bluuebunny/crossref_metadata_2025 huggingface dataset:
Adding context to the pneumococcal core genes using bioinformatic analysis of the intergenic pangenome of Streptococcus pneumoniae
Authors: Nielsen Flemming Damgaard , Møller-Jensen Jakob , Jørgensen Mikkel Girke
Published: February 2023

Introduction: Whole genome sequencing offers great opportunities for linking genotypes to phenotypes aiding in our understanding of human disease and bacterial pathogenicity. However, these analyses often overlook non-coding intergenic regions (IGRs). By disregarding the IGRs, crucial information is lost, as genes have little biological function without expression.

Methods/Results: In this study, we present the first complete pangenome of the important human pathogen Streptococcus pneumoniae (pneumococcus), spanning both the genes and IGRs. We show that the pneumococcus species retains a small core genome of IGRs that are present across all isolates. Gene expression is highly dependent on these core IGRs, and often several copies of these core IGRs are found across each genome. Core genes and core IGRs show a clear linkage as 81% of core genes are associated with core IGRs. Additionally, we identify a single IGR within the core genome that is always occupied by one of two highly distinct sequences, scattered across the phylogenetic tree.

Discussion: Their distribution indicates that this IGR is transferred between isolates through horizontal regulatory transfer independent of the flanking genes and that each type likely serves different regulatory roles depending on their genetic context.
Biomechanical evaluation of a novel intervertebral disc repair technique for large box-shaped ruptures
Authors: Nie Mao-Dan , Huang Ze-Bin , Zhang Ning-Ze , Fu Ling-Jie , Cheng Cheng-Kung
Published: February 2023

Objective: The purpose of this study was to analyze the feasibility of repairing a ruptured intervertebral disc using a patch secured to the inner surface of the annulus fibrosus (AF). Different material properties and geometries for the patch were evaluated.

Methods: Using finite element analysis, this study created a large box-shaped rupture in the posterior-lateral region of the AF and then repaired it with a circular and square inner patch. The elastic modulus of the patches ranged from 1 to 50 MPa to determine the effect on the nucleus pulposus (NP) pressure, vertical displacement, disc bulge, AF stress, segmental range of motion (ROM), patch stress, and suture stress. The results were compared against the intact spine to determine the most suitable shape and properties for the repair patch.

Results: The intervertebral height and ROM of the repaired lumbar spine was similar to the intact spine and was independent of the patch material properties and geometry. The patches with a modulus of 2–3 MPa resulted in an NP pressure and AF stresses closest to the healthy disc, and produced minimal contact pressure on the cleft surfaces and minimal stress on the suture and patch of all models. Circular patches caused lower NP pressure, AF stress and patch stress than the square patch, but also caused greater stress on the suture.

Conclusion: A circular patch with an elastic modulus of 2–3 MPa secured to the inner region of the ruptured annulus fibrosus was able to immediately close the rupture and maintain an NP pressure and AF stress similar to the intact intervertebral disc. This patch had the lowest risk of complications and produced the greatest restorative effect of all patches simulated in this study.
The Usher syndrome 1C protein harmonin regulates canonical Wnt signaling
Authors: Schäfer Jessica , Wenck Nicole , Janik Katharina , Linnert Joshua , Stingl Katarina , Kohl Susanne , Nagel-Wolfrum Kerstin , Wolfrum Uwe
Published: February 2023

Human Usher syndrome (USH) is the most common form of hereditary combined deaf-blindness. USH is a complex genetic disorder, and the pathomechanisms underlying the disease are far from being understood, especially in the eye and retina. The USH1C gene encodes the scaffold protein harmonin which organizes protein networks due to binary interactions with other proteins, such as all USH proteins. Interestingly, only the retina and inner ear show a disease-related phenotype, although USH1C/harmonin is almost ubiquitously expressed in the human body and upregulated in colorectal cancer. We show that harmonin binds to β-catenin, the key effector of the canonical Wnt (cWnt) signaling pathway. We also demonstrate the interaction of the scaffold protein USH1C/harmonin with the stabilized acetylated β-catenin, especially in nuclei. In HEK293T cells, overexpression of USH1C/harmonin significantly reduced cWnt signaling, but a USH1C-R31* mutated form did not. Concordantly, we observed an increase in cWnt signaling in dermal fibroblasts derived from an USH1CR31*/R80Pfs*69 patient compared with healthy donor cells. RNAseq analysis reveals that both the expression of genes related to the cWnt signaling pathway and cWnt target genes were significantly altered in USH1C patient-derived fibroblasts compared to healthy donor cells. Finally, we show that the altered cWnt signaling was reverted in USH1C patient fibroblast cells by the application of Ataluren, a small molecule suitable to induce translational read-through of nonsense mutations, hereby restoring some USH1C expression. Our results demonstrate a cWnt signaling phenotype in USH establishing USH1C/harmonin as a suppressor of the cWnt/β-catenin pathway.
May the force be with you: The role of hyper-mechanostability of the bone sialoprotein binding protein during early stages of Staphylococci infections
Authors: Gomes Priscila S. F. C. , Forrester Meredith , Pace Margaret , Gomes Diego E. B. , Bernardi Rafael C.
Published: February 2023

