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Background: Tetracyclines are a class of antibacterial drugs commonly used in clinical practice, but there is no systematic analysis of the adverse effects (AEs) of these drugs. We performed such pharmacovigilance analyses using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to explore tetracycline-related AEs., Research Design and Methods: We used the pharmacovigilance analysis tool Open Vigil 2.1 to access FAERS data and obtained AE reports from January 2004 to June 2023, including doxycycline, minocycline, tigecycline, omadacycline, sarecycline, and eravacycline as the top suspect drugs. The signal value of the AE of the analyzed drug was calculated by the reporting odds ratio (ROR)., Results: A total of 15,020 cases were identified by analyzing drugs. In terms of adverse signals, doxycycline caused gastrointestinal mucosal necrosis (ROR = 1699.652); minocycline was reported to cause bone hyperpigmentation (ROR = 30976.223); tigecycline is responsible for blood fibrinogen decreased (ROR = 1714.078)., Conclusions: AE reports of tetracycline drugs varied significantly. We found some AEs not mentioned in the instruction, such as the ototoxicity of tetracyclines. Doxycycline was associated with psychiatric side effects; minocycline presented in thyroid and skin tissue-associated tumors; abnormal signals were detected with eravacycline in the blood system.

During enteric nervous system (ENS) development, pioneering wavefront enteric neural crest cells (ENCCs) initiate gut colonization. However, the molecular mechanisms guiding their specification and niche interaction are not fully understood. We used single-cell RNA sequencing and spatial transcriptomics to map the spatiotemporal dynamics and molecular landscape of wavefront ENCCs in mouse embryos. Our analysis shows a progressive decline in wavefront ENCC potency during migration and identifies transcription factors governing their specification and differentiation. We further delineate key signaling pathways (ephrin-Eph, Wnt-Frizzled, and Sema3a-Nrp1) utilized by wavefront ENCCs to interact with their surrounding cells. Disruptions in these pathways are observed in human Hirschsprung's disease gut tissue, linking them to ENS malformations. Additionally, we observed region-specific and cell-type-specific transcriptional changes in surrounding gut tissues upon wavefront ENCC arrival, suggesting their role in shaping the gut microenvironment. This work offers a roadmap of ENS development, with implications for understanding ENS disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Collective behaviors efficiently impart benefits to a diversity of species ranging from bacteria to humans. Fly larvae tend to cluster and form coordinated digging groups under crowded conditions, yet understanding the rules governing this behavior is in its infancy. We primarily took advantage of the Drosophila model to investigate cooperative foraging behavior. Here, we report that Drosophila-related species and the black soldier fly have evolved a conserved strategy of cluster digging in food foraging. Subsequently, we investigated relative factors, including larval stage, population density, and food stiffness and quality, that affect the cluster digging behavior. Remarkably, oxygen supply through the posterior breathing spiracles is necessary for the organization of digging clusters. More importantly, we theoretically devise a mathematical model to accurately calculate how the cluster digging behavior expands food resources by diving depth, cross-section area, and food volume. We found that cluster digging behavior approximately increases 2.2 fold depth, 1.7-fold cross-section area, and 1.9 fold volume than control groups, respectively. Amplification of food sources significantly facilitates survival, larval development, and reproductive success of Drosophila challenged with competition for limited food resources, thereby conferring trophic benefits to fitness in insects. Overall, our findings highlight that the cluster digging behavior is a pivotal behavior for their adaptation to food scarcity, advancing a better understanding of how this cooperative behavior confers fitness benefits in the animal kingdom., (© 2023 Institute of Zoology, Chinese Academy of Sciences.)

The gut microbiome is a key partner of animals, influencing various aspects of their physiology and behaviors. Among the diverse behaviors regulated by the gut microbiome, locomotion is vital for survival and reproduction, although the underlying mechanisms remain unclear. Here, we reveal that the gut microbiome modulates the locomotor behavior of Drosophila larvae via a specific neuronal type in the brain. The crawling speed of germ-free (GF) larvae was significantly reduced compared to the conventionally reared larvae, while feeding and excretion behaviors were unaffected. Recolonization with Acetobacter and Lactobacillus can fully and partially rescue the locomotor defects in GF larvae, respectively, probably due to the highest abundance of Acetobacter as a symbiotic bacterium in the larval gut, followed by Lactobacillus. Moreover, the gut microbiome promoted larval locomotion, not by nutrition, but rather by enhancing the brain levels of tyrosine decarboxylase 2 (Tdc2), which is an enzyme that synthesizes octopamine (OA). Overexpression of Tdc2 rescued locomotion ability in GF larvae. These findings together demonstrate that the gut microbiome specifically modulates larval locomotor behavior through the OA signaling pathway, revealing a new mechanism underlying larval locomotion regulated by the gut microbiome., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Red-green colour blindness is a classic example for the teaching of X-linked recessive inheritance in genetics course. However, there are lots of types of color vision deficiencies besides red-green colour blindness. Different color vision deficiencies caused by different genes may have different modes of inheritance. In recent years, many research achievements on colour blindness have been made. These achievements could be used as teaching resources in genetics course. Here, we summarize the construction of genetics teaching resources related to colour blindness and their application in genetics teaching in several chapters such as introduction, cellular and molecular basis of genetics, sex-linked inheritance, chromosomal aberration, gene mutation and advances in genetics. Teacher could use the resources in class or after class with different teaching methods such as questioning teaching method and task method. It may expand students' academic horizons and inspire students' interest in genetics besides grasping basic genetic knowledge.

