bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Actin Cytoskeleton Reorganization in Polarized Secretory Traffic at the Immunological Synapse
Authors: Calvo Victor , Izquierdo Manuel
Published: February 2021

T cell receptor (TCR) and B cell receptor (BCR) stimulation by antigen presented on an antigen-presenting cell (APC) induces the formation of the immune synapse (IS), the convergence of secretory vesicles from T and B lymphocytes toward the centrosome, and the polarization of the centrosome to the immune synapse. Immune synapse formation is associated with an initial increase in cortical F-actin at the synapse, followed by a decrease in F-actin density at the central region of the immune synapse, which contains the secretory domain. These reversible, actin cytoskeleton reorganization processes occur during lytic granule degranulation in cytotoxic T lymphocytes (CTL) and cytokine-containing vesicle secretion in T-helper (Th) lymphocytes. Recent evidences obtained in T and B lymphocytes forming synapses show that F-actin reorganization also occurs at the centrosomal area. F-actin reduction at the centrosomal area appears to be involved in centrosome polarization. In this review we deal with the biological significance of both cortical and centrosomal area F-actin reorganization and some of the derived biological consequences.
In silico Exploration of Inhibitors for SARS-CoV-2's Papain-Like Protease
Authors: Huynh Tien , Cornell Wendy , Luan Binquan
Published: February 2021

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with very limited treatments so far. Demonstrated with good druggability, two major proteases of SARS-CoV-2, namely main protease (Mpro) and papain-like protease (PLpro) that are essential for viral maturation, have become the targets for many newly designed inhibitors. Unlike Mpro that has been heavily investigated, PLpro is not well-studied so far. Here, we carried out the in silico high-throughput screening of all FDA-approved drugs via the flexible docking simulation for potential inhibitors of PLpro and explored the molecular mechanism of binding between a known inhibitor rac5c and PLpro. Our results, from molecular dynamics simulation, show that the chances of drug repurposing for PLpro might be low. On the other hand, our long (about 450 ns) MD simulation confirms that rac5c can be bound stably inside the substrate-binding site of PLpro and unveils the molecular mechanism of binding for the rac5c-PLpro complex. The latter may help perform further structural optimization and design potent leads for inhibiting PLpro.
Plasticity of Anterior Pituitary Gonadotrope Cells Facilitates the Pre-Ovulatory LH Surge
Authors: Clay Colin M. , Cherrington Brian D. , Navratil Amy M.
Published: February 2021

Gonadotropes cells located in the anterior pituitary gland are critical for reproductive fitness. A rapid surge in the serum concentration of luteinizing hormone (LH) secreted by anterior pituitary gonadotropes is essential for stimulating ovulation and is thus required for a successful pregnancy. To meet the requirements to mount the LH surge, gonadotrope cells display plasticity at the cellular, molecular and morphological level. First, gonadotrope cells heighten their sensitivity to an increasing frequency of hypothalamic GnRH pulses by dynamically elevating the expression of the GnRH receptor (GnRHR). Following ligand binding, GnRH initiates highly organized intracellular signaling cascades that ultimately promote the synthesis of LH and the trafficking of LH vesicles to the cell periphery. Lastly, gonadotrope cells display morphological plasticity, where there is directed mobilization of cytoskeletal processes towards vascular elements to facilitate rapid LH secretion into peripheral circulation. This mini review discusses the functional and organizational plasticity in gonadotrope cells including changes in sensitivity to GnRH, composition of the GnRHR signaling platform within the plasma membrane, and changes in cellular morphology. Ultimately, multimodal plasticity changes elicited by gonadotropes are critical for the generation of the LH surge, which is required for ovulation.
Modeling a Sustainable, Self-Energized Pine Dust Pyrolysis System With Staged Condensation for Optimal Recovery of Bio-Oil
Authors: Charis Gratitude , Danha Gwiranai , Muzenda Edison , Nhubu Trust
Published: February 2021

This simulation study explores sustainable improvements that could be made to a pine dust pyrolysis system to eliminate total dependence on external electrical energy supply and improve the yield of high-quality dry bio-oil. The components, stoichiometric yield and composition of oil, char and gas were modeled in ChemCAD using data from literature and results from biomass characterization and pyrolysis. A fast pyrolysis regime was used to increase the overall yield of dry oil fraction recovered and the char by-product was utilized to make the system energy self-sufficient. The optimization study focused on the condensation system whose parameters were varied at the provided optimum pyrolysis temperature. The recommended temperature for the primary condenser was 96–110°C which yielded 23.3–29.8 wt% dry oil with 2.4–4.4 wt% water content. The optimum temperature for the secondary condenser was 82°C whose bio-oil (∼2.92 wt%) had a moisture content of 7.5–10 wt% at constant primary condenser temperature between 96–110°C. The third condenser could be operated at ambient temperature. The results were validated using both information reported in literature and results from the previous experimental study. Such a simple model built by careful selection of the model bio-oil components is useful in estimating the optimal parameters for the biomass pyrolysis staged condensation system.
The Pandemic as a Conservation Marketing Intervention: Could COVID-19 Lower Global Demand for Wildlife Products?
Authors: Moorhouse Tom P. , D'Cruze Neil C. , Macdonald David W.
Published: February 2021

