However, the coefficient of variation was significantly lower in the Life4C group (−0.0039, P = 0.03). After adjustment for above factors, corneas in Life4C demonstrated a 3.1% decreased likelihood of exhibiting coefficient of variation (CV) values greater than 0.40 (P = 0.009).

Conclusions:

This study demonstrates comparable and favorable outcomes using both storage media and confirms their overall efficacy. The decreased CV in Life4C is not of clinically significant magnitude but merits further research in clinical and long-term settings.
Herbicide, fumigant, and fungicide use and breast cancer risk among farmers’ wives
Authors: Werder Emily J. , Engel Lawrence S. , Satagopan Jaya , Blair Aaron , Koutros Stella , Lerro Catherine C. , Alavanja Michael C. , Sandler Dale P. , Beane Freeman Laura E.
Published: December 2023

Background:

Evidence from epidemiologic and laboratory studies relating pesticides to breast cancer risk is inconsistent. Women engaging in agricultural work or living in agricultural areas may experience appreciable exposures to a wide range of pesticides, including herbicides, fumigants, and fungicides.

Methods:

We examined exposure to herbicides, fumigants, and fungicides in relation to breast cancer risk among farmers’ wives with no prior history of breast cancer in the Agricultural Health Study. Women provided information on pesticide use, demographics, and reproductive history at enrollment (1993–1997) and at a 5-year follow-up interview. We used Cox proportional hazards regression to estimate associations (hazard ratios [HRs] and 95% confidence intervals [CIs]) between the women’s and their husbands’ self-reported use of individual pesticides and incident breast cancer risk.

Results:

Out of 30,594 women, 38% reported using herbicides, fumigants, or fungicides and 1,081 were diagnosed with breast cancer during a median 15.3 years of follow-up. We found elevated risk in relation to women’s ever use of the fungicide benomyl (HR = 1.6; 95% CI = 0.9, 2.7) and the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) (HR = 1.6; 95% CI = 0.8, 3.1) and to their husbands’ use of the herbicide 2-(2,4,5-trichlorophenoxy) propionic acid (2,4,5-TP) (HR = 1.5; 95% CI = 0.9, 2.7). We observed few other chemical associations and little evidence of differential risk by tumor estrogen receptor status or linear exposure-response relationships.

Conclusion:

We did not observe clear excesses between use of specific pesticides and breast cancer risk across exposure metrics, although we did observe elevated risk associated with women’s use of benomyl and 2,4,5-T and husbands’ use of 2,4,5-TP.
Waitlist and posttransplant outcomes of pregnancy-related acute liver failure in the United States
Authors: Jalil Sajid , Elfeki Mohamed A. , Kiefer Miranda K. , Kuo Yong-Fang , Singal Ashwani K.
Published: December 2023

Data on the liver transplant (LT) outcomes of women with acute liver failure (ALF) due to liver diseases unique to pregnancy (P-ALF) are limited. Using United Network of Organ Sharing (UNOS) data (1987–2021), we analyzed waitlist and post-LT outcomes of ALF in women of childbearing age comparing P-ALF versus ALF due to liver diseases not unique to pregnancy. Baseline characteristics were compared between groups at the time of listing for LT. Of 3542 females aged 16–43 years and listed for LT for ALF, 84 (2%) listed for P-ALF were less likely to be Black (11 vs. 21%, p=0.033), have lower international normalized ratio (2.74 vs. 4.53 p<0.002), but more likely to have respiratory failure (56% vs. 41%, p<0.005), be on pressors (58% vs. 43%, p<0.005), and require dialysis (23% vs. 10%, p<0.001). The cumulative 90-day waitlist mortality (WLM) was lower in P-ALF vs. ALF due to liver diseases not unique to pregnancy (7.4 vs. 16.6%, p<0.001). Posttransplant survival rates at 5 years were similar (82% vs. 79%, p=0.89). In a Fine and Gray regression model controlled for listing year and Model for End-Stage Liver Disease score, 90-day WLM was lower in P-ALF with a sub-HR of 0.42 (95% CI: 0.19–0.94, p=0.035). Of 84 women with P-ALF and listed for LT, 45 listed for hemolysis-elevated liver enzymes-low platelets (HELLP) versus 39 for acute fatty liver of pregnancy had higher 90-day WLM (19.3% vs. 5.7% p<0.005). The 90-day WLM was about 10-fold higher in HELLP versus acute fatty liver of pregnancy with a sub-HR of 9.97 (95% CI: 1.64–60.55, p=0.013). In this UNOS database analysis of ALF among women of childbearing age, the waitlist outcome is better in women with P-ALF compared to women with ALF due to liver diseases not unique to pregnancy. Among women with P-ALF, the 90-day WLM is worse for HELLP versus acute fatty liver of pregnancy. Further studies are needed to improve the management of HELLP and prevent the development of ALF in this subgroup population.
Novel FDA-approved zavegepant drug for treating migraine
Authors: Ahmed Usaid , Saleem Muhammad Meeran , Osman Mohamed Ashraf , Shamat Shamat Fathi
Published: December 2023

