Outer Arm Research Articles

Short-term skin carotenoid changes following consumption of a typical Australian diet versus a healthy Australian diet: findings from a randomised crossover feeding trial

Carotenoids, a group of phytochemicals found in plant-based foods with yellow, red, or orange pigments, have been shown to be stored in the skin upon consumption of carotenoid-rich foods(1). Skin carotenoid levels can be measured using skin reflectance spectroscopy, which assesses skin lightness (L*), redness (a*), and yellowness (b*)(2). Previous research has demonstrated significant increases in skin yellowness (b*) after a 4-week high-carotenoid diet(2). The aim was to examine shorter-term changes (two weeks) in skin yellowness following the consumption of a Healthy Australian Diet rich in carotenoids compared to a Typical Australian Diet with low carotenoid content. The study analysed data from an eight-week randomised, cross-over feeding trial involving 34 adults (53% female, aged 38.44 ± 18.05 years). Participants were randomly assigned to each diet for two weeks, separated by a two-week washout period. The Healthy Australian Diet adhered to the Australian Dietary Guidelines(3), emphasising the consumption of carotenoid-rich fruits and vegetables such as carrots, pumpkin, tomatoes, red capsicum, and sweet potatoes. In contrast, the Typical Australian Diet was formulated based on apparent consumption patterns in Australia(4) and emphasised the intake of fruits and vegetables low in beta-carotene, such as white potatoes, onions, cauliflower, and pears. Skin carotenoids were measured using skin reflectance spectroscopy at three sites (palm, inner and outer arm), and each measurement was taken thrice. Overall skin yellowness (b*) was calculated as the average of all three measurements at all three sites. Measurements were conducted at four key visits: week 0 (end of run-in; baseline 1), week 2 (post-feeding phase 1), week 4 (end of washout; baseline 2), and week 8 (post-feeding phase 2). Differential changes in skin carotenoid levels between intervention groups were assessed using linear mixed-effect models, adjusting for diet sequence, feeding phase, body fat percentage, total fat intake, and subject ID as a random variable to account for potential autocorrelation. Post-hoc pairwise comparisons were conducted to evaluate the relative effects of each diet. Although there was a trend towards higher skin yellowness (0.215 ± 0.517; p = 0.41) following consumption of the Healthy Australian diet relative to baseline, and an inverse trend following the Typical Australian Diet (−0.118 ± 0.539, p = 0.56), the difference in change between the two diets was not statistically significant (p = 0.32). Notably, baseline values within this participant cohort were higher than previously reported at b* = 16.7(1) (baseline 1 b*: 17.57 ± 2.23, baseline 2 b*: 17.71 ± 2.26), which may influence the magnitude of observable change. The findings suggest that the two-week intervention duration may be insufficient to achieve statistically significant changes in skin carotenoid levels. Future investigations into whether plasma carotenoids increase first, with skin changes occurring later, could offer valuable insights into the potential utility of this as a biomarker validation of change in fruit and vegetable intake.

Star formation histories of dwarf lenticular galaxies

ABSTRACT Star formation histories (SFHs) are essential for understanding galaxy formation and evolution. We present the mean SFHs of 148 dwarf lenticular galaxies (dS0s) derived from the Sloan Digital Sky Survey spectra. These SFHs reveal two distinct periods of active star formation. The first period, concluding approximately 6 Gyr ago, witnessed the formation of predominantly old, metal-poor (Z = 0.0004) stars, accounting for approximately 60 per cent of the stellar mass and 30 per cent of the luminosity. The scarcity of extremely metal-poor (Z = 0.0001) stars suggests pre-enrichment during the reionization era. Star formation gradually waned during this initial phase. In contrast, the second period, ending around 1 Gyr ago, exhibited a peak in the middle of the period, contributing to the formation of moderately old stellar populations with intermediate metallicity. The SFHs of dS0 galaxies show a clear dependence on stellar mass, with more massive dS0s forming stars earlier. However, we find no significant correlation with morphological properties such as outer spiral arms and nucleation. The SFHs of dS0 galaxies share many similarities with those of dwarf elliptical galaxies, suggesting a common origin, mostly not primordial.

