bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testis-specific serine protease PRSS54 regulates acrosomal granule localization and sperm head morphogenesis in mice
Authors: Shen Chunling , Xiong Wenfeng , Li Chaojie , Ge Haoyang , Shen Yan , Tang Lingyun , Zhang Hongxin , Lu Shunyuan , Fei Jian , Wang Zhugang 
Published: July 2022

Abstract
Serine proteases (PRSS) constitute nearly one-third of all proteases, and many of them have been identified to be testis-specific and play significant roles during sperm development and male reproduction. PRSS54 is one of the testis-specific PRSS in mouse and human but its physiological function remains largely unclear. In the present study, we demonstrate in detail that PRSS54 exists not only in testis but also in mature sperm, exhibiting a change in protein size from 50 kDa in testis to 42 kDa in sperm. Loss of PRSS54 in mice results in male subfertility, acrosome deformation, defective sperm–zona penetration, and phenotypes of male subfertility and acrosome deformation can be rescued by Prss54 transgene. Ultrastructure analyses by transmission electronic microscopy further reveal various morphological abnormalities of Prss54−/− spermatids during spermiogenesis, including unfused vacuoles in acrosome, detachment and eccentrical localization of the acrosomal granules, and asymmetrical elongation of the nucleus. Subcellular localization of PRSS54 display that it appears in the acrosomal granule at the early phase of acrosome biogenesis, then extends along the inner acrosomal membrane, and ultimately presents in the acrosome region of the mature sperm. PRSS54 interacts with acrosomal proteins ZPBP1, ZPBP2, ACRBP, and ZP3R, and loss of PRSS54 affects the distribution of these proteins in testis and sperm, although their protein levels are largely unaffected. Moreover, Prss54−/− sperm are more sensitive to acrosome reaction inducers.
RNA profiling of human dorsal root ganglia reveals sex differences in mechanisms promoting neuropathic pain
Authors: Ray Pradipta R , Shiers Stephanie , Caruso James P , Tavares-Ferreira Diana , Sankaranarayanan Ishwarya , Uhelski Megan L , Li Yan , North Robert Y , Tatsui Claudio , Dussor Gregory , Burton Michael D , Dougherty Patrick M , Price Theodore J 
Published: July 2022

Abstract
Neuropathic pain is a leading cause of high-impact pain, is often disabling and is poorly managed by current therapeutics. Here we focused on a unique group of neuropathic pain patients undergoing thoracic vertebrectomy where the dorsal root ganglia is removed as part of the surgery allowing for molecular characterization and identification of mechanistic drivers of neuropathic pain independently of preclinical models. Our goal was to quantify whole transcriptome RNA abundances using RNA-seq in pain-associated human dorsal root ganglia from these patients, allowing comprehensive identification of molecular changes in these samples by contrasting them with non-pain-associated dorsal root ganglia.
We sequenced 70 human dorsal root ganglia, and among these 50 met inclusion criteria for sufficient neuronal mRNA signal for downstream analysis.
Our expression analysis revealed profound sex differences in differentially expressed genes including increase of IL1B, TNF, CXCL14 and OSM in male and CCL1, CCL21, PENK and TLR3 in female dorsal root ganglia associated with neuropathic pain. Coexpression modules revealed enrichment in members of JUN-FOS signalling in males and centromere protein coding genes in females. Neuro-immune signalling pathways revealed distinct cytokine signalling pathways associated with neuropathic pain in males (OSM, LIF, SOCS1) and females (CCL1, CCL19, CCL21). We validated cellular expression profiles of a subset of these findings using RNAscope in situ hybridization.
Our findings give direct support for sex differences in underlying mechanisms of neuropathic pain in patient populations.
Long-term structural brain changes in adult rats after mild ischaemic stroke
Authors: Syeda Warda , Ermine Charlotte M , Khilf Mohamed Salah , Wright David , Brait Vanessa H , Nithianantharajah Jess , Kolbe Scott , Johnston Leigh A , Thompson Lachlan H , Brodtmann Amy 
Published: July 2022

