Recent Submissions

  • Journal Article

    Plasma YKL-40 in the spectrum of neurodegenerative dementia 

    Villar-Piqué, Anna; Schmitz, Matthias; Hermann, Peter; Goebel, Stefan; Bunck, Timothy; Varges, Daniela; Ferrer, Isidre; Riggert, Joachim; Llorens, Franc; Zerr, Inga
    Journal of Neuroinflammation. 2019 Jul 12;16(1):145
    Abstract Background Increased plasma YKL-40 has been reported in Alzheimer’s disease (AD), but its levels in other neurodegenerative diseases are unknown. Here, we aimed to investigate plasma YKL-40 in the spectrum of neurodegenerative dementias. Methods YKL-40 was quantified in the plasma of 315 cases, including healthy controls (HC), neurological disease controls (ND), AD, vascular dementia (VaD), frontotemporal dementia (FTD), sporadic Creutzfeldt-Jakob disease (CJD) and Lewy body dementia (LBD). Diagnostic accuracy in the differential diagnostic context and influence of age and gender was assessed. Results Highest YKL-40 levels were detected in CJD, followed by LBD, VaD, AD, FTD, ND and HC. YKL-40 was associated to age but not to sex. After controlling for age, YKL-40 was significantly elevated in CJD compared to HC (p < 0.001), ND, AD and VaD (p < 0.01) and in LBD compared to HC (p < 0.05). In CJD, YKL-40 concentrations were significantly higher at late disease stages. Conclusions Plasma YKL-40 is significantly elevated in CJD regardless of clinical and genetic parameters, with moderate diagnostic accuracy in the discrimination from control cases. Our study discards a potential use of this biomarker in the differential diagnostic context but opens the possibility to be explored as a marker for CJD monitoring.
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  • Journal Article

    Interactive effects of nitrogen and potassium on photosynthesis and photosynthetic nitrogen allocation of rice leaves 

    Hou, Wenfeng; Tränkner, Merle; Lu, Jianwei; Yan, Jinyao; Huang, Siyuan; Ren, Tao; Cong, Rihuan; Li, Xiaokun
    BMC Plant Biology. 2019 Jul 10;19(1):302
    Abstract Background Nitrogen (N) and potassium (K) are two important mineral nutrients in regulating leaf photosynthesis. Studying the interactive effects of N and K on regulating N allocation and photosynthesis (Pn) of rice leaves will be of great significance for further increasing leaf Pn, photosynthetic N use efficiency (PNUE) and grain yield. We measured the gas exchange of rice leaves in a field experiment and tested different kinds of leaf N based on N morphology and function, and calculated the interactive effects of N and K on N allocation and the PNUE. Results Compared with N0 (0 kg N ha− 1) and K0 (0 kg K2O ha− 1) treatments, the Pn was increased by 17.1 and 12.2% with the supply of N and K. Compared with N0K0 (0 kg N and 0 kg K2O ha− 1), N0K120 (0 kg N and 120 kg K2O ha− 1) and N0K180 (0 kg N and 180 kg K2O ha− 1), N supply increased the absolute content of photosynthetic N (Npsn) by 15.1, 15.5 and 10.5% on average, and the storage N (Nstore) was increased by 32.7, 64.9 and 72.7% on average. The relative content of Npsn was decreased by 5.6, 12.1 and 14.5%, while that of Nstore was increased by 8.7, 27.8 and 33.8%. Supply of K promoted the transformation of Nstore to Npsn despite the leaf N content (Na) was indeed decreased. Compared with N0K0, N180K0 (180 kg N and 0 kg K2O ha− 1) and N270K0 (270 kg N and 0 kg K2O ha− 1), K supply increased the relative content of Npsn by 17.7, 8.8 and 7.3%, and decreased the relative content of Nstore by 24.2, 11.4 and 8.7% respectively. Conclusions This study indicated the mechanism that K supply decreased the Na but increased the Npsn content and then increased leaf Pn and PNUE from a new viewpoint of leaf N allocation. The supply of K promoted the transformation of Nstore to Npsn and increased the PNUE. The decreased Nstore mainly resulted from the decrease of non-protein N. Combined use of N and K could optimize leaf N allocation and maintain a high leaf Npsn content and PNUE.
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  • Journal Article

    Pathological changes are associated with shifts in the employment of synonymous codons at the transcriptome level 

