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Achondroplasia (ACH), the most common form of dwarfism, is caused by a missense mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3). The resulting increase in FGFR3 signaling perturbs the proliferation and differentiation of chondrocytes (CCs), alters the process of endochondral ossification and thus reduces bone elongation. Increased FGFR3 signaling in osteoblasts (OBs) might also contribute to bone anomalies in ACH. In the present study of a mouse model of ACH, we sought to determine whether FGFR3 overactivation in OBs leads to bone modifications. The model carries an Fgfr3-activating mutation (Fgfr3Y367C/+) that accurately mimics ACH; we targeted the mutation to either immature OBs and hypertrophic CCs or to mature OBs by using the Osx-cre and collagen 1α1 (2.3 kb Col1a1)-cre mouse strains, respectively. We observed that Fgfr3 activation in immature OBs and hypertrophic CCs (Osx-Fgfr3) not only perturbed the hypertrophic cells of the growth plate (thus affecting long bone growth) but also led to osteopenia and low cortical thickness in long bones in adult (3-month-old) mice but not growing (3-week-old) mice. Importantly, craniofacial membranous bone defects were present in the adult mice. In contrast, activation of Fgfr3 in mature OBs (Col1-Fgfr3) had very limited effects on skeletal shape, size and micro-architecture. In vitro, we observed that Fgfr3 activation in immature OBs was associated with low mineralization activity. In conclusion, immature OBs appear to be affected by Fgfr3 overactivation, which might contribute to the bone modifications observed in ACH independently of CCs.Cardiolipin (CL) localizes to curved membranes such as cristae in mitochondria as well as cell poles and division sites in rod-shaped bacteria. CL is believed to stabilize the membrane curvature by localizing to sites of negative curvature. However, this hypothesis has not been tested because of a lack of appropriate tools to distinguish CL inside and outside lipid bilayers. In this study, we provided the first evidence that CL localized to regions of negative curvature in Escherichia coli using the novel CL probe erylysin A-EGFP (EryA-EGFP). Staining in E. coli illustrated that CL localized to the inner leaflets at cell poles and the outer leaflets at division sites. Furthermore, we revealed that EryA-EGFP inhibited cytokinesis. We propose that cytokinesis completes after CL in the outer leaflets transfers to the inner leaflets at division sites by inspecting the mechanism of inhibition of cytokinesis. Moreover, the cytoskeletal protein RodZ was abnormally distributed when cytokinesis was inhibited by EryA-EGFP, suggesting that RodZ participates in cytokinesis. In summary, we revealed the detailed distribution of CL and proposed a new model of cytokinesis.We report the first outbreak of a new type of mass sociogenic illness (MSI) that in contrast to all previously reported episodes is spread solely via social media. Accordingly, we suggest the more specific term "mass social media-induced illness" (MSMI). In Germany, current outbreak of MSMI is initiated by a "virtual" index case, who is the second most successful YouTube creator in Germany and enjoys enormous popularity among young people. Affected teenagers present with similar or identical functional "Tourette-like" behaviours, which can be clearly differentiated from tics in Tourette syndrome. Functional "Tourette-like" symptoms can be regarded as the "modern" form of the well-known motor variant of MSI. Moreover, they can be viewed as the 21th century expression of a culture-bound stress reaction of our post-modern society emphasizing the uniqueness of individuals and valuing their alleged exceptionality, thus promoting attention-seeking behaviours and aggravating the permanent identity crisis of modern man. We wish to raise awareness of the current global "Tourette-like" MSMI outbreak. A large number of young people across different countries are affected, with considerable impact on health care systems and society as a whole, since spread via social media is no longer restricted to specific locations such as local communities or school environments.spread via social media is no longer restricted to specific locations such as schools or towns.

The in utero pathologies underlying the link between preterm birth and offspring high blood pressure (BP) are still unknown. We investigated the prospective association of placental histopathological findings among preterm births with childhood BP.

Our prospective birth cohort included 546 mother-child pairs with preterm birth enrolled from 1999 to 2013 at the Boston Medical Center. Early preterm birth was defined as gestational age between 23 and 34 weeks. We histologically classified maternal placental pathology using the latest recommended categories no placental complications, histologic chorioamnionitis, maternal vascular malperfusion, and other placental complications. We calculated age-, sex- and height-specific systolic BP (SBP) percentiles for children using the 2017 American Academy of Pediatrics Hypertension guideline US reference. We used linear regression models with generalized estimating equations (GEE) to examine the associations.

The mean (SD) postnatal follow-up of the study children was 9.29 (4.1) years. After adjusting for potential confounders, histologic chorioamnionitis was associated with 5.42 percentile higher childhood SBP (95% CI 0.32, 10.52) compared to no placental pathologic findings. This association was stronger among early preterm children. Maternal vascular malperfusion was associated with 8.44 percentile higher childhood SBP among early preterm children (95% CI 1.54, 15.34) but the association was attenuated [6.25 higher SBP percentile (-0.76, 13.26)] after additional adjustment for child standardized birthweight, a potential mediator of the association.

