Unique function of the bacterial chromosome segregation machinery in apically growing streptomyces - targeting the chromosome to new hyphal tubes and its anchorage at the tips

The coordination of chromosome segregation with cell growth is fundamental to the proliferation of any organism. In most unicellular bacteria, chromosome segregation is strictly coordinated with cell division and involves ParA that moves the ParB nucleoprotein complexes bi- or unidirectionally toward the cell pole(s). However, the chromosome organization in multiploid, apically extending and branching Streptomyces hyphae challenges the known mechanisms of bacterial chromosome segregation. The complex Streptomyces life cycle involves two stages: vegetative growth and sporulation. In the latter stage, multiple cell divisions accompanied by chromosome compaction and ParAB assisted segregation turn multigenomic hyphal cell into a chain of unigenomic spores. However, the requirement for active chromosome segregation is unclear in the absence of canonical cell division during vegetative growth except in the process of branch formation. The mechanism by which chromosomes are targeted to new hyphae in streptomycete vegetative growth has remained unknown until now. Here, we address the question of whether active chromosome segregation occurs at this stage. Applied for the first time in Streptomyces, labelling of the chromosomal replication initiation region (oriC) and time-lapse microscopy, revealed that in vegetative hyphae every copy of the chromosome is complexed with ParB, whereas ParA, through interaction with the apical protein complex (polarisome), tightly anchors only one chromosome at the hyphal tip. The anchor is maintained during replication, when ParA captures one of the daughter oriCs. During spore germination and branching, ParA targets one of the multiple chromosomal copies to the new hyphal tip, enabling efficient elongation of hyphal tube. Thus, our studies reveal a novel role for ParAB proteins during hyphal tip establishment and extension

6,4–PP Photolyase Encoded by AtUVR3 is Localized in Nuclei, Chloroplasts and Mitochondria and its Expression is Down-Regulated by Light in a Photosynthesis-Dependent Manner

search input Abstract Pyrimidine dimers are the most important DNA lesions induced by UVB irradiation. They can be repaired directly by photoreactivation or indirectly by the excision repair pathways. Photoreactivation is carried out by photolyases, enzymes which bind to the dimers and use the energy of blue light or UVA to split bonds between adjacent pyrimidines. Arabidopsis thaliana has three known photolyases: AtPHR1, AtCRY3 and AtUVR3. Little is known about the cellular localization and regulation of AtUVR3 expression. We have found that its transcript level is down-regulated by light (red, blue or white) in a photosynthesis-dependent manner. The down-regulatory effect of red light is absent in mature leaves of the phyB mutant, but present in leaves of phyAphyB. UVB irradiation does not increase AtUVR3 expression in leaves. Transiently expressed AtUVR3–green fluorescent protein (GFP) is found in the nuclei, chloroplasts and mitochondria of Nicotiana benthamiana epidermal cells. In the nucleoplasm, AtUVR3–GFP is distributed uniformly, while in the nucleolus it forms speckles. Truncated AtUVR3 and muteins were used to identify the sequences responsible for its subcellular localization. Mitochondrial and chloroplast localization of AtUVR3 is independent of its N-terminal sequence. Amino acids located at the C-terminal loop of the protein are involved in its transport into chloroplasts and its retention inside the nucleolus

Characterization and prognostic factors of secondary to MDS/MPN and therapy-related AML: a single-center study