Migraine is a complex neurological disorder characterized by recurring episodes of severe headaches. The pathophysiology of migraine involves abnormalities in neuronal networks, cortical spreading depression, and sensitization of trigeminovascular pathways. The global prevalence of migraine has increased substantially, warranting advancements in treatment strategies. A significant trigger in migraine pathophysiology is calcitonin gene-related peptide (CGRP). Several drugs, such as gepants and monoclonal antibodies (MABs) targeting CGRP or its receptor, have been developed to antagonize CGRP signaling. Zavegepant (Zavzpret), a novel CGRP receptor antagonist, has recently been approved by the FDA for the acute treatment of migraine. Clinical trials have demonstrated its efficacy in providing headache and symptom relief, with a statistically significant percentage of patients achieving freedom from headaches and most bothersome symptoms. Despite mild adverse effects, such as taste disorders and nausea, Zavzpret’s overall safety profile remains acceptable.
18F-FDG and 18F-AIF-NOTA-Octreotide PET/CT Confirmed a Rare Case of Cutaneous Merkel Cell Carcinoma With a Solitary Local Nodal Metastasis
Authors: Mi Yanxia , Jia Yuan , Du Dongni , Du Yong , Zhao Ming
Published: December 2023

Cutaneous Merkel cell carcinoma with local nodal metastasis is a rare entity. A 56-year-old man presented with a nontender left inguinal mass, and ultrasound-guided biopsy of this nodal mass confirmed nodal metastasis with strong neuroendocrine differentiation from cutaneous Merkel cell carcinoma. Staging 18F-FDG PET/CT showed a solitary 3.9 × 6.8-cm hypermetabolic left groin mass with no other suspicious lesions elsewhere. To confirm the patient’s eligibility for radical curative treatment, taking into consideration of its neuroendocrine differentiation, a subsequent 18F-AIF-NOTA-octreotide PET/CT was performed, which demonstrated only solitary somatostatin receptor–positive left inguinal mass. The patient underwent radical treatment.
Pseudomonas aphyarum sp. nov., Pseudomonas fontis sp. nov., Pseudomonas idahonensis sp. nov. and Pseudomonas rubra sp. nov., isolated from in, and around, a rainbow trout farm
Authors: Testerman Todd , Varga Jackie , Schiffer Molly M. , Donohue Hailey , Vieira Da Silva Caroline , Graf Joerg
Published: December 2023

During a large-scale bacterial culturing effort of biofilms in the vicinity of a rainbow trout aquaculture facility in Idaho, USA, 10 isolates were identified as having pathogen-inhibiting activity and were characterized further. These isolates were shown to be Gram-negative, rod-shaped bacteria belonging to the genus

Pseudomonas

. Whole-genome comparisons and multi-locus sequence analysis using four housekeeping genes (16S rRNA, gyrA, rpoB and rpoD) showed that these 10 isolates clustered into four distinct species groups. These comparisons also indicated that these isolates were below the established species cutoffs for the genus

Pseudomonas

. Further phenotypic characterization using API 20NE, API ZYM and Biolog GENIII assays and chemotaxonomic analysis of cellular fatty acids were carried out. Based on the genomic, physiological and chemotaxonomic properties of these isolates, we concluded that these strains composed four novel species of the genus

Pseudomonas

. The proposed names are as follows: Pseudomonas aphyarum sp. nov. consisting of strains ID233, ID386T and ID387 with ID386T (=DSM 114641T=ATCC TSD-305T) as the type strain; Pseudomonas rubra sp. nov. consisting of strains ID291T, ID609 and ID1025 with ID291T (=DSM 114640T=ATCC TSD-303T) as the type strain; Pseudomonas idahonensis sp. nov. consisting of strains ID357T and ID1048 with ID357T (=DSM 114609T=ATCC TSD-304T) as the type strain; and Pseudomonas fontis sp. nov. consisting of strains ID656T and ID681 with ID656T (=DSM 114610T=ATCC TSD-306T) as the type strain.
Antiquaquibacter oligotrophicus gen. nov., sp. nov., a novel oligotrophic bacterium from groundwater
Authors: Toumi Marwene , Whitman William B. , Kyrpides Nikos C. , Woyke Tanja , Wolf Jacqueline , Neumann-Schaal Meina , Abbaszade Gorkhmaz , Károly Bóka , Tóth Erika
Published: December 2023

In this study, a Gram-stain-positive, non-motile, oxidase- and catalase-negative, rod-shaped, bacterial strain (SG_E_30_P1T) that formed light yellow colonies was isolated from a groundwater sample of Sztaravoda spring, Hungary. Based on 16S rRNA phylogenetic and phylogenomic analyses, the strain was found to form a distinct linage within the family

Microbacteriaceae

. Its closest relatives in terms of near full-length 16S rRNA gene sequences are

Salinibacterium hongtaonis

MH299814 (97.72 % sequence similarity) and

Leifsonia psychrotolerans

GQ406810 (97.57 %). The novel strain grows optimally at 20–28 °C, at neutral pH and in the presence of NaCl (1–2 w/v%). Strain SG_E_30_P1T contains MK-7 and B-type peptidoglycan with diaminobutyrate as the diagnostic amino acid. The major cellular fatty acids are anteiso-C15 : 0, iso-C16 : 0 and iso-C14 : 0, and the polar lipid profile is composed of diphosphatidylglycerol and phosphatidylglycerol, as well as an unidentified aminoglycolipid, aminophospholipid and some unidentified phospholipids. The assembled draft genome is a contig with a total length of 2 897 968 bp and a DNA G+C content of 65.5 mol%. Amino acid identity values with it closest relatives with sequenced genomes of <62.54 %, as well as other genome distance results, indicate that this bacterium represents a novel genus within the family

Microbacteriaceae

. We suggest that SG_E_30_P1T (=DSM 111415T=NCAIM B.02656T) represents the type strain of a novel genus and species for which the name Antiquaquibacter oligotrophicus gen. nov., sp. nov. is proposed.
Trustworthiness of Systematic Review Automation An interview at Coventry University
Authors: Jiang Xiaorui
Published: December 2023

To reduce both time and labour for systematic review, much effort has been made on developing automated tools using artificial intelligence and machine learning in nearly two decades. Unfortunately, systematic review automation tools still face a serious problem of social acceptance. Previous studies identified lack of trust as one important adoption barrier for systematic review automation. However, further discussion about building trust was limited to building trusted evidence base by benchmarked large-scale evaluation. This study extended the previous discussions of the trustworthiness of systematic review automation. Through semi-structure interviews with regular systematic reviewers, we tried to not only get answers for to what extent human reviewers trust automated tools and why, but also reveal more measures of building trust from human reviewers’ points of view and the impact of such measures on the trust in and adoption of systematic review automation tools. We believe that the results of this study may also shed light on some new directions of systematic review automation research.
Selected humanization of yeast U1 snRNP leads to global suppression of pre-mRNA splicing and mitochondrial dysfunction in the budding yeast
Authors: Chalivendra Subbaiah , Shi Shasha , Li Xueni , Kuang Zhiling , Giovinazzo Joseph , Zhang Lingdi , Rossi John , Saviola Anthony J. , Wang Jingxin , Welty Robb , Liu Shiheng , Vaeth Katherine , Zhou Z. Hong , Hansen Kirk C. , Taliaferro J. Matthew , Zhao Rui
Published: December 2023

The recognition of 5’ splice site (5’ ss) is one of the earliest steps of pre-mRNA splicing. To better understand the mechanism and regulation of 5’ ss recognition, we selectively humanized components of the yeast U1 snRNP to reveal the function of these components in 5’ ss recognition and splicing. We targeted U1C and Luc7, two proteins that interact with and stabilize the yeast U1 (yU1) snRNA and the 5’ ss RNA duplex. We replaced the Zinc-Finger (ZnF) domain of yU1C with its human counterpart, which resulted in cold-sensitive growth phenotype and moderate splicing defects. Next, we added an auxin-inducible degron to yLuc7 protein and found that Luc7-depleted yU1 snRNP resulted in the concomitant loss of PRP40 and Snu71 (two other essential yeast U1 snRNP proteins), and further biochemical analyses suggest a model of how these three proteins interact with each other in the U1 snRNP. The loss of these proteins resulted in a significant growth retardation accompanied by a global suppression of pre-mRNA splicing. The splicing suppression led to mitochondrial dysfunction as revealed by a release of Fe2+into the growth medium and an induction of mitochondrial reactive oxygen species. Together, these observations indicate that the human U1C ZnF can substitute that of yeast, Luc7 is essential for the incorporation of the Luc7-Prp40-Snu71 trimer into yeast U1 snRNP, and splicing plays a major role in the regulation of mitochondria function in yeast.
A Blood Immunological Signature of Subclinical Coronary Artery Atherosclerosis in People Living with HIV-1 Receiving Antiretroviral Therapy
Authors: Wiche Salinas Tomas Raul , Zhang Yuwei , Gosselin Annie , Do Rosario Natalia Fonseca , El-Far Mohamed , Filali-Mouhim Ali , Routy Jean-Pierre , Chartrand-Lefebvre Carl , Landay Alan L. , Durand Madeleine , Tremblay Cécile L. , Ancuta Petronela ,   the Canadian HIV and Aging Cohort Study (CHACS)
Published: December 2023

Cardiovascular disease (CVD) remains an important co-morbidity in people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Our previous studies performed on the Canadian HIV/Aging Cohort Study (CHACS) (>40 years-old; Framingham Risk Score (FRS) >5%), revealed a 2-3-fold increase in non-calcified coronary artery atherosclerosis (CAA) plaque burden, measured by Computed tomography angiography scan (CTAScan) as total (TPV) and low attenuated plaque volume (LAPV) in ART-treated PLWH (HIV+)versusuninfected controls (HIV-). In an effort to identify novel correlates of subclinical CAA, markers of intestinal damage (sCD14, LBP, FABP2); cell trafficking/inflammation (CCL20, CX3CL1, MIF, CCL25); subsets of Th17-polarized and regulatory (Tregs) CD4+T-cells, classical/intermediate/non-classical monocytes, and myeloid/plasmacytoid dendritic cells, were studied in relationship with HIV and TPV/LAPV status. The TPV detection/values coincided with higher plasma sCD14, FABP2, CCL20, MIF, CX3CL1 and triglyceride levels, lower Th17/Treg ratios, and classical monocyte expansion. Among HIV+, TPV+versusTPV−exhibited lower Th17 frequencies, reduced Th17/Treg ratios, higher frequencies of non-classical CCR9lowHLADRhighmonocyte, and increased plasma fibrinogen levels. Finally, Th17/Treg ratios and non-classical CCR9lowHLADRhighmonocyte frequencies remained associated with TPV/LAPV after adjusting for FRS and HIV/ART duration in a logistic regression model. These findings point to Th17 paucity and non-classical monocyte abundance as novel immunological correlates of subclinical CAA that may fuel the CVD risk in ART-treated PLWH.
Pseudoreplication and inappropriate statistical tests in the analysis of preference index data from the T-maze group assay forDrosophila behaviour
Authors: Winklhofer Michael
Published: December 2023

The binary choice chamber (T-maze) assay has been used as a standard behavioural screen in Drosophila research to test mutants in terms of sensory discrimination skills and synaptic plasticity during memory consolidation and decay. Typically, ca. 100 individuals are tested as a group at the same time and the behavioural readout consists in counting the number of individuals in the testing tube exposed to a stimulus versus the number of flies in the control tube, with the normalized difference in fly count being defined as the batch preference index (PI). Unfortunately, the batch PI has widely been taken as a precise metric of group behaviour, to the point where ANOVA/t-tests have been considered the most powerful statistical tests for analyzing samples in terms of batch PI values, which has led to a hyperinflation of apparently very highly significant effects for small differences in PI values (e.g. -0.1 vs 0.1), leading to problems with replicability. Here it is shown on the basis of a well-established statistical model for binary decisions that application of the t-test to PI data implicitly assumes that each fly in a batch is an independent biological replicate in the extremely strict sense that the decision of each individual was interrogated independently of the other flies. Therefore, t-test analysis of PI data obtained with the intrinsically pseudoreplicative group assay is the cause of extremely optimistic P-values, as suggested recently by Bassetto et al. (2023) on the basis of effect size considerations for proportions. Thus, rather than using inferential statistics, PI data should be assessed on the basis of effect size. A more fundamental problem with the batch PI value is the uncertainty in whether it measures the mean individual preference and if so, with what precision, given the simple readout? This aspect is illustrated here by modelling distributions of flies in the T-maze, which suggest that the effective precision of the PI value is clearly worse than the nominal precision of +/- 0.01 for 100 flies, so that the batch PI can only serve as a rough indicator of group tendencies.
Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice
Authors: Poudel Sher Bahadur , Ruff Ryan R , Yildirim Gozde , Miller Richard A , Harrison David E , Strong Randy , Kirsch Thorsten , Yakar Shoshana
Published: December 2023

This study investigated the prevalence and progression of primary osteoarthritis (OA) in aged UM-HET3 mice. Using the Osteoarthritis Research Society International (OARSI) scoring system, we assessed articular cartilage (AC) integrity in 182 knee joints of 22-25 months old mice.

Aged UM-HET3 mice showed a high prevalence of primary OA in both sexes. Significant positive correlations were found between cumulative AC (cAC) scores and synovitis in both sexes, and osteophyte formation in female mice. Ectopic chondrogenesis did not show significant correlations with cAC scores. Significant direct correlations were found between AC scores and inflammatory markers in chondrocytes, including matrix metalloproteinase-13 (MMP-13), inducible nitric oxide synthase (iNOS), and the NLR family pyrin domain containing-3 (NLRP3) inflammasome in both sexes, indicating a link between OA severity and inflammation. Additionally, markers of cell cycle arrest, such as p16 and β-galactosidase, also correlated with AC scores. Using micro-CT, we examined the correlations between subchondral bone (SCB) morphology traits and AC scores. In male mice, no significant correlations were found between SCB morphology traits and cAC scores, while in female mice, significant correlations were found between cAC scores and tibial SCB plate bone mineral density.

Finally, we explored the effects of methylene blue (MB) and mitoquinone (MitoQ), two agents that affect mitochondrial function, on the prevalence and progression of OA during aging. Notably, MB and MitoQ treatments influenced the disease’s progression in a sex-specific manner. MB treatment significantly reduced cAC scores at the medial knee joint, while MitoQ treatment reduced cAC scores, but these did not reach significance.

In conclusion, our study provides comprehensive insights into the prevalence and progression of primary OA in aged UM-HET3 mice, highlighting the sex-specific effects of MB and MitoQ treatments. The correlations between AC scores and various pathological factors underscore the multifaceted nature of OA and its association with inflammation and subchondral bone changes.
Motor mirror neurons may not be a predictor of learning but reflect the effect of motor learning
Authors: Ekaterina Pomelova , Matteo Feurra , Alena Popyvanova , Vadim Nikulin , Roman Solodkov , Tamara Banjevich , Evgeny Blagovechtchenski
Published: December 2023

