bluuebunny/crossref_metadata_2025 huggingface dataset:
Provenance of Aeolian Sediments in the Ordos Deserts and Its Implication for Weathering, Sedimentary Processes
Authors: Chen Guoxiang , Dong Zhibao , Li Chao , Shi Weikang , Shao Tianjie , Nan Weige , Yang Junhuai
Published: July 2021

Identifying the provenance of aeolian deposits in semi-arid zones of China is beneficial in understanding Earth’s surface processes and helping to alleviate ecological stress. In this paper, we use grain-size, geochemical elements, heavy-minerals, and quartz grain morphology data to investigate the potential source of aeolian sands from the Ordos Deserts (Mu Us Sandy Land and Hobq Desert). Sedimentological, geochemical and geomorphological results indicate that significant provenance differences exist among various parts of the Mu Us Sandy Land, i.e., aeolian sediments from the southwest region are obviously distinct from other areas in the Mu Us Sandy Land but show the same external provenance with the Hobq Desert referring to the sorting, mineralogical maturity, geochemical characteristics, heavy-minerals, and quartz grain morphology. Comparing the samples from the Ordos Deserts with felsic rocks from potential sources via a serious of geochemical methods, we conclude that: 1) Aeolian sands from other regions of the Mu Us are a mixture of binary provenance, i.e., one originated from local lacustrine sediments and underlying sandstones, and another from the Alxa Plateau (AP) carried by northwesterly Asian winter monsoon. 2) The fluvial deposits denuded from the Qilian Orogenic Belt in the Northeastern Tibetan Plateau (NTP) and carried by the Yellow River are likely the initial material source for the southwest region of the Mu Us Sandy Land and the Hobq Desert. 3) The Yellow River plays a significant and critical role in sediment transport for sand seas in arid and semi-arid areas of northern China.
Usefulness of FT3 to FT4 Ratio to Predict Mortality in Euthyroid Patients With Prior Cardiovascular Events Undergoing PCI: Five-Year Findings From a Large Single-Center Cohort Study
Authors: Yuan Deshan , Jia Sida , Zhu Pei , Zhang Ce , Liu Yue , Liu Ru , Xu Jingjing , Tang Xiaofang , Zhao Xueyan , Gao Runlin , Yang Yuejin , Xu Bo , Gao Zhan , Yuan Jinqing
Published: July 2021

Background

In euthyroid patients undergoing percutaneous coronary intervention (PCI), it is still unclear whether free triiodothyronine to free thyroxine (FT3/FT4) ratio can predict the recurrence of cardiovascular events (CVEs). We aim to investigate its association with recurrent long-term adverse events in this population.

Methods

3549 euthyroid patients with prior CVEs history undergoing PCI were consecutively enrolled in our study and subsequently divided into three FT3/FT4 ratio tertiles (T1<2.41, n=1170; 2.41≤T2<2.75, n=1198; T3>2.75, n=1181). The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), a composite of all-cause death, myocardial infarction, stroke and revascularization. The secondary endpoints were all-cause death and cardiac death.

Results

The median follow-up time was 5 years. The incidence of all-cause death, cardiac death and MACCE were significantly higher among patients in the lowest FT3/FT4 tertile (P<0.05). After adjustment of confounding factors, decreased FT3/FT4 ratio was independently associated with an increased risk of all-cause death (HR 1.82, 95% CI 1.13-2.93, P=0.014), cardiac death (HR 1.90, 95% CI 1.04-3.46, P=0.036) and MACCE (HR 1.33, 95% CI 1.10-1.60, P=0.003) which was driven mainly by all-cause death.

Conclusions

In euthyroid patients with prior cardiovascular events undergoing PCI, FT3/FT4 ratio might be a potential predictor of all-cause and cardiac mortality. Routine assessment of FT3/FT4 ratio might be a simple and effective tool for risk stratification in this specific patient population.
Human Growth and Growth Hormone: From Antiquity to the Recominant Age to the Future
Authors: Graber Evan , Reiter Edward O. , Rogol Alan D.
Published: July 2021

Since antiquity Man has been fascinated by the variations in human (and animal) growth. Stories and art abound about giants and little people. Modern genetics have solved some of etiologies at both extremes of growth. Serious study began with the pathophysiology of acromegaly followed by early attempts at treatment culminating in modern endoscopic surgery and multiple pharmacologic agents. Virtually at the same time experiments with the removal of the pituitary from laboratory animals noted the slowing or stopping of linear growth and then over a few decades the extraction and purification of a protein within the anterior pituitary that restored, partially or in full, the animal’s growth. Human growth hormone was purified decades after those from large animals and it was noted that it was species specific, that is, only primate growth hormone was metabolically active in primates. That was quite unlike the beef and pork insulins which revolutionized the care of children with diabetes mellitus. A number of studies included mild enzymatic digestion of beef growth hormone to determine if those “cores” had biologic activity in primates and man. Tantalizing data showed minimal but variable metabolic efficacy leading to the “active core” hypothesis, for these smaller peptides would be amenable to peptide synthesis in the time before recombinant DNA. Recombinant DNA changed the landscape remarkably promising nearly unlimited quantities of metabolically active hormone. Eight indications for therapeutic use have been approved by the Food and Drug Administration and a large number of clinical trials have been undertaken in multiple other conditions for which short stature in childhood is a sign. The future predicts other clinical indications for growth hormone therapy (and perhaps other components of the GH?IGF-1 axis), longer-acting analogues and perhaps a more physiologic method of administration as virtually all methods at present are far from physiologic.
A Catalog of Human Genes Associated With Pathozoospermia and Functional Characteristics of These Genes
Authors: Ignatieva Elena V. , Osadchuk Alexander V. , Kleshchev Maxim A. , Bogomolov Anton G. , Osadchuk Ludmila V.
Published: July 2021

