bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Restore Invertebrate Diversity of Degraded Heathlands? A Case Study on the Reproductive Performance of the Field Cricket Gryllus campestris (L.)
Authors: Vogels Joost J. , Verberk W. C. E. P. , Kuper J. T. , Weijters M. J. , Bobbink R. , Siepel H.
Published: May 2021

Background

Nitrogen (NOx, NHy) and acidifying (NOx, NHy, SOx) deposition has reduced the biodiversity of European dry heathlands. Restoration efforts such as sod-cutting (removal of vegetation, litter and humus layer) often shifted these systems from N to P limitation and have had limited success in restoring the invertebrate community. Possible reasons for this include the unresolved acidification and a change in food plant stoichiometry. Here, we investigate how liming and P addition change food nutritional quality and their consequences for invertebrate performance.

Methods

We performed feeding experiments with field crickets (Gryllus campestris), using plant material collected from a full factorial field experiment with liming and P addition. We related female reproduction as measure of individual fitness to elemental ratios of plants fed to the crickets.

Results

P addition stimulated cricket daily reproduction and shortened their reproductive period, resulting in no difference in total reproduction. Liming greatly reduced both daily and total reproduction and resulted in more females cannibalizing on their male mates. Females that did so could partly offset the liming induced reduction in reproduction, suggesting dietary deficiency. P-addition improved food quality (lower N:P ratios) while liming led to skewed Mn:Mg and Fe:Mg ratios that compare unfavorably to ratios found in terrestrial invertebrates.

Conclusion

Increased plant N:P ratio following sod-cutting constrains the reproductive potential inGryllus campestrisin a non-linear way. Liming reduced nutritional quality, likely by inducing deficiencies in Fe or Mn.

Management Implications

High-impact restoration management practices such as sod cutting and liming cause new problems for invertebrates rooted in ecological stoichiometry. Since P-addition only partially offsets these negative effects, we instead advocate the use of less intensive N removal management and weaker buffering agents to reduce soil acidification. Furthermore, a reduction in N emission is paramount as it will remove the need for disruptive interventions.
Vegetation Reconstruction From Siberia and the Tibetan Plateau Using Modern Analogue Technique–Comparing Sedimentary (Ancient) DNA and Pollen Data
Authors: Liu Sisi , Li Kai , Jia Weihan , Stoof-Leichsenring Kathleen Rosmarie , Liu Xingqi , Cao Xianyong , Herzschuh Ulrike
Published: May 2021

To reconstruct past vegetation from pollen or, more recently, lake sedimentary DNA (sedDNA) data is a common goal in palaeoecology. To overcome the bias of a researcher’s subjective assessment and to assign past assemblages to modern vegetation types quantitatively, the modern analogue technique (MAT) is often used for vegetation reconstruction. However, a rigorous comparison of MAT-derived pollen-based and sedDNA-based vegetation reconstruction is lacking. Here, we assess the dissimilarity between modern taxa assemblages from lake surface-sediments and fossil taxa assemblages from four lake sediment cores from the south-eastern Tibetan Plateau and northern Siberia using receiver operating characteristic (ROC) curves, ordination methods, and Procrustes analyses. Modern sedDNA samples from 190 lakes and pollen samples from 136 lakes were collected from a variety of vegetation types. Our results show that more modern analogues are found with sedDNA than pollen when applying similarly derived thresholds. In particular, there are few modern pollen analogues for open vegetation such as alpine or arctic tundra, limiting the ability of treeline shifts to be clearly reconstructed. In contrast, the shifts in the main vegetation communities are well captured by sedimentary ancient DNA (sedaDNA). For example, pronounced shifts from late-glacial alpine meadow/steppe to early–mid-Holocene coniferous forests to late Holocene Tibetan shrubland vegetation types are reconstructed for Lake Naleng on the south-eastern Tibetan Plateau. Procrustes and PROTEST analyses reveal that intertaxa relationships inferred from modern sedaDNA datasets align with past relationships generally, while intertaxa relationships derived from modern pollen spectra are mostly significantly different from fossil pollen relationships. Overall, we conclude that a quantitative sedaDNA-based vegetation reconstruction using MAT is more reliable than a pollen-based reconstruction, probably because of the more straightforward taphonomy that can relate sedDNA assemblages to the vegetation surrounding the lake.
Follow-up in Patients With Non-invasive Prenatal Screening Failures: A Reflection on the Choice of Further Prenatal Diagnosis
Authors: Liu Sha , Liu Hongqian , Liu Jianlong , Bai Ting , Jing Xiaosha , Xia Tianyu , Deng Cechuan , Liu Yunyun , Cheng Jing , Wei Xiang , Xing Lingling , Luo Yuan , Zhou Quanfang , Zhu Qian
Published: May 2021

Background

Our aim was to provide a theoretical basis for clinicians to conduct genetic counseling and choose further prenatal diagnosis methods for pregnant women who failed non-invasive prenatal screening (NIPS).

Methods

A retrospective analysis was performed on pregnant women who had failed NIPS tests.

Results

Among the 123,291 samples, 394 pregnant women did not obtain valid results due to test failures. A total of 378 pregnant women were available for follow-up, while 16 patients were lost to follow-up. Of these 378, 135 pregnant women chose further prenatal diagnosis through amniocentesis, and one case of dysplasia was recalled for postpartum chromosome testing. The incidence rate of congenital chromosomal abnormalities in those who failed the NIPS was 3.97% (15/378), which was higher than that of the chromosomal abnormalities in the common population (1.8%). Among the pregnant women who received prenatal diagnosis, the positive rates of chromosomal abnormalities in the chromosomal microarray analysis/copy number variation sequencing (CMA/CNV-seq) group and in the karyotyping group were 15.28 and 4.76%, respectively.

