bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinoic acid receptor regulation of decision-making for cell differentiation
Authors: Brown Geoffrey
Published: April 2023

All-trans retinoic acid (ATRA) activation of retinoic acid receptors (RARs) is crucial to an organism’s proper development as established by findings for mouse foetuses from dams fed a vitamin A-deficient diet. ATRA influences decision-making by embryonic stem (ES) cells for differentiation including lineage fate. From studies of knockout mice, RARα and RARγ regulate haematopoiesis whereby active RARα modulates the frequency of decision-making for myeloid differentiation, but is not essential for myelopoiesis, and active RARγ supports stem cell self-renewal and maintenance. From studies of zebrafish embryo development, active RARγ plays a negative role in stem cell decision-making for differentiation whereby, in the absence of exogenous ATRA, selective agonism of RARγ disrupted stem cell decision-making for differentiation patterning for development. From transactivation studies, 0.24 nM ATRA transactivated RARγ and 19.3 nM (80-fold more) was needed to transactivate RARα. Therefore, the dose of ATRA that cells are exposed to in vivo, from gradients created by cells that synthesize and metabolize, is important to RARγ versus RARα and RARγ activation and balancing of the involvements in modulating stem cell maintenance versus decision-making for differentiation. RARγ activation favours stemness whereas concomitant or temporal activation of RARγ and RARα favours differentiation. Crosstalk with signalling events that are provoked by membrane receptors is also important.
Incorporation and solidification mechanism of manganese doped cement clinker
Authors: Yang Nan , Li Aihong , Liu Qing , Cui Yanshuai , Wang Zhaojia , Gao Yukun , Guo Jianping
Published: April 2023

Using municipal and industrial solid waste as a substitute raw material and fuel in cement rotary kiln co-processing is considered an economic and environmentally friendly alternative to the use of traditional fuels. However, the presence of heavy metals in solid waste is a growing concern in the cement rotary kiln co-processing technique. The solidification mechanism of heavy metals in cement clinker is directly related to their stabilization. Cement clinkers doped with manganese oxide (MnO2: 0.0%–5.0% wt%) were prepared in a laboratory to investigate the impacts of extrinsic Mn on cement clinker calcination. The insignificant changes in X-ray diffractometer patterns indicated that the fixed Mn had little influence on the mineral lattice structure. Raman spectra and X-ray photoelectron spectroscopy revealed the transformation of the silicate phase when the Mn dose was increased. Moreover, the satisfactory solidification ratio confirmed the incorporation of Mn in the cement clinker. These results provided evidence of the influence rule of Mn in the cement clinker calcination process. Furthermore, Raman spectroscopy showed great potential for the qualitative and semi-quantitative analysis of the cementitious materials derived from cement rotary kiln co-processing. These results will be important for the further development of green cement manufacturing technology.
Effects of paternal obesity on maternal-neonatal outcomes and long-term prognosis in adolescents
Authors: Lin Yingying , Chen Zhiwei , Qian Qinfang , Wang Yanxia , Xiu Xiaoyan , Ou Ping , Fang Jiaoning , Li Guobo
Published: April 2023

Objective

This study evaluated whether paternal body mass index (BMI) before pregnancy was a risk factor for maternal-neonatal outcomes and long-term prognosis in offspring.

Methods

This study included 29,518 participants from eight cities in Fujian, China using a stratified cluster random sampling method from May to September 2019. They were divided into four groups based on paternal BMI. Univariate and multivariate logistic regression were used to explore the relationship between paternal BMI groups, maternal-neonatal outcomes, and long-term prognosis in offspring. Further subgroup analysis was conducted to examine the stability of the risk.

Results

The incidences of hypertensive disorder complicating pregnancy (HDCP), cesarean delivery, gestational weight gain (GWG) over guideline, and macrosomia were significantly higher in the paternal overweight and obesity group. Importantly, this study demonstrated that the incidence of asthma, hand-foot-and-mouth disease (HFMD), anemia, dental caries, and obesity of adolescents in paternal obesity increased. Furthermore, logistic regression and subgroup analysis confirm paternal obesity is a risk factor for HDCP, cesarean delivery, and macrosomia. It caused poor long-term prognosis in adolescents, including asthma, dental caries, and HFMD.

Conclusions

Paternal obesity is a risk factor for adverse maternal-neonatal outcomes and poor long-term prognosis in adolescents. In addition to focusing on maternal weight, expectant fathers should pay more attention to weight management since BMI is a modifiable risk factor. Preventing paternal obesity can lead to better maternal and child outcomes. It would provide new opportunities for chronic diseases.
Obstructive sleep apnea risk and determinant factors among type 2 diabetes mellitus patients at the chronic illness clinic of the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia
Authors: Worku Abebe , Ayele Eleni , Alemu Shitaye , Legese Gebrehiwot Lema , Yimam Samrawit Meles , Kassaw Getasew , Diress Mengistie , Asres Mezgebu Silamsaw
Published: April 2023

Introduction

Obstructive sleep apnea is a sleep complaint among type 2 diabetes mellitus patients that has a deleterious effect on health with immediate and long-term impacts. Despite its impacts, data on the magnitude and predictors of obstructive sleep apnea among type 2 diabetes mellitus patients in Ethiopia is still limited. Thus, this study was conducted to determine how common a high risk of obstructive sleep apnea is and its predictors among type 2 diabetes mellitus patients receiving follow-up care at the chronic illness follow-up clinic at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2022.

Methods

An institution-based cross-sectional study was conducted. Interviewer-administered questionnaires and physical measurements with standard instruments were used to collect the required data. The collected data were entered into EpiData 4.6 and exported into STATA 14. Both Bivariable and multivariable binary logistic regression analyses were done to identify factors associated with a high risk of obstructive sleep apnea. Variables with a p-value ≤0.05 in the multivariable logistic regression analysis were declared as significantly associated with a high risk of obstructive sleep apnea.

Results

A total of 319 type 2 diabetes mellitus patients with a median age of 58 years participated in our current study. The overall prevalence of a high risk of obstructive sleep apnea among the study participants was 31.97% (95%CI: 27.06, 37.32). On multivariable logistic analysis, a neck circumference of ≥40 cm (AOR=4.33, 95%CI 1.37, 13.72), physical inactivity (AOR=2.29, 95%CI 1.15, 4.53), comorbid hypertension (AOR=4.52, 95%CI 2.30, 9.18), and male sex (AOR=8.01, 95%CI 3.02, 21.24) were associated with a high risk of obstructive sleep apnea.

Conclusion and recommendation

The prevalence of a high risk of obstructive sleep apnea among type 2 diabetes mellitus patients remains high. A neck circumference of ≥40 cm, physical inactivity, comorbid hypertension, and male sex were significantly associated with a high risk of obstructive sleep apnea among type 2 diabetes mellitus patients. Screening and evaluation of type 2 diabetes mellitus patients for obstructive sleep apnea are recommended to avoid the negative impacts.
Stormwater best management practices: Experimental evaluation of chemical cocktails mobilized by freshwater salinization syndrome
Authors: Galella Joseph G. , Kaushal Sujay S. , Mayer Paul M. , Maas Carly M. , Shatkay Ruth R. , Stutzke Robert A.
Published: April 2023

Freshwater Salinization Syndrome (FSS) refers to the suite of physical, biological, and chemical impacts of salt ions on the degradation of natural, engineered, and social systems. Impacts of FSS on mobilization of chemical cocktails has been documented in streams and groundwater, but little research has focused on the effects of FSS on stormwater best management practices (BMPs) such as: constructed wetlands, bioswales, ponds, and bioretention. However emerging research suggests that stormwater BMPs may be both sources and sinks of contaminants, shifting seasonally with road salt applications. We conducted lab experiments to investigate this premise; replicate water and soil samples were collected from four distinct stormwater feature types (bioretention, bioswale, constructed wetlands and retention ponds) and were used in salt incubation experiments conducted under six different salinities with three different salts (NaCl, CaCl2, and MgCl2). Increased salt concentrations had profound effects on major and trace element mobilization, with all three salts showing significant positive relationships across nearly all elements analyzed. Across all sites, mean salt retention was 34%, 28%, and 26% for Na+, Mg2+ and Ca2+ respectively, and there were significant differences among stormwater BMPs. Salt type showed preferential mobilization of certain elements. NaCl mobilized Cu, a potent toxicant to aquatic biota, at rates over an order of magnitude greater than both CaCl2 and MgCl2. Stormwater BMP type also had a significant effect on elemental mobilization, with ponds mobilizing significantly more Mn than other sites. However, salt concentration and salt type consistently had significant effects on mean concentrations of elements mobilized across all stormwater BMPs (p < 0.05), suggesting that processes such as ion exchange mobilize metals mobilize metals and salt ions regardless of BMP type. Our results suggest that decisions regarding the amounts and types of salts used as deicers can have significant effects on reducing contaminant mobilization to freshwater ecosystems.
Evaluation of the triangle-relationship of industrial pollution, foreign direct investment, and economic growth in China’s transformation
Authors: Zhang Juanfeng , Han Rui , Song Zongjun , Zhang Lihua
Published: April 2023

Unlike previous research on foreign direct investment (FDI), economic growth, and pollution, this study focuses on investigating complex interactions specifically. A dynamic simultaneous equation model is adopted, together with the one-step systematic GMM, drawn upon to empirically analyze 30 Chinese provinces between 2006 and 2017. The results show that FDI does promote economic growth in China which, in turn, positively affects FDI. However, FDI inflow and economic growth both have negative environmental effects. A higher level of environmental pollution corresponds with FDI becoming more attractive. In the case of China, therefore, the pollution-haven hypothesis holds weight. Specifically, industrial environmental pollution is found to positively affect economic growth, indicating this growth to fall on the left side of the environmental Kuznets Curve. Accordingly, therefore, policymakers should look to optimize China’s industrial structure, guide the inflow of high-quality FDI, and promote healthy and sustainable development under the country’s new development philosophy.
Learning from monitoring networks: Few-large vs. many-small plots and multi-scale analysis
Authors: Tang Becky , Kamakura Renata P. , Barnett David T. , Clark James S.
Published: April 2023