    Fornasiero, Eugenio F; Rizzoli, Silvio O
    BMC Genomics. 2019 Jul 09;20(1):566
    Abstract Background The usage of different synonymous codons reflects the genome organization and has been connected to parameters such as mRNA abundance and protein folding. It is also been established that mutations targeting specific synonymous codons can trigger disease. Results We performed a systematic meta-analysis of transcriptome results from 75 datasets representing 40 pathologies. We found that a subset of codons was preferentially employed in abundant transcripts, while other codons were preferentially found in low-abundance transcripts. By comparing control and pathological transcriptomes, we observed a shift in the employment of synonymous codons for every analyzed disease. For example, cancerous tissue employed preferentially A- or U-ending codons, shifting from G- or C-ending codons, which were preferred by control tissues. This analysis was able to discriminate patients and controls with high specificity and sensitivity. Conclusions Here we show that the employment of specific synonymous codons, quantified at the whole transcriptome level, changes profoundly in many diseases. We propose that the changes in codon employment offer a novel perspective for disease studies, and could be used to design new diagnostic tools.
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  • Journal Article

    Single and simultaneous effects of acrylamide and ethanol on bone microstructure of mice after one remodeling cycle 

    Sarocka, Anna; Kovacova, Veronika; Omelka, Radoslav; Grosskopf, Birgit; Kapusta, Edyta; Goc, Zofia; Formicki, Grzegorz; Martiniakova, Monika
    BMC Pharmacology and Toxicology. 2019 Jul 01;20(1):38
    Abstract Background This study aimed to examine femoral bone microstructure of mice after single and simultaneous administration to acrylamide and ethanol since both substances are often consumed separately and/or together by humans. Interactive effects of these toxins were analysed after one remodeling cycle. Methods Twenty clinically healthy adult mice were randomly divided into four groups following 2 weeks administration of toxins: A group - mice were fed with acrylamide (40 mg/kg bw); E group - mice were ethanol-fed (15% ethanol); AE group - mice were simultaneously fed with both toxins, and a C group – control (without acrylamide and/or ethanol supplementation). Generally, 2D and 3D imaging methods were used to determine cortical and trabecular bone tissues microstructure. Biochemical analyses of plasma parameters were also realized using commercially available ELISA tests and spectrophotometrically. Results Single and simultaneous exposure to acrylamide and ethanol affected only cortical bone microstructure. No significant changes in trabecular bone morphometry were detected among all groups. In mice from the A group, increased endocortical remodeling associated with a higher level of serum calcium and vasoconstriction of primary osteon’s vascular canals (POVC) were identified. On the contrary, increased cortical porosity consistent with a decreased relative bone volume, bone mineral density (BMD) and lower levels of alkaline phosphatase (ALP), glutathione (GSH), calcium in plasma and also with vasodilation of POVC were observed in the E group. In the AE group, the highest density of secondary osteons associated with a lower BMD and decreased levels of ALP, GSH were documented. The parameters of POVC and Haversian canals approximated to the C group. In addition, single and simultaneous exposure to both toxins caused liver disease consistent with a higher values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in plasma of all experimental groups. Conclusions Single administration to acrylamide and ethanol had negative effects on cortical bone structure of mice after one remodeling cycle. However, we identified possible antagonistic impact of these toxins on the structure of the cortical bone.
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  • Journal Article