The microtubule network is an essential component of the nervous system. Mutations in many microtubules regulatory proteins are associated with neurodevelopmental disorders and neurological diseases, such as microtubule-associated protein Tau to neurodegenerative diseases, microtubule severing protein Spastin and Katanin 60 cause hereditary spastic paraplegia and neurodevelopmental abnormalities, respectively. Detection of microtubule networks in neurons is advantageous for elucidating the pathogenesis of neurological disorders. However, the small size of neurons and the dense arrangement of axonal microtubule bundles make visualizing the microtubule networks challenging. In this study, we describe a method for dissection of the larval neuromuscular junction and muscle cells, as well as immunostaining of α-tubulin and microtubule-associated protein Futsch to visualize microtubule networks in Drosophila melanogaster. The neuromuscular junction permits us to observe both pre-and post-synaptic microtubules, and the large size of muscle cells in Drosophila larva allows for clear visualization of the microtubule network. Here, by mutating and overexpressing Katanin 60 in Drosophila melanogaster, and then examining the microtubule networks in the neuromuscular junction and muscle cells, we accurately reveal the regulatory role of Katanin 60 in neurodevelopment. Therefore, combined with the powerful genetic tools of Drosophila melanogaster, this protocol greatly facilitates genetic screening and microtubule dynamics analysis for the role of microtubule network regulatory proteins in the nervous system.

Background: Fusarium fujikuroi is the pathogenic agent of rice bakanae disease and has developed serious resistance to prochloraz, a 14α-demethylase inhibitor (DMI). Prochloraz resistance in F. fujikuroi is caused by cooperation between FfCyp51B with Cyp51A and shows cross-resistance only to prothioconazole but not to tebuconazole, difenoconazole, propiconazole, metconazole, hexaconazole, and triadimefon. This study aimed to analyze the functions of the three Cyp51s in F. fujikuroi, especially their role in determining sensitivity to DMIs., Results: The respective deletion of FfCyp51A, Cyp51B, and Cyp51C had no obvious effect on morphology, conidium germination, or pathogenicity. The involvement of growth, growth and ergosterol biosynthesis, and conidium production and ergosterol biosynthesis was observed for FfCyp51A, Cyp51B, and Cyp51C, respectively. Compared with the sensitive isolate of F. fujikuroi, the effect on sensitivity to the tested DMIs was divided into four groups: (i) both of Cyp51A and Cyp51B positively regulate the sensitivity to prochloraz and prothioconazole; (ii) Cyp51B positively regulate the sensitivity to tebuconazole and metconazole, but negatively regulate the sensitivity to difenoconazole; (iii) Cyp51A and Cyp51B play opposite roles in the sensitivity to triadimefon. Therefore, deletion of Cyp51A in F. fujikuroi confers a higher sensitivity to triadimefon, while deletion of Cyp51B results in a triadimefon-resistant mutant isolate; (iv) deletion of Cyp51B yielded a mutant isolate that was more resistant to propiconazole and hexaconazole., Conclusion: Sophisticated interactions exist within the three Cyp51 genes to DMIs fungicides sensitivity in F. fujikuroi, and Cyp51B probably plays a more critical role than Cyp51A and Cyp51C. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Posttranslational modification of tubulin increases the dynamic complexity and functional diversity of microtubules. Acetylation of α-tubulin at Lys-40 is a highly conserved posttranslational modification that has been shown to improve the flexibility and resilience of microtubules. Here we studied the in vivo functions of α-tubulin acetylation by knocking-out Atat, the Drosophila α-tubulin acetyltransferase, and by mutating Lys-40 to Arg in α1-tubulin. We found a reduction in the dendritic arborization of larval class I dendritic arborization (da) neurons in both mutants. The dendritic developmental defects in atat mutants could be reversed by enhancing the stability of microtubules either through knocking down the microtubule severing protein Katanin 60 or through overexpressing tubulin-specific chaperone E, suggesting that α-tubulin deacetylation impairsed dendritic morphology by decreasing the stability of microtubules. Using time-lapse recordings, we found that atat and α1-tubulinK40R mutations dramatically increased the number of dendritic protrusions that were likely to be immature dendritic precursors. Finally, we showed that both Atat and α-tubulin acetylation were required in class I da neurons to control larval locomotion. These findings add novel insight into the current knowledge of the role of α-tubulin acetylation in regulating neuronal development and functions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Niu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown., Methods: We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively., Results: Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10 - 6 , OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia)., Conclusions: Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy., Trial Registration: Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2)., (© 2022. The Author(s).)

Background: Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive., Objective: To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients., Methods: Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor., Results: We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease's progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance., Conclusion: These findings can offer a fresh perspective on GRE-induced brain network changes., (© 2022. The Author(s).)

A prominent line of cultural evolutionary theory hypothesizes that religiously inspired prosocial behavior enhances the fecundity of pious groups, causing them to outcompete non-religious communities and spread their prosocial values. We present evidence concerning contemporary workplace safety, in the United States, that unexpectedly tested implications of this cultural evolutionary hypothesis. Avoiding workplace injury requires cooperation and injury influences fitness, thus cultural evolutionary theory would anticipate that religious communities should exhibit fewer workplace injuries. Indeed, we find that the proportion of a community adhering to a religion correlates negatively with rates of workplace injury in its private-sector establishments. This correlation emerges primarily when secular workplace safety authorities are not prominent, thus echoing evidence that religiously inspired prosocial behavior mainly occurs absent "earthly" sanctioning authorities. Furthermore, the percent of religiously affiliated individuals in a community correlates with safety investments, suggesting that workplace injury reductions in religious communities result from individually costly, group-benefitting cooperation., (© 2022. The Author(s).)

Acute myeloid leukemia (AML) with T lymphoblastic lymphoma (T-LBL) is a hematologic tumor of two origins, myeloid and lymphoblastic, and is relatively rare in the same patient. We report a rare case of AML with T-LBL. After the patient was diagnosed, he received standard chemotherapy, which decreased the primitive bone marrow cell percentage from 84% to 5%; however, the enlarged superficial lymph nodes showed no obvious change in size. Immunohistochemistry revealed the following: cluster of differentiation (CD)3 (+), CD5 (+), CD7 (+), transmission disequilibrium test (TDT) (+), myeloperoxidase (MPO) (-), and lysozyme (Lys) (-). The lymph node morphology and immunohistochemical results indicated T-LBL. Therefore, the final diagnosis was AML with T-LBL, with both diseases occurring independently and concurrently.

Background: Fusarium fujikuroi is a plant pathogen that causes rice bakanae disease. Prochloraz is an imidazole-class sterol, 14α-demethylase inhibitor (DMI), which has been in use for several years as a foliar spray to control Fusarium spp. on agriculturally important monocot crops. F. fujikuroi is highly resistant to prochloraz treatment, and the aim of this study was to clarify the mechanism by which F. fujikuroi renders itself resistant to prochloraz., Results: Recently, prochloraz-resistant strains were identified over a vast geographical area in the agricultural regions of Zhejiang Province, China. It was found that 21.13% and 3.96% of the strains examined were highly resistant (HR) to prochloraz during 2017 to 2018. The HR strains contained a point mutation (S312T) in the FfCYP51B protein, while the strains identified with prochloraz susceptibility had no such point mutation in FfCYP51A/B/C. To confirm whether the mutations in FfCYP51B confer resistance to prochloraz, we exchanged the CYP51B locus between the sensitive strain and the resistant strain by homologous double exchange. The transformed mutants with a copy of the resistant fragment exhibited resistance to prochloraz, and the transformed mutants with a copy of the sensitive fragment exhibited sensitivity to prochloraz. Furthermore, qRT-PCR analysis of Ffcyp51a/b/c gene expression revealed that Ffcyp51a and Ffcyp51b were significantly up-regulated in the prochloraz-resistant strains relative to the sensitive strains in F. fujikuroi. Contrary to our expectation, docking of prochloraz into the modeled binding pocket of FfCYP51B indicated that the affinity between prochloraz and the FfCYP51B increased after the amino acid at codon 312 changed to Thr., Conclusion: The point mutation S312T in FfCYP51B and overexpression of Ffcyp51a and Ffcyp51b together lead to the prochloraz-resistant phenotype in F. fujikuroi., (© 2020 Society of Chemical Industry.)

Platinum-based chemotherapy remains the cornerstone of treatment for many malignancies. However, although therapeutic efficiency varies greatly among individuals, there is a lack of pharmacogenomic biomarkers that can be used in clinical settings to identify chemosensitive patients and allow stratification. With the development of high-throughput screening techniques and systems biology approaches, a growing body of evidence has shown that platinum resistance is a multifactorial, multi-dimensional, dynamic process incorporating genetic background, tumor evolution and gut microbes. This review critically summarizes potential pharmacogenomic biomarkers for predicting the efficacy of platinum drugs and provides a comprehensive, time-varying perspective that integrates multiple markers., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To study the high risk factors for the transformation into acute myeloid leukemia(AML) in patients with intermediate and high risk myelodysplastic syndrome(MDS) treated by decitabine-based regimen., Methods: The clinical characterstics of 60 intermediate and high risk MDS patients and the factors of its transformed into AML were retrospectively analyzed., Results: The overall response rate(ORR) of the patients suffered from intermediate and high risk MDS treated by decitabine-based regimen was 65.0％(39/60), among the 60 cases 17 achieved complete remission(CR), 5 achieved morrow complete remission(mCR), 4 achieved partial remission(PR) and 13 achieved hematologic improvement(HI). Twenty-one cases(35.0%) were transformed into AML among 60 cases of intermediate and high risk MDS treated by decitabine-based regimen. The median time of transformation from intermediate and high risk MDS into AML was 10.0 months(1.6-32.0). χ 2 or Fisher's exact test showed that 2016 WHO MDS diagnostic subgrouping, myeloid hyperplasia markedly active, delayed interval of decitabine-based treatment associated with the transformation from intermediate to high risk MDS into AML (χ 2 =9.878，P=0.031；χ 2 =4.319，P=0.038；χ 2 =6406，P=0.011); Univariate analysis of Kaplan-Meier test showed that 2016 WHO MDS diagnostic subgroups, bone marrow blast cell ratio, bone marrow dysplasia coefficients, prolonged interval of decitabine-based treatment associated with the transformation from intermediate and high risk MDS into AML (P=0.015，P=0.008，P=0.012，P=0.032); multivariate analysis showed the bone marrow blast cell ratio and the bone marrow dysplasia coefficients were independent risk factors for the transformation from intermediate to high risk MDS into AML (P=0.022，P=0.018)., Conclusion: The bone marrow blast cell ratio and the bone marrow dysplasia coefficients are independent risk factors of transformation into AML in the patients with intermediate and high risk MDS treated by decitabine-based regimen. The regular interval of dicitabine treatment is beneficial to maintain the stability of patients conditions.