Conclusion

Prenatal diagnosis should be strongly recommended in posttest genetic counseling for pregnant women with NIPS failures. Further, high-resolution detection methods should be recommended for additional prenatal diagnoses.
Aluminum or Low pH – Which Is the Bigger Enemy of Barley? Transcriptome Analysis of Barley Root Meristem Under Al and Low pH Stress
Authors: Szurman-Zubrzycka Miriam , Chwiałkowska Karolina , Niemira Magdalena , Kwaśniewski Mirosław , Nawrot Małgorzata , Gajecka Monika , Larsen Paul B. , Szarejko Iwona
Published: May 2021

Aluminum (Al) toxicity is considered to be the most harmful abiotic stress in acidic soils that today comprise more than 50% of the world’s arable lands. Barley belongs to a group of crops that are most sensitive to Al in low pH soils. We present the RNA-seq analysis of root meristems of barley seedlings grown in hydroponics at optimal pH (6.0), low pH (4.0), and low pH with Al (10 μM of bioavailable Al3+ ions). Two independent experiments were conducted: with short-term (24 h) and long-term (7 days) Al treatment. In the short-term experiment, more genes were differentially expressed (DEGs) between root meristems grown at pH = 6.0 and pH = 4.0, than between those grown at pH = 4.0 with and without Al treatment. The genes upregulated by low pH were associated mainly with response to oxidative stress, cell wall organization, and iron ion binding. Among genes upregulated by Al, overrepresented were those related to response to stress condition and calcium ion binding. In the long-term experiment, the number of DEGs between hydroponics at pH = 4.0 and 6.0 were lower than in the short-term experiment, which suggests that plants partially adapted to the low pH. Interestingly, 7 days Al treatment caused massive changes in the transcriptome profile. Over 4,000 genes were upregulated and almost 2,000 genes were downregulated by long-term Al stress. These DEGs were related to stress response, cell wall development and metal ion transport. Based on our results we can assume that both, Al3+ ions and low pH are harmful to barley plants. Additionally, we phenotyped the root system of barley seedlings grown in the same hydroponic conditions for 7 days at pH = 6.0, pH = 4.0, and pH = 4.0 with Al. The results correspond to transcriptomic data and show that low pH itself is a stress factor that causes a significant reduction of root growth and the addition of aluminum further increases this reduction. It should be noted that in acidic arable lands, plants are exposed simultaneously to both of these stresses. The presented transcriptome analysis may help to find potential targets for breeding barley plants that are more tolerant to such conditions.
Immunomodulatory Effects of Rhinovirus and Enterovirus Infections During the First Year of Life
Authors: Ruohtula Terhi , Kondrashova Anita , Lehtonen Jussi , Oikarinen Sami , Hämäläinen Anu-Maaria , Niemelä Onni , Peet Aleksandr , Tillmann Vallo , Nieminen Janne K. , Ilonen Jorma , Knip Mikael , Vaarala Outi , Hyöty Heikki ,   the DIABIMMUNE Study Group
Published: May 2021

Early childhood infections have been implicated in the development of immune-mediated diseases, such as allergies, asthma, and type 1 diabetes. We set out to investigate the immunomodulatory effects of early viral infections experienced before the age of one year on the peripheral regulatory T cell population (Treg) and circulating cytokines in a birth-cohort study of Estonian and Finnish infants. We show here a temporal association of virus infection with the expression of FOXP3 in regulatory T cells. Infants with rhinovirus infection during the preceding 30 days had a higher FOXP3 expression in Treg cells and decreased levels of several cytokines related to Th1 and Th2 responses in comparison to the children without infections. In contrast, FOXP3 expression was significantly decreased in highly activated (CD4+CD127−/loCD25+FOXP3high) regulatory T cells (TregFOXP3high) in the infants who had enterovirus infection during the preceding 30 or 60 days. After enterovirus infections, the cytokine profile showed an upregulation of Th1- and Th17-related cytokines and a decreased activation of CCL22, which is a chemokine derived from dendritic cells and associated with Th2 deviation. Our results reveal that immunoregulatory mechanisms are up-regulated after rhinovirus infections, while enterovirus infections are associated with activation of proinflammatory pathways and decreased immune regulation.
High Dose Intravenous IgG Therapy Modulates Multiple NK Cell and T Cell Functions in Patients With Immune Dysregulation
Authors: McAlpine Sarah M. , Roberts Sarah E. , Heath John J. , Käsermann Fabian , Issekutz Andrew C. , Issekutz Thomas B. , Derfalvi Beata
Published: May 2021