Abstract
Preclinical studies of remote degeneration have largely focused on brain changes over the first few days or weeks after stroke. Accumulating evidence suggests that neurodegeneration occurs in other brain regions remote to the site of infarction for months and even years following ischaemic stroke. Brain atrophy appears to be driven by both axonal degeneration and widespread brain inflammation. The evolution and duration of these changes are increasingly being described in human studies, using advanced brain imaging techniques. Here, we sought to investigate long-term structural brain changes in a model of mild focal ischaemic stroke following injection of endothlin-1 in adult Long–Evans rats (n = 14) compared with sham animals (n = 10), over a clinically relevant time-frame of 48 weeks. Serial structural and diffusion-weighted MRI data were used to assess dynamic volume and white matter trajectories. We observed dynamic regional brain volume changes over the 48 weeks, reflecting both normal changes with age in sham animals and neurodegeneration in regions connected to the infarct following ischaemia. Ipsilesional cortical volume loss peaked at 24 weeks but was less prominent at 36 and 48 weeks. We found significantly reduced fractional anisotropy in both ipsi- and contralesional motor cortex and cingulum bundle regions of infarcted rats (P &lt; 0.05) from 4 to 36 weeks, suggesting ongoing white matter degeneration in tracts connected to but distant from the stroke. We conclude that there is evidence of significant cortical atrophy and white matter degeneration up to 48 weeks following infarct, consistent with enduring, pervasive stroke-related degeneration.
Protection Against the Omicron Variant Offered by Previous Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Retrospective Cohort Study
Authors: Rothberg Michael B , Kim Priscilla , Shrestha Nabin K , Kojima Lisa , Tereshchenko Larisa G 
Published: July 2022

Abstract

Background
Previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides strong protection against future infection. There is limited evidence on whether such protection extends to the Omicron variant.

Methods
This retrospective cohort study included 635 341 patients tested for SARS-CoV-2 via polymerase chain reaction from 9 March 2020 to 1 March 2022. Patients were analyzed according to the wave in which they were initially infected. The primary outcome was reinfection during the Omicron period (20 December 2021–1 March 2022). We used a multivariable model to assess the effects of prior infection and vaccination on hospitalization.

Results
Among the patients tested during the Omicron wave, 30.6% tested positive. Protection of prior infection against reinfection with Omicron ranged from 18.0% (95% confidence interval [CI], 13.0–22.7) for patients infected in wave 1 to 69.2% (95% CI, 63.4–74.1) for those infected in the Delta wave. In adjusted models, previous infection reduced hospitalization by 28.5% (95% CI, 19.1–36.7), whereas full vaccination plus a booster reduced it by 59.2% (95% CI, 54.8–63.1).

Conclusions
Previous infection offered less protection against Omicron than was observed in past waves. Immunity against future waves will likely depend on the degree of similarity between variants.
Spatio-temporal Influences on Cereal Aphid (Hemiptera: Aphididae) Population Dynamics and the Incidence of Barley Yellow Dwarf Virus
Authors: Van den Eynde Renik , De Keukelaere Laura , Landschoot Sofie , Pycke Bart , Claeys Jonas , Smets Sander , Van Leeuwen Thomas , Haesaert Geert 
Published: July 2022

Abstract
Problems with aphids in small grain cereals, either direct by feeding, or indirect by transmission of Barley Yellow Dwarf Virus, are expected to increase due to climate change and a recent ban on neonicotinoid seed treatments by the European Union. Moreover, insecticide resistance against pyrethroid insecticides is reported at multiple locations throughout the world. Therefore, a better understanding of cereal aphid population dynamics and increased attention towards an integrated pest management is needed. In this study, cereal aphids were monitored on 193 maize and small grain cereal fields throughout Flanders, Belgium. The population dynamics and species distribution were observed throughout the year and the effects of spatio-temporal variables were explored. A significant negative effect was found of grassland in a 1,000 m radius and a positive effect of grain maize in a 3,000 m radius around a small grain cereals field on the maximum infestation rate with aphids in autumn within this field. In a 3,000 m and 5,000 m radius, a significant positive effect of grain maize and a significant negative effect of other small grain cereals was found on the maximum infestation rate during the whole growing season within this field. The mean daily average temperature from 118 to 19 d before sowing had a significant positive effect on the maximum infestation rate in autumn. Mean precipitation, wind speed, and humidity from 52 to 26, 46 to 23, and 107 to 13 d before sowing respectively, had a significant negative effect on the maximum infestation rate in autumn.
Phylogenetic prioritization of HIV-1 transmission clusters with viral lineage-level diversification rates
Authors: Miller Rachel L , McLaughlin Angela , Liang Richard H , Harding John , Wong Jason , Le Anh Q , Brumme Chanson J , Montaner Julio S G , Joy Jeffrey B 
Published: July 2022

Abstract

Background and objectives
Public health officials faced with a large number of transmission clusters require a rapid, scalable and unbiased way to prioritize distribution of limited resources to maximize benefits. We hypothesize that transmission cluster prioritization based on phylogenetically derived lineage-level diversification rates will perform as well as or better than commonly used growth-based prioritization measures, without need for historical data or subjective interpretation.

Methodology
9822 HIV pol sequences collected during routine drug resistance genotyping were used alongside simulated sequence data to infer sets of phylogenetic transmission clusters via patristic distance threshold. Prioritized clusters inferred from empirical data were compared to those prioritized by the current public health protocols. Prioritization of simulated clusters was evaluated based on correlation of a given prioritization measure with future cluster growth, as well as the number of direct downstream transmissions from cluster members.

Results
Empirical data suggest diversification rate-based measures perform comparably to growth-based measures in recreating public heath prioritization choices. However, unbiased simulated data reveals phylogenetic diversification rate-based measures perform better in predicting future cluster growth relative to growth-based measures, particularly long-term growth. Diversification rate-based measures also display advantages over growth-based measures in highlighting groups with greater future transmission events compared to random groups of the same size. Furthermore, diversification rate measures were notably more robust to effects of decreased sampling proportion.

Conclusions and implications
Our findings indicate diversification rate-based measures frequently outperform growth-based measures in predicting future cluster growth and offer several additional advantages beneficial to optimizing the public health prioritization process.
Examination of phase-variable haemoglobin–haptoglobin binding proteins in non-typeable Haemophilus influenzae reveals a diverse distribution of multiple variants
Authors: Phillips Zachary N , Jennison Amy V , Whitby Paul W , Stull Terrence L , Staples Megan , Atack John M 
Published: July 2022

Abstract
Non-typeable Haemophilus influenzae (NTHi) is a major human pathogen for which there is no globally licensed vaccine. NTHi has a strict growth requirement for iron and encodes several systems to scavenge elemental iron and heme from the host. An effective NTHi vaccine would target conserved, essential surface factors, such as those involved in iron acquisition. Haemoglobin–haptoglobin binding proteins (Hgps) are iron-uptake proteins localized on the outer-membrane of NTHi. If the Hgps are to be included as components of a rationally designed subunit vaccine against NTHi, it is important to understand their prevalence and diversity. Following analysis of all available Hgp sequences, we propose a standardized grouping method for Hgps, and demonstrate increased diversity of these proteins than previously determined. This analysis demonstrated that genes encoding variants HgpB and HgpC are present in all strains examined, and almost 40% of strains had a duplicate, nonidentical hgpB gene. Hgps are also phase-variably expressed; the encoding genes contain a CCAA(n) simple DNA sequence repeat tract, resulting in biphasic ON–OFF switching of expression. Examination of the ON–OFF state of hgpB and hgpC genes in a collection of invasive NTHi isolates demonstrated that 58% of isolates had at least one of hgpB or hgpC expressed (ON). Varying expression of a diverse repertoire of hgp genes would provide strains a method of evading an immune response while maintaining the ability to acquire iron via heme. Structural analysis of Hgps also revealed high sequence variability at the sites predicted to be surface exposed, demonstrating a further mechanism to evade the immune system—through varying the surface, immune-exposed regions of the membrane anchored protein. This information will direct and inform the choice of candidates to include in a vaccine against NTHi.
3-indoleacetonitrile attenuates biofilm formation and enhances sensitivity to imipenem in Acinetobacter baumannii
Authors: Kashyap Shruti , Sidhu Harsimran , Sharma Prince , Capalash Neena 
Published: July 2022

