The effect of the interaction of sleep onset latency and age on ischemic stroke severity via inflammatory chemokines

ObjectiveProlonged sleep onset latency (PSOL) and age have been linked to ischemic stroke (IS) severity and the production of chemokines and inflammation, both of which contribute to IS development. This study aimed to explore the relationship between chemokines, inflammation, and the interplay between sleep onset latency (SOL) and age in influencing stroke severity.MethodsA cohort of 281 participants with mild to moderate IS was enrolled. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and SOL was recorded. Serum levels of macrophage inflammatory protein-1alpha (MIP-1α), macrophage inflammatory protein-1beta (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured.ResultsNIHSS scores of middle-aged participants with PSOL were significantly higher than those with normal sleep onset latency (NSOL) (p = 0.046). This difference was also observed when compared to both the elderly with NSOL (p = 0.022), and PSOL (p < 0.001). Among middle-aged adults with PSOL, MIP-1β exhibited a protective effect on NIHSS scores (β = −0.01, t = −2.11, p = 0.039, R2 = 0.13). MIP-1α demonstrated a protective effect on NIHSS scores in the elderly with NSOL (β = −0.03, t = −2.27, p = 0.027, R2 = 0.12).ConclusionThis study reveals a hitherto undocumented association between PSOL and IS severity, along with the potential protective effects of MIP-1β in mitigating stroke severity, especially among middle-aged patients

KIF21A Mutations in Two Chinese Families with Congenital Fibrosis of the Extraocular Muscles (CFEOM)

Purpose: Two Chinese families (XT and YT) with congenital fibrosis of the extraocular muscles (CFEOM) were identified. The purpose of this study was to determine if previously described Homo sapiens kinesin family member 21A (KIF21A) mutations were responsible for CFEOM in these two Chinese pedigrees. Methods: Clinical characterization and genetic studies were performed. Microsatellite genotyping for linkage to the CFEOM1 and CFEOM3 loci was performed. The probands were screened for KIF21A mutations by bidirectional direct sequencing. Once a mutation was detected in the proband, all other participating family members and 100 unrelated control normal individuals were screened for the mutation. Results: All affected individuals in family XT shared the common manifestations of CFEOM1. Family YT had two affected individuals, a mother and a daughter. The daughter had CFEOM1, while her mother never had congential ptosis but did have limited extraocular movements status post strabismus surgery. Haplotype analysis revealed that pedigree XT was linked to the 12q CFEOM1 locus and the affected memberes harbored the second most common missense mutation in KIF21A (2,861G>A, R954Q). Family YT harbored the most common missense de novo mutation in KIF21A (2,860C>T, R954W). Both of these mutations have been previously described. Conclusions: The observation of these two KIF21A mutations in a Chinese pedigree underscores the homogeneity of these mutations as a cause of CFEOM1 and CFEOM3 across ethnic divisions

The Identification of Lymphocyte-Like Cells and Lymphoid-Related Genes in Amphioxus Indicates the Twilight for the Emergency of Adaptive Immune System

To seek evidence of a primitive adaptive immune system (AIS) before vertebrate, we examined whether lymphocytes or lymphocyte-like cells and the related molecules participating in the lymphocyte function existed in amphioxus. Anatomical analysis by electron microscopy revealed the presence of lymphocyte-like cells in gills, and these cells underwent morphological changes in response to microbial pathogens that are reminiscent of those of mammalian lymphocytes executing immune response to microbial challenge. In addition, a systematic comparative analysis of our cDNA database of amphioxus identified a large number of genes whose vertebrate counterparts are involved in lymphocyte function. Among these genes, several genes were found to be expressed in the vicinity of the lymphocyte-like cells by in situ hybridization and up-regulated after exposure to microbial pathogens. Our findings in the amphioxus indicate the twilight for the emergency of AIS before the invertebrate-vertebrate transition during evolution

The signalling pathways and physiological roles of the Rif GTPase

Abstract The small Rho GTPases are a family of signalling proteins that act as molecular switches to regulate a number of key cellular processes, including actin remodelling, cell adhesion, cell polarity and cell migration. Recently, they were also found to play vital roles in nervous system development, immune system development and angiogenesis. The human family of Rho GTPases contains 20 members; however, only three of them; RhoA, Racl and Cdc42, have been studied in detail. Solving the pathways controlled by the other members of this important signalling protein family is clearly essential to our understanding of the actin cytoskeleton. The research within this thesis focused on the characterization of the signalling pathways of one novel and poorly-defined Rho GTPase: Rif. The Rif GTPase is a relatively recent addition to the Rho family; it is found only in chordates and displays a relatively low homology to other family members. Activated Rif was found to be an alternative trigger for the formation of actin stress fibers in epithelial cells through effector mDial. Unlike the classical stress fiber inducer RhoA, Rif does not raise ROCK activity in cells, instead Rif appears to regulate the localization of myosin light chain phosphorylation. This study establishes Rif as a general regulator of Diaphanous-related formins and shows how non-classical Rho family members can access classical Rho pathways to create new signalling interfaces in cytoskeletal regulation. Proteomics were carried out in this thesis to identify potential binding partners of Rif. Through these studies I have shown that Rif interacts with FARPl, which is a RhoA GEF; and plexinA4, which is a developing nervous system guidance cue receptor. PlexinA4, FARPl and Rif form a heterotrimer at the cell membrane. At low local expression levels, the priority for Rif is to bind the C-terminus of FARPl and enhances its RhoGEF activity. In contrast, at higher local expression levels, Rif competes with the FERM domain ofFARPl for plexinA4 binding and forms a feedback loop to prevent overactivation of plexinA4/FARPl signalling pathway. These results suggest that Rif can not only work as a GTPase to remodel actin cytoskeleton, but also act as a regulator to regulate the activity of the other small Rho GTPases.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The small Rho GTPase Rif and actin cytoskeletal remodelling