Intravenous immunoglobulin (IVIG) is an effective immunomodulatory treatment for immune dysregulation diseases. However, the mechanisms by which it reduces systemic inflammation are not well understood. NK cell cytotoxicity is decreased by IVIG in women with reduced fertility, but IVIG effects on NK cells in immune dysregulation are less clear. We hypothesized that IVIG modulation of lymphocyte function, especially in NK cells, is important for resolution of inflammation. Our aim was to identify IVIG-induced changes in a cohort of patients with Kawasaki disease (KD) and those that occur broadly in pediatric patients with various immune dysregulatory diseases. Peripheral blood mononuclear cells (PBMCs) of patients with KD or autoimmune/inflammatory diseases were phenotyped pre and post high dose IVIG treatment by flow cytometry. In KD patients, after IVIG infusion Treg cell frequency and the proportion of activated CD25+ immunoregulatory CD56bright NK cells was increased, and multiple lymphocyte subsets showed increased expression of the lymphoid tissue homing receptor CD62L. Importantly, IVIG treatment decreased the frequency of cells expressing the degranulation marker CD107a among cytotoxic CD56dim NK cells, which was reflected in a significant reduction in target cell killing and in decreased production of multiple pro-inflammatory mediators. Interestingly, the activating receptor CD336 was expressed on a higher proportion of CD56bright NK cells after IVIG in both KD and autoimmune/inflammatory patients while other NK receptors were increased differentially in each cohort. In autoimmune/inflammatory patients IVIG induced the proliferation marker CD71 on a higher percentage of CD56dim NK cells, and in contrast to KD patients, CD107a+ cells were increased in this subset. Furthermore, when PBMCs were stimulated ex vivo with IL-2 or Candida antigen in autologous plasma, more of the CD4+ T cells of KD patients expressed CD25 after IVIG therapy but fewer cytotoxic T cells were degranulated based on CD107a expression. In summary, IVIG treatment in patients with immune dysregulation has multiple effects, especially on NK cell subsets and CD4+ T cells, which are compatible with promoting resolution of inflammation. These novel findings provide insight into the immunomodulatory actions of IVIG in autoimmune and inflammatory conditions.
The Roles of Host Noncoding RNAs in Mycobacterium tuberculosis Infection
Authors: Wei Li , Liu Kai , Jia Qingzhi , Zhang Hui , Bie Qingli , Zhang Bin
Published: May 2021

Tuberculosis remains a major health problem. Mycobacterium tuberculosis, the causative agent of tuberculosis, can replicate and persist in host cells. Noncoding RNAs (ncRNAs) widely participate in various biological processes, including Mycobacterium tuberculosis infection, and play critical roles in gene regulation. In this review, we summarize the latest reports on ncRNAs (microRNAs, piRNAs, circRNAs and lncRNAs) that regulate the host response against Mycobacterium tuberculosis infection. In the context of host-Mycobacterium tuberculosis interactions, a broad and in-depth understanding of host ncRNA regulatory mechanisms may lead to potential clinical prospects for tuberculosis diagnosis and the development of new anti-tuberculosis therapies.
The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead
Authors: Hosseinkhani Negar , Derakhshani Afshin , Shadbad Mahdi Abdoli , Argentiero Antonella , Racanelli Vito , Kazemi Tohid , Mokhtarzadeh Ahad , Brunetti Oronzo , Silvestris Nicola , Baradaran Behzad
Published: May 2021

Immune checkpoints (ICs) have pivotal roles in regulating immune responses. The inhibitory ICs in the tumor microenvironment (TME) have been implicated in the immune evasion of tumoral cells. Therefore, identifying and targeting these inhibitory ICs might be critical for eliminating tumoral cells. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory IC that is expressed on myeloid cells, lymphoid cells, and tumoral cells; therefore, VISTA can substantially regulate innate and adaptive anti-tumoral immune responses. Besides, growing evidence indicates that VISTA blockade can enhance the sensitivity of tumoral cells to conventional IC-based immunotherapy, e.g., cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. In this regard, the current study aimed to review the current evidence about the structure and expression pattern of VISTA, its role in TME, the clinicopathological significance of VISTA, and its prognostic values in various cancers. Besides, this review intended to collect the lessons from the recent pre-clinical and clinical studies and propose a strategy to overcome tumor immune-resistance states.
Obstacles and Coping Strategies of CAR-T Cell Immunotherapy in Solid Tumors
Authors: Miao Lele , Zhang Zhengchao , Ren Zhijian , Tang Futian , Li Yumin
Published: May 2021

Chimeric antigen receptor (CAR) T-cell immunotherapy refers to an adoptive immunotherapy that has rapidly developed in recent years. It is a novel type of treatment that enables T cells to express specific CARs on their surface, then returns these T cells to tumor patients to kill the corresponding tumor cells. Significant strides in CAR-T cell immunotherapy against hematologic malignancies have elicited research interest among scholars in the treatment of solid tumors. Nonetheless, in contrast with the efficacy of CAR-T cell immunotherapy in the treatment of hematologic malignancies, its general efficacy against solid tumors is insignificant. This has been attributed to the complex biological characteristics of solid tumors. CAR-T cells play a better role in solid tumors, for instance by addressing obstacles including the lack of specific targets, inhibition of tumor microenvironment (TME), homing barriers of CAR-T cells, differentiation and depletion of CAR-T cells, inhibition of immune checkpoints, trogocytosis of CAR-T cells, tumor antigen heterogeneity, etc. This paper reviews the obstacles influencing the efficacy of CAR-T cell immunotherapy in solid tumors, their mechanism, and coping strategies, as well as economic restriction of CAR-T cell immunotherapy and its solutions. It aims to provide some references for researchers to better overcome the obstacles that affect the efficacy of CAR-T cells in solid tumors.
Synthesis of Thresholds of Ocean Acidification Impacts on Echinoderms
Authors: Bednaršek Nina , Calosi Piero , Feely Richard A. , Ambrose Richard , Byrne Maria , Chan Kit Yu Karen , Dupont Sam , Padilla-Gamiño Jacqueline L. , Spicer John I. , Kessouri Faycal , Roethler Miranda , Sutula Martha , Weisberg Stephen B.
Published: May 2021

Assessing the vulnerability of marine invertebrates to ocean acidification (OA) requires an understanding of critical thresholds at which developmental, physiological, and behavioral traits are affected. To identify relevant thresholds for echinoderms, we undertook a three-step data synthesis, focused on California Current Ecosystem (CCE) species. First, literature characterizing echinoderm responses to OA was compiled, creating a dataset comprised of >12,000 datapoints from 41 studies. Analysis of this data set demonstrated responses related to physiology, behavior, growth and development, and increased mortality in the larval and adult stages to low pH exposure. Second, statistical analyses were conducted on selected pathways to identify OA thresholds specific to duration, taxa, and depth-related life stage. Exposure to reduced pH led to impaired responses across a range of physiology, behavior, growth and development, and mortality endpoints for both larval and adult stages. Third, through discussions and synthesis, the expert panel identified a set of eight duration-dependent, life stage, and habitat-dependent pH thresholds and assigned each a confidence score based on quantity and agreement of evidence. The thresholds for these effects ranged within pH from 7.20 to 7.74 and duration from 7 to 30 days, all of which were characterized with either medium or low confidence. These thresholds yielded a risk range from early warning to lethal impacts, providing the foundation for consistent interpretation of OA monitoring data or numerical ocean model simulations to support climate change marine vulnerability assessments and evaluation of ocean management strategies. As a demonstration, two echinoderm thresholds were applied to simulations of a CCE numerical model to visualize the effects of current state of pH conditions on potential habitat.
Adapting Simple Index-Based Catch Rules for Data-Limited Stocks to Short-Lived Fish Stocks’ Characteristics
Authors: Sánchez-Maroño Sonia , Uriarte Andrés , Ibaibarriaga Leire , Citores Leire
Published: May 2021

Most of the methods developed for managing data-limited stocks have been designed for long-lived species and result in a poor performance when applied to short-lived fish due to their high interannual variability of stock size (IAV). We evaluate the performance of several catch rules in managing two typical short-lived fish (anchovy-like: characterized by high natural mortality, and hence, IAV, and full maturity at age 1; and sprat/sardine-like: with medium natural mortality and IAV, being fully mature at age 2). We followed the management strategy evaluation approach implemented in FLBEIA software to test several model-free harvest control rules, where the Total Allowable Catch (TAC) is yearly modified according to the recent trends in an abundance index (n-over-m rules: means of the most recent n values over the precedent m ones). The performance of these rules was assessed across a range of settings, such as time-lags between the index availability and management implementation, and alternative restrictions on TACs’ interannual variability (the uncertainty caps, UC). Moreover, we evaluated the sensitivity of the rule performance to the operating model assumptions (stock type, productivity, recruitment variability and initial depletion level) and to the observation error of the index. In general, the shorter the lag between observations, advice and management, the bigger the catches and the smaller the biological risks. For in-year management, 1-over-m rules are reactive enough to stock fluctuations as to gradually reduce risks. The 1-over-2 rule with symmetric 80% UCs reduces catches and risks toward precautionary levels in about 10 years, faster than if applied unconstrained (i.e., without UC), whilst the ICES default 2-over-3 rule with symmetric 20% UC is not precautionary. We prove that unconstrained rules gradually reduce the fishing opportunities, with amplified effects with increasing IAV. This property explains the stronger reductions of catches and risks achieved for the anchovy compared to the sprat/sardine-like stocks for any rule and the balance between catches and risks as the index CV increases. However, to avoid unnecessary long-term losses of catches from such reduction properties, it is suggested that the rules should be applied provisionally until a better assessment and management system is set up.
Essential Fatty Acid Requirements in Tropical and Cold-Water Marine Fish Larvae and Juveniles
Authors: Mejri Sahar Chauffour , Tremblay Réjean , Audet Céline , Wills Paul S. , Riche Marty
Published: May 2021

To improve survival at early developmental stages (larvae and juveniles) of captive fish species, essential nutrients [i.e., essential fatty acids (EFA)] need to be identified. The physiological needs are likely to be different among species, particularly among those using different thermal habitats, because lipids are largely used to maintain cell membrane integrity (homeoviscous adaptation) in fishes. This review paper will focus on currently published research and the main results from our laboratories regarding optimum qualitative EFA requirements during larval and early juvenile stages in a warm-water marine species, the Florida pompano (Trachinotus carolinus), and a cold-water marine species, the winter flounder (Pseudopleuronectes americanus). To identify the qualitative optimal EFA requirements, we calculated the ratio of certain fatty acids (FA) in larval or early juvenile tissues to total FA present in the diet. This ratio indicates whether a specific FA from prey is selectively incorporated by larvae and juveniles. Overall, we found that young larvae from both cold- and warm-water species have greater demands for n-3 and n-6 highly unsaturated fatty acids (HUFA) than do larvae at weaning stages. However, the qualitative EFA requirements of the cold-water species at all early developmental stages were higher than those of the warm-water species. Enriched rotifer diets provided satisfactory amounts of omega 3 and omega 6 in Florida pompano, with small selective retention for docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), suggesting a potential minor diet deficiency in these EFA. There were higher deficiencies in the cold-water species fed enriched rotifers, as demonstrated by the higher selective retentions of all EFA (DHA, EPA, and ARA), with the exception of larvae fed with copepods. The physiological needs in EFA for juvenile development seemed to be better met for both species when they were fed micro pellets. From the beginning of settlement and in young juveniles, qualitative values of 12% DHA, 10% EPA, 5% ARA, and 40% PUFA of total FA seem to be required for winter flounder juvenile development. In Florida pompano, these requirements could be met until larger juvenile stages, with 15% DHA, 3% EPA, 2% ARA, 2% DPA, and total PUFA below 30% of total FA. This review was done to aid future research aiming to develop nutritionally balanced microdiets or live-prey enrichment diets to satisfy the physiological requirements of captive tropical and cold-water marine fish species.
Computed Tomography-Guided Transthoracic Needle Biopsy: Predictors for Diagnostic Failure and Tissue Adequacy for Molecular Testing
Authors: Lin Chia-Ying , Chang Chao-Chun , Chu Chang-Yao , Huang Li-Ting , Chung Ta-Jung , Liu Yi-Sheng , Yen Yi-Ting
Published: May 2021

Background: Adequate and representative tissue from lung tumor is important in the era of precision medicine. The aim of this study is to identify detailed procedure-related variables and factors influencing diagnostic success and tissue adequacy for molecular testing in CT-guided TTNB.

Methods: Consecutive patients undergoing CT-guided TTNB were retrospectively enrolled between January 2013 and May 2020. Multivariate analysis was performed for predictors for diagnostic accuracy and tissue adequacy for molecular testing. Logistic regression was used to identify risk factors for procedure-related complications.

Results: A total of 2,556 patients undergoing CT-guided TTNB were enrolled and overall success rate was 91.5% (2,338/2,556). For lung nodules ≤3 cm, predictors for diagnostic success included coaxial needle use [OR = 0.34 (0.16–0.71), p = 0.004], CT scan slice thickness of 2.5 mm [OR = 0.42 (0.15–0.82), p = 0.011] and additional prefire imaging [OR = 0.31 (0.14–0.68), p = 0.004]. For lung tumor >3 cm, ground glass opacity part more than 50% [OR = 7.53 (2.81–20.23), p < 0.001] or presence of obstructive pneumonitis [OR = 2.31 (1.53–3.48), p < 0.001] had higher risk of diagnostic failure. For tissue adequacy, tissue submitted in two cassettes (98.9 vs. 94.9%, p = 0.027) was a positive predictor; while male (5.7 vs. 2.5%, p = 0.032), younger age (56.61 ± 11.64 vs. 65.82 ± 11.98, p < 0.001), and screening for clinical trial (18.5 vs. 0.7%, p < 0.001) were negative predictors.

Conclusions: Using a coaxial needle, with thin CT slice thickness (2.5 mm), and obtaining additional prefire imaging improved diagnostic success, while obtaining more than two tissue cores and submitting in two cassettes improved tissue adequacy for molecular testing.
Clinical Characteristics and Risk Factors Associated With Acute Kidney Injury Inpatient With Exertional Heatstroke: An Over 10-Year Intensive Care Survey
Authors: Wu Ming , Wang Conglin , Liu Zheying , Zhong Li , Yu Baojun , Cheng Biao , Liu Zhifeng
Published: May 2021

Background: Exertional heat stroke (EHS) is a life-threatening injury that can lead to acute kidney injury (AKI). The clinical characteristics of and risk factors for EHS complicated with AKI have been poorly documented.

Methods: A retrospective study with EHS admitted to the intensive care unit (ICU) from January 2008 to June 2019 was performed. Data including baseline clinical information at admission, main organ dysfunction, 90-day mortality and total cost of hospitalization were collected.

Results: A total of 187 patients were finally included, of which 82 (43.9%) had AKI. AKI patients had more severe organ injury and higher total hospitalization costs than non-AKI patients. Multivariate logistic analysis showed that lymphocyte, neutrophil, D-dimer and myoglobin (MB) ≥ 1,000 ng/ml were independent risk factors for AKI caused by EHS. In addition, SOFA score [hazard ratio (HR) 4.1, 95% confidence interval (95% CI) 1.6–10.8, P = 0.004] and GCS score (HR 3.2, 95% CI 1.2–8.4 P = 0.017) were the risk factor for 90-day mortality in patients with EHS complicated with AKI, with an area under the curve (AUC) of 0.920 (95% CI 0.842–0.998, P < 0.001) and 0.851 (95% CI 0.739–0.962, P < 0.001), respectively. Survival analysis showed that the 90-day mortality in AKI patients was significantly high (P < 0.0001) and the mortality rate of patients with AKI stage 2 was the highest than other stages.

Conclusions: EHS complicated with AKI is associated with higher hospitalization costs and poorly clinical outcomes. MB ≥1,000 ng/ml, Inflammation, coagulation were associated with the occurrence and development of AKI. Early treatment strategies based reducing the SOFA and GCS score may be pivotal for improving the prognosis of EHS.
Understanding How Staphylococcal Autolysin Domains Interact With Polystyrene Surfaces
Authors: Somarathne Radha P. , Chappell Emily R. , Perera Y. Randika , Yadav Rahul , Park Joo Youn , Fitzkee Nicholas C.
Published: May 2021

Biofilms, when formed on medical devices, can cause malfunctions and reduce the efficiency of these devices, thus complicating treatments and serving as a source of infection. The autolysin protein of Staphylococcus epidermidis contributes to its biofilm forming ability, especially on polystyrene surfaces. R2ab and amidase are autolysin protein domains thought to have high affinity to polystyrene surfaces, and they are involved in initial bacterial attachment in S. epidermidis biofilm formation. However, the structural details of R2ab and amidase binding to surfaces are poorly understood. In this study, we have investigated how R2ab and amidase influence biofilm formation on polystyrene surfaces. We have also studied how these proteins interact with polystyrene nanoparticles (PSNPs) using biophysical techniques. Pretreating polystyrene plates with R2ab and amidase domains inhibits biofilm growth relative to a control protein, indicating that these domains bind tightly to polystyrene surfaces and can block bacterial attachment. Correspondingly, we find that both domains interact strongly with anionic, carboxylate-functionalized as well as neutral, non-functionalized PSNPs, suggesting a similar binding interaction for nanoparticles and macroscopic surfaces. Both anionic and neutral PSNPs induce changes to the secondary structure of both R2ab and amidase as monitored by circular dichroism (CD) spectroscopy. These changes are very similar, though not identical, for both types of PSNPs, suggesting that carboxylate functionalization is only a small perturbation for R2ab and amidase binding. This structural change is also seen in limited proteolysis experiments, which exhibit substantial differences for both proteins when in the presence of carboxylate PSNPs. Overall, our results demonstrate that the R2ab and amidase domains strongly favor adsorption to polystyrene surfaces, and that surface adsorption destabilizes the secondary structure of these domains. Bacterial attachment to polystyrene surfaces during the initial phases of biofilm formation, therefore, may be mediated by aromatic residues, since these residues are known to drive adsorption to PSNPs. Together, these experiments can be used to develop new strategies for biofilm eradication, ensuring the proper long-lived functioning of medical devices.
Molecular Analysis of Bacterial Isolates From Necrotic Wheat Leaf Lesions Caused by Xanthomonas translucens, and Description of Three Putative Novel Species, Sphingomonas albertensis sp. nov., Pseudomonas triticumensis sp. nov. and Pseudomonas foliumensis sp. nov.
Authors: Tambong James T. , Xu Renlin , Gerdis Suzanne , Daniels Greg C. , Chabot Denise , Hubbard Keith , Harding Michael W.
Published: May 2021

Xanthomonas translucensis the etiological agent of the wheat bacterial leaf streak (BLS) disease. The isolation of this pathogen is usually based on the Wilbrink’s-boric acid–cephalexin semi-selective medium which eliminates 90% of other bacteria, some of which might be novel species. In our study, a general purpose nutrient agar was used to isolate 49 bacterial strains includingX. translucensfrom necrotic wheat leaf tissues. Maximum likelihood cluster analysis of 16S rRNA sequences grouped the strains into 10 distinct genera.Pseudomonas(32.7%) andPantoea(28.6%) were the dominant genera whileXanthomonas, ClavibacterandCurtobacteriumhad 8.2%, each.ErwiniaandSphingomonashad two strains, each. BLAST and phylogenetic analyses of multilocus sequence analysis (MLSA) of specific housekeeping genes taxonomically assigned all the strains to validly described bacterial species, except three strains (10L4B, 12L4D and 32L3A) ofPseudomonasand two (23L3C and 15L3B) ofSphingomonas. Strains 10L4B and12L4D hadPseudomonas caspianaas their closest known type strain while strain 32L3A was closest toPseudomonas asturiensis.Sphingomonassp. strains 23L3C and 15L3B were closest toS. faenibased on MLSA analysis. Our data on MLSA, whole genome-based cluster analysis, DNA-DNA hybridization and average nucleotide identity, matrix-assisted laser desorption/ionization-time-of-flight, chemotaxonomy and phenotype affirmed that these 5 strains constitute three novel lineages and are taxonomically described in this study. We propose the names,Sphingomonas albertensissp. nov. (type strain 23L3CT= DOAB 1063T= CECT 30248T= LMG 32139T),Pseudomonas triticumensissp. nov. (type strain 32L3AT= DOAB 1067T= CECT 30249T= LMG 32140T) andPseudomonas foliumensissp.nov.(type strain 10L4BT= DOAB 1069T= CECT 30250T= LMG 32142T). Comparative genomics of these novel species, relative to their closest type strains, revealed unique repertoires of core secretion systems and secondary metabolites/antibiotics. Also, the detection of CRISPR-Cas systems in the genomes of these novel species suggests an acquired mechanism for resistance against foreign mobile genetic elements. The results presented here revealed a cohabitation, within the BLS lesions, of diverse bacterial species, including novel lineages.
Metagenome Assembled Genome of a Novel Verrucomicrobial Methanotroph From Pantelleria Island
Authors: Picone Nunzia , Blom Pieter , Hogendoorn Carmen , Frank Jeroen , van Alen Theo , Pol Arjan , Gagliano Antonina L. , Jetten Mike S. M. , D’Alessandro Walter , Quatrini Paola , Op den Camp Huub J. M.
Published: May 2021

Verrucomicrobial methanotrophs are a group of aerobic bacteria isolated from volcanic environments. They are acidophiles, characterized by the presence of a particulate methane monooxygenase (pMMO) and a XoxF-type methanol dehydrogenase (MDH). Metagenomic analysis of DNA extracted from the soil of Favara Grande, a geothermal area on Pantelleria Island, Italy, revealed the presence of two verrucomicrobial Metagenome Assembled Genomes (MAGs). One of these MAGs did not phylogenetically classify within any existing genus. After extensive analysis of the MAG, we propose the name of “Candidatus Methylacidithermus pantelleriae” PQ17 gen. nov. sp. nov. The MAG consisted of 2,466,655 bp, 71 contigs and 3,127 predicted coding sequences. Completeness was found at 98.6% and contamination at 1.3%. Genes encoding the pMMO and XoxF-MDH were identified. Inorganic carbon fixation might use the Calvin-Benson-Bassham cycle since all genes were identified. The serine and ribulose monophosphate pathways were incomplete. The detoxification of formaldehyde could follow the tetrahydrofolate pathway. Furthermore, “Ca. Methylacidithermus pantelleriae” might be capable of nitric oxide reduction but genes for dissimilatory nitrate reduction and nitrogen fixation were not identified. Unlike other verrucomicrobial methanotrophs, genes encoding for enzymes involved in hydrogen oxidation could not be found. In conclusion, the discovery of this new MAG expands the diversity and metabolism of verrucomicrobial methanotrophs.
Serial Electron Diffraction Data Processing With diffractem and CrystFEL
Authors: Bücker Robert , Hogan-Lamarre Pascal , Miller R. J. Dwayne
Published: May 2021

Serial electron diffraction (SerialED) is an emerging technique, which applies the snapshot data-collection mode of serial X-ray crystallography to three-dimensional electron diffraction (3D Electron Diffraction), forgoing the conventional rotation method. Similarly to serial X-ray crystallography, this approach leads to almost complete absence of radiation damage effects even for the most sensitive samples, and allows for a high level of automation. However, SerialED also necessitates new techniques of data processing, which combine existing pipelines for rotation electron diffraction and serial X-ray crystallography with some more particular solutions for challenges arising in SerialED specifically. Here, we introduce our analysis pipeline for SerialED data, and its implementation using the CrystFEL and diffractem program packages. Detailed examples are provided in extensive supplementary code.
NAD+ Metabolism, Metabolic Stress, and Infection
Authors: Groth Benjamin , Venkatakrishnan Padmaja , Lin Su-Ju
Published: May 2021

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite with wide-ranging and significant roles in the cell. Defects in NAD+ metabolism have been associated with many human disorders; it is therefore an emerging therapeutic target. Moreover, NAD+ metabolism is perturbed during colonization by a variety of pathogens, either due to the molecular mechanisms employed by these infectious agents or by the host immune response they trigger. Three main biosynthetic pathways, including the de novo and salvage pathways, contribute to the production of NAD+ with a high degree of conservation from bacteria to humans. De novo biosynthesis, which begins with l-tryptophan in eukaryotes, is also known as the kynurenine pathway. Intermediates of this pathway have various beneficial and deleterious effects on cellular health in different contexts. For example, dysregulation of this pathway is linked to neurotoxicity and oxidative stress. Activation of the de novo pathway is also implicated in various infections and inflammatory signaling. Given the dynamic flexibility and multiple roles of NAD+ intermediates, it is important to understand the interconnections and cross-regulations of NAD+ precursors and associated signaling pathways to understand how cells regulate NAD+ homeostasis in response to various growth conditions. Although regulation of NAD+ homeostasis remains incompletely understood, studies in the genetically tractable budding yeast Saccharomyces cerevisiae may help provide some molecular basis for how NAD+ homeostasis factors contribute to the maintenance and regulation of cellular function and how they are regulated by various nutritional and stress signals. Here we present a brief overview of recent insights and discoveries made with respect to the relationship between NAD+ metabolism and selected human disorders and infections, with a particular focus on the de novo pathway. We also discuss how studies in budding yeast may help elucidate the regulation of NAD+ homeostasis.
Repetitive Transcranial Magnetic Stimulation on the Affected Hemisphere Enhances Hand Functional Recovery in Subacute Adult Stroke Patients: A Randomized Trial
Authors: Yang Yawen , Pan Huijuan , Pan Wenxiu , Liu Yang , Song Xiaohui , Niu Chuanxin M. , Feng Wuwei , Wang Jixian , Xie Qing
Published: May 2021

Objectives: Either motor training or repetitive transcranial magnetic stimulation (rTMS) could modulate the neural plasticity after stroke. Therefore, synchronizing the two interventions may optimize the efficiency of recovery. In the present study, we aim to investigate the effect of rTMS along with hand grip training on the neurobehavioral and hand functional recovery in one cohort of subacute stroke patients.

Methods: Thirty-nine stroke patients were enrolled in a single-center, single-blinded, randomized clinical trial. We tested different intervention effects of rTMS and hand grip training (group A), rTMS alone (group B), and hand grip training alone (group C). For the rTMS-treated groups, patients received 10 consecutive sessions of 5-Hz stimulation over the affected hemisphere with 750 pulses. Jebsen–Taylor Hand Function Test (JTHFT), Fugl-Meyer assessment of upper extremity (FMA-UE), grip strength, modified Barthel index (mBI), and ipsilesional motor evoked potential (iMEP) latency were assessed and compared across the groups.

Results: We found that only rTMS along with hand grip training group all improved in JTHFT, FMA-UE, grip strength, and mBI (p ≤ 0.01) compared with the baseline among the three groups. Furthermore, this study demonstrated that rTMS plus hand grip training had much better results in improvement of neurobehavioral outcomes compared to the rTMS alone- and hand grip training alone-treated patients (p < 0.05). However, no significant differences were detected in neurophysiologic outcome between intra-groups and inter-groups (p > 0.05).

Conclusion: These proof-of-concept results suggested that rTMS alone with hand grip training was a unique approach to promote hand functional recovery in stroke patients. It provided important information to design a large-scale multi-center clinical trial to further demonstrate the efficiency of the combination of central and peripheral stimulation.

Clinical Trial Registration:http://www.chictr.org.cn (#ChiCTR1900023443).
Dopamine Neurons That Cotransmit Glutamate, From Synapses to Circuits to Behavior
Authors: Eskenazi Daniel , Malave Lauren , Mingote Susana , Yetnikoff Leora , Ztaou Samira , Velicu Vlad , Rayport Stephen , Chuhma Nao
Published: May 2021

Discovered just over 20 years ago, dopamine neurons have the ability to cotransmit both dopamine and glutamate. Yet, the functional roles of dopamine neuron glutamate cotransmission and their implications for therapeutic use are just emerging. This review article encompasses the current body of evidence investigating the functions of dopamine neurons of the ventral midbrain that cotransmit glutamate. Since its discovery in dopamine neuron cultures, further work in vivo confirmed dopamine neuron glutamate cotransmission across species. From there, growing interest has led to research related to neural functioning including roles in synaptic signaling, development, and behavior. Functional connectome mapping reveals robust connections in multiple forebrain regions to various cell types, most notably to cholinergic interneurons in both the medial shell of the nucleus accumbens and the lateral dorsal striatum. Glutamate markers in dopamine neurons reach peak levels during embryonic development and increase in response to various toxins, suggesting dopamine neuron glutamate cotransmission may serve neuroprotective roles. Findings from behavioral analyses reveal prominent roles for dopamine neuron glutamate cotransmission in responses to psychostimulants, in positive valence and cognitive systems and for subtle roles in negative valence systems. Insight into dopamine neuron glutamate cotransmission informs the pathophysiology of neuropsychiatric disorders such as addiction, schizophrenia and Parkinson Disease, with therapeutic implications.
Novel Compound Missense and Intronic Splicing Mutation in ALDH18A1 Causes Autosomal Recessive Spastic Paraplegia
Authors: Chen Yi-Jun , Zhang Zai-Qiang , Wang Meng-Wen , Qiu Yu-Sen , Yuan Ru-Ying , Dong En-Lin , Zhao Zhe , Zhou Hai-Tao , Wang Ning , Chen Wan-Jin , Lin Xiang
Published: May 2021

Background: Hereditary spastic paraplegia (HSP) caused by mutations in ALDH18A1 have been reported as spastic paraplegia 9 (SPG9), with autosomal dominant and autosomal recessive transmission (SPG9A and SPG9B). SPG9 is rare and has shown phenotypic and genotypic heterogeneity in previous reports.

Methods: This study screened ALDH18A1 mutations in autosomal recessive HSP patients using combined whole exome sequencing and RNA splicing analysis. We conducted in silico investigations, co-segregation analysis, and ELISA-based analysis of P5CS (Δ1-pyrroline-5-carboxylate synthetase; encoded by ALDH18A1) concentration to validate the pathogenicity of the detected ALDH18A1 variants. All previously reported bi-allelic ALDH18A1 mutations and cases were reviewed to summarize the genetic and clinical features of ALDH18A1-related HSP.

Results: A novel missense mutation c.880T>C, p.S294P and an intronic splicing mutation c.-28-13A>G were both detected in ALDH18A1 in an autosomal recessive family presenting with a complicated form HSP. ELISA assays revealed significantly decreased P5CS concentration in the proband's plasma compared with that in the healthy controls. Moreover, review of previously reported recessive cases showed that SPG9B patients in our cohort presented with milder symptoms, i.e., later age at onset and without cognitive impairment.

Conclusion: The present study expands the genetic and clinical spectrum of SPG9B caused by ALDH18A1 mutation. Our work defines new genetic variants to facilitate future diagnoses, in addition to demonstrating the highly informative value of splicing mutation prediction in the characterization of disease-related intronic variants.
Differential Functional Changes of Nav1.2 Channel Causing SCN2A-Related Epilepsy and Status Epilepticus During Slow Sleep
Authors: Miao Pu , Tang Siyang , Ye Jia , Tang Jihong , Wang Jianda , Zheng Chaoguang , Li Yuezhou , Feng Jianhua
Published: May 2021

Background: Nav1.2 encoded by the SCN2A gene is a brain-expressed voltage-gated sodium channel known to be associated with neurodevelopment disorders ranging from benign familial neonatal infantile seizures (BFIS) to developmental and epileptic encephalopathy (DEE) and autism spectrum disorder. Interestingly, status epilepticus during slow sleep (ESES), which aggravates cognitive impairment, has been found in SCN2A-related epilepsy. However, the functional features and the relationship between SCN2A and ESES have not been researched.

Method: We herein investigated the functional consequences of an unpublished de novo V911A and the other two published variants in patients with SCN2A-related disorder and ESES by whole-cell patch-clamp studies in transfected HEK293T cells.

Results: The unpublished V911A and published K1933M variants detected in patients with DEE exhibited a profound gain-of-functional (GOF) change. Another published BFIS variant S863F significantly reduced current density as a loss-of-functional (LOF) change. The refractory epilepsy in the patient with V911A was controlled by using the precise treatment of oxcarbazepine (OXC) since the age of 3 months. ESES was found at 18 months during the seizure-free period. We finally chose an aggressive treatment for eliminating ESES by using methylprednisolone combined with levetiracetam and nitrazepam instead of the precise treatment of OXC.

Conclusion: Both GOF and LOF variants in the SCN2A gene can lead to ESES among the phenotypes of DEE and BFIS. We should monitor the electroencephalogram regularly in the patients with SCN2A-related epilepsy even during their seizure-free period.