ABSTRACT
Acinetobacter baumannii poses a global danger due to its ability to resist most of the currently available antimicrobial agents. Furthermore, the rise of carbapenem-resistant A. baumannii isolates has limited the treatment options available. In the present study, plant auxin 3-indoleacetonitrile (3IAN) was found to inhibit biofilm formation and motility of A. baumannii at sublethal concentration. Mechanistically, 3IAN inhibited the synthesis of the quorum sensing signal 3-OH-C12-HSL by downregulating the expression of the abaI autoinducer synthase gene. 3IAN was found to reduce the minimum inhibitory concentration of A. baumannii ATCC 17978 against imipenem, ofloxacin, ciprofloxacin, tobramycin, and levofloxacin, and significantly decreased persistence against imipenem. Inhibition of efflux pumps by downregulating genes expression may be responsible for enhanced sensitivity and low persistence. 3IAN reduced the resistance to imipenem in carbapenem-resistant A. baumannii isolates by downregulating the expression of OXA β-lactamases (blaoxa-51 and blaoxa-23), outer membrane protein carO, and transporter protein adeB. These findings demonstrate the therapeutic potential of 3IAN, which could be explored as an adjuvant with antibiotics for controlling A. baumannii infections.
The Phylogenetic Position of the Enigmatic, Polypodium hydriforme (Cnidaria, Polypodiozoa): Insights from Mitochondrial Genomes
Authors: Novosolov Maria , Yahalomi Dayana , Chang E Sally , Fiala Ivan , Cartwright Paulyn , Huchon Dorothée 
Published: July 2022

Abstract
Polypodium hydriforme is an enigmatic parasite that belongs to the phylum Cnidaria. Its taxonomic position has been debated: whereas it was previously suggested to be part of Medusozoa, recent phylogenomic analyses based on nuclear genes support the view that P. hydriforme and Myxozoa form a clade called Endocnidozoa. Medusozoans have linear mitochondrial (mt) chromosomes, whereas myxozoans, as most metazoan species, have circular chromosomes. In this work, we determined the structure of the mt genome of P. hydriforme, using Illumina and Oxford Nanopore Technologies reads, and showed that it is circular. This suggests that P. hydriforme is not nested within Medusozoa, as this would entail linearization followed by recirculation. Instead, our results support the view that P. hydriforme is a sister clade to Myxozoa, and mt linearization in the lineage leading to medusozoans occurred after the divergence of Myxozoa + P. hydriforme. Detailed analyses of the assembled P. hydriforme mt genome show that: (1) it is encoded on a single circular chromosome with an estimated size of ∼93,000 base pairs, making it one of the largest metazoan mt genomes; (2) around 78% of the genome encompasses a noncoding region composed of several repeat types; (3) similar to Myxozoa, no mt tRNAs were identified; (4) the codon TGA is a stop codon and does not encode for tryptophan as in other cnidarians; (5) similar to myxozoan mt genomes, it is extremely fast evolving.
The Parkinson’s disease variant rs356182 regulates neuronal differentiation independently from alpha-synuclein
Authors: Prahl Jordan D , Pierce Steven E , van der Schans Edwin J C , Coetzee Gerhard A , Tyson Trevor 
Published: July 2022