Introduction: Secondary acute myeloid leukemia (sAML) accounts for 15–30% of overall AML cases and is associated with shorter survival compared to de novo AML. The pathogenetic spectrum of sAML is heterogeneous, i.e. therapy-related AML (tAML) arises from prior cytotoxic, radiation, or immunosuppressive therapy, while myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN)-AML develops from a previous clonal disorder of hematopoiesis. Material and methods: We performed a single-center retrospective analysis of MDS/MPN-AML and tAML patients diagnosed between 2013 and 2018 in the Hematology Department of the Medical University in Lodz, Poland. Simultaneously, demographic data, clinical factors, and laboratory findings were collected. For statistical analysis, we used Cox proportional hazard models and log-rank tests. Results: The study included 110 patients with either MDS/MPN-AML (n = 78) or tAML (n = 32), with a median age of 66 years (range 31–86). The median follow-up was 3.2 months [95% confidence interval (CI): 2.5–5.3]. The median overall survival (OS) for MDS/MPN-AML patients was 4.1 months (95% CI: 2.5–7.0) and for tAML it was 2.8 months (95% CI: 1.6-5.6). In multivariate Cox regression model for OS, factors such as age at diagnosis [hazard ratio (HR) 1.03, 95% CI: 1.00–1.06], higher Eastern Cooperative Oncology Group score (HR 1.85, 95% CI: 1.08–3.15), hypoalbuminemia (HR 3.20, 95% CI: 1.95–5.24) and percentage of bone marrow blasts infiltration (HR 1.01, 95% CI: 1.00–1.03) were independent predictors of poor survival for the whole cohort. On the other hand, the intensive treatment approach was related to longer survival (HR 0.42, 95% CI: 0.21–0.82). There were no differences in OS between MDS/MPN-AML and tAML (p = 0.81). Conclusion: The poor treatment outcomes for sAML consist of a combination of low response rate and high early mortality. The positive influence of intensive chemotherapy should be highlighted, but nevertheless, optimizing treatment for thishigh-risk subpopulation remains crucial

Fine tuning chloroplast movements through physical interactions between phototropins

Phototropins are plant photoreceptors which regulate numerous responses to blue light, including chloroplast relocation. Weak blue light induces chloroplast accumulation, whereas strong light leads to an avoidance response. Two Arabidopsis phototropins are characterized by different light sensitivities. Under continuous light, both can elicit chloroplast accumulation, but the avoidance response is controlled solely by phot2. As well as continuous light, brief light pulses also induce chloroplast displacements. Pulses of 0.1s and 0.2s of fluence rate saturating the avoidance response lead to transient chloroplast accumulation. Longer pulses (up to 20s) trigger a biphasic response, namely transient avoidance followed by transient accumulation. This work presents a detailed study of transient chloroplast responses in Arabidopsis. Phototropin mutants display altered chloroplast movements as compared with the wild type: phot1 is characterized by weaker responses, while phot2 exhibits enhanced chloroplast accumulation, especially after 0.1s and 0.2s pulses. To determine the cause of these differences, the abundance and phosphorylation levels of both phototropins, as well as the interactions between phototropin molecules are examined. The formation of phototropin homo- and heterocomplexes is the most plausible explanation of the observed phenomena. The physiological consequences of this interplay are discussed, suggesting the universal character of this mechanism that fine-tunes plant reactions to blue light. Additionally, responses in mutants of different protein phosphatase 2A subunits are examined to assess the role of protein phosphorylation in signaling of chloroplast movements

The importance of nutritional aspects in the assessment of inflammation and intestinal barrier in patients with inflammatory bowel disease

Intestinal inflammation in inflammatory bowel disease (IBD) is closely linked to nutrition. This study aimed to evaluate associations between nutritional, inflammatory, and intestinal barrier parameters in patients with IBD. We assessed nutritional status, fecal short-chain fatty acid profile, serum cytokine levels, and mRNA expression of enzymes and tight junction proteins in intestinal biopsies obtained from 35 patients, including 11 patients with inactive IBD, 18 patients with active IBD, and six controls. Patients with active IBD were characterized by hypoalbuminemia, fluctuations in body weight, and restriction of fiber-containing foods. In addition, they had significantly reduced levels of isovaleric acid and tended to have lower levels of butyric, acetic, and propionic acids. Patients with active IBD had higher mRNA expression of peroxisome proliferator-activated receptor γ and inducible nitric oxide synthase, and lower mRNA expression of claudin-2 and zonula occludens-1, compared with patients with inactive IBD. Moreover, patients with a body mass index (BMI) of ≥25 kg/m(2) had higher median tumor necrosis factor-α levels that those with a lower BMI. We comprehensively evaluated inflammatory parameters in relation to IBD activity and nutritional status. The discrepancies between proinflammatory and anti-inflammatory parameters depending on IBD activity may be related to nutritional factors, including diet and abnormal body weight

