Abnormal outer and inner retina in a mouse model of Huntington’s disease with age

Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction and cognitive decline. While retinal abnormalities have been documented in some HD patients and animal models, the nature of these abnormalities—specifically whether they originate in the inner or outer retina—remains unclear, particularly regarding their progression with age. This study investigates the retinal structure and function in HD transgenic mice (R6/1) compared to C57BL/6 J control mice at 2, 4, and 6 months of age, encompassing both pre-symptomatic and symptomatic stages of HD. Pathological assessments of the striatum and evaluations of motor function confirmed significant HD-related alterations in R6/1 mice at 6 months. Visual function was subsequently analyzed, accompanied by immunofluorescent staining of retinal and optic nerve tissues over time. Our findings revealed that R6/1 mice exhibited pronounced HD symptoms at 6 months, characterized by neuronal loss in the striatum and impaired locomotor abilities. Functionally, visual acuity declined at 6 months, while retinal light responses began to deteriorate by 4 months. Structurally, R6/1 mice demonstrated a global reduction in cone opsin expression as early as 2 months, with a decrease in rhodopsin levels at 4 months, alongside a thinner retinal structure compared to controls. Notably, rod bipolar cell populations were decreased at 6 months, exhibiting shorter dendritic branches and reduced synaptic connections with photoreceptors in the outer retina. Additionally, ganglion cell numbers in the inner retina decreased at 6 months, accompanied by aberrant neural fibers in the optic nerve. Microglial activation was evident at 4 months, while astrocytic activation was observed at 6 months. Aggregates of mutant huntingtin (mHTT) were first detected in the ganglion cell layer and optic nerve at 2 months, subsequently disseminating throughout all retinal layers with advancing age. These results indicate that retinal pathology in R6/1 mice manifests earlier in the outer retina than in the inner retina, which does not align with the progression of mHTT aggregation. Consequently, the R6/1 mouse retina may serve as a more effective model for elucidating the mechanisms underlying HD and evaluating potential therapeutic strategies, rather than functioning as an early diagnostic tool for the disease

Modulation of local immunity by the vaginal microbiome is associated with triggering spontaneous preterm birth

ObjectiveThis study aimed to identify immune states associated with a high risk of preterm birth by immunophenotyping in pregnant populations, and to elucidate the characteristics of immune subtypes and their relationships with preterm birth. Additionally, it sought to uncover the microbial composition and functional characteristics of immune states linked to preterm birth, and to evaluate the impact of bacterial interactions on the initiation of preterm birth.MethodsUtilizing 16S rRNA sequencing data and local immune factor expression data from a publicly available longitudinal pregnancy cohort, we conducted immunophenotyping through unsupervised clustering of the immune factors. We compared the differences in vaginal microbiota richness, diversity, and composition between identified immune subtypes using α and β diversity analysis. Signature microbiotas were identified using LEfSe analysis, and functional pathway enrichment variations were analyzed using PICRUSt2. Bidirectional mediation analysis was employed to construct a network of mediating roles, and preliminary in vitro validation of the Microbial-Cytokine-Preterm Birth pathway was performed to explore the effects of microbial and immune characteristics on vaginal epithelial cell function.ResultsPregnant women were categorized into three immune subtypes based on local immune status. Microbial functional analysis identified 31 distinct functional pathways, six of which were downregulated in the preterm birth and excessive inflammatory response group. Significant differences in vaginal microbial diversity and composition were observed among pregnant women with different immune subtypes. Bidirectional mediation analysis revealed multiple intermediary roles in preterm birth, highlighting C3b/iC3b and IL-8 in mid-pregnancy and IgE and IgM in late pregnancy.ConclusionThis study classified pregnant women into three immune subtypes, with the excessive inflammatory response subtype showing a higher predisposition to preterm birth. Mid-pregnancy immune status emerged as a key indicator of preterm birth risk, associated with the vaginal microbiome composition. Microorganisms affected the occurrence of preterm birth by modulating immune factor levels, with time-specific mediation roles observed. Lactobacillus crispatus demonstrated potential in protecting against preterm birth by modulating vaginal immune status

Analysis of Large Phenotypic Variability of EEC and SHFM4 Syndromes Caused by K193E Mutation of the TP63 Gene

EEC (ectrodactyly, ectodermal dysplasia, clefting; OMIM 604292) is an autosomal dominant developmental disorder resulting mainly from pathogenic mutations of the DNA-binding domain (DBD) of the TP63 gene. In this study, we showed that K193E mutation in nine affected individuals of a four-generation kindred with a large degree of phenotypic variability causes four different syndromes or TP63-related disorders: EEC, Ectrodactyly-ectodermal dysplasia (EE), isolated ectodermal dysplasia, and isolated Split Hand/Foot Malformation type 4 (SHFM4). Genotype-phenotype and DBD structural modeling analysis showed that the K193-located loop L2-A is associated with R280 through hydrogen bonding interactions, while R280 mutations also often cause large phenotypic variability of EEC and SHFM4. Thus, we speculate that K193 and several other DBD mutation-associated syndromes may share similar pathogenic mechanisms, particularly in the case of the same mutation with different phenotypes. Our study and others also suggest that the phenotypic variability of EEC is attributed, at least partially, to genetic and/or epigenetic modifiers

Antipodal Linearly Tapered Slot Antenna with Quasi-Hemispherical Pattern Using Subwavelength Elements

Antennas with quasi-hemispherical radiation patterns are preferred in many wide−area wireless communication systems which require the signals to uniformly cover a wide two−dimensional region. In this work, a simple but effective beamwidth broadening technique based on an antipodal linearly tapered slot antenna (ALTSA) is first proposed and then experimentally verified. Compared with most of the reported designs, the proposed antenna can significantly widen beamwidth and achieve a quasi-hemispherical radiation pattern without increasing the overall size and structural complexity. Only two rows of subwavelength metallic elements (eight elements in total) are simply and skillfully printed at specified positions on the dielectric substrate (relative permittivity εr = 2.94 and thickness h = 1.5 mm) of a general ALTSA whose peak gain is 11.7 dBi, approximately 200% half-power beamwidth (HPBW) enlargement can be obtained in all cut-planes containing the end-fire direction at the central frequency of 15 GHz, and the HPBW extensions in different cut-planes have good consistency. Thus, a quasi-hemispherical beam pattern can be acquired. Thanks to the simplicity of this method, the antenna size and structural complexity do not increase, resulting in the characteristics of easy fabrication and integration, being lightweight, and high reliability. This proposed method provides a good choice for wide−beam antenna design and will have a positive effect on the potential applications of wide-area wireless communication systems.</jats:p

High Efficiency Covering Technology for Covered Yarn Production: Controlling the Spandex Yarn Draw Ratio

This paper proposes a new covered yarn system in which the tension of spandex elastic yarn drawing is controlled. By analysing the relationship between the draw ratio and yarn tension, it was verified that the new tension controlled drawing system is feasible and results in yarns of superior quality and process stability. </jats:p

Antipodal Linearly Tapered Slot Antenna with Quasi-Hemispherical Pattern Using Subwavelength Elements

Antennas with quasi-hemispherical radiation patterns are preferred in many wide&minus;area wireless communication systems which require the signals to uniformly cover a wide two&minus;dimensional region. In this work, a simple but effective beamwidth broadening technique based on an antipodal linearly tapered slot antenna (ALTSA) is first proposed and then experimentally verified. Compared with most of the reported designs, the proposed antenna can significantly widen beamwidth and achieve a quasi-hemispherical radiation pattern without increasing the overall size and structural complexity. Only two rows of subwavelength metallic elements (eight elements in total) are simply and skillfully printed at specified positions on the dielectric substrate (relative permittivity &epsilon;r = 2.94 and thickness h = 1.5 mm) of a general ALTSA whose peak gain is 11.7 dBi, approximately 200% half-power beamwidth (HPBW) enlargement can be obtained in all cut-planes containing the end-fire direction at the central frequency of 15 GHz, and the HPBW extensions in different cut-planes have good consistency. Thus, a quasi-hemispherical beam pattern can be acquired. Thanks to the simplicity of this method, the antenna size and structural complexity do not increase, resulting in the characteristics of easy fabrication and integration, being lightweight, and high reliability. This proposed method provides a good choice for wide&minus;beam antenna design and will have a positive effect on the potential applications of wide-area wireless communication systems

Wysokowydajna technologia produkcji przędzy oplatanej z zastosowaniem kontroli współczynnika rozciągania przędzy spandexowej

This paper proposes a new covered yarn system in which the tension of spandex elastic yarn drawing is controlled. By analysing the relationship between the draw ratio and yarn tension, it was verified that the new tension controlled drawing system is feasible and results in yarns of superior quality and process stability.W pracy zaproponowano nowy system wytwarzania przędzy oplatanej, w którym kontrolowane jest naprężenie rozciągania przędzy elastycznej spandex. Analizując zależność między współczynnikiem rozciągania a naprężeniem przędzy, zweryfikowano, że zaproponowany system ciągnienia z kontrolowanym naprężeniem jest wykonalny i zapewnia wytworzenie przędzy o najwyższej jakości z zachowaniem stabilności procesu

Neuroimmune Crosstalk in Rheumatoid Arthritis

Recent studies have demonstrated that immunological disease progression is closely related to abnormal function of the central nervous system (CNS). Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis-based systemic immune disease of unknown etiology. In addition to joint pathological damage, RA has been linked to neuropsychiatric comorbidities, including depression, schizophrenia, and anxiety, increasing the risk of neurodegenerative diseases in life. Immune cells and their secreted immune factors will stimulate the peripheral and central neuronal systems that regulate innate and adaptive immunity. The understanding of autoimmune diseases has largely advanced insights into the molecular mechanisms of neuroimmune interaction. Here, we review our current understanding of CNS comorbidities and potential physiological mechanisms in patients with RA, with a focus on the complex and diverse regulation of mood and distinct patterns of peripheral immune activation in patients with rheumatoid arthritis. And in our review, we also discussed the role that has been played by peripheral neurons and CNS in terms of neuron mechanisms in RA immune challenges, and the related neuron-immune crosstalk