In order to learn about broad scale ecological patterns, data from large-scale surveys must allow us to either estimate the correlations between the environment and an outcome and/or accurately predict ecological patterns. An important part of data collection is the sampling effort used to collect observations, which we decompose into two quantities: the number of observations or plots (n) and the per-observation/plot effort (E; e.g., area per plot). If we want to understand the relationships between predictors and a response variable, then lower model parameter uncertainty is desirable. If the goal is to predict a response variable, then lower prediction error is preferable. We aim to learn if and when aggregating data can help attain these goals. We find that a small sample size coupled with large observation effort coupled (few large) can yield better predictions when compared to a large number of observations with low observation effort (many small). We also show that the combination of the two values (n and E), rather than one alone, has an impact on parameter uncertainty. In an application to Forest Inventory and Analysis (FIA) data, we model the tree density of selected species at various amounts of aggregation using linear regression in order to compare the findings from simulated data to real data. The application supports the theoretical findings that increasing observational effort through aggregation can lead to improved predictions, conditional on the thoughtful aggregation of the observational plots. In particular, aggregations over extremely large and variable covariate space may lead to poor prediction and high parameter uncertainty. Analyses of large-range data can improve with aggregation, with implications for both model evaluation and sampling design: testing model prediction accuracy without an underlying knowledge of the datasets and the scale at which predictor variables operate can obscure meaningful results.
Pan-cancer analysis of ADAMs: A promising biomarker for prognosis and response to chemotherapy and immunotherapy
Authors: Ma Bo , Yu Riyue
Published: April 2023

Background: Members of a disintegrin and metalloproteinase (ADAM) family play a vital role in cancer development. However, a comprehensive analysis of the landscape of the ADAM family in pan-cancer remains to be performed.

Methods: The correlation of the expression level and prognostic value with ADAMs in a pan-cancer cohort and the relationship between ADAMs and the stemness score, tumour microenvironment (TME), chemotherapy-related drug sensitivity, immune subtype, and immunotherapy outcome were investigated.

Results: ADAMs were differentially expressed between tumour and para-carcinoma tissues in the pan-cancer cohort, and the expression of ADAMs was significantly correlated with patient prognosis. Furthermore, ADAMs were significantly correlated with the stromal score and immune score based on the TME analysis. Additionally, ADAMs were also correlated with DNAss and RNAss in the pan-cancer cohort. On investigating the CellMiner database, ADAMs were revealed to be significantly correlated with the sensitivity of various drugs, including raloxifene and tamoxifen. Moreover, in the IMvigor210 and GSE78220 cohorts, ADAMs were correlated with immunotherapy response and immune activation genes. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were utilised to determine the differential level of ADAM9 in cancer and para-carcinoma tissues in patients’ samples.

Conclusion: This study elucidates the importance of ADAMs in cancer progression and lays a foundation for further exploration of ADAMs as potential pan-cancer targets.
GCK exonic mutations induce abnormal biochemical activities and result in GCK-MODY
Authors: Dai Tongtong , Yang Yun , Zhang Juanjuan , Ma Xiaoyu , Chen Lifen , Zhang Caiping , Lv Sheng , Li Lin , Tang Renqiao , Zhen Ni , Lu Wenli , Li Chuanyin , Hu Ronggui , Xiao Yuan , Dong Zhiya
Published: April 2023

Objective: Glucokinase-maturity-onset diabetes of the young (GCK-MODY; MODY2) is a rare genetic disorder caused by mutations in the glucokinase (GCK) gene. It is often under- or misdiagnosed in clinical practice, but correct diagnosis can be facilitated by genetic testing. In this study, we examined the genes of three patients diagnosed with GCK-MODY and tested their biochemical properties, such as protein stability and half-life, to explore the function of the mutant proteins and identify the pathogenic mechanism of GCK-MODY.

Methods: Three patients with increased blood glucose levels were diagnosed with MODY2 according to the diagnostic guidelines of GCK-MODY proposed by the International Society for Pediatric and Adolescent Diabetes (ISPAD) in 2018. Next-generation sequencing (whole exome detection) was performed to detect gene mutations. The GCK gene and its mutations were introduced into the pCDNA3.0 and pGEX-4T-1 vectors. Following protein purification, enzyme activity assay, and protein immunoblotting, the enzyme activity of GCK was determined, along with the ubiquitination level of the mutant GCK protein.

Results: Genetic testing revealed three mutations in the GCK gene of the three patients, including c.574C>T (p.R192W), c.758G>A (p.C253Y), and c.794G>A (p.G265D). The biochemical characteristics of the protein encoded by wild-type GCK and mutant GCK were different, compared to wild-type GCK, the enzyme activity encoded by the mutant GCK was reduced, suggesting thermal instability of the mutant GST-GCK. The protein stability and expression levels of the mutant GCK were reduced, and the enzyme activity of GCK was negatively correlated with the levels of fasting blood glucose and HbA1c. In addition, ubiquitination of the mutant GCK protein was higher than that of the wild-type, suggesting a higher degradation rate of mutant GCK than WT-GCK.

Conclusion:GCK mutations lead to changes in the biochemical characteristics of its encoded proteins. The enzyme activities, protein expression, and protein stability of GCK may be reduced in patients with GCK gene mutations, which further causes glucose metabolism disorders and induces MODY2.
Inhibitory effects of Clostridium butyricum culture and supernatant on inflammatory colorectal cancer in mice
Authors: Pu Wenfeng , Zhang Hong , Zhang Tao , Guo Xiaoguang , Wang Xiaoqing , Tang Shaohui
Published: April 2023

Clostridium butyricum (CB) is a spore-forming, gram-positive and obligate anaerobic rod bacterium. CB can modulate the composition of the gut microbiome and promote the growth of beneficial microbes in the intestine by generating short-chain fatty acids (SCFAs), which in turn protect against colitis and prevents the formation of inflammatory-associated colorectal cancer (CRC) by ameliorating colon inflammatory processes. Yet, it remains unclear whether the culture and supernatant of CB could directly influence inflammatory CRC in mice. In this study, azoxymethane (AOM)+dextran sodium sulphate (DSS) was used to induce CRC model in C57BL/6 mice. Next, the serum levels of inflammatory cytokines, including interleukin-6 (IL-6), interleukin-10 (IL-10), and cytokines TNF-α, were measured and the pathohistological examination of the large intestine was performed. Both CB culture and supernatant were found to have anti-inflammatory properties. Subsequently, Western blot and Real-Time Quantitative PCR (RT-qPCR) revealed that CB and supernatant regulate the NF-κB/p65 pathway to inhibit the development and progression of inflammatory CRC in AOM+DSS-treated mice, which could be due to the high levels of butyric acid in the supernatant.
NLRP3 inflammasome-induced pyroptosis in digestive system tumors
Authors: Wen Jiexia , Xuan Bin , Liu Yang , Wang Liwei , He Li , Meng Xiangcai , Zhou Tao , Wang Yimin
Published: April 2023

Programmed cell death (PCD) refers to cell death in a manner that depends on specific genes encoding signals or activities. PCD includes apoptosis, pyroptosis, autophagy and necrosis (programmed necrosis). Among these mechanisms, pyroptosis is mediated by the gasdermin family and is accompanied by inflammatory and immune responses. When pathogens or other danger signals are detected, cytokine action and inflammasomes (cytoplasmic multiprotein complexes) lead to pyroptosis. The relationship between pyroptosis and cancer is complex and the effect of pyroptosis on cancer varies in different tissue and genetic backgrounds. On the one hand, pyroptosis can inhibit tumorigenesis and progression; on the other hand, pyroptosis, as a pro-inflammatory death, can promote tumor growth by creating a microenvironment suitable for tumor cell growth. Indeed, the NLRP3 inflammasome is known to mediate pyroptosis in digestive system tumors, such as gastric cancer, pancreatic ductal adenocarcinoma, gallbladder cancer, oral squamous cell carcinoma, esophageal squamous cell carcinoma, in which a pyroptosis-induced cellular inflammatory response inhibits tumor development. The same process occurs in hepatocellular carcinoma and some colorectal cancers. The current review summarizes mechanisms and pathways of pyroptosis, outlining the involvement of NLRP3 inflammasome-mediated pyroptosis in digestive system tumors.
Host A-to-I RNA editing signatures in intracellular bacterial and single-strand RNA viral infections
Authors: Wei Zhi-Yuan , Wang Zhi-Xin , Li Jia-Huan , Wen Yan-Shuo , Gao Di , Xia Shou-Yue , Li Yu-Ning , Pan Xu-Bin , Liu Yan-Shan , Jin Yun-Yun , Chen Jian-Huan
Published: April 2023

Background

Microbial infection is accompanied by remodeling of the host transcriptome. Involvement of A-to-I RNA editing has been reported during viral infection but remains to be elucidated during intracellular bacterial infections.

Results

Herein we analyzed A-to-I RNA editing during intracellular bacterial infections based on 18 RNA-Seq datasets of 210 mouse samples involving 7 tissue types and 8 intracellular bacterial pathogens (IBPs), and identified a consensus signature of RNA editing for IBP infections, mainly involving neutrophil-mediated innate immunity and lipid metabolism. Further comparison of host RNA editing patterns revealed remarkable similarities between pneumonia caused by IBPs and single-strand RNA (ssRNA) viruses, such as altered editing enzyme expression, editing site numbers, and levels. In addition, functional enrichment analysis of genes with RNA editing highlighted that the Rab GTPase family played a common and vital role in the host immune response to IBP and ssRNA viral infections, which was indicated by the consistent up-regulated RNA editing of Ras-related protein Rab27a. Nevertheless, dramatic differences between IBP and viral infections were also observed, and clearly distinguished the two types of intracellular infections.

Conclusion

Our study showed transcriptome-wide host A-to-I RNA editing alteration during IBP and ssRNA viral infections. By identifying and comparing consensus signatures of host A-to-I RNA editing, our analysis implicates the importance of host A-to-I RNA editing during these infections and provides new insights into the diagnosis and treatment of infectious diseases.
A machine learning approach to discover migration modes and transition dynamics of heterogeneous dendritic cells
Authors: Song Taegeun , Choi Yongjun , Jeon Jae-Hyung , Cho Yoon-Kyoung
Published: April 2023