These findings suggest that among children born preterm, especially those born early preterm, both placental histologic chorioamnionitis and vascular malperfusion may further modify a child's risk of high BP.

These findings suggest that among children born preterm, especially those born early preterm, both placental histologic chorioamnionitis and vascular malperfusion may further modify a child's risk of high BP.

To evaluate the use of genipin in delaying enzymatic digestion of corneal stroma.

Human corneal stromal tissue was treated with genipin, a known chemical crosslinker, and then along with control tissue was subjected to enzymatic digestion with collagenase. The effects of genipin treatment in retarding stromal digestion were analyzed with phase contrast microscopy, a protein quantification assay, second harmonic generation imaging, and transmission electron microscopy.

Genipin increased stromal resistance to enzymatic digestion when compared with untreated stroma. learn more A morphologic analysis and protein quantification showed increased stromal resistance to enzymatic digestion once stromal tissue was treated with genipin. Second harmonic generation imaging revealed persistent fibrillar collagen signaling in genipin-treated tissue in contrast with untreated tissue suggesting that genipin retards collagenolysis.

Genipin increases stromal resistance to enzymatic digestion in controlled experiments as demonstrated by protein quantification studies and through morphologic imaging.

This study explores the novel use of genipin in delaying enzymatic stromal digestion. Delaying stromal melting in the setting of corneal infectious or autoimmune keratitis can potentially decrease clinical morbidity.

This study explores the novel use of genipin in delaying enzymatic stromal digestion. Delaying stromal melting in the setting of corneal infectious or autoimmune keratitis can potentially decrease clinical morbidity.

Infections with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) lead to poor clinical outcomes in endophthalmitis patients, and its interactions with the host immune system remain largely unknown. The current study aimed to determine the association of MDR-PA infection with the cytokine expression profile in patients with endophthalmitis.

Vitreous of 12 patients with culture-proven MDR-PA along with 12 samples from antibiotic-susceptible P. aeruginosa (S-PA) and 20 non-infectious controls were included in the study. Expression patterns of IL-6, IL-10, IL-1α, IL-1β, IFN-γ, TNF-α, IL-8, and GM-CSF in the vitreous were analyzed by multiplex immunoassay and correlated with the clinical severity. We also assessed the phosphorylation level of different immune pathway molecules.

In the MDR-PA group, significantly (P < 0.05) increased expression of IL-6, IL-8, IL-10, IL-1β, and TNF-α was observed in comparison with the S-PA group. The increased inflammatory mediators in MDR-PA correlated with the disease severity. Additionally, the increased expression of inflammatory mediators was positively correlated to the activation levels of Akt, STAT3, JNK, p70 S6 kinase, and NF-кB (P < 0.05) in the MDR-PA group.

The current study shows the differential host immune response and phosphorylation levels of signaling molecules in MDR-PA endophthalmitis, thereby linking antibiotic resistance with distinct immune regulation.

This study provides evidence for the use of inflammatory mediator levels of IL-6, IL-8, IL-10, IL-1β, and TNF-α as potential diagnostic biomarkers of MDR endophthalmitis warranting prompt administration of immune modulators to avoid irreversible damage to the retina and vision loss.

This study provides evidence for the use of inflammatory mediator levels of IL-6, IL-8, IL-10, IL-1β, and TNF-α as potential diagnostic biomarkers of MDR endophthalmitis warranting prompt administration of immune modulators to avoid irreversible damage to the retina and vision loss.Citrus nucellar poly-embryony (NPE) is a mode of sporophytic apomixis (SA) that asexual embryos formed in the seed through adventitious embryogenesis from the somatic nucellar cells. NPE allows clonal propagation of rootstocks, but it impedes citrus cross breeding. To understand the cellular processes involved in NPE initiation, we profiled the transcriptomes and DNA methylomes in laser microdissection (LMD) captured citrus apomictic cells. In apomictic cells, ribosome biogenesis and protein degradation were activated, whereas auxin polar transport was repressed. Reactive oxygen species (ROS) accumulated in the poly-embryonic ovules, and response to oxidative stress was provoked. The global DNA methylation level, especially that of CHH context, was decreased, whereas the methylation level of the NPE-controlling key gene CitRWP was increased. A C2H2 domain-containing transcription factor (TF) gene and CitRWP co-expressed specifically in apomictic cells may coordinate to initiate NPE. The activated embryogenic development and callose deposition processes indicated embryogenic fate of nucellar embryo initial (NEI) cells. In our working model for citrus NPE initiation, DNA hyper-methylation may activate transcription of CitRWP, which increases C2H2 expression and ROS accumulation, triggers epigenetic regulation, and regulates cell fate transition and NEI cell identity in the apomictic cells.