bluuebunny/crossref_metadata_2025 huggingface dataset:
CO2 Storage Potential Reconnaissance of the Newly Identified Red Beds of Hazlehurst in the Southeastern United States
Authors: Cao Ruoshi , Knapp James , Bikkina Prem , Esposito Richard
Published: December 2021

The states of Georgia and South Carolina emitted ∼100 million tons (Mt) of CO2 in 2019 from point sources. Integration and interpretation of subsurface data enabled identification of a previously unrecognized, regionally extensive, and thick (up to 450 m) sedimentary sequence—the Red beds of Hazlehurst (RbH)—as a potential saline reservoir for CO2 storage in the southeastern United States. Based on the renewed stratigraphic framework and structural interpretation of the RbH interval, we analyzed detailed well logs and the depositional environments to provide reconnaissance-level regional scale estimations of the storage resource. The volumetric results suggest the effective storage area (∼85,000 km2) has a maximum resource potential for 390 gigatons (Gt) of anthropogenic CO2. Petrophysical measurements suggest the permeability of RbH ranges from 0.001 to 48 mD, and the porosity ranges from 11.1 to 18.4%. Residual/capillary trapping and solubility trapping act as the main trapping mechanisms for long term storage and prevent vertical migration of CO2 into the shallow freshwater aquifers. Due to the heterogeneity observed in geophysical logs and the scarcity of well penetrations, future data collection is needed to characterize the storage aquifer and confining aquitards of a site-specific system at this stage.
Moderate Grazing Increases Water Use Efficiency for Environmental Health in Alpine Meadows of the Tibetan Plateau
Authors: Wang Yunying , Pei Weiwei , Cao Guangmin , Guo Xiaowei , Zhou Huakun , Du Yangong
Published: December 2021

Water use efficiency is an important indicator of drought tolerance in plants. The response of the water use efficiency to different grazing intensities and adaptive mechanisms in alpine meadows remains unclear. To understand the changes in water use in alpine meadow ecosystems under different grazing gradients, grazing systems have to be optimized, and severely receding grasslands should be effectively restored. This study analyzed the response of water use efficiency of plant dominant species, coexisting species, and functional group-level plants to grazing intensity using the δ13C index in an alpine meadow. We found that grazing increased the leaf carbon isotope composition in plants (δ13C) of Gramineae by 3.37% and grazing at a moderate level significantly increased it by 4.84% (P < 0.05). In addition, an increase in δ13C was observed in the functional groups of Cyperaceae (3.45%), Leguminosae (0.81%), and Forb (1.40%). However, some dominant species and coexisting species showed the highest δ13C values under moderate grazing. These results indicate that moderate grazing may significantly improve the water use efficiency of species in alpine meadows. The path analysis showed that water use efficiency was negatively correlated with evapotranspiration (P < 0.05), soil water content, soil organic carbon, and soil bulk density. Nevertheless, there was a positive correlation between water use efficiency and the available nitrogen. This study concluded that moderate grazing could improve the efficiency of grassland water use to a certain extent. Additionally, soil evapotranspiration was the main driving factor affecting the water use efficiency of alpine meadows.
Multiple Anthropogenic Pressures Lead to Seed Dispersal Collapse of the Southernmost Palm Jubaea chilensis
Authors: Cordero Sebastián , Gálvez Francisca , Fontúrbel Francisco E.
Published: December 2021

Seed dispersal is a critical process for plant reproduction and regeneration. Successful recruitment depends on pre- and post-dispersal processes that complete a seed’s journey until becoming a new plant. However, anthropogenic stressors may disrupt the seed dispersal process at some stages, collapsing plant regeneration and hampering its long-term persistence. The Chilean palm tree Jubaea chilensis is the southernmost and the only non-tropical palm species, which currently relies on the scatter-hoarding rodent Octodon degus for seed dispersal. We assessed seed fate by measuring predation and dispersal rates through experimental fieldwork in the Palmar de Ocoa site (located within La Campana National Park) and the Palmar El Salto. We also used previous reports on seed harvest and seedling herbivory to depict the whole J. chilensis seed dispersal process and assess the relative importance of different anthropogenic pressures. We asked the following questions: (1) What is the effect of human harvesting on J. chilensis recruitment? (2) Do native and exotic rodents predate J. chilensis seeds in the same way? and (3) Does post-dispersal herbivory matter? We found that J. chilensis fruits are harvested for human consumption, reducing pre-dispersal available seeds by removing about 23 tons per season. Then, post-dispersal seeds at the Ocoa palm grove are heavily predated by exotic (Rattus rattus) and native (Octodon spp.) rodents; only 8.7% of the seeds are effectively dispersed by Octodon degus. At Palmar El Salto, 100% of the seeds were predated by Rattus rattus, precluding further analysis. Finally, 70% of the seedlings were consumed by exotic herbivores (mainly rabbits), resulting in a success rate of 1.81%. Only 7.9% of the surviving seedlings become infantile plants (4 year-old). Our assessment suggests that J. chilensis has aging populations with very few young individuals in disturbed sites to replace the old ones. For those reasons, we suggest increasing its conservation category to critically endangered as land-use change is rapidly fragmenting and shrinking the extant J. chilensis populations. We urge to take urgent actions to protect this relict palm, which otherwise may go extinct in the next decades.
Climate Warming Increased Spring Leaf-Out Variation Across Temperate Trees in China
Authors: Zhang Yaru , Fu Yongshuo , Geng Xiaojun , Chen Shouzhi , Guo Yahui , Wu Zhaofei , De Boeck Hans J.
Published: December 2021