The mirror neurons system (MNS) fires during both the performance of an action and observation of the same action being performed by another. On the level of motor output, activation of the MNS is thought to be represented in the phenomenon of motor resonance, which manifests in a muscle-specific increase in corticospinal excitability during action observation. This study focused on how and to what extent sensorimotor learning alters the initial mirror response and whether the rate of sensorimotor learning is associated with pretraining or post-training levels of mirror response. The study involved 23 healthy adults aged 22.7 years. The experiment consisted of six sessions. On the first and last days, a transcranial magnetic stimulation session was held to assess the putative activity of mirror neurons, as reflected in the level of motor-evoked potential facilitation during action observation in different conditions. From the second to the fifth sessions (four sessions in total), the sensorimotor learning part was performed, as represented in the form of a serial reaction time (SRT) task. We observed a statistically significant decrease of reaction time in the process of learning in the SRT task and motor facilitation during action observation, thus reflecting the process of putative mirror neurons’ activity. However, our data demonstrate that the sensorimotor learning rate was not associated with either pretraining or post-training estimates of motor facilitation during action observation and that sensorimotor learning does not affect the pattern of motor resonance.
Imaging the master regulator of the antioxidant response in non-small cell lung cancer with positron emission tomography
Authors: Greenwood Hannah E. , Edwards Richard S. , Tyrrell Will E. , Barber Abigail R. , Baark Friedrich , Tanc Muhammet , Khalil Eman , Falzone Aimee , Ward Nathan P. , DeBlasi Janine M. , Torrente Laura , Pearce David R. , Firth George , Smith Lydia M. , Timmermand Oskar Vilhelmsson , Huebner Ariana , George Madeleine E. , Swanton Charles , Hynds Robert E. , DeNicola Gina M. , Witney Timothy H.
Published: December 2023

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. The cystine/glutamate antiporter, system xc−, is one of the >200 cytoprotective proteins controlled by NRF2, which can be non-invasively imaged by (S)-4-(3-18F-fluoropropyl)-ʟ-glutamate ([18F]FSPG) positron emission tomography (PET). Through genetic and pharmacologic manipulation, we show that [18F]FSPG provides a sensitive and specific marker of NRF2 activation in advanced preclinical models of NSCLC. We validate imaging readouts with metabolomic measurements of system xc−activity and their coupling to intracellular glutathione concentration. A redox gene signature was measured in patients from the TRACERx 421 cohort, suggesting an opportunity for patient stratification prior to imaging. Furthermore, we reveal that system xc−is a metabolic vulnerability that can be therapeutically targeted for sustained tumour growth suppression in aggressive NSCLC. Our results establish [18F]FSPG as predictive marker of therapy resistance in NSCLC and provide the basis for the clinical evaluation of both imaging and therapeutic agents that target this important antioxidant pathway.
Assessing Immune Factors in Maternal Milk and Paired Infant Plasma Antibody Binding to Human Rhinoviruses
Authors: Vera Jessica M. , McIlwain Sean J. , Fye Samantha , Palmenberg Ann , Bochkov Yury , Li Hanying , Pinapati Richard , Tan John , Gern James E. , Seroogy Christine , Ong Irene M.
Published: December 2023

Before they can produce their own antibodies, newborns are protected from infections by transplacental transfer of maternal IgG antibodies and after birth through breast milk IgA antibodies. Rhinovirus (RV) infections are extremely common in early childhood, and while RV infections often result in only mild upper respiratory illnesses, they can also cause severe lower respiratory illnesses such as bronchiolitis and pneumonia. We used high-density peptide arrays to profile infant and maternal antibody reactivity to capsid and full proteome sequences of three human RVs - A16, B52, and C11. Numerous plasma IgG and breast milk IgA RV epitopes were identified that localized to regions of the RV capsid surface and interior, and also to several non-structural proteins. While most epitopes were bound by both IgG and IgA, there were several instances where isotype-specific and RV-specific binding were observed. We also profiled 62 unique RV-C dominant protein loop sequences characteristic of this species’ capsid VP1 protein. Many of these RV-C sites were highly bound by IgG from one-year-old infants, indicating recent or ongoing active infections, or alternatively, a level of cross-reactivity among homologous RV-C sites.
Aerosol deposition increases conductance to water in immobilized stomata closed with abscisic acid or opened with fusicoccin
Authors: Grantz David A. , Chi Chia-JuEllen , Burkhardt Juergen
Published: December 2023

Hypothesized effects of aerosol deposition on plant water balance have been difficult to establish. This is due to variability between species, stomatal response to the treatment itself, and to environmental effects. Here we attempt a quantitative evaluation with a defined aerosol application, a paired leaf experimental design, and immobilized stomata.

Attached leaves of poplar were treated with ammonium nitrate aerosol. After 17 or 20 days for deliquescence to develop an aqueous film, leaves were excised and stomata held closed with abscisic acid or open with fusicoccin. Transpiration and stomatal conductance were measured in a greenhouse with a porometer and leaf health was assessed by fluorescence.

Median stomatal conductance was increased significantly, by 60 and 65%, following aerosol loading of 31.3 μg cm-2in ABA- and FC-treated leaves, respectively.