Recurrence rates of diabetic foot ulcers vary widely in the published literature. The aim of this systematic review is to estimate recurrence rates of diabetic foot ulcers. We did a PubMed search and performed a review of reference lists for studies reporting recurrence of diabetic foot ulcers. The weighted relative risk (RR) and corresponding 95% confidence interval (CI) for recurrence was estimated. Forty-nine studies reporting recurrence of diabetic foot ulcers were included. A pooled estimate for recurrence rate was 22.1% per person-year (py) (95% CI, 19.0-25.2%). Recurrence rate was 24.9% per py in Europe (95% CI, 20.0%-29.7%), 17.8% per py in North America (95% CI, 12.7%-22.9%), 16.9% per py in Africa (95% CI, 4.7%-29.0%), and 17.0% per py in Asia (95% CI, 11.1%-23.0%). Turkey had the highest recurrence rate of 44.4% per py (95% CI, 24.9%-63.9%), and Bangladesh had the lowest of 4.3% per py (95% CI, 2.3%-6.3%). Recurrence rates of diabetic foot ulcers before 2002, between 2002 and 2008, and after 2008 were 22.2% per py (95% CI, 17.6%-26.8%), 21.9% per py (95% CI, 17.0%-26.8%), and 21.8% per py (95% CI, 16.3%-27.2%), respectively. Recurrence rates of diabetic foot ulcers are high. Recurrence rates vary widely in different regions and have decreased recently. More attention towards recurrence of diabetic foot ulcers is urgently required., (© 2019 John Wiley & Sons, Ltd.)

Aim: This study will explore the genetic and epigenetic alterations in astrocytomas, and identify the critical molecular signatures and signaling pathways for prognosis assessment by multiplatform comprehensive analysis., Method: We performed integration analyses of incorporating DNA methylation, mRNA expression, microRNA expression, and long non-coding RNA (lncRNA) expression in 33 astrocytic tumor tissues and 9 non-tumor brain tissues., Result: We observed that 11,795 DNA methylation sites, 3,627 genes, 136 microRNAs, and 3,334 lncRNAs were significantly differential between tumors and non-tumor brain tissues, and the filtered signatures through comprehensive analysis were significantly enriched in calcium signaling pathway. Furthermore, four signatures involved in calcium signaling pathway and age could contribute to predicting the patients' overall survival. Additionally, we identified differentially expressed signatures between IDH-mutated and IDH wild-type astrocytic tumors, and complement and coagulation cascades pathway was the most significant pathway in functional enrichment analysis using multiplatform data. The IDH wild-type astrocytomas were divided into two subtypes by Cluster of Cluster (CoC) analysis, one of which was enriched for astrocytomas overexpressed in chemokine signaling pathway., Conclusion: The calcium signaling pathway played a key role in astrocytoma tumorigenesis and prognosis. IDH mutation was a vital biomarker, and resulted in the change of expression level in complement and coagulation cascades pathway. The chemokine signaling pathway could characterize subtypes of IDH wild-type astrocytomas., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Tau normally associates with and stabilizes microtubules (MTs), but is hyperphosphorylated and aggregated into neurofibrillary tangles in Alzheimer's disease and related neurodegenerative diseases, which are collectively known as tauopathies. MTs are regulated by different forms of post-translational modification, including acetylation; acetylated MTs represent a more stable microtubule population. In our previous study, we showed that inhibition of histone deacetylase 6 (HDAC6), which deacetylates tubulin at lysine 40, rescues defects in MTs and in neuromuscular junction growth caused by tau overexpression. However, HDAC6 also acts on other proteins that are involved in distinct biological processes unrelated to tubulins. In order to examine directly the role of increased tubulin acetylation against tau toxicity, we generated a site-directed α-tubulin K40Q mutation by CRISPR/Cas9 technology to mimic the acetylated MTs and found that acetylation-mimicking α-tubulin rescued tau-induced MT defects and neuromuscular junction developmental abnormalities. We also showed that late administration of ACY-1215 and tubastatin A, two potent and selective inhibitors of HDAC6, rescued the tau-induced MT defects after the abnormalities had already become apparent. Overall, our results indicate that increasing MT acetylation by either genetic manipulations or drugs might be used as potential strategies for intervention in tauopathies., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

We use a nonparametric mixture model for the purpose of estimating the size of a population from multiple lists in which both the individual effects and list effects are allowed to vary. We propose a lower bound of the population size that admits an analytic expression. The lower bound can be estimated without the necessity of model-fitting. The asymptotical normality of the estimator is established. Both the estimator itself and that for the estimable bound of its variance are adjusted. These adjusted versions are shown to be unbiased in the limit. Simulation experiments are performed to assess the proposed approach and real applications are studied., (© 2016, The International Biometric Society.)

Despite the extensive role of Forkhead box transcription factors in the development and progression of various cancers, little is known about their role in glioma. We examined the expression and function of Forkhead box D1 (FOXD1) in glioma cell behavior and found that FOXD1 was upregulated and directly correlated with the glioma grade. Data analysis also revealed significant differences in FOXD1 expression for both gene expression profiles (GSE4290 and GSE7696) and the TCGA datasets. Additionally, decreased FOXD1 expression in U251 and U87 glioma cells caused a delay in cell growth and a disruption in colony formation. FOXD1 silencing also promoted generation of apoptotic bodies containing nuclear fragments. Cells with suppressed expression of FOXD1 markedly reduced glioma cell migration. Our results suggest that FOXD1 may serve as a novel regulator of glioblastoma cell behavior that may offer a novel target for gene targeted glioma therapies.

With the development of whole genome and transcriptome sequencing technologies, a growing body of long non-coding RNAs (lncRNAs) has been identified and is receiving increasing attention. LncRNAs are non-protein encoding transcripts whose functions are crucial for advancing our comprehensive understanding of biological processes in human health and diseases, specifically glioma. It has been established that lncRNAs are differently expressed in the central nervous system and may play a vital role in glioma. As of June 2016, 20 lncRNAs have been identified that may play a role in glioma pathogenesis. Investigation into the role of lncRNAs in glioma may help to identify potential biomarkers which can improve the diagnosis and treatment of glioma. In this paper, we review current understanding of the function of lncRNAs in glioma initiation and progression.

Current treatment methods for patients diagnosed with gliomas have shown limited success. This is partly due to the lack of prognostic genes available to accurately predict disease outcomes. The aim of this study was to investigate novel prognostic genes based on the molecular profile of tumor samples and their correlation with clinical parameters. In the current study, microarray data (GSE4412 and GSE7696) downloaded from Gene Expression Omnibus were used to identify differentially expressed prognostic genes (DEPGs) by significant analysis of microarray (SAM) between long-term survivors (>2 years) and short-term survivors (≤2 years). DEPGs generated from these two datasets were intersected to obtain a list of common DEPGs. The expression of a subset of common DEPGs was then independently validated by real-time reverse transcription quantitative PCR (qPCR). Survival value of the common DEPGs was validated using known survival data from the GSE4412 and TCGA dataset. After intersecting DEPGs generated from the above two datasets, three genes were identified which may potentially be used to determine glioma patient prognosis. Independent validation with glioma patients tissue ( n = 70) and normal brain tissue ( n = 19) found PPIC , EMP3 and CHI3L1 were up-regulated in glioma tissue. Survival value validation showed that the three genes correlated with patient survival by Kaplan-Meir analysis, including grades, age and therapy., Competing Interests: The authors declare no conflict of interest.

Although patients with glioblastoma (GBM) have grave prognosis, significant variability in patient outcome is observed. This study aims to identify novel targets for GBM diagnosis and therapy. Microarray data (GSE4290, GSE7696, and GSE4412) obtained from the Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) by significant analysis of microarray (SAM). Intersection of the identified DEGs for each profile revealed 46 DEGs in GBM. A subset of common DEGs were validated by real-time reverse transcription quantitative PCR (qPCR). The prognostic value of some of the markers was also studied. We determined that RRM2 and COL3A1 were increased and directly correlated with glioma grade, while SH3GL2 and SNAP91 were decreased in GBM and inversely correlated with glioma grade. Kaplan-Meir analysis of GSE7696 revealed that COL3A1 and SNAP91 correlated with survival, suggesting that COL3A1 and SNAP91 may be suitable biomarkers for diagnostic or therapeutic strategies for GBM.

In this study, we aimed to establish a platinum-based chemotherapy response and toxicity prediction model in advanced non-small cell lung cancer (NSCLC) patients. 416 single nucleotide polymorphisms (SNPs) in 185 genes were genotyped, and their association with drug response and toxicity were estimated using logistic regression. Nine data mining techniques were employed to establish the prediction model; the sensitivity, specificity, overall accuracy and receiver operating characteristic (ROC) curve were used to assess the models' performance. Finally, selected models were validated in an independent cohort. The models established by naïve Bayesian algorithm had the best performance. The response prediction model achieved a sensitivity of 0.90 and a specificity of 0.47 with the ROC area under curve (AUC) of 0.80. The overall toxicity prediction model achieved a sensitivity of 0.86 and a specificity of 0.46 with the ROC AUC of 0.73. The hematological toxicity prediction model achieved a sensitivity of 0.89 and a specificity of 0.39 with the ROC AUC of 0.76. The gastrointestinal toxicity prediction model achieved a sensitivity of 0.93 and a specificity of 0.35 with the ROC AUC of 0.80. In conclusion, we provided platinum-based chemotherapy response and toxicity prediction models for advanced NSCLC patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

MicroRNA (miR)-138 was found to have suppressive effects on the growth and metastasis of different human cancers. In this study, we aimed to investigate the regulatory mechanism of miR-138 in non-small cell lung cancer (NSCLC). We applied the Quantitative real-time PCR (qRT-PCR) to detect the miR-138 levels in NSCLC tissues (n=21) and cell lines, Bioinformatical predication, luciferase reporter assay and western blot to identify the target gene of miR-138. We also applied Cell transfection, MTT, transwell, and wound healing assays to reveal the role of miR-138 in NSCLC cell proliferation and malignant transformation. We observed that miR-138 expression level was significantly decreased in NSCLC tissues compared to their matched adjacent normal tissues. It was also downregulated in tissues with poor differentiation, advanced stage or lymph nodes metastasis, as well as in several NSCLC cell lines compared to normal lung epithelial cell. We further identified YAP1 as a direct target gene of miR-138, and observed that the protein level of YAP1 was negatively mediated by miR-138 in NSCLC A549 cells. Moreover, overexpression of miR-138 significantly inhibited A549 cell growth, invasion and migration, while knockdown of miR-138 enhanced such capacities. Further investigation showed that the cell proliferation capacity was higher in the miR-138+YAP1 group, when compared with that in the miR-138 group, suggesting that overexpression of YAP1 rescued the suppressive effects of miR-138 upregulation on NSCLC cell proliferation. However, we found no difference of cell invasion and migration capacities between miR-138+YAP1 group and miR-138 group. Finally, YAP1 was markedly upregulated in NSCLC tissues compared to their marched adjacent normal tissues. Its mRNA levels were reversely correlated with the miR-138 levels in NSCLC tissues. In summary, our study suggests that miR-138 may play a suppressive role in the growth and metastasis of NSCLC cells partly at least by targeting YAP1., Competing Interests: No conflict of interest exists in this study.

Objective: ATP1A2 and ATP1A3 are genes that code for catalytic subunits of Na/K-ATPases, which play important roles in the basal electrophysiological states of nerve cells. The aim of this study was to investigate whether genetic polymorphisms of ATP1A2 and ATP1A3 influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of anti-epileptic drugs in a Chinese population., Method: Six ATP1A2 tagged single-nucleotide polymorphisms (tagSNPs) and two ATP1A3 tagSNPs were were genotyped by allele-specific MALDI-TOF mass spectrometry in 484 Chinese GGE patients (280 drug-responsive and 204 drug-resistant patients) and 284 healthy controls., Results: Significant differences were found in the frequencies of the ATP1A3 rs8107107 C allele and the CC genotype between the GGEs and the healthy controls (11% vs. 15%, odds ratio (OR)=0.807 (0.68-0.960), p=0.021 and 0.4% vs. 3.2%, OR=0.121 (0.026-0.565), p=0.002, respectively). The frequency of the rs8107107 CT+CC genotype was significantly lower among the GGE patients than among the healthy controls (15% vs. 26.8%, OR=0.327 (0.248-0.942), p=0.001). No significant differences in the frequencies of six ATP1A2 tagSNPs or ATP1A2 haplotypes were found between the GGEs and the healthy controls. No tagSNPs were involved in anti-epileptic drug resistance., Conclusion: Our findings demonstrated that common variants of ATP1A3 but not ATP1A2 were associated with the susceptibility to GGEs in a Chinese population, which indicates that the ATP1A3 gene plays a significant role in the pathophysiology of genetic generalized epilepsies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Previous studies reported that the proline-rich transmembrane protein 2 (PRRT2) gene was identified to be related to paroxysmal kinesigenic dyskinesia (PKD), infantile convulsions with PKD, PKD with migraine and benign familial infantile epilepsy (BFIE). The present study explores whether the PRRT2 mutation is a potential cause of febrile seizures, including febrile seizures plus (FS+), generalized epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS); thus, it may provide a new drug target for personalized medicine for febrile seizure patients. We screened PRRT2 exons in a cohort of 136 epileptic patients with febrile seizures, including FS+, GEFS+ and DS. PRRT2 genetic mutations were identified in 25 out of 136 (18.4%) febrile seizures in epileptic patients. Five loss-of-function and coding missense mutations were identified: c.649delC (p.R217Efs*12), c.649&#95;650insC (p.R217Pfs*8), c.412C>G (p.Pro138Ala), c.439G>C (p.Asp147His) and c.623C>A (p.Ser208Tyr). PRRT2 variants were probably involved in the etiology of febrile seizures in epileptic patients.

The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.

Microtubules (MTs) are crucial for diverse biological processes including cell division, cell growth and motility, intracellular transport and the maintenance of cell shape. MT abnormalities are associated with neurodevelopmental and neurodegenerative diseases such as hereditary spastic paraplegia. Among many MT regulators, katanin was the first identified MT-severing protein, but its neuronal functions have not yet been examined in a multicellular organism. Katanin consists of two subunits; the catalytic subunit katanin 60 contains an AAA (ATPases associated with a variety of cellular activities) domain and breaks MT fibers while hydrolyzing ATP, whereas katanin 80 is a targeting and regulatory subunit. To dissect the in vivo functions of Katanin, we generated mutations in Drosophila Katanin 60 and manipulated its expression in a tissue-specific manner. Null mutants of Katanin 60 are pupal lethal, demonstrating that it is essential for viability. Loss-of-function mutants of Katanin 60 showed excess satellite boutons, reduced neurotransmission efficacy, and more enlarged cisternae at neuromuscular junctions. In peripheral sensory neurons, loss of Katanin 60 led to increased elaboration of dendrites, whereas overexpression of Katanin 60 resulted in the opposite. Genetic interaction analyses indicated that increased levels of MT acetylation increase its susceptibility to Katanin-mediated severing in neuronal and non-neuronal systems. Taken together, our results demonstrate for the first time that Katanin 60 is required for the normal development of neuromuscular synapses and dendrites.

Estimating population sizes via capture-recapture experiments has enormous applications. The Poisson mixture model can be adopted for those applications with a single list in which individuals appear one or more times. We compare several nonparametric estimators, including the Chao estimator, the Zelterman estimator, two jackknife estimators and the bootstrap estimator. The target parameter of the Chao estimator is a lower bound of the population size. Those of the other four estimators are not lower bounds, and they may produce lower confidence limits for the population size with poor coverage probabilities. A simulation study is reported and two examples are investigated., (© 2013, The International Biometric Society.)

Altered intracellular calcium homeostasis and oxidative stress are involved in the pathophysiology of bipolar disorder (BD)-I. To explore the genes contributing to these abnormalities, we examined the association with BD of the iPLA2β (PLA2G6), a signaling enzyme that mobilizes the arachidonic acid signaling cascade and activates oxidative stress, and assessed whether it interacts genetically with type 2 transient receptor potential channel gene (TRPM2), an oxidative stress-responsive calcium channel implicated both functionally and genetically in BD-I. Two tag single nucleotide polymorphisms rs4375 and rs3788533 in iPLA2β were genotyped in 446 White case-control individuals and 296 BD families using a 5'-nuclease TaqMan assay. The results were analyzed using χ-test and transmission disequilibrium tests, and Haploview. In a secondary analysis, we tested gene-gene interactions between TRPM2 and iPLA2β on BD vulnerability by logistic regression using a case-only design in PLINK. iPLA2β-rs3788533 showed a borderline association with BD-I in patients with a history of psychosis in both case-control and family designs. Association with BD as a whole was observed in the family study (significant over transmissions of rs3788533-allele C, P=0.015, PBonferroni=0.03, TDTPHASE). A borderline interaction was found between rs749909 within TRPM2 and rs4375 within iPLA2β (Puncorrected=0.009), on the basis of the case-only design analyzed with PLINK. A significant association of iPLA2β variants with BD-I and a trend gene-gene interaction between iPLA2β and TRPM2 provides additional support for the notion that genetic variation in these two functionally implicated candidates contributes toward the risk and pathophysiology of this illness.

Effects of cerium ion (Ce(III)) on water relations of soybean seedlings (Glycine max L.) under ultraviolet B radiation (UV-B, 280-320 nm) stress were investigated under laboratory conditions. UV-B radiation not only affected the contents of two osmolytes (proline, soluble sugar) in soybean seedlings, but also inhibited the transpiration in soybean seedlings by decreasing the stomatal density and conductance. The two effects caused the inhibition in the osmotic and metabolic absorption of water, which decreased the water content and the free water/bound water ratio. Obviously, UV-B radiation led to water stress, causing the decrease in the photosynthesis in soybean seedlings. The pretreatment with 20 mg L(-1) Ce(III) could alleviate UV-B-induced water stress by regulating the osmotic and metabolic absorption of water in soybean seedlings. The alleviated effect caused the increase in the photosynthesis and the growth of soybean seedlings. It is one of the protective effect mechanisms of Ce(III) against the UV-B radiation-induced damage to plants.

In humans, heme iron is the most abundant iron source, and bacterial pathogens such as Staphylococcus aureus acquire it for growth. IsdB of S. aureus acquires Fe(III)-protoporphyrin IX (heme) from hemoglobin for transfer to IsdC via IsdA. These three cell-wall-anchored Isd (iron-regulated surface determinant) proteins contain conserved NEAT (near iron transport) domains. The purpose of this work was to delineate the mechanism of heme binding and transfer between the NEAT domains of IsdA, IsdB, and IsdC using a combination of structural and spectroscopic studies. X-ray crystal structures of IsdA NEAT domain (IsdA-N1) variants reveal that removing the native heme-iron ligand Tyr166 is compensated for by iron coordination by His83 on the distal side and that no single mutation of distal loop residues is sufficient to perturb the IsdA-heme complex. Also, alternate heme-iron coordination was observed in structures of IsdA-N1 bound to reduced Fe(II)-protoporphyrin IX and Co(III)-protoporphyrin IX. The IsdA-N1 structural data were correlated with heme transfer kinetics from the NEAT domains of IsdB and IsdC. We demonstrated that the NEAT domains transfer heme at rates comparable to full-length proteins. The second-order rate constant for heme transfer from IsdA-N1 was modestly affected (<2-fold) by the IsdA variants, excluding those at Tyr166. Substituting Tyr166 with Ala or Phe changed the reaction mechanism to one with two observable steps and decreased observed rates >15-fold (to 100-fold excess IsdC). We propose a heme transfer model wherein NEAT domain complexes pass heme iron directly from an iron-coordinating Tyr of the donor protein to the homologous Tyr residues of the acceptor protein., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Toll-like receptor 2 (TLR2) represents a reasonable functional and positional candidate gene for Alzheimer's disease (AD) as it is located under the linkage region of AD on chromosome 4q, and functionally is involved in the microglia-mediated inflammatory response and amyloid-β clearance. The -196 to -174 del polymorphism affects the TLR2 gene and alters its promoter activity., Methods: We recruited 800 unrelated Northern Han Chinese individuals comprising 400 late-onset AD (LOAD) patients and 400 healthy controls matched for gender and age. The -196 to -174 del polymorphism in the TLR2 gene was genotyped using the polymerase chain reaction (PCR) method., Results: There were significant differences in genotype (P = 0.026) and allele (P = 0.009) frequencies of the -196 to -174 del polymorphism between LOAD patients and controls. The del allele was associated with an increased risk of LOAD (OR = 1.31, 95% CI = 1.07-1.60, Power = 84.9%). When these data were stratified by apolipoprotein E (ApoE) ε4 status, the observed association was confined to ApoE ε4 non-carriers. Logistic regression analysis suggested an association of LOAD with the polymorphism in a recessive model (OR = 1.64, 95% CI = 1.13-2.39, Bonferroni corrected P = 0.03)., Conclusions: Our data suggest that the -196 to -174 del/del genotype of TLR2 may increase risk of LOAD in a Northern Han Chinese population.

Objective: To evaluate the usefulness of nested PCR method in the diagnosis of imported malaria., Methods: A total of 210 blood smears and blood samples on filter paper were taken from persons returned from highly malaria endemic countries. The results of both nested PCR and microscopy for 210 samples were compared., Results: Among the 210 persons, 43 were hospitalized due to malaria, and positive by nested PCR test Among the rest 157 people at high risk of getting malaria, 3 were found plasmodium-positive by microscope (1.91%), and 5 were positive by nested PCR (3.18%). In four samples with discrepancy between the two methods, 1 was microscopy positive and PCR negative, and 3 were microscopy negative and PCR positive. Positive and negative coincidence rate between the two tests was 66.7% and 98.1%, respectively. The coincidence between the two methods was 97.5%., Conclusion: Nested PCR is useful for monitoring, identification and diagnosis of imported malaria.

