bluuebunny/crossref_metadata_2025 huggingface dataset:
A Role for Liquid-Ordered Plasma Membrane Nanodomains Coordinating the Unconventional Secretory Pathway of Fibroblast Growth Factor 2?
Authors: Lolicato Fabio , Nickel Walter
Published: April 2022

Fibroblast growth factor 2 (FGF2) is a tumor cell survival factor that belongs to a subgroup of extracellular proteins lacking N-terminal signal peptides. Whereas this phenomenon was already recognized in the early 1990s, detailed insights into the molecular mechanisms underlying alternative pathways of protein secretion from eukaryotic cells were obtained only recently. Today, we know about a number of alternative secretory mechanisms, collectively termed unconventional protein secretion (UPS). FGF2 belongs to a subgroup of cargo proteins secreted by direct translocation across the plasma membrane. This feature has been classified as type I UPS and is shared with other unconventionally secreted proteins, such as HIV-Tat and Tau. FGF2 translocation across the membrane is initiated through sequential interactions with the Na,K-ATPase, Tec kinase, and phosphoinositide PI(4,5)P2 at the inner plasma membrane leaflet. Whereas the first two are auxiliary factors of this pathway, the interaction of FGF2 with PI(4,5)P2 triggers the core mechanism of FGF2 membrane translocation. It is based on a lipidic membrane pore that is formed by PI(4,5)P2-induced oligomerization of FGF2. Membrane-inserted FGF2 oligomers are recognized as translocation intermediates that are resolved at the outer plasma membrane leaflet by glypican-1, a heparan sulfate proteoglycan that captures and disassembles FGF2 oligomers on cell surfaces. Here, we discuss recent findings suggesting the molecular machinery mediating FGF2 membrane translocation to be highly organized in liquid-ordered plasma membrane nanodomains, the core process underlying this unusual pathway of protein secretion.
Disordered Intestinal Microbial Communities During Clostridioides difficile Colonization and Subsequent Infection of Hepatic Cirrhosis Patients in a Tertiary Care Hospital in China
Authors: Chen Yunbo , Lv Tao , Yan Dong , Zheng Lisi , Zheng Beiwen , Wang Jingxia , Gu Silan , Li Lanjuan
Published: April 2022

Patients with hepatic cirrhosis are more susceptible to Clostridioides difficile infection (CDI) and colonization with Clostridioides difficile (C. difficile). Asymptomatic C. difficile colonization is thought to predispose to subsequent CDI. However, the dynamic gut microbiota changes remain unclear. In this study, we used 16S rRNA gene sequencing to longitudinally monitor alterations in the intestinal microbiota of 22 hepatic cirrhosis patients with toxigenic C. difficile colonization at admission (pre-CDI) and developed CDI during hospitalization, subdivided into pre-CDI and CDI. 21 hospitalized cirrhotic patients without C. difficile colonization served as controls (HC). Compared with HC, pre-CDI and CDI samples had significantly decreased microbial richness and diversity, a significantly higher relative abundance of opportunistic pathogen Enterococcus, and a lower relative abundance of beneficial symbionts, such as Faecalibacterium, Dorea, and Roseburia. Three biomarkers showed high accuracy for distinguishing pre-CDI samples from HC with an area under the curve (AUC) up to 0.81. In conclusion, our study explored the changes of the gut microbiome before and after CDI. The gut microbial richness as well as diversity in CDI patients were notably reduced, relative to controls. Imbalance of the intestinal flora may be related to the risk for development of CDI. Identifying key members of the gut microbiota and illustrating their roles and mechanisms of action in CDI development are important avenues for future research.
Self-Organizing Maps Identify Windows of Opportunity for Seasonal European Summer Predictions
Authors: Carvalho-Oliveira Julianna , Borchert Leonard F. , Zorita Eduardo , Baehr Johanna
Published: April 2022

We combine a machine learning method and ensemble climate predictions to investigate windows of opportunity for seasonal predictability of European summer climate associated with the North Atlantic jet stream. We particularly focus on the impact of North Atlantic spring sea surface temperatures (SST) on the four dominant atmospheric teleconnections associated with the jet stream: the summer North Atlantic Oscillation (NAO) in positive and negative phases, the Atlantic Ridge (At. Ridge), and Atlantic Low (At. Low). We go beyond standard forecast practices by not only identifying these atmospheric teleconnections and their SST precursors but by making use of these identified precursors in the analysis of a dynamical forecast ensemble. Specifically, we train the neural network-based classifier Self-Organizing Maps (SOM) with ERA-20C reanalysis and combine it with model simulations from the Max Planck Institute Earth System Model in mixed resolution (MPI-ESM-MR). We use two different sets of 30-member hindcast ensembles initialized every May, one for training and evaluation between 1902 and 2008, and one for verification between 1980–2016, respectively. Among the four summer atmospheric teleconnections analyzed here, we find that At. Ridge simulated by MPI-ESM-MR shows the best agreement with ERA-20C, thereby representing with its occurrence windows of opportunity for skillful summer predictions. Conversely, At. Low shows the lowest agreement, which might limit the model skill for early warning of warmer than average summers. In summary, we find that spring SST patterns identified with a SOM analysis can be used to guess the dominant summer atmospheric teleconnections at initialization and guide a sub-selection of potential skillful ensemble members. This holds especially true for At. Ridge and At. Low and is unclear for summer NAO. We show that predictive skill in the selected ensemble exceeds that of the full ensemble over regions in the Euro-Atlantic domain where spring SST significantly correlates with summer sea level pressure (SLP). In particular, we find a significant improvement in predictive skill for SLP, geopotential height at 500 hPa, and 2 m temperature at 3–4 months lead time over Scandinavia, which is robust among the two sets of hindcast ensembles.
Curricula Design & Pedagogy for Sketching Within HCI & UX Education
Authors: Lewis Makayla , Sturdee Miriam
Published: April 2022

Sketching is recognised as an important tool in the journey of research and practical processes of Human Computer Interaction (HCI) and User Experience Design (UX). However, it is not always included in higher education curriculum, in which HCI and UX is often a single module in one year group amongst more “traditional” approaches in computer science. The benefits of sketching and visualisation practice can be used by students across the board in computing degrees, but especially so within HCI and UX, where novel approaches and ideation are valued and practiced. By the time learners leave higher education, they may or may not have engaged with this valuable skill. HCI has a lot in common with UX, and the two are commonly conflated to be the same thing, though despite this, there is not a focus on practical sketching and visualisation skills. In comparison, within the UX workplace environment, sketching is part of design thinking and vital for the structuring of ideas, storyboards, user journey maps and more. We focus on the incorporation and exploration of sketching as an educational tool, technique and output within HCI, and how this learning is given and received over a number of contexts. This paper outlines case studies where sketching has been included in both formal and informal learning with both undergraduate, postgraduate, and post education populations, and how this knowledge exchange has been both enhanced and changed by the recent compulsory move to online teaching during the COVID-19 pandemic. We discuss practice and learning in the context of four case studies:Data-Sketching in a First Year Minor; Sketching in a 2nd Year HCI Cohort; Sketching as a Foundational Tool for MSc User Experience Design;and,Sketching in HCI for Peer-to-Peer Learning. Further, we make recommendations for incorporating sketching practice and theory into both undergraduate and postgraduate university programs, as well as for peer-to-peer learning in both public and private contexts.
HSP60-Derived Peptide as an LPS/TLR4 Modulator: An in silico Approach
Authors: Vila-Casahonda Rafael Gustavo , Lozano-Aponte Jorge , Guerrero-Beltrán Carlos Enrique
Published: April 2022

As a part of innate immunity mechanisms, the Toll-like receptor (TLR) signaling pathway serves as one of the mainstay lines of defense against pathogenic microorganisms and cell dysfunction. Nevertheless, TLR overactivation induces a systemic proinflammatory environment compromising organ function or causing the patient’s death. TLRs modulators, specially those focused for TLR4, remain a promising approach for inflammatory diseases treatment, being peptide-based therapy a trendy approach. Heat shock protein 60 (HSP60) not only plays a pivotal role in the development of several maladies with strong inflammatory components but also HSP60 peptides possess anti-inflammatory properties in TLR4-mediated diseases, such as diabetes, arthritis, and atherosclerosis. The experimental treatment using HSP60 peptides has proven to be protective in preclinical models of the heart by hampering inflammation and modulating the activity of immune cells. Nonetheless, the effect that these peptides may exert directly on cells that express TLR and its role to inhibit overactivation remain elusive. The aim of this study is to evaluate by molecular docking, a 15 amino acid long-HSP60 peptide (Peptide-2) in the lipopolysaccharide (LPS) binding site of TLR4/MD2, finding most Peptide-2 resulting conformations posed into the hydrophobic pocket of MD2. This observation is supported by binding energy obtained for the control antagonist Eritoran, close to those of Peptide-2. This last does not undergo drastic structural changes, moving into a delimited space, and maintaining the same orientation during molecular dynamics simulation. Based on the two computational techniques applied, interaction patterns were defined for Peptide-2. With these results, it is plausible to propose a peptidic approach for TLR4 modulation as a new innovative therapy to the treatment of TLR4-related cardiovascular diseases.
Lack of Effects of Renin-Angiotensin-Aldosterone System Activity and Beta-Adrenoceptor Pathway Polymorphisms on the Response to Bisoprolol in Hypertension
Authors: Zeng Weiwei , Chu Tanya T. W. , Ho Chung Shun , Lo Clara W. S. , Chan Alan S. L. , Kong Alice P. S. , Tomlinson Brian , Chan Sze Wa
Published: April 2022

Purpose

This study examined the effects of plasma renin activity (PRA), angiotensin II (Ang II) and aldosterone (PAC) concentrations as well as common polymorphisms in the β1-Adrenoceptor gene (ADRB1) and the G-protein α-Subunit (Gαs) protein gene the G protein α-Subunit 1 gene (GNAS) on the blood pressure (BP) and heart rate (HR) response to bisoprolol in Chinese patients with hypertension.

Methods

Patients with sitting clinic systolic BP (SBP) 140–169 mmHg and/or diastolic BP (DBP) 90–109 mmHg after placebo run-in were treated with open-label bisoprolol 2.5 mg daily for 6 weeks. Patients diagnosed as having primary aldosteronism or renal artery stenosis were excluded. PRA, Ang II and PAC concentrations were measured after the placebo run-in and after 6 weeks of treatment. The Ser49Gly and Arg389Gly polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS were genotyped by the TaqMan® assay.

Results

In 99 patients who completed the study, baseline PAC levels were significantly associated with baseline DBP and plasma potassium on univariate but not on multivariate linear regression analysis. PRA, Ang II, and PAC concentrations at baseline were not associated with changes in BP with bisoprolol treatment, but the values were all significantly reduced (PRA −0.141 ± 0.595 ng/mL/h, Ang II −2.390 ± 5.171 pmol/L and aldosterone −51.86 ± 119.1 pg/mL; all P < 0.05) following 6 weeks of bisoprolol treatment. There were no significant differences in BP or HR responses in patients with baseline PRA above or below the PRA cut-point of 0.65 ng/mL/h or the median value of 0.9 ng/ml/hour. There were no significant associations of the ADRB1 and GNAS polymorphisms with the clinic and ambulatory BP and HR responses to bisoprolol.

Conclusion

Baseline PRA, PAC and Ang II concentrations showed no significant association with the BP response to bisoprolol treatment, but all these parameters were reduced after 6 weeks of treatment with bisoprolol. The two common polymorphisms in ADRB1 and the c.393C > T polymorphism in GNAS had no significant association with the BP and HR response to bisoprolol in these patients.
Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits
Authors: Galian-Gay Laura , Escalona Silva Roxana Andreina , Teixidó-Turà Gisela , Casas Guillem , Ferrer-Sistach Elena , Mitroi Cristina , Mingo Susana , Monivas Vanessa , Saura Daniel , Vidal Bàrbara , Trasca Livia , Moral Sergio , Calvo Francisco , Castiñeira Busto Maria , Sánchez Violeta , Gonzalez Ariana , Guzman Gabriela , Mora Marta Noris , Arnau Vives MiguelÁngel , Peteiro Jesús , Bouzas Alberto , Mas-Stachurska Aleksandra , González-Alujas Teresa , Gutiérrez Laura , Fernandez-Galera Rubén , Valente Filipa , Guala Andrea , Ruiz-Muñoz Aroa , Avilés Cesar Augusto Sao , Palomares José F. Rodríguez , Ferreira Ignacio , Evangelista Artur
Published: April 2022

Objectives

To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS).

Methods

A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2).

Results

Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3–30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12–0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13–0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20–0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively.

Conclusions

Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.
Screening of Lipid Metabolism-Related Gene Diagnostic Signature for Patients With Dilated Cardiomyopathy
Authors: Xu Man , Guo Ying-ying , Li Dan , Cen Xian-feng , Qiu Hong-liang , Ma Yu-lan , Huang Si-hui , Tang Qi-zhu
Published: April 2022

Background

Dilated cardiomyopathy (DCM) is characterized by enlarged ventricular dimensions and systolic dysfunction and poor prognosis. Myocardial lipid metabolism appears abnormal in DCM. However, the mechanism of lipid metabolism disorders in DCM remains unclear.

Methods

A gene set variation analysis (GSVA) were performed to estimate pathway activity related to DCM progression. Three datasets and clinical data downloaded from the Gene Expression Omnibus (GEO), including dilated cardiomyopathy and donor hearts, were integrated to obtain gene expression profiles and identify differentially expressed genes related to lipid metabolism. GO enrichment analyses of differentially expressed lipid metabolism-related genes (DELs) were performed. The clinical information used in this study were obtained from GSE21610 dataset. Data from the EGAS00001003263 were used for external validation and our hospital samples were also tested the expression levels of these genes through RT-PCR. Subsequently, logistic regression model with the LASSO method for DCM prediction was established basing on the 7 DELs.

Results

GSVA analysis showed that the fatty acid metabolism was closely related to DCM progression. The integrated dataset identified 19 DELs, including 8 up-regulated and 11 down-regulated genes. A total of 7 DELs were identified by further external validation of the data from the EGAS00001003263 and verified by RT-PCR. By using the LASSO model, 6 genes, including CYP2J2, FGF1, ETNPPL, PLIN2, LPCAT3, and DGKG, were identified to construct a logistic regression model. The area under curve (AUC) values over 0.8 suggested the good performance of the model.

Conclusion

Integrated bioinformatic analysis of gene expression in DCM and the effective logistic regression model construct in our study may contribute to the early diagnosis and prevention of DCM in people with high risk of the disease.
A Novel Strategy to Simplify the Procedures in Treating Complicated Coronary Bifurcation Lesions: From a Bench Test to Clinical Application
Authors: Li Dongdong , Ma Wenshuai , Liu Pengyun , Liu Hao , Bai Baobao , Zhang Mingming , Guo Wangang
Published: April 2022

Background

Although provisional stenting strategy based on jailed balloon side branch (SB) protection could be useful for high-risk bifurcation lesion in certain clinical scenarios, its complexity still gives rise to procedure complications. We proposed a novel strategy, the jailed balloon proximal optimization technique (JB-POT), to simplify the procedures in treating complex coronary bifurcation lesions (CBLs). The present study was designed to verify the safety and efficacy of JB-POT under bench testing and clinical circumstances.

Methods

After a stent was deployed in main vessel (MV) with a balloon jailed in SB, POT and post-dilation of the stent were performed without retrieving the jailed balloon. A re-POT was performed 2 mm away from SB branching point to minimize proximal stent malapposition. The JB-POT procedure was performed on 10 samples of a silicone bifurcation bench model, and optical coherence tomography (OCT) was utilized to evaluate stent deployment. From December 2018 to July 2021, a total of 28 consecutive patients with true CBLs treated with JB-POT were enrolled. Immediate procedure results were observed, and clinical follow-ups were performed.

Results

The bench test showed that JB-POT did not induce significant stent malapposition, underexpansion or distortion, as indexed by the malapposition rate, minimum stent area (MSA), eccentricity index and symmetry index determined through OCT. Under clinical circumstances, JB-POT did not induce significant malapposition, underexpansion or distortion. Among the 30 lesions, there was no primary endpoint event defined as SB occlusion, need to rewire the SB with a polymer-covered guide wire, or failure to retrieve a jailed wire or balloon. One rewiring event and 0 double stenting events occurred as secondary endpoint events. One patient died of heart failure in the 8th month after discharge.

Conclusions

The JB-POT protocol, which tremendously simplifies the current standard provisional stenting procedure in complicated bifurcation lesions, shows acceptability in safety and efficacy. Hence, it might become an applicable strategy for treating high-risk bifurcation lesions, especially those with multiple risked SBs.
Mantle and Crustal Xenoliths in a Tephriphonolite From La Palma (Canary Islands): Implications for Phonolite Formation at Oceanic Island Volcanoes
Authors: Klügel Andreas , Albers Elmar , Hansteen Thor H.
Published: April 2022

The occurrence of mantle-derived peridotite xenoliths in phonolitic melts is a rare phenomenon, and is commonly ascribed to a mantle origin of the phonolite. The alternative possibility, that xenoliths are transported into evolving phonolite melts by mafic magmas, has received little attention. A unique tephriphonolite lava with phonolitic groundmass composition, from the active Cumbre Vieja volcano of La Palma (Canary Islands), allows to test these models. The lava contains abundant inclusions that represent the island’s major xenolith types: kaersutite-dominated cumulates, gabbros from the lower oceanic crust, and peridotites from the mantle. Our petrological investigations indicate that the tephriphonolite magma contained 3–4 wt% H2O and was stored in the lower crust at around 250–350 MPa and 900–950°C, at oxidized conditions (∆NNO of 2–3). The peridotite xenoliths are mantled by complex polyphase selvages, with adjacent up to 1.6 mm wide zonations where olivine compositions change from Fo78-86at the selvage contact to Fo89-91inside the xenoliths. We carried out diffusion modelling for Fe-Mg exchange and found that the peridotites had contact with intermediate to evolved alkaline melts over decades to centuries. This timescale is comparable to that inferred for basanite-hosted peridotite xenoliths from Cumbre Vieja. The following model is proposed: differentiation of evolved melts occurs in a magma accumulation zone in the lowermost oceanic crust beneath La Palma. The evolving melts receive periodic recharge by mantle-derived mafic magmas at intervals on the order of decades to a few centuries, comparable to historic eruption recurrences (80 years on average). Some of these recharge pulses carry mantle peridotite fragments that become deposited in the accumulation zone. Thus, these xenoliths do not reflect formation of the evolved melts in the mantle. Final ascent of the tephriphonolite was triggered by magma recharge some weeks before its eruption, resulting in entrainment and thorough mingling of a mixed xenolith population (cumulates, oceanic crust gabbros, peridotites). We infer that formation of phonolites in the lower crust beneath oceanic island volcanoes, and subsequent eruption, requires a balance between rates and volumes of magma recharge pulses and of eruptive events.
Quantification of the Fracture Complexity of Shale Cores After Triaxial Fracturing
Authors: Zhang Yonghao , Ma Jinfeng , Wang Yang , Wang Fei , Li Xin , Zhao Luanxiao
Published: April 2022

Diagnosing fractures under compression is of great importance in optimizing hydraulic fracturing stimulation strategies for unconventional reservoirs. However, a lot of information, such as fracture morphology and fracture complexity, is far from being fully excavated in the laboratory limited by the immature fracture identification techniques. In the current study, we propose a set of methods to analyze the fracture complexity of cylindrical cores after triaxial fracturing. Rock failure under conventional compression tests is real-time controlled by monitoring the stress–strain evolutions to ensure that the cores remain cylindrical after failure. The lateral surface of the core cylinders is scanned with a 2D optical scanner to extract the fracture parameters, surface fracture rate, and inclination dispersion, which are normalized and averaged to derive the fracture complexity. After analyzing the data for 24 shale gas reservoir cores from the Sichuan Basin, the fractal dimension of fracture images shows a good linear correlation with the surface fracture rate but has no correlation with the dip dispersion. The calculated fracture complexity has nearly no relationship with the E-v–based brittleness index but demonstrates a positive correlation with the mineral content–based brittleness index. Moreover, the fracture complexity is associated with the core mineralogical compositions. The fracture complexity is positively correlated with the content of quartz, calcite, and dolomite and negatively correlated with the content of clay minerals and has no obvious relationship with the content of feldspar. The proposed method provides an experimental basis for the evaluation of fracturability of unconventional oil and gas reservoirs.
Sex Differences in Obesity and Cognitive Function in Chinese Elderly Patients With Chronic Schizophrenia
Authors: Li Wei , Lin Sun , Yue Ling , Fang Yuan , Xiao Shifu
Published: April 2022

Background

It is well known that schizophrenia is associated with sex differences. However, no study has explored the sex differences in obesity and cognitive function in elderly Chinese patients with schizophrenia.

Objective

This study aimed to compare sex differences in obesity and cognitive function in elderly Chinese individuals with schizophrenia.

Methods

A total of 304 elderly patients with schizophrenia and 130 sex- and age-matched healthy controls from the community were recruited. Demographic, clinical, and lipid parameters were collected for all subjects. The Montreal Cognitive Assessment (MoCA) was used to assess the global cognitive functions of the participants, while the Positive and Negative Syndrome Scale (PANSS) was used to assess psychopathological symptoms in patients with schizophrenia.

Results

Of the patients with schizophrenia, the prevalence of obesity in men and women was 11.7% (19/163) and 21.3% (30/141), respectively. The score (14.51 ± 6.504) of MOCA in elderly male patients with schizophrenia was significantly higher than that (11.40 ± 6.822) in female patients. There was a positive correlation between the MOCA scores and body mass index (BMI) (r=0.206, p=0.018) in male elderly patients with schizophrenia. Conversely, the MOCA scores of female elderly patients with schizophrenia did not correlate with BMI (p>0.05). However, we found no sex differences in obesity and cognition among control older adults.

Conclusions

Our findings suggest that there are significant sex differences in obesity and cognitive function in elderly Chinese patients with schizophrenia.
The Origination of Growth Hormone/Insulin-Like Growth Factor System: A Story From Ancient Basal Chordate Amphioxus
Authors: Li Mengyang
Published: April 2022

The growth hormone/insulin-like growth factor (GH/IGF) system, also called the pituitary-liver axis, has a somatotrophic role in the body. Although the GH/IGF system has always been regarded as a vertebrate-specific endocrine system, its actual origin remained unknown for a long time. The basal chordate, amphioxus, occupies an evolutionary position between vertebrates and invertebrates. Impressively, most of the members of the GH/IGF system are present in the amphioxus. The GH-like molecule in the amphioxus is mainly expressed in Hatschek’s pit. It functions similarly to vertebrate GH and has a GH receptor-like binding partner. The amphioxus IGF-like peptide shows mitogenic activity and an expression pattern resembling that of vertebrate IGF-I. The receptor of IGF-like peptide and IGF binding protein (IGFBP) have also been demonstrated to exist in the amphioxus. These results reveal the origin of the gene families in the GH/IGF system, providing strong evidence that this system emerged in the amphioxus.
Progranulin and Its Receptor Predict Kidney Function Decline in Patients With Type 2 Diabetes
Authors: Murakoshi Maki , Gohda Tomohito , Sakuma Hiroko , Shibata Terumi , Adachi Eri , Kishida Chiaki , Ichikawa Saki , Koshida Takeo , Kamei Nozomu , Suzuki Yusuke
Published: April 2022

Progranulin (PGRN), a growth factor, is abundantly expressed in a broad range of tissues and cell types with pleiotropic functions including inflammation, neurodegeneration, and facilitating lysosome acidification. PGRN binds to TNF receptors (TNFR) and inhibits downstream inflammatory signaling pathways. TNFR is a well-known predictor of glomerular filtration rate (GFR) decline in a variety of diseases. Therefore, we measured circulating PGRN in addition to TNFR using an enzyme-linked immunosorbent assay and explored whether it predicted renal prognosis in 201 Japanese patients with type 2 diabetes. During a median follow-up of 7.6 years, 21 participants reached primary renal endpoint, which involves a decline of at least 57% in eGFR from baseline, or the onset of end-stage renal disease. Univariate Cox regression analysis revealed that classical renal measures (GFR and albuminuria), two TNF-related biomarkers (PGRN and TNFR), and BMI were associated with this outcome. Multivariate analysis demonstrated that high levels of PGRN [HR 2.50 (95%CI 2.47–2.52)] or TNFR1 [HR 5.38 (95%CI 5.26–5.50)] were associated with this outcome after adjusting for relevant covariates. The high levels of PGRN as well as TNFR1 were associated with a risk of primary renal outcome in patients with type 2 diabetes after adjusting for established risk factors.
Optimal Sizing Grid-Connected Hybrid PV/Generator/Battery Systems Following the Prediction of CO2 Emission and Electricity Consumption by Machine Learning Methods (MLP and SVR): Aseer, Tabuk, and Eastern Region, Saudi Arabia
Authors: Almutairi Khalid , Almutairi Mubarak , Harb Kamal , Marey Omar
Published: April 2022

Researchers’ concentration has been on hybrid systems that can fulfill economic and environmental goals in recent years. In this study, first, the prediction of CO2 emission and electricity consumption of Saudi Arabia by 2040 is made by employing multi-layer perceptron (MLP) and support vector regression (SVR) methods to see the rate of CO2 emission and electricity consumption. In this regard, the most important parameters such as gross domestic product (GDP), population, oil consumption, natural gas consumption, and renewable consumption are considered. Estimating CO2 emission by MLP and electricity consumption by SVR showed 815 Mt/year and 475 TWh/year, respectively, where R2 for MLP and SVR was 0.99. Prediction results showed a 31% and 39% increase in CO2 emission and electricity consumption by 2040 compared to 2020. Second, the optimum combination of components for supplying demand load and desalination load in residential usages are found where 0% capacity shortage, 20–60$/t penalty for CO2 emission, sell back to the grid, and both fixed and random grid outages are considered. Load demands were considered under two winter and non-winter times so that 4,266, 2,346, and 3,300 kWh/day for Aseer, Tabuk, and the Eastern Region were shown, respectively. Results show that 0.12, 0.11, and 0.12 (kW (PV))/(kWh/day(load)) and 0.1, 0.08, and 0.08 (kW(Bat))/(kWh/day(load)) are required under the assumption of this study for Aseer, Tabuk, and the Eastern Region, respectively. Also, COEs for the proposed systems are 0.0934, 0.0915, and 0.0910 $/kWh for Aseer, Tabuk, and the Eastern Region, respectively. Also, it was found that renewable fractions (RFs) between 46% and 48% for all of the case studies could have rational COE and NPCs and fulfill the increasing rate of CO2 emission and electricity consumption. Finally, sensitivity analysis on grid CO2 emission and its penalty, load and solar Global Horizontal Irradiance (GHI), PV, and battery prices showed 45%–55%, 42%–52%, and 43%–49% RFs for Aseer, Tabuk, and the Eastern Region, respectively.
Manta Net: The Golden Method for Sampling Surface Water Microplastics in Aquatic Environments
Authors: Pasquier Gabriel , Doyen Périne , Kazour Maria , Dehaut Alexandre , Diop Mamadou , Duflos Guillaume , Amara Rachid
Published: April 2022

Microplastics (MPs) (plastic particles < 5 mm in size) have become the most ubiquitous type of anthropogenic litter contaminating aquatic environments worldwide, and are capable of harming aquatic organisms and entering the food web. Microplastic research has rapidly evolved over several decades, with many studies sampling microplastic in surface waters. For sea surface sampling of MPs, different net devices have been used. But although there is an increasing number of studies using these devices to quantifying MPs in different aquatic environments, data comparison is difficult due to the lack of standardised, harmonised sampling methods and data reporting units. The Manta net device is actually the most commonly used method for sea surface sampling of MPs. The three main parts of this net are: the floating/stabilizing part, the opening mouth and the net bag, and each of them can have its own specifications. These specifications, along with the sampling methods, can be critical for the efficiency of the sampling accurate quantification of MPs in the aquatic environments. The use of different mesh sizes, inconsistency in trawling duration, speed and distance, and in the net opening dimensions, make it impossible to compare the studies between each other. This review analyzes the methodologies and characteristics of Manta nets used for MPs sampling, discussing factors that can impact the efficiency of the sampling and the quantification of MPs, and proposes recommendations in order to improve and standardize the sampling protocol.
Gut Bacterial Flora of Open Nested Honeybee, Apis florea
Authors: Ganeshprasad D. N. , Lone Jafar K. , Jani Kunal , Shouche Yogesh S. , Khan Khalid Ali , Sayed Samy , Shukry Mustafa , Dar Showket A. , Mushtaq Muntazir , Sneharani A. H.
Published: April 2022

Honeybees are eusocial insects with close interaction with their surrounding environment. Gut microbiota in honeybees play a significant role in host health, biology, and interaction behavior with the surrounding environment. Apis florea, a wild bee, is the most primitive among all honeybees and is indigenous to the Indian subcontinent. Previous reports on reared honeybee species provide information on the gut microbiome. No such studies are reported on the gut microbiota of the wild honeybee species. This study aimed at studying the gut microbiome of the wild honeybee species, A. florea. The study reports the analysis and the identification of gut bacteria in the wild honeybee species, A. florea, employing culture-based and culture-independent methods. Cultured bacteria were identified and characterized by MALDI-TOF MS and 16S rRNA sequencing. A comprehensive analysis and identification of non-culturable bacteria were performed by 16S rRNA amplicon next-generation sequencing. This approach splits gut bacteria into four bacterial phyla, four families, and 10 genera in major. The dominant taxa identified in A. florea belonged to the family Enterobacteriaceae (79.47%), Lactobacillaceae (12.75%), Oxalobacteraceae (7.45%), and Nocardiaceae (0.13%). The prevailing bacteria belonged to Enterobacter, Lactobacillus, Escherichia-Shigella, Massilia, Klebsiella, Citrobacter, Pantoea, Serratia, Rhodococcus, and Morganella genera, belonging to phyla Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. This study observed the occurrence of a few bacteria that are not previously reported for their occurrence in other species of the Apis genus, making this investigation highly relevant with regard to the bee microbiome.
Relating Invasibility and Invasiveness: Case Study of Impatiens parviflora
Authors: Krokaitė Edvina , Janulionienė Rasa , Jocienė Lina , Rekašius Tomas , Rajackaitė Giedrė , Paulauskas Algimantas , Marozas Vitas , Kupčinskienė Eugenija
Published: April 2022

Data on alien species show that plant invasions are caused by a complex combination of characteristics of invasive species (invasiveness) and characteristics of invaded environment (invasibility).Impatiens parviflorais one of Europe’s top invasive species. The present study aimed to evaluate molecular diversity of populations of highly invasive in LithuaniaI. parvifloraby applying several DNA markers and relating genetic parameters to abiotic and biotic environment. For sampling, urban forests, riparian forests, and agrarian shrublands were selected. Three different DNA-based techniques, Simple Sequence Repeats (SSR), Inter Simple Sequence Repeat (ISSR) markers, and Random Amplified Polymorphic DNA (RAPD), were used for detecting genetic variation between 21 populations. All population individuals were monomorphic and homozygotic for four loci and heterozygotic for one locus by SSR analysis. Hierarchical analyses of molecular variance at ISSR and RAPD loci revealed significant differentiation of populations depending on geographic zones of the country. Bayesian Structure analyses of molecular data demonstrated existence of many genetic clusters and this finding is in support to multiple introduction of the species. The polymorphism extent at ISSR loci was positively correlated with the total coverage of herbaceous plant species. The coverage byI. parviflorawas negatively correlated with the total number of herbaceous species and light in the sites. Our results indicate that Lithuanian sites withI. parvifloramight be distinguished by high soil nutrient levels. According to the principal component analysis, the coverage byI. parviflorawas a more important variable of populations compared to molecular data or parameters of abiotic environment. In conclusion, complexity of invasibility and invasiveness factors determine the variability ofI. parviflorasites, including genetic traits, coverage of invasive species and conditions of environment that were significant and interrelated.
IFITM3, FURIN, ACE1, and TNF-α Genetic Association With COVID-19 Outcomes: Systematic Review and Meta-Analysis
Authors: de Araújo João Locke Ferreira , Menezes Diego , Aguiar Renato Santana de , Souza Renan Pedra de
Published: April 2022

Human polymorphisms may contribute to SARS-CoV-2 infection susceptibility and COVID-19 outcomes (asymptomatic presentation, severe COVID-19, death). We aimed to evaluate the association of IFITM3, FURIN, ACE1, and TNF-α genetic variants with both phenotypes using meta-analysis. The bibliographic search was conducted on the PubMed and Scielo databases covering reports published until February 8, 2022. Two independent researchers examined the study quality using the Q-Genie tool. Using the Mantel–Haenszel weighted means method, odds ratios were combined under both fixed- and random-effect models. Twenty-seven studies were included in the systematic review (five with IFITM3, two with Furin, three with TNF-α, and 17 with ACE1) and 22 in the meta-analysis (IFITM3 n = 3, TNF-α, and ACE1 n = 16). Meta-analysis indicated no association of 1) ACE1 rs4646994 and susceptibility, 2) ACE1 rs4646994 and asymptomatic COVID-19, 3) IFITM3 rs12252 and ICU hospitalization, and 4) TNF-α rs1800629 and death. On the other hand, significant results were found for ACE1 rs4646994 association with COVID-19 severity (11 studies, 692 severe cases, and 1,433 nonsevere controls). The ACE1 rs4646994 deletion allele showed increased odds for severe manifestation (OR: 1.45; 95% CI: 1.26–1.66). The homozygous deletion was a risk factor (OR: 1.49, 95% CI: 1.22–1.83), while homozygous insertion presented a protective effect (OR: 0.57, 95% CI: 0.45–0.74). Further reports are needed to verify this effect on populations with different ethnic backgrounds.

Systematic Review Registration: https://www.crd.york.ac.uk/prosperodisplay_record.php?ID=CRD42021268578, identifier CRD42021268578
Cellular Immune Signal Exchange From Ischemic Stroke to Intestinal Lesions Through Brain-Gut Axis
Authors: Yang Zizhao , Wei Fei , Zhang Bin , Luo Yun , Xing Xiaoyan , Wang Min , Chen Rongchang , Sun Guibo , Sun Xiaobo
Published: April 2022

As a vital pivot for the human circulatory system, the brain-gut axis is now being considered as an important channel for many of the small immune molecules’ transductions, including interleukins, interferons, neurotransmitters, peptides, and the chemokines penetrating the mesentery and blood brain barrier (BBB) during the development of an ischemic stroke (IS). Hypoxia-ischemia contributes to pituitary and neurofunctional disorders by interfering with the molecular signal release and communication then providing feedback to the gut. Suffering from such a disease on a long-term basis may cause the peripheral system’s homeostasis to become imbalanced, and it can also lead to multiple intestinal complications such as gut microbiota dysbiosis (GMD), inflammatory bowel disease (IBD), necrotizing enterocolitis (NEC), and even the tumorigenesis of colorectal carcinoma (CRC). Correspondingly, these complications will deteriorate the cerebral infarctions and, in patients suffering with IS, it can even ruin the brain’s immune system. This review summarized recent studies on abnormal immunological signal exchange mediated polarization subtype changes, in both macrophages and microglial cells as well as T-lymphocytes. How gut complications modulate the immune signal transduction from the brain are also elucidated and analyzed. The conclusions drawn in this review could provide guidance and novel strategies to benefit remedies for both IS and relative gut lesions from immune-prophylaxis and immunotherapy aspects.
Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia
Authors: Chen Yuwen , Luo Liping , Zheng Yongzhi , Zheng Qiaoyun , Zhang Na , Gan Donghui , Yirga Shimuye Kalayu , Lin Zhenxing , Shi Qizhen , Fu Lin , Hu Jianda , Chen Yingyu
Published: April 2022

Thrombocytopenia is a multifactorial condition that frequently involves concomitant defects in platelet production and clearance. The physiopathology of low platelet count in thrombocytopenia remains unclear. Sialylation on platelet membrane glycoprotein and follicular helper T cells (TFHs) are thought to be the novel platelet clearance pathways. The aim of this study was to clarify the roles of platelet desialylation and circulating TFHs in patients with immune thrombocytopenia (ITP) and non-ITP thrombocytopenia. We enrolled 190 patients with ITP and 94 patients with non-ITP related thrombocytopenia including case of aplastic anemia (AA) and myelodysplastic syndromes (MDS). One hundred and ten healthy volunteers were included as controls. We found significantly increased desialylated platelets in patients with ITP or thrombocytopenia in the context of AA and MDS. Platelet desialylation was negatively correlated with platelet count. Meanwhile, the circulating TFH levels in patients with thrombocytopenia were significantly higher than those of normal controls, and were positively correlated with desialylated platelet levels. Moreover, TFHs-related chemokine CXCL13 and apoptotic platelet levels were abnormally high in ITP patients. The upregulation of pro-apoptotic proteins and the activation of the MAPK/mTOR pathway were observed in the same cohort. These findings suggested that platelet desialylation and circulating TFHs may become the potential biomarkers for evaluating the disease process associated with thrombocytopenia in patients with ITP and non-ITP.
Identification of Genes Linking Natural Killer Cells to Apoptosis in Acute Myocardial Infarction and Ischemic Stroke
Authors: Feng Lele , Tian Ruofei , Mu Xingdou , Chen Cheng , Zhang Yuxi , Cui Jun , Song Yujie , Liu Yingying , Zhang Miao , Shi Lei , Sun Yang , Li Ling , Yi Wei
Published: April 2022

Natural killer (NK) cells are a type of innate lymphoid cell that are involved in the progression of acute myocardial infarction and ischemic stroke. Although multiple forms of programmed cell death are known to play important roles in these diseases, the correlation between NK cells and apoptosis-related genes during acute myocardial infarction and ischemic stroke remains unclear. In this study, we explored the distinct patterns of NK cell infiltration and apoptosis during the pathological progression of acute myocardial infarction and ischemic stroke using mRNA expression microarrays from the Gene Expression Omnibus database. Since the abundance of NK cells correlated positively with apoptosis in both diseases, we further examined the correlation between NK cell abundance and the expression of apoptosis-related genes. Interestingly, APAF1 and IRAK3 expression correlated negatively with NK cell abundance in both acute myocardial infarction and ischemic stroke, whereas ATM, CAPN1, IL1B, IL1R1, PRKACA, PRKACB, and TNFRSF1A correlated negatively with NK cell abundance in acute myocardial infarction. Together, these findings suggest that these apoptosis-related genes may play important roles in the mechanisms underlying the patterns of NK cell abundance and apoptosis in acute myocardial infarction and ischemic stroke. Our study, therefore, provides novel insights for the further elucidation of the pathogenic mechanism of ischemic injury in both the heart and the brain, as well as potential useful therapeutic targets.
Current Topics of Relevance to the Xenotransplantation of Free Pig Islets
Authors: Mou Lisha , Shi Guanghan , Cooper David K.C. , Lu Ying , Chen Jiao , Zhu Shufang , Deng Jing , Huang Yuanyuan , Ni Yong , Zhan Yongqiang , Cai Zhiming , Pu Zuhui
Published: April 2022

Pig islet xenotransplantation is a potential treatment for patients with type 1 diabetes. Current efforts are focused on identifying the optimal pig islet source and overcoming the immunological barrier. The optimal age of the pig donors remains controversial since both adult and neonatal pig islets have advantages. Isolation of adult islets using GMP grade collagenase has significantly improved the quantity and quality of adult islets, but neonatal islets can be isolated at a much lower cost. Certain culture media and coculture with mesenchymal stromal cells facilitate neonatal islet maturation and function. Genetic modification in pigs affords a promising strategy to prevent rejection. Deletion of expression of the three known carbohydrate xenoantigens (Gal, Neu5Gc, Sda) will certainly be beneficial in pig organ transplantation in humans, but this is not yet proven in islet transplantation, though the challenge of the ‘4th xenoantigen’ may prove problematic in nonhuman primate models. Blockade of the CD40/CD154 costimulation pathway leads to long-term islet graft survival (of up to 965 days). Anti-CD40mAbs have already been applied in phase II clinical trials of islet allotransplantation. Fc region-modified anti-CD154mAbs successfully prevent the thrombotic complications reported previously. In this review, we discuss (I) the optimal age of the islet-source pig, (ii) progress in genetic modification of pigs, (iii) the immunosuppressive regimen for pig islet xenotransplantation, and (iv) the reduction in the instant blood-mediated inflammatory reaction.
Oyster Aquaculture Site Selection Using High-Resolution Remote Sensing: A Case Study in the Gulf of Maine, United States
Authors: Jiang Binbin , Boss Emmanuel , Kiffney Thomas , Hesketh Gabriel , Bourdin Guillaume , Fan Daidu , Brady Damian C.
Published: April 2022

Aquaculture of the eastern oyster, Crassostrea virginica, is an expanding industry in the US, particularly in the Gulf of Maine. High resolution ocean color satellites launched in the last decade potentially provide aquaculture-relevant water-quality parameters at farm scales. However, these parameters, such as temperature, suspended particulate matter (SPM), and Chlorophyll a (Chl a), need to be derived by interested users. Water quality parameters are derived first by applying an atmospheric correction and then estimating the target parameter with a specific algorithm. Here, we use five atmospheric correction schemes and two algorithms to derive SPM and Chl a from the Sentinel 2A&B satellites’ multispectral instrument data. The best estimates of SPM and Chl a are determined by comparison with in situ observations from buoys. Together with SST from Landsat-8, we estimated an Oyster Suitability Index (OSI) along the transects in five estuaries in the Gulf of Maine as well as applied a novel particulate organic matter algorithm, a function of Chl a and SPM in low turbidity estuaries. We then apply the optimal approaches to derive water quality parameters to study five different estuaries in Maine and find that existing high-yield oyster aquaculture farms are found in areas with elevated OSI values. Additionally, we suggest new areas, currently under-exploited, where oyster aquaculture is likely to succeed, showcasing the utility of the approach.