Genetic causes of the global decline in male fertility are among the hot spots of scientific research in reproductive genetics. The most common way to evaluate male fertility in clinical trials is to determine semen quality. Lower semen quality is very often accompanied by subfertility or infertility, occurs in many diseases and can be caused by many factors, including genetic ones. The following forms of lowered semen quality (pathozoospermia) are known: azoospermia, oligozoospermia, asthenozoospermia, teratozoospermia, and some combined forms. To systematize information about the genetic basis of impaired spermatogenesis, we created a catalog of human genes associated with lowered semen quality (HGAPat) and analyzed their functional characteristics. The catalog comprises data on 126 human genes. Each entry of the catalog describes an association between an allelic variant of the gene and a particular form of lowered semen quality, extracted from the experimental study. Most genes included into the catalog are located on autosomes and are associated with such pathologies as non-obstructive azoospermia, oligozoospermia or asthenozoospermia. Slightly less than half of the included genes (43%) are expressed in the testes in a tissue-specific manner. Functional annotation of genes from the catalog showed that spermatogenic failure can be associated with mutations in genes that control biological processes essential for spermiogenesis (regulating DNA metabolism, cell division, formation of cellular structures, which provide cell movement) as well as with mutations in genes that control cellular responses to unfavorable conditions (stress factors, including oxidative stress and exposure to toxins).
Expression of AOX1 Predicts Prognosis of Clear Cell Renal Cell Carcinoma
Authors: Xiong Luyang , Feng Yuchen , Hu Wei , Tan Jiahong , Li Shusheng , Wang Hongjie
Published: July 2021

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer worldwide, and appropriate cancer biomarkers facilitate early diagnosis, treatment, and prognosis prediction in cancer management. However, an accurate biomarker for ccRCC is lacking. This study identified 356 differentially expressed genes in ccRCC tissues compared with normal kidney tissues by integrative analysis of eight ccRCC datasets. Enrichment analysis of the differentially expressed genes unveiled improved adaptation to hypoxia and metabolic reprogramming of the tumor cells. Aldehyde oxidase 1 (AOX1) gene was identified as a biomarker for ccRCC among all the differentially expressed genes. ccRCC tissues expressed significantly lower AOX1 than normal kidney tissues, which was further validated by immunohistochemistry at the protein level and The Cancer Genome Atlas (TCGA) data mining at the mRNA level. Higher AOX1 expression predicted better overall survival in ccRCC patients. Furthermore, AOX1 DNA copy number deletion and hypermethylation were negatively correlated with AOX1 expression, which might be the potential mechanism for its dysregulation in ccRCC. Finally, we illustrated that the effect of AOX1 as a tumor suppressor gene is not restricted to ccRCC but universally exists in many other cancer types. Hence, AOX1 may act as a potential prognostic biomarker and therapeutic target for ccRCC.
RNAi-Mediated Knockdown of Imaginal Disc Growth Factors (IDGFs) Genes Causes Developmental Malformation and Mortality in Melon Fly, Zeugodacus cucurbitae
Authors: Ahmad Shakil , Jamil Momana , Fahim Muhammad , Zhang Shujing , Ullah Farman , Lyu Baoqian , Luo Yanping
Published: July 2021

This study reports the first successful use of oral feeding dsRNA technique for functional characterization of imaginal disc growth factors (IDGFs) genes (IDGF1, IDGF3_1, IDGF4_0, IDGF4_1, and IDGF6) in melon fly Zeugodacus cucurbitae. Phylogenetic and domain analysis indicates that these genes had high similarity with other Tephritidae fruit flies homolog and contain only one conserved domain among these five genes, which is glyco-18 domain (glyco-hydro-18 domain). Gene expression analysis at different developmental stages revealed that these genes were expressed at larval, pupal, and adult stages. To understand their role in different developmental stages, larvae were fed dsRNA-corresponding to each of the five IDGFs, in an artificial diet. RNAi-mediated knockdown of IDGF1 shows no phenotypic effects but caused mortality (10.4%), while IDGF4_0 caused malformed pharate at the adult stage where insects failed to shed their old cuticle and remained attached with their body, highest mortality (49.2%) was recorded compared to dsRNA-green fluorescent protein (GFP) or DEPC. Silencing of IDGF3_1 and IDGF4_1 cause lethal phenotype in larvae, (17.2%) and (40%) mortality was indexed in Z. cucurbitae. IDGF6 was mainly expressed in pupae and adult stages, and its silencing caused a malformation in adult wings. The developmental defects such as malformation in wings, larval–larval lethality, pupal–adult malformation, and small body size show that IDGFs are key developmental genes in the melon fly. Our results provide a baseline for the melon fly management and understanding of IDGFs specific functions in Z. cucurbitae.
Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes
Authors: Spenlé Caroline , Loustau Thomas , Burckel Hélène , Riegel Gilles , Abou Faycal Chérine , Li Chengbei , Yilmaz Alev , Petti Luciana , Steinbach Fanny , Ahowesso Constance , Jost Camille , Paul Nicodème , Carapito Raphael , Noël Georges , Anjuère Fabienne , Salomé Nathalie , Orend Gertraud
Published: July 2021

Radiotherapy, the most frequent treatment of oral squamous cell carcinomas (OSCC) besides surgery is employed to kill tumor cells but, radiotherapy may also promote tumor relapse where the immune-suppressive tumor microenvironment (TME) could be instrumental. We established a novel syngeneic grafting model from a carcinogen-induced tongue tumor, OSCC13, to address the impact of radiotherapy on OSCC. This model revealed similarities with human OSCC, recapitulating carcinogen-induced mutations found in smoking associated human tongue tumors, abundant tumor infiltrating leukocytes (TIL) and, spontaneous tumor cell dissemination to the local lymph nodes. Cultured OSCC13 cells and OSCC13-derived tongue tumors were sensitive to irradiation. At the chosen dose of 2 Gy mimicking treatment of human OSCC patients not all tumor cells were killed allowing to investigate effects on the TME. By investigating expression of the extracellular matrix molecule tenascin-C (TNC), an indicator of an immune suppressive TME, we observed high local TNC expression and TIL infiltration in the irradiated tumors. In a TNC knockout host the TME appeared less immune suppressive with a tendency towards more tumor regression than in WT conditions. Altogether, our novel syngeneic tongue OSCC grafting model, sharing important features with the human OSCC disease could be relevant for future anti-cancer targeting of OSCC by radiotherapy and other therapeutic approaches.
Patterns of Immune Activation in HIV and Non HIV Subjects and Its Relation to Cardiovascular Disease Risk
Authors: Vos Alinda G. , Dodd Caitlin N. , Delemarre Eveline M. , Nierkens Stefan , Serenata Celicia , Grobbee Diederick E. , Klipstein-Grobusch Kerstin , Venter W. D. Francois
Published: July 2021

Introduction

Insight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT).

Methods

A cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression while adjusting for classic CVD risk factors.

Results

In total, 185 HIV-positive and 104 HIV negative participants, 63% females, median age 40.7 years (IQR 35.4 – 47.7) were included. HIV-positive individuals were older (+6 years, p <0.01) and had a higher CIMT (p <0.01). No clear patterns of inflammation were identified by use of PCA. Following ANCOVA, nine immune markers differed significantly between HIV-positive and HIV-negative participants, including PDL1. PDL1 was independently associated with CIMT, but upon stratification this effect remained for HIV-negative individuals only.

Conclusion

HIV positive patients on stable ART and HIV negative controls had similar immune activation patterns. CVD risk in HIV-positive participants was mediated by inflammation markers included in this study.
Influence of IL10 (rs1800896) Polymorphism and TNF-α, IL-10, IL-17A, and IL-17F Serum Levels in Ankylosing Spondylitis
Authors: Braga Matheus , Lara-Armi Fernanda Formaggi , Neves Janisleya Silva Ferreira , Rocha-Loures Marco Antônio , Terron-Monich Mariana de Souza , Bahls-Pinto Larissa Danielle , de Lima Neto Quirino Alves , Zacarias Joana Maira Valentini , Sell Ana Maria , Visentainer Jeane Eliete Laguila
Published: July 2021

Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines have been associated with AS, which can interfere with the production of these cytokines and contribute to the development of AS. In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 −1082 A>G SNP (rs1800896) with AS and to evaluate the serum levels of TNF-α, IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780). Patients and controls were selected from the Maringá University Hospital and the Maringá Rheumatism Clinic, in Paraná State, Southern Brazil, and they were diagnosed by the ASAS Criteria. In total, 149 patients and 169 controls were genotyped for the IL10 −1082 A>G polymorphism using a polymerase chain reaction with sequence specific primers (PCR-SSP); the measurement of TNF-α serum levels was performed through the immunofluorimetric test and IL-10, IL-17A, and IL-17F using an ELISA test. There was a high frequency of the IL10 −1082 G allele in AS patients compared with controls with an odds ratio of 1.83 and 95% confidence interval of 1.32 to 2.54, and a significant difference in the genotype frequencies of the IL10 −1082 A/G+G/G between patients and healthy controls, with an odds ratio of 3.01 and 95% confidence interval of 1.75 to 5.17. In addition, increased serum levels of IL-10 were observed in AS patients: 2.38 (IQR, 0.91) pg/ml compared with controls 1.72 (IQR 0.93) pg/ml (P = 0.01). Our results also showed an association between IL17F rs763780 C/T+T/T genotypes and increased serum levels of IL-17F in patients with AS and also in controls. We can conclude that patients with the A/G and G/G genotypes for −1082 A>G (rs1800896) in the IL10 gene are three times more likely to develop AS, that the serum level of IL-10 was higher in AS patients and that the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum of patients and controls in the same way.
Hypopharyngeal Ulcers in COVID-19: Histopathological and Virological Analyses – A Case Report
Authors: Porzionato Andrea , Stocco Elena , Emmi Aron , Contran Martina , Macchi Veronica , Riccetti Silvia , Sinigaglia Alessandro , Barzon Luisa , De Caro Raffaele
Published: July 2021

In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral cavity, oropharynx, esophagus, stomach and bowel. In this report, we describe an autopsy case of a COVID-19 patient who showed two undiagnosed ulcers at the level of the anterior and posterior walls of the hypopharynx. Molecular testing of viruses involved in pharyngeal ulcers demonstrated the presence of severe acute respiratory syndrome – coronavirus type 2 (SARS-CoV-2) RNA, together with herpes simplex virus 1 DNA. Histopathologic analysis demonstrated full-thickness lympho-monocytic infiltration (mainly composed of CD68-positive cells), with hemorrhagic foci and necrosis of both the mucosal layer and deep skeletal muscle fibers. Fibrin and platelet microthrombi were also found. Cytological signs of HSV-1 induced damage were not found. Cells expressing SARS-CoV-2 spike subunit 1 were immunohistochemically identified in the inflammatory infiltrations. Immunohistochemistry for HSV1 showed general negativity for inflammatory infiltration, although in the presence of some positive cells. Thus, histopathological, immunohistochemical and molecular findings supported a direct role by SARS-CoV-2 in producing local ulcerative damage, although a possible contributory role by HSV-1 reactivation cannot be excluded. From a clinical perspective, this autopsy report of two undiagnosed lesions put the question if ulcers along the GI tract could be more common (but frequently neglected) in COVID-19 patients.
Testing if Micro-CT Is Capable of Quantitating the Extent of Proteoglycan-Aggrecan Induced Axial Spondyloarthritis in Mice
Authors: Han Qing , Zheng ZhaoHui , Liang Qiang , Zhang Kui , Yang FengFan , Fu XiangHui , Luo Xing , Ding Jin , Xie Ronghua , Zhu WenXiao , Zhu Ping
Published: July 2021

Objective

Injections of proteoglycan aggrecan (PGA) have been reported to induce axial spondyloarthritis (ax-SpA) in BALB/c mice. It is considered to be a model for radiographic ax-SpA. However, evaluation of the extent of axial disease by histopathological assessment of every intervertebral space is labor-intensive. The objective of our paper is to test the feasibility of Micro Computed Tomography (Micro-CT) in rapidly enumerating the number of intervertebral spaces affected in each mouse.

Methods

Arthritis was induced in BALB/c mice by intraperitoneal injections of PGA. Involvement of several spinal segments, and selected sacroiliac and hip joints were evaluated by histopathology. The involvement of all intervertebral spaces, sacroiliac and hip joints was evaluated by Micro-CT.

Results

BALB/c mice injected with PGA developed histopathology of SpA-like axial lesions, including spondylitis, sacroiliac joint arthritis and hip joint arthritis. Micro-CT allowed us to clearly enumerate the number of lesions in each mouse.

Conclusion

Micro-CT allows quantitative assessment of the extent of axial involvement in PGA-induced mouse spondylitis. This can be a useful tool in assessing therapeutic interventions.
Total Glucosides of Paeony Ameliorate Pristane-Induced Lupus Nephritis by Inducing PD-1 ligands+ Macrophages via Activating IL-4/STAT6/PD-L2 Signaling
Authors: Liang Chun-Ling , Jiang Hongliang , Feng Wenxuan , Liu Huazhen , Han Ling , Chen Yuchao , Zhang Qunfang , Zheng Fang , Lu Chuan-Jian , Dai Zhenhua
Published: July 2021

Macrophages, a major subset of innate immune cells, are main infiltrating cells in the kidney in lupus nephritis. Macrophages with different phenotypes exert diverse or even opposite effects on the development of lupus nephritis. Substantial evidence has shown that macrophage M2 polarization is beneficial to individuals with chronic kidney disease. Further, it has been reported that PD-1 ligands (PD-Ls) contribute to M2 polarization of macrophages and their immunosuppressive effects. Total glucosides of paeony (TGP), originally extracted from Radix Paeoniae Alba, has been approved in China to treat some autoimmune diseases. Here, we investigated the potentially therapeutic effects of TGP on lupus nephritis in a pristane-induced murine model and explored the molecular mechanisms regulating macrophage phenotypes. We found that TGP treatment significantly improved renal function by decreasing the urinary protein and serum creatinine, reducing serum anti-ds-DNA level and ameliorating renal immunopathology. TGP increased the frequency of splenic and peritoneal F4/80+CD11b+CD206+ M2-like macrophages with no any significant effect on F4/80+CD11b+CD86+ M1-like macrophages. Immunofluorescence double-stainings of the renal tissue showed that TGP treatment increased the frequency of F4/80+Arg1+ subset while decreasing the percentage of F4/80+iNOS+ subset. Importantly, TGP treatment increased the percentage of both F4/80+CD11b+PD-L1+ and F4/80+CD11b+PD-L2+ subsets in spleen and peritoneal lavage fluid as well as the kidney. Furthermore, TGP augmented the expressions of CD206, PD-L2 and phosphorylated STAT6 in IL-4-treated Raw264.7 macrophages in vitro while its effects on PD-L2 were abolished by pretreatment of the cells with an inhibitor of STAT6, AS1517499. However, TGP treatment did not affect the expressions of STAT1 and PD-L1 in Raw264.7 macrophages treated with LPS/IFN-γ in vitro, indicating a possibly indirect effect of TGP on PD-L1 expression on macrophages in vivo. Thus, for the first time, we demonstrated that TGP may be a potent drug to treat lupus nephritis by inducing F4/80+CD11b+CD206+ and F4/80+CD11b+PD-L2+ macrophages through IL-4/STAT6/PD-L2 signaling pathway.
Oral Versus Gastrointestinal Mucosal Immune Niches in Homeostasis and Allostasis
Authors: Suárez Lina J. , Arboleda Silie , Angelov Nikola , Arce Roger M.
Published: July 2021

Different body systems (epidermis, respiratory tract, cornea, oral cavity, and gastrointestinal tract) are in continuous direct contact with innocuous and/or potentially harmful external agents, exhibiting dynamic and highly selective interaction throughout the epithelia, which function as both a physical and chemical protective barrier. Resident immune cells in the epithelia are constantly challenged and must distinguish among antigens that must be either tolerated or those to which a response must be mounted for. When such a decision begins to take place in lymphoid foci and/or mucosa-associated lymphoid tissues, the epithelia network of immune surveillance actively dominates both oral and gastrointestinal compartments, which are thought to operate in the same immune continuum. However, anatomical variations clearly differentiate immune processes in both the mouth and gastrointestinal tract that demonstrate a wide array of independent immune responses. From single vs. multiple epithelia cell layers, widespread cell-to-cell junction types, microbial-associated recognition receptors, dendritic cell function as well as related signaling, the objective of this review is to specifically contrast the current knowledge of oral versus gut immune niches in the context of epithelia/lymphoid foci/MALT local immunity and systemic output. Related differences in 1) anatomy 2) cell-to-cell communication 3) antigen capture/processing/presentation 4) signaling in regulatory vs. proinflammatory responses and 5) systemic output consequences and its relations to disease pathogenesis are discussed.
Ocean and Atmospheric Observations at the Remote Ieodo Ocean Research Station in the Northern East China Sea
Authors: Byun Do-Seong , Jeong Jin-Yong , Kim Duk-jin , Hong Sungmin , Lee Kyu-Tae , Lee Kitack
Published: July 2021

For open ocean environments, it is rare to find continuous, simultaneous air and sea observation records due to the challenges of instrument installation and maintenance. The Ieodo Ocean Research Station (Ieodo ORS), a remote ocean site located in the northern East China Sea with its harsh oceanic and atmospheric environment, provides a platform for the concurrent monitoring of air and sea environments. Since 2014, the Korea Hydrographic and Oceanographic Agency has run the “Ieodo ORS field trip program,” via which researchers are able to stay at the station for a week or more. This work reports technical lessons learned over 5 years from five Ieodo ORS research projects launched in 2016. Over the course of these projects, Ieodo ORS has monitored sea surface temperature, temperature and salinity in the water column, seawater pH, air pollutants, and solar radiation. The purpose of this paper is to facilitate the success of future research activities in similar environments by sharing our experiences and “best practices.”
Favorable Pregnancy Outcomes in Women With Well-Controlled Pulmonary Arterial Hypertension
Authors: Corbach Nadine , Berlier Charlotte , Lichtblau Mona , Schwarz Esther I. , Gautschi Fiorenza , Groth Alexandra , Schüpbach Rolf , Krähenmann Franziska , Saxer Stéphanie , Ulrich Silvia
Published: July 2021

Introduction: Since pregnancy in women with pulmonary arterial hypertension (PAH) is associated with a high risk of morbidity and mortality, it is recommended that pregnancy should be avoided in PAH. However, some women with mild PAH may consider this recommendation as unsuitable. Unfortunately knowledge on pregnancy outcomes and best management of PAH during pregnancy is limited.

Methods: Data from all women with PAH who were followed during pregnancy by a multidisciplinary team at a tertiary referral center for PAH and who delivered between 2004 and 2020 were retrospectively analyzed in a case series. PAH risk factor profiles including WHO functional class (WHO-FC), NT-pro-BNP, echocardiographic pulmonary arterial pressure (PAP) and right heart function were analyzed prior to, during and following pregnancy.

Results: In seven pregnancies of five women with PAH (median age 29 (27; 31) years), there were no abortions or terminations. Five pregnancies were planned (all in WHO-FC I-II), two incidental (WHO-FC II, III). During pregnancy none of the women had complications or clinical worsening of PAH. After a median pregnancy duration of 37 1/7 weeks all gave birth to healthy babies by cesarean section in spinal anesthesia. During pregnancy, PAP tended to increase, whilst the course of WHO-FC and NT-pro-BNP were variable and no trend could be detected.

Conclusion: Women with PAH with a low risk profile closely followed by a multidisciplinary team had a favorable course during and after pregnancy, resulting in successful deliveries of healthy newborns.
Non-invasive Clinical Measurement of Ocular Rigidity and Comparison to Biomechanical and Morphological Parameters in Glaucomatous and Healthy Subjects
Authors: Ma Yanhui , Moroi Sayoko E. , Roberts Cynthia J.
Published: July 2021

Purpose: To assess ocular rigidity using dynamic optical coherence tomography (OCT) videos in glaucomatous and healthy subjects, and to evaluate how ocular rigidity correlates with biomechanical and morphological characteristics of the human eye.

Methods: Ocular rigidity was calculated using Friedenwald's empirical equation which estimates the change in intraocular pressure (IOP) produced by volumetric changes of the eye due to choroidal pulsations with each heartbeat. High-speed OCT video was utilized to non-invasively measure changes in choroidal volume through time-series analysis. A control-case study design was based on 23 healthy controls and 6 glaucoma cases. Multiple diagnostic modalities were performed during the same visit including Spectralis OCT for nerve head video, Pascal Dynamic Contour Tonometry for IOP and ocular pulse amplitude (OPA) measurement, Corvis ST for measuring dynamic biomechanical response, and Pentacam for morphological characterization.

Results: Combining glaucoma and healthy cohorts (n = 29), there were negative correlations between ocular rigidity and axial length (Pearson R = −0.53, p = 0.003), and between ocular rigidity and anterior chamber volume (R = −0.64, p = 0.0002). There was a stronger positive correlation of ocular rigidity and scleral stiffness (i.e., stiffness parameter at the highest concavity [SP-HC]) (R = 0.62, p = 0.0005) compared to ocular rigidity and corneal stiffness (i.e., stiffness parameter at the first applanation [SP-A1]) (R = 0.41, p = 0.033). In addition, there was a positive correlation between ocular rigidity and the static pressure-volume ratio (P/V ratio) (R = 0.72, p < 0.0001).

Conclusions: Ocular rigidity was non-invasively assessed using OCT video and OPA in a clinic setting. The significant correlation of ocular rigidity with biomechanical parameters, SP-HC and P/V ratio, demonstrated the validity of the ocular rigidity measurement. Ocular rigidity is driven to a greater extent by scleral stiffness than corneal stiffness. These in vivo methods offer an important approach to investigate the role of ocular biomechanics in glaucoma.
Distinct Human Gut Microbial Taxonomic Signatures Uncovered With Different Sample Processing and Microbial Cell Disruption Methods for Metaproteomic Analysis
Authors: García-Durán Carmen , Martínez-López Raquel , Zapico Inés , Pérez Enrique , Romeu Eduardo , Arroyo Javier , Hernáez María Luisa , Pitarch Aida , Monteoliva Lucía , Gil Concha
Published: July 2021

The use of metaproteomics for studying the human gut microbiota can shed light on the taxonomic profile and the functional role of the microbial community. Nevertheless, methods for extracting proteins from stool samples continue to evolve, in the pursuit of optimal protocols for moistening and dispersing the stool sample and for disrupting microbial cells, which are two critical steps for ensuring good protein recovery. Here, we evaluated different stool sample processing (SSP) and microbial cell disruption methods (CDMs). The combination of a longer disintegration period of the stool sample in a tube rotator with sonication increased the overall number of identified peptides and proteins. Proteobacteria, Bacteroidetes, Planctomycetes, and Euryarchaeota identification was favored by mechanical cell disruption with glass beads. In contrast, the relative abundance of Firmicutes, Actinobacteria, and Fusobacteria was improved when sonication was performed before bead beating. Tenericutes and Apicomplexa identification was enhanced by moistening the stool samples during processing and by disrupting cells with medium-sized glass beads combined with or without sonication. Human protein identifications were affected by sonication. To test the reproducibility of these gut metaproteomic analyses, we examined samples from six healthy individuals using a protocol that had shown a good taxonomic diversity and identification of proteins from Proteobacteria and humans. We also detected proteins involved in microbial functions relevant to the host and related mostly to specific taxa, such as B12 biosynthesis and short chain fatty acid (SCFA) production carried out mainly by members in the Prevotella genus and the Firmicutes phylum, respectively. The taxonomic and functional profiles obtained with the different protocols described in this work provides the researcher with valuable information when choosing the most adequate protocol for the study of certain pathologies under suspicion of being related to a specific taxon from the gut microbiota.
Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma
Authors: Feng Zi-Yi , Wang Ting , Su Xin , Guo Shu
Published: July 2021

Background: The purpose of our research was to establish a gene signature and determine the prognostic value of m6A methylation regulators in cutaneous melanoma and WTAP as a protective gene in cutaneous melanoma prognosis, we also evaluated gene mutations in cutaneous melanoma.

Methods: We downloaded the RNA-seq transcriptome data and the clinical information for cutaneous melanoma patients from the GTEx and TCGA databases. Consensus clustering analysis was applied to divide the samples into two groups. Then the least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk signature, and we use external and internal datasets to verify its predictive value. We further searched the cBioPortal tools to detect genomic alterations and WTAP mutations. Finally, WTAP was further identified as a prognostic factor, and the related mechanisms mediated by WTAP were predicted by gene set enrichment analysis (GSEA). Experimental validations and have been further carried out.

Results: Notably, m6A RNA methylation regulators play significant roles in tumorigenesis and development. In total, we selected three subtypes of cutaneous melanoma according to consensus clustering of the m6A RNA methylation regulators, and the stage of cutaneous melanoma was proven to be related to the subtypes. The Cox regression and LASSO analyses built a risk signature including ELF3, ZC3H13 and WTAP. The prognostic value of the risk signature in internal and external datasets have been proven then. The whole-genome and selected gene WTAP mutations were further explored. WTAP as a single prognostic factor was also explored and found to serve as an independent protective prognostic factor.

Conclusions: Our study constructed a stable risk signature composed of m6A RNA methylation regulators in cutaneous melanoma. Moreover, WTAP was identified as a valuable prognostic factor and potential molecular target for cutaneous melanoma treatment.
LncRNA LINC00944 Promotes Tumorigenesis but Suppresses Akt Phosphorylation in Renal Cell Carcinoma
Authors: Chen Chiheng , Zheng Hanxiong
Published: July 2021

Long non-coding RNA (lncRNA) is a kind of RNA that possesses longer than 200 nucleotides and lacks protein coding function. It was recognized as a junk sequence for a long time. Recent studies have found that lncRNAs are actively functioning in almost every aspect of cell biology and involved in a variety of biological functions. LncRNAs are closely related to a variety of human diseases, especially tumors. Recently, lncRNAs are being increasingly reported in renal cancer. In our study, we identified the expression of lncRNA LINC00944 is significantly elevated in renal cell carcinoma (RCC) tissues and cell lines and high LINC00944 expression is significantly correlated with the tumor stage and prognosis of RCC. The knockdown of LINC00944 by CRISPR/dCas9-KRAB in higher expressing 786-O and 769-P RCC cells could significantly decrease proliferation and migration and also promote phosphorylation of Akt compared with the control group. Our study is the first to report the function of lncRNA LINC00944 in RCC. And we provide clinicopathological and experimental evidence that lncRNA LINC00944 acts as an oncogene in RCC, suggesting that targeting lncRNA LINC00944 expression might be a promising therapeutic strategy for the treatment of RCC.
Biochemical and Phylogenetic Characterization of a Novel NADP+-Specific Isocitrate Dehydrogenase From the Marine Microalga Phaeodactylum tricornutum
Authors: Huang Shiping , Zhao Jiaxin , Li Wenjing , Wang Peng , Xue Zhenglian , Zhu Guoping
Published: July 2021

Isocitrate dehydrogenase (IDH) family of proteins is classified into three subfamilies, namely, types I, II, and III. Although IDHs are widely distributed in bacteria, archaea, and eukaryotes, all type III IDHs reported to date are found only in prokaryotes. Herein, a novel type III IDH subfamily member from the marine microalga Phaeodactylum tricornutum (PtIDH2) was overexpressed, purified, and characterized in detail for the first time. Relatively few eukaryotic genomes encode this type of IDH and PtIDH2 shares the highest homology with marine bacterial monomeric IDHs, suggesting that PtIDH2 originated through a horizontal gene transfer event between a marine alga and a bacterium. Size-exclusion chromatography revealed that the native PtIDH2 is a homotetramer (∼320 kDa) in solution, comprising four monomeric IDH-like subunits (80 kDa each). Enzymatic characterization showed that PtIDH2 is a bivalent metal ion-dependent enzyme and Mn2+ is the optimal activator. The recombinant PtIDH2 protein exhibited maximal activity at 35°C and pH 8.0 in the presence of Mn2+. Heat-inactivation analysis revealed that PtIDH2 is a cold-adapted enzyme. Kinetic analysis demonstrated that PtIDH2 is a completely NADP+-specific IDH with no detectable NAD+-associated catalytic activity. The three putative key NADP+-binding residues (His604, Arg615, and Arg664) in PtIDH2 were also evaluated by site-directed mutagenesis. The H604L/R615D/R664S triple mutant showed a 3.25-fold preference for NAD+ over NADP+, implying that the coenzyme specificity of PtIDH2 can be converted from NADP+ to NAD+ through rational engineering approaches. Additionally, the roles of the conserved residues Ala718 and Leu742 in the thermostability of PtIDH2 were also explored by site-directed mutagenesis. We found that the L742F mutant displayed higher thermostability than wild-type PtIDH2. This study expands the phylogeny of the IDH family and provides new insights into the evolution of IDHs.
Functional Connectivity and Compensation of Phonemic Fluency in Aging
Authors: Mohanty Rosaleena , Gonzalez-Burgos Lissett , Diaz-Flores Lucio , Muehlboeck J-Sebastian , Barroso José , Ferreira Daniel , Westman Eric
Published: July 2021

Neural compensatory mechanisms associated with broad cognitive abilities have been studied. However, those associated with specific cognitive subdomains (e.g., verbal fluency) remain to be investigated in healthy aging. Here, we delineate: (a) neural substrates of verbal (phonemic) fluency, and (b) compensatory mechanisms mediating the association between these neural substrates and phonemic fluency. We analyzed resting-state functional magnetic resonance imaging from 133 right-handed, cognitively normal individuals who underwent the Controlled Oral Word Association Test (COWAT) to record their phonemic fluency. We evaluated functional connectivity in an established and extended language network comprising Wernicke, Broca, thalamic and anti-correlated modules. (a) We conducted voxel-wise multiple linear regression to identify the brain areas associated with phonemic fluency. (b) We used mediation effects of cognitive reserve, measured by the Wechsler Adult Intelligence Scale—Information subtest, upon the association between functional connectivity and phonemic fluency tested to investigate compensation. We found that: (a) Greater functional connectivity between the Wernicke module and brain areas within the anti-correlated module was associated with better performance in phonemic fluency, (b) Cognitive reserve was an unlikely mediator in younger adults. In contrast, cognitive reserve was a partial mediator of the association between functional connectivity and phonemic fluency in older adults, likely representing compensation to counter the effect of aging. We conclude that in healthy aging, higher performance in phonemic fluency at older ages could be attributed to greater functional connectivity partially facilitated by higher cognitive reserve, presumably reflecting compensatory mechanisms to minimize the effect of aging.
Compromised Brain Activity With Age During a Game-Like Dynamic Balance Task: Single- vs. Dual-Task Performance
Authors: de Rond Veerle , Orcioli-Silva Diego , Dijkstra Bauke Wybren , Orban de Xivry Jean-Jacques , Pantall Annette , Nieuwboer Alice
Published: July 2021

Background: Postural control and cognition are affected by aging. We investigated whether cognitive distraction influenced neural activity differently in young and older adults during a game-like mediolateral weight-shifting task with a personalized task load.

Methods: Seventeen healthy young and 17 older adults performed a balance game, involving hitting virtual wasps, serial subtractions and a combination of both (dual-task). A motion analysis system estimated each subject's center of mass position. Cortical activity in five regions was assessed by measuring oxygenated hemoglobin (HbO2) with a functional Near-Infrared Spectroscopy system.

Results: When adding cognitive load to the game, weight-shifting speed decreased irrespective of age, but older adults reduced the wasp-hits more than young adults. Accompanying these changes, older adults decreased HbO2 in the left pre-frontal cortex (PFC) and frontal eye fields (FEF) compared to single-tasking, a finding not seen in young adults. Additionally, lower HbO2 levels were found during dual-tasking compared to the summed activation of the two single tasks in all regions except for the right PFC. These relative reductions were specific for the older age group in the left premotor cortex (PMC), the right supplementary motor area (SMA), and the left FEF.

Conclusion: Older adults showed more compromised neural activity than young adults when adding a distraction to a challenging balance game. We interpret these changes as competitive downgrading of neural activity underpinning the age-related deterioration of game performance during dual-tasking. Future work needs to ascertain if older adults can train their neural flexibility to withstand balance challenges during daily life activities.
Genetic Overlap Between Alzheimer’s Disease and Depression Mapped Onto the Brain
Authors: Monereo-Sánchez Jennifer , Schram Miranda T. , Frei Oleksandr , O’Connell Kevin , Shadrin Alexey A. , Smeland Olav B. , Westlye Lars T. , Andreassen Ole A. , Kaufmann Tobias , Linden David E. J. , van der Meer Dennis
Published: July 2021

Background: Alzheimer’s disease (AD) and depression are debilitating brain disorders that are often comorbid. Shared brain mechanisms have been implicated, yet findings are inconsistent, reflecting the complexity of the underlying pathophysiology. As both disorders are (partly) heritable, characterising their genetic overlap may provide aetiological clues. While previous studies have indicated negligible genetic correlations, this study aims to expose the genetic overlap that may remain hidden due to mixed directions of effects.

Methods: We applied Gaussian mixture modelling, through MiXeR, and conjunctional false discovery rate (cFDR) analysis, through pleioFDR, to genome-wide association study (GWAS) summary statistics of AD (n = 79,145) and depression (n = 450,619). The effects of identified overlapping loci on AD and depression were tested in 403,029 participants of the UK Biobank (UKB) (mean age 57.21, 52.0% female), and mapped onto brain morphology in 30,699 individuals with brain MRI data.

Results: MiXer estimated 98 causal genetic variants overlapping between the 2 disorders, with 0.44 concordant directions of effects. Through pleioFDR, we identified a SNP in the TMEM106B gene, which was significantly associated with AD (B = −0.002, p = 9.1 × 10–4) and depression (B = 0.007, p = 3.2 × 10–9) in the UKB. This SNP was also associated with several regions of the corpus callosum volume anterior (B > 0.024, p < 8.6 × 10–4), third ventricle volume ventricle (B = −0.025, p = 5.0 × 10–6), and inferior temporal gyrus surface area (B = 0.017, p = 5.3 × 10–4).

Discussion: Our results indicate there is substantial genetic overlap, with mixed directions of effects, between AD and depression. These findings illustrate the value of biostatistical tools that capture such overlap, providing insight into the genetic architectures of these disorders.
A Differential Threshold of Breakfast, Caffeine and Food Groups May Be Impacting Mental Well-Being in Young Adults: The Mediation Effect of Exercise
Authors: Begdache Lina , Kianmehr Hamed , Najjar Helen , Witt Dylan , Sabounchi Nasim S.
Published: July 2021

Diet and exercise are known to influence mental health. However, the interaction between diet, dietary practices, and exercise and its impact on the mood of young adults (YA) is poorly understood. YA are inherently at risk for mental distress. They tend to consume a low-quality diet and are generally active. The purpose of the study was to assess these relationships through validating causal loop diagrams (CLD) that describe these connections by using a system dynamic (SD) modeling methodology. Adults 18–29 years were invited to complete the Food-Mood questionnaire. The anonymous questionnaire link was distributed to several institutional listservs and via several social media platforms targeting young adults. A multi-level analysis, including machine learning techniques, was used to assess these relationships. The key findings were then built into gender based CLD, which suggest that a differential repertoire may be needed to optimize diet quality, exercise, and mental well-being. Additionally, a potential net threshold for dietary factors and exercise may be needed to achieve mental well-being in young adults. Moreover, our findings suggest that exercise may boost the enhancing effect of food groups on mental well-being and may lessen the negative impact of dietary impediments of mental well-being.
Total Fat Content and Fatty Acid Profile of Fine-Aroma Cocoa From Northeastern Peru
Authors: Oliva-Cruz Manuel , Mori-Culqui Pati Llanina , Caetano Aline C. , Goñas Malluri , Vilca-Valqui Nuri C. , Chavez Segundo G.
Published: July 2021

Cocoa beans are the raw material for the chocolate industry. In this study, the total fat contents and fatty acid profiles of fine-aroma cocoa beans of 30 cocoa ecotypes from northeastern Peru were evaluated. Results showed that SJJ-1 and ACJ-11 ecotypes from San Martin and Amazonas regions, respectively, presented highest percentages of total fat with an average of 30.49%. With respect to fatty acid profiles, it was found that cocoa ecotypes are composed of 10 fatty acids (C14:0, C16:0, C16:1, C18:0, C17:0, C18:1, C18:2, C18:3, C20:0, and C22:0); based on this profile, 5 clusters were determined. Cluster 5 had the highest content of C17:0 fatty acid (0.47%); however, the clusters 1, 2, 3, and 4 had the lowest content of this fatty acid (0.37%, 0.32%, 0.32%, respectively). The clusters 3 and 4 showed the highest content of C16:0 fatty acid (31.13% y 28.97%, respectively). The clusters 3 and 5 contained the highest content of the acid C18:1 (27.08% y 26.82%, respectively). The PCA found that C18:0 and C20:0 fatty acids are correlated, and are fundamentally opposite to C18:1, C16:0, and C18:3 acids. These results may be useful in identifying raw material for the development of specialty chocolates with better nutritional value than traditional cocoa.