Phototropin interactions with SUMO proteins

The disruption of the sumoylation pathway affects processes controlled by the two phototropins (phots) of Arabidopsis thaliana, phot1 and phot2. Phots, plant UVA/blue light photoreceptors, regulate growth responses and fast movements aimed at optimizing photosynthesis, such as phototropism, chloroplast relocations and stomatal opening. Sumoylation is a posttranslational modification, consisting of the addition of a SUMO (SMALL UBIQUITIN-RELATED MODIFIER) protein to a lysine residue in the target protein. In addition to affecting the stability of proteins, it regulates their activity, interactions and subcellular localization. We examined physiological responses controlled by phots, phototropism and chloroplast movements, in sumoylation pathway mutants. Chloroplast accumulation in response to both continuous and pulse light was enhanced in the E3 ligase siz1 mutant, in a manner dependent on phot2. A significant decrease in phot2 protein abundance was observed in this mutant after blue light treatment both in seedlings and mature leaves. Using plant transient expression and yeast two-hybrid assays, we found that phots interacted with SUMO proteins mainly through their N-terminal parts, which contain the photosensory LOV domains. The covalent modification in phots by SUMO was verified using an Arabidopsis sumoylation system reconstituted in bacteria followed by the mass spectrometry analysis. Lys 297 was identified as the main target of SUMO3 in the phot2 molecule. Finally, sumoylation of phot2 was detected in Arabidopsis mature leaves upon light or heat stress treatment

Using simulation to calibrate real data acquisition in veterinary medicine

This paper explores the innovative use of simulation environments to enhance data acquisition and diagnostics in veterinary medicine, focusing specifically on gait analysis in dogs. The study harnesses the power of Blender and the Blenderproc library to generate synthetic datasets that reflect diverse anatomical, environmental, and behavioral conditions. The generated data, represented in graph form and standardized for optimal analysis, is utilized to train machine learning algorithms for identifying normal and abnormal gaits. Two distinct datasets with varying degrees of camera angle granularity are created to further investigate the influence of camera perspective on model accuracy. Preliminary results suggest that this simulation-based approach holds promise for advancing veterinary diagnostics by enabling more precise data acquisition and more effective machine learning models. By integrating synthetic and real-world patient data, the study lays a robust foundation for improving overall effectiveness and efficiency in veterinary medicine

Intestinal alkaline phosphatase combined with voluntary physical activity alleviates experimental colitis in obese mice : involvement of oxidative stress, myokines, adipokines and proinflammatory biomarkers

Intestinal alkaline phosphatase (IAP) is an essential mucosal defense factor involved in the process of maintenance of gut homeostasis. We determined the effect of moderate exercise (voluntary wheel running) with or without treatment with IAP on the course of experimental murine 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis by assessing disease activity index (DAI), colonic blood flow (CBF), plasma myokine irisin levels and the colonic and adipose tissue expression of proinflammatory cytokines, markers of oxidative stress (SOD2, GPx) and adipokines in mice fed a standard diet (SD) or high-fat diet (HFD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant decrease in CBF, and a significant increase in the colonic expression of tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β and leptin mRNAs and decrease in the mRNA expression of adiponectin. These effects were aggravated in sedentary HFD mice but reduced in exercising animals, potentiated by concomitant treatment with IAP, especially in obese mice. Exercising HFD mice demonstrated a substantial increase in the mRNA for adiponectin and a decrease in mRNA leptin expression in intestinal mucosa and mesenteric fat as compared to sedentary animals. The expression of SOD2 and GPx mRNAs was significantly decreased in adipose tissue in HFD mice, but these effects were reversed in exercising mice with IAP administration. Our study shows for the first time that the combination of voluntary exercise and oral IAP treatment synergistically favored healing of intestinal inflammation, strengthened the antioxidant defense and ameliorated the course of experimental colitis; thus, IAP may represent a novel adjuvant therapy to alleviate inflammatory bowel disease (IBD) in humans