    The E3 ubiquitin ligase RNF40 suppresses apoptosis in colorectal cancer cells 

    Schneider, Deborah; Chua, Robert L; Molitor, Nicole; Hamdan, Feda H; Rettenmeier, Eva M; Prokakis, Evangelos; Mishra, Vivek K; Kari, Vijayalakshmi; Wegwitz, Florian; Johnsen, Steven A; et al.
    Kosinsky, Robyn L
    Clinical Epigenetics. 2019 Jul 02;11(1):98
    Abstract Background Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide, and deciphering underlying molecular mechanism is essential. The loss of monoubiquitinated histone H2B (H2Bub1) was correlated with poor prognosis of CRC patients and, accordingly, H2Bub1 was suggested as a tumor-suppressive mark. Surprisingly, our previous work revealed that the H2B ubiquitin ligase RING finger protein 40 (RNF40) might exert tumor-promoting functions. Here, we investigated the effect of RNF40 loss on tumorigenic features of CRC cells and their survival in vitro. Methods We evaluated the effects of RNF40 depletion in several human CRC cell lines in vitro. To evaluate cell cycle progression, cells were stained with propidium iodide and analyzed by flow cytometry. In addition, to assess apoptosis rates, caspase 3/7 activity was assessed in a Celigo® S-based measurement and, additionally, an Annexin V assay was performed. Genomic occupancy of H2Bub1, H3K79me3, and H3K27ac was determined by chromatin immunoprecipitation. Transcriptome-wide effects of RNF40 loss were evaluated based on mRNA-seq results, qRT-PCR, and Western blot. To rescue apoptosis-related effects, cells were treated with Z-VAD-FMK. Results Human CRC cell lines displayed decreased cell numbers in vitro after RNF40 depletion. While the differences in confluence were not mediated by changes in cell cycle progression, we discovered highly increased apoptosis rates after RNF40 knockdown due to elevated caspase 3/7 activity. This effect can be explained by reduced mRNA levels of anti-apoptotic and upregulation of pro-apoptotic BCL2 family members. Moreover, the direct occupancy of the RNF40-mediated H2B monoubiquitination was observed in the transcribed region of anti-apoptotic genes. Caspase inhibition by Z-VAD-FMK treatment rescued apoptosis in RNF40-depleted cells. However, knockdown cells still displayed decreased tumorigenic features despite the absence of apoptosis. Conclusions Our findings reveal that RNF40 is essential for maintaining tumorigenic features of CRC cells in vitro by controlling the expression of genes encoding central apoptotic regulators.
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  • Journal Article

    Big data research guided by sociological theory: a triadic dialogue among big data analysis, theory, and predictive models 

    Luo, Jar-Der; Liu, Jifan; Yang, Kunhao; Fu, Xiaoming
    The Journal of Chinese Sociology. 2019 Jul 05;6(1):11
    Abstract Computational social science has integrated social science theories and methodology with big data analysis. It has opened a number of new topics for big data analysis and enabled qualitative and quantitative sociological research to provide the ground truth for testing the results of data mining. At the same time, threads of evidence obtained by data mining can inform the development of theory and thereby guide the construction of predictive models to infer and explain more phenomena. Using the example of the Internet data of China’s venture capital industry, this paper shows the triadic dialogue among data mining, sociological theory, and predictive models and forms a methodology of big data analysis guided by sociological theories.
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  • Journal Article

    Stapled EGFR peptide reduces inflammatory breast cancer and inhibits additional HER-driven models of cancer 

    Maisel, Sabrina A; Broka, Derrick; Atwell, Benjamin; Bunch, Thomas; Kupp, Robert; Singh, Shiv K; Mehta, Shwetal; Schroeder, Joyce
    Journal of Translational Medicine. 2019 Jun 18;17(1):201
    Abstract Background The human epidermal growth factor receptor (HER) family of transmembrane tyrosine kinases is overexpressed and correlates with poor prognosis and decreased survival in many cancers. The receptor family has been therapeutically targeted, yet tyrosine kinase inhibitors (TKIs) do not inhibit kinase-independent functions and antibody-based targeting does not affect internalized receptors. We have previously demonstrated that a peptide mimicking the internal juxtamembrane domain of HER1 (EGFR; EJ1) promotes the formation of non-functional HER dimers that inhibit kinase-dependent and kinase-independent functions of HER1 (ERBB1/EGFR), HER2 (ERBB2) and HER3 (ERBB3). Despite inducing rapid HER-dependent cell death in vitro, EJ1 peptides are rapidly cleared in vivo, limiting their efficacy. Method To stabilize EJ1 activity, hydrocarbon staples (SAH) were added to the active peptide (SAH-EJ1), resulting in a 7.2-fold increase in efficacy and decreased in vivo clearance. Viability assays were performed across HER1 and HER2 expressing cell lines, therapeutic-resistant breast cancer cells, clinically relevant HER1-mutated lung cancer cells, and patient-derived glioblastoma cells, in all cases demonstrating improved efficacy over standard of care pan-HER therapeutics. Tumor burden studies were also performed in lung, glioblastoma, and inflammatory breast cancer mouse models, evaluating tumor growth and overall survival. Results When injected into mouse models of basal-like and inflammatory breast cancers, EGFRvIII-driven glioblastoma, and lung adenocarcinoma with Erlotinib resistance, tumor growth is inhibited and overall survival is extended. Studies evaluating the toxicity of SAH-EJ1 also demonstrate a broad therapeutic window. Conclusions Taken together, these data indicate that SAH-EJ1 may be an effective therapeutic for HER-driven cancers with the potential to eliminate triple negative inflammatory breast cancer.
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  • Journal Article

    Parental military deployment as risk factor for children’s mental health: a meta-analytical review 

