Computational analyses reveal spatial relationships between nuclear pore complexes and specific lamins

Nuclear lamin isoforms form fibrous meshworks associated with nuclear pore complexes (NPCs). Using datasets prepared from subpixel and segmentation analyses of 3D–structured illumination microscopy images of WT and lamin isoform knockout mouse embryo fibroblasts, we determined with high precision the spatial association of NPCs with specific lamin isoform fibers. These relationships are retained in the enlarged lamin meshworks of Lmna^−/− and Lmnb1^−/− fibroblast nuclei. Cryo-ET observations reveal that the lamin filaments composing the fibers contact the nucleoplasmic ring of NPCs. Knockdown of the ring-associated nucleoporin ELYS induces NPC clusters that exclude lamin A/C fibers but include LB1 and LB2 fibers. Knockdown of the nucleoporin TPR or NUP153 alters the arrangement of lamin fibers and NPCs. Evidence that the number of NPCs is regulated by specific lamin isoforms is presented. Overall the results demonstrate that lamin isoforms and nucleoporins act together to maintain the normal organization of lamin meshworks and NPCs within the nuclear envelope.     

GAR22β regulates cell migration,sperm motility,and axoneme structure

Spatiotemporal cytoskeleton remodeling is pivotal for cell adhesion and migration. Here we investigated the function of Gas2-related protein on chromosome 22 (GAR22β), a poorly characterized protein that interacts with actin and microtubules. Primary and immortalized GAR22β^−/− Sertoli cells moved faster than wild-type cells. In addition, GAR22β^−/− cells showed a more prominent focal adhesion turnover. GAR22β overexpression or its reexpression in GAR22β^−/− cells reduced cell motility and focal adhesion turnover. GAR22β–actin interaction was stronger than GAR22β–microtubule interaction, resulting in GAR22β localization and dynamics that mirrored those of the actin cytoskeleton. Mechanistically, GAR22β interacted with the regulator of microtubule dynamics end-binding protein 1 (EB1) via a novel noncanonical amino acid sequence, and this GAR22β–EB1 interaction was required for the ability of GAR22β to modulate cell motility. We found that GAR22β is highly expressed in mouse testes, and its absence resulted in reduced spermatozoa generation, lower actin levels in testes, and impaired motility and ultrastructural disorganization of spermatozoa. Collectively our findings identify GAR22β as a novel regulator of cell adhesion and migration and provide a foundation for understanding the molecular basis of diverse cytoskeleton-dependent processes.     

The effect of reticulocyte hemoglobin content on the diagnosis of iron deficiency anemia: A meta-analysis study

BackgroundIron deficiency anemia (IDA) is the most common type of anemia worldwide and has many adverse effects on life quality. This meta-analysis study aims to show that reticulocyte hemoglobin content (CHr) is more effective than routinely used parameters in the diagnosis of IDA.MethodsComprehensive and systematic research was done using international databases including PubMed, Web of Science, Cochrane Library, Science Direct, and Google Scholar, which contain all articles published on IDA until December 29, 2020. Seventeen articles were included in the meta-analysis.ResultsThe analyses found the Cohen''s deffect size (Standardized Mean Difference) values of the parameters. Accordingly, CHr is 2.84 (95% CI 2.36 to 3.31), mean corpus volume (MCV) is 2.46 (95% CI 1.97 to 2.95), ferritin is 2.37 (95% CI 1.63 to 3.11), and transferrin saturation (TSAT) is 3.76 (95% CI 2.14 to 5.38). To diagnose IDA, the sensitivity value of the CHr concentration was found as 83.5% (95% CI 76.1 to 89.8), specificity value to be 91.8% (95% CI 85.5 to 96.4), and mean cut-off value as 28.2 pg.ConclusionsThe results of our study reveal the findings that CHr is a better biomarker than MCV and ferritin used in determining IDA, and its efficacy is lower than TSAT. It is very important to use it routinely for the pre-diagnosis of IDA, which is very important for public health. The groups in the study are heterogeneous but contain bias. Therefore, meta-analyses of studies with less heterogeneity of CHr are needed.     

