bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Woody Tree Thinning and Season Have Effect on Grass Species’ Composition and Biomass in a Semi-Arid Savanna? The Case of a Semi-Arid Savanna, Southern Ethiopia
Authors: Hare Malicha Loje , Xu Xin Wen , Wang Yong Dong , Yuan You , Gedda Abule Ebro
Published: July 2021

Encroachment of woody plants has negative effects on grass species and seriously challenging livestock production and pastoral livelihood in semi-arid savanna. The effect of thinning and season on grass species composition and biomass was investigated in lowland grazing area for three seasons. The study consisted of 15 plots (each 50 m × 50 m), thinned to differing intensities. The plots were located next to each other on a homogeneous area of 3.8 ha. Five thinning intensities (0, 25, 50, 75, and 100%) were allocated randomly to the plots and replicated three times. The 0% plot was left unthinned referred to as the control plot. The remaining plots were thinned to the equivalents of 25, 50, 75, and 100% of the tree density of that of the control plot. A two-way analysis of variance and Tukey Honest Significant Differences tests were used to compare responses of grass species. Ordination of variables was carried out by multivariate technique using correspondence analysis to explore the similarity relationship of plots, seasons and species. The differences in species composition and biomass in the control and the thinned plots were significant (p< 0.05). Higher grass species composition and biomass were documented in thinned plots than in the control plot. Species abundance in thinned plots ranged from 11 to 12, while that of the 0% plot was six species. Grass biomass (Kg ha-1) varied from 2,688.4 ± 736.8 to 5,035.8 ± 743.9 across thinned plots, whereas in the control plot the yield was 885.8 ± 369.1. The result showed that grass species composition and biomass increased with the increasing intensity of thinning. Grass values appeared to be optimum at the heavy intensity of thinning woody plants. Seasons were also significant with the highest values recorded in the rainy season. Rainfall played an important role by interacting with thinning and influenced total grass values. Overall, thinning that combined improved soil moisture negatively influenced woody cover and enhanced grass species composition and biomass production. Thinning of bushes to the 75% of tree density would sustain the original savanna and maximize forage production for grazers.
Identification of CXCL10-Relevant Tumor Microenvironment Characterization and Clinical Outcome in Ovarian Cancer
Authors: Jin Jing , Li Yi , Muluh Tobias Achu , Zhi Liangke , Zhao Qijie
Published: July 2021

Background

Chemokines are implicated in tumor microenvironment (TME) cell infiltration. Development of ovarian cancer involves heterologous cells together with the adjacent microenvironment. Nonetheless, our understanding of the chemokine-related TME characteristics in ovarian cancer remains obscure.

Methods

In this large-scale multi-platform study of 10 microarray datasets consisting of 1,673 ovarian cancer patients, we comprehensively evaluated CXCL10 and CXCL9 expression risk classifications for predicting overall survival (OS) and TME immune characteristics. The cross-validation between a standard cohort (TCGA: The Cancer Genome Atlas) and three test cohorts (GEO: Gene-Expression Omnibus) was applied. We investigated differences in the biological functions and the underlying mechanisms between high- and low-risk classifications.

Results

We identified that evaluation of CXCL10 expression could predict the tumor development, immune cell infiltration, TME signature, genetic alteration, and patient prognosis in ovarian cancer. Low-risk classification was characterized by high CXCL10 expression and prolonged prognosis, which was positively associated with specific immune cell infiltration (i.e., T cells, DCs, aDC, and Th2 cells) and TME immune-relevant signatures. Meanwhile, the high-risk classification was defined by lower CXCL10/CXCL9 expression and relevant poor prognosis and immune infiltrations. The CXCL10-based low-risk classification was also linked to antitumor biological function of specific immune gene sets, such as IL2-STAT5 signaling. Additionally, a mutational pattern featured by enrichment of C > T transition was further identified to be associated with immune cell infiltration.

Conclusions

This work proposed a promising biomarker for evaluating TME immune characteristics and clinical outcomes in patients with ovarian cancer. Estimation of CXCL10 risk pattern sheds a novel insight on ovarian cancer TME immune characteristics and provides strategies for ovarian cancer immunotherapy.
Identification and Splicing Characterization of Novel TMC6 and TMC8 Variants Associated With Epidermodysplasia Verruciformis in Three Chinese Families
Authors: Wang Rongrong , Liu Jiawei , Yang Xueting , Habulieti Xiaerbati , Yu Xue , Sun Liwei , Zhang Han , Sun Yang , Ma Donglai , Zhang Xue
Published: July 2021

Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to human beta papillomavirus infections and a particular propensity to develop non-melanoma skin cancers (NMSCs). The majority of EV cases are caused by biallelic null variants in TMC6, TMC8, and CIB1. This study aimed to identify disease-causing variants in three Chinese families with EV and to elucidate their molecular pathogenesis.

Methods: Genomic DNA from the probands of three EV families was analyzed by whole-exome sequencing (WES). cDNA sequencing was performed to investigate abnormal splicing of the variants. Quantitative RT-PCR (qRT-PCR) was conducted to quantify the mRNA expression of mutant TMC6 and TMC8.

Results: Whole-exome sequencing identified two novel homozygous variants (c.2278-2A > G in TMC6 and c.559G > A in TMC8) in families 1 and 2, respectively. In family 3, WES revealed a recurrent and a novel compound heterozygous variant, c.559G > A and c.1389G > A, in TMC8. The c.2278-2A > G TMC6 variant led to the skipping of exon 19 and resulted in premature termination at codon 776. Subsequent qRT-PCR revealed that the aberrantly spliced transcript was partly degraded. Notably, the TMC8 c.559G > A variant created a novel acceptor splice site at c.561 and yielded three different aberrant transcripts. qRT-PCR revealed that most of the mutant transcripts were degraded via nonsense-mediated mRNA decay (NMD).