The Rif GTPase is a recent addition to small Rho GTPase family; it shares low homology with other members in the family and evolutionarily parallels with the development of vertebrates. Rif has the conserved Rho GTPase domain structures and cycles between a GDP-bound inactive form and a GTP-bound active form. In its active form, Rif signals through multiple downstream effectors. In the present review, our aim is to summarize the current information about the Rif effectors and how Rif remodels actin cytoskeleton in many aspects.</jats:p

Spatio-temporal evolution of economic polycentric pattern at county level in Shandong Province

From the perspective of economy and comprehensive development level, this study used the gravity model, spatial autocorrelation analysis and principal component analysis to quantitatively measure the spatiotemporal evolution pattern of multi-centers at county level in Shandong Province. The results show that the economic ties among counties in Shandong Province are getting closer and closer. By 2016, Jinan-Zibo-Qingdao and Jining, Zaozhuang have basically formed three strong economic ties. The amount of counties with high-high GDP and low-low GDP are decreasing, while the amount of counties with lowhigh GDP are increasing. The gap between the density of output value and the level of economic development is narrowing, showing a trend of multicenter development. In the future development, Shandong Province should strengthen the integration of resources within the province, form a reasonable industrial division of labor, strengthen the cooperation among enterprises, promote the regional integration construction, and realize the multi-center spatial development model of cooperation

Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage of both eyes after COVID-19 infection: a case report

Abstract Background Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage is commonly observed in myopia with tilted optic disc. It presents with typical features on the fundus and follows a self-limiting course. However, due to its complex etiology, clinicians sometimes lack sufficient understanding of it which can easily lead to misdiagnosis or overtreatment. In this case report, we describe a rare case of intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage in both eyes. Case presentation An 18-year-old female who has no past medical history experienced sudden black shadow blocking of her right eye in the right eye for the past 2 days after a 5-day history of COVID-19 infection. The best corrected visual acuity is 0.5 in the right eye and 0.6 in the left eye. Optical coherence tomography (OCT) showed tilted optic discs in both eyes, bulged nasal optic discs, and the presence of strong reflective material under the parafoveal retina of the optic discs. Fundus fluorescein angiography (FFA) showed subretinal fluorescence occlusion above and nasolateral to the optic disc in the right eye, with hypofluorescence below the optic disc; the subretinal below the optic disc was obscured by vitreous hemorrhage; hypofluorescence was seen in the optic disc region of the left eye.COVID-19 antigen was positive. The patient was in the early stage of the third COVID-19 infection when the disease occurred. We speculate that it may be related to it. After 5 months of conservative treatment, the patient’s hemorrhage disappeared in both eyes and her best corrected visual acuity returned to normal. Conclusions Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage usually occurs in myopia with tilted optic disc. In most patients, the cause of the bleeding is unknown, but it can gradually resolve under clinical observation or conservative treatment

A Spatial Control for Correct Timing of Gene Expression during the Escherichia coli Cell Cycle

Temporal transcriptions of genes are achieved by different mechanisms such as dynamic interaction of activator and repressor proteins with promoters, and accumulation and/or degradation of key regulators as a function of cell cycle. We find that the TorR protein localizes to the old poles of the Escherichia coli cells, forming a functional focus. The TorR focus co-localizes with the nucleoid in a cell-cycle-dependent manner, and consequently regulates transcription of a number of genes. Formation of one TorR focus at the old poles of cells requires interaction with the MreB and DnaK proteins, and ATP, suggesting that TorR delivery requires cytoskeleton organization and ATP. Further, absence of the protein–protein interactions and ATP leads to loss in function of TorR as a transcription factor. We propose a mechanism for timing of cell-cycle-dependent gene transcription, where a transcription factor interacts with its target genes during a specific period of the cell cycle by limiting its own spatial distribution

Mutations of DnaA-boxes in the oriR region increase replication frequency of the MiniR1–1 plasmid

Abstract Background The MiniR1–1 plasmid is a derivative of the R1 plasmid, a low copy cloning vector. Results Nucleotide sequencing analysis shows that the MiniR1–1 plasmid is a 6316 bp circular double-stranded DNA molecule with an oriR1 (origin for replication). The plasmid carries the repA, tap, copA and bla genes, and genes for ORF1 and ORF2. MiniR1–1 contains eight DnaA-binding sites (DnaA-boxes). DnaA-box1 is in the oriR1 region and fully matched to the DnaA-box consensus sequence, and DnaA-box8, with one mismatch, is close to the copA gene. The presence of the MiniR1–1 plasmid leads to an accumulation of the D-period cells and an increase in cell size of slowly growing Escherichia coli cells, suggesting that the presence of MiniR1–1 delays cell division. Mutations in the MiniR1–1 DnaA-box1 and DnaA-box8 significantly increase the copy number of the plasmid and the mutations in DnaA-box1 also affect cell size. It is likely that titration of DnaA to DnaA-boxes negatively controls replication of the MiniR1–1 plasmid and delays cell division. Interestingly, DnaA weakly interacts with the initiator protein RepA in vivo. Conclusion DnaA regulates the copy number of MiniR1–1 as a negative factor through interacting with the RepA protein