bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radotinib enhances cytarabine (Ara-C)-induced acute myeloid leukemia cell death
Authors: Heo Sook-Kyoung , Noh Eui-Kyu , Yu Ho-Min , Kim Do Kyoung , Seo Hye Jin , Lee Yoo Jin , Cheon Jaekyung , Koh SuJin , Min Young Joo , Choi Yunsuk , Jo Jae-Cheol 
Published: November 2020

Abstract
Background: Acute myeloid leukemia (AML) is a heterogeneous disease that frequently relapses after standard chemotherapy. Therefore, there is a need for the development of novel chemotherapeutic agents that could treat AML effectively. Radotinib, an oral BCR-ABL tyrosine kinase inhibitor, was developed as a drug for the treatment of chronic myeloid leukemia. Previously, we reported that radotinib exerts increased cytotoxic effects towards AML cells. However, little is known about the effects of combining radotinib with Ara-C, a conventional chemotherapeutic agent for AML, with respect to cell death in AML cells. Therefore, we investigated combination effects of radotinib and Ara-C on AML in this study. Methods: Synergistic anti-cancer effects of radotinib and Ara-C in AML cells including HL60, HEL92.1.7, THP-1 and bone marrow cells from AML patients have been examined. Diverse cell biological assays such as cell viability assay, Annexin V-positive cells, caspase-3 activity, cell cycle distribution, and related signaling pathway have been performed. Results: The combination of radotinib and Ara-C was found to induce AML cell apoptosis, which involved the mitochondrial pathway. In brief, combined radotinib and Ara-C significantly induced Annexin V-positive cells, cytosolic cytochrome C , and the pro-apoptotic protein Bax in AML cells including HL60, HEL92.1.7, and THP-1. In addition, mitochondrial membrane potential and Bcl-xl protein were markedly decreased by radotinib and Ara-C. Moreover, this combination induced caspase-3 activity. Cleaved caspase-3, 7, and 9 levels were also increased by combined radotinib and Ara-C. Additionally, radotinib and Ara-C co-treatment induced G 0 /G 1 arrest via the induction of CDKIs such as p21 and p27 and the inhibition of CDK2 and cyclin E. Thus, radotinib/Ara-C induces mitochondrial-dependent apoptosis and G 0 /G 1 arrest via the regulation of the CDKI–CDK–cyclin cascade in AML cells. In addition, our results showed that combined treatment with radotinib and Ara-C inhibits AML cell growth, including tumor volumes and weights in vivo . Also, the combination of radotinib and Ara-C can sensitize cells to chemotherapeutic agents such as daunorubicin or idarubicin in AML cells. Conclusions: Therefore, our results can be concluded that radotinib in combination with Ara-C possesses a strong anti-AML activity.
Consolidated bioprocessing of cellulose to itaconic acid by a co-culture of Trichoderma reesei and Ustilago maydis.
Authors: Schlembach Ivan , Tehrani Hamed , Blank Lars Mathias , Büchs Jochen , Wierckx Nick , Regestein Lars , Rosenbaum Miriam 
Published: November 2020

Abstract
Background: Itaconic acid is a bio-derived platform chemical with uses ranging from polymer synthesis to biofuel production. The efficient conversion of cellulosic waste streams into itaconic acid could thus enable the sustainable production of a variety of substitutes for fossil oil based products. However, the realization of such a process is currently hindered by an expensive conversion of cellulose into fermentable sugars. Here, we present the stepwise development of a fully consolidated bioprocess (CBP), which is capable to directly convert recalcitrant cellulose into itaconic acid without the need for separate cellulose hydrolysis including the application of commercial cellulases. The process is based on a synthetic microbial consortium of the cellulase producer Trichoderma reesei and the itaconic acid producing yeast Ustilago maydis. A method for process monitoring was developed to estimate cellulose consumption, itaconic acid formation as well as the actual itaconic acid production yield online during co-cultivation. Results: The efficiency of the process was compared to a simultaneous hydrolysis and fermentation setup (SSF). Because of the additional substrate consumption of T. reesei in the CBP, the itaconic acid yield was significantly lower in the CBP than in the SSF. In order to increase yield and productivity of itaconic acid in the CBP, the population dynamics was manipulated by varying the inoculation delay between T. reesei and U. maydis . Surprisingly, neither inoculation delay nor inoculation density significantly affected the population development or the CBP performance. Instead, the substrate availability was the most important parameter. U. maydis was only able to grow and to produce itaconic acid when the cellulose concentration and thus, the sugar supply rate, was high. Finally, the metabolic processes during fed-batch CBP were analyzed in depth by online respiration measurements. Thereby, substrate availability was again identified as the key factor also controlling itaconic acid yield. In summary, an itaconic acid titer of 34 g/L with a total productivity of up to 0.07 g/L/h and a yield of 0.16 g/g could be reached during fed-batch cultivation. Conclusion: This study demonstrates the feasibility of consortium based CBP for itaconic acid production and also lays the fundament for the development and improvement of similar microbial consortia for cellulose based organic acid production.
Relationship between blood Lead status and anemia in Ugandan children with malaria infection
Authors: Mukisa Ambrose K , Kasozi Denis M , Aguttu Claire , Vuzi Peter C. , Kyambadde Joseph 
Published: November 2020

Abstract
BackgroundIn Uganda, childhood anemia remains a health challenge and is associated with malaria infection as well as iron deficiency. Iron deficiency is intertwined with nutritional status, age and other comorbidities including helminths and Lead toxicity. Environmental Lead levels accounts for one’s blood Lead (BL) levels. Blood Lead competitively blocks iron absorption, inhibits hemoglobin (Hb) biosynthesis and elevates free erythrocyte protoporphyrin (FEP) levels. Lead toxicity’s contribution towards anemia pathogenesis, especially during malaria infection has not been studied. Concomitant exposure to both malaria infection and Lead pollution, exacerbates the anemia status. This study therefore aimed at expounding the anemia status of these Ugandan children aged under 5years who are exposed to both malaria infection and environmental Lead pollution.MethodsBriefly, venous blood samples from 198 children were microscopically assayed for malaria parasite density (PD), and hemoglobin (Hb) concentrations using the cyanmethemoglobin method, while BL and FEP levels were determined by the standard atomic absorption spectrophotometric and fluorometric methods respectively.ResultsOne hundred and fifty-one (76.3%) of the children analyzed had moderate anemia (Hb <10>5 g/dL) with Means of BLL=8.6 µg/dL, Hb =7.5 g/dL, FEP/Hb =8.3 µg/g and PD =3.21×103 parasites / µL, while eight (4%) were severely anemic (<5 g/dL). Regression analysis and statistical correlation between PD and Hb (r = -0.231, R2= 0.15 P-value < 0.001) was negative and weak as compared to that between FEP/Hb and Hb (r = -0.6, R2=0.572 P-value=0.001).ConclusionBased on the study’s findings, we conclude that BL significantly contributes to the pathogenesis of anemia and therefore its co-existence with malaria infection in the host exacerbates the anemia status.Trial registration Not applicable
tRFTar: predicting the targets of tRNA-derived fragments
Authors: Xiao Qiong , Gao Peng , Huang Xuanzhang , Chen Xiaowan , Chen Quan , Lv Xinger , Fu Yu , Song Yongxi , Wang Zhen-Ning 
Published: November 2020

Abstract
Background: tRNA-derived fragments (tRFs) are 14–40-nucleotide-long, small non-coding RNAs derived from specific tRNA cleavage events with key regulatory functions in many biological processes. Many studies have shown that tRFs are associated with Argonaute (AGO) complexes and inhibit gene expression in the same manner as miRNAs. However, there are currently no tools for accurately predicting tRF target genes. Methods: We used tRF-mRNA pairs identified by crosslinking, ligation, and sequencing of hybrids (CLASH) and covalent ligation of endogenous AGO-bound RNAs (CLEAR)-CLIP to assess features that may participate in tRF targeting, including the sequence context of each site and tRF-mRNA interactions. We applied genetic algorithm (GA) to select key features and support vector machine (SVM) to construct tRF prediction models. Results: We first identified features that globally influenced tRF targeting. Among these features, the most significant were the minimum free folding energy (MFE), position 8 match, number of bases paired in the tRF-mRNA duplex, and length of the tRF, which were consistent with previous findings. Our constructed model yielded an area under the receiver operating characteristic (ROC) curve (AUC) = 0.980 (0.977-0.983) in the training process and an AUC = 0.847 (0.83-0.861) in the test process. The model was applied to all the sites with perfect Watson-Crick complementarity to the seed in the 3' untranslated region (3'-UTR) of the human genome. Seven of nine target/nontarget genes of tRFs confirmed by reporter assay were predicted. Conclusions: Predictions can be obtained online, tRFTar, freely available at http://trftar.cmuzhenninglab.org:3838/tar/, which is the first tool to predict targets of tRFs in humans with a user-friendly interface.
Pretreatments for enhancing sewage sludge reduction and reuse in lipid production
Authors: Chen Jiaxin , Li Ji , Zhang Xiaolei , Wu Zhaoyang 
Published: November 2020

Abstract
Background: Converting wastewater sludge to lipid is considered as one of the best strategies of sludge management. The current problem of lipid production from wastewater sludge is the low yield (0.10-0.16 g lipid/g dry sludge) due to the low availability of easily uptaken materials (such as soluble monosaccharide and oligosaccharide) in sludge to oleaginous microorganism (Rhodotorula glutini, Trichosporon oleaginosus, Lipomyces starkey). Pretreatments are efficient methods to improve sludge bioavailability. This study is aimed to achieve high lipid production from sludge and high sludge reduction. Results: In this study, it was observed that the soluble chemical oxygen demand (SCOD) had significantly increased after different pretreatment.The SCOD in the supernatant was increased from 32.64 to 180.25 mg/L, 924.16 mg/L, 1029.89mg/L and 3708.31 mg/L after acidic (pH 2 for 2 h), alkaline (pH 12 for 2 h), microwave irradiation (15 min with 5 min interval) and ultrasonication (30 min at 450 W and 20 kHz frequency with 5 s on and 2 s off mode) pretreatment, respectively. Pretreatments have also increased the release in total nitrogen (TN) and total phosphorus (TP) from solids. The sludge after different pretreatments were used as medium for lipid production, and the highest lipid content (36.67% g/g) was obtained in the fermentation with ultrasonication pretreatment sludge, and the sludge reduction was 63.10%. For other pretreatment, the lipid content and sludge reduction were 18.42% and 32.63% in acid pretreatment case, 21.08% and 36.44% in alkaline pretreatment case, and 26.31% and 43.03% in microwave pretreatment case, respectively.Conclusion: It was found that ultrasonication pretreatment was the most efficient way to increase the sludge biodegradability (SCOD) and to release TN and TP from solid phase to liquid phase. Pretreated sludge for lipid production achieved significant improvement in lipid yield and sludge reduction. Lipids produced from pretreated sludge was transesterified to biodiesel and the analysis showed that the biodiesel had similar composition as commercial biodiesel. The study reveals that pretreatment on sludge is a promising method for enhancing biological sludge management efficiency.
Engineering prokaryotic regulator IrrE to enhance stress tolerance in budding yeast
Authors: Wang Li , Wang Xin , He Zhi-Qiang , Zhou Si-Jie , Xu Li , Tan Xiao-Yu , Xu Tao , Li Bing-Zhi , Yuan Ying-Jin 
Published: November 2020

Abstract
BackgroundStress tolerance is one of the important desired microbial traits for industrial bioprocesses, and global regulatory protein engineering is an efficient approach to improve strain tolerance. In our study, IrrE, a global regulatory protein from the prokaryotic organism Deinococcus radiodurans, was engineered to confer yeast the improved tolerances to the inhibitors in lignocellulose hydrolysates or high temperatures.ResultsThree IrrE mutations were developed through directed evolution, and the expression of these mutants could improve the yeast fermentation rate by 3-fold or more in the presence of multiple inhibitors. Subsequently, the tolerance to multiple inhibitors of single-site mutants based on the mutations from the variants were then evaluated, and eleven mutants, including L65P, I103T, E119V, L160F, P162S, M169V, V204A, R244G, Base 824 Deletion, V299A, and A300V were identified to be critical for the improved representative inhibitors, i.e., furfural, acetic acid and phenol (FAP) tolerance. Further studies indicated that IrrE caused genome-wide transcriptional perturbation in yeast, and the mutant I24 led to the rapid growth of Saccharomyces cerevisiae by primarily regulating the transcription level of transcription activators/factors, protecting the intracellular environment and enhancing the antioxidant capacity under inhibitor environments, which reflected IrrE plasticity. Meanwhile, we observed that the expression of the wild-type or mutant IrrE could also protect Saccharomyces cerevisiae from the damage caused by thermal stress. The recombinant yeast strains were able to grow with glucose at 42 ºC.ConclusionsIrrE from Deinococcus radiodurans can be engineered as a tolerance-enhancer for Saccharomyces cerevisiae. Systematic research on the regulatory model and mechanism of a prokaryotic global regulatory factor IrrE to increase yeast tolerance provided valuable insights for the improvements in microbial tolerance to complex industrial stress conditions.
De novo assembly and analysis of the transcriptome of the Dermacentor marginatus genes differentially expressed after blood-feeding and long-term starvation
Authors: Hu Ercha , Meng Yuan , Ma Ying , Song Ruiqi , Hu Zhengxiang , Li Min , Hao Yunwei , Fan Xinli , Wei Liting Wei , Fan Shilong , Chen Songqin , Zhai Xuejie , Li Yongchang , Wei Zhang , Zhang Yang , Guo Qingyong , Bayin Chahan 
Published: November 2020

Abstract
Background: The ixodid tick Dermacentor marginatus is a vector of many pathogens wide spread in Eurasia. Studies of gene sequence on many tick species have greatly increased the information on tick protective antigen which might have the potential to function as effective vaccine candidates or drug targets for eco-friendly acaricide development. In the current study, RNA-seq was applied to identify D. marginatus sequences and analyze differentially expressed unigenes.Methods: To obtain a broader picture of gene sequences and changes in expression level, RNA-seq was performed to obtain the whole-body transcriptome data of D. marginatus adult female ticks after engorgement and long-term starvation. Subsequently, the real-time quantitative PCR (RT-qPCR) was applied to validate the RNA-seq data.Results: RNA-seq produced 30,251 unigenes, of which 32% were annotated. Gene expression was compared among groups that differed by status as newly molted, starved and engorged female adult ticks. Nearly one third of the unigenes in each group were differentially expressed compared to the other two groups, and the most numerous were genes encoding proteins involved in catalytic and binding activities and apoptosis. Selected up-regulated differentially expressed genes in each group were associated to protein, lipids, carbohydrate and chitin metabolism. Blood-feeding and long-term starvation also caused genes differentially expressed in the defense response and antioxidant response. RT-qPCR results indicated 6 differentially expressed transcripts showed similar trends in expression changes with RNA-seq results confirming that the gene expression profiles in transcriptome data is in consistent with RT-qPCR validation.Conclusions: Obtaining the sequence information of D. marginatus and characterizing the expression pattern of the genes involved in blood-feeding and during starvation would be helpful in understanding molecular physiology of D. marginatus and provides data for anti-tick vaccine and drug development for controlling the tick.
Reduced human-biting preferences of the African malaria vectors Anopheles arabiensis and Anopheles gambiae in an urban context: Controlled, competitive host-preference experiments in Tanzania
Authors: Mlacha Yeromin P , Chaki Prosper P. , Muhili Athuman , Massue Dennis J. , Tanner Marcel , Majambere Silas , Killen Gerry F , Govella Nicodem J. 
Published: November 2020

Abstract
Background: Host preference is a critical determinant of human exposure to vector-borne infections and the impact of vector control interventions. Widespread use of long-lasting insecticide treated nets (LLINs) and indoor residual spraying (IRS) across sub-Saharan Africa, which protect humans against mosquitoes, may select for altered host preference traits of malaria vectors over the long term. Here, the host preferences of Anopheles arabiensis and Anopheles gambiae sensu stricto were experimentally assessed in the field, using direct host-preference assays in two distinct ecological settings in Tanzania.Methods: Eight Ifakara Tent Trap (ITT), four baited with humans and four with bovine calves, were simultaneously used to catch malaria vectors in open field sites in urban and rural Tanzania. The numbers of mosquitoes collected in human-baited traps versus calf-baited traps were used to estimate human feeding preference for each site's vector species.Results: The estimated proportion [95% confidence interval (CI)] of mosquitoes attacking humans rather than cattle was 0.60 [0.40, 0.77] for An. arabiensis in the rural setting and 0.61 [0.32, 0.85] for An. gambiae s.s. in the urban setting, indicating no preference for either host in both cases (P=0.32 and 0.46, respectively) and no difference in preference between the two (Odds Ratio (OR) [95%] = 0.95 [0.30, 3.01], P=0.924). However, only a quarter of An. arabiensis in the urban setting attacked humans (0.25 [0.09, 0.53]), indicating a preference for cattle that approached significance (P=0.08). Indeed, urban An. arabiensis were less likely to attack humans rather than cattle when compared to the same species in the rural setting (OR [95%] = 0.21 [0.05, 0.91], P =0.037).Conclusion. Urban An. arabiensis had a stronger preference for cattle than the rural population and urban An. gambiae s.s. showed no clear preference for either humans or cattle. In the urban setting, both species exhibited stronger tendencies to attack cattle than previous studies of the same species in rural contexts. Cattle keeping may, therefore, particularly limit the impact of human-targeted vector control interventions in Dar es Salaam and perhaps in other African towns and cities.
What is the added value of CT-angiography in patients with transient ischemic attack?
Authors: Herpertz Gerrit U. , Maier Ilko L , Bähr Mathias , Psychiogios Marios-Nikos , Liman Jan 
Published: November 2020

Abstract
BackgroundTransient ischemic attack (TIA) is an important predictor for a pending stroke. Guidelines recommend similar workup for TIA-patients as for stroke patients to directly assess the extra- and intracranial arteries via Computed tomography angiography (CTA) regarding vascular pathologies with direct therapeutic implications. Aim of our study was a systematic analysis of CTA-findings in TIA-patients and evaluate possible predictive TIA scores for ipsilateral vascular pathology. MethodsWe analysed data from TIA patients, admitted to our University Medical Centre, between September 2015 and March 2018, to identify predictors for high-risk vascular pathologies, like high-grade stenosis, dissection, thrombi or occlusion and the for need for an intervention. Following subgroups were identified: 1) no- or low-grade-stenosis (<50%) 2) ipsilateral high-risk vascular pathology and 3) high risk findings needing surgical or interventional treatment. As predictive tools for ipsilateral vascular findings we used the ABCD2-, the ABCD3- and the SPI-II score.ResultsOf 833 patients, 549 (65.9%) underwent initial CTA in the emergency department. In 126 (23.0%) patients, ipsilateral vascular findings were identified from which 40 (7.3%) needed treatment. The ABCD2-, ABCD3- and SPI-II-scores were not predictive for ipsilateral vascular pathologies. We identified coronary heart disease (OR 2.13, 1.35-3.39 95% CI; p=0.001) and short duration of symptoms (OR 0.7, 0.55-0,89 95% CI; p=0.004) as predictors for ipsilateral vascular pathologies. ConclusionMore than every fifth TIA-patient had relevant vascular findings revealed by acute CTA. TIA-scores were not predictive for these findings. Patients with a history of coronary heart disease and short duration of symptoms most likely might benefit from acute CTA to streamline further diagnostics and therapy.
Photomap of the polythenic chromosomes of Drosophila malerkotliana and in situ mapping of the Hsp83 locus
Authors: Felix Pierre Teodosio , Santos José Ferreira dos 
Published: November 2020

Abstract
A photomap of the polythenic chromosomes of D. malerkotliana was constructed to facilitate the identification of the chromosomal arms and their sections, in order to allow the identification of the breaking points of inversions and the location of the bands marked by in situ hybridization. The photomap of the polythenic chromosomes of D. malerkotliana was constructed with the six chromosome arms corresponding to pairs I (chromosome X), II and III, which are submetacentric and pair IV and Y chromosome were not included because they were not visualized in the material examined, probably due to their small size. The in-situ hybridization was performed on polythenic chromosome slides of 3 individuals. Fourteen marks were observed in Sect. 98 of the chromosomal arm IIIR, representing 70% of the markings. Other marks were found in Sect. 91 (2 marks, 10%), 87 (2 marks, 10%) and 85 (1 mark, 5%) of the same arm and in Sect. 25 (1 mark, 5%) of the IIL chromosomal arm. In this work, a photomap was made and mapped by in situ hybridization a physiologically important gene, the first being mapped in D. malerkotliana, representing the beginning of a complete study of the chromosomal evolution of the species, which will also include the induction of poufs by stress or hormones such as ecdysone.