Conclusion: We identified three novel disease-causing variants in TMC6 or TMC8 in three Chinese families with EV. The EV phenotypes of the three patients were due to a reduction in TMC6 or TMC8. Our findings expand the genetic causes of EV in the Chinese population.
Multifaceted Impacts of Periodontal Pathogens in Disorders of the Intestinal Barrier
Authors: Liu Yingman , Huang Wenxuan , Wang Jiaqi , Ma Jiaojiao , Zhang Manman , Lu Xiaoying , Liu Jie , Kou Yurong
Published: July 2021

Periodontal disease, a common inflammatory disease, is considered a hazardous factor that contributes to the development of diseases of the digestive system as well as other systems. The bridge between periodontitis and systemic diseases is believed to be periodontal pathogens. The intestine, as part of the lower gastrointestinal tract, has a close connection with the oral cavity. Within the intestine, the intestinal barrier acts as a multifunctional system including microbial, mucous, physical and immune barrier. The intestinal barrier forms the body’s first line of defense against external pathogens; its breakdown can lead to pathological changes in the gut and other organs or systems. Reports in the literature have described how oral periodontal pathogens and pathobiont-reactive immune cells can transmigrate to the intestinal mucosa, causing the destruction of intestinal barrier homeostasis. Such findings might lead to novel ideas for investigating the relationship between periodontal disease and other systemic diseases. This review summarizes studies on the effects of periodontal pathogens on the intestinal barrier, which might contribute to understanding the link between periodontitis and gastrointestinal diseases.
Antibody Mediated Immunity to SARS-CoV-2 and Human Coronaviruses: Multiplex Beads Assay and Volumetric Absorptive Microsampling to Generate Immune Repertoire Cartography
Authors: Wang Jiong , Li Dongmei , Zhou Qian , Wiltse Alexander , Zand Martin S.
Published: July 2021

The COVID-19 pandemic is caused by SARS-CoV-2, a novel zoonotic coronavirus. Emerging evidence indicates that preexisting humoral immunity against other seasonal human coronaviruses (HCoVs) plays a critical role in the specific antibody response to SARS-CoV-2. However, current work to assess the effects of preexisting and cross-reactive anti-HCoVs antibodies has been limited. To address this issue, we have adapted our previously reported multiplex assay to simultaneously and quantitatively measure anti-HCoV antibodies. The full mPlex-CoV panel covers the spike (S) and nucleocapsid (N) proteins of three highly pathogenic HCoVs (SARS-CoV-1, SARS-CoV-2, MERS) and four human seasonal strains (OC43, HKU1, NL63, 229E). Combining this assay with volumetric absorptive microsampling (VAMS), we measured the anti-HCoV IgG, IgA, and IgM antibodies in fingerstick blood samples. The results demonstrate that the mPlex-CoV assay has high specificity and sensitivity. It can detect strain-specific anti-HCoV antibodies down to 0.1 ng/ml with 4 log assay range and with low intra- and inter-assay coefficients of variation (%CV). We also estimate multiple strain HCoVs IgG, IgA and IgM concentration in VAMS samples in three categories of subjects: pre-COVID-19 (n=21), post-COVID-19 convalescents (n=19), and COVID-19 vaccine recipients (n=14). Using metric multidimensional scaling (MDS) analysis, HCoVs IgG concentrations in fingerstick blood samples were well separated between the pre-COVID-19, post-COVID-19 convalescents, and COVID-19 vaccine recipients. In addition, we demonstrate how multi-dimensional scaling analysis can be used to visualize IgG mediated antibody immunity against multiple human coronaviruses. We conclude that the combination of VAMS and the mPlex-Cov assay is well suited to performing remote study sample collection under pandemic conditions to monitor HCoVs antibody responses in population studies.
Combined Blockade of GARP:TGF-β1 and PD-1 Increases Infiltration of T Cells and Density of Pericyte-Covered GARP+ Blood Vessels in Mouse MC38 Tumors
Authors: Bertrand Charlotte , Van Meerbeeck Pierre , de Streel Grégoire , Vaherto-Bleeckx Noora , Benhaddi Fatima , Rouaud Loïc , Noël Agnès , Coulie Pierre G. , van Baren Nicolas , Lucas Sophie
Published: July 2021