Aerosol induced transpiration, probably associated with a liquid film that lines the stomatal pore and not effectively regulated by stomatal closure, may be significant in magnitude. As aerosol deposition is ubiquitous, and its chemical nature may be changing, this factor should be considered in models of transpiration from leaf to canopy scale.
Estradiol regulates local synthesis of synaptic proteome via sex-specific mechanisms
Authors: Raval Pooja , Rae Hannah , Duarte Rodrigo R. R. , Watson Iain A. , Sellers Katherine J. , Pachon Kathryn M. C. , Sichlinger Laura , Powell Timothy R. , Yasvoina Marina V. , Mukherjee Jayanta , Moss Stephen J. , Brandon Nicholas J. , Srivastava Deepak P.
Published: December 2023

Estrogens, specifically 17β-estradiol (estradiol), can modulate synaptic function by regulating the expression and localisation of synaptic proteins. However, the mechanisms underlying estradiol’s regulation of synaptic protein expression, and whether if they occur in a sex specific manner, is not well understood. In this study, using sex-specific hippocampal slice cultures and mixed-sex primary hippocampal neurons, we investigated whether local protein synthesis is required for estradiol- induced synaptic protein expression. Estradiol rapidly increased the rate of protein synthesis and the number of actively translating ribosomes along dendrites and near synapses in both male and female hippocampal neurons. Importantly, these effects occurred independently of gene transcription. Moreover, estradiol also increased the abundance of nascent proteins localised to synapses, independently of gene transcription. Specifically, estradiol increased the synaptic expression of GluN2B- containingN-methyl-D-aspartate receptors and PSD-95 in male and female hippocampus. Mechanistically, mTOR signalling was required for estradiol-induced increases in overall local protein synthesis only in male but not female hippocampus. Consistent with this, mTOR signalling mediated estradiol increases in GluN2B in male, but not female, hippocampus. Conversely, mTOR inhibition, blocked estradiol-induced increased PSD-95 expression in both male and female hippocampus. Collectively, these data suggest that the rapid modulation of local protein synthesis by estradiol is required for changes in the synaptic proteome in male and female hippocampus, and that the requirement of the mTOR signalling pathway in these effects occur in both a sex-specific and protein-dependent manner, with this signalling pathway have a greater role in male compared to female hippocampus.
Identifying patterns to uncover the importance of biological pathways on known drug repurposing scenarios
Authors: Otero-Carrasco Belén , Ugarte Carro Esther , Prieto Santamaría Lucía , Diaz Uzquiano Marina , Caraça-Valente Hernández Juan Pedro , Rodríguez-González Alejandro
Published: December 2023

Background

Drug repurposing plays a significant role in bringing effective treatments for certain diseases faster and more cost-effectively. Successful repurposing cases are mostly supported by a classical paradigm that stems from de novo drug development. This paradigm is based on the “one-drug-one-target-one-disease” idea. It consists of designing drugs specifically for a single disease and its drug’s gene target. In this article, we investigated the use of biological pathways as potential elements to achieve effective drug repurposing.

Methods

Considering a total of 4.214 successful cases of drug repurposing, we identified cases in which biological pathways serve as the underlying basis for successful repurposing, referred to as DREBIOP. Once the repurposing cases based on pathways were identified, we studied the inherent patterns within them by considering the different biological elements associated with this dataset, as well as the pathways involved in these cases. Furthermore, we obtained gene-disease association values to demonstrate the diminished significance of the drug’s gene target in these repurposing cases. To achieve this, we compared the values obtained for the DREBIOP set with the overall association values found in DISNET, as well as with the drug’s target gene (DREGE) based repurposing cases using the Mann-Whitney U Test.

Results

A collection of drug repurposing cases, known as DREBIOP, was identified as a result. DREBIOP cases exhibit distinct characteristics when compared to DREGE cases. Notably, DREBIOP cases are associated with a higher number of biological pathways, with Vitamin D Metabolism and ACE inhibitor being the most prominent pathways involved. Additionally, it was observed that the association values of GDAs in DREBIOP cases are significantly lower than those in DREGE cases (p-value < 0.05).

Conclusions

Biological pathways assume a pivotal role in drug repurposing cases. This investigation successfully revealed patterns that distinguish drug repurposing instances associated with biological pathways. These identified patterns can be applied to any known repurposing case, enabling the detection of pathway-based repurposing scenarios or the classical paradigm.
An ovine model for investigation of the microenvironment of the male mammary gland
Authors: Davies Benjamin P. , Crew Rachael C. , Cochrane Anna L. K. , Davies Katie , Baptista Andre Figueiredo , Jeckel Sonja , McCrone Ian , Niu Youguo , Strugnell Benjamin W. , Waine Katie , Fowden Abigail L. , Bryant Clare E. , Wills John W. , Giussani Dino A. , Hughes Katherine
Published: December 2023

The specific biology of the male breast remains relatively unexplored in spite of the increasing global prevalence of male breast cancer. Delineation of the microenvironment of the male breast is restricted by the low availability of human samples and a lack of characterisation of appropriate animal models. Unlike the mouse, the male ovine gland persists postnatally. We suggest that the male ovine mammary gland constitutes a promising adjunctive model for the male human breast. In this study we evaluate the male ovine mammary gland microenvironment, comparing intact and neutered males. Assessment of the glandular histo-anatomy highlights the resemblance of the male gland to that of the neonatal female sheep and confirms the presence of rudimentary terminal duct lobular units. Irrespective of neutered status, cell proliferation in epithelial and stromal compartments is low in males, and cell proliferation in epithelial cells and in the intralobular stroma is significantly lower than in pubertal female sheep. Between 42% and 72% of the luminal mammary epithelial cells in the male gland express the androgen receptor, and expression is significantly reduced by neutering. Luminal epithelial cells within the intact and neutered male gland also express oestrogen receptor alpha, but minimal progesterone receptor expression is observed. The distrubution of mammary leukocytes within the ducts and stroma is similar in the female mammary gland of sheep and other species. Both macrophages and T lymphocytes are intercalated in the epithelial bilayer and are more abundant in the intralobular stroma than the interlobular stroma, suggesting that they may have a protective immunological function within the vestigial glandular tissue of the male sheep. Mast cells are also observed within the stroma. These cells cluster nearer the glandular tissue and are frequently located adjacent to blood vessels. The abundance of mast cells is significantly higher in intact males compared to neutered males, suggesting that hormone signalling may impact mast cell recruitment. In this study, we demonstrate the utility of the male ovine mammary gland as a model for furthering our knowledge of postnatal male mammary biology.
Active membrane deformations of a minimal synthetic cell
Authors: Sciortino Alfredo , Faizi Hammad A. , Uplap Sarvesh , Frechette Layne , Peterson Matthew S. E. , Vlahovska Petia , Baskaran Aparna , Hagan Michael F. , Bausch Andreas R.
Published: December 2023

Biological cells exhibit the remarkable ability to adapt their shape in response to their environment, a phenomenon that hinges on the intricate interplay between their deformable membrane and the underlying activity of their cytoskeleton. Yet, the precise physical mechanisms of this coupling remain mostly elusive. Here, we introduce a synthetic cell model, comprised of an active cytoskeletal network of microtubules, crosslinkers and molecular motors encapsulated inside giant vesicles. Remarkably, these active vesicles exhibit large shape fluctuations and life-like morphing abilities. Active forces from the encapsulated cytoskeleton give rise to large-scale traveling membrane deformations. Quantitative analysis of membrane and microtubule fluctuations shows how the intricate coupling of confinement, membrane material properties and cytoskeletal forces yields fluctuation spectra whose characteristic scales in space and time are distinctly different from passive vesicles. We demonstrate how activity leads to uneven probability fluxes between fluctuation modes and hence sets the temporal scale of membrane fluctuations. Using simulations and theoretical modelling, we extend the classical approach to membrane fluctuations to active cytoskeleton-driven vesicles, highlighting the effect of correlated activity on the dynamics of membrane deformations and paving the way for quantitative descriptions of the shape-morphing ability typical of living systems.
Performance of localization prediction algorithms decreases rapidly with the evolutionary distance to the training set increasing
Authors: Gould Sven B. , Magiera Jonas , García Carolina García , Raval Parth K.
Published: December 2023

Mitochondria and plastids import thousands of proteins. Their experimental localisation remains a frequent task, but can be resource-intensive and sometimes impossible. Hence, hundreds of studies make use of algorithms that predict a localisation based on a protein’s sequence. Their reliability across evolutionary diverse species is unknown. Here, we evaluate the performance of common algorithms (TargetP, Localizer and WoLFPSORT) for four photosynthetic eukaryotes for which experimental plastid and mitochondrial proteome data is available, and 171 eukaryotes using orthology inferences. The match between predictions and experimental data ranges from 75% to as low as 2%. Results worsen as the evolutionary distance between training and query species increases, especially for plant mitochondria for which performance borders on random sampling. Specificity, sensitivity and precision analyses highlight cross-organelle errors and uncover the evolutionary divergence of organelles as the main driver of current performance issues. The results encourage to train the next generation of neural networks on an evolutionary more diverse set of organelle proteins for optimizing performance and reliability.
Cold metal transfer welding of 316L/430 dissimilar stainless-steel welds
Authors: Tembhurkar Chetan , Ambade Sachin , Kataria Ravinder , Verma Jagesvar , Moon Abhijeet
Published: December 2023

Purpose

This paper aims to examine dissimilar joints for various applications in chemical, petrochemical, oil, gas, shipbuilding, defense, rail and nuclear industry.

Design/methodology/approach

This study examined the effects of cold metal transfer welding on stainless steel welds for 316L austenitic and 430 ferritic dissimilar welds with ER316L, ER309L and without (autogenous) fillers. The microstructural observation was done with an optical microscope. The mechanical test was done to reveal the strength, hardness and toughness of the joint. The electrochemical polarization tests were done to reveal intergranular and pitting corrosion in the dissimilar joints.

Findings

This microstructural study shows the presence of austenitic and ferritic phases with vermicular ferrite for ER309L filler weld, and for ER316L filler weld specimen shows predominately martensitic phase in the weld region, whereas the autogenous weld shows lathy ferrite mixed with martensitic phase. Mechanical test results indicated that filler welded specimen (ER316L and ER309L) has relatively higher strength and hardness than the autogenous weld, whereas ER316L filler weld exhibited the highest impact toughness than ER309L filler weld and lowest in autogenous weld. The electrochemical corrosion results displayed the highest degree of sensitization (DOS) in without filler welded specimen (45.62%) and lower in case of filler welded specimen ER309L (4.95%) and least in case of ER316L filler welded specimen (3.51%). The high DOS in non-filler welded specimen is correlated with the chromium carbide formation. The non-filler welded specimen shows the highest pitting corrosion attack as compared to the ER316L filler weld specimen and relatively better in ER309L filler welded specimen. The highest pitting corrosion resistance is related with the high chromium content in ER309L composition.

