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•Swine wastewater is a suitable medium for microalgae growth and biomass production.•Pollutants in swine wastewater can be removed by harvesting microalgae.•Correlations between ...microalgae and toxicants/bacteria need further investigation.•Harvested biomass from wastewater has great potential to convert into bioenergy.
Ever-increasing swine wastewater (SW) has become a serious environmental concern. High levels of nutrients and toxic contaminants in SW significantly impact on the ecosystem and public health. On the other hand, swine wastewater is considered as valuable water and nutrient source for microalgae cultivation. The potential for converting the nutrients from SW into valuable biomass and then generating bioenergy from it has drawn increasing attention. For this reason, this review comprehensively discussed the biomass production, SW treatment efficiencies, and bioenergy generation potentials through cultivating microalgae in SW. Microalgae species grow well in SW with large amounts of biomass being produced, despite the impact of various parameters (e.g., nutrients and toxicants levels, cultivation conditions, and bacteria in SW). Pollutants in SW can effectively be removed by harvesting microalgae from SW, and the harvested microalgae biomass elicits high potential for conversion to valuable bioenergy.
Non-human primates are valuable for modelling human disorders and for developing therapeutic strategies; however, little work has been reported in establishing transgenic non-human primate models of ...human diseases. Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor impairment, cognitive deterioration and psychiatric disturbances followed by death within 10-15 years of the onset of the symptoms. HD is caused by the expansion of cytosine-adenine-guanine (CAG, translated into glutamine) trinucleotide repeats in the first exon of the human huntingtin (HTT) gene. Mutant HTT with expanded polyglutamine (polyQ) is widely expressed in the brain and peripheral tissues, but causes selective neurodegeneration that is most prominent in the striatum and cortex of the brain. Although rodent models of HD have been developed, these models do not satisfactorily parallel the brain changes and behavioural features observed in HD patients. Because of the close physiological, neurological and genetic similarities between humans and higher primates, monkeys can serve as very useful models for understanding human physiology and diseases. Here we report our progress in developing a transgenic model of HD in a rhesus macaque that expresses polyglutamine-expanded HTT. Hallmark features of HD, including nuclear inclusions and neuropil aggregates, were observed in the brains of the HD transgenic monkeys. Additionally, the transgenic monkeys showed important clinical features of HD, including dystonia and chorea. A transgenic HD monkey model may open the way to understanding the underlying biology of HD better, and to the development of potential therapies. Moreover, our data suggest that it will be feasible to generate valuable non-human primate models of HD and possibly other human genetic diseases.
Antibiotics and hormones in swine wastewater have become a critical concern worldwide due to the severe threats to human health and the eco-environment. Removal of most detectable antibiotics and ...hormones, such as sulfonamides (SAs), SMs, tetracyclines (TCs), macrolides, and estrogenic hormones from swine wastewater utilizing various biological processes were summarized and compared. In biological processes, biosorption and biodegradation are the two major removal mechanisms for antibiotics and hormones. The residuals in treated effluents and sludge of conventional activated sludge and anaerobic digestion processes can still pose risks to the surrounding environment, and the anaerobic processes' removal efficiencies were inferior to those of aerobic processes. In contrast, membrane bioreactors (MBRs), constructed wetlands (CWs) and modified processes performed better because of their higher biodegradation of toxicants. Process modification on activated sludge, anaerobic digestion and conventional MBRs could also enhance the performance (e.g. removing up to 98% SMs, 88.9% TCs, and 99.6% hormones from wastewater). The hybrid process combining MBRs with biological or physical technology also led to better removal efficiency. As such, modified conventional biological processes, advanced biological technologies and MBR hybrid systems are considered as a promising technology for removing toxicants from swine wastewater.
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•Biological antibiotics and hormones treatment process for swine wastewater was reviewed.•Mechanisms of antibiotics/hormones removal can be biosorption and biodegradation.•Conventional AS and AD are ineffective for antibiotics & hormones removal.•MBRs/hybrid MBRs and constructed wetlands can improve toxicants removal.•Modified conventional bioreactors are also efficient in antibiotics and hormones removal.
Cell-free DNA (cfDNA) in human plasma is a class of biomarkers with many current and potential future diagnostic applications. Recent studies have shown that cfDNA molecules are not randomly ...fragmented and possess information related to their tissues of origin. Pathologies causing death of cells from particular tissues result in perturbations in the relative distribution of DNA from the affected tissues. Such tissue-of-origin analysis is particularly useful in the development of liquid biopsies for cancer. It is therefore of value to accurately determine the relative contributions of the tissues to the plasma DNA pool in a simultaneous manner. In this work, we report that in open chromatin regions, cfDNA molecules show characteristic fragmentation patterns reflected by sequencing coverage imbalance and differentially phased fragment end signals. The latter refers to differences in the read densities of sequences corresponding to the orientation of the upstream and downstream ends of cfDNA molecules in relation to the reference genome. Such cfDNA fragmentation patterns preferentially occur in tissue-specific open chromatin regions where the corresponding tissues contributed DNA into the plasma. Quantitative analyses of such signals allow measurement of the relative contributions of various tissues toward the plasma DNA pool. These findings were validated by plasma DNA sequencing data obtained from pregnant women, organ transplantation recipients, and cancer patients. Orientation-aware plasma DNA fragmentation analysis therefore has potential diagnostic applications in noninvasive prenatal testing, organ transplantation monitoring, and cancer liquid biopsy.
Primitive cancers have so-called hot-spot mutations in
DICER1
that alter the function of
DICER1,
an enzyme that processes microRNA. Some of these cancers harbor a loss-of-function mutation in the ...other
DICER1
allele, suggesting a new mutational mechanism of oncogenesis.
Sex cord–stromal tumors and germ-cell tumors account for less than 10% of ovarian cancers.
1
Unlike epithelial ovarian cancers, both sex cord–stromal tumors and germ-cell tumors can also occur in the testicle; testicular germ-cell tumors are the most common cancer in boys and men of European descent between the ages of 15 and 34 years.
2
,
3
Other than a pathognomonic somatic mutation in
FOXL2
in adult granulosa-cell tumors,
4
–
6
little is known about the pathogenesis of ovarian sex cord–stromal tumors and germ-cell tumors. Recently, germline mutations in the microRNA processing gene
DICER1
have been reported in probands with pleuropulmonary blastoma or . . .
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•Antibiotic impacts on performance/microbes of anaerobic processes were reviewed.•Higher dose and combined antibiotics had more inhibition on anaerobic processes.•Antibiotics ...inhibited the VFAs degrading bacteria and acetoclastic methanogens.•Acetoclastic methanogens shifted to hydrogenotrophic methanogens due to antibiotics.
Swine wastewaters with high levels of organic pollutants and antibiotics have become serious environmental concerns. Anaerobic technology is a feasible option for swine wastewater treatment due to its advantage in low costs and bioenergy production. However, antibiotics in swine wastewater have problematic effects on micro-organisms, and the stability and performance of anaerobic processes. Thus, this paper critically reviews impacts of antibiotics on pH, COD removal efficiencies, biogas and methane productions as well as the accumulation of volatile fatty acids (VFAs) in the anaerobic processes. Meanwhile, impacts on the structure of bacteria and methanogens in anaerobic processes are also discussed comprehensively. Furthermore, to better understand the effect of antibiotics on anaerobic processes, detailed information about antimicrobial mechanisms of antibiotics and microbial functions in anaerobic processes is also summarized. Future research on deeper knowledge of the effect of antibiotics on anaerobic processes are suggested to reduce their adverse environmental impacts.
Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for ...precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.
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•Living biobank includes 17 normal and 46 gastric cancer organoid lines•Organoid biobank encompasses most of the known molecular subtypes of gastric cancer•Organoids recapitulate the genomic and transcriptomic features of original tumors•High-throughput screen revealed potential target drugs for personalized therapy
Leung and colleagues established a biobank of patient-derived gastric cancer organoids that encompasses a diverse array of subtypes and maintained long-term similarity to the original tumors. They used the organoids to perform large-scale drug screening that identified potential target drugs and could guide patient drug selection.
Next-generation sequencing of follicular lymphoma and diffuse-large B-cell lymphoma has revealed frequent somatic, heterozygous Y641 mutations in the histone methyltransferase EZH2. Heterozygosity ...and the presence of equal quantities of both mutant and wild-type mRNA and expressed protein suggest a dominant mode of action. Surprisingly, B-cell lymphoma cell lines and lymphoma samples harboring heterozygous EZH2Y641 mutations have increased levels of histone H3 Lys-27–specific trimethylation (H3K27me3). Expression of EZH2Y641F/N mutants in cells with EZH2WT resulted in an increase of H3K27me3 levels in vivo. Structural modeling of EZH2Y641 mutants suggests a “Tyr/Phe switch” model whereby structurally neutral, nontyrosine residues at position 641 would decrease affinity for unmethylated and monomethylated H3K27 substrates and potentially favor trimethylation. We demonstrate, using in vitro enzyme assays of reconstituted PRC2 complexes, that Y641 mutations result in a decrease in monomethylation and an increase in trimethylation activity of the enzyme relative to the wild-type enzyme. This represents the first example of a disease-associated gain-of-function mutation in a histone methyltransferase, whereby somatic EZH2 Y641 mutations in lymphoma act dominantly to increase, rather than decrease, histone methylation. The dominant mode of action suggests that allele-specific EZH2 inhibitors should be a future therapeutic strategy for this disease.
CDK12 (cyclin-dependent kinase 12) is a regulatory kinase with evolutionarily conserved roles in modulating transcription elongation. Recent tumor genome studies of breast and ovarian cancers ...highlighted recurrent CDK12 mutations, which have been shown to disrupt DNA repair in cell-based assays. In breast cancers, CDK12 is also frequently co-amplified with the HER2 (ERBB2) oncogene. The mechanisms underlying functions of CDK12 in general and in cancer remain poorly defined. Based on global analysis of mRNA transcripts in normal and breast cancer cell lines with and without CDK12 amplification, we demonstrate that CDK12 primarily regulates alternative last exon (ALE) splicing, a specialized subtype of alternative mRNA splicing, that is both gene- and cell type-specific. These are unusual properties for spliceosome regulatory factors, which typically regulate multiple forms of alternative splicing in a global manner. In breast cancer cells, regulation by CDK12 modulates ALE splicing of the DNA damage response activator ATM and a DNAJB6 isoform that influences cell invasion and tumorigenesis in xenografts. We found that there is a direct correlation between CDK12 levels, DNAJB6 isoform levels and the migration capacity and invasiveness of breast tumor cells. This suggests that CDK12 gene amplification can contribute to the pathogenesis of the cancer.
The human transcriptome annotation is regarded as one of the most complete of any eukaryotic species. However, limitations in sequencing technologies have biased the annotation toward multi-exonic ...protein coding genes. Accurate high-throughput long read transcript sequencing can now provide additional evidence for rare transcripts and genes such as mono-exonic and non-coding genes that were previously either undetectable or impossible to differentiate from sequencing noise.
We developed the Transcriptome Annotation by Modular Algorithms (TAMA) software to leverage the power of long read transcript sequencing and address the issues with current data processing pipelines. TAMA achieved high sensitivity and precision for gene and transcript model predictions in both reference guided and unguided approaches in our benchmark tests using simulated Pacific Biosciences (PacBio) and Nanopore sequencing data and real PacBio datasets. By analyzing PacBio Sequel II Iso-Seq sequencing data of the Universal Human Reference RNA (UHRR) using TAMA and other commonly used tools, we found that the convention of using alignment identity to measure error correction performance does not reflect actual gain in accuracy of predicted transcript models. In addition, inter-read error correction can cause major changes to read mapping, resulting in potentially over 6 K erroneous gene model predictions in the Iso-Seq based human genome annotation. Using TAMA's genome assembly based error correction and gene feature evidence, we predicted 2566 putative novel non-coding genes and 1557 putative novel protein coding gene models.
Long read transcript sequencing data has the power to identify novel genes within the highly annotated human genome. The use of parameter tuning and extensive output information of the TAMA software package allows for in depth exploration of eukaryotic transcriptomes. We have found long read data based evidence for thousands of unannotated genes within the human genome. More development in sequencing library preparation and data processing are required for differentiating sequencing noise from real genes in long read RNA sequencing data.
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