When combined with anti-PD-1, monoclonal antibodies (mAbs) against GARP:TGF-β1 complexes induced more frequent immune-mediated rejections of CT26 and MC38 murine tumors than anti-PD-1 alone. In both types of tumors, the activity of anti-GARP:TGF-β1 mAbs resulted from blocking active TGF-β1 production and immunosuppression by GARP-expressing regulatory T cells. In CT26 tumors, combined GARP:TGF-β1/PD-1 blockade did not augment the infiltration of T cells, but did increase the effector functions of already present anti-tumor T cells. Here we show that, in contrast, in MC38, combined GARP:TGF-β1/PD-1 blockade increased infiltration of T cells, as a result of increased extravasation of T cells from blood vessels. Unexpectedly, combined GARP:TGF-β1/PD-1 blockade also increased the density of GARP+blood vessels covered by pericytes in MC38, but not in CT26 tumors. This appears to occur because anti-GARP:TGF-β1, by blocking TGF-β1 signals, favors the proliferation of and expression of adhesion molecules such as E-selectin by blood endothelial cells. The resulting densification of intratumoral blood vasculature probably contributes to increased T cell infiltration and to the therapeutic efficacy of GARP:TGF-β1/PD-1 blockade in MC38. We conclude from these distinct observations in MC38 and CT26, that the combined blockades of GARP:TGF-β1 and PD-1 can exert anti-tumor activityviamultiple mechanisms, including the densification and normalization of intratumoral blood vasculature, the increase of T cell infiltration into the tumor and the increase of the effector functions of intratumoral tumor-specific T cells. This may prove important for the selection of cancer patients who could benefit from combined GARP:TGF-β1/PD-1 blockade in the clinics.
Ongoing Exposure to Peritoneal Dialysis Fluid Alters Resident Peritoneal Macrophage Phenotype and Activation Propensity
Authors: Sutherland Tara E. , Shaw Tovah N. , Lennon Rachel , Herrick Sarah E. , Rückerl Dominik
Published: July 2021

Peritoneal dialysis (PD) is a more continuous alternative to haemodialysis, for patients with chronic kidney disease, with considerable initial benefits for survival, patient independence and healthcare costs. However, long-term PD is associated with significant pathology, negating the positive effects over haemodialysis. Importantly, peritonitis and activation of macrophages is closely associated with disease progression and treatment failure. However, recent advances in macrophage biology suggest opposite functions for macrophages of different cellular origins. While monocyte-derived macrophages promote disease progression in some models of fibrosis, tissue resident macrophages have rather been associated with protective roles. Thus, we aimed to identify the relative contribution of tissue resident macrophages to PD induced inflammation in mice. Unexpectedly, we found an incremental loss of homeostatic characteristics, anti-inflammatory and efferocytic functionality in peritoneal resident macrophages, accompanied by enhanced inflammatory responses to external stimuli. Moreover, presence of glucose degradation products within the dialysis fluid led to markedly enhanced inflammation and almost complete disappearance of tissue resident cells. Thus, alterations in tissue resident macrophages may render long-term PD patients sensitive to developing peritonitis and consequently fibrosis/sclerosis.
Genetically Determined Chronic Low-Grade Inflammation and Hundreds of Health Outcomes in the UK Biobank and the FinnGen Population: A Phenome-Wide Mendelian Randomization Study
Authors: Si Shucheng , Li Jiqing , Tewara Marlvin Anemey , Xue Fuzhong
Published: July 2021

Background

C-reactive protein (CRP) has been used as a biomarker of chronic low-grade inflammation in observational studies. We aimed to determine whether genetically determined CRP was associated with hundreds of human phenotypes to guide anti-inflammatory interventions.

Methods

We used individual data from the UK Biobank to perform a phenome-wide two-stage least squares (2SLS) Mendelian randomization (MR) analysis for CRP with 879 diseases. Summary-level data from the FinnGen consortium were utilized to perform phenome-wide two-sample MR analysis on 821 phenotypes. Systematic two-sample MR methods included MR-IVW, MR-WME, MR-Mod, and MR-PRESSO as sensitivity analyses combined with multivariable MR to identify robust associations. Genetic correlation analysis was applied to identify shared genetic risks.

Results

We found genetically determined CRP was robustly associated with 15 diseases in the UK Biobank and 11 diseases in the FinnGen population (P < 0.05 for all MR analyses). CRP was positively associated with tongue cancer, bronchitis, hydronephrosis, and acute pancreatitis and negatively associated with colorectal cancer, colon cancer, cerebral ischemia, electrolyte imbalance, Parkinson’s disease, epilepsy, anemia of chronic disease, encephalitis, psychophysical visual disturbances, and aseptic necrosis of bone in the UK Biobank. There were positive associations with impetigo, vascular dementia, bipolar disorders, hypercholesterolemia, vertigo, and neurological diseases, and negative correlations with degenerative macular diseases, metatarsalgia, interstitial lung disease, and idiopathic pulmonary fibrosis, and others. in the FinnGen population. The electrolyte imbalance and anemia of chronic disease in UK Biobank and hypercholesterolemia and neurological diseases in FinnGen pass the FDR corrections. Neurological diseases and bipolar disorders also presented positive genetic correlations with CRP. We found no overlapping causal associations between the populations. Previous causal evidence also failed to support these associations (except for bipolar disorders).

Conclusions

Genetically determined CRP was robustly associated with several diseases in the UK Biobank and the FinnGen population, but could not be replicated, suggesting heterogeneous and non-repeatable effects of CRP across populations. This implies that interventions at CRP are unlikely to result in decreased risk for most human diseases in the general population but may benefit specific high-risk populations. The limited causal evidence and potential double-sided effects remind us to be cautious about CRP interventions.
Engineered T Cell Therapy for Gynecologic Malignancies: Challenges and Opportunities
Authors: Xu Yifan , Jiang Jin , Wang Yutong , Wang Wei , Li Haokun , Lai Wenyu , Zhou Zhipeng , Zhu Wei , Xiang Zheng , Wang Zhiming , Zhu Zhe , Yu Lingfeng , Huang Xiaolan , Zheng Hua , Wu Sha
Published: July 2021

Gynecologic malignancies, mainly including ovarian cancer, cervical cancer and endometrial cancer, are leading causes of death among women worldwide with high incidence and mortality rate. Recently, adoptive T cell therapy (ACT) using engineered T cells redirected by genes which encode for tumor-specific T cell receptors (TCRs) or chimeric antigen receptors (CARs) has demonstrated a delightful potency in B cell lymphoma treatment. Researches impelling ACT to be applied in treating solid tumors like gynecologic tumors are ongoing. This review summarizes the preclinical research and clinical application of engineered T cells therapy for gynecologic cancer in order to arouse new thoughts for remedies of this disease.
HLA Does Not Impact on Short-Medium-Term Antibody Response to Preventive Anti-SARS-Cov-2 Vaccine
Authors: Ragone Concetta , Meola Serena , Fiorillo Pasqualina C. , Penta Roberta , Auriemma Laura , Tornesello Maria Lina , Miscio Leonardo , Cavalcanti Ernesta , Botti Gerardo , Buonaguro Franco M. , Bianchi Attilio , Buonaguro Luigi , Tagliamonte Maria
Published: July 2021

The response to anti-SARS-Cov-2 preventive vaccine shows high interpersonal variability at short and medium term. One of the explanations might be the individual HLA allelic variants. Indeed, B cell response is stimulated and sustained by CD4+ T helper cells activated by antigens presented by HLA-class II alleles on antigen-presenting cells (APCs). The impact of the number of antigens binding to HLA class-II alleles on the antibody response to the COVID vaccine has been assessed in a cohort of 56 healthcare workers who received the full schedule of the Pfizer-BioNTech BNT162b2 vaccine. Such vaccine is based on the entire spike protein of the SARS-CoV-2. Ab titers have been evaluated 2 weeks after the first dose as well as 2 weeks and 4 months after the boosting dose. HLA-DRB1 and DBQ1 for each of the vaccinees have been assessed, and strong binders have been predicted. The analysis showed no significant correlation between the short-medium-term Ab titers and the number of strong binders (SB) for each individual. These results indicate that levels of Ab response to the spike glycoprotein is not dependent on HLA class II allele, suggesting an equivalent efficacy at global level of the currently used vaccines. Furthermore, the pattern of persistence in Ab titer does not correlate with specific alleles or with the number of SBs.
Evidence-Based Selection on the Appropriate FIT Cut-Off Point in CRC Screening Programs in the COVID Pandemic
Authors: Aznar-Gimeno Rocío , Carrera-Lasfuentes Patricia , del-Hoyo-Alonso Rafael , Doblaré Manuel , Lanas Ángel
Published: July 2021

Background: The COVID pandemic has forced the closure of many colorectal cancer (CRC) screening programs. Resuming these programs is a priority, but fewer colonoscopies may be available. We developed an evidence-based tool for decision-making in CRC screening programs, based on a fecal hemoglobin immunological test (FIT), to optimize the strategy for screening a population for CRC.

Methods: We retrospectively analyzed data collected at a regional CRC screening program between February/2014 and November/2018. We investigated two different scenarios: not modifying vs. modifying the FIT cut-off value. We estimated program outcomes in the two scenarios by evaluating the numbers of cancers and adenomas missed or not diagnosed in due time (delayed).

Results: The current FIT cut-off (20-μg hemoglobin/g feces) led to 6,606 colonoscopies per 100,000 people invited annually. Without modifying this FIT cut-off value, when the optimal number of individuals invited for colonoscopies was reduced by 10–40%, a high number of CRCs and high-risk adenomas (34–135 and 73–288/100.000-people invited, respectively) will be undetected every year. When the FIT cut-off value was increased to where the colonoscopy demand matched the colonoscopy availability, the number of missed lesions per year was remarkably reduced (9–36 and 29–145/100.000 people, respectively). Moreover, the unmodified FIT scenario outcome was improved by prioritizing the selection process based on sex (males) and age, rather than randomly reducing the number invited.

Conclusions: Assuming a mismatch between the availability and demand for annual colonoscopies, increasing the FIT cut-off point was more effective than randomly reducing the number of people invited. Using specific risk factors to prioritize access to colonoscopies should be also considered.
Pathogenic Characterization of Clostridium perfringens Strains Isolated From Patients With Massive Intravascular Hemolysis
Authors: Suzaki Ai , Ohtani Kaori , Komine-Aizawa Shihoko , Matsumoto Asami , Kamiya Shigeru , Hayakawa Satoshi
Published: July 2021

Sepsis caused by Clostridium perfringens infection is rare but often fatal. The most serious complication leading to poor prognosis is massive intravascular hemolysis (MIH). However, the molecular mechanism underlying this fulminant form of hemolysis is unclear. In the present study, we employed 11 clinical strains isolated from patients with C. perfringens septicemia and subdivided these isolates into groups H and NH: septicemia with (n = 5) or without (n = 6) MIH, respectively. To elucidate the major pathogenic factors of MIH, biological features were compared between these groups. The isolates of two groups did not differ in growth rate, virulence-related gene expression, or phospholipase C (CPA) production. Erythrocyte hemolysis was predominantly observed in culture supernatants of the strains in group H, and the human erythrocyte hemolysis rate was significantly correlated with perfringolysin O (PFO) production. Correlations were also found among PFO production, human peripheral blood mononuclear cell (PBMC) cytotoxicity, and production of interleukin-6 (IL-6) and interleukin-8 (IL-8) by human PBMCs. Analysis of proinflammatory cytokines showed that PFO induced tumor necrosis factor-α (TNF-α), IL-5, IL-6, and IL-8 production more strongly than did CPA. PFO exerted potent cytotoxic and proinflammatory cytokine induction effects on human blood cells. PFO may be a major virulence factor of sepsis with MIH, and potent proinflammatory cytokine production induced by PFO may influence the rapid progression of this fatal disease caused by C. perfringens.
BETting on a Transcriptional Deficit as the Main Cause for Cornelia de Lange Syndrome
Authors: García-Gutiérrez Pablo , García-Domínguez Mario
Published: July 2021

Cornelia de Lange Syndrome (CdLS) is a human developmental syndrome with complex multisystem phenotypic features. It has been traditionally considered a cohesinopathy together with other phenotypically related diseases because of their association with mutations in subunits of the cohesin complex. Despite some overlap, the clinical manifestations of cohesinopathies vary considerably and, although their precise molecular mechanisms are not well defined yet, the potential pathomechanisms underlying these diverse developmental defects have been theoretically linked to alterations of the cohesin complex function. The cohesin complex plays a critical role in sister chromatid cohesion, but this function is not affected in CdLS. In the last decades, a non-cohesion-related function of this complex on transcriptional regulation has been well established and CdLS pathoetiology has been recently associated to gene expression deregulation. Up to 70% of CdLS cases are linked to mutations in the cohesin-loading factorNIPBL, which has been shown to play a prominent function on chromatin architecture and transcriptional regulation. Therefore, it has been suggested that CdLS can be considered a transcriptomopathy. Actually, CdLS-like phenotypes have been associated to mutations in chromatin-associated proteins, as KMT2A, AFF4, EP300, TAF6, SETD5, SMARCB1, MAU2, ZMYND11, MED13L, PHIP, ARID1B, NAA10, BRD4 or ANKRD11, most of which have no known direct association with cohesin. In the case of BRD4, a critical highly investigated transcriptional coregulator, an interaction with NIPBL has been recently revealed, providing evidence on their cooperation in transcriptional regulation of developmentally important genes. This new finding reinforces the notion of an altered gene expression program during development as the major etiological basis for CdLS. In this review, we intend to integrate the recent available evidence on the molecular mechanisms underlying the clinical manifestations of CdLS, highlighting data that favors a transcription-centered framework, which support the idea that CdLS could be conceptualized as a transcriptomopathy.
Habitual Physical Activity and Sleep Duration in Institutionalized Older Adults
Authors: Vogel Oliver , Niederer Daniel , Wilke Jan , El-Rajab Inaam , Vogt Lutz
Published: July 2021

Background: Physical activity and sleep quality are both major factors for improving one's health. Knowledge on the interactions of sleep quality and the amount of physical activity may be helpful for implementing multimodal health interventions in older adults.

Methods: This preliminary cross-sectional study is based on 64 participants [82.1 ± 6.4 years (MD ± SD); 22 male: 42 female]. The amount of physical activity was assessed by means of an accelerometer (MyWellness Key). Self-reported sleep parameters were obtained using the Pittsburgh Sleep Quality Index. The Barthel Index was used for physical disability rating. Bivariate correlations (Spearman's Rho) were used to explore relationships between the amount of physical activity and sleep quality. To analyse differences between categorial subgroups univariate ANOVAs were applied; in cases of significance, these were followed by Tukey-HSD post-hoc analyses.

Results: No linear association between physical activity and sleep quality was found (r = 0.119; p > 0.05). In subgroup analyses (n = 41, Barthel Index ≥90 pts, free of pre-existing conditions), physical activity levels differed significantly between groups of different sleep duration (≥7 h; ≥6 to <7 h; ≥5 to <6 h; <5h; p = 0.037).

Conclusion: There is no general association between higher activity levels and better sleep quality in the investigated cohort. However, a sleep duration of ≥5 to <6 h, corresponding to 7.6 h bed rest time, was associated with a higher level of physical activity.
The Roles of Lpar1 in Central Nervous System Disorders and Diseases
Authors: Xiao Dongqiong , Su Xiaojuan , Gao Hu , Li Xihong , Qu Yi
Published: July 2021

Lysophosphatidic acid receptor 1(Lpar1), which is found in almost all human tissues but is most abundant in the brain, can couple to G protein-coupled receptors (GPCRs) and participate in regulating cell proliferation, migration, survival, and apoptosis. Endothelial differentiation gene-2 receptor (Edg2), the protein encoded by theLpar1gene, is present on various cell types in the central nervous system (CNS), such as neural stem cells (NSCs), oligodendrocytes, neurons, astrocytes, and microglia.Lpar1deletion causes neurodevelopmental disorders and CNS diseases, such as brain cancer, neuropsychiatric disorders, demyelination diseases, and neuropathic pain. Here, we summarize the possible roles and mechanisms ofLpar1/Edg2 in CNS disorders and diseases and propose thatLpar1/Edg2 might be a potential therapeutic target for CNS disorders and diseases.
Complete Elimination of Peripheral Auditory Input Before Onset of Hearing Causes Long-Lasting Impaired Social Memory in Mice
Authors: Guo Rui , Li Yang , Liu Jiao , Gong Shusheng , Liu Ke
Published: July 2021

Hearing is one of the most important senses needed for survival, and its loss is an independent risk factor for dementia. Hearing loss (HL) can lead to communication difficulties, social isolation, and cognitive dysfunction. The hippocampus is a critical brain region being greatly involved in the formation of learning and memory and is critical not only for declarative memory but also for social memory. However, until today, whether HL can affect learning and memory is poorly understood. This study aimed to identify the relationship between HL and hippocampal-associated cognitive function. Mice with complete auditory input elimination before the onset of hearing were used as the animal model. They were first examined via auditory brainstem response (ABR) to confirm hearing elimination, and behavior estimations were applied to detect social memory capacity. We found significant impairment of social memory in mice with HL compared with the controls (p < 0.05); however, no significant differences were seen in the tests of novel object recognition, Morris water maze (MWM), and locomotion in the open field (p > 0.05). Therefore, our study firstly demonstrates that hearing input is required for the formation of social memory, and hearing stimuli play an important role in the development of normal cognitive ability.
Analysis of Thermal Sensitivity of Human Cytomegalovirus Assayed in the Conventional Conditions of a Human Milk Bank
Authors: Gayà Antoni , Rittà Massimo , Lembo David , Tonetto Paola , Cresi Francesco , Sottemano Stefano , Bertino Enrico , Moro Guido E. , Calvo Javier , Donalisio Manuela
Published: July 2021

One of the main concerns in human milk banks (HMB) is the transmission of human cytomegalovirus (HCMV) that could be present in the milk of infected women. There are consistent data showing that this virus is destroyed by Holder pasteurization (62.5°C for 30 min), but there is a lack of information about the response of the virus to the treatment at lower temperatures in strict HMB conditions. In order to analyze the effectiveness of different temperatures of pasteurization to eliminate HCMV in human milk, a preliminary assay was performed incubating HCMV-spiked raw milk samples from donor mothers at tested temperatures in a PCR thermocycler and the viral infectivity was assayed on cell cultures. No signs of viral replication were observed after treatments at temperatures equal or >53°C for 30, 20, and 10 min, 58°C for 5 min, 59°C for 2 min, and 60°C for 1 min. These data were confirmed in a pasteurizer-like model introducing HCMV-spiked milk in disposable baby bottles. No viral infectivity was detected on cell cultures after heating treatment of milk for 30 min at temperatures from 56 to 60°C. Thus, our results show that by using conventional pasteurization conditions, temperatures in the range of 56–60°C are enough to inactivate HCMV. Consequently, we consider that, in order to provide a higher quality product, the current recommendation to pasteurize both mother's own milk and donated milk at 62.5°C must be re-evaluated.
Macrophage Receptor With Collagenous Structure Polymorphism and Recurrent Respiratory Infections and Wheezing During Infancy: A 5-Years Follow-Up Study
Authors: Savino Francesco , Pellegrino Francesco , Daprà Valentina , Calvi Cristina , Alliaudi Carla , Montanari Paola , Galliano Ilaria , Bergallo Massimiliano
Published: July 2021

Background: Recurrent wheezing is a common clinical manifestation in childhood, and respiratory syncytial virus infection is a well-known risk factor. However, the genetic background favoring the development of recurrent wheezing is not fully understood. A possible role of macrophage receptor with collagenous gene (MARCO) polymorphism has been recently proposed.

Objective: To investigate a correlation between MARCO rs1318645 polymorphisms and susceptibility to recurrent wheezing during childhood.

Methods: We prospectively recruited 116 infants, of which 58 with respiratory syncytial virus bronchiolitis and 58 controls hospitalized at Regina Margherita Children's Hospital, Turin, Italy, between November 2014 and April 2015. All subjects were investigated for MARCO rs1318645 polymorphisms in the first period of life. Genotyping of rs1318645 was carried out by TaqMan mismatch amplification mutation assay real-time polymerase chain reaction procedure. Subjects were then enrolled in a 5-year follow-up study to monitor the occurrence of wheezing and respiratory infections.

Results: The analysis of MARCO rs1318645 of allelic frequencies shows an increasingly significant risk to develop recurrent infection (p = 0.00065) and recurrent wheezing (p = 0.000084) with a wild-type C allele compared with a G allele. No correlation was found between wheezing and past respiratory syncytial virus infection (p = 0.057) and for a history of atopy in the family (p = 0.859).

Conclusion: Our finding showed that subjects with C allelic MARCO rs1318645 polymorphism are at higher risk for recurrent infection and wheezing episodes during the first 5 years of life. Future studies of genetic associations should also consider other types of polymorphisms.
Neuropathic Injury–Induced Plasticity of GABAergic System in Peripheral Sensory Ganglia
Authors: Wang Caixue , Hao Han , He Kaitong , An Yating , Pu Zeyao , Gamper Nikita , Zhang Hailin , Du Xiaona
Published: July 2021

GABA is a major inhibitory neurotransmitter in the mammalian central nervous system (CNS). Inhibitory GABAA channel circuits in the dorsal spinal cord are the gatekeepers of the nociceptive input from the periphery to the CNS. Weakening of these spinal inhibitory mechanisms is a hallmark of chronic pain. Yet, recent studies have suggested the existence of an earlier GABAergic “gate” within the peripheral sensory ganglia. In this study, we performed systematic investigation of plastic changes of the GABA-related proteins in the dorsal root ganglion (DRG) in the process of neuropathic pain development. We found that chronic constriction injury (CCI) induced general downregulation of most GABAA channel subunits and the GABA-producing enzyme, glutamate decarboxylase, consistent with the weakening of the GABAergic inhibition at the periphery. Strikingly, the α5 GABAA subunit was consistently upregulated. Knock-down of the α5 subunit in vivo moderately alleviated neuropathic hyperalgesia. Our findings suggest that while the development of neuropathic pain is generally accompanied by weakening of the peripheral GABAergic system, the α5 GABAA subunit may have a unique pro-algesic role and, hence, might represent a new therapeutic target.
A Nested Eight-Channel Transmit Array With Open-Face Concept for Human Brain Imaging at 7 Tesla
Authors: Williams Sydney N. , Allwood-Spiers Sarah , McElhinney Paul , Paterson Gavin , Herrler Jürgen , Liebig Patrick , Nagel Armin M. , Foster John E. , Porter David A. , Gunamony Shajan
Published: July 2021

Purpose: Parallel transmit technology for MRI at 7 tesla will significantly benefit from high performance transmit arrays that offer high transmit efficiency and low mutual coupling between the individual array elements. A novel dual-mode transmit array with nested array elements has been developed to support imaging the human brain in both the single-channel (sTx) and parallel-transmit (pTx) excitation modes of a 7 tesla MRI scanner. In this work, the design, implementation, validation, specific absorption rate (SAR) management, and performance of the head coil is presented.

Methods: The transmit array consisted of a nested arrangement to improve decoupling between the second-neighboring elements. Two large cut-outs were introduced in the RF shield for an open-face design to reduce claustrophobia and to allow patient monitoring. A hardware interface allows the coil to be used in both the sTx and pTx modes. SAR monitoring is done with virtual observation points (VOP) derived from human body models. The transmit efficiency and coverage is compared with the commercial single-channel and parallel-transmit head coils.

Results: Decoupling inductors between the second-neighboring coil elements reduced the coupling to less than −20 dB. Local SAR estimates from the electromagnetic (EM) simulations were always less than the EM-based VOPs, which in turn were always less than scanner predictions and measurements for static and dynamic pTx waveforms. In sTx mode, we demonstrate improved coverage of the brain compared to the commercial sTx coil. The transmit efficiency is within 10% of the commercial pTx coil despite the two large cut-outs in the RF shield. In pTx mode, improved signal homogeneity was shown when the Universal Pulse was used for acquisition in vivo.

Conclusion: A novel head coil which includes a nested eight-channel transmit array has been presented. The large cut-outs improve patient monitoring and reduce claustrophobia. For pTx mode, the EM simulation and VOP-based SAR management provided greater flexibility to apply pTx methods without the limitations of SAR constraints. For scanning in vivo, the coil was shown to provide an improved coverage in sTx mode compared to a standard commercial head coil.
Cloning and Functional Identification of Phosphoethanolamine Methyltransferase in Soybean (Glycine max)
Authors: Ji Xiaomin , Wu Xiaoyue , Chen Wei , Yuan Qianhui , Shen Yixin , Chi Yingjun
Published: July 2021

Phosphoethanolamine methyltransferase (PEAMT), a kind of S-adenosylmethionine-dependent methyltransferases, plays an essential role in many biological processes of plants, such as cell metabolism, stress response, and signal transduction. It is the key rate-limiting enzyme that catalyzes the three-step methylation of ethanolamine-phosphate (P-EA) to phosphocholine (P-Cho). To understand the unique function of PEAMT in soybean (Glycine max) lipid synthesis, we cloned two phosphoethanolamine methyltransferase genes GmPEAMT1 and GmPEAMT2, and performed functional identification. Both GmPEAMT1 and GmPEAMT2 contain two methyltransferase domains. GmPEAMT1 has the closest relationship with MtPEAMT2, and GmPEAMT2 has the closest relationship with CcPEAMT. GmPEAMT1 and GmPEAMT2 are located in the nucleus and endoplasmic reticulum. There are many light response elements and plant hormone response elements in the promoters of GmPEAMT1 and GmPEAMT2, indicating that they may be involved in plant stress response. The yeast cho2 opi3 mutant, co-expressing Arabidopsis thaliana phospholipid methyltransferase (PLMT) and GmPEAMT1 or GmPEAMT2, can restore normal growth, indicating that GmPEAMTs can catalyze the methylation of phosphoethanolamine to phosphate monomethylethanolamine. The heterologous expression of GmPEAMT1 and GmPEAMT2 can partially restore the short root phenotype of the Arabidopsis thaliana peamt1 mutant, suggesting GmPEAMTs have similar but different functions to AtPEAMT1.
ATBS1-INTERACTING FACTOR 2 Negatively Modulates Pollen Production and Seed Formation in Arabidopsis
Authors: Kim Yoon , Kim Sun-Ho , Shin Dong-Min , Kim Soo-Hwan
Published: July 2021

ATBS1-INTERACTING FACTOR 2 (AIF2) is a non-DNA-binding basic-helix-loop-helix (bHLH) transcription factor. Here, we demonstrate that AIF2 negatively modulates brassinosteroid (BR)-induced, BRASSINAZOLE RESISTANT 1 (BZR1)-mediated pollen and seed formation. AIF2-overexpressing Arabidopsis plants (AIF2ox) showed defective pollen grains and seed production while two AIF2 knockout mutants, aif2-1 and aif2-1/aif4-1, displayed opposite phenotypes. Genes encoding BZR1-regulated positive factors of seed size determination (SHB1, IKU1, MINI3) were suppressed in AIF2ox and genes for negative factors (AP2 and ARF2) were enhanced. Surprisingly, BZR1-regulated pollen genes such as SPL, MS1, and TDF1 were aberrantly up-regulated in AIF2ox plants. This stage-independent abnormal expression may lead to a retarded and defective progression of microsporogenesis, producing abnormal tetrad microspores and pollen grains with less-effective pollen tube germination. Auxin plays important roles in proper development of flower and seeds: genes for auxin biosynthesis such as TCPs and YUCCAs as well as for positive auxin signalling such as ARFs were suppressed in AIF2ox flowers. Moreover, lipid biosynthesis- and sucrose transport-related genes were repressed, resulting in impaired starch accumulation. Contrarily, sucrose and BR repressed ectopic accumulation of AIF2, thereby increasing silique length and the number of seeds. Taken together, we propose that AIF2 is negatively involved in pollen development and seed formation, and that sucrose- and BR-induced repression of AIF2 positively promotes pollen production and seed formation in Arabidopsis.
Testing Whether Suicide Capability Has a Dynamic Propensity: The Role of Affect and Arousal on Momentary Fluctuations in Suicide Capability
Authors: Law Keyne C. , Anestis Michael D.
Published: July 2021

To prevent suicidal behaviors, it is crucial to understand the mechanisms and processes that enable an individual to act on suicidal thoughts. Suicide capability, which involves an increased pain tolerance and fearlessness of death, is a critical factor that enables an individual to endure the physical pain necessary to make a lethal suicide attempt. Extant research has largely conceptualized suicide capability as developing linearly in response to painful and provocative experiences, but the emerging literature on the temporal dynamics of suicide has been challenging the notion of linearity in suicide risk. Few studies have directly measured and compared changes in suicide capability in response to rumination on different affective states. We sought to experimentally test if rumination in the context of low vs. high arousal emotions will prompt distinct changes in two core components of suicide capability: pain tolerance and fearlessness of death on two undergraduate student samples. In both studies, participants provided measures of subjective emotional state as well as pain threshold, tolerance, and persistence before and after completing experimental manipulations which included both emotion and rumination induction procedures. In the second study, measures of fearlessness about death and physiological arousal (heart rate) were added to the experimental procedures. We found significant decreases in pain threshold, tolerance, and persistence following the experimental manipulations but found no main effects of rumination or suicide risk. These findings suggest that suicide capability can fluctuate but these changes may occur through a different mechanism and/or differ between individuals at varying levels of suicide risk.
Post-traumatic Stress Disorder in Sexually Abused Children: Secure Attachment as a Protective Factor
Authors: Ensink Karin , Fonagy Peter , Normandin Lina , Rozenberg Abby , Marquez Christina , Godbout Natacha , Borelli Jessica L.
Published: July 2021

The aim of the present study was to examine the hypothesis that attachment and childhood sexual abuse (CSA) interacted such that school aged CSA survivors with insecure attachment to parents would be at an elevated risk of developing post-traumatic stress disorder (PTSD) and trauma symptoms. Participants (n= 111, ages 7–12) comprised two groups, child CSA survivors (n= 43) and a matched comparison group of children (n= 68) recruited from the community. Children completed the Child Attachment Interview (CAI) as well as the Trauma Symptom Checklist for Children (TSCC). There was a significant interaction between sexual abuse history and attachment security, such that sexually abused children with insecure attachment representations had significantly more PTSD and trauma symptoms than sexually abused children with secure attachment to parents. The findings show that using a dual lens of attachment and CSA can facilitate the identification of children most at risk and has important implications for understanding risk and resilience processes.
Committing to Keep Clean: Nudging Complements Standard Policy Measures to Reduce Illegal Urban Garbage Disposal in a Neighborhood With High Levels of Social Cohesion
Authors: Merkelbach Inge , Dewies Malte , Denktas Semiha
Published: July 2021

Illegal garbage disposals are a persistent urban problem, resulting in high clean-up costs, and nuisance and decreased satisfaction with the neighborhood among residents. We compared three adjacent city-areas in Rotterdam in the Netherlands which, for 2 weeks, either: (1) no action to decrease illegal garbage disposals was taken; (2) standard door-to-door canvassing was carried out; or (3) door-to-door canvassing was enriched with several nudges, most importantly a commitment-nudge. The nudge treatment proved highly effective, reducing illegal disposals at post-test and follow-up (2 months later) with two-thirds, resulting in a very large effect size (d = 2.60). At post-test, standard door-to-door canvassing did not differ from the control treatment, but at follow-up results were comparable to the nudging-treatment. This could, however, be due to spill-over effects. Using a commitment nudge thus proved highly effective in decreasing illegal garbage disposals, however, effects might be specific to neighborhoods with strong social cohesion.
A Sound Prediction: EEG-Based Neural Synchrony Predicts Online Music Streams
Authors: Leeuwis Nikki , Pistone Daniela , Flick Niels , van Bommel Tom
Published: July 2021

Neuroforecasting predicts population-wide choices based on neural data of individuals and can be used, for example, in neuromarketing to estimate campaign successes. To deliver true value, the brain activity metrics should deliver predictive value above and beyond traditional stated preferences. Evidence from movie trailer research has proposed neural synchrony, which compares the similarity of brain responses across participants and has shown to be a promising tool in neuroforecasting for movie popularity. The music industry might also benefit from these increasingly accurate success predictors, but only one study has been forecasting music popularity, using functional magnetic resonance imaging measures. Current research validates the strength of neural synchrony as a predictive measure for popularity of music, making use of electroencephalogram to capture moment-to-moment neural similarity between respondents while they listen to music. Neural synchrony is demonstrated to be a significant predictor for public appreciation on Spotify 3 weeks and 10 months after the release of the albums, especially when combined with the release of a single. On an individual level, other brain measures were shown to relate to individual subjective likeability ratings, including Frontal Alpha Asymmetry and engagement when combined with the factors artist and single release. Our results show the predictive value of brain activity measures outperforms stated preferences. Especially, neural synchrony carries high predictive value for the popularity on Spotify, providing the music industry with an essential asset for efficient decision making and investments, in addition to other practical implications that include neuromarketing and advertising industries.