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Background: Multiple myeloma is a plasma cell dyscrasia characterized by transformation of B cells into malignant cells. Although there are data regarding the molecular pathology of multiple myeloma, the molecular mechanisms of the disease have not been fully elucidated. Aims: To investigate the gene expression profiles in bone marrow myeloma cells via RNA-sequencing technology. Study Design: Cell study. Methods: Myeloma cells from four patients with untreated multiple myeloma and B cells from the bone marrow of four healthy donors were sorted using a FACSAria II flow cytometer. The patient pool of myeloma cells and the control pool of B cells were the two comparative groups. A transcriptome analysis was performed and the results were analyzed using bioinformatics tools. Results: In total, 18.806 transcripts (94.4%) were detected in the pooled multiple myeloma patient cells. A total of 992 regions were detected as new exon candidates or alternative splicing regions. In addition, 490 mutations (deletions or insertions), 1.397 single nucleotide variations, 415 fusion transcripts, 132 frameshift mutations, and 983 fusions, which were reported before in the National Center for Biotechnology Information, were detected with unknown functions in patients. A total of 35.268 transcripts were obtained (71%) (25.355 transcripts were defined previously) in the control pool. In this preliminary study, the first 50 genes were analyzed with the MSigDB, Enrichr, and Panther gene set enrichment analysis programs. The molecular functions, cellular components, pathways, and biological processes of the genes were obtained and statistical values were determined using bioinformatics tools and are presented as a supplemental file. Conclusion: EEF1G, ITM2C, FTL, CLPTM1L, and CYBA are identified as possible candidate genes associated with myelomagenesis.

The Anammox-based processes are suitable for the treatment of wastewaters characterized by a low carbon to nitrogen (C/N) ratio. The application of the Anammox process requires the availability of an effluent with a NO2−‒ N/NH4+‒ N ratio composition around 1 g g−1, which involves the necessity of a previous step where the partial nitrification is performed. In this step, the inhibition of the nitrite-oxidizing bacteria (NOB) is crucial. In the present work, a combined partial nitrification-ANaerobic AMmonia OXidation (Anammox) two-units system operated at room temperature (20°C) has been tested for the nitrogen removal of pre-treated pig slurry. To achieve the successful partial nitrification and inhibit the NOB activity, different ammonium/inorganic carbon (NH4+/IC ) ratios were assayed from 1.19 to 0.82 g NH4+-N g−1HCO3‒ C. This procedure provoked a decrease of the pH value to 6.0 to regulate the inhibitory effect over ammonia-oxidizing bacteria caused by free ammonia. Simultaneously, the NOB experienced the inhibitory effect of free nitrous acid which avoided the presence of nitrate in the effluent. The NH4+/IC ratio which allowed the obtaining of the desired effluent composition (50% of both ammonium and nitrite) was 0.82±0.02 g NH4+‒ N g−1HCO3−‒ C. The Anammox reactor was fed with the effluent of the partial nitrification unit containing a NO2−‒ N/NH4+‒ N ratio of 1 g g−1where a nitrogen loading rate of 0.1 g N L−1d−1was efficiently removed. [ABSTRACT FROM PUBLISHER]

Aim: Analysis of genes that play roles in multiple myeloma pathogenesis and their pathways are current research topics. We aimed to detect expression of some genes in ErbB and insulin signaling pathways. Methods: Bone marrow samples were taken from three healthy volunteers and 17 treatment-naive patients. Firstly RNA isolation was made and then cDNA were synthesized. There are eight genes that are related to ErbB and insulin signaling pathways. Specific primers for these genes were designed. Gene expression analysis was performed by the real-time polymerase chain reaction method. Results: In the patient group, expressions of MTOR, RPTOR, PIK3CA, AKT1, ErbB4, PRKAR2A and PRKACB genes were detected to be 3-10 times up-regulated than in control group. There were no differences in the expression levels of RICTOR and GYS1 genes between control group and patient group. GYS1, PRKACB and PRKAR2A genes have been analyzed for the first time. Conclusion: In this study, PRKAR2A and PRKACB genes expressions were detected to be upregulated and this has not been reported in the literature before. MTOR, RPTOR, PIK3CA, AKT1, and ErbB4 genes expression were detected to be upregulated as has been reported in the literature. All these results will be useful to understand the pathogenesis of multiple myeloma.

Background: Probiotics are “live”, beneficial microbes that provide important health benefits in their hosts. There is significant interest in the modulation and regulation of the immune function by probiotics. Objective: To investigate the immunomodulatory effects of a probiotic mixture, including Lactobacillus and Bifidobacterium species, by detecting serum cytokine and immunoglobulin levels. Methods: The rats were randomly divided into 4 groups. The first group was “Control group” and other 3 groups were probiotic application groups who received different doses of probiotics. The probiotic mixture included 12 probiotic bacteria, mostly Lactobacillus and Bifidobacterium strains. Probiotic mixture was administered to rats for 12 consecutive days. TNF-α, TGF-β, IL-1-β, IL-6, and IL-10 levels as well as serum IgG and IgA concentrations were detected in the sera after 12 days. Results: Probiotics led to a decrease in the levels of TNF-α, IL-6 and TGF-β; however, they led to increase in the serum levels of IL-10, IgG and IgA. There were significant differences between control group and probiotic application groups (pConclusion: These data suggest that the commensal microbiota are important for stimulating both proinflammatory and regulatory responses in order to rapidly clear infections and minimize inflammation-associated tissue damage.

In this paper, the authors consider the Carlitz's generalized twisted q-Bernoulli polynomials attached to χ and investigate some novel symmetric identities for these polynomials arising from the p-adic q-integral on Zp under S3.

Francisella tularensis DNA extractions and isolates from the environment and humans were genetically characterized to elucidate environmental sources that cause human tularemia in Turkey. Extensive genetic diversity consistent with genotypes from human outbreaks was identified in environmental samples and confirmed water as a source of human tularemia in Turkey.

ABSTRACT Epstein-Barr virus (EBV) is associated with several B and epithelial cell cancers. EBV-encoded latent membrane protein 2A (LMP2A) contributes to cellular transformation by mimicking B cell receptor signaling. LMP2A/MYC double transgenic mice develop splenomegaly and B cell lymphoma much faster than MYC transgenic mice do. In this study, we explored the potential therapeutic efficacy of a novel spleen tyrosine kinase (SYK) and FLT3 inhibitor TAK-659 for development of a treatment option for EBV-associated malignancies. In our transgenic model, TAK-659 treatment totally abrogated splenomegaly and tumor development in LMP2A/MYC mice in both pretumor and tumor cell transfer experiments. TAK-659 treatment killed tumor cells, but not host cells within the spleen and tumors. Furthermore, TAK-659 treatment abrogated metastasis of tumor cells into bone marrow. Our data also show that TAK-659 inhibits SYK phosphorylation and induces apoptosis in LMP2A/MYC tumor cells at low nanomolar concentrations. Therefore, TAK-659 may provide an effective therapeutic option for treatment of LMP2A-positive EBV-associated malignancies and should be explored further in clinical trials. IMPORTANCE The novel SYK and FLT3 inhibitor TAK-659 prevents the enlargement of spleen and tumor development in a mouse model of EBV-associated lymphoma by counteracting the activation of cellular kinase SYK through the viral LMP2A gene by inducing cell death in tumor cells but not in nontumor cells. These findings indicate that TAK-659 may be a very effective nontoxic therapeutic molecule especially for EBV-positive hematologic malignancies.

Objectives: The genetic risk factors that contribute to the risk of developing aortic dissection (AD) have been studied. We assessed the association of endothelial nitric oxide synthase (eNOS) gene polymorphism with AD. Study design: Patients who underwent surgery with the diagnosis of AD and survived after the operation in our center between May 2007 and June 2011 were recruited retrospectively. The eNOS intron 4a/b polymorphism was determined by polymerase chain reaction (PCR) using oligonucleotide primers (sense: 5'-AGGCCCTATGGTAGTGCCTTT-3'; antisense: 5'-TCTCTTAGTGCTGTGGTCAC-3') that flank the region of the 27 bp VNTR in intron 4. Results: Thirty-nine patients (88%) had type A AD, while the remainder (12%) had type B AD. The distribution of eNOS4 a/b gene polymorphism differed significantly from the control group, with higher frequencies of eNOS 4a/a and 4a/b genotypes in the AD group (χ2=7.16, p=0.03). Conclusion: In this study, the distribution of eNOS genotypes differed between the AD and control groups; however, this polymorphism was not found to be an independent factor for the development of AD.

Finding large deletions in genome sequences has become increasingly more useful in bioinformatics, such as in clinical research and diagnosis. Although there are a number of publically available next generation sequencing mapping and sequence alignment programs, these software packages do not correctly align fragments containing deletions larger than one kb. We present a fast alignment software package, BinaryPartialAlign, that can be used by wet lab scientists to find long structural variations in their experiments. For BinaryPartialAlign, we make use of the Smith-Waterman (SW) algorithm with a binary-search-based approach for alignment with large gaps that we called partial alignment. BinaryPartialAlign implementation is compared with other straight-forward applications of SW. Simulation results on mtDNA fragments demonstrate the effectiveness (runtime and accuracy) of the proposed method.

Due to the high concentration of pollutants, swine wastewater needs to be treated prior to disposal. The combination of anaerobic and aerobic technologies in one hybrid system allows to obtain higher removal efficiencies compared to those achieved via conventional biological treatment, and the performance of a hybrid system depends on the microbial community in the bioreactor. Here, we evaluated the community assembly of an anaerobic-aerobic hybrid reactor for swine wastewater treatment. Sequencing of partial 16S rRNA coding genes was performed using Illumina from DNA and retrotranscribed RNA templates (cDNA) extracted from samples from both sections of the hybrid system and from a UASB bioreactor fed with the same swine wastewater influent. Proteobacteria and Firmicutes were the dominant phyla and play a key role in anaerobic fermentation, followed by Methanosaeta and Methanobacterium. Several differences were found in the relative abundances of some genera between the DNA and cDNA samples, indicating an increase in the diversity of the metabolically active community, highlighting Chlorobaculum, Cladimonas, Turicibacter and Clostridium senso stricto. Nitrifying bacteria were more abundant in the hybrid bioreactor. Beta diversity analysis revealed that the microbial community structure significantly differed among the samples (p < 0.05) and between both anaerobic treatments. The main predicted metabolic pathways were the biosynthesis of amino acids and the formation of antibiotics. Also, the metabolism of C5-branched dibasic acid, Vit B5 and CoA, exhibited an important relationship with the main nitrogen-removing microorganisms. The anaerobic-aerobic hybrid bioreactor showed a higher ammonia removal rate compared to the conventional UASB system. However, further research and adjustments are needed to completely remove nitrogen from wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The New World screwworm, Cochliomyia hominivorax (Coquerel 1858) (Diptera: Calliphoridae), is a serious parasite of livestock, humans, and other warm-blooded animals. It has been eradicated from the northern parts of its historical range down to the Panama-Colombian border where a permanent barrier zone is maintained. This eradication was accomplished through using the sterile insect technique (SIT). In 2016 there was an outbreak of C. hominivorax in the Florida Keys. In only six months, this pest was successfully re-eradicated using SIT, but the geographic origin of the invasion has yet to be resolved. It was previously determined that the Florida flies most likely represented a single invasion, and it was recommended that a finer-scale genetic assessment should be completed. Thus, this current proof-of-concept study aimed to develop a population genetic database using single nucleotide polymorphisms (SNPs) to reference outbreaks and potentially identify the origin of the Florida outbreak. This initial database consists of wild-caught samples from 4 geographic locations as well as laboratory colony samples that originated from 7 additional locations using a genotyping by sequencing (GBS) approach. Geographic population structuring was identified for twelve populations that clustered according to geographic location. The Florida outbreak samples appeared similar to samples from the outer Caribbean cluster which included samples from Dominican Republic and Trinidad and Tobago, however, these results will be further clarified with the replacement of laboratory colony samples with future wild-caught samples., (Published by Oxford University Press on behalf of Entomological Society of America 2022.)

Methanogenic-aerobic coupled processes were used to biological degradation of vinyl acetate (VA) to provide evidence of oxygen role for their complete elimination from different angles. First, physiological characterization of a continuous methanogenic-aerobic reactor fed by VA and glucose (G) showed that by adding G, the VA got 100% hydrolyzed to acetate, and then, by adding 1 mg·L -1 ·d -1 of dissolved oxygen (DO), this acetate got methanized by 40% and aerobically mineralized by 60%. Second, batch assays in the presence and absence of sodium azide suggest that VA at different concentrations was eliminated by both anaerobic and aerobic metabolic pathways, because without azide and in the presence of 1 mg DO·L -1 increased methane and carbon dioxide formation rates at 80% and 75%, respectively. Finally, microbial population dynamics analysis of the reactor by DGGE-sequencing highlighted that Brevibacillus agri (aerobic) and Methanosarcina barkeri (anaerobic) were identified as responsible for VA elimination by up to 98.6%. PRACTITIONER POINTS: Vinyl acetate is removed by simultaneous methanation and aerobic respiration. Methanosarcina barkeri and Brevibacillus agri removed up to 99% of vinyl acetate. DO and VA have a selective effect on the metabolism and population dynamics., (© 2021 Water Environment Federation.)