AbstractOne of the most significant risk variants for Parkinson’s disease (PD), rs356182, is located at the PD-associated locus near the alpha-synuclein (α-syn) encoding gene, SNCA. SNCA-proximal variants, including rs356182, are thought to function in PD risk through enhancers via allele-specific regulatory effects on SNCA expression. However, this interpretation discounts the complex activity of genetic enhancers and possible non-conical functions of α-syn. Here we investigated a novel risk mechanism for rs356182. We use CRISPR-Cas9 in LUHMES cells, a model for dopaminergic midbrain neurons, to generate precise hemizygous lesions at rs356182. The PD-protective (A/−), PD-risk (G/−) and wild-type (A/G) clones were neuronally differentiated and then compared transcriptionally and morphologically. Among the affected genes was SNCA, whose expression was promoted by the PD-protective allele (A) and repressed in its absence. In addition to SNCA, hundreds of genes were differentially expressed and associated with neurogenesis and axonogenesis—an effect not typically ascribed to α-syn. We also found that the transcription factor FOXO3 specifically binds to the rs356182 A-allele in differentiated LUHMES cells. Finally, we compared the results from the rs356182-edited cells to our previously published knockouts of SNCA and found only minimal overlap between the sets of significant differentially expressed genes. Together, the data implicate a risk mechanism for rs356182 in which the risk-allele (G) is associated with abnormal neuron development, independent of SNCA expression. We speculate that these pathological effects manifest as a diminished population of dopaminergic neurons during development leading to the predisposition for PD later in life.
Taking Dignity Seriously to Protect Manual Scavengers in India: Lessons from the UN Human Rights Committee
Authors: Gupta Aishani 
Published: July 2022

Abstract
This article analyses the Indian caste-based occupation of sanitation work undertaken without protective equipment—manual scavenging. The current legal framework on manual scavenging in India suggests that demolishing dry latrines will abolish manual scavenging. This approach overlooks the coercive nature of the caste system and is therefore an inadequate solution for abolishing manual scavenging. Hence, this article asks ‘how can the legal system provide better legal protections to manual scavengers when the caste system that underpins the practice is deeply entrenched in Indian society?’ The article examines one possible answer—taking dignity more seriously. It demonstrates that manual scavenging is a dignitarian problem by mapping the main dignitarian harms that arise from it, such as humiliation, loss of autonomy and tensions with group dignity. Ultimately, it proposes using dignity in line with the jurisprudence of the UN Human Rights Committee to provide more comprehensive legal protections for manual scavengers.
Testing Mechanisms of Vision: Sea Urchin Spine Density Does Not Correlate with Vision-Related Environmental Characteristics
Authors: Notar Julia C , Meja Bernice , Johnsen Sönke 
Published: July 2022

Synopsis
Sea urchins do not have eyes, yet they are capable of resolving simple images. One suggestion as to the mechanism of this capability is that the spines shade off-axis light from reaching the photosensitive test (skeleton). Following this hypothesis, the density of spines across the body determines the resolution (or sharpness) of vision by restricting the incidence of light on the photosensitive skin of the animal, creating receptive areas of different minimum resolvable angles. Previous studies have shown that predicted resolutions in several species closely match behaviorally determined resolutions, ranging from 10° to 33°. Here, we present a comparative morphological survey of spine density with species representatives from 22 of the 24 families of regular sea urchins (Class Echinoidea) in order to better understand the relative influences of phylogenetic history and three visually relevant environmental variables on this trait. We estimated predicted resolutions by calculating spine densities from photographs of spineless sea urchin tests (skeletons). Analyses showed a strong phylogenetic signal in spine density differences between species. Phylogenetically-corrected Generalized Least Squares models incorporating all habitat parameters were the most supported, and no particular parameter was significantly correlated with spine density. Spine density is subject to multiple, overlapping selective pressures and therefore it is possible that either (1) spine density does not mediate spatial vision in echinoids, or (2) visual resolution via spine density is a downstream consequence of sea urchin morphology rather than a driving force of adaptation in these animals.
Novel Human Parechovirus 3 Diversity, Recombination, and Clinical Impact Across 7 Years: An Australian Story
Authors: Bialasiewicz Seweryn , May Meryta , Tozer Sarah , Day Rebecca , Bernard Anne , Zaugg Julian , Gartrell Kyana , Alexandersen Soren , Chamings Anthony , Wang Claire Y T , Clark Julia , Grimwood Keith , Heney Claire , Schlapbach Luregn J , Ware Robert S , Speers David , Andrews Ross M , Lambert Stephen 
Published: July 2022

Abstract

Background
A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections.

Methods
HPeV3-positive samples collected from hospitalized infants aged 5–252 days in 2 Australian states (2013–2020) and from a community-based birth cohort (2010–2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples.

Results
Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3′ end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (&gt;75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019–2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants.

Conclusions
HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence.