bluuebunny/crossref_metadata_2025 huggingface dataset:
Gestational Diabetes Mellitus and Energy-Dense Diet: What Is the Role of the Insulin/IGF Axis?
Authors: Martín-Estal Irene , Castorena-Torres Fabiola
Published: June 2022

Gestational diabetes mellitus (GDM), is one of the most important pregnancy complications affecting approximately 15% of pregnant women. It is related to several gestational adverse outcomes in the fetus, e.g., macrosomia, shoulder dystocia, stillbirth, neonatal hypoglycemia, and respiratory distress. Women with GDM have a high risk of developing type 2 diabetes in the future. The pathogenesis of GDM is not completely understood; nevertheless, two factors could contribute to its development: β-cell dysfunction and failure in insulin secretion in response to insulin resistance induced by gestation. Both processes, together with the physiological activities of the insulin-like growth factors (IGFs), play a crucial role in glucose transport to the fetus and hence, fetal growth and development. IGFs (both IGF-1 and IGF-2) and their binding proteins (IGFBPs) regulate glucose metabolism and insulin sensitivity. Maternal nutritional status determines the health of the newborn, as it has substantial effects on fetal growth and development. Maternal obesity and an energy-dense diet can cause an increase in insulin and IGF-1 serum levels, producing metabolic disorders, such as insulin resistance, GDM, and high birth weight (> 4,000 g) due to a higher level of body fat. In this way, in GDM pregnancies there is an increase in IGF-1 and IGF-2 serum levels, and a decrease in IGFBP-1 and 4 serum levels, suggesting the crucial role of the insulin/IGF system in this gestational outcome. Here, the present review tries to elucidate the role that energy-dense diets and the insulin/IGF-1 signaling pathway perform in GDM pregnancies.
Chemometric Optimization of Solid-Phase Extraction Followed by Liquid Chromatography-Tandem Mass Spectrometry and Probabilistic Risk Assessment of Ultraviolet Filters in an Urban Recreational Lake
Authors: Lukić Jelena , Radulović Jelena , Lučić Milica , Đurkić Tatjana , Onjia Antonije
Published: June 2022

Solid-phase extraction (SPE) of eleven ultraviolet filters (UVFs): benzophenone-1 (BP-1); benzophenone-3 (BP-3); benzophenone-4 (BP-4); isoamyl p-methoxycinnamate (IAMC), homosalate (HMS); 4-hydroxybenzophenone (4-HB); 4-methylbenzylidene camphor (4-MBC); octocrylene (OC); octyl dimethyl-p-aminobenzoate (OD-PABA); 2-ethylhexyl-4-methoxycinnamate (EHMC); and avobenzone (AVO), has been optimized using Plackett-Burman design, Box-Behnken design, and Derrindzer desirability function. Of the six SPE variables studied, the most influencing is the type of eluent followed by pH and the methanol content in the rinsing solvent. A method with good analytical performance was obtained by applying optimal SPE conditions and liquid chromatography-tandem mass spectrometry (LC-MS/MS), with the method detection limit ranging from 0.1 to 5 ng/L, recovery from 44% to 99%, and relative standard deviation (RSD) within 19%. This method was used to analyze the content of UVFs in an urban lake (Sava Lake, Serbia). UVFs occurrence, geostatistical distribution, and associated environmental risk are highly dependent on recreational activities. The average concentrations of UVFs ranged from 0.3 to 113 ng/L, and the most present substance was EHMC, followed by 4-MBC and BP-3. The spatial distribution of the risk quotient (RQ = 0.04–1.7) inside the lake is highly correlated with the number of people bathing and swimming. Human exposure through the dermal pathway is higher than ingestion for most UVFs. Monte Carlo simulation of probabilistic risk assessment estimated the percentile P10, P50, P90 of 12.7; 17.3; 47.5 and 20.1; 27.6; 77.5 ng/kg∙day for total human exposure of adults and children, respectively. The sensitivity analysis revealed that the health risk estimate depends mostly on the content of EHMC, HMS, and 4-MBC, while the most influential exposure variables were human body weight and skin surface area. There is no serious concern to human health due to UVFs in the short term; however, a high ecological risk in some parts of the lake is estimated.
Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome
Authors: Ali Alghamdi Malak , Benabdelkamel Hicham , Masood Afshan , Saheb Sharif-Askari Narjes , Hachim Mahmood Y. , Alsheikh Hamad , Hamad Muddathir H. , Salih Mustafa A. , Bashiri Fahad A. , Alhasan Khalid , Kashour Tarek , Guatibonza Moreno Pilar , Schröder Sabine , Karageorgou Vasiliki , Bertoli-Avella Aida M. , Alkhalidi Hisham , Jamjoom Dima Z. , Alorainy Ibrahim A. , Alfadda Assim A. , Halwani Rabih
Published: June 2022

Galloway-Mowat syndrome is a rare autosomal recessive disease characterized by a unique combination of renal and neurological manifestations, including early-onset steroid-resistant nephrotic syndrome, microcephaly, psychomotor delay, and gyral abnormalities of the brain. Most patients die during early childhood. Here, we identified a novel homozygous O-sialoglycoprotein endopeptidase (OSGEP) variant, NM_017807.3:c.973C>G (p.Arg325Gly), in four affected individuals in an extended consanguineous family from Saudi Arabia. We have described the detailed clinical characterization, brain imaging results, and muscle biopsy findings. The described phenotype varied from embryonic lethality to early pregnancy loss or death at the age of 9. Renal disease is often the cause of death. Protein modeling of this OSGEP variant confirmed its pathogenicity. In addition, proteomic analysis of the affected patients proposed a link between the KEOPS complex function and human pathology and suggested potential pathogenic mechanisms.
Identification of Haplotypes Associated With Resistance to Bacterial Cold Water Disease in Rainbow Trout Using Whole-Genome Resequencing
Authors: Liu Sixin , Martin Kyle E. , Gao Guangtu , Long Roseanna , Evenhuis Jason P. , Leeds Timothy D. , Wiens Gregory D. , Palti Yniv
Published: June 2022

Bacterial cold water disease (BCWD) is an important disease in rainbow trout aquaculture. Previously, we have identified and validated two major QTL (quantitative trait loci) for BCWD resistance, located on chromosomes Omy08 and Omy25, in the odd-year Troutlodge May spawning population. We also demonstrated that marker-assisted selection (MAS) for BCWD resistance using the favorable haplotypes associated with the two major QTL is feasible. However, each favorable haplotype spans a large genomic region of 1.3–1.6 Mb. Recombination events within the haplotype regions will result in new haplotypes associated with BCWD resistance, which will reduce the accuracy of MAS for BCWD resistance over time. The objectives of this study were 1) to identify additional SNPs (single nucleotide polymorphisms) associated with BCWD resistance using whole-genome sequencing (WGS); 2) to validate the SNPs associated with BCWD resistance using family-based association mapping; 3) to refine the haplotypes associated with BCWD resistance; and 4) to evaluate MAS for BCWD resistance using the refined QTL haplotypes. Four consecutive generations of the Troutlodge May spawning population were evaluated for BCWD resistance. Parents and offspring were sequenced as individuals and in pools based on their BCWD phenotypes. Over 12 million SNPs were identified by mapping the sequences from the individuals and pools to the reference genome. SNPs with significantly different allele frequencies between the two BCWD phenotype groups were selected to develop SNP assays for family-based association mapping in three consecutive generations of the Troutlodge May spawning population. Among the 78 SNPs derived from WGS, 77 SNPs were associated with BCWD resistance in at least one of the three consecutive generations. The additional SNPs associated with BCWD resistance allowed us to reduce the physical sizes of haplotypes associated with BCWD resistance to less than 0.5 Mb. We also demonstrated that the refined QTL haplotypes can be used for MAS in the Troutlodge May spawning population. Therefore, the SNPs and haplotypes reported in this study provide additional resources for improvement of BCWD resistance in rainbow trout.
Heterologous Expression and Evaluation of Novel Plasmodium falciparum Transmission Blocking Vaccine Candidates
Authors: de Jong Roos M. , Singh Susheel K. , Teelen Karina , van de Vegte-Bolmer Marga , van Gemert Geert-Jan , Stone Will J. R. , Locke Emily , Plieskatt Jordan , Theisen Michael , Bousema Teun , Jore Matthijs M.
Published: June 2022

Malaria transmission blocking vaccines (TBV) aim to induce antibodies that can interrupt Plasmodium falciparum development in the mosquito midgut and thereby prevent onward malaria transmission. A limited number of TBV candidates have been identified and only three (Pfs25, Pfs230 and Pfs48/45) have entered clinical testing. While one of these candidates may emerge as a highly potent TBV candidate, it is premature to determine if they will generate sufficiently potent and sustained responses. It is therefore important to explore novel candidate antigens. We recently analyzed sera from naturally exposed individuals and found that the presence and/or intensity of antibodies against 12 novel putative surface expressed gametocyte antigens was associated with transmission reducing activity. In this study, protein fragments of these novel TBV candidates were designed and heterologously expressed in Drosophila melanogaster S2 cells and Lactococcus lactis. Eleven protein fragments, covering seven TBV candidates, were successfully produced. All tested antigens were recognized by antibodies from individuals living in malaria-endemic areas, indicating that native epitopes are present. All antigens induced antigen-specific antibody responses in mice. Two antigens induced antibodies that recognized a native protein in gametocyte extract, and antibodies elicited by four antigens recognized whole gametocytes. In particular, we found that antigen Pf3D7_0305300, a putative transporter, is abundantly expressed on the surface of gametocytes. However, none of the seven novel TBV candidates expressed here induced an antibody response that reduced parasite development in the mosquito midgut as assessed in the standard membrane feeding assay. Altogether, the antigen fragments used in this study did not prove to be promising transmission blocking vaccine constructs, but led to the identification of two gametocyte surface proteins that may provide new leads for studying gametocyte biology.
Peptidome Surveillance Across Evolving SARS-CoV-2 Lineages Reveals HLA Binding Conservation in Nucleocapsid Among Variants With Most Potential for T-Cell Epitope Loss in Spike
Authors: Wnuk Kamil , Sudol Jeremi , Spilman Patricia , Soon-Shiong Patrick
Published: June 2022

To provide a unique global view of the relative potential for evasion of CD8+ and CD4+ T cells by SARS-CoV-2 lineages as they evolve over time, we performed a comprehensive analysis of predicted HLA-I and HLA-II binding peptides in Spike (S) and Nucleocapsid (N) protein sequences of all available SARS-CoV-2 genomes as provided by NIH NCBI at a bi-monthly interval between March and December of 2021. A data supplement of all B.1.1.529 (Omicron) genomes from GISAID in early December was also used to capture the rapidly spreading variant. A key finding is that throughout continued viral evolution and increasing rates of mutations occurring at T-cell epitope hotspots, protein instances with worst-case binding loss did not become the most frequent for any Variant of Concern (VOC) or Variant of Interest (VOI) lineage; suggesting T-cell evasion is not likely to be a dominant evolutionary pressure on SARS-CoV-2. We also determined that throughout the course of the pandemic in 2021, there remained a relatively steady ratio of viral variants that exhibit conservation of epitopes in the N protein, despite significant potential for epitope loss in S relative to other lineages. We further localized conserved regions in N with high epitope yield potential, and illustrated heterogeneity in HLA-I binding across the S protein consistent with empirical observations. Although Omicron’s high volume of mutations caused it to exhibit more epitope loss potential than most frequently observed versions of proteins in almost all other VOCs, epitope candidates across its most frequent N proteins were still largely conserved. This analysis adds to the body of evidence suggesting that N may have merit as an additional antigen to elicit immune responses to vaccination with increased potential to provide sustained protection against COVID-19 disease in the face of emerging variants.
Pathogenetic Aspects of Systemic Sclerosis: A View Through the Prism of B Cells
Authors: Melissaropoulos Konstantinos , Iliopoulos George , Sakkas Lazaros I. , Daoussis Dimitrios
Published: June 2022

Systemic sclerosis (SSc) is a rare fibrotic rheumatic disease, associated with psychological distress and increased morbidity and mortality due to skin involvement and internal organ damage. The current understanding of the complex pathogenesis is yet incomplete and disease therapeutic algorithms are far from optimal. Immunologic aberrations are considered key factors for the disease, along with vascular involvement and excess fibrosis. Adaptive immunity and its specialized responses are an attractive research target and both T and B cells have been extensively studied in recent years. In the present review, the focus is placed on B cells in SSc. B cell homeostasis is deranged and B cell subsets exhibit an activated phenotype and abnormal receptor signaling. Autoantibodies are a hallmark of the disease and the current perception of their diagnostic and pathogenetic role is analyzed. In addition, B cell cytokine release and its effect on immunity and fibrosis are examined, together with B cell tissue infiltration of the skin and lung. These data support the concept of targeting B cells as part of the therapeutic plan for SSc through well designed clinical trials.
Fetotoxicity and Subacute Toxicity of Some Plants Involved in the Treatment of Infectious Diarrhea in Benin
Authors: Hounsa Edna , Dougnon Tamegnon Victorien , Agbankpe Alidehou Jerrold , Assogba Phénix , Koudokpon Charles Hornel , Klotoe Jean-Robert , Moussa Rachida Tari , Agbodjento Eric , Fabiyi Kafayath , Deguenon Esther , Bankole Honore Sourou , Diallo Aboudoulatif
Published: June 2022

This study aimed to provide data on the subacute toxicity and fetotoxicity of aqueous and hydroethanolic extracts of Daniellia oliveri (Rolfe) Hutch. & Dalziel, Anacardium occidentale L., Diospyros mespiliformis Hochst. ex A. DC., Khaya senegalensis (Desv.) A. Juss., Ocimum gratissimum L., Vernonia amygdalina Delile, Pterocarpus erinaceus Poir., and Manihot esculenta Crantz used in the treatment of diarrheal diseases in Benin. For subacute toxicity, each male and female Wistar rat received by esophageal gavage a maximum of 1000 mg/kg over 28 days following the Organization for Economic Co-operation and Development (OECD) Guideline No. 407. Bodyweight changes, biochemical and hematological parameters were assessed. The fetotoxicity of the extracts was evaluated on Dutch Blue hen eggs at 100 mg/kg and 300 mg/kg. The hatching rate, biochemical and hematological constants were subsequently determined. The subacute toxicity data did not indicate any mortality or signs of toxicity. Also, no significant difference in the bodyweight of the rats and the hematological parameters was noted. Concerning fetotoxicity, a low hatching rate (varying from 20% to 50%) was observed in the batches treated with the extracts at 300mg/kg compared to the rate obtained in the negative control batch (80%). The batches that received the hydroethanolic extracts of Vernonia amygdalina and Manihot esculenta at the tested doses had a hatching rate of 0%. When looking at hematological parameters, no significant difference was noted for all batches. However, an increase in the Aspartate Amino-Transferase (ASAT) values was noted in the batches that received the hydroethanolic extract of Khaya senegalensis and the aqueous extract of Diospyros mespiliformis at 100 and 300 mg/kg. These results explicitly show that the hydroethanolic extracts of Manihot esculenta and Vernonia amygdalina are fetotoxic at the tested doses.
Noctiluca Scintillans Distribution Largely Regulated by Phytoplankton Biomass in the East China Sea and Southern Yellow Sea
Authors: Sheng Liuyang , Jiang Zhibing , Sun Zhenhao , Zhu Yuanli , Zhai Hongchang , Ding Ling , Tong Mengmeng , Chen Jianfang , Chen Quanzhen , Zeng Jiangning
Published: June 2022

Noctiluca scintillans feeds on a large number of phytoplankton, including diatoms and dinoflagellates, and frequently forms a red tide in the East China Sea (ECS) and southern Yellow Sea (SYS). However, the spatiotemporal distribution pattern, controlling factors, and long-term change of N. scintillans in the ECS and SYS remain unclear. In the present study, we collected N. scintillans samples from the ECS and SYS throughout the four seasons of 2011. We sampled phytoplankton and environmental parameters simultaneously. The depth-integrated abundance (DIA) of N. scintillans was the highest and lowest in summer and winter, respectively. N. scintillans is distributed abundantly in eutrophic coastal waters and the Changjiang Estuary, which are characterized by high concentrations of phytoplankton and chlorophyll-a. A Spearman correlation test demonstrated that its DIA in the upper 30-m water column was generally more significantly associated with phytoplankton abundance and chlorophyll-a concentration than with temperature and salinity. The results of the generalized additive models revealed that chlorophyll-a concentration explained more of the variation in N. scintillans abundance than temperature and salinity throughout the year, particularly in warm seasons. These findings indicate that the seasonal and spatial changes of N. scintillans are largely regulated by phytoplankton biomass. Compared with the historical data from 1959 and 2002, the abundance of N. scintillans in the Changjiang Estuary increased considerably in 2011 with increasing phytoplankton abundance resulting from accelerated eutrophication and warming. These results clarify the controlling factors, red-tide formation mechanism, and changing trends associated with the N. scintillans in the ECS and SYS.
A Review: Contact Electrification on Special Interfaces
Authors: Zhang Wenhao , Shi Yuxiang , Li Yufang , Chen Xiangyu , Shen Honglie
Published: June 2022

The contact electrification of materials plays an important role in developing and applying triboelectric nanogenerators (TENGs). By exploring the contact electrification phenomena at different interfaces, we can improve the understanding of the electrification mechanism and expand the application field of TENGs. In this way, the rate of energy utilization can be improved while the harm caused by the electrostatic effect is reduced. This article systematically summarized the different interface contacts between the research status quo of electricity. This article expounds the solid–solid interface, liquid–solid interface, and liquid–liquid interface, as well as the gas and other interface contact electrification mechanism, and the research and application of these are introduced; finally, it prospects the contact between the different interfaces of electric potential applications as well as the challenge.
Experimental Study on UHPC-Based Grouting Materials and Mechanical Performance of Grouted Splice Sleeve Joints
Authors: Fu Tao , Hou Jianpu , Zhu Zhixin , Meng Lingxiao , Sun Zhonghua , Wang Kai , Ren Xiaoqian
Published: June 2022

The prefabricated concrete structure is regarded as the main body of the green construction technology, while the joint connection of the prefabricated components is the weak link of force. In addition, the grouting sleeve connection is a widely used connection method in the prefabricated component joints. The effective anchorage of reinforcement is realized by the implementation of a mechanical bite force, friction force and bonding force between reinforcement, grouting material and sleeve inner wall, respectively. Along these lines, in this work, a UHPC-based grouting material was prepared, and its main technical performance was tested. The influence of the grouting mix proportion and anchorage length on the stress performance was thoroughly investigated by carrying out a unidirectional tension test of eight grout-filled splice sleeves. The acquired results show that UHPC grouting containing micro and particles possess high mechanical strength and durability. The incorporation of UHPC grouting containing steel fibers can further improve the compressive and flexural strength. However, its fluidity will be reduced and grouting difficulties will be induced. For that reason, the utilization of UHPC-based grouting material without steel fibers is recommended. The grout-filled splice sleeve joints with UHPC meet also the strength requirements, and the sleeve can be found in the elastic stage in the test, indicating that sleeve joints possess a higher safety margin.
Atomic Force Microscopy of Polymer Brushes: Insights into Controversies
Authors: Argatov Ivan , Borodich Feodor M. , Jin Xiaoqing
Published: June 2022

Atomic force microscopes (AFM) and nanoindenters have been used for decades to evaluate mechanical properties of thin films at the nanoscale. It is argued that the elastic solutions to the indentation problem, which are most often associated with the names of Galin or Sneddon, may be used for extracting elastic contact modulus of bulk samples and continual films, while their application to contact between an AFM probe and a polymer brush is a priori questionable. This is because the character of compression of a polymer brush is drastically different from the response of an elastic half-space to indentation. In the present paper, a number of controversial issues related to the interpretation of the AFM data obtained for polymer brushes tested with a rigid probe are studied. In particular, a correct relation has been established between the constitutive equation for a single polymer brush in compression with a bare rigid surface and the constitutive equation for two identical polymer brushes in compression under the assumption of lack of interpenetration of compressed brushes. It is shown that the so-called apparent elastic modulus of a polymer brush introduced based on the Hertzian force-displacement relation depends on the indenter radius and, thus, may not serve as a characteristic of polymer brush. Also, the Derjaguin’s approximation-based method of identifying the point of initial contact is given in opposition to controversial methods, which are broadly based on the Hertzian contact mechanics.
A Predictive Web-Based Nomogram for Elderly Patients Newly Diagnosed as Uveal Melanoma: A Population-Based Study
Authors: Lv Meng , Yan Xinhua , Tu Yuanxing
Published: June 2022

Background

Uveal melanoma (UM) is the most frequent primary intraocular tumor in adults. This study aims to develop a nomogram and an individualized web-based calculator to predict the overall survival (OS) of elderly patients with UM.

Methods

Patients aged more than 60 years and diagnosed with UM were derived from the Surveillance, Epidemiology, and End Results (SEER) database during 2004–2015. The selected patients were randomly divided into training and validation cohorts. In the training cohort, the univariate and multivariate Cox analyses were carried out to determine the independent prognostic factors, and the predictors were integrated to establish a nomogram for predicting the 1-, 2-, and 3-year OS of elderly patients with UM. The discrimination of the nomogram was validated by receiver operating characteristic (ROC) curves and the area under the curve (AUC). The clinical practicability and accuracy of the nomogram were evaluated by the calibration curves and decision curve analysis (DCA). A web-based survival calculator was then constructed using a fitted survival prediction model (https://yuexinupup.shinyapps.io/DynNomapp/).

Results

A total of 1,427 patients with UM were included in this study. Age, T stage, N stage, M stage, marital status, sex, and radiotherapy (RT) were identified as independent prognostic factors. Based on the abovementioned factors, the nomogram was then constructed. The AUC values of the nomogram predicting 1-, 2-, and 3-year OS were 0.841, 0.801, and 0.768 in the training cohort, and 0.745, 0.717, and 0.710 in the validation cohort, respectively. The calibration curves and DCA also indicated the good performance of the predictive model.

Conclusion

This study established and validated a novel nomogram risk stratification model and a web-based survival rate calculator that can dynamically predict the long-term OS for elderly patients with UM.
Comparison of Vault Measurements Using a Swept-Source OCT-Based Optical Biometer and Anterior Segment OCT
Authors: Du Yali , Jin Chuang , Yin Shengjie , Wang Geng , Ma Qian , Li Yuancun , Chen Binyao , Wang Hongxi , Qiu Kunliang , Zhang Mingzhi
Published: June 2022

Background

To newly describe the vault measurement by using a widely used swept-source OCT-based optical biometer (IOLMaster700) and accessd the accuracy of vault measurement.

Methods

This was a retrospective, cross-sectional study. All patients underwent implantable Collamer lens (ICL) implantation surgery without complications. IOLMaster700 and AS-OCT analyses were conducted for each eye on the same day in the same condition. Measurements of anterior chamber depth (ACD), corneal-ICL (C-ICL), and vault values were made and recorded. The repeatability of the IOL Master700 measurements was quantified based upon intraclass correlation coefficient (ICC) values. Correlations between IOL Master700 and AS-OCT measurements made with these different analytical approaches were assessed. The agreement of instruments was evaluated using Bland-Altman plots.

Results

The IOLMaster700 instrument yielded highly reliable measurements of vault, C-ICL, and ACD (ICC = 0.996, 0.995, 0.995, respectively). Vault, C-ICL and ACD values as measured using the IOLMaster700, was slightly smaller than that measured via AS-OCT, but these differences were not significant (p = 0.652, p = 0.121 and p = 0.091, respectively). The vault, C-ICL, and ACD measurements by these two instruments were strongly correlated (r = 0.971, r = 0.944, and r = 0.963, respectively; all p < 0.001). The 95% limits of agreement for vault, C-ICL, and ACD measurements between the two devices were−0.08 to 0.08 mm,−0.14 to 0.11 mm, and−0.13 to 0.10 mm, respectively.

Conclusions

The IOLMasrer700 can measure implanted ICL vault with a high degree of accuracy and repeatability. Good correlations and agreement were observed between IOLMaster700 and AS-OCT in measuring vault, C-ICL, and ACD measurements.
The Severity of Acute Kidney and Lung Injuries Induced by Cecal Ligation and Puncture Is Attenuated by Menthol: Role of Proliferating Cell Nuclear Antigen and Apoptotic Markers
Authors: Anter Aliaa , Ahmed Al-Shaimaa F. , Hammad Asmaa S. A. , Almalki Waleed Hassan , Abdel Hafez Sara Mohamed Naguib , Kasem AlShaimaa W. , El-Moselhy Mohamed A. , Alrabia Mohammad W. , Ibrahim Ahmed R. N. , El-Daly Mahmoud
Published: June 2022

Objective

Sepsis-induced acute lung injury (ALI) and acute kidney injury (AKI) are major causes of mortality. Menthol is a natural compound that has anti-inflammatory and antioxidative actions. Since exaggerated inflammatory and oxidative stress are characteristics of sepsis, the aim of this study was to evaluate the effect of menthol against sepsis-induced mortality, ALI, and AKI.

Methods

The cecal ligation and puncture (CLP) procedure was employed as a model of sepsis. Rats were grouped into sham, sham-Menthol, CLP, and CLP-Menthol (100 mg/kg, p.o).

Key Findings

A survival study showed that menthol enhanced the survival after sepsis from 0% in septic group to 30%. Septic rats developed histological evidence of ALI and AKI. Menthol markedly suppressed sepsis induced elevation of tissue TNF-a, ameliorated sepsis-induced cleavage of caspase-3 and restored the antiapoptotic marker Bcl2.

Significance

We introduced a role of the proliferating cell nuclear antigen (PCNA) in these tissues with a possible link to the damage induced by sepsis. PCNA level was markedly reduced in septic animals and menthol ameliorated this effect. Our data provide novel evidence that menthol protects against organ damage and decreases mortality in experimental sepsis.
Symbiotic Modulation as a Driver of Niche Expansion of Coastal Plants in the San Juan Archipelago of Washington State
Authors: Redman Regina S. , Anderson Joe A. , Biaggi Taylor M. , Malmberg Katie E. L. , Rienstra Melissa N. , Weaver Jamie L. , Rodriguez Rusty J.
Published: June 2022

Modern evolutionary theory and population genetics posit that adaptation and habitat expansion of plants result from processes exclusive to their genomes. Here, we present studies showing that plants can grow across complex habitat gradients by modulating symbiotic associations with Class 2 fungal endophytes. Endophyte analysis of three native (Leymus mollis, Distichlis spicata, and Salicornia pacifica) and one invasive (Spartina anglica) plant growing across adjacent microhabitats in the San Juan Archipelago altered associations with Class 2 fungal endophytes in response to soil salinity levels. At the microhabitat interfaces where the gradation of salinity varied, the plants were colonized by endophytes from both microhabitats. A reciprocal transplant study along a salt gradient demonstrated that Leymus mollis (dunegrass) required endophytes indigenous to each microhabitat for optimal fitness and/or survival. In contrast, when dunegrass and Grindelia integrifolia (gumweed) were found growing in low salinity, but high drought habitats, these plant species had their own unique dominant endophyte association regardless of geographic proximity and conferred drought but not high salt stress tolerance. Modulation of endophyte abundance occurred in planta based on the ability of the symbiont to confer tolerance to the stress imposed on plants. The ability of an endophyte to confer appropriate stress tolerance resulted in a significant increase of in planta fungal abundance. Conversely, the inability of an endophyte to confer stress tolerance resulted in a decrease of in planta fungal abundance. Our studies indicate that Class 2 fungal endophytes can provide a symbiotic mechanism for niche expansion and phenotypic plasticity across environmental gradients.
TRAF3IP3 Is Cleaved by EV71 3C Protease and Exhibits Antiviral Activity
Authors: Li Hui , Yao Yunfang , Chen Yu , Zhang Shuangling , Deng Zhi , Qiao Wentao , Tan Juan
Published: June 2022

Enterovirus 71 (EV71) is one of the major pathogens of hand, foot, and mouth disease, which poses a major risk to public health and infant safety. 3C protease (3Cpro), a non-structural protein of EV71, promotes viral protein maturation by cleaving polyprotein precursors and facilitates viral immune escape by cleaving host proteins. In this study, we screened for human proteins that could interact with EV71 3Cpro using a yeast two-hybrid assay. Immune-associated protein TRAF3 Interacting Protein 3 (TRAF3IP3) was selected for further study. The results of co-immunoprecipitation and immunofluorescence demonstrated the interaction between TRAF3IP3 and EV71 3Cpro. A cleavage band was detected, indicating that both transfected 3Cpro and EV71 infection could cleave TRAF3IP3. 87Q-88G was identified as the only 3Cpro cleavage site in TRAF3IP3. In Jurkat and rhabdomyosarcoma (RD) cells, TRAF3IP3 inhibited EV71 replication, and 3Cpro cleavage partially resisted TRAF3IP3-induced inhibition. Additionally, the nuclear localization signal (NLS) and nuclear export signal (NES) of TRAF3IP3 were identified. The NES contributed to TRAF3IP3 alteration of 3Cpro localization and inhibition of EV71 replication. Together, these results indicate that TRAF3IP3 inhibits EV71 replication and 3Cpro resists such inhibition via proteolytic cleavage, providing a new example of virus-host interaction.
Broad-Spectrum Antimicrobial Action of Cell-Free Culture Extracts and Volatile Organic Compounds Produced by Endophytic Fungi Curvularia Eragrostidis
Authors: Santra Hiran K. , Banerjee Debdulal
Published: June 2022

Endophytes are the mutualistic microorganisms that reside within the host plant and promote plant growth in adverse conditions. Plants and their endophytes are engaged in a symbiotic relationship that enables endophytes to access bioactive genes of the ethnomedicinal plants, and, as a result, endophytes are constantly addressed in the sector of pharmaceuticals and agriculture for their multidomain bio-utility. The gradual increase of antimicrobial resistance can be effectively countered by the endophytic metabolites. In these circumstances, in the present investigation, endophyticCurvularia eragrostidisHelS1 was isolated from an ethnomedicinally valuable plantHelecteris isorafrom East India’s forests. The secondary volatile and non-volatile metabolites are extracted from HelS1 and are found to be effective broad-spectrum antimicrobials. A total of 26 secondary metabolites (9 volatiles and 17 non-volatiles) are extracted from the isolate, which exhibits effective antibacterial [against six Gram-positive and seven Gram-negative pathogens with a minimum inhibitory concentrations (MIC) value ranging from 12.5 to 400 μg ml–1] and antifungal (against seven fungal plant pathogens) activity. The secondary metabolite production was optimised by one variable at a time technique coupled with the response surface methodology. The results revealed that there was a 34% increase in antibacterial activity in parameters with 6.87 g L–1of fructose (as a carbon source), 3.79 g L–1of peptone (as a nitrogen source), pH 6.75, and an inoculation period of 191.5 h for fermentation. The volatile metabolite production was also found to be optimum when the medium was supplemented with yeast extract and urea (0.2 g L–1) along with dextrose (40 g L–1). Amongst extracted volatile metabolites, 1-H-indene 1 methanol acetate, tetroquinone,N,N-diphenyl-2-nitro-thio benzamide,Trans1, 2-diethyl-trans-2-decalinol, naphthalene, and azulene are found to be the most effective. Our investigation opens up opportunities in the sector of sustainable agriculture as well as the discovery of novel antimicrobials against dreadful phyto and human pathogens.
A Periplasmic Lanthanide Mediator, Lanmodulin, in Methylobacterium aquaticum Strain 22A
Authors: Fujitani Yoshiko , Shibata Takeshi , Tani Akio
Published: June 2022

Methylobacterium and Methylorubrum species oxidize methanol via pyrroloquinoline quinone-methanol dehydrogenases (MDHs). MDHs can be classified into two major groups, Ca2+-dependent MDH (MxaF) and lanthanide (Ln3+)-dependent MDH (XoxF), whose expression is regulated by the availability of Ln3+. A set of a siderophore, TonB-dependent receptor, and an ABC transporter that resembles the machinery for iron uptake is involved in the solubilization and transport of Ln3+. The transport of Ln3+ into the cytosol enhances XoxF expression. A unique protein named lanmodulin from Methylorubrum extorquens strain AM1 was identified as a specific Ln3+-binding protein, and its biological function was implicated to be an Ln3+ shuttle in the periplasm. In contrast, it remains unclear how Ln3+ levels in the cells are maintained, because Ln3+ is potentially deleterious to cellular systems due to its strong affinity to phosphate ions. In this study, we investigated the function of a lanmodulin homolog in Methylobacterium aquaticum strain 22A. The expression of a gene encoding lanmodulin (lanM) was induced in response to the presence of La3+. A recombinant LanM underwent conformational change upon La3+ binding. Phenotypic analyses on lanM deletion mutant and overexpressing strains showed that LanM is not necessary for the wild-type and XoxF-dependent mutant’s methylotrophic growth. We found that lanM expression was regulated by MxcQE (a two-component regulator for MxaF) and TonB_Ln (a TonB-dependent receptor for Ln3+). The expression level of mxcQE was altered to be negatively dependent on Ln3+ concentration in ∆lanM, whereas it was constant in the wild type. Furthermore, when exposed to La3+, ∆lanM showed an aggregating phenotype, cell membrane impairment, La deposition in the periplasm evidenced by electron microscopy, differential expression of proteins involved in membrane integrity and phosphate starvation, and possibly lower La content in the membrane vesicle (MV) fractions. Taken together, we concluded that lanmodulin is involved in the complex regulation mechanism of MDHs and homeostasis of cellular Ln levels by facilitating transport and MV-mediated excretion.
Exposure to Nepalese Propolis Alters the Metabolic State of Mycobacterium tuberculosis
Authors: Sawicki Rafał , Widelski Jarosław , Okińczyc Piotr , Truszkiewicz Wiesław , Glous Joanna , Sieniawska Elwira
Published: June 2022

Propolis is a natural product proved to be efficient against Mycobacterium tuberculosis. Although it is produced by bees, its active alcoholic-aqueous fraction contains plant-derived molecules. To gain some insight into its mechanism of antimycobacterial activity, we studied the metabolic changes in bacterial cells treated with extract of Trigona sp. propolis from Nepal. The detailed metabolomic and transcriptomic analysis performed in this study indicated target points in bacterial cells under propolis extract influence. The profile of lipids forming the outer and middle layer of the mycobacterial cell envelope was not changed by propolis treatment, however, fluctuations in the profiles of amphipathic glycerophospholipids were observed. The enrichment analysis revealed bacterial metabolic pathways affected by Trigona sp. propolis treatment. The early metabolic response involved much more pathways than observed after 48 h of incubation, however, the highest enrichment ratio was observed after 48 h, indicating the long-lasting influence of propolis. The early bacterial response was related to the increased demand for energy and upregulation of molecules involved in the formation of the cell membrane. The transcriptomic analysis confirmed that bacteria also suffered from oxidative stress, which was more pronounced on the second day of exposure. This was the first attempt to explain the action of Nepalese propolis extract against mycobacteria.
Biophysical Screening Pipeline for Cryo-EM Grid Preparation of Membrane Proteins
Authors: Niebling Stephan , Veith Katharina , Vollmer Benjamin , Lizarrondo Javier , Burastero Osvaldo , Schiller Janina , Struve García Angelica , Lewe Philipp , Seuring Carolin , Witt Susanne , García-Alai María
Published: June 2022

Successful sample preparation is the foundation to any structural biology technique. Membrane proteins are of particular interest as these are important targets for drug design, but also notoriously difficult to work with. For electron cryo-microscopy (cryo-EM), the biophysical characterization of sample purity, homogeneity, and integrity as well as biochemical activity is the prerequisite for the preparation of good quality cryo-EM grids as these factors impact the result of the computational reconstruction. Here, we present a quality control pipeline prior to single particle cryo-EM grid preparation using a combination of biophysical techniques to address the integrity, purity, and oligomeric states of membrane proteins and its complexes to enable reproducible conditions for sample vitrification. Differential scanning fluorimetry following the intrinsic protein fluorescence (nDSF) is used for optimizing buffer and detergent conditions, whereas mass photometry and dynamic light scattering are used to assess aggregation behavior, reconstitution efficiency, and oligomerization. The data collected on nDSF and mass photometry instruments can be analyzed with web servers publicly available at spc.embl-hamburg.de. Case studies to optimize conditions prior to cryo-EM sample preparation of membrane proteins present an example quality assessment to corroborate the usefulness of our pipeline.
On the Role of Neural Oscillations Across Timescales in Speech and Music Processing
Authors: Gnanateja G. Nike , Devaraju Dhatri S. , Heyne Matthias , Quique Yina M. , Sitek Kevin R. , Tardif Monique C. , Tessmer Rachel , Dial Heather R.
Published: June 2022

This mini review is aimed at a clinician-scientist seeking to understand the role of oscillations in neural processing and their functional relevance in speech and music perception. We present an overview of neural oscillations, methods used to study them, and their functional relevance with respect to music processing, aging, hearing loss, and disorders affecting speech and language. We first review the oscillatory frequency bands and their associations with speech and music processing. Next we describe commonly used metrics for quantifying neural oscillations, briefly touching upon the still-debated mechanisms underpinning oscillatory alignment. Following this, we highlight key findings from research on neural oscillations in speech and music perception, as well as contributions of this work to our understanding of disordered perception in clinical populations. Finally, we conclude with a look toward the future of oscillatory research in speech and music perception, including promising methods and potential avenues for future work. We note that the intention of this mini review is not to systematically review all literature on cortical tracking of speech and music. Rather, we seek to provide the clinician-scientist with foundational information that can be used to evaluate and design research studies targeting the functional role of oscillations in speech and music processing in typical and clinical populations.
Augmenting Human Selves Through Artificial Agents – Lessons From the Brain
Authors: Northoff Georg , Fraser Maia , Griffiths John , Pinotsis Dimitris A. , Panangaden Prakash , Moran Rosalyn , Friston Karl
Published: June 2022

Much of current artificial intelligence (AI) and the drive toward artificial general intelligence (AGI) focuses on developing machines for functional tasks that humans accomplish. These may be narrowly specified tasks as in AI, or more general tasks as in AGI – but typically these tasks do not target higher-level human cognitive abilities, such as consciousness or morality; these are left to the realm of so-called “strong AI” or “artificial consciousness.” In this paper, we focus on how a machine can augment humans rather than do what they do, and we extend this beyond AGI-style tasks to augmenting peculiarly personal human capacities, such as wellbeing and morality. We base this proposal on associating such capacities with the “self,” which we define as the “environment-agent nexus”; namely, a fine-tuned interaction of brain with environment in all its relevant variables. We consider richly adaptive architectures that have the potential to implement this interaction by taking lessons from the brain. In particular, we suggest conjoining the free energy principle (FEP) with the dynamic temporo-spatial (TSD) view of neuro-mental processes. Our proposed integration of FEP and TSD – in the implementation of artificial agents – offers a novel, expressive, and explainable way for artificial agents to adapt to different environmental contexts. The targeted applications are broad: from adaptive intelligence augmenting agents (IA’s) that assist psychiatric self-regulation to environmental disaster prediction and personal assistants. This reflects the central role of the mind and moral decision-making in most of what we do as humans.
Carmustine Wafers Implantation in Patients With Newly Diagnosed High Grade Glioma: Is It Still an Option?
Authors: Ricciardi Luca , Manini Ivana , Cesselli Daniela , Trungu Sokol , Piazza Amedeo , Mangraviti Antonella , Miscusi Massimo , Raco Antonino , Ius Tamara
Published: June 2022

Background

The implantation protocol for Carmustine Wafers (CWs) in high grade glioma (HGG) was developed to offer a bridge between surgical resection and adjuvant treatments, such as radio- and chemotherapy. In the last years, however, a widespread use of CWs has been limited due to uncertainties regarding efficacy, in addition to increased risk of infection and elevated costs of treatment.

Objective

The aims of our study were to investigate the epidemiology of patients that underwent surgery for HGG with CW implantation, in addition to the assessment of related complications, long-term overall survival (OS), and associated prognostic factors.

Methods

Three different medical databases were screened for conducting a systematic review of the literature, according to the PRISMA statement guidelines, evaluating the role of BCNU wafer implantation in patients with newly diagnosed HGG. The search query was based on a combination of medical subject headings (MeSH): “high grade glioma” [MeSH] AND “Carmustine” [MeSH] and free text terms: “surgery” OR “BCNU wafer” OR “Gliadel” OR “systemic treatment options” OR “overall survival.”

Results

The analysis of the meta-data demonstrated that there was a significant advantage in using CWs in newly diagnosed GBM in terms of OS, and a very low heterogeneity among the included studies [mean difference 2.64 (95% CI 0.85, 4.44); p = 0.004; I2149 = 0%]. Conversely, no significant difference between the two treatment groups in terms of PFS wad detected (p = 0.55). The analysis of complications showed a relatively higher rate in Carmustine implanted patients, although this difference was not significant (p = 0.53).

Conclusions

This meta-analysis seems to suggest that CWs implantation plays a significant role in improving the OS, when used in patients with newly diagnosed HGG. To minimize the risk of side effects, however, a carful patient selection based mainly on patient age and tumor volume should be desirable.
Different Doses of Intravenous Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: A Network Meta-Analysis
Authors: Li Bing-Hu , Wang Jian-Hong , Wang Han , Wang Duo-Zi , Yang Shu , Guo Fu-Qiang , Yu Neng-Wei
Published: June 2022

Background

This study aims to assess the efficacy and safety of different doses of intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) by adopting a network meta-analysis (NMA).

Methods

Studies comparing different doses of tPA in AIS were identified by retrieving electronic databases. NMAs of outcome measures included favorable functional outcome with a modified Rankin scale score (mRS) of 0 or 1 at 3 months after treatment (3M-FF), the functional independence with a mRS of 0, 1, or 2 at 3 months (3M-FI), symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M). Symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M) were assessed. Probability-based ranking and surface under cumulative ranking (SUCRA) were performed to identify the best dose of tPA. Inconsistency was evaluated by node-splitting analysis and a loop-specific approach. Publication bias was analyzed by funnel plots.

Results

A total of 14 studies were included in the quantitative synthesis. The NMA results revealed no difference among low (<0.7 mg/kg), moderate (0.8 mg/kg), and standard (0.9 mg/kg) doses of tPA with regard to efficacy and safety. The SUCRAs of 3M-FF and 3M-FI showed that the standard dose ranked first, the moderate dose ranked second, and the low dose ranked third. The SUCRA of sICH showed that the standard dose ranked first (78.1%), the low dose ranked second (61.0%), and the moderate dose ranked third (11.0%). The SUCRAs of 3-month mortality showed that the standard dose ranked first (73.2%), the moderate dose ranked second (40.8%), and the low dose ranked third (36.1%). No significant inconsistency was shown by node-splitting analysis and no publication bias was shown in funnel plots.

Conclusion

Lower dose tPA was comparable to the standard dose with regard to efficacy and safety. Based on the SUCRA results and American Heart Association/American Stroke Association (AHA/ASA) guidelines, the standard dose was still the optimal selection for AIS.