Leaf-out phenology plays a key role in ecosystem structure and functioning. Phenological changes have often been linked to climatic factors and have received considerable attention, with most studies focusing on trends of leaf-out phenology. Leaf-out variation (LOV), which reflects the stability of phenological responses, may also be affected by climate change, yet this has received less scientific attention. In this study, we examined spring LOV in response to climate change in China during the period 1963–2008 using in situ records of 15 species at 25 phenological observation sites across several climate zones and explored spatiotemporal changes of LOV and the underlying mechanisms. We observed a significant decrease of LOV toward higher latitudes (−0.2 ± 0.1 days⋅°N–1;P < 0.001) across all species. Temporally, we found that the LOV was significantly increased from the period 1963–1986 (6.9 ± 2.8 days) to the period 1987–2008 (7.9 ± 3.7 days, P < 0.05). Furthermore, the LOV changes between 1987–2008 and 1963–1986 were significantly smaller at high latitudes (average decrease of 1.0 day) than at low latitudes (average increase of 1.5 days). The spatial pattern of LOV is likely due to both increased heat requirements and greater temperature sensitivity at low latitudes compared with high latitudes. The temporal pattern of LOV is likely related to increased heat requirements for leaf-out during 1987–2008 when the average air temperature was higher. Our analysis indicated that the phenology response to climate change is reflected not only in the temporal trends for long time series but also in the variation of phenological dates. Results from this study improve our understanding of phenological responses to climate change and could be applied in the assessment of regional phenology changes to evaluate better the impacts of climate change on ecosystem structure and function.
Synaptic Protein Phosphorylation Networks Are Associated With Electroacupuncture-Induced Circadian Control in the Suprachiasmatic Nucleus
Authors: Lu Xiaoxiao , Zhou Minjie , Liu Nannan , Zhang Chengshun , Zhao Zhengyu , Cai Dingjun
Published: December 2021

Phosphorylation is one of the most important posttranslational modifications and regulates the physiological process. While recent studies highlight a major role of phosphorylation in the regulation of sleep–wake cycles to a lesser extent, the phosphoproteome in the suprachiasmatic nucleus (SCN) is not well-understood. Herein, we reported that the EA treatment elicits partial reparation of circadian rhythmicity when mice were exposure to constant darkness for long time. We investigated the effects of EA on circadian rhythms in constant darkness between EA stimulation and free-running control. Next, mass spectrometry–based phosphoproteome was utilized to explore the molecular characteristics of EA-induced phosphorylation modification in the SCN. A total of 6,192 distinct phosphosites on 2,488 proteins were quantified. Functional annotation analysis and protein–protein interaction networks demonstrated the most significant enriched phosphor-proteins and phosphosites involved in postsynapse and glutamatergic synapse. The current data indicated that most of the altered molecules are structural proteins. The target proteins, NMDAR and CAMK2, were selected for verification, consistent with the results of LC–MS/MS. These findings revealed a complete profile of phosphorylation modification in response to EA.
CSF-Neurofilament Light Chain Levels in NMDAR and LGI1 Encephalitis: A National Cohort Study
Authors: Nissen Mette Scheller , Ryding Matias , Nilsson Anna Christine , Madsen Jonna Skov , Olsen Dorte Aalund , Halekoh Ulrich , Lydolph Magnus , Illes Zsolt , Blaabjerg Morten
Published: December 2021

Background and Objectives

The two most common autoimmune encephalitides (AE), N-methyl-D-Aspartate receptor (NMDAR) and Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis, have been known for more than a decade. Nevertheless, no well-established biomarkers to guide treatment or estimate prognosis exist. Neurofilament light chain (NfL) has become an unspecific screening marker of axonal damage in CNS diseases, and has proven useful as a diagnostic and disease activity marker in neuroinflammatory diseases. Only limited reports on NfL in AE exist. We investigated NfL levels at diagnosis and follow-up in NMDAR and LGI1-AE patients, and evaluated the utility of CSF-NfL as a biomarker in AE.

Methods

Patients were included from the National Danish AE cohort (2009-present) and diagnosed based upon autoantibody positivity and diagnostic consensus criteria. CSF-NfL was analyzed by single molecule array technology. Clinical and diagnostic information was retrospectively evaluated and related to NfL levels at baseline and follow-up. NMDAR-AE patients were subdivided into: idiopathic/teratoma associated or secondary NMDAR-AE (post-viral or concomitant with malignancies/demyelinating disease).

Results

A total of 74 CSF samples from 53 AE patients (37 NMDAR and 16 LGI1 positive) were included in the study. Longitudinal CSF-NfL levels was measured in 21 patients. Median follow-up time was 23.8 and 43.9 months for NMDAR and LGI1-AE respectively. Major findings of this study are: i) CSF-NfL levels were higher in LGI1-AE than in idiopathic/teratoma associated NMDAR-AE at diagnosis; ii) CSF-NfL levels in NMDAR-AE patients distinguished idiopathic/teratoma cases from cases with other underlying etiologies (post-viral or malignancies/demyelinating diseases) and iii) Elevated CSF-NfL at diagnosis seems to be associated with worse long-term disease outcomes in both NMDAR and LGI1-AE.