Originality/value

This experimental study is original and conducted with 316L and 430 stainless steel with ER316L, ER309 and without fillers, which will help the oil, shipbuilding and chemical industries.
Assembling fire: beyond engineering solutions
Authors: Vaiciulyte Sandra , Underhill Helen , Reddy Elizabeth
Published: December 2023

Purpose

Fires have the potential to destroy, resulting in the loss of property and livelihoods, as well as injury, death and repeated trauma for those who are already vulnerable. However, fire as a hazard has been treated rigidly and un-critically, a model that has influenced how it is perceived by policy makers, first responders, engineers and academics and subsequently approaches to implementing and better understanding fire prevention, mitigation, response and recovery from the impacts of fire.

Design/methodology/approach

This article deals with fire, arguing that its case can help imagine what liberation might mean within and for disaster studies. The study argues against dogmatic, outdated, technological and solution-focused perspectives that have constrained how fire and its effects are understood and discuss what disciplinary liberation could mean for the study of fire and its integration within DRR. The study’s approach is based on the DRR Assemblage Theory, which points to fire as an issue at a societal level.

Findings

The study explores the themes of fire and liberation through contributions and insights that have emerged through the authors' professional experience in research and practice. It offers an original and timely engagement with disaster studies through the lens of fire, an increasingly pertinent phenomenon for disaster scholars and practitioners alike.

Originality/value

By drawing on the example of fire as a socio-technical-environmental phenomenon, this paper contributes a novel perspective on the intellectual and practical possibilities that can emerge from disciplinary liberation.
Employee education level and efficiency of corporate investment
Authors: Jin Yige , Li Xing , Tian Gaoliang , Shi Jing , Wang Yunyi
Published: December 2023

Purpose

In this study, the authors explore the association between employee education level and the efficiency of corporate investment using data from a sample of Chinese listed firms during the period from 2011 to 2018. By examining the impact of education on investment efficiency, the authors' study provides valuable insights that contribute to a deeper understanding of the underlying economic mechanisms related to education.

Design/methodology/approach

The authors conduct multivariate regression analyses to examine the relationship between investment efficiency (following Richardson, 2006) and the level of employee education, along with a series of control variables. To ensure the reliability of the authors' findings, the authors subject the their results to a comprehensive set of robustness tests, such as a staggered difference-in-difference (DiD) regression approach, an instrumental variable (IV) method and the use of alternative employee education level and investment efficiency measurements.

Findings

The findings offer compelling evidence that higher levels of education have a positive impact on firms' investment efficiency, and this effect remains robust across various model specifications and endogeneity considerations. Moreover, the influence of education is more pronounced in firms that prioritize employee training, maintain effective internal communication and offer attractive financial rewards. Furthermore, the results suggest that the relationship between education and investment efficiency is influenced by the firms' business nature and competitive environment. Factors such as business complexity, labor intensity and business location also play a role in shaping the impact of education on investment outcomes.

Originality/value

The study emphasizes the crucial role of education in influencing investment decisions and performance within firms. By delving into this previously unexplored area, the authors' research contributes to the existing literature, establishing that the level of employee education is a significant determinant of corporate investment efficiency. This valuable insight has substantial implications for firms aiming to enhance their investment decision-making processes and overall performance. Understanding the positive impact of education on investment efficiency can empower organizations to leverage their human capital effectively and achieve better investment outcomes, ultimately contributing to long-term success and competitiveness in the market.
Deeper professional learning: how leaders design for teachers to share their deeper learning practices
Authors: Kallio Julie
Published: December 2023

Purpose

A core challenge for leaders for deeper learning is scaling promising practices to provide students with systematic access to deeper learning experiences. This case illuminates how a group of researchers organized professional learning activities around conferring, a promising deeper learning practice.

Design/methodology/approach

The author examines how the leaders of a Networked Improvement Community (NIC) created the conditions for teachers to share their deeper learning practices through a case study. The case study centers on one school team’s learning through their participation in the NIC activities, as evidenced by the artifacts they created and their exchanges with their team, participants from other schools and researchers.

Findings

The trajectory of one team through three NIC activities – a video club, a pitch and user testing – shows how they examined their own conferring practice, got ideas for change and shifted their thinking and practice toward a more student-centered approach. Insights from the case suggest three design principles – a common problem of practice, shared representations of practice and intentional network configurations – for deeper professional learning, or learning experiences that engage educators in purposeful and collaborative inquiry into deeper learning practices.

Research limitations/implications

Two limitations of the case are a lack of data on the perceived experience of participants, which could speak to the depth of Irving’s shift toward student-centered conferring, and the narrow time scope of the NIC, which limits exploration of the sustainability of the changes to conferring.

Practical implications

The design principles represent important features for researchers and leaders to consider in ongoing efforts to scale deeper learning. Leaders might use the principles to examine existing or future professional learning efforts.

Originality/value

This case study extends an understanding of one facet of leadership for deeper learning: fostering professional community. Future research is needed to examine the educator experience of participating in deeper professional learning and its sustained impact on practices.