We wished to assess whether the COVID-19 pandemic, thought to have a zoonotic origin, may lead to a reduction in consumer demand for wildlife products. In 2018, we surveyed the effect of demand reduction messaging on consumers' desire to own exotic pets with 1,000 respondents in each of Brazil, China, the USA, and Vietnam. In July 2020, during the pandemic, we repeated the survey with 100 new respondents in each country. Mean desire to own a given exotic pet was 40–60% lower in 2020 during the pandemic, but only for respondents from Brazil, China, and the USA, and only for the group of respondents who had high a priori purchase likelihoods: those who had already owned an exotic pet. The stated desire to own of non-owners was no different in 2020, but this group already had extremely low purchase likelihoods. Vietnamese pet owners, in contrast to those in other countries, exhibited higher purchase desire during the pandemic than previously. We speculate that this arose because Vietnam has a long history of dealing with epidemic disease, had no COVID-19 related deaths by the time of survey, and so population uncertainty about the consequences of exotic pet ownership may have decreased. While limited, our initial evidence indicates that the global pandemic is unlikely to permanently curb demand for wildlife products.
Serum Urate Polygenic Risk Score Can Improve Gout Risk Prediction: A Large-Scale Cohort Study
Authors: Zhang Yanfei , Lee Ming Ta Michael
Published: February 2021

Gout is a painful inflammatory arthritis affecting more than 8 million Americans. Identifying high-risk patients in early life could potentially encourage people to adopt lifestyle changes to prevent gout. Polygenic risk score (PRS) provides an overall estimate of an individual's genetic liability to develop a disease and can be used for early identification of high-risk individuals. In this study, we validated a previously reported PRS in an independent cohort. The urate-PRS was constructed from 110 significant urate-associated variants identified in Europeans. Phenome-wide and PRS-wide association study showed the urate-PRS is highly specifically associated with gout (phecode: 274.10; beta = 1.495 [1.372, 1.619], p = 4.37e-124). Urate-PRS alone did not performed in the gout prediction (area under the receiver operating characteristic curve, AUROC = 0.640); however, the addition of PRS upon demographics significantly improved the model performance, yielding an AUROC of 0.804 from 0.777 (DeLong test p = 3.66e−9). Trans-ethnic PRS and European-specific PRS showed similar prediction performance. We observed increasing gout prevalence and odds ratio (OR) across the PRS quintiles. Our study showed 8.2% of the cohort had more than 2.5 odds for gout than remainders, indicating that urate-PRS may be a better marker than age and sex to stratify patient risk. With the rapid growth of large biorepositories, such as All of Us, urate-PRS can be applied quickly and widely in population to estimate individual's risk, providing a powerful tool for gout preventive purpose in population health.
Genome-Wide Characterization of HSP90 Gene Family in Cucumber and Their Potential Roles in Response to Abiotic and Biotic Stresses
Authors: Zhang Kaijing , He Shuaishuai , Sui Yihu , Gao Qinghai , Jia Shuangshuang , Lu Xiaomin , Jia Li
Published: February 2021

Heat shock protein 90 (HSP90) possesses critical functions in plant developmental control and defense reactions. The HSP90 gene family has been studied in various plant species. However, the HSP90 gene family in cucumber has not been characterized in detail. In this study, a total of six HSP90 genes were identified from the cucumber genome, which were distributed to five chromosomes. Phylogenetic analysis divided the cucumber HSP90 genes into two groups. The structural characteristics of cucumber HSP90 members in the same group were similar but varied among different groups. Synteny analysis showed that only one cucumber HSP90 gene, Csa1G569290, was conservative, which was not collinear with any HSP90 gene in Arabidopsis and rice. The other five cucumber HSP90 genes were collinear with five Arabidopsis HSP90 genes and six rice HSP90 genes. Only one pair of paralogous genes in the cucumber HSP90 gene family, namely one pair of tandem duplication genes (Csa1G569270/Csa1G569290), was detected. The promoter analysis showed that the promoters of cucumber HSP90 genes contained hormone, stress, and development-related cis-elements. Tissue-specific expression analysis revealed that only one cucumber HSP90 gene Csa3G183950 was highly expressed in tendril but low or not expressed in other tissues, while the other five HSP90 genes were expressed in all tissues. Furthermore, the expression levels of cucumber HSP90 genes were differentially induced by temperature and photoperiod, gibberellin (GA), downy mildew, and powdery mildew stimuli. Two cucumber HSP90 genes, Csa1G569270 and Csa1G569290, were both differentially expressed in response to abiotic and biotic stresses, which means that these two HSP90 genes play important roles in the process of cucumber growth and development. These findings improve our understanding of cucumber HSP90 family genes and provide preliminary information for further studies of cucumber HSP90 gene functions in plant growth and development.
Crosstalk Between mRNA 3'-End Processing and Epigenetics
Authors: Soles Lindsey V. , Shi Yongsheng
Published: February 2021

The majority of eukaryotic genes produce multiple mRNA isoforms by using alternative poly(A) sites in a process called alternative polyadenylation (APA). APA is a dynamic process that is highly regulated in development and in response to extrinsic or intrinsic stimuli. Mis-regulation of APA has been linked to a wide variety of diseases, including cancer, neurological and immunological disorders. Since the first example of APA was described 40 years ago, the regulatory mechanisms of APA have been actively investigated. Conventionally, research in this area has focused primarily on the roles of regulatory cis-elements and trans-acting RNA-binding proteins. Recent studies, however, have revealed important functions for epigenetic mechanisms, including DNA and histone modifications and higher-order chromatin structures, in APA regulation. Here we will discuss these recent findings and their implications for our understanding of the crosstalk between epigenetics and mRNA 3'-end processing.
Poly(dA:dT) Suppresses HSV-2 Infection of Human Cervical Epithelial Cells Through RIG-I Activation
Authors: Shao Dan-Dan , Meng Feng-Zhen , Liu Yu , Xu Xi-Qiu , Wang Xu , Hu Wen-Hui , Hou Wei , Ho Wen-Zhe
Published: February 2021

Epithelial cells of the female reproductive tract (FRT) participate in the initial innate immunity against viral infections. Poly(dA:dT) is a synthetic analog of B form double-stranded (ds) DNA which can activate the interferon (IFN) signaling pathway-mediated antiviral immunity through DNA-dependent RNA Polymerase III. Here we investigated whether poly(dA:dT) could inhibit herpes simplex virus type 2 (HSV-2) infection of human cervical epithelial cells (End1/E6E7). We demonstrated that poly(dA:dT) treatment of End1/E6E7 cells could significantly inhibit HSV-2 infection. Mechanistically, poly(dA:dT) treatment of the cells induced the expression of the intracellular IFNs and the multiple antiviral IFN-stimulated genes (ISGs), including IFN-stimulated gene 15 (ISG15), IFN-stimulated gene 56 (ISG56), 2’-5’-oligoadenylate synthetase 1 (OAS1), 2’-5’-oligoadenylate synthetase 2 (OAS2), myxovirus resistance protein A (MxA), myxovirus resistance protein B (MxB), virus inhibitory protein, endoplasmic reticulum-associated, IFN-inducible (Viperin), and guanylate binding protein 5 (GBP5). Further investigation showed that the activation of RIG-I was largely responsible for poly(dA:dT)-mediated HSV-2 inhibition and IFN/ISGs induction in the cervical epithelial cells, as RIG-I knockout abolished the poly(dA:dT) actions. These observations demonstrate the importance for design and development of AT-rich dsDNA-based intervention strategies to control HSV-2 mucosal transmission in FRT.
Outcome Predictors of Biopsy-Proven Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis
Authors: Ge Yifei , Yang Guang , Yu Xiangbao , Sun Bin , Zhang Bo , Yuan Yanggang , Zeng Ming , Wang Ningning , Mao Huijuan , Xing Changying
Published: February 2021

Objective

To determine the prognostic values of histopathologic classification of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and other clinical and laboratory features at the time of presentation on renal and patient survival associated with myeloperoxidase-ANCA-associated glomerulonephritis (MPO-ANCA-GN).

Methods

A total of 112 patients diagnosed with MPO-ANCA-GN from October 2005 to December 2018 were enrolled. The baseline clinical characteristics, renal histopathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed.

Results

All 112 patients underwent renal biopsy. Disease in 32 patients was classified as focal, 26 as mixed, 29 as crescentic, and 25 as sclerotic. Over a median follow-up period of 41.5 months, there were 44 patients dialysis-dependent. The renal survival rate was significantly higher in the focal group than the other groups (p < 0.001) and significantly lower in the sclerotic group (p < 0.05). In addition, disease histopathologically classified as sclerotic (p = 0.044), high serum creatinine level (≥320 μmol/L, p < 0.001), low albumin (<30 g/L, p = 0.024) and hemoglobin level (<90 g/L, p = 0.044) were associated with a greater risk of ESRD. After follow-up, 70 (62.5%) of 112 patients survived. Old age (≥60 years, p = 0.018) and low serum albumin (<30 g/L, p = 0.006) was significant risk factor for patient survival.

Conclusion

Among patients with MPO-ANCA-GN, those with poor renal function, disease histopathologically classified as sclerotic, and lower albumin and hemoglobin levels were risk factors for ESRD, while older age and low serum albumin level were associated with a greater risk for all-cause mortality.
A New Record of Oxytricha granulifera granulifera Foissner and Adam, 1983 (Protozoa, Ciliophora, Oxytrichidae) From a Hot Spring in Iceland, With Notes on Its Abnormal Form During Cultivation
Authors: Zhu Rong , Qu Zhishuai , Zhang Qi , Filker Sabine , Stoeck Thorsten , Li Fengchao , Hu Xiaozhong
Published: February 2021

We isolated a population of Oxytricha granulifera granuliferaFoissner and Adam (1983) from a hot spring in Iceland. The pure culture of this isolate was established at room temperature in the laboratory. This allowed for a detailed investigation, informed by integrated approaches, of the isolate’s morphology and morphogenesis, as well as molecular phylogeny. Results showed that the morphological and morphogenetic characteristics of the Iceland population are consistent with those of other populations. During the 3-year long period of laboratory cultivation, some abnormal individuals appeared repeatedly in the culture system. Interestingly, the morphological characteristics of these abnormal cells were rather stable, and were as follows: 1) body slender and elliptical-shaped; 2) remarkably shortened adoral zone and significantly reduced number of adoral membranelles; and 3) loss of undulating membranes. Resting cysts, binary fission and conjugate reproduction were not found in abnormal specimens. Although the morphology of abnormal individuals changed significantly, the sequences of the SSU rDNA of the normal and abnormal morphotypes were the same. Phylogenetic analyses showed that the two morphotypes clustered in a clade with other populations of O. granulifera granulifera.
Carbon-Based Materials as Catalyst Supports for Fischer–Tropsch Synthesis: A Review
Authors: Valero-Romero María José , Rodríguez-Cano Miguel Ángel , Palomo José , Rodríguez-Mirasol José , Cordero Tomás
Published: February 2021

The use of carbon-based materials as catalyst supports for Fischer–Tropsch synthesis (FTS) is thoroughly reviewed. The main factors to consider when using a carbonaceous catalyst support for FTS are first discussed. Then, the most relevant and recent literature on the topic from the last 2 decades is reviewed, classifying the different examples according to the carbon structure and shape. Some aspects such as the carbon textural properties, carbon support modification (functionalization and doping), catalyst preparation methods, metal particle size and location, catalyst stability and reducibility, the use of promoters, and the catalyst performance for FTS are summarized and discussed. Finally, the main conclusions, advantages, limitations, and perspectives of using carbon catalyst supports for FTS are outlined.
Risk Factors and Outcomes of Klebsiella pneumoniae Infection Before and After Allogeneic Hematopoietic Cell Transplantation
Authors: Gavriilaki Eleni , Sakellari Ioanna , Chatzikonstantinou Thomas , Mallouri Despina , Batsis Ioannis , Katsifa Eleni , Papadimitriou Stergios , Panteliadou Alkistis , Baldoumi Eirini , Demosthenous Christos , Bousiou Zoi , Constantinou Varnavas , Sotiropoulos Damianos , Anagnostopoulos Achilles
Published: February 2021

Objectives:Klebsiella pneumoniae carbapenemase (KPC)–producing K. pneumoniae (KPC-Kp) emerge as a major healthcare concern worldwide. Despite the significance of infections before and after allogeneic hematopoietic cell transplantation (alloHCT), the burden of KP infections has not been extensively evaluated.

Methods: We studied the incidence, risk factors, and outcomes of consecutive alloHCT recipients with Kp isolates before and after alloHCT.

Results: Among 424 patients who underwent alloHCT in 2008–2018, we studied two groups: those with Kp isolates before (group 1, 52 patients) and those with Kp isolates after alloHCT (group 2, 66 patients). prE-transplant infections were associated with post-transplant infections (p = 0.010), despite secondary prophylaxis. KPC-Kp was isolated in 29% of group 1, and 80% of group 2. Both groups were characterized by a significant burden of moderate–severe acute graft- vs.-host disease (GVHD) [cumulative incidence (CI) of 44.5 and 61.9%, respectively] and severe chronic (CI of 56.7 and 61.9%). Kp infections and GVHD were independent predictive factors of treatment-related mortality (TRM) in both groups.

Conclusions: Our study highlights the significant impact of Kp infections on TRM, with GVHD consisting an important underlying factor. As prophylactic measures did not improve rates of post-transplant infections, innovative interventions need to be further investigated to address this major healthcare concern.
Early Initiation of Anticoagulation Improves the Long-Term Prognosis in Patients With Antiphospholipid Syndrome Associated Portal Vein Thrombosis
Authors: You Hanxiao , Zhao Jiuliang , Huang Can , Tian Xinping , Li Mengtao , Zeng Xiaofeng
Published: February 2021

Objectives: Portal vein thrombosis (PVT) is a rare and severe clinical phenotype of antiphospholipid syndrome (APS) with a poor prognosis. Anticoagulation therapy is efficient but is associated with potentially severe bleeding episodes, especially for those patients with thrombocytopenia. We conducted this case-control study to explore the clinical features and associated factors of PVT in APS patients, the re-canalization rate of the PVT after anticoagulation and investigate the beneficial effects of early initiation of anticoagulation in patients with APS associated PVT.

Methods: We enrolled patients with APS associated PVT as the case group, and age-, and entry-time-matched APS patients without PVT (1:2) as the control group. We explored the associated factors of PVT in APS patients using multivariate logistic regression analysis. The re-canalization rate of the PVT after anticoagulation was analyzed using the survival analysis.

Results: A total of 34 patients (8 males and 26 females) with APS-PVT were enrolled, with a median follow-up time of 3 years (1.5, 7 years). Multivariate logistic regression analysis showed that thrombocytopenia (OR 6.4, 95%CI 1.561–26.218, P = 0.01), hypersensitive c-reactive protein >3 mg/L (OR 4.57, 95%CI 1.426–14.666, P = 0.011), anti β2GPI positive (OR 5, 95%CI 1.816–13.772, P = 0.002) and aPL double-positive (OR 4.08, 95%CI 1.312–12.429, P = 0.013) were independent associated factors for PVT in APS. Survival analysis revealed that effective anticoagulation could increase re-canalization rate significantly (log-rank p = 0.001), with better prognosis (lower mortality rate, log-rank p = 0.045).

Conclusions: PVT could be the first presentation of APS with insidious onset and atypical clinical symptoms and easily be misdiagnosed. For patients with APS, double aPLs positive, thrombocytopenia, and inflammation could be the associated factors of PVT. Early diagnosis and anticoagulation treatment can bring thrombus re-canalization thereby significantly improving the prognosis.
Active Surveillance of Asymptomatic, Presymptomatic, and Oligosymptomatic SARS-CoV-2-Infected Individuals in Communities Inhabiting Closed or Semi-closed Institutions
Authors: Ambrosis Nicolás , Martin Aispuro Pablo , Belhart Keila , Bottero Daniela , Crisp Renée Leonor , Dansey María Virginia , Gabrielli Magali , Filevich Oscar , Genoud Valeria , Giordano Alejandra , Lin Min Chih , Lodeiro Anibal , Marceca Felipe , Pregi Nicolás , Lenicov Federico Remes , Rocha-Viegas Luciana , Rudi Erika , Solovey Guillermo , Zurita Eugenia , Pecci Adali , Etchenique Roberto , Hozbor Daniela
Published: February 2021

Background: The high COVID-19 dissemination rate demands active surveillance to identify asymptomatic, presymptomatic, and oligosymptomatic (APO) SARS-CoV-2-infected individuals. This is of special importance in communities inhabiting closed or semi-closed institutions such as residential care homes, prisons, neuropsychiatric hospitals, etc., where risk people are in close contact. Thus, a pooling approach—where samples are mixed and tested as single pools—is an attractive strategy to rapidly detect APO-infected in these epidemiological scenarios.

Materials and Methods: This study was done at different pandemic periods between May 28 and August 31 2020 in 153 closed or semi-closed institutions in the Province of Buenos Aires (Argentina). We setup pooling strategy in two stages: first a pool-testing followed by selective individual-testing according to pool results. Samples included in negative pools were presumed as negative, while samples from positive pools were re-tested individually for positives identification.

Results: Sensitivity in 5-sample or 10-sample pools was adequate since only 2 Ct values were increased with regard to single tests on average. Concordance between 5-sample or 10-sample pools and individual-testing was 100% in the Ct ≤ 36. We tested 4,936 APO clinical samples in 822 pools, requiring 86–50% fewer tests in low-to-moderate prevalence settings compared to individual testing.

Conclusions: By this strategy we detected three COVID-19 outbreaks at early stages in these institutions, helping to their containment and increasing the likelihood of saving lives in such places where risk groups are concentrated.
Rapid Microbial Quality Assessment of Chicken Liver Inoculated or Not With Salmonella Using FTIR Spectroscopy and Machine Learning
Authors: Dourou Dimitra , Grounta Athena , Argyri Anthoula A. , Froutis George , Tsakanikas Panagiotis , Nychas George-John E. , Doulgeraki Agapi I. , Chorianopoulos Nikos G. , Tassou Chrysoula C.
Published: February 2021

Chicken liver is a highly perishable meat product with a relatively short shelf-life and that can get easily contaminated with pathogenic microorganisms. This study was conducted to evaluate the behavior of spoilage microbiota and of inoculated Salmonella enterica on chicken liver. The feasibility of Fourier-transform infrared spectroscopy (FTIR) to assess chicken liver microbiological quality through the development of a machine learning workflow was also explored. Chicken liver samples [non-inoculated and inoculated with a four-strain cocktail of ca. 103 colony-forming units (CFU)/g Salmonella] were stored aerobically under isothermal (0, 4, and 8°C) and dynamic temperature conditions. The samples were subjected to microbiological analysis with concomitant FTIR measurements. The developed FTIR spectral analysis workflow for the quantitative estimation of the different spoilage microbial groups consisted of robust data normalization, feature selection based on extra-trees algorithm and support vector machine (SVM) regression analysis. The performance of the developed models was evaluated in terms of the root mean square error (RMSE), the square of the correlation coefficient (R2), and the bias (Bf) and accuracy (Af) factors. Spoilage was mainly driven by Pseudomonas spp., followed closely by Brochothrix thermosphacta, while lactic acid bacteria (LAB), Enterobacteriaceae, and yeast/molds remained at lower levels. Salmonella managed to survive at 0°C and dynamic conditions and increased by ca. 1.4 and 1.9 log CFU/g at 4 and 8°C, respectively, at the end of storage. The proposed models exhibited Af and Bf between observed and predicted counts within the range of 1.071 to 1.145 and 0.995 to 1.029, respectively, while the R2 and RMSE values ranged from 0.708 to 0.828 and 0.664 to 0.949 log CFU/g, respectively, depending on the microorganism and chicken liver samples. Overall, the results highlighted the ability of Salmonella not only to survive but also to grow at refrigeration temperatures and demonstrated the significant potential of FTIR technology in tandem with the proposed spectral analysis workflow for the estimation of total viable count, Pseudomonas spp., B. thermosphacta, LAB, Enterobacteriaceae, and Salmonella on chicken liver.
Abnormal Expression of Dysferlin in Blood Monocytes Supports Primary Dysferlinopathy in Patients Confirmed by Genetic Analyses
Authors: Zhang Huili , Li Yaqin , Cheng Qiusheng , Chen Xi , Yu Qiuxia , Li Ze
Published: February 2021

Objective: Dysferlin deficiency causes dysferlinopathy. This study aimed to expand the mutational spectrum of dysferlinopathies, to further study one case with diagnostic ambiguity, and to identify the diagnostic value of dysferlin expression in total peripheral blood mononuclear cells (PBMC).

Methods: The clinical and molecular profiles of dysferlinopathies in eight Chinese patients were evaluated. We also conducted magnetic resonance imaging (6/8) and determined dysferlin protein expression in muscle (7/8) and PBMC (3/8).

Results: Nine of the 13 DYSF mutations identified were novel. One patient was homozygous for the Gln111Ter mutation by genomic DNA sequencing but was found to be heterozygous by sequencing of cDNA from total PBMC. A daughter of this patient did not carry any Gln111Ter mutation. Abnormal muscle MRI with predominant involvement of the medial gastrocnemius and soleus muscle was observed in 5/6 patients. Dysferlin levels were significantly reduced (immunohistochemistry/immunoblot) or absent (immunohistochemistry) in muscle and total PBMC (26–39%) for most patients. Sarcoplasmic accumulation of dysferlin was detected in one patient.

Conclusion: Genomic DNA sequencing detects frequent homozygous mutations, while fewer heterozygous mutations in cDNA are detected after posttranscription. Total PBMC may serve as an alternative to confirm diagnosis and to guide further testing in dysferlinopathies. Our results contribute to the mutational spectrum of dysferlinopathies.
Peripheral Blood and Salivary Biomarkers of Blood–Brain Barrier Permeability and Neuronal Damage: Clinical and Applied Concepts
Authors: Janigro Damir , Bailey Damian M. , Lehmann Sylvain , Badaut Jerome , O'Flynn Robin , Hirtz Christophe , Marchi Nicola
Published: February 2021

Within the neurovascular unit (NVU), the blood–brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from peripheral blood and compartments. Increased BBB permeability is clinically relevant for at least two reasons: it actively participates to the etiology of central nervous system (CNS) diseases, and it enables the diagnosis of neurological disorders based on the detection of CNS molecules in peripheral body fluids. In pathological conditions, a suite of glial, neuronal, and pericyte biomarkers can exit the brain reaching the peripheral blood and, after a process of filtration, may also appear in saliva or urine according to varying temporal trajectories. Here, we specifically examine the evidence in favor of or against the use of protein biomarkers of NVU damage and BBB permeability in traumatic head injury, including sport (sub)concussive impacts, seizure disorders, and neurodegenerative processes such as Alzheimer's disease. We further extend this analysis by focusing on the correlates of human extreme physiology applied to the NVU and its biomarkers. To this end, we report NVU changes after prolonged exercise, freediving, and gravitational stress, focusing on the presence of peripheral biomarkers in these conditions. The development of a biomarker toolkit will enable minimally invasive routines for the assessment of brain health in a broad spectrum of clinical, emergency, and sport settings.
The Weak Link: Hypotonia in Infancy and Autism Early Identification
Authors: Gabis Lidia V. , Shaham Meirav , Leon Attia Odelia , Shefer Shahar , Rosenan Ruth , Gabis Tal , Daloya Michal
Published: February 2021

Background: Presenting symptoms and age specific differential diagnosis of Autism Spectrum Disorder (ASD), determine the age of initial assessment and the age of a definite diagnosis. The AAP recommends screening all children for ASD at 18 and 24 months followed by a comprehensive evaluation for children with developmental concerns. More recently it has been recommended that the evaluation should be performed at a younger age, with a diagnosis being made as early as the beginning of the second year of life resulting in earlier intensive intervention.

Objective: To assess early developmental milestones in a cohort of children diagnosed with Autism Spectrum Disorder (ASD) in order to find an objective and reliable early marker. We suggest that low muscle tone- hypotonia, is a sign that meets the above criteria of consistency and reliability and may be related to early diagnosis.

Methods: We compared age distributions of ASD diagnosis in the presence of hypotonia in a dataset of 5,205 children diagnosed at Keshet Center. One thousand, one hundred eighty-two children (953 males) were diagnosed with ASD and compared to other developmental diagnoses. Within the ASD cohort we further analyzed for gender and pre-maturity differences.

Results: In the presence of hypotonia, the mean age for ASD diagnosis was significantly lower (by 1.5 years for males and females) and this effect increased in children born at term as compared to pre-maturity.

Conclusions: Hypotonia is a recognizable marker of ASD and may serve as a “red flag” to prompt earlier recognition and neurodevelopmental evaluation toward an autism diagnosis.
Neural Correlates of Long-Term Memory Enhancement Following Retrieval Practice
Authors: Marin-Garcia Eugenia , Mattfeld Aaron T. , Gabrieli John D. E.
Published: February 2021

Retrieval practice, relative to further study, leads to long-term memory enhancement known as the “testing effect.” The neurobiological correlates of the testing effect at retrieval, when the learning benefits of testing are expressed, have not been fully characterized. Participants learned Swahili-English word-pairs and were assigned randomly to either the Study-Group or the Test-Group. After a week delay, all participants completed a cued-recall test while undergoing functional magnetic resonance imaging (fMRI). The Test-Group had superior memory for the word-pairs compared to the Study-Group. While both groups exhibited largely overlapping activations for remembered word-pairs, following an interaction analysis the Test-Group exhibited differential performance-related effects in the left putamen and left inferior parietal cortex near the supramarginal gyrus. The same analysis showed the Study-Group exhibited greater activations in the dorsal MPFC/pre-SMA and bilateral frontal operculum for remembered vs. forgotten word-pairs, whereas the Test-Group showed the opposite pattern of activation in the same regions. Thus, retrieval practice during training establishes a unique striatal-supramarginal network at retrieval that promotes enhanced memory performance. In contrast, study alone yields poorer memory but greater activations in frontal regions.
Combining Observation and Physical Practice: Benefits of an Interleaved Schedule for Visuomotor Adaptation and Motor Memory Consolidation
Authors: Larssen Beverley C. , Ho Daniel K. , Kraeutner Sarah N. , Hodges Nicola J.
Published: February 2021

Visuomotor adaptation to novel environments can occur via non-physical means, such as observation. Observation does not appear to activate the same implicit learning processes as physical practice, rather it appears to be more strategic in nature. However, there is evidence that interspersing observational practice with physical practice can benefit performance and memory consolidation either through the combined benefits of separate processes or through a change in processes activated during observation trials. To test these ideas, we asked people to practice aiming to targets with visually rotated cursor feedback or engage in a combined practice schedule comprising physical practice and observation of projected videos showing successful aiming. Ninety-three participants were randomly assigned to one of five groups: massed physical practice (Act), distributed physical practice (Act+Rest), or one of 3 types of combined practice: alternating blocks (Obs_During), or all observation before (Obs_Pre) or after (Obs_Post) blocked physical practice. Participants received 100 practice trials (all or half were physical practice). All groups improved in adaptation trials and showed savings across the 24-h retention interval relative to initial practice. There was some forgetting for all groups, but the magnitudes were larger for physical practice groups. The Act and Obs_During groups were most accurate in retention and did not differ, suggesting that observation can serve as a replacement for physical practice if supplied intermittently and offers advantages above just resting. However, after-effects associated with combined practice were smaller than those for physical practice control groups, suggesting that beneficial learning effects as a result of observation were not due to activation of implicit learning processes. Reaction time, variable error, and post-test rotation drawings supported this conclusion that adaptation for observation groups was promoted by explicit/strategic processes.
Orexin-A/Hypocretin-1 Controls the VTA-NAc Mesolimbic Pathway via Endocannabinoid-Mediated Disinhibition of Dopaminergic Neurons in Obese Mice
Authors: Tunisi Lea , D'Angelo Livia , Fernández-Rilo Alba Clara , Forte Nicola , Piscitelli Fabiana , Imperatore Roberta , de Girolamo Paolo , Di Marzo Vincenzo , Cristino Luigia
Published: February 2021

Disinhibition of orexin-A/hypocretin-1 (OX-A) release occurs to several output areas of the lateral hypothalamus (LH) in the brain of leptin knockout obese ob/ob mice. In this study, we have investigated whether a similar increase of OX-A release occurs to the ventral tegmental area (VTA), an orexinergic LH output area with functional effects on dopaminergic signaling at the mesolimbic circuit. By confocal and correlative light and electron microscopy (CLEM) morphological studies coupled to molecular, biochemical, and pharmacological approaches, we investigated OX-A-mediated dopaminergic signaling at the LH-VTA-nucleus accumbens (NAc) pathway in obese ob/ob mice compared to wild-type (wt) lean littermates. We found an elevation of OX-A trafficking and release to the VTA of ob/ob mice and consequent orexin receptor-1 (OX1R)-mediated over-activation of dopaminergic (DA) neurons via phospholipase C (PLC)/diacylglycerol lipase (DAGL-α)-induced biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). In fact, by retrograde signaling to cannabinoid receptor type 1 (CB1R) at inhibitory inputs to DA neurons, 2-AG inhibited GABA release thus inducing an increase in DA concentration in the VTA and NAc of ob/ob mice. This effect was prevented by the OX1R antagonist SB-334867 (30 mg/Kg, i.p.), or the CB1R antagonist AM251 (10 mg/Kg, i.p.) and mimicked by OX-A injection (40 μg/Kg, i.p.) in wt lean mice. Enhanced DA signaling to the NAc in ob/ob mice, or in OX-A-injected wt mice, was accompanied by β-arrestin2-mediated desensitization of dopamine D2 receptor (D2R) in a manner prevented by SB-334867 or the D2R antagonist L741 (1.5 mg/Kg, i.p.). These results further support the role of OX-A signaling in the control of neuroadaptive responses, such as compulsive reward-seeking behavior or binge-like consumption of high palatable food, and suggest that aberrant OX-A trafficking to the DA neurons in the VTA of ob/ob mice influences the D2R response at NAc, a main target area of the mesolimbic pathway, via 2-AG/CB1-mediated retrograde signaling.
An Evaluation of the COVID-19 Pandemic and Perceived Social Distancing Policies in Relation to Planning, Selecting, and Preparing Healthy Meals: An Observational Study in 38 Countries Worldwide
Authors: De Backer Charlotte , Teunissen Lauranna , Cuykx Isabelle , Decorte Paulien , Pabian Sara , Gerritsen Sarah , Matthys Christophe , Al Sabbah Haleama , Van Royen Kathleen ,   the Corona Cooking Survey Study Group
Published: February 2021

Objectives

To examine changes in planning, selecting, and preparing healthy foods in relation to personal factors (time, money, stress) and social distancing policies during the COVID-19 crisis.

Methods

Using cross-sectional online surveys collected in 38 countries worldwide in April-June 2020 (N = 37,207, Mage 36.7 SD 14.43, 73.6% women), we compared changes in food literacy behaviors to changes in personal factors and social distancing policies, using hierarchical multiple regression analyses controlling for sociodemographic variables.

Results

Increases in planning (4.7 SD 1.2, 4.9 SD 1.3), selecting (3.8 SD 1.7, 3.8 SD 1.7), and preparing (4.6 SD 1.3, 4.7 SD 1.3) healthy foods were found for women and men, and positively related to perceived time availability among women and stay-at-home policies for planning and preparing in women. Psychological distress was a barrier for women, and an enabler for men. COVID-19 induced financial stress was a barrier depending on various sociodemographic variables (all p < 0.01).

Conclusion

Stay-at-home policies and feelings of having more time during COVID-19 seem to have improved food literacy among women. Stress and other social distancing policies relate to food literacy in more complex ways, highlighting the necessity of a health equity lens.
CyTOF Analysis Reveals a Distinct Immunosuppressive Microenvironment in IDH Mutant Anaplastic Gliomas
Authors: Fu Weilun , Wang Wenjing , Li Hao , Jiao Yuming , Weng Jiancong , Huo Ran , Yan Zihan , Wang Jie , Xu Hongyuan , Wang Shuo , Wang Jiangfei , Chen Dexi , Cao Yong , Zhao Jizong
Published: February 2021

The immune microenvironment is important for the development, progression, and prognosis of anaplastic glioma (AG). This complex milieu has not been fully elucidated, and a high-dimensional analysis is urgently required. Utilizing mass cytometry (CyTOF), we performed an analysis of immune cells from 5 patients with anaplastic astrocytoma, IDH-mutant (AAmut) and 10 patients with anaplastic oligodendroglioma, IDH-mutant and 1p/19q codeletion (AOD) and their paired peripheral blood mononuclear cells (PBMCs). Based on a panel of 33 biomarkers, we demonstrated the tumor-driven immune changes in the AG immune microenvironment. Our study confirmed that mononuclear phagocytes and T cells are the most abundant immunocytes in the AG immune microenvironment. Glioma-associated microglia/macrophages in both AAmut and AOD samples showed highly immunosuppressive characteristics. Compared to those in the PBMCs, the ratios of immune checkpoint-positive exhausted CD4+ T cells and CD8+ T cells were higher at the AG tumor sites. The AAmut immune milieu exhibits more immunosuppressive characteristics than that in AOD.
A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA
Authors: Ottaviano Margaret , Giuliano Mario , Tortora Marianna , La Civita Evelina , Liotti Antonietta , Longo Michele , Bruzzese Dario , Cennamo Michele , Riccio Vittorio , De Placido Pietro , Picozzi Fernanda , Parola Sara , Daniele Bruno , Botti Gerardo , Formisano Pietro , Beguinot Francesco , De Placido Sabino , Terracciano Daniela , Palmieri Giovannella
Published: February 2021

Background

Thymic epithelial tumors (TETs) are rare thoracic malignancies, commonly divided into two different histopathological entities, thymoma (T) and thymic carcinoma (TC). To date, there are no specific biomarkers for monitoring the biological course of these rare tumors. We carried out a single center study aiming at the detection of circulating cell-free DNA (ccfDNA) and the correlation of its levels with metastatic dissemination and histological subtype in patients with TETs.

Methods

From July 2018 to January 2020, 5-ml blood samples from 26 patients with advanced TET (aTET) (11 patients with TC and 15 patients with T) and from six patients with completely resected TET (cr-TET), were prospectively obtained before the initiation of systemic therapy. Blood samples from 10 healthy donors were used as control. The QIAamp MinElute ccfDNA Kits was used for ccfDNA isolation from plasma; real-time PCR was used for cfDNA quantification.

Results

We found significantly higher ccfDNA amount in patients with T and TC compared to controls, with median ccfDNA level of 3.3 ng/µl, 11.4 ng/µl and 25.6 ng/µl, for healthy donors, T and TC patients, respectively (p<0.001). No significant difference was found between cr-TET and controls (p = 0.175). ccfDNA concentrations were higher in metastatic (M1a and M1b) compared to non-metastatic (M0) TETs (25.6 ng/µl versus 7.2 ng/µl; p= 0.037). No significant correlation was found either between ccfDNA and disease stage, according to both the Masaoka-Koga (p= 0.854) and the TNM 8th edition staging systems (p = 0.66), or between ccfDNA levels and overall tumor burden, estimated according RECIST 1.1 criteria (r = 0.07, p = 0.725).

Conclusions

To the best of our knowledge, this is the first study that prospectively explores detection and quantification of ccfDNA in TETs. Higher baseline cfDNA levels have been observed in both advanced T and TC comparing to the control group.
A Novel Androgen-Induced lncRNA FAM83H-AS1 Promotes Prostate Cancer Progression via the miR-15a/CCNE2 Axis
Authors: Liu Bo , Qian Duocheng , Zhou Weidong , Jiang Huiyang , Xiang Zhendong , Wu Denglong
Published: February 2021

Prostate cancer (PCa) is one of the most common types of tumors among males worldwide. However, the roles of long noncoding RNAs (lncRNAs) in PCa remain unclear. This study shows that lncRNA FAM83H-AS1 is upregulated in prostate adenocarcinoma, bladder urothelial carcinoma, and kidney renal papillary cell carcinoma samples. Androgen receptor (AR) signaling plays the most important role in PCa tumorigenesis and development. In this study, the results validate that AR signaling is involved in upregulating FAM83H-AS1 expression in PCa cells. Loss-of-function assays demonstrate that FAM83H-AS1 acts as an oncogene in PCa by modulating cell proliferation, cell cycle, and migration. Bioinformatics analysis demonstrates that FAM83H-AS1 is remarkably related to the regulation of the cell cycle and DNA replication through affecting multiple regulators related to these pathways, such as CCNE2. Mechanically, we found that FAM83H-AS1 plays its roles through sponging miR-15a to promote CCNE2 expression. These findings indicate that FAM83H-AS1 is a novel diagnostic and therapeutic marker for PCa.
Case Report: Complete Remission of C1q Nephropathy Treated With a Single Low-Dose Rituximab, a Reality or Coincidence?
Authors: Ma Rui , Wu Dengyan , He Zhiqin , Chang Qian , Yang Yonghong
Published: February 2021

C1q nephropathy is a glomerulopathy that is characterized by large amount of C1q deposits in the glomerular mesangium. It is a diagnosis of exclusion after ruling out systemic lupus erythematosus and membranoproliferative glomerulonephritis by systemic and serological examination. The pathogenesis of C1q nephropathy is unclear. In addition, there is very little generalizability in the treatment and prognosis for pediatric C1q nephropathy due to diversities in clinical manifestations and pathological types. Rituximab is a human/mouse chimeric monoclonal antibody against CD20, which is primarily used for treating lymphomas and, most recently, has been used to treat certain kidney diseases including C1q nephropathy. In this report, we used one quarter of the typical dose of rituximab for lymphoma treatment to achieve complete remission in a C1q nephropathy patient, significantly reducing deposition of immune complexes and glomerular damage. This case indicates that dosage reconsiderations may be necessary for rituximab in treatment of pediatric C1q nephropathy.