Discussion

CSF-NfL measurement may be beneficial as a prognostic biomarker in NMDAR and LGI1-AE, and high CSF-NfL could foster search for underlying etiologies in NMDAR-AE. Further studies on larger cohorts, using standardized methods, are warranted.
Cryo-Electron Microscopy and Biochemical Analysis Offer Insights Into the Effects of Acidic pH, Such as Occur During Acidosis, on the Complement Binding Properties of C-Reactive Protein
Authors: Noone Dylan P. , van der Velden Tijn T. , Sharp Thomas H.
Published: December 2021

The pentraxin family of proteins includes C-reactive protein (CRP), a canonical marker for the acute phase inflammatory response. As compared to normal physiological conditions in human serum, under conditions associated with damage and inflammation, such as acidosis and the oxidative burst, CRP exhibits modulated biochemical properties that may have a structural basis. Here, we explore how pH and ligand binding affect the structure and biochemical properties of CRP. Cryo-electron microscopy was used to solve structures of CRP at pH 7.5 or pH 5 and in the presence or absence of the ligand phosphocholine (PCh), which yielded 7 new high-resolution structures of CRP, including pentameric and decameric complexes. Structures previously derived from crystallography were imperfect pentagons, as shown by the variable angles between each subunit, whereas pentameric CRP derived from cryoEM was found to have C5 symmetry, with subunits forming a regular pentagon with equal angles. This discrepancy indicates flexibility at the interfaces of monomers that may relate to activation of the complement system by the C1 complex. CRP also appears to readily decamerise in solution into dimers of pentamers, which obscures the postulated binding sites for C1. Subtle structural rearrangements were observed between the conditions tested, including a putative change in histidine protonation that may prime the disulphide bridges for reduction and enhanced ability to activate the immune system. Enzyme-linked immunosorbent assays showed that CRP had markedly increased association to the C1 complex and immunoglobulins under conditions associated with acidosis, whilst a reduction in the Ca2+concentration lowered this pH-sensitivity for C1q, but not immunoglobulins, suggesting different modes of binding. These data suggest a model whereby a change in the ionic nature of CRP and immunological proteins can make it more adhesive to potential ligands without large structural rearrangements.
A Role for B Cells to Transmit Hepatitis C Virus Infection
Authors: Desombere Isabelle , Van Houtte Freya , Farhoudi Ali , Verhoye Lieven , Buysschaert Caroline , Gijbels Yvonne , Couvent Sibyl , Swinnen Wilfried , Van Vlierberghe Hans , Elewaut André , Magri Andrea , Stamataki Zania , Meuleman Philip , McKeating Jane A , Leroux-Roels Geert
Published: December 2021

Hepatitis C virus (HCV) is highly variable and transmits through infected blood to establish a chronic liver infection in the majority of patients. Our knowledge on the infectivity of clinical HCV strains is hampered by the lack of in vitro cell culture systems that support efficient viral replication. We and others have reported that HCV can associate with and infect immune cells and may thereby evade host immune surveillance and elimination. To evaluate whether B cells play a role in HCV transmission, we assessed the ability of B cells and sera from recent (<2 years) or chronic (≥ 2 years) HCV patients to infect humanized liver chimeric mice. HCV was transmitted by B cells from chronic infected patients whereas the sera were non-infectious. In contrast, B cells from recently infected patients failed to transmit HCV to the mice, whereas all serum samples were infectious. We observed an association between circulating anti-glycoprotein E1E2 antibodies and B cell HCV transmission. Taken together, our studies provide evidence for HCV transmission by B cells, findings that have clinical implications for prophylactic and therapeutic antibody-based vaccine design.
A Novel Strategy to Identify Haematology Patients at High Risk of Developing Aspergillosis
Authors: Griffiths James S. , White P. Lewis , Thompson Aiysha , da Fonseca Diogo M. , Pickering Robert J. , Ingram Wendy , Wilson Keith , Barnes Rosemary , Taylor Philip R. , Orr Selinda J.
Published: December 2021

Invasive Aspergillosis (IA), typically caused by the fungusAspergillus fumigatus, is a leading cause of morbidity and mortality in immunocompromised patients. IA remains a significant burden in haematology patients, despite improvements in the diagnosis and treatment ofAspergillusinfection. Diagnosing IA is challenging, requiring multiple factors to classify patients into possible, probable and proven IA cohorts. Given the low incidence of IA, using negative results as exclusion criteria is optimal. However, frequent false positives and severe IA mortality rates in haematology patients have led to the empirical use of toxic, drug-interactive and often ineffective anti-fungal therapeutics. Improvements in IA diagnosis are needed to reduce unnecessary anti-fungal therapy. Early IA diagnosis is vital for positive patient outcomes; therefore, a pre-emptive approach is required. In this study, we examined the sequence and expression of four C-type Lectin-like receptors (Dectin-1, Dectin-2, Mincle, Mcl) from 42 haematology patients and investigated each patient’s anti-Aspergillusimmune response (IL-6, TNF). Correlation analysis revealed novel IA disease risk factors which we used to develop a pre-emptive patient stratification protocol to identify haematopoietic stem cell transplant patients at high and low risk of developing IA. This stratification protocol has the potential to enhance the identification of high-risk patients whilst reducing unnecessary treatment, minimizing the development of anti-fungal resistance, and prioritising primary disease treatment for low-risk patients.
Innate Receptors Expression by Lung Nociceptors: Impact on COVID-19 and Aging
Authors: Hiroki Carlos H. , Sarden Nicole , Hassanabad Mortaza F. , Yipp Bryan G.
Published: December 2021

The lungs are constantly exposed to non-sterile air which carries harmful threats, such as particles and pathogens. Nonetheless, this organ is equipped with fast and efficient mechanisms to eliminate these threats from the airways as well as prevent pathogen invasion. The respiratory tract is densely innervated by sensory neurons, also known as nociceptors, which are responsible for the detection of external stimuli and initiation of physiological and immunological responses. Furthermore, expression of functional innate receptors by nociceptors have been reported; however, the influence of these receptors to the lung function and local immune response is poorly described. The COVID-19 pandemic has shown the importance of coordinated and competent pulmonary immunity for the prevention of pathogen spread as well as prevention of excessive tissue injury. New findings suggest that lung nociceptors can be a target of SARS-CoV-2 infection; what remains unclear is whether innate receptor trigger sensory neuron activation during SARS-CoV-2 infection and what is the relevance for the outcomes. Moreover, elderly individuals often present with respiratory, neurological and immunological dysfunction. Whether aging in the context of sensory nerve function and innate receptors contributes to the disorders of these systems is currently unknown. Here we discuss the expression of innate receptors by nociceptors, particularly in the lungs, and the possible impact of their activation on pulmonary immunity. We then demonstrate recent evidence that suggests lung sensory neurons as reservoirs for SARS-CoV-2 and possible viral recognition via innate receptors. Lastly, we explore the mechanisms by which lung nociceptors might contribute to disturbance in respiratory and immunological responses during the aging process.
Pharmacomicrobiology of Methotrexate in Rheumatoid Arthritis: Gut Microbiome as Predictor of Therapeutic Response
Authors: Yan Huanhuan , Su Rui , Xue Hongwei , Gao Chong , Li Xiaofeng , Wang Caihong
Published: December 2021

Rheumatoid arthritis (RA) is a disabling autoimmune disease with invasive arthritis as the main manifestation and synovitis as the basic pathological change, which can cause progressive destruction of articular cartilage and bone, ultimately leading to joint deformity and loss of function. Since its introduction in the 1980s and its widespread use in the treatment of RA, low-dose methotrexate (MTX) therapy has dramatically changed the course and outcome of RA treatment. The clinical use of this drug will be more rational with a better understanding of the pharmacology, anti-inflammatory mechanisms of action and adverse reaction about it. At present, the current clinical status of newly diagnosed RA is that MTX is initiated first regardless of the patients’ suitability. But up to 50% of patients could not reach adequate clinical efficacy or have severe adverse events. Prior to drug initiation, a prognostic tool for treatment response is lacking, which is thought to be the most important cause of the situation. A growing body of studies have shown that differences in microbial metagenomes (including bacterial strains, genes, enzymes, proteins and/or metabolites) in the gastrointestinal tract of RA patients may at least partially determine their bioavailability and/or subsequent response to MTX. Based on this, some researchers established a random forest model to predict whether different RA patients (with different gut microbiome) would respond to MTX. Of course, MTX, in turn, alters the gut microbiome in a dose-dependent manner. The interaction between drugs and microorganisms is called pharmacomicrobiology. Then, the concept of precision medicine has been raised. In this view, we summarize the characteristics and anti-inflammatory mechanisms of MTX and highlight the interaction between gut microbiome and MTX aiming to find the optimal treatment for patients according to individual differences and discuss the application and prospect of precision medicine.
Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding
Authors: Paudyal Basudev , McNee Adam , Rijal Pramila , Carr B. Veronica , Nunez Alejandro , McCauley John , Daniels Rodney S. , Townsend Alain R. , Hammond John A. , Tchilian Elma
Published: December 2021

We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing the therapeutic potential of monoclonal antibodies (mAbs). In this study we demonstrated that prophylactic intravenous administration of 15 mg/kg of porcine mAb pb18, against the K160–163 site of the hemagglutinin, significantly reduced lung pathology and nasal virus shedding and eliminated virus from the lung of pigs following H1N1pdm09 challenge. When given at 1 mg/kg, pb18 significantly reduced lung pathology and lung and BAL virus loads, but not nasal shedding. Similarly, when pb18 was given in combination with pb27, which recognized the K130 site, at 1 mg/kg each, lung virus load and pathology were reduced, although without an apparent additive or synergistic effect. No evidence for mAb driven virus evolution was detected. These data indicate that intravenous administration of high doses was required to reduce nasal virus shedding, although this was inconsistent and seldom complete. In contrast, the effect on lung pathology and lung virus load is consistent and is also seen at a one log lower dose, strongly indicating that a lower dose might be sufficient to reduce severity of disease, but for prevention of transmission other measures would be needed.
Immunotherapy for Refractory Autoimmune Encephalitis
Authors: Yang Jiawei , Liu Xueyan
Published: December 2021

Autoimmune encephalitis (AE) is an immune-mediated disease involving the central nervous system, usually caused by antigen-antibody reactions. With the advent of autoantibody-associated diseases, AE has become a hot research frontier in neuroimmunology. The first-line conventional treatments of autoimmune encephalitis consist of steroids, intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and second-line therapy includes rituximab. Despite considerable research and expanding clinical experience, current treatments are still ineffective for a significant number of patients. Although there is no clear consensus, clinical trial evidence limited, and the level of evidence for some of the drugs based on single reports, third-line therapy is a viable alternative for refractory encephalitis patients. With the current rapid research progress, a breakthrough in the treatment of AE is critical. This article aims to review the third-line therapy for refractory AE
The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells
Authors: Lee Sang Hag , Kang Sung Hoon , Han Mun Soo , Kwak Ji Won , Kim Hyeon Geun , Lee Tae Hoon , Lee Da Bin , Kim Tae Hoon
Published: December 2021

EphA2 receptor and its ephrin ligands are involved in virus infection, epithelial permeability, and chemokine secretion. We hypothesized that ephrinA1/ephA2 signaling participates in rhinovirus (RV)-induced antiviral immune response in sinonasal mucosa of patients with chronic rhinosinusitis (CRS). Therefore, we investigated the expression of ephrinA1/ephA2 in normal and inflamed sinonasal mucosa and evaluated whether they regulate chemokine secretion and the production of antiviral immune mediators including interferons (IFNs) in RV-infected human primary sinonasal epithelial cells. For this purpose, the expression and distribution of ephrinA1/ephA2 in sinonasal mucosa were evaluated with RT-qPCR, immunofluorescence, and western blot. Their roles in chemokine secretion and the production of antiviral immune mediators such as type I and III IFNs, and interferon stimulated genes were evaluated by stimulating ephA2 with ephrinA1 and inactivating ephA2 with ephA2 siRNA or inhibitor in cells exposed to RV and poly(I:C). We found that ephrinA1/ephA2 were expressed in normal mucosa and their levels increased in inflamed sinonasal mucosa of CRS patients. RV infection or poly(I:C) treatment induced chemokine secretion which were attenuated by blocking the action of ephA2 with ephA2 siRNA or inhibitor. The production of antiviral immune mediators enhanced by rhinovirus or poly (I:C) is increased by blocking ephA2 compared with that of cells stimulated by either rhinovirus or poly(I:C) alone. In addition, blocking ephA2 attenuated RV replication in cultured cells. Taken together, these results describe a novel role of ephrinA1/ephA2 signaling in antiviral innate immune response in sinonasal epithelium, suggesting their participation in RV-induced development and exacerbations of CRS.
Comparison of C-Reactive Protein in Dried Blood Spots and Saliva of Healthy Adolescents
Authors: Plank Anne-Christine , Maschke Janina , Rohleder Nicolas , Fasching Peter A. , Beckmann Matthias W. , Kornhuber Johannes , Eichler Anna , Moll Gunther H. , Kratz Oliver
Published: December 2021

Background/Aim

Determining C-reactive protein (CRP) by non-invasive methods is of great interest for research addressing inflammation in young people. However, direct comparisons of such methods applied in children and adolescents are lacking so far. This study aimed to evaluate the association between CRP measured in dried blood spots (DBS CRP) and in saliva (sCRP), two less invasive alternatives to venipuncture, in 12- to 14-year-old adolescents. To evaluate the validity of both measurements in the context of biobehavioral studies, the potential of DBS CRP and sCRP to discriminate between defined BMI subgroups was assessed.

Materials and Methods

CRP levels in DBS and saliva collected from 87 healthy adolescents (M = 13.25 years, SD = 0.30, 51.7% females) were determined using high sensitive CRP ELISA for serum and salivary CRP ELISA, respectively. Characteristics and correlation of both measurements were assessed for the total sample and for three subgroups classified by BMI percentile ranges (A: ≤ 25; B: 26–74; C: ≥ 75).

Results

In the total sample, DBS CRP and sCRP were significantly associated (r = 0.59, p < 0.001). Splitting the sample into BMI-dependent subgroups revealed similarly strong associations of DBS CRP with sCRP for all three groups (A: r = 0.51; B: r = 0.61; C: r = 0.53). However, comparing the mean CRP values per BMI subgroup, one-way ANOVA reported significant differences for DBS CRP, but not for sCRP mean values.

Conclusions

The significant correlation of DBS CRP with sCRP was independent of the investigated BMI range groups, yet BMI-dependent distinction was only provided by DBS CRP mean values. Overall, our results suggest that DBS CRP is likely to reflect systemic inflammation more precisely. Salivary CRP can be alternatively determined in studies with adolescents when conditions require it, given the oral health status is assessed. Considering that DBS CRP and sCRP share only 35% of common variance, further studies should examine their specific validity.
Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry
Authors: Palacios-Rápalo Selvin Noé , De Jesús-González Luis Adrián , Cordero-Rivera Carlos Daniel , Farfan-Morales Carlos Noe , Osuna-Ramos Juan Fidel , Martínez-Mier Gustavo , Quistián-Galván Judith , Muñoz-Pérez Armando , Bernal-Dolores Víctor , del Ángel Rosa María , Reyes-Ruiz José Manuel
Published: December 2021