The bone sialoprotein-binding protein (Bbp) is a mechanoactive MSCRAMM protein expressed on the surface of Staphylococcus aureus that mediates adherence of the bacterium to fibrinogen-α (Fgα), a component of the bone and dentine extracellular matrix of the host cell. Mechanoactive proteins like Bbp have key roles in several physiological and pathological processes. Particularly, the Bbp: Fgα interaction is important in the formation of biofilms, an important virulence factor of pathogenic bacteria. Here, we investigated the mechanostability of the Bbp: Fgα complex using in silico single-molecule force spectroscopy (SMFS), in an approach that combines results from all-atom and coarse-grained steered molecular dynamics (SMD) simulations. Our results show that Bbp is the most mechanostable MSCRAMM investigated thus far, reaching rupture forces beyond the 2 nN range in typical experimental SMFS pulling rates. Our results show that high force-loads, which are common during initial stages of bacterial infection, stabilize the interconnection between the protein’s amino acids, making the protein more “rigid”. Our data offer new insights that are crucial on the development of novel anti-adhesion strategies.
Incidence and predictors of HBV functional cure in patients with HIV/HBV coinfection: A retrospective cohort study
Authors: Zhang Qingrong , Wang Hu , Jin Yi , Zhou Na , Sun Lijun , Wu Hao , Chen Haitao , Jiang Taiyi
Published: February 2023

Background

This study was the first to examine the association of baseline clinical factors with the rate of HBsAg clearance in a large retrospective cohort of Chinese patients with HIV/HBV coinfection treated with combination antiretroviral therapy (ART).

Methods

Our retrospective cohort included 431 patients with HIV/HBV coinfection treated with TDF-containing ART. The median follow-up was 6.26 years. Logistic regression was used to investigate the association of baseline variables with HBsAg clearance, and Cox regression was used to investigate the association of baseline variables with time to HBsAg clearance.

Results

The clearance rate of HBsAg in our study was 0.072 (95% CI 0.049~0.101). In the multivariate logistic regression, advanced age (OR=1.1, P=0.007), high CD4 cell count (OR=2.06, P=0.05), and HBeAg positivity (OR=8.00, P=0.009) were significantly associated with the rate of HBsAg clearance. The AUC of the model integrating the above three predictors was 0.811. Similar results were found in the multivariate Cox regression (HR = 1.09, P = 0.038 for age, HR = 1.05, P = 0.012 for CD4 count and HR = 7.00, P = 0.007 for HBeAg).

Conclusions

Long-term TDF-containing ART can lead to HBsAg clearance of 7.2% in Chinese patients with HIV/HBV coinfection. Advanced age, high CD4 cell count, and positive HBeAg at baseline could be regarded as potential predictors and biological markers for HBsAg clearance in patients with HIV/HBV coinfection.
Andrographolide suppresses hypoxia-induced embryonic hyaloid vascular system development through HIF-1a/VEGFR2 signaling pathway
Authors: Jin Zhong , Guo Qiru , Wang Zheng , Wu Xiao , Hu Wangming , Li Jiali , Li Hongfei , Zhu Song , Zhang Haidi , Chen Zixian , Xu Huan , Shi Liangqin , Yang Lan , Wang Yong
Published: February 2023

Introduction

Ocular abnormalities and the development of retinal vasculature may cause postnatal retinopathy. In the past decade, tremendous progress has been made in identifying the mechanisms that regulate retina vasculature. However, the means of regulating embryonic hyaloid vasculature development is largely unknown. This study aims to determine whether and how andrographolide regulates embryonic hyaloid vasculature development.

Methods

Murine embryonic retinas were used in this study. Whole mount isolectin B4 (IB4) staining, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and immunofluorescence staining (IF) were performed to determine whether andrographolide is critical for embryonic hyaloid vasculature development. BrdU incorporation assay, Boyden chamber migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay were performed to evaluate whether andrographolide regulates the proliferation and migration of vascular endothelial cells. Molecular docking simulation and Co-immunoprecipitation assay were used to observe protein interaction.

Results

Hypoxia conditions exist in murine embryonic retinas. Hypoxia induces HIF-1a expression; high-expressed HIF-1a interacts with VEGFR2, resulting in the activation of the VEGF signaling pathway. Andrographolide suppresses hypoxia-induced HIF-1a expression and, at least in part, interrupts the interaction between HIF-1a and VEGFR2, causing inhibiting endothelial proliferation and migration, eventually inhibiting embryonic hyaloid vasculature development.

Conclusion

Our data demonstrated that andrographolide plays a critical role in regulating embryonic hyaloid vasculature development.
Lithospheric thinning beneath the Tengchong volcanic field, Southern China: Insight from Cenozoic calc-alkaline basalts
Authors: Chen Kefei , Liu Shaolin , Yang Dinghui , Xu Xiwei , Wu Yadong , Yang Shuang , Yang Shuxin , Zhang Haodong
Published: February 2023