Dendritic cell (DC) migration is crucial for mounting immune responses. Immature DCs (imDCs) reportedly sense infections, while mature DCs (mDCs) move quickly to lymph nodes to deliver antigens to T cells. However, their highly heterogeneous and complex innate motility remains elusive. Here, we used an unsupervised machine learning (ML) approach to analyze long-term, two-dimensional migration trajectories of Granulocyte-macrophage colony-stimulating factor (GMCSF)-derived bone marrow-derived DCs (BMDCs). We discovered three migratory modes independent of the cell state: slow-diffusive (SD), slow-persistent (SP), and fast-persistent (FP). Remarkably, imDCs more frequently changed their modes, predominantly following a unicyclic SD→FP→SP→SD transition, whereas mDCs showed no transition directionality. We report that DC migration exhibits a history-dependent mode transition and maturation-dependent motility changes are emergent properties of the dynamic switching of the three migratory modes. Our ML-based investigation provides new insights into studying complex cellular migratory behavior.
A tryptophan metabolite prevents depletion of circulating endothelial progenitor cells in systemic low-grade inflammation
Authors: Mannarino Massimo R. , Bianconi Vanessa , Scalisi Giulia , Franceschini Luca , Manni Giorgia , Cucci Alessia , Bagaglia Francesco , Mencarelli Giulia , Giglioni Francesco , Ricciuti Doriana , Figorilli Filippo , Pieroni Benedetta , Cosentini Elena , Padiglioni Eleonora , Colangelo Cecilia , Fuchs Dietmar , Puccetti Paolo , Follenzi Antonia , Pirro Matteo , Gargaro Marco , Fallarino Francesca
Published: April 2023

Background

Chronic systemic inflammation reduces the bioavailability of circulating endothelial progenitor cells (EPCs). Indoleamine 2,3-dioxygenase 1 (IDO1), a key enzyme of immune tolerance catalyzing the initial step of tryptophan degradation along the so-called l-kynurenine (l-kyn) pathway, that is induced by inflammatory stimuli and exerts anti-inflammatory effects. A specific relationship between IDO1 activity and circulating EPC numbers has not yet been investigated.

Methods

In this study, circulating EPCs were examined in mice treated with low doses of lipopolysaccharide (LPS) to mimic low-grade inflammation. Moreover, the association between IDO1 activity and circulating EPCs was studied in a cohort of 277 patients with variable systemic low-grade inflammation.

Results

Repeated low doses of LPS caused a decrease in circulating EPCs and l-kyn supplementation, mimicking IDO1 activation, significantly increased EPC numbers under homeostatic conditions preventing EPC decline in low-grade endotoxemia. Accordingly, in patients with variable systemic low-grade inflammation, there was a significant interaction between IDO1 activity and high-sensitivity C-reactive protein (hs-CRP) in predicting circulating EPCs, with high hs-CRP associated with significantly lower EPCs at low IDO1 activity but not at high IDO1 activity.

Interpretation

Overall, these findings demonstrate that systemic low-grade inflammation reduces circulating EPCs. However, high IDO1 activity and l-kyn supplementation limit circulating EPC loss in low-grade inflammation.
Property owner shoreline modification decisions vary based on their perceptions of shoreline change and interests in ecological benefits
Authors: Guthrie Amanda G. , Stafford Sarah , Scheld Andrew M. , Nunez Karinna , Bilkovic Donna Marie
Published: April 2023

Even under current sea level conditions, many communities are working to protect their coastlines against flooding and shoreline erosion. Coastal communities often protect their shorelines against excessive erosion by using armoring techniques (e.g., bulkheads, riprap). Yet hardened structures reduce many of the natural adaptive mechanisms present in coastal ecosystems and reduce the sustainability of the coastal system. In contrast, natural and nature-based features (e.g., living shorelines) can better protect coastal properties from storm damage and reduce erosion while also having the potential to adapt to new conditions. Since property owners are installing armoring structures more often than living shorelines, we sought to understand the factors motivating their shoreline modification decision. We surveyed property owners in Virginia, U.S. that applied for a shoreline modification permit. Most property owners, regardless of modification sought, perceive riprap revetment to be effective, able to withstand storm damage, and able to adapt to sea level rise. Interestingly, property owners that sought out living shorelines were not highly confident in living shorelines’ protection benefits. While most property owners perceived the ecological benefits of living shorelines, these benefits did not substantially impact the decision over what type of shoreline modification to implement. Our work highlights pathways that can improve coastal resilience given the important role that shoreline property owner decisions contribute to coastal community resiliency. Our results indicate there is a need to better engage property owners about the protection and adaptation benefits of living shorelines as their perceptions were not aligned with scientific assessments of living shorelines. Concurrently, coastal policies could be strengthened to support more natural approaches to shoreline management, as the more common armoring techniques are not resilient to sea level rise or storm damage.
Genetic markers associated with divergent selection against the parasite Marteilia cochillia in common cockle (Cerastoderma edule) using transcriptomics and population genomics data
Authors: Pampín M. , Casanova A. , Fernández C. , Blanco A. , Hermida M. , Vera M. , Pardo B. G. , Coimbra R. M. , Cao A. , Iglesias D. , Carballal M.J. , Villalba A. , Martínez P.
Published: April 2023

The common cockle (Cerastoderma edule) plays an important role in marine ecosystems and represents a valuable socioeconomic resource for coastal communities. In 2012, the cockle beds from Rı́a de Arousa (Galicia, NW Spain) were seriously decimated by the protozoan Marteilia cochillia responsible for marteiliosis. We aimed to identify single nucleotide polymorphisms (SNP) markers potentially associated with resilience to marteiliosis to be used in marker-assisted selection programs for restoring affected cockle beds and recovering their production. For this, we carried out a population genomics approach using 2b-RADseq, where 38 naive samples (before the first detection of M. cochillia in 2012) from two beds of Rı́a de Arousa were compared with 39 affected samples collected in 2018/2019 (after several years of marteiliosis occurring in the area), collected either before (15 non-exposed samples) or during (24 exposed samples) the marteiliosis outbreak. Additionally, 767 differentially expressed genes (DEG) from a previous transcriptomic study addressed during the aforementioned 2018/19 marteiliosis outbreak, were evaluated to identify SNPs showing signals of selection. Using 2b-RADseq, 9,154 SNPs were genotyped and among them, 110 consistent outliers for divergent selection were identified. This set of SNPs was able to discriminate the samples according to their marteiliosis status (naive vs affected; exposed vs non-exposed), while another 123 SNPs were identified linked to DEGs associated with the level of infection across a temporal series. Finally, combining the population genomics and transcriptomics information, we selected the 60 most reliable SNPs associated with marteiliosis resilience. These SNPs were close to or within DEGs, and many of them were related to immune response (phagocytosis and cell adhesion), defence, such as apoptosis, stress, and cellular cycle, among other functions. This set of SNPs will eventually be validated to develop a cost-effective genotyping tool for their application for obtaining cockle-resilient strains for marteiliosis.
Underwater ice adaptive mapping and reconstruction using autonomous underwater vehicles
Authors: Fan Shuangshuang , Zhang Xinyu , Zeng Guangxian , Cheng Xiao
Published: April 2023

The undersides of floating ice shelves and sea ice in the Antarctic and Arctic are among the least accessible environments on Earth. The interactions between ice shelves, sea ice, and the ocean are of considerable scientific interest. In order to fully understand the complex picture of sea ice, and not just its surface, it is quite necessary to map the underside to comprehend the full context of its growth and decay patterns. Autonomous Underwater Vehicles (AUVs) are rapidly becoming the desired platform of choice for mapping the underside of sea ice to provide high-resolution 3D views of sea ice topography. To increase the efficiency and accuracy of AUV sampling behaviors is significant for the under-ice observation mission given its limited endurance. In this paper, we present a low-cost underwater ice mapping framework for small-sized AUVs using adaptive sampling and map reconstruction methods. A small-sized AUV is cost-effective and convenient for operation in polar regions; however, due to its limited loading capacity and energy, it is more applicable for the vehicle to carry single-beam sonar for ice bottom mapping but not multi-beam. Thus, the essential issue in this application is how to obtain the key information of ice topography and how to reconstruct the map of ice draft (namely underwater ice thickness) with AUV sparse mapping swathes. To address this, we propose a graphics-based adaptive mapping method to densify the measuring of ice bottom surface with ‘noticeable’ variations; moreover, we also present a sparse approximation method for ice draft map reconstruction using the sparse mapping swathes from a single-beam sonar. Our efforts are to introduce an effective and efficient approach for underwater ice mapping using low-cost small-sized AUVs. Our proposed adaptive mapping and reconstruction methods are validated in the under-ice scenario created using the field data.
Association between treatment failure in patients with early syphilis and penicillin resistance-related gene mutations of Treponema pallidum: Protocol for a multicentre nested case–control study
Authors: Mi Hong-Fei , Shen Xu , Chen Xiao-Qing , Zhang Xiao-Luo , Ke Wu-Jian , Xiao Yao
Published: April 2023

Background

The widespread occurrence of syphilis remains a global public health problem. Although penicillin has been recommended as the first-line therapy for syphilis for more than 70 years, treatment failure occurs in 10–20% of patients with early syphilis. Recent studies have reported varied single-nucleotide polymorphisms (SNPs) of Treponema pallidum related to penicillin resistance. The clinical relevance of these SNPs to treatment failure in patients with early syphilis is unresolved. In this work, a protocol is developed to evaluate the association between treatment failure in patients with early syphilis and penicillin resistance-related gene mutations of T. pallidum.

Methods

A multicentre nested case–control study is designed, and patients who are diagnosed with early syphilis and treated with penicillin will be recruited for the study cohort. Before the first treatment, baseline information and biological specimens will be collected from the subjects, and serological tests for syphilis will be performed. Each participant will be followed up at 1, 3, 6, 9, and 12 months after the first treatment, and the clinical manifestations and serum non-treponemal test titres will be evaluated at each follow-up. Patients who will fail treatment are defined as cases, and those who will respond to treatment are defined as controls. Tests for SNPs related to penicillin-binding proteins and Tp47 will be performed in these cases and controls. Survival analysis is used performed to identify gene mutations of T. pallidum related to penicillin resistance and their combinations associated with treatment failure.

Discussion

This protocol provides a practical clinical study design that illustrates the role of gene mutations of T. pallidum related to penicillin resistance in the treatment outcome of patients with early syphilis.
Current clinical understanding and effectiveness of portopulmonary hypertension treatment
Authors: Tamura Yuichi , Tamura Yudai , Taniguchi Yu , Atsukawa Masanori
Published: April 2023

Portopulmonary hypertension (PoPH) is a rare subtype of Group 1 pulmonary arterial hypertension (PAH) with a poor prognosis. According to the most up-to-date definition, PoPH is characterized by a mean pulmonary arterial pressure (PAP) of >20 mmHg at rest, a pulmonary artery wedge pressure of ≤15 mmHg, and a pulmonary vascular resistance (PVR) of >2 Wood units with portal hypertension. Like PAH, PoPH is underpinned by an imbalance in vasoactive substances. Therefore, current guidelines recommend PAH-specific therapies for PoPH treatment; however, descriptions of the actual treatment approaches are inconsistent. Given the small patient population, PoPH is often studied in combination with idiopathic PAH; however, recent evidence suggests important differences between PoPH and idiopathic PAH in terms of hemodynamic parameters, treatment approaches, survival, socioeconomic status, and healthcare utilization. Therefore, large, multi-center registry studies are needed to examine PoPH in isolation while obtaining statistically meaningful results. PoPH has conventionally been excluded from clinical drug trials because of concerns over hepatotoxicity. Nevertheless, newer-generation endothelin receptor antagonists have shown great promise in the treatment of PoPH, reducing PVR, PAP, and World Health Organization functional class without causing hepatotoxicity. The role of liver transplantation as a treatment option for PoPH has also been controversial; however, recent evidence shows that this procedure may be beneficial in this patient population. In the future, given the shortage of liver donors, predictors of a favorable response to liver transplantation should be determined to select the most eligible patients. Collectively, advances in these three areas could help to standardize PoPH treatment in the clinic.
Identification of DYNLT1 associated with proliferation, relapse, and metastasis in breast cancer
Authors: Miao Sen , Ju Gaoda , Jiang Chonghua , Xue Bing , Zhao Lihua , Zhang Rui , Diao Han , Yu Xingzhou , Zhang Linlin , Pan Xiaozao , Zhang Hua , Zang Lijuan , Wang Lei , Zhou Tianhao
Published: April 2023

Background

Breast cancer (BC) is the most common malignant disease worldwide. Although the survival rate is improved in recent years, the prognosis is still bleak once recurrence and metastasis occur. It is vital to investigate more efficient biomarkers for predicting the metastasis and relapse of BC. DYNLT1 has been reported that participating in the progression of multiple cancers. However, there is still a lack of study about the correlation between DYNLT1 and BC.

Methods

In this study, we evaluated and validated the expression pattern and prognostic implication of DYNLT1 in BC with multiple public cohorts and BC tumor microarrays (TMAs) of paraffin-embedded tissues collected from the Affiliated Hospital of Jining Medical University. The response biomarkers for immune therapy, such as tumor mutational burden (TMB), between different DYNLT1 expression level BC samples were investigated using data from the TCGA-BRCA cohort utilizing public online tools. In addition, colony formation and transwell assay were conducted to verify the effects of DYNLT1 in BC cell line proliferation and invasion.

Results

The results demonstrated that DYNLT1 overexpressed in BC and predicted poor relapse-free survival in our own BC TMA cohort. In addition, DYNLT1 induced BC development by promoting MDA-MB-231 cell proliferation migration, and metastasis.

Conclusion

Altogether, our findings proposed that DYNLT1 could be a diagnostic and prognostic indicator in BC.
Repurposing drugs with specific activity against L-form bacteria
Authors: Emami Kaveh , Banks Peter , Wu Ling Juan , Errington Jeffery
Published: April 2023

Cell wall deficient “L- form” bacteria are of growing medical interest as a possible source of recurrent or persistent infection, largely because of their complete resistance to cell wall active antibiotics such as β-lactams. Antibiotics that specifically kill L-forms would be of potential interest as therapeutics, but also as reagents with which to explore the role of L-forms in models of recurrent infection. To look for specific anti-L-form antibiotics, we screened a library of several hundred FDA-approved drugs and identified compounds highly selective for L-form killing. Among the compounds identified were representatives of two different classes of calcium channel blockers: dihydropyridines, e.g., manidipine; and diphenylmethylpiperazine, e.g., flunarizine. Mode of action studies suggested that both classes of compound work by decreasing membrane fluidity. This leads to a previously recognized phenotype of L-forms in which the cells can continue to enlarge but fail to divide. We identified a considerable degree of variation in the activity of different representatives of the two classes of compounds, suggesting that it may be possible to modify them for use as drugs for L-form-dependent infections.
Culture and transfection: Two major bottlenecks in understanding Plasmodium vivax biology
Authors: Kumari Sanju , Sinha Abhinav
Published: April 2023

The long term in vitro culture of Plasmodium falciparum was successfully established by Trager and Jensen in 1976; however it largely remains unachieved for P. vivax. The major obstacle associated with Plasmodium vivax in vitro culture is its predilection for invading younger reticulocytes and the complex remodelling of invaded reticulocytes. There are many factors under exploration for this predilection and host–parasite interactions between merozoites and invaded reticulocytes. These include various factors related to parasite, host and environment such as compromised reticulocyte osmotic stability after invasion, abundance of iron in the reticulocytes which makes them favourable for P. vivax growth and propagation and role of a hypoxic environment in P. vivax in vitro growth. P. vivax blood stage transfection represents another major hurdle towards understanding this parasite’s complex biology. Efforts in making this parasite amenable for molecular investigation by genetic modification are limited. Newer approaches in sustaining a longer in vitro culture and thereby help advancing transfection technologies in P. vivax are urgently needed that can be explored to understand the unique biology of this parasite.
Coupled model for microbial growth and phase mass transfer in pressurized batch reactors in the context of underground hydrogen storage
Authors: Strobel Gion , Hagemann Birger , Lüddeke Christian Truitt , Ganzer Leonhard
Published: April 2023

A rising interest in a strong hydrogen economy as a part of the future net-zero economy results in an increasing necessity to store hydrogen as a raw material or an energy carrier. Experience and studies show that storing hydrogen in deep underground sites could enable microbial conversion of hydrogen. To predict and examine the loss of hydrogen, laboratory studies, and analysis are essential. A growth model is required to interpret batch or chemostat experiments. With this model, the parameters of microbial growth, and the conversion of hydrogen can be specified. This study presents experiments with methanogens and a hydrogen/carbon dioxide gas mixture performed in batch reactors. Further, the microbial growth was modeled by a double Monod model with hydrogen and carbon dioxide as the limiting substrates. As the amount of carbon dioxide dissolved in the water phase can not be neglected, both phases were considered in the proposed model. The mass-transfer rate between the gas and water phase was implemented by a linear relation including the concentrations in both phases and the mass-transfer coefficient. With the resulting coupled model, it was possible to match the pressure behavior in the reactor and conclude the microbial growth kinetics. Two types of methanogenic species were tested to validate the model. The mass transfer coefficient proves to impact the growth behavior in porous media. The mathematical model and experimental data are necessary to determine the growth rate and yield coefficient.
Inactivation of the lysine binding sites of human plasminogen (hPg) reveals novel structural requirements for the tight hPg conformation, M-protein binding, and rapid activation
Authors: Ayinuola Yetunde A. , Castellino Francis J.
Published: April 2023

Accelerated activation of the human plasminogen zymogen (hPg) to two-chain active plasmin (hPm) is achieved following conformational changes induced by ligand-binding at the lysine-binding sites (LBSs) in four of the five hPg kringle domains. In this manner, pattern D skin-trophic strains of Group A streptococci (GAS), through the expression of surface plasminogen-binding M-protein (PAM), immobilize surface hPg, thereby enabling rapid hPg activation by GAS-secreted streptokinase (SK). Consequently, GAS enhances virulence by digesting extracellular and tight cellular junctional barriers using hPm activity. Many studies have demonstrated the singular importance of the kringle-2 domain of hPg (K2hPg) to PAM-binding using hPg fragments. Recently, we showed, using full-length hPg, that K2hPg is critical for PAM binding. However, these studies did not eliminate any modulatory effects of the non-K2hPg LBS on this interaction. Moreover, we sought to establish the significance of the intramolecular interaction between Asp219 of the LBS of K2hPg and its serine protease domain binding partner, Lys708, to conformational changes in hPg. In the current study, selective inactivation of the LBS of K1hPg, K4hPg, and K5hPg revealed that the LBS of these kringle domains are dispensable for hPg binding to PAM. However, the attendant conformational change upon inactivation of K4hPg LBS increased the affinity of hPg for PAM by an order of magnitude. This finding suggests that the native hPg conformation encloses PAM-binding exosites or sterically hinders access to K2hPg. While simultaneous inactivation of the LBS of K1hPg, K4hPg, and K5hPg inhibited hPg/SK association alongside hPg activation, the replacement of Lys708 generated a slight conformational change that optimally accelerated hPg activation. Thus, we accentuate disparate functions of hPg LBS and conclude, using intact proteins, that K2hPg plays a central role in regulating hPg activation.
Gait pattern analysis in the home environment as a key factor for the reliable assessment of shunt responsiveness in patients with idiopathic normal pressure hydrocephalus
Authors: Dias Sandra Fernandes , Graf Christina , Jehli Elisabeth , Oertel Markus Florian , Mahler Julia , Schmid Daners Marianne , Stieglitz Lennart Henning
Published: April 2023

Background

The identification of patients with gait disturbance associated with idiopathic normal pressure hydrocephalus (iNPH) is challenging. This is due to the multifactorial causes of gait disturbance in elderly people and the single moment examination of laboratory tests.

Objective

We aimed to assess whether the use of gait sensors in a patient's home environment could help establish a reliable diagnostic tool to identify patients with iNPH by differentiating them from elderly healthy controls (EHC).

Methods

Five wearable inertial measurement units were used in 11 patients with iNPH and 20 matched EHCs. Data were collected in the home environment for 72 h. Fifteen spatio-temporal gait parameters were analyzed. Patients were examined preoperatively and postoperatively. We performed an iNPH sub-group analysis to assess differences between responders vs. non-responders. We aimed to identify parameters that are able to predict a reliable response to VP-shunt placement.

Results

Nine gait parameters significantly differ between EHC and patients with iNPH preoperatively. Postoperatively, patients with iNPH showed an improvement in the swing phase (p = 0.042), and compared to the EHC group, there was no significant difference regarding the cadence and traveled arm distance. Patients with a good VP-shunt response (NPH recovery rate of ≥5) significantly differ from the non-responders regarding cycle time, cycle time deviation, number of steps, gait velocity, straight length, stance phase, and stance to swing ratio. A receiver operating characteristic analysis showed good sensitivity for a preoperative stride length of ≥0.44 m and gait velocity of ≥0.39 m/s.

Conclusion

There was a significant difference in 60% of the analyzed gait parameters between EHC and patients with iNPH, with a clear improvement toward the normalization of the cadence and traveled arm distance postoperatively, and a clear improvement of the swing phase. Patients with iNPH with a good response to VP-shunt significantly differ from the non-responders with an ameliorated gait pattern.