Since its appearance, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), the causal agent of Coronavirus Disease 2019 (COVID-19), represents a global problem for human health that involves the host lipid homeostasis. Regarding, lipid rafts are functional membrane microdomains with highly and tightly packed lipid molecules. These regions enriched in sphingolipids and cholesterol recruit and concentrate several receptors and molecules involved in pathogen recognition and cellular signaling. Cholesterol-rich lipid rafts have multiple functions for viral replication; however, their role in SARS-CoV-2 infection remains unclear. In this review, we discussed the novel evidence on the cholesterol-rich lipid rafts as a platform for SARS-CoV-2 entry, where receptors such as the angiotensin-converting enzyme-2 (ACE-2), heparan sulfate proteoglycans (HSPGs), human Toll-like receptors (TLRs), transmembrane serine proteases (TMPRSS), CD-147 and HDL-scavenger receptor B type 1 (SR-B1) are recruited for their interaction with the viral spike protein. FDA-approved drugs such as statins, metformin, hydroxychloroquine, and cyclodextrins (methyl-β-cyclodextrin) can disrupt cholesterol-rich lipid rafts to regulate key molecules in the immune signaling pathways triggered by SARS-CoV-2 infection. Taken together, better knowledge on cholesterol-rich lipid rafts in the SARS-CoV-2-host interactions will provide valuable insights into pathogenesis and the identification of novel therapeutic targets.
Current State of Carbohydrate Recognition and C-Type Lectin Receptors in Pneumocystis Innate Immunity
Authors: Kottom Theodore J. , Carmona Eva M. , Limper Andrew H.
Published: December 2021

Pneumocystis jirovecii is one of the most common fungal pathogens in immunocompromised individuals. Pneumocystis jirovecii pneumonia (PJP) causes a significant host immune response that is driven greatly by the organism’s cell wall components including β-glucans and major surface glycoprotein (Msg). These ligands interact with a number of C-type lectin receptors (CLRs) leading to downstream activation of proinflammatory signaling pathways. This minireview provides a brief overview summarizing known CLR/Pneumocystis interactions.
Single-Cell Analysis of Target Antigens of CAR-T Reveals a Potential Landscape of “On-Target, Off-Tumor Toxicity”
Authors: Zhang Yinyin , Li Yingmei , Cao Weijie , Wang Fang , Xie Xinsheng , Li Yadan , Wang Xiaoyi , Guo Rong , Jiang Zhongxing , Guo Rongqun
Published: December 2021

Cellular immunotherapy represented by CD19-directed chimeric antigen receptor T (CAR-T) cells has achieved great success in recent years. An increasing number of CAR-T therapies are being developed for cancer treatment, but the frequent and varied adverse events, such as “on-target, off-tumor toxicity”, limit CAR-T application. Here, we identify the target antigen expression patterns of CAR therapies in 18 tissues and organs (peripheral blood mononuclear cells, bone marrow, lymph nodes, spleen, heart, ascending aortic tissue, trachea, lung, skin, kidney, bladder, esophagus, stomach, small intestine, rectum, liver, common bile duct, and pancreas) from healthy human samples. The atlas determines target antigens expressed on some normal cell types, which facilitates elucidating the cause of “on-target, off-tumor toxicity” in special tissues and organs by targeting some antigens, but not others. Moreover, we describe the target antigen expression patterns of B-lineage-derived malignant cells, acute myeloid leukemia (AML), and solid tumors. Overall, the present study indicates the pathogenesis of “on-target, off-tumor toxicity” during CAR therapies and provides guidance on taking preventive measures during CAR treatment.
T Cell-Mediated Autoimmunity in Glaucoma Neurodegeneration
Authors: Wang Lixiang , Wei Xin
Published: December 2021

Glaucoma as the leading neurodegenerative disease leads to blindness in 3.6 million people aged 50 years and older worldwide. For many decades, glaucoma therapy has primarily focused on controlling intraocular pressure (IOP) and sound evidence supports its role in delaying the progress of retinal ganglial cell (RGC) damage and protecting patients from vision loss. Meanwhile, accumulating data point to the immune-mediated attack of the neural retina as the underlying pathological process behind glaucoma that may come independent of raised IOP. Recently, some scholars have suggested autoimmune aspects in glaucoma, with autoreactive T cells mediating the chief pathogenic process. This autoimmune process, as well as the pathological features of glaucoma, largely overlaps with other neurodegenerative diseases in the central nervous system (CNS), including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. In addition, immune modulation therapy, which is regarded as a potential solution for glaucoma, has been boosted in trials in some CNS neurodegenerative diseases. Thus, novel insights into the T cell-mediated immunity and treatment in CNS neurodegenerative diseases may serve as valuable inspirations for ophthalmologists. This review focuses on the role of T cell-mediated immunity in the pathogenesis of glaucoma and discusses potential applications of relevant findings of CNS neurodegenerative diseases in future glaucoma research.
Deciphering the Role of Leptospira Surface Protein LigA in Modulating the Host Innate Immune Response
Authors: Kumar Ajay , Varma Vivek P. , Sridhar Kavela , Abdullah Mohd , Vyas Pallavi , Ashiq Thalappil Muhammed , Chang Yung-Fu , Faisal Syed M.
Published: December 2021

Leptospira, a zoonotic pathogen, is known to infect various hosts and can establish persistent infection. This remarkable ability of bacteria is attributed to its potential to modulate (activate or evade) the host immune response by exploiting its surface proteins. We have identified and characterized the domain of the variable region of Leptospira immunoglobulin-like protein A (LAV) involved in immune modulation. The 11th domain (A11) of the variable region of LigA (LAV) induces a strong TLR4 dependent innate response leading to subsequent induction of humoral and cellular immune responses in mice. A11 is also involved in acquiring complement regulator FH and binds to host protease Plasminogen (PLG), there by mediating functional activity to escape from complement-mediated killing. The deletion of A11 domain significantly impaired TLR4 signaling and subsequent reduction in the innate and adaptive immune response. It also inhibited the binding of FH and PLG thereby mediating killing of bacteria. Our study discovered an unprecedented role of LAV as a nuclease capable of degrading Neutrophil Extracellular Traps (NETs). This nuclease activity was primarily mediated by A11. These results highlighted the moonlighting function of LigA and demonstrated that a single domain of a surface protein is involved in modulating the host innate immune defenses, which might allow the persistence of Leptospira in different hosts for a long term without clearance.
Leopard Seals (Hydrurga leptonyx) in New Zealand Waters Predating on Chondrichthyans
Authors: van der Linde Krista , Visser Ingrid N. , Bout Rick , Lalas Chris , Shepherd Lara , Hocking David , Finucci Brittany , Fyfe Jim , Pinkerton Matthew
Published: December 2021

Leopard seals (Hydrurga leptonyx) are top-order predators that prey on a wide variety of species including crustaceans, cephalopods, fishes, birds, and pinnipeds. While multiple diet studies have been conducted worldwide, there are no previous accounts of leopard seals predating on chondrichthyans. As part of a wider study on the diet of leopard seals in New Zealand (NZ) waters, researchers and citizen scientists recorded 39 observations of predation and collected 127 scats (166 total records) between 1942 and 2019. Predation on chondrichthyans was detected in 23.1% (n = 9) of observations of predation and 7.1% (n = 9) of scats (the latter via morphological examination and DNA sequencing). From both observations of predations and scats, three chondrichthyan species or genus were identified; elephantfish (Callorhinchus milii), ghost sharks (Hydrolagus spp.) and spiny dogfish (Squalus acanthias). While this is the first published record of leopard seals feeding on chondrichthyans, the relatively high frequency of occurrence within our NZ records, and that certain individuals appeared to target this type of prey, indicates that these species could constitute a substantial, or important, part of the diet for some leopard seals in this region. As chondrichthyans form an important part of the NZ marine ecosystems, our recognition of an additional top-order predator of these species contributes to understanding the overall health of, and future impacts of predators on, the wider NZ marine ecosystem.
Case Report: Successful Treatment of Acute Generalized Exanthematous Pustulosis With Secukinumab
Authors: Zhang Liangliang , Xu Qiuyun , Lin Tingting , Ruan Shifan , Lin Mengting , Bao Chengbei , Zhang Jing , Liu Tao , Gong Ting , Ji Chao
Published: December 2021

Acute generalized exanthematous pustulosis is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base. Most cases of acute generalized exanthematous pustulosis (AGEP) clear quickly with a systemic corticosteroid, but severe or recalcitrant cases may need other systemic therapies. In this case, a man in his 40 s with a history of psoriasis consulted a physician about widespread erythema, pustules, target lesions, and fever after the administration of a quadruple antituberculosis drug. Routine laboratory testing revealed elevated white blood cell count and C-reactive protein. The histopathology showed subcorneal pustules, spongiosis as well as lymphocyte and eosinophils infiltration in the dermis. The patient was diagnosed with definitive AGEP according to the diagnostic score from the EuroSCAR study. Cutaneous lesions especially pustules and erythema multiforme-like lesions on the upper arms and palms are crucial for distinguishing AGEP from Generalized pustular psoriasis. The patient was treated with secukinumab as a result of his failure to respond to topical corticosteroids and constrain of systemic steroids. Remission with secukinumab therapy was safe without increased risks of infections. This case indicates that secukinumab is a potential therapy that can rapidly improve the clinical symptoms of AGEP.
An Introduction to Machine Learning Approaches for Biomedical Research
Authors: Jovel Juan , Greiner Russell
Published: December 2021

Machine learning (ML) approaches are a collection of algorithms that attempt to extract patterns from data and to associate such patterns with discrete classes of samples in the data—e.g., given a series of features describing persons, a ML model predicts whether a person is diseased or healthy, or given features of animals, it predicts weather an animal is treated or control, or whether molecules have the potential to interact or not, etc. ML approaches can also find such patterns in an agnostic manner, i.e., without having information about the classes. Respectively, those methods are referred to as supervised and unsupervised ML. A third type of ML is reinforcement learning, which attempts to find a sequence of actions that contribute to achieving a specific goal. All of these methods are becoming increasingly popular in biomedical research in quite diverse areas including drug design, stratification of patients, medical images analysis, molecular interactions, prediction of therapy outcomes and many more. We describe several supervised and unsupervised ML techniques, and illustrate a series of prototypical examples using state-of-the-art computational approaches. Given the complexity of reinforcement learning, it is not discussed in detail here, instead, interested readers are referred to excellent reviews on that topic. We focus on concepts rather than procedures, as our goal is to attract the attention of researchers in biomedicine toward the plethora of powerful ML methods and their potential to leverage basic and applied research programs.
B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization
Authors: Cucchiari David , Tubita Valeria , Rovira Jordi , Ramirez-Bajo Maria J. , Banon-Maneus Elisenda , Lazo-Rodriguez Marta , Hierro-Garcia Natalia , Borràs Francesc E. , Ventura-Aguiar Pedro , Piñeiro Gastón J. , Martorell Jaume , Peri Lluís , Musquera Mireia , Hertig Alexandre , Oppenheimer Federico , Campistol Josep M. , Diekmann Fritz , Revuelta Ignacio
Published: December 2021

Background: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could be estimated by the presence of circulating B cell-derived extracellular vesicles (BEVs).

Methods: BEVs were isolated by Sepharose-based size exclusion chromatography and defined as CD19+ and HLA-II+ extracellular vesicles. We analyzed stored serum samples from positive crossmatch LDKT recipients before and after desensitization at first post-transplant biopsy and at 12-month protocol biopsy (n = 11). Control groups were formed by hypersensitized patients who were not submitted to desensitization (n = 10) and by low-risk recipients (n = 9). A prospective validation cohort of 11 patients also included the analysis of B cells subpopulations in recipients' blood and lymph nodes recovered upon graft implantation, along with BEVs analysis before and after desensitization.

Results: We found out that CD19+ and HLA-II+BEVs dropped significantly after desensitization and relapse in patients who later developed ABMR was evident. We validated these findings in a proof-of-concept prospective cohort of 6 patients who received the same desensitization protocol and also in a control group of 5 LDKT recipients. In these patients, B cell subpopulations were also studied in recipients' blood and lymph nodes that were recovered before the graft implantation. We confirmed the significant drop in BEVs after desensitization and that this paralleled the reduction in CD19+cells in lymph nodes, while in peripheral blood B cells, this change was almost undetectable.

Conclusions: BEVs reflected B cell residual activity after desensitization and this could be a valid surrogate of humoral alloreactivity in this setting.
Seasonal Dynamics and Persistency of Endophyte Communities in Kalidium schrenkianum Shifts Under Radiation Stress
Authors: Zhu Jing , Sun Xiang , Tang Qi-Yong , Zhang Zhi-Dong
Published: December 2021

Endophytes are essential components of plant microbiota. Studies have shown that environmental factors and seasonal alternation can change the microbial community composition of plants. However, most studies have mainly emphasized the transitive endophyte communities and seasonal alternation but paid less attention to their persistence through multiple seasons. Kalidium schrenkianum is a perennial halophyte growing in an arid habitat with radiation stress (137Cs) in northwest China. In this study, K. schrenkianum growing under different environmental stresses were selected to investigate the dynamics and persistency of endophytic microbial communities amid seasons in a year. The results showed that Gammaproteobacteria and unassigned Actinobacteria were the most dominant bacterial communities, while the most dominant fungal communities were Dothideomycetes, unassigned Fungi, and Sodariomycetes. The bacterial community diversity in roots was higher than that in aerial tissues, and root communities had higher diversity in summer and autumn. In contrast, the fungal community diversity was higher in aerial tissues comparing to roots, and the highest diversity was in spring. Season was a determinant factor in the microbial community composition in the roots but not in the aerial tissues. RaupCrick index suggested that the bacterial communities were mainly shaped by stochastic processes. Our research investigated the community traits and members with temporal persistency. For example, bacterial taxa Afipia, Delftia, Stenotrophomonas, Xanthomonadaceae_B_OTU_211, and fungal taxa Neocamarosporium F_OTU_388, F_OTU_404, F_OTU_445, and unassigned Fungi F_OTU_704, F_OTU_767 showed higher frequencies than predicted in all the four seasons tested with neutral community model. The networks of co-occurrence associations presented in two or more seasons were visualized which suggested potential time-continuous core modules in most communities. In addition, the community dynamics and persistency also showed different patterns by radiation levels. Our findings would enhance our understanding of the microbial community assembly under environmental stress, and be promising to improve the development of integrated concept of core microbiome in future.
Regulation of Antiviral Immune Response by N6-Methyladenosine of mRNA
Authors: Zhao Baoxin , Wang Weijie , Zhao Yan , Qiao Hongxiu , Gao Zhiyun , Chuai Xia
Published: December 2021

Host innate and adaptive immune responses play a vital role in clearing infected viruses. Meanwhile, viruses also evolve a series of mechanisms to weaken the host immune responses and evade immune defense. Recently, N6-methyladenosine (m6A), the most prevalent mRNA modification, has been revealed to regulate multiple steps of RNA metabolism, such as mRNA splicing, localization, stabilization, and translation, thus participating in many biological phenomena, including viral infection. In the process of virus–host interaction, the m6A modification that presents on the virus RNA impedes capture by the pattern recognition receptors, and the m6A modification appearing on the host immune-related molecules regulate interferon response, immune cell differentiation, inflammatory cytokine production, and other immune responses induced by viral infection. This review summarizes the research advances about the regulatory role of m6A modification in the innate and adaptive immune responses during viral infections.