The presence of promatrix metalloproteinase-3 and its relation with different categories of coal workers' pneumoconiosis

Extracellular matrix formation (ECM) and remodeling are critical events related to the pathogenesis of pulmonary fibrosis. Matrix metalloproteinases play an essential role in degrading and remodeling the ECM. In this study, we tried to show the presence and correlation of promatrix metalloproteinase-3 (proMMP-3) (the inactive form of metalloproteinase-3) levels in coal workers' pneumoconiosis (CWP) with different categories. The study population consisted of 44 coal miners with CWP (pos CWP). Coal miners without CWP (neg CWP, n = 24) and non-underground personnel (controls, n = 17) were taken as controls. All coal miners were stable and had no systemic infection or disease. Standard posterio-anterior chest radiographs and pulmonary function tests were performed to exclude any diseases other than CWP. Serum proMMP-3 was analysed using the sandwich enzyme-linked immunosorbent assay according to the manufacturer's instructions (The Binding Site, Birmingham, UK). Mean proMMP-3 values of the all three groups were compared and a significant statistical difference obtained (p < 0.001). In addition, a statistically significant difference was found between categories of the disease and proMMP-3 values (p < 0.05). The effects of age, exposure duration and cigarette smoking on proMMP-3 values in coal miners with CWP were investigated. There were no correlations between age, smoking and proMMP-3 values. However, a positive correlation was found between exposure duration and proMMP-3 values (r = 0.447, p = 0.008). In conclusion, proMMP-3 (prostromelysin 1) may play an essential role in degrading and remodeling the ECM in workers with pneumoconiosis. ProMMP-3 may also reflect the stage of pneumoconiosis disease.     

Nuatigenin-type steroidal saponins from Veronica fuhsii and V. muldtfida

A new nuatigenin-type steroidal saponin, multifidoside (2), was isolated from the aerial parts of Veronica fuhsii and V multifida and its structure was identified as 3-O-([alpha-L-rhamnopyranosyl-(1-->2glu)]-[beta-D-glucopyranosyl-(1-->4rha)-alpha-L-rhamnopyranosyl (1-->4glu)]-beta-D-glucopyranosyl]nuatigenin 26-O-beta-D-glucopyranoside. Additionally, a known steroidal saponoside, aculeatiside A (1), from V. fuhsii, a phenylethanoid glycoside, verpectoside A (3), and a flavon glycoside, isoscutellarein 7-O-(2"-O-6"-O-acetyl-beta-D-allopyranosyl-beta-D-glucopyranoside) (4) from V. multifida were isolated.     

Effects of lactulose and lactitol on coliform bacteria and bacterial translocation in the caecum during 72-h starvation in rats

Lactulose and lactitol, non-absorbable disaccharides, prevent bacterial translocation (BT) arising from the gut. In contrast, lack of food into the gut leads to coliform bacterial overgrowth and even if it does not cause BT, can induce the risk from other stimuli for BT. In this study, we tested whether lactulose and lactitol affected populations of coliform bacteria in the caecum during starvation in Sprague-Dawley rats. Three groups of rats were starved for 72 h and given oral 2 ml undiluted lactulose (670 mg/ml), 2 ml undiluted lactitol (666 mg/ml) or 2 ml physiological saline, respectively, once a day. The caecum and mesenteric lymph nodes (MLNs) were removed for microbiological and histopathological analyses. The highest degree of coliform bacterial overgrowth, BT to MLNs and histopathological damage were observed in lactulose-treated rats, followed by the group treated with lactitol. As a result of this study, both drugs, especially lactulose augmented the proliferation and translocation tendency of coliform bacteria in the caecum during 72-h starvation in rats.     

Successful Medical Management of Recalcitrant Fusarium solani Keratitis: Molecular Identification and Susceptibility Patterns

Fungal keratitis is a rare but sight-threatening infection of the cornea that may be caused by several fungal pathogens. A delay in diagnosis and inadequate treatment may even lead to loss of the affected eye. Fungal keratitis is often misdiagnosed as bacterial keratitis because isolation and identification of the fungal pathogen is difficult and requires experience, and fungal growth in culture requires time. In this report, a 14-year-old boy with recalcitrant Fusarium solani keratitis, unresponsive to initial therapy, is presented. CLSI M38-A2 in vitro antifungal susceptibility tests demonstrated that only amphotericin B (0.5 μg/ml) had potent activity against F. solani; however, fluconazole (>64 μg/ml), itraconazole (>16 μg/ml), voriconazole (8 μg/ml), and posaconazole (>16 μg/ml) had high minimum inhibitory concentrations. In addition, caspofungin (>16 μg/ml) and anidulafungin (>16 μg/ml) exhibited high minimum effective concentrations. Repeated intrastromal voriconazole injections, topical voriconazole, and caspofungin combined with systemic antifungal agents improved of the corneal lesion with a significant increase in visual acuity. Intrastromal voriconazole injection may be used as an adjunctive treatment method for recalcitrant fungal keratitis with no prominent complications. The intrastromal route could be an effective route of administration of antifungal agents, especially for F. solani keratitis, as in this case. A combination of various antifungal agents administered by different routes prevented loss of the eye.