    Cunitz, Katrin; Dölitzsch, Claudia; Kösters, Markus; Willmund, Gerd-Dieter; Zimmermann, Peter; Bühler, Antje H; Fegert, Jörg M; Ziegenhain, Ute; Kölch, Michael
    Child and Adolescent Psychiatry and Mental Health. 2019 Jun 21;13(1):26
    Abstract There is evidence that military service increases the risk of psychosocial burden for not only service members but also their spouses and children. This meta-analysis aimed to systematically assess the association between military deployment of (at least one) parent and impact on children’s mental health. For this meta-analytic review, publications were systematically searched and assessed for eligibility based on predefined inclusion criteria (studies between 2001 until 2017 involving children with at least one parent working in military services). Measurements were determined by total problem scores of the children as well as symptoms of anxiety/depression, hyperactivity/inattention, and aggressive behavior. Meta-analyses aggregated the effect sizes in random-effect models and were calculated separately for the relation between parental deployment and civilian/normative data and for the relation between parental deployment and non-deployment. Age of the children was used as moderator variable to explore any potential source of heterogeneity between studies. Parental military deployment was associated with problems in children and adolescents compared to civilian/normative samples. Significant effect sizes reached from small to moderate values; the largest effect sizes were found for overall problems and specifically for anxious/depressive symptoms and aggressive behavior. Within the military group, children of deployed parents showed more problem behavior than children of non-deployed parents, but effect sizes were small. Age of the children had no moderating effect. The results emphasize that children of military members, especially with a deployed parent, should be assessed for emotional and behavioral problems.
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  • Journal Article

    Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy 

    Wu, Jia-Zhen; Ardah, Mustafa; Haikal, Caroline; Svanbergsson, Alexander; Diepenbroek, Meike; Vaikath, Nishant N; Li, Wen; Wang, Zhan-You; Outeiro, Tiago F; El-Agnaf, Omar M; et al.
    Li, Jia-Yi
    Translational Neurodegeneration. 2019 Jun 15;8(1):18
    Abstract Background Progressive accumulation of α-synuclein is a key step in the pathological development of Parkinson’s disease. Impaired protein degradation and increased levels of α-synuclein may trigger a pathological aggregation in vitro and in vivo. The chaperone-mediated autophagy (CMA) pathway is involved in the intracellular degradation processes of α-synuclein. Dysfunction of the CMA pathway impairs α-synuclein degradation and causes cytotoxicity. Results In the present study, we investigated the effects on the CMA pathway and α-synuclein aggregation using bioactive ingredients (Dihydromyricetin (DHM) and Salvianolic acid B (Sal B)) extracted from natural medicinal plants. In both cell-free and cellular models of α-synuclein aggregation, after administration of DHM and Sal B, we observed significant inhibition of α-synuclein accumulation and aggregation. Cells were co-transfected with a C-terminal modified α-synuclein (SynT) and synphilin-1, and then treated with DHM (10 μM) and Sal B (50 μM) 16 hours after transfection; levels of α-synuclein aggregation decreased significantly (68% for DHM and 75% for Sal B). Concomitantly, we detected increased levels of LAMP-1 (a marker of lysosomal homeostasis) and LAMP-2A (a key marker of CMA). Immunofluorescence analyses showed increased colocalization between LAMP-1 and LAMP-2A with α-synuclein inclusions after treatment with DHM and Sal B. We also found increased levels of LAMP-1 and LAMP-2A both in vitro and in vivo, along with decreased levels of α-synuclein. Moreover, DHM and Sal B treatments exhibited anti-inflammatory activities, preventing astroglia- and microglia-mediated neuroinflammation in BAC-α-syn-GFP transgenic mice. Conclusions Our data indicate that DHM and Sal B are effective in modulating α-synuclein accumulation and aggregate formation and augmenting activation of CMA, holding potential for the treatment of Parkinson’s disease.
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  • Journal Article

    Extracorporeal gas exchange: when to start and how to end? 

    Gattinoni, L.; Vassalli, F.; Romitti, F.; Vasques, F.; Pasticci, I.; Duscio, E.; Quintel, M.
    Critical Care. 2019 Jun 14;23(Suppl 1):203
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  • Journal Article

    Thinking forward: promising but unproven ideas for future intensive care 

    Marini, John J; DeBacker, Daniel; Gattinoni, Luciano; Ince, Can; Martin-Loeches, Ignacio; Singer, Pierre; Singer, Mervyn; Westphal, Martin; Vincent, Jean-Louis
    Critical Care. 2019 Jun 14;23(Suppl 1):197
    Abstract Progress toward determining the true worth of ongoing practices or value of recent innovations can be glacially slow when we insist on following the conventional stepwise scientific pathway. Moreover, a widely accepted but flawed conceptual paradigm often proves difficult to challenge, modify or reject. Yet, most experienced clinicians, educators and clinical scientists privately entertain untested ideas about how care could or should be improved, even if the supporting evidence base is currently thin or non-existent. This symposium encouraged experts to share such intriguing but unproven concepts, each based upon what the speaker considered a logical but unproven rationale. Such free interchange invited dialog that pointed toward new or neglected lines of research needed to improve care of the critically ill. In this summary of those presentations, a brief background outlines the rationale for each novel and deliberately provocative unconfirmed idea endorsed by the presenter.
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  • Journal Article

    Assessing biological dissimilarities between five forest communities 

    Hao, Minhui; Corral-Rivas, J. J; González-Elizondo, M. S; Ganeshaiah, K. N; Nava-Miranda, M. G; Zhang, Chunyu; Zhao, Xiuhai; von Gadow, Klaus
    Forest Ecosystems. 2019 Jun 06;6(1):30
    Abstract Background Dissimilarity in community composition is one of the most fundamental and conspicuous features by which different forest ecosystems may be distinguished. Traditional estimates of community dissimilarity are based on differences in species incidence or abundance (e.g. the Jaccard, Sørensen, and Bray-Curtis dissimilarity indices). However, community dissimilarity is not only affected by differences in species incidence or abundance, but also by biological heterogeneities among species. Methods The objective of this study is to present a new measure of dissimilarity involving the biological heterogeneity among species. The “discriminating Avalanche” introduced in this study, is based on the taxonomic dissimilarity between tree species. The application is demonstrated using observations from five stem-mapped forest plots in China and Mexico. We compared three traditional community dissimilarity indices (Jaccard, Sørensen, and Bray-Curtis) with the “discriminating Avalanche” index, which incorporates information, not only about species frequencies, but also about their taxonomic hierarchies. Results Different patterns emerged for different measures of community dissimilarity. Compared with the traditional approaches, the discriminating Avalanche values showed a more realistic estimate of community dissimilarities, indicating a greater similarity among communities when species were closely related. Conclusions Traditional approaches for assessing community dissimilarity disregard the taxonomic hierarchy. In the traditional analysis, the dissimilarity between Pinus cooperi and Pinus durangensis would be the same as the dissimilarity between P. cooperi and Arbutus arizonica. The dissimilarity Avalanche dissimilarity between P. cooperi and P. durangensis is considerably lower than the dissimilarity between P. cooperi and A. arizonica, because the taxonomic hierarchies are incorporated. Therefore, the discriminating Avalanche is a more realistic measure of community dissimilarity. This main result of our study may contribute to improved characterization of community dissimilarities.
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  • Journal Article

    Risk factors for catheter-related infections in patients receiving permanent dialysis catheter 

    Delistefani, Fani; Wallbach, Manuel; Müller, Gerhard A; Koziolek, Michael J; Grupp, Clemens
    BMC Nephrology. 2019 May 31;20(1):199
    Abstract Background Due to rising vascular comorbidities of patients undergoing dialysis, the prevalence of permanent hemodialysis catheters as hemodialysis access is increasing. However, infection is a major complication of these catheters. Therefore, identification of potential predicting risk factors leading to early infection related complications is valuable, in particular the significance the CRP (C-reactive protein)-value is of interest. Methods In this retrospective study 151 permanent hemodialysis catheters implanted in 130 patients were examined. The following data were collected at the time of catheter implantation: CRP-value, history of catheter-related infection, microbiological status, immunosuppression and diabetes mellitus. The primary outcomes were recorded over the 3 months following the implantation: catheter-related infection, days of hospital stay and death. Catheter removal or revision, rehospitalization and use of antibiotics were identified as secondary outcomes. Results We identified a total of 27 (17.9%) infections (systemic infection: 2.26 episodes/ 1000 catheter days, local infection: 0.6 episodes/ 1000 catheter days). The development of an infection was independent of the CRP-value (p = 0.66) as well as the presence of diabetes mellitus (p = 0.64) or immunosuppression (p = 0.71). Univariate analysis revealed that infection was more frequent in patients with MRSA-carriage (p < 0.001), in case of previous catheter-related infection (p < 0.05) and of bacteremia or bacteriuria in the period of 3 months before catheter implantation (p < 0.001). Catheter removal or revision (p = 0.002), rehospitalization (p = 0.001) and use of antibiotics (p = 0.02) were also more often observed in patients with MRSA-carriage. Conclusions The CRP-value at the time of implantation of a permanent hemodialysis catheter is not associated with the development of early catheter related infections, but an individual history of catheter-related infection, MRSA-carriage and bacteremia or bacteriuria in the period of 3 months prior to catheter implantation are significant risk factors.
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  • Journal Article

    Designing near-natural planting patterns for plantation forests in China 

    Zhang, Gongqiao; Hui, Gangying; Hu, Yanbo; Zhao, Zhonghua; Guan, Xiuling; von Gadow, Klaus; Zhang, Ganggang
    Forest Ecosystems. 2019 May 29;6(1):28
    Abstract Background China has a long tradition of managing planted forests. Different species of Populus, Eucalyptus, Larix, Cunninghamia and Pinus are planted to satisfy the local demand for wood products and provide ecological services at the same time. Evidence of the greater resilience of natural forests provides the motivation to develop asymmetric planting patterns, which is the focus of this study. We present a new method for designing plantation patterns that follow those observed in natural ecosystems and to maintain some regularity for operational convenience. Methods Based on the uniform angle index, we analyzed the spatial structure of six natural forests in different regions of China. The uniform angle index describes the degree of spatial uniformity of the n nearest neighbors of a given reference tree. Accordingly, we identified all possible patterns of a neighborhood group within a regular planting pattern and developed a method to optimize planting point arrangements that contain some randomness as well as a minimum degree of regularity. Results (1) There are 13 types of structural units in a regular planting, including seven random units, five even units and one cluster unit; (2) Five near-natural arrangements are presented with a minimum proportion of 50% of random units. These five arrangements represent a combination of regularity for operational convenience and asymmetry. Conclusions The new planting patterns developed in this study are expected to increase the asymmetric competition and resilience of these important ecosystems. Some experimental plantings, based on our findings, have already been established, e.g., in Pinus tabulaeformis plantations in Tianshui, Gansu Province, and in a Populus deltoides plantation in Fangshan near Beijing.
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  • Journal Article

    Variation in health system performance for managing diabetes among states in India: a cross-sectional study of individuals aged 15 to 49 years 

    Prenissl, Jonas; Jaacks, Lindsay M; Mohan, Viswanathan; Manne-Goehler, Jennifer; Davies, Justine I; Awasthi, Ashish; Bischops, Anne C; Atun, Rifat; Bärnighausen, Till; Vollmer, Sebastian; et al.
    Geldsetzer, Pascal
    BMC Medicine. 2019 May 13;17(1):92
    Abstract Background Understanding where adults with diabetes in India are lost in the diabetes care cascade is essential for the design of targeted health interventions and to monitor progress in health system performance for managing diabetes over time. This study aimed to determine (i) the proportion of adults with diabetes in India who have reached each step of the care cascade and (ii) the variation of these cascade indicators among states and socio-demographic groups. Methods We used data from a population-based household survey carried out in 2015 and 2016 among women and men aged 15–49 years in all states of India. Diabetes was defined as a random blood glucose (RBG) ≥ 200 mg/dL or reporting to have diabetes. The care cascade—constructed among those with diabetes—consisted of the proportion who (i) reported having diabetes (“aware”), (ii) had sought treatment (“treated”), and (iii) had sought treatment and had a RBG < 200 mg/dL (“controlled”). The care cascade was disaggregated by state, rural-urban location, age, sex, household wealth quintile, education, and marital status. Results This analysis included 729,829 participants. Among those with diabetes (19,453 participants), 52.5% (95% CI, 50.6–54.4%) were “aware”, 40.5% (95% CI, 38.6–42.3%) “treated”, and 24.8% (95% CI, 23.1–26.4%) “controlled”. Living in a rural area, male sex, less household wealth, and lower education were associated with worse care cascade indicators. Adults with untreated diabetes constituted the highest percentage of the adult population (irrespective of diabetes status) aged 15 to 49 years in Goa (4.2%; 95% CI, 3.2–5.2%) and Tamil Nadu (3.8%; 95% CI, 3.4–4.1%). The highest absolute number of adults with untreated diabetes lived in Tamil Nadu (1,670,035; 95% CI, 1,519,130–1,812,278) and Uttar Pradesh (1,506,638; 95% CI, 1,419,466–1,589,832). Conclusions There are large losses to diabetes care at each step of the care cascade in India, with the greatest loss occurring at the awareness stage. While health system performance for managing diabetes varies greatly among India’s states, improvements are particularly needed for rural areas, those with less household wealth and education, and men. Although such improvements will likely have the greatest benefits for population health in Goa and Tamil Nadu, large states with a low diabetes prevalence but a high absolute number of adults with untreated diabetes, such as Uttar Pradesh, should not be neglected.
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  • Journal Article

    Loss of sphingosine 1-phosphate (S1P) in septic shock is predominantly caused by decreased levels of high-density lipoproteins (HDL) 

    Winkler, Martin S.; Märtz, Konstantin B.; Nierhaus, Axel; Daum, Günter; Schwedhelm, Edzard; Kluge, Stefan; Gräler, Markus H.
    Journal of Intensive Care. 2019 Apr 17;7(1):23
    Background Sphingosine 1-phosphate (S1P) is a signaling lipid essential in regulating processes involved in sepsis pathophysiology, including endothelial permeability and vascular tone. Serum S1P is progressively reduced in sepsis patients with increasing severity. S1P function depends on binding to its carriers: serum albumin (SA) and high-density lipoproteins (HDL). The aim of this single-center prospective observational study was to determine the contribution of SA- and HDL-associated S1P (SA-S1P and HDL-S1P) to sepsis-induced S1P depletion in plasma with regard to identify future strategies to supplement vasoprotective S1P. Methods Sequential precipitation of lipoproteins was performed with plasma samples obtained from 100 ICU patients: surgical trauma (n = 20), sepsis (n = 63), and septic shock (n = 17) together with healthy controls (n = 7). Resultant fractions with HDL and SA were analyzed by liquid chromatography coupled to triple-quadrupole mass spectrometry (LC-MS/MS) for their S1P content. Results Plasma S1P levels significantly decreased with sepsis severity and showed a strong negative correlation with increased organ failure, quantified by the Sequential Organ Failure Assessment (SOFA) score (rho − 0.59, P < 0.001). In controls, total plasma S1P levels were 208 μg/L (187–216 μg/L). In trauma patients, we observed an early loss of SA-S1P (− 70%) with a concurrent increase of HDL-S1P (+ 20%), resulting in unaltered total plasma S1P with 210 μg/L (143–257 μg/L). The decrease of plasma S1P levels with increasing SOFA score in sepsis patients with 180.2 μg/L (123.3–253.0 μg/L) and in septic shock patients with 99.5 μg/L (80.2–127.2 μg/L) was mainly dependent on equivalent reductions of HDL and not SA as carrier protein. Thus, HDL-S1P contributed most to total plasma S1P in patients and progressively dropped with increasing SOFA score. Conclusions Reduced plasma S1P was associated with sepsis-induced organ failure. A constant plasma S1P level during the acute phase after surgery was maintained with increased HDL-S1P and decreased SA-S1P, suggesting the redistribution of plasma S1P from SA to HDL. The decrease of plasma S1P levels in patients with increasing sepsis severity was mainly caused by decreasing HDL and HDL-S1P. Therefore, strategies to reconstitute HDL-S1P rather than SA-S1P should be considered for sepsis patients.
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  • Journal Article

    Correction to: Agricultural trade policies and child nutrition in low- and middle-income countries: a cross-national analysis 

    Adjaye-Gbewonyo, Kafui; Vollmer, Sebastian; Avendano, Mauricio; Harttgen, Kenneth
    Globalization and Health. 2019 Apr 10;15(1):28
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  • Journal Article

    On and off the rocks: persistence and ecological diversification in a tropical Australian lizard radiation 

    Oliver, Paul M; Ashman, Lauren G; Bank, Sarah; Laver, Rebecca J; Pratt, Renae C; Tedeschi, Leonardo G; Moritz, Craig C
    BMC Evolutionary Biology. 2019 Mar 20;19(1):81
    Abstract Background Congruent patterns in the distribution of biodiversity between regions or habitats suggest that key factors such as climatic and topographic variation may predictably shape evolutionary processes. In a number of tropical and arid biomes, genetic analyses are revealing deeper and more localised lineage diversity in rocky ranges than surrounding habitats. Two potential drivers of localised endemism in rocky areas are refugial persistence through climatic change, or ecological diversification and specialisation. Here we examine how patterns of lineage and phenotypic diversity differ across two broad habitat types (rocky ranges and open woodlands) in a small radiation of gecko lizards in the genus Gehyra (the australis group) from the Australian Monsoonal Tropics biome. Results Using a suite of approaches for delineating evolutionarily independent lineages, we find between 26 and 41 putative evolutionary units in the australis group (versus eight species currently recognised). Rocky ranges are home to a greater number of lineages that are also relatively more restricted in distribution, while lineages in open woodland habitats are fewer, more widely distributed, and, in one case, show evidence of range expansion. We infer at least two shifts out of rocky ranges and into surrounding woodlands. Phenotypic divergence between rocky ranges specialist and more generalist taxa is detected, but no convergent evolutionary regimes linked to ecology are inferred. Conclusions In climatically unstable biomes such as savannahs, rocky ranges have functioned as zones of persistence, generators of diversity and a source of colonists for surrounding areas. Phenotypic divergence can also be linked to the use of differing habitat types, however, the extent to which ecological specialisation is a primary driver or secondary outcome of localised diversification remains uncertain.
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  • Journal Article

    Signal peptide replacement resulted in recombinant homologous expression of laccase Lcc8 in Coprinopsis cinerea 

    Schulze, Marcus; Geisler, Lukas; Majcherczyk, Andrzej; Rühl, Martin
    AMB Express. 2019 Mar 15;9(1):36
    Abstract Although the model agaricomycete Coprinopsis cinerea possess 17 different laccase genes, up to now only four C. cinerea laccases have been purified and characterized to some degree. By exchanging the nucleotide sequence of the deduced signal peptide of Lcc8 it was possible to homologously express lcc8 in C. cinerea under control of the Agaricus bisporus gdpII promoter and the C. cinerea lcc1 terminator. The purified Lcc8 showed two bands in the SDS-PAGE with a molecular weight of 64 kDa and 77 kDa, respectively. The IEF determined pI values of 3.3 and 3.4 for both bands. The optimal pH for oxidation of the substrates ABTS, 2,6-dimethoxyphenol, guaiacol and syringaldazine was pH 4.0, pH 5.0, pH 4.5 and pH 5.0, respectively. Best pH for enzyme storage was pH 8.0. The optimal temperature for oxidation of ABTS was 63 °C, while Lcc8 showed activity of at least 50% over 300 min at 50 °C. The comparable high stability of Lcc8 at alkaline pH and higher temperatures can be of interest for biotechnical applications.
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  • Journal Article

    The central nervous system of Oweniidae (Annelida) and its implications for the structure of the ancestral annelid brain 

    Beckers, Patrick; Helm, Conrad; Purschke, Günter; Worsaae, Katrine; Hutchings, Pat; Bartolomaeus, Thomas
    Frontiers in Zoology. 2019 Mar 12;16(1):6
    Abstract Background Recent phylogenomic analyses congruently reveal a basal clade which consists of Oweniidae and Mageloniidae as sister group to the remaining Annelida. These results indicate that the last common ancestor of Annelida was a tube-dwelling organism. They also challenge traditional evolutionary hypotheses of different organ systems, among them the nervous system. In textbooks the central nervous system is described as consisting of a ganglionic ventral nervous system and a dorsally located brain with different tracts that connect certain parts of the brain to each other. Only limited information on the fine structure, however, is available for Oweniidae, which constitute the sister group (possibly together with Magelonidae) to all remaining annelids. Results The brain of Oweniidae is ring- shaped and basiepidermal. Ganglia, higher brain centers or complex sensory organs do not exist; instead the central nervous system is medullary. Posterior to the brain the ventral medullary cord arises directly from the ventral region of the brain in Myriowenia sp. while in Owenia fusiformis two medullary cords arise perpendicular to the brain ring, extend caudally and fuse posterior. The central nervous system is composed of a central neuropil and surrounding somata of the neurons. According to ultrastructural and histological data only one type of neuron is present in the central nervous system. Conclusion The central nervous system of Oweniidae is the simplest in terms of enlargement of the dorsal part of the brain and neuron distribution found among Annelida. Our investigation suggests that neither ganglia nor commissures inside the brain neuropil or clusters of polymorphic neurons were present in the annelid stem species. These structures evolved later within Annelida, most likely in the stem lineage of Amphinomidae, Sipuncula and Pleistoannelida. Palps were supposedly present in the last common ancestor of annelids and innervated by two nerves originating in the dorsal part of the brain. A broader comparison with species of each major spiralian clade shows the medullary nervous system to be a common feature and thus possibly representing the ancestral state of the spiralian nervous system. Moreover, ganglia and clusters of polymorphic neurons seemingly evolved independently in the compared taxa of Spiralia and Annelida.
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