Background: Several genome wide screens and candidate gene studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to late-onset Alzheimer's disease (LOAD). Recently, the strongest significant association was reported for the single nucleotide polymorphism (SNP) rs11610206 on chromosome 12q13 in an independent genome-wide association study (GWAS) in Caucasians., Methods: We investigated whether the SNP on chromosome 12q13 was associated with LOAD in a Han Chinese population. The common rs11610206 SNP on chromosome 12q13 was genotyped using MALDI-TOF mass spectrometry in 322 patients with LOAD and in 391 healthy controls matched for sex and age., Results: Patients with LOAD had higher frequencies of T allele (56.0% versus 49.2%) compared with controls [odds ratio (OR)=1.45, 95% confidence intervals (CI)=1.08-1.95, and P=0.01]. After stratification by APOE ε4-carrying status, the T allele of rs11610206 was significantly associated with LOAD only in APOE ε4 allele carriers (OR=2.05, 95% CI=1.21-3.47, and P=0.007). Furthermore, multivariate logistic regression analysis showed that the TT genotype carriers demonstrated a 1.52-fold risk when compared with (TC+CC) genotype carriers (OR=1.52, 95% CI=1.07-2.17, and P=0.02)., Conclusions: This study demonstrates an association of rs11610206 polymorphism locus on chromosome 12q13 with risk for LOAD in Han Chinese., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The title compound, C(20)H(33)ClN(2)O(3), was obtained via a tandem asymmetric Michael addition-elimination reaction of 3,4-dichloro-5-(S)-(l-menth-yloxy)furan-2(5H)-one and 1-ethyl-piperazine in the presence of potassium fluoride. The mol-ecular structure contains an approximately planar five-membered furan-one ring [maximum atomic deviation = 0.024 (2) Å] and two six-membered rings adopting chair conformations. Weak inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

Comparing species assemblages given incidence-based data is of importance in ecological studies, often done by a visual inspection of estimated species accumulation curves or by an ad hoc use of 95% pointwise confidence bands of these curves. It is shown that comparing species assemblages is a challenging problem. A chi(2) test is proposed. An adjustment using an eigenvalue decomposition is proposed to overcome computational difficulties. The bootstrap method is also suggested to approximate the distribution of the proposed test statistic. The eigenvalue adjusted (Eva) chi(2) test and the Eva-bootstrap test are assessed by a simulation study. Both the Eva-chi(2) and the Eva-bootstrap tests are applied to a study that involves two woody seedling species assemblages.

Binomial and geometric mixtures can be used to model data gathered in capture-recapture surveys of animal populations, removal surveys of harvest populations, registrations of disease populations, ecological species census, and so on. To compute a nonparametric maximum likelihood estimator for the mixing distribution of heterogeneous capture probabilities, we consider a conditional approach and use a reliable and fast integrative procedure which combines the EM algorithm to increase the likelihood and the vertex-exchange method to update the number of support points. A convergent Newtonian algorithm is used in the M-step of the EM algorithm., (((c) 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).)

When a nonparametric mixture model is adopted to deal with the heterogeneity among individual capture probabilities, the population size is nonidentifiable (Link, 2003, Biometrics 59, 1123-1130). Holzmann, Munk, and Zucchini (2006, Biometrics 62, 934-936) discussed the conditions under which a subfamily of mixing distributions is identifiable. Link (2006, Biometrics 92, 936-939) found that the nonidentifiability occurs across identifiable subfamilies. It is shown that there is a subfamily in which each mixing distribution is determined by its mixture, and the population size admits estimable lower bounds that can be used to construct lower confidence limits.

Detection of differentially expressed genes from expressed sequence tags (ESTs) data has received much attention. An empirical Bayesian method is introduced in which gene expression patterns are estimated and used to define detection statistics. Significantly differentially expressed genes can be declared given detection statistics. Simulation is done to evaluate the performance of proposed method. Two real applications are studied.

Adult bean thrips, Caliothrips fasciatus (Pergande), overwintering inside the navel of navel oranges shipped from California to Australia, are an actionable pest for the importing country, i.e. infested lots are fumigated with methyl bromide. Strict quarantine regulations regarding C. fasciatus prompted studies on the best colour sticky trap that might be used to monitor for bean thrips populations in the vicinity of California citrus groves prior to harvesting fruit for export. Preliminary experiments identified the most attractive trap of each of four colours (blue, green, white, yellow) commonly used to sample adult Thysanoptera. Three trials of a field study were conducted, comparing C. fasciatus capture on the best card of each colour using asparagus ferns naturally infested with high levels of this pest. Based on significantly higher catch on green sticky cards, this colour trap is recommended for potential use in California's bean thrips mitigation plan designed to reduce thrips levels on citrus exported to Australia.

As a significant tool in ecological studies, the species accumulation curve or the collector's curve is the graph of the expected number of detected species as a function of sampling effort. The problem of estimating the species accumulation curve based on an empirical data set arising from quadrat sampling is studied in a nonparametric binomial mixture model. It will be shown that estimating the species accumulation curve not only is independent of the unknown number of species but also includes estimating the number of species as a limiting case. For the purpose of interpolation, moment-based estimators, associated with asymptotic confidence intervals, are developed from several points of view. A likelihood-based procedure is developed for the purpose of extrapolation, associated with bootstrap confidence intervals. The proposed methods are illustrated by ecological data sets.