The Tengchong Cenozoic volcanic field lies in SE margin of the Tibetan Plateau. The basalts of the Tengchong field exhibit evident spatial-temporal variations, but consensus on their meaning has not been reached yet. In this study, we collected basalts from western, central and eastern areas in the Tengchong volcanic field and measured the whole-rock and olivine major and trace elements of basalts. Tengchong basalts exhibit remarkable chemical and isotopic diversity, showing a strong correlation with eruption locations and ages. Specifically, basalts in the western and eastern areas (formed at 7.2–2.8 Ma) are characterized by high 87Sr/86Sr and low 3He/4He ratios, while those in the central area (formed at 0.6–0.02 Ma) feature low 87Sr/86Sr and high 3He/4He ratios. Based on the temperature- and pressure-dependent elemental partition coefficients, this phenomenon is interpreted as mainly caused by the difference in lithospheric thickness among these areas. On the one hand, the estimated primary magmas in the eastern and western areas show higher SiO2, Na2O, (La/Sm)N, Hf/Lu and Ba/Zr ratios than those in the central area. On the other hand, the Ni contents in olivine phenocrysts are higher in the western and eastern areas than in the central area. As different amounts of extension result in different degrees of decompression of the asthenosphere, finally influencing the compositional variation of magmas, these results indicate that the lithosphere in the eastern and western areas is thicker than that in the central area. In addition, basalts erupted in the eastern and western areas are older than those in the central area, suggesting lithospheric thinning. We propose that lithospheric extension due to slab rollback may have caused lithospheric thinning. In addition, according to the different deformation modes of the crust and lithospheric mantle, our study supports mantle-crust decoupling south of ∼26°N in SE margin of the Tibetan Plateau.
Multiphase dolomitization mechanisms of the Cambrian upper Changping Formation, North China Platform, China
Authors: Bai Ying , Zhao Zhenyu , Zhao Zhe , Gao Jianrong
Published: February 2023

The Cambrian dolomite reservoirs of the North China Platform offer good exploration prospects, but their occurrence and the impacts of dolomitization on reservoir quality are not yet clearly understood. The study herein assesses outcrop samples in the Cambrian upper Changping Formation, Dingjiatan area, and highlights the important role of multiphase dolomitization in the formation of paleo-reservoirs of acceptable porosity, where oil pools and fields may be discovered. A combination of petrology, fluid inclusion microthermometry, isotopes, and trace element compositions has been used to explain multiphase dolomitization mechanisms and their impacts on dolomite reservoirs. Five types of dolomites are identified through outcrop observation, thin section identification via transmitted light, and cathodoluminescence. The following geochemical analyses reveal various dolomitization mechanisms. In the (pene) contemporaneous stage, microbial dolomite is commonly related to microbial metabolic activities with significant carbon isotopic depletion compared to the Cambrian seawater values. With the influence of microbial dolomitization, dolomicrite corresponds to the sabkha dolomitization mode in a low-salinity seawater environment and early-stage dolomitization. The structureless dolomite (ssD) in the early highstand systems tract (EHST), characterized by elevated 87Sr/88Sr ratios and low oxygen isotopic values, forms from stratum brine water in the shallow-middle burial stage rather than in the (pene) contemporaneous stage. In contrast, ssD in the late highstand systems tract (LHST) undergoes (pene) contemporaneous dolomitization at salinities between 6% and 28% before later pore water transformation, with the participation of atmospheric freshwater through faults and unconformities exhibiting the lowest inclusion temperature and salinity values. The medium to coarse crystalline dolomite (MCD) in the LHST and the saddle dolomite (SD) in the EHST with low REE values are atypical hydrothermal dolomites caused by a combined superposition of middle-deep burial hydrothermal fluids at temperatures >150°C and stratigraphic brines. The MCD is also influenced by terrigenous water characterized by relatively low Eu anomaly values. Finally, the mechanisms of porosity increase are investigated, and it is concluded that the pore increase caused by the (pene) contemporaneous reflux interaction and the later pore retention both lead to better ssD reservoirs in the LHST than in the EHST.
Shed female caribou antlers extend records of calving activity on the Arctic National Wildlife Refuge by millennia
Authors: Miller Joshua H. , Wald Eric J. , Druckenmiller Patrick
Published: February 2023

Caribou (Rangifer tarandus) have among the longest annual migrations of any terrestrial mammal as they move from winter ranges to spring calving grounds. Biomonitoring records indicate broad consistencies in calving geography across the last several decades, but how long have herds used particular calving grounds? Furthermore, how representative are modern patterns of calving geography to periods that pre-date recent climatic perturbations and increased anthropogenic stresses? While modern ecological datasets are not long enough to address these questions, bones from past generations of caribou lying on the tundra provide unique opportunities to study historical calving geography. This is possible because female caribou shed their antlers within days of giving birth, releasing a skeletal indicator of calving. Today, the Coastal Plain of the Arctic National Wildlife Refuge (Alaska) is a key calving ground for the Porcupine Caribou Herd (PCH). To test the duration across which caribou have used this area as a calving ground, we radiocarbon dated three highly weathered female antlers collected from tundra surfaces on the Coastal Plain. Calibrated radiocarbon dates indicate that these antlers were shed between ~1,600 and more than 3,000 calendar years ago. The antiquity of these shed antlers provides the first physical evidence of calving activity on the PCH calving grounds from previous millennia, substantiating the long ecological legacy of the Coastal Plain as a caribou calving ground. Comparisons to published lake core records also reveal that dates of two of the antlers correspond to periods with average summer temperatures that were warmer than has been typical during the last several decades of biomonitoring. This finding expands the range of climatic settings in which caribou are known to use the current PCH calving grounds and suggests that the Coastal Plain of the Arctic Refuge may remain an important caribou calving ground during at least portions of predicted future warming. Discarded skeletal materials provide opportunities to assess the historical states of living populations, including aspects of reproductive biology and migration. Particularly in high-latitude settings, these insights can extend across millennia and offer rare glimpses into the past that can inform current and future management policies.
Role of lncRNAs in the pathogenic mechanism of human decreased ovarian reserve
Authors: Lv Zhexi , Lv Zekai , Song Linjiang , Zhang Qinxiu , Zhu Shaomi
Published: February 2023

Decreased ovarian reserve (DOR) is defined as a decrease in the quality and quantity of oocytes, which reduces ovarian endocrine function and female fertility. The impaired follicular development and accelerated follicle atresia lead to a decrease in the number of follicles, while the decline of oocyte quality is related to the disorder of DNA damage-repair, oxidative stress, and the dysfunction of mitochondria. Although the mechanism of DOR is still unclear, recent studies have found that long non-coding RNA (lncRNA) as a group of functional RNA molecules participate in the regulation of ovarian function, especially in the differentiation, proliferation and apoptosis of granulosa cells in the ovary. LncRNAs participate in the occurrence of DOR by affecting follicular development and atresia, the synthesis and secretion of ovarian hormones. This review summarizes current research on lncRNAs associated with DOR and reveals the potential underlying mechanisms. The present study suggests that lncRNAs could be considered as prognostic markers and treatment targets for DOR.
Relationship between single nucleotide polymorphism of NOS2 gene and inheritance of allergic rhinitis in children
Authors: Wu Xionghui , Zhao Sijun , Huang Weiqing , Huang Min , Xie Jiang , Liu Guangliang , Chang Shuting
Published: February 2023

Allergic rhinitis is a common chronic disease, and its high incidence has a great negative impact on the quality of life of many people, especially children. In this paper, through in-depth analysis of NOS2 gene polymorphism, the protective mechanism of NOS2 gene against AR was studied to provide theoretical and scientific basis for the diagnosis of children with AR. It was concluded that the concentration of Immunoglobulin E (IgE) in rs2297516 was 0.24 IU/mL compared with that in normal children. rs3794766 specific IgE concentration in the children group was increased by 0.36 IU/mL, which was higher than that in the healthy children group; the difference of rs7406657 specific IgE concentration between the children group and the healthy group was 0.03 IU/mL. The total serum IgE concentration in the healthy children group was lower than that in the infant group, and the change of Rs3794766 was the least, followed by rs2297516 and rs7406657. This means that rs7406657 is the highest, rs2297516 had general genetic correlation with AR patients, and rs3794766 had the least genetic correlation with AR patients. Among the three groups of SNP loci, the healthy children group was higher than the patient children group, indicating that AR reduces the gene frequency of the three loci, and the reduction of gene frequency will also increase the susceptibility of children to AR, because the frequency of gene occurrence will affect the gene sequence. In conclusion, smart medicine and gene SNPS can promote the detection and treatment of AR.
Immunoproteomics and phage display in the context of leishmaniasis complexity
Authors: Ludolf Fernanda , Ramos Fernanda F. , Coelho Eduardo A. F.
Published: February 2023

Leishmaniasis is defined as a complex of diseases caused by protozoan parasites of the genus Leishmania, which comprises 20 parasite species pathogenic to mammalians, such as humans and dogs. From a clinical point of view, and considering the diversity and biological complexity of the parasites, vectors, and vertebrate hosts, leishmaniasis is classified according to the distinct clinical manifestations, such as tegumentary (involving the cutaneous, mucosal, and cutaneous-diffuse forms) and visceral leishmaniasis. Many issues and challenges remain unaddressed, which could be attributed to the complexity and diversity of the disease. The current demand for the identification of new Leishmania antigenic targets for the development of multicomponent-based vaccines, as well as for the production of specific diagnostic tests, is evident. In recent years, biotechnological tools have allowed the identification of several Leishmania biomarkers that might potentially be used for diagnosis and have an application in vaccine development. In this Mini Review, we discuss the different aspects of this complex disease that have been addressed by technologies such as immunoproteomics and phage display. It is extremely important to be aware of the potential applications of antigens selected in different screening context, so that they can be used appropriately, so understanding their performance, characteristics, and self-limitations.
SHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis
Authors: Zhang Linlin , Bang Sangsu , He Qianru , Matsuda Megumi , Luo Xin , Jiang Yong-Hui , Ji Ru-Rong
Published: February 2023

Excessive inflammation has been implicated in autism spectrum disorder (ASD), but the underlying mechanisms have not been fully studied. SHANK3 is a synaptic scaffolding protein and mutations of SHANK3 are involved in ASD. Shank3 expression in dorsal root ganglion sensory neurons also regulates heat pain and touch. However, the role of Shank3 in the vagus system remains unknown. We induced systemic inflammation by lipopolysaccharide (LPS) and measured body temperature and serum IL-6 levels in mice. We found that homozygous and heterozygous Shank3 deficiency, but not Shank2 and Trpv1 deficiency, aggravates hypothermia, systemic inflammation (serum IL-6 levels), and sepsis mortality in mice, induced by lipopolysaccharide (LPS). Furthermore, these deficits can be recapitulated by specific deletion of Shank3 in Nav1.8-expressing sensory neurons in conditional knockout (CKO) mice or by selective knockdown of Shank3 or Trpm2 in vagal sensory neurons in nodose ganglion (NG). Mice with Shank3 deficiency have normal basal core temperature but fail to adjust body temperature after perturbations with lower or higher body temperatures or auricular vagus nerve stimulation. In situ hybridization with RNAscope revealed that Shank3 is broadly expressed by vagal sensory neurons and this expression was largely lost in Shank3 cKO mice. Mechanistically, Shank3 regulates the expression of Trpm2 in NG, as Trpm2 but not Trpv1 mRNA levels in NG were significantly reduced in Shank3 KO mice. Our findings demonstrated a novel molecular mechanism by which Shank3 in vagal sensory neurons regulates body temperature, inflammation, and sepsis. We also provided new insights into inflammation dysregulation in ASD.
Effects of ethanol storage and lipid extraction on stable isotope compositions of twelve pelagic predators
Authors: Shen Yongfu , David Mboglen , Gong Yi , Wu Feng , Li Yunkai
Published: February 2023

Stable isotope analysis (SIA) has proven to be a powerful tool in reconstructing diets and characterizing trophic relationships for pelagic predators. Ethanol has been a common preservative solution for biopsy samples from remote areas and archived collections. It is still under debate whether the effects of ethanol (ET) would bias the trophic interpretation of the stable isotope values. Further, lipid extraction (LE) is becoming more popular as a general treatment for standardization prior to SIA, particularly for investigating intra and interspecific variation of sympatric species, because lipids have lower δ13C values. In this study, the long-term (up to 448 days) effects of treatment ET and combined treatments ET and LE (ET+LE) on stable carbon and nitrogen isotope values (δ13C and δ15N, respectively) of twelve pelagic predators from the open ocean were evaluated. Results showed that compared with control values, δ15N values displayed a positive change (δ15Nmean offset was 0.71 ± 0.56‰) but δ13C values had variable results (δ13Cmean offset was 0.42 ± 0.64‰) among all species following treatment with ET during the first 28 days and then remained stable throughout the experiment. Compared with treatment LE results, no difference was observed in δ13C, δ15N values, and C/N ratios through time following treatment ET+LE. These results indicated that treatment ET may have species-specific effects on stable isotope values, and the shifts from treatment LE could counter the changes caused by treatment ET. In addition, after 28 days of preservation, the values following treatment ET were similar to those following treatment LE in low C/N species (C/N<3.5), which suggested ethanol may also affect some of lipid contents from muscle tissues. Nevertheless, further research is needed to focus on the mechanisms that control changes in stable isotope composition in tissues stored in ethanol. Given the effects on pelagic predators, muscle tissue samples stored in ethanol from the open ocean or a museum after LE treatment could be used to develop SIA.
Diarrhetic shellfish toxins production appears to be driven by photosynthesis and phosphate–revealed by different light-adapted strains of Prorocentrum lima complex and P. caipirignum
Authors: Chen Heng , Huang Kaixuan , Guan Wanchun , Zhang Hua , Liu Shasha , Lu Songhui
Published: February 2023

Introduction

Diarrhetic shellfish toxins (DST) harm shellfish aquaculture and endanger human health, and include well-known marine dinoflagellate-produced toxins such as okadaic acid (OA) and analogues, such as dinophysistoxin-1 (DTX-1). Toxin-producing species have different toxin profiles and contents, with unclear interactions, with the toxins hypothesized to be produced under stress conditions.

Methods

Five morphotypes of Prorocentrum lima complex, a well-studied DST-producing species with remarkable phylogenetic variability, were chosen and exposed to three distinct light conditions (photosynthetic active radiation, PAR; PAR+UVA; PAR+UVA and UVB) for 18 or 24 days.

Results and discussion

The studied morphotypes were classified as either light-sensitive (LS) or light-tolerant (LT) types based on their light responses and varying abilities to produce DTX-1 across three orders of magnitude (0.001-1 pg cell-1 d-1, abbreviated as LL, ML, and HL in order of rank). All toxin production rates (Rtox) initially increased and then decreased, with the first peaks varying between days 3 to 12. The results of earlier peaks in LL and ML and a linear correlation between Rtox values for OA and DTX-1 in HL indicated that the two compounds may be competitive. When light conditions initially altered, Rtox was either stagnant or negative under all light treatments in the LS cohort, and with UV addition in LT, which subsequently delayed the early peaks. The Rtox data for DTX-1 all demonstrated earlier and higher peaks with UVA addition in LL and ML. Likewise, their growth was facilitated following the addition of UVA light. Therefore, Rtox of pre-peaks is relevant to photosynthetic status and photoprotection ability. As decreasing Rtox data points corresponded closely with phosphate depletion, the phosphate consumption rate was calculated and shown to be linearly or exponentially associated with all downward Rtox. This study proposes a supply-demand link between photosynthetic products and phosphate with DST biosynthesis, inferring a likely competitive interaction between OA and DTX-1 production.
Optimal tropical cyclone size parameter for determining storm-induced maximum significant wave height
Authors: Oh Youjung , Oh Sang Myeong , Chang Pil-Hun , Moon Il-Ju
Published: February 2023

The maximum significant wave height (Hsmax) induced by a tropical cyclone (TC) can be estimated from an empirical fetch formula using the TC’s size, maximum wind speed, and translation speed, in which larger, stronger, and faster-moving TCs generally have higher the Hsmax. In the formula, the radius of maximum wind (RMW) has been widely used as the TC size parameter under the assumption that Hsmax is mainly generated by strong winds near the RMW. This study investigates whether RMW is the optimal parameter for determining TC-induced Hsmax through extensive wave model simulations for North Atlantic hurricanes from 1988–2017. The correlation analysis between the estimated Hsmax and TC size parameters revealed that the radius of the 34-kt wind speed (R34, r = 0.84–0.95) was much higher than the widely used RMW (r = 0.33–0.58), which suggests that R34 is a more important TC size parameter for determining TC-induced Hsmax than RMW. This result can be explained by the fact that R34 showed a significantly higher correlation (r = 0.96) than RMW (r = 0.31) with cumulative TC wind speeds, which are closely related to Hsmax. These findings also indicate that the TC-induced Hsmax is more affected by the region containing moderately strong winds outside the TC than by the region of maximum wind speed near the RMW. Our paper provides additional insight into the mechanisms by which extreme wave heights, which cause severe damage during TC passage, occur.
X-Ray Diffraction Contrast Tomography for Probing Hydrogen Embrittlement in Heat-Treated Lean Duplex Stainless Steel
Authors: Eguchi Kenichiro , Burnett Timothy L. , Engelberg Dirk L.
Published: February 2023

Laboratory-based diffraction contrast tomography (DCT) was applied to heat-treated lean duplex stainless steel (DSS) to observe microstructural changes by hydrogen infusion treatment. The feasibility of the DCT technique for the in situ assessment of a dual-phase material with exposure to aqueous solution was investigated, with DCT observations carried out before and after cathodic hydrogen charging. The movement of diffraction spots was observed after charging for 7 days, which cannot be explained by sample lateral movements. An experimental method to apply the DCT techniques for investigating the hydrogen–microstructure interaction is introduced here, but a more accurate experimental methodology is required to verify that the movement of diffraction spot derives from lattice parameter changes.
Simple acoustic metagrating for perfect two- and three-beam splitting
Authors: Song Ailing , Sun Chaoyu , Xiang Yanxun , Xuan Fu-Zhen
Published: February 2023

Acoustic metasurfaces have been widely explored and attracted great attention for their extraordinary wavefront manipulation abilities. In this paper, we propose a simple acoustic metagrating with periodic grooves that can split a normally incident beam into two or three reflected beams. The amplitudes and power flows of different reflected beams can be manipulated by changing the groove parameters. The mirror reflected wave is suppressed for equal two-beam splitting case and allowed for three-beam splitting case. Theoretical analysis and numerical simulations are performed to demonstrate the perfect two- and three-beam splitting performances based on local power conservation. Our research work provides a simple method for designing acoustic beam splitters and has extensive applications in acoustic sensing and communication.
Identifying patients with psychosocial problems in general practice: A scoping review
Authors: Schwenker Rosemarie , Deutsch Tobias , Unverzagt Susanne , Frese Thomas
Published: February 2023

Objective

We conducted a scoping review with the aim of comprehensively investigating what tools or methods have been examined in general practice research that capture a wide range of psychosocial problems (PSPs) and serve to identify patients and highlight their characteristics.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews and the Joanna Briggs Institute Reviewer’s Manual on scoping reviews. A systematic search was conducted in four electronic databases (Medline [Ovid], Web of Science Core Collection, PsycInfo, Cochrane Library) for quantitative and qualitative studies in English, Spanish, French, and German with no time limit. The protocol was registered with Open Science Framework and published in BMJ Open.

Results

Of the 839 articles identified, 66 met the criteria for study eligibility, from which 61 instruments were identified. The publications were from 18 different countries, with most studies employing an observational design and including mostly adult patients. Among all instruments, 22 were reported as validated, which we present in this paper. Overall, quality criteria were reported differently, with studies generally providing little detail. Most of the instruments were used as paper and pencil questionnaires. We found considerable heterogeneity in the theoretical conceptualisation, definition, and measurement of PSPs, ranging from psychiatric case findings to specific social problems.

Discussion and conclusion

This review presents a number of tools and methods that have been studied and used in general practice research. Adapted and tailored to local circumstances, practice populations, and needs, they could be useful for identifying patients with PSPs in daily GP practice; however, this requires further research. Given the heterogeneity of studies and instruments, future research efforts should include both a more structured evaluation of instruments and the incorporation of consensus methods to move forward from instrument research to actual use in daily practice.
Antibodies of the immunoglobulin a isotype to novel antigens in early axial spondyloarthritis
Authors: Ruytinx Pieter , Vandormael Patrick , Quaden Dana , Luyten Elien , Geusens Piet , Vanhoof Johan , Agten Anouk , Vandenabeele Frank , de Vlam Kurt , Somers Veerle
Published: February 2023

Introduction

There is an unmet need for biomarkers to identify patients with axial spondyloarthritis (axSpA). Increasing evidence suggest the presence of autoantibodies in a subset of axSpA patients. The aim of this study was to identify novel IgA antibodies in early axSpA patients and to determine their diagnostic potential in combination with previously determined IgG antibodies against UH (Hasselt University)-axSpA-IgG antigens.

Methods

An axSpA cDNA phage display library constructed from axSpA hip synovium, was used to screen for novel IgA antibodies in plasma from early axSpA patients. The presence of these antibodies against novel UH-axSpA-IgA antigens was determined in two independent axSpA cohorts, in healthy controls and in patients with chronic low back pain.

Results

We identified antibodies to 7 novel UH-axSpA-IgA antigens, of which 6 correspond to non-physiological peptides and 1 to the human histone deacetylase 3 (HDAC3) protein. IgA antibodies against 2 of these 7 novel UH-axSpA-IgA antigens and IgG antibodies against 2 of the previously identified antigens were significantly more present in early axSpA patients from the UH cohort (18/70, 25.7%) and the (Bio)SPAR cohort (26/164, 15.9%), compared to controls with chronic low back pain (2/66, 3%). Antibodies to this panel of 4 antigens were present in 21.1% (30/142) of patients with early axSpA from the UH and (Bio)SPAR cohorts. The positive likelihood ratio for confirming early axSpA using antibodies to these 4 UH-axSpA antigens was 7.0. So far, no clinical correlation between the novel identified IgA antibodies and inflammatory bowel disease could be identified.

Discussion

In conclusion, screening an axSpA cDNA phage display library for IgA reactivity resulted in the identification of 7 novel UH-axSpA-IgA antigens, of which 2 show promising biomarker potential for the diagnosis of a subset of axSpA patients, in combination with previously identified UH-axSpA-IgG antigens.
A founder COL4A4 pathogenic variant resulting in autosomal recessive Alport syndrome accounts for most genetic kidney failure in Romani people
Authors: Plevova Pavlina , Indrakova Jana , Savige Judy , Kuhnova Petra , Tvrda Petra , Cerna Dita , Hilscherova Sarka , Kudrejova Monika , Polendova Daniela , Jaklova Radka , Langova Martina , Jahnova Helena , Lastuvkova Jana , Dusek Jiri , Gut Josef , Vlckova Marketa , Solarova Pavla , Kreckova Gabriela , Kantorova Eva , Soukalova Jana , Slavkovsky Rastislav , Zapletalova Jana , Tichy Tomas , Thomasova Dana
Published: February 2023

Introduction

Romani people have a high prevalence of kidney failure. This study examined a Romani cohort for pathogenic variants in the COL4A3, COL4A4, and COL4A5 genes that are affected in Alport syndrome (AS), a common cause of genetic kidney disease, characterized by hematuria, proteinuria, end-stage kidney failure, hearing loss, and eye anomalies.

Materials and methods

The study included 57 Romani from different families with clinical features that suggested AS who underwent next-generation sequencing (NGS) of the COL4A3, COL4A4, and COL4A5 genes, and 83 family members.

Results

In total, 27 Romani (19%) had autosomal recessive AS caused by a homozygous pathogenic c.1598G>A, p.Gly533Asp variant in COL4A4 (n = 20) or a homozygous c.415G>C, p.Gly139Arg variant in COL4A3 (n = 7). For p.Gly533Asp, 12 (80%) had macroscopic hematuria, 12 (63%) developed end-stage kidney failure at a median age of 22 years, and 13 (67%) had hearing loss. For p.Gly139Arg, none had macroscopic hematuria (p = 0.023), three (50%) had end-stage kidney failure by a median age of 42 years (p = 0.653), and five (83%) had hearing loss (p = 0.367). The p.Gly533Asp variant was associated with a more severe phenotype than p.Gly139Arg, with an earlier age at end-stage kidney failure and more macroscopic hematuria. Microscopic hematuria was very common in heterozygotes with both p.Gly533Asp (91%) and p.Gly139Arg (92%).

Conclusion

These two founder variants contribute to the high prevalence of kidney failure in Czech Romani. The estimated population frequency of autosomal recessive AS from these variants and consanguinity by descent is at least 1:11,000 in Czech Romani. This corresponds to a population frequency of autosomal dominant AS from these two variants alone of 1%. Romani with persistent hematuria should be offered genetic testing.
Tolerance to intraoral biofilms and their effectiveness in improving mouth dryness and modifying oral microbiota in patients with primary Sjögren’s syndrome: “Predelfi study”
Authors: Orliaguet Marie , Fong Shao Bing , Le Pottier Laëtitia , Meuric Vincent , Boisramé Sylvie , Bonnaure-Mallet Martine , Pers Jacques-Olivier
Published: February 2023

Introduction

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by exocrine gland dysfunction. No therapeutic strategy is sufficient on its own for the management of dry mouth and therapeutic innovations are required.

Methods

This Predelfi study was a single-center, prospective, comparative, randomized, double-blind, cross-over controlled study with the primary objective of assessing the tolerance to and effectiveness of two adhesive biofilms (containing prebiotics and, sodium alginate, respectively) in patients with pSS and hyposialia (#NCT04206826 in ClinicalTrials.gov). Secondary objectives were to obtain initial data regarding the clinical effectiveness of such biofilms in the improvement of signs and symptoms related to dry mouth and potential changes in the oral microbiota. Ten pSS patients with pSS were included (9 females and 1 male) with a mean age of 58.1 ± 14.0 years.

Results and discussion

Tolerance to the prebiotic and sodium alginate biofilms was assessed by the patients (visual analog scale [VAS] score 66.7 and 87.6, respectively) and the practitioner (90 and 100, respectively). The absolute changes in the VAS scores at the start and end of each treatment period highlighted an improvement in mouth dryness for the sodium alginate versus the prebiotic biofilm. The VAS scores for other parameters (mouth burning sensation; taste alteration; chewing; swallowing and speech difficulties) remained globally comparable between the two groups. Unstimulated salivary flow showed no changes regardless of the biofilm used. Regarding the oral microbiota, the sodium alginate biofilm increased the abundance of the Treponema genus, whereas the use of the prebiotic biofilm as the first treatment increased the abundance of the genera Veillonella and Prevotella. Nevertheless, the prebiotic biofilm appeared to stimulate “milder” genera with regard to periodontal infections. Furthermore, pre-treatment with the prebiotic biofilm prevented the emergence of the Treponema genus induced by subsequent treatment with the sodium alginate biofilm, suggesting a potential protective effect.
Interaction between the VP2 protein of deformed wing virus and host snapin protein and its effect on viral replication
Authors: Sun Li , Li Ming , Ma Yueyu , Huang Sichao , Ma Mingxiao , Fei Dongliang
Published: February 2023

Introduction

Deformed wing virus (DWV) is one of the causative agents of colony collapse disorder. The structural protein of DWV plays a vital role in the process of viral invasion and host infection; however, there is limited research on DWV.

Methods and Results

In this study, we screened the host protein snapin, which can interact with the VP2 protein of DWV, using the yeast two-hybrid system. Through computer simulation and GST pull-down and CO-IP assays, an interaction between snapin and VP2 was confirmed. Furthermore, immunofluorescence and co-localization experiments revealed that VP2 and snapin primarily co-localized in the cytoplasm. Consequently, RNAi was used to interfere with the expression of snapin in worker bees to examine the replication of DWV after the interference. After silencing of snapin, the replication of DWV in worker bees was significantly downregulated. Hence, we speculated that snapin was associated with DWV infection and involved in at least one stage of the viral life cycle. Finally, we used an online server to predict the interaction domains between VP2 and snapin, and the results indicate that the interaction domain of VP2 was approximately located at 56–90, 136–145, 184–190, and 239–242 aa and the snapin interaction domain was approximately located at 31–54 and 115–136 aa.

Conclusion

This research confirmed that DWV VP2 protein could interacts with the snapin of host protein, which provides a theoretical basis for further investigation of its pathogenesis and development of targeted therapeutic drugs.
Redundant potassium transporter systems guarantee the survival of Enterococcus faecalis under stress conditions
Authors: Acciarri Giuliana , Gizzi Fernán O. , Torres Manno Mariano A. , Stülke Jörg , Espariz Martín , Blancato Víctor S. , Magni Christian
Published: February 2023

Enterococcusis able to grow in media at pH from 5.0 to 9.0 and a high concentration of NaCl (8%). The ability to respond to these extreme conditions requires the rapid movement of three critical ions: proton (H+), sodium (Na+), and potassium (K+). The activity of the proton F0F1ATPase and the sodium Na+V0V1type ATPase under acidic or alkaline conditions, respectively, is well established inthese microorganisms. The potassium uptake transporters KtrI and KtrII were described inEnterococcus hirae, which were associated with growth in acidic and alkaline conditions, respectively. InEnterococcus faecalis, the presence of the Kdp (potassium ATPase) system was early established. However, the homeostasis of potassium in this microorganism is not completely explored. In this study, we demonstrate that Kup and KimA are high-affinity potassium transporters, and the inactivation of these genes inE.faecalisJH2-2 (a Kdp laboratory natural deficient strain) had no effect on the growth parameters. However, in KtrA defective strains (ΔktrA, ΔkupΔktrA) an impaired growth was observed under stress conditions, which was restored to wild type levels by external addition of K+ions. Among the multiplicity of potassium transporters identify in the genusEnterococcus, Ktr channels (KtrAB and KtrAD), and Kup family symporters (Kup and KimA) are present and may contribute to the particular resistance of these microorganisms to different stress conditions. In addition, we found that the presence of the Kdp system inE.faecalisis strain-dependent, and this transporter is enriched in strains of clinical origin as compared to environmental, commensal, or food isolates.
Peanut lipids influence the response of bronchial epithelial cells to the peanut allergens Ara h 1 and Ara h 2 by decreasing barrier permeability
Authors: Palladino Chiara , Ellinger Isabella , Kalic Tanja , Humeniuk Piotr , Ret Davide , Mayr Vanessa , Hafner Christine , Hemmer Wolfgang , Hoffmann-Sommergruber Karin , Untersmayr Eva , Bublin Merima , Radauer Christian , Breiteneder Heimo
Published: February 2023

Background: Peanut-allergic individuals react upon their first known ingestion of peanuts, suggesting sensitization occurs through non-oral exposure. Increasing evidence suggests that the respiratory tract is a probable site for sensitization to environmental peanuts. However, the response of the bronchial epithelium to peanut allergens has never been explored. Furthermore, food matrix-derived lipids play an important role in allergic sensitization.

Objective: To contribute to a better understanding of the mechanisms of allergic sensitization to peanuts via inhalation, by exploring the direct effect of the major peanut allergens Ara h 1 and Ara h 2 and peanut lipids on bronchial epithelial cells.

Methods: Polarized monolayers of the bronchial epithelial cell line 16HBE14o- were stimulated apically with peanut allergens and/or peanut lipids (PNL). Barrier integrity, transport of allergens across the monolayers, and release of mediators were monitored.

Results: Ara h 1 and Ara h 2 impacted the barrier integrity of the 16HBE14o- bronchial epithelial cells and crossed the epithelial barrier. Ara h 1 also induced the release of pro-inflammatory mediators. PNL improved the barrier function of the cell monolayers, decreased paracellular permeability and reduced the amount of allergens crossing the epithelial layer.

Conclusion: Our study provides evidence of the transport of Ara h 1 and Ara h 2 across the airway epithelium, of the induction of a pro-inflammatory milieu, and identifies an important role for PNL in controlling the amount of allergens that can cross the epithelial barrier. These, all together, contribute to a better understanding of the effects of peanuts exposure on the respiratory tract.