Comparative characteristics of patients with primary ciliary dyskinesia with or without Kartagener’s syndrome

Primary ciliary dyskinesia (PCD) is a rare hereditary disease, a ciliopathy that is based on a defect in the ultrastructure of the cilia of the epithelium of the respiratory tract and similar structures. All parts of the respiratory tract are affected. About half of the patients with PCD have transposition of the internal organs (Kartagener syndrome – KS).The aim was to investigate the clinical and genetic characteristics of patients with PCD with and without KS.Methods. An assessment of clinical and genetic characteristics was performed in a sample of 127 patients with PCD, who were divided into 2 groups: patients with KS (n = 60) and without KS (n = 67). The groups were compared on the basis of their medical history (according to the PICADAR scale), clinical, instrumental and laboratory data, including the results of light and video microscopy, transmission electron microscopy (TEM) and genetic testing.Results. According to the results of comparative characterization of patients with PCD with and without KS, there were similarities in the medical history, decreased lung function indices, videomicroscopy results – ciliated epithelium beating below 6 Hz, TEM – predominance of dynein arm defect. The PICADAR score was higher in the group with KS than in the group without it; congenital heart defects and renal pathology were found more frequently in patients with KS, while hearing loss and nasal polyposis were found more frequently in patients without KS. Electron microscopy revealed defects in the outer and inner dynein arms of the cilia in 50% of patients in both groups, and a tendency to lack of the central pair of microtubules in 18% of patients without KS. The following genes responsible for PCD were found in both groups: DNAH5, CFAP300 and HYDIN. DNAH5 gene variants were more common for KS patients (61.1%), while HYDIN gene variants were only found in patients with PCD without KS (15.8%).Conclusion. The identified differences may help in the diagnosis of the groups studied.

Gene dosage of independent dynein arm motor preassembly factors influences cilia assembly in Chlamydomonas reinhardtii.

Motile cilia assembly utilizes over 800 structural and cytoplasmic proteins. Variants in approximately 58 genes cause primary ciliary dyskinesia (PCD) in humans, including the dynein arm (pre)assembly factor (DNAAF) gene DNAAF4. In humans, outer dynein arms (ODAs) and inner dynein arms (IDAs) fail to assemble motile cilia when DNAAF4 function is disrupted. In Chlamydomonas reinhardtii, a ciliated unicellular alga, the DNAAF4 ortholog is called PF23. The pf23-1 mutant assembles short cilia and lacks IDAs, but partially retains ODAs. The cilia of a new null allele (pf23-4) completely lack ODAs and IDAs and are even shorter than cilia from pf23-1. In addition, PF23 plays a role in the cytoplasmic modification of IC138, a protein of the two-headed IDA (I1/f). As most PCD variants in humans are recessive, we sought to test if heterozygosity at two genes affects ciliary function using a second-site non-complementation (SSNC) screening approach. We asked if phenotypes were observed in diploids with pairwise heterozygous combinations of 21 well-characterized ciliary mutant Chlamydomonas strains. Vegetative cultures of single and double heterozygous diploid cells did not show SSNC for motility phenotypes. When protein synthesis is inhibited, wild-type Chlamydomonas cells utilize the pool of cytoplasmic proteins to assemble half-length cilia. In this sensitized assay, 8 double heterozygous diploids with pf23 and other DNAAF mutations show SSNC; they assemble shorter cilia than wild-type. In contrast, double heterozygosity of the other 203 strains showed no effect on ciliary assembly. Immunoblots of diploids heterozygous for pf23 and wdr92 or oda8 show that PF23 is reduced by half in these strains, and that PF23 dosage affects phenotype severity. Reductions in PF23 and another DNAAF in diploids affect the ability to assemble ODAs and IDAs and impedes ciliary assembly. Thus, dosage of multiple DNAAFs is an important factor in cilia assembly and regeneration.

Temperature-dependent augmentation of ciliary motility by the TRP2 channel in Chlamydomonas reinhardtii.

Temperature is a critical factor for living organisms. Many microorganisms migrate toward preferable temperatures, and this behavior is called thermotaxis. In this study, the molecular and physiological bases for thermotaxis are examined in Chlamydomonas reinhardtii. A mutant with knockout of a transient receptor potential (TRP) channel, trp2-3, showed defective thermotaxis. The swimming velocity and ciliary beat frequency of wild-type Chlamydomonas increase with temperature; however, this temperature-dependent enhancement of motility was almost absent in the trp2-3 mutant. Wild-type Chlamydomonas showed negative thermotaxis, but mutants deficient in the outer or inner dynein arm showed positive thermotaxis and a defect in temperature-dependent increase in swimming velocity, suggesting involvement of both dynein arms in thermotaxis.

A Case of a 50-Year-Old Female with Dermatomyositis Secondary to a Paraneoplasm (Infiltrating Ductal Carcinoma, Grade 2)

Introduction: Dermatomyositis is an autoimmune disorder with an incidence of 5 to 10 per 1 million per year. 10 to 20% of patients with adult-onset Dermatomyositis have an underlying malignancy. There are currently no specific cutaneous markers for Paraneoplastic Dermatomyositis. This case highlights a patient with uncommon features of paraneoplasm after breast malignancy. Case Report: A 50-year-old female with Infiltrating Ductal Carcinoma, presented with patches on the face, neck, chest, upper back, outer arms, dorsal hands, thighs, hair loss and weakness. Histopathology revealed widened basal layer vacuolization with widened spaces between collagen bundles filled with mucin deposition, and pigment incontinence in the papillary dermis. Direct immunofluorescence showed granular deposits of IgG, C3, IgM and IgA in the basement membrane zone, which are consistent with Dermatomyositis. The patient was prescribed with Clobetasol ointment mixed equally with petrolatum on the body and Mometasone cream on the face. She was subsequently started on Prednisone at 0.5 mkd with eventual tapering, Omeprazole, and Calcium + Vitamin D tablet daily. Hydroxychloroquine 200 mg/tab daily was added. Referral to Rheumatology for co-management and Surgery for management of the breast mass was also done. Conclusion: This case emphasizes the rare occurrence of a Paraneoplastic Dermatomyositis following a diagnosis of breast malignancy. A careful review upon diagnosis may detect occult malignancies especially in patients who present primarily with cutaneous Dermatomyositis. Clinicopathologic correlation and a multi-disciplinary approach, with Surgery, Oncology, Rheumatology and Dermatopathology are needed to identify the underlying cause and facilitate successful treatment of a neoplasm followed by improvement of Dermatomyositis.

Next-Generation Sequencing-Based Copy Number Variation Analysis in Chinese Patients with Primary Ciliary Dyskinesia Revealed Novel DNAH5 Copy Number Variations.

The online version contains supplementary material available at 10.1007/s43657-023-00130-0.

Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation.

Cytosine base editing achieves C•G-to-T•A substitutions and can convert four codons (CAA/CAG/CGA/TGG) into STOP-codons (induction of STOP-codons, iSTOP) to knock out genes with reduced mosaicism. iSTOP enables direct phenotyping in founders' somatic cells, but it remains unknown whether this works in founders' germ cells so as to rapidly reveal novel genes for fertility. Here, we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders' germ cells: Cfap43-iSTOP male founders manifest expected sperm features resembling human "multiple morphological abnormalities of the flagella" syndrome (i.e., MMAF-like features), while oocytes of Zp3-iSTOP female founders have no zona pellucida. We further illustrate iSTOP's utility for dissecting the functions of unknown genes with Ccdc183, observing MMAF-like features and male infertility in Ccdc183-iSTOP founders, phenotypes concordant with those of Ccdc183-KO offspring. We ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar transport. Our study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation, and rapidly reveals the essentiality of Ccdc183 in fertility, thus providing a time-saving approach for validating genetic defects (like nonsense mutations) for human infertility.

Methylation of ciliary dynein motors involves the essential cytosolic assembly factor DNAAF3/PF22

Axonemal dynein motors drive ciliary motility and can consist of up to twenty distinct components with a combined mass of ~2 MDa. In mammals, failure of dyneins to assemble within the axonemal superstructure leads to primary ciliary dyskinesia. Syndromic phenotypes include infertility, rhinitis, severe bronchial conditions, and situs inversus. Nineteen specific cytosolic factors (Dynein Axonemal Assembly Factors; DNAAFs) are necessary for axonemal dynein assembly, although the detailed mechanisms involved remain very unclear. Here, we identify the essential assembly factor DNAAF3 as a structural ortholog of S-adenosylmethionine-dependent methyltransferases. We demonstrate that dynein heavy chains, especially those forming the ciliary outer arms, are methylated on key residues within various nucleotide-binding sites and on microtubule-binding domain helices directly involved in the transition to low binding affinity. These variable modifications, which are generally missing in a Chlamydomonas null mutant for the DNAAF3 ortholog PF22 (DAB1), likely impact on motor mechanochemistry fine-tuning the activities of individual dynein complexes.

Local modeling method for multi-field coupling of electric-magnetic-thermal-structure of pulsed high current linear driving device

The pulsed high current linear driving device operates under extreme conditions, and various forms of metