Thermal disinfection is probably the oldest water treatment method ever used. Similarly to other disinfection processes, it targets the inactivation of pathogenic (micro)organisms present in water, ...wastewater and other media. In this work, a pilot-scale continuous-flow thermal disinfection system was investigated using highly contaminated hospital wastewater as influent without any pre-treatment step for turbidity removal. The results proved that the tested system can be used with influent turbidity as high as 100 NTU and still provide up to log 8 microbial inactivation. Further results have shown energy consumption comparable to other commercially available thermal disinfection systems and relatively low influence on the investigated physical–chemical parameters.
The ubiquitin ligase SCF
FBXO38
controls centromeric chromatin by promoting the degradation of the ZXDB protein. To determine the importance of this pathway during development,
Fbxo38
-deficient mice ...were generated. The loss of FBXO38 resulted in growth retardation affecting several organs, including the male reproductive system. A detailed analysis of the mutant testes revealed pathological changes in the seminiferous tubules, accompanied by a significant decrease in sperm production and reduced fertility. In adult testes, FBXO38 was specifically expressed in Sertoli cells, a somatic population essential for spermatogenesis initiation and progression. Sertoli cells lacking FBXO38 exhibited stabilized ZXDB protein and upregulated centromeric chromatin. Furthermore, the gene expression profile revealed that the absence of FBXO38 led to a defect in Sertoli cell maturation, specifically characterized by dysregulation in genes controlling retinoic acid metabolism and intercellular communication. Consequently, we documented significant changes in their ability to initiate spermatogonial differentiation. In conclusion, we show that FBXO38 acts as a Sertoli cell maturation factor, affecting the Sertoli cell transcription program, centromere integrity, and, subsequently, the ability to control spermatogenesis.
Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that affect the gastrointestinal tract. Changes in the microbiome and its interaction with the immune ...system are thought to play a key role in their development. The aim of this study was to determine whether metagenomic analysis is a feasible non-invasive diagnostic tool for IBD in paediatric patients. A pilot study of oral and faecal microbiota was proposed with 36 paediatric patients divided in three cohorts 12 with CD, 12 with UC and 12 healthy controls (HC) with 6 months of follow-up. Finally, 30 participants were included: 13 with CD, 11 with UC and 8 HC (6 dropped out during follow-up). Despite the small size of the study population, a differential pattern of microbial biodiversity was observed between IBD patients and the control group. Twenty-one bacterial species were selected in function of their discriminant accuracy, forming three sets of potential markers of IBD. Although IBD diagnosis requires comprehensive medical evaluation, the findings of this study show that faecal metagenomics or a reduced set of bacterial markers could be useful as a non-invasive tool for an easier and earlier diagnosis.
Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system. NB is mainly driven by copy number alterations, such as
amplification, large deletions of chromosome arm 11q and gain ...of chromosome arm 17q, which are all markers of high‑risk disease. Genes targeted by recurrent, smaller, focal alterations include
and
. Our previous study on relapsed NB detected recurrent structural alterations centered at limbic system‑associated membrane protein (
; HUGO Gene Nomenclature Committee: 6705; chromosomal location 3q13.31), which is a gene frequently reported to be deleted or downregulated in other types of cancer. Notably, in cancer,
has been shown to have tumor‑suppressing functions. The present study performed an expanded investigation using whole genome sequencing of tumors from 35 patients, mainly with high‑risk NB. Focal duplications or deletions targeting
were detected in six cases (17%), whereas single nucleotide polymorphism‑microarray analysis of 16 NB cell lines detected segmental alterations at 3q13.31 in seven out of the 16 NB cell lines (44%). Furthermore, low expression of
in NB tumors was significantly associated with poor overall and event‑free survival.
, knockdown of
in NB cell lines increased cell proliferation, whereas overexpression decreased proliferation and viability. These findings supported a tumor suppressor role for
in NB. However, the higher incidence of
aberrations in cell lines and in relapsed NB tumors suggested that these alterations were a late event predominantly in advanced NB with a poor prognosis, indicating a role of
in tumor progression rather than in tumor initiation. In conclusion, the present study demonstrated recurrent genomic aberrations of chromosomal region 3q13.31 that targeted the
gene, which encodes a membrane protein involved in cell adhesion, central nervous system development and neurite outgrowth. The frequent aberrations affecting
, together with functional evidence, suggested an anti‑proliferative role of
in NB.
Neuroblastoma is the most common and deadly childhood tumor. Relapsed or refractory neuroblastoma has a very poor prognosis despite recent treatment advances. To investigate genomic alterations ...associated with relapse and therapy resistance, whole-genome sequencing was performed on diagnostic and relapsed lesions together with constitutional DNA from seven children. Sequencing of relapsed tumors indicates somatic alterations in diverse genes, including those involved in RAS-MAPK signaling, promoting cell cycle progression or function in telomere maintenance and immortalization. Among recurrent alterations, CCND1-gain, TERT-rearrangements, and point mutations in POLR2A, CDK5RAP, and MUC16 were shown in ≥ 2 individuals. Our cohort contained examples of converging genomic alterations in primary-relapse tumor pairs, indicating dependencies related to specific genetic lesions. We also detected rare genetic germline variants in DNA repair genes (e.g., BARD1, BRCA2, CHEK2, and WRN) that might cooperate with somatically acquired variants in these patients with highly aggressive recurrent neuroblastoma. Our data indicate the importance of monitoring recurrent neuroblastoma through sequential genomic characterization and that new therapeutic approaches combining the targeting of MAPK signaling, cell cycle progression, and telomere activity are required for this challenging patient group.
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Cell transplantation therapies in the nervous system are frequently hampered by glial scarring and cell drain from the damaged site, among others. To improve this situation, new ...biomaterials may be of help. Here, novel single-channel tubular conduits based on hyaluronic acid (HA) with and without poly-l-lactide acid fibers in their lumen were fabricated. Rat Schwann cells were seeded within the conduits and cultured for 10days. The conduits possessed a three-layered porous structure that impeded the leakage of the cells seeded in their interior and made them impervious to cell invasion from the exterior, while allowing free transport of nutrients and other molecules needed for cell survival. The channel’s surface acted as a template for the formation of a cylindrical sheath-like tapestry of Schwann cells continuously spanning the whole length of the lumen. Schwann-cell tubes having a diameter of around 0.5mm and variable lengths can thus be generated. This structure is not found in nature and represents a truly engineered tissue, the outcome of the specific cell–material interactions. The conduits might be useful to sustain and protect cells for transplantation, and the biohybrids here described, together with neuronal precursors, might be of help in building bridges across significant distances in the central and peripheral nervous system.
The paper entitled “Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity” reports on the development of a novel tubular scaffold and on how this scaffold acts on Schwann cells seeded in its interior as a template to produce macroscopic hollow continuous cylinders of tightly joined Schwann cells. This cellular structure is not found in nature and represents a truly engineered novel tissue, which obtains as a consequence of the specific cell-material interactions within the scaffold.
Transgenic animal models are crucial for the study of gene function and disease, and are widely utilized in basic biological research, agriculture and pharma industries. Since the current methods for ...generating transgenic animals result in the random integration of the transgene under study, the phenotype may be compromised due to disruption of known genes or regulatory regions. Unfortunately, most of the tools that predict transgene insertion sites from high-throughput data are not publicly available or not properly maintained.
We implemented TC-hunter, Transgene-Construct hunter, an open tool that identifies transgene insertion sites and provides simple reports and visualization aids. It relies on common tools used in the analysis of high-throughput data and makes use of chimeric reads and discordant read pairs to identify and support the transgenic insertion site. To demonstrate its applicability, we applied TC-hunter to four transgenic mice samples harboring the human PPM1D gene, a model used in the study of malignant tumor development. We identified the transgenic insertion site in each sample and experimentally validated them with Touchdown-polymerase chain reaction followed by Sanger sequencing.
TC-hunter is an accessible bioinformatics tool that can automatically identify transgene insertion sites from DNA sequencing data with high sensitivity (98%) and precision (92.45%). TC-hunter is a valuable tool that can aid in evaluating any potential phenotypic complications due to the random integration of the transgene and can be accessed at https://github.com/bcfgothenburg/SSF .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High-risk neuroblastomas typically display an undifferentiated or poorly differentiated morphology. It is therefore vital to understand molecular mechanisms that block the differentiation process. We ...identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in the maintenance of undifferentiated neural crest-derived progenitors through the repression of DLG2, a candidate tumor suppressor gene in neuroblastoma. DLG2 is expressed in the murine “bridge signature” that represents the transcriptional transition state when neural crest cells or Schwann cell precursors differentiate to chromaffin cells of the adrenal gland. We show that the restoration of DLG2 expression spontaneously drives neuroblastoma cell differentiation, highlighting the importance of DLG2 in this process. These findings are supported by genetic analyses of high-risk 11q deletion neuroblastomas, which identified genetic lesions in the DLG2 gene. Our data also suggest that further exploration of other bridge genes may help elucidate the mechanisms underlying the differentiation of NC-derived progenitors and their contribution to neuroblastomas.
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•ALK-ERK-SP1 signaling promotes an undifferentiated state in neuroblastoma cells•ALK signaling suppresses DLG2 transcription•DLG2 expression drives differentiation of neuroblastoma cells•11q deletion neuroblastomas exhibit genetic lesions in the DLG2 locus
Siaw et al. show that oncogenic ALK-ERK1/2-SP1 signaling maintains neuroblastoma cells in an undifferentiated state through the suppression of DLG2 transcription. The expression of DLG2 drives differentiation and inhibits tumor growth. Genetic analysis of high-risk 11q deletion neuroblastoma identifies genetic lesions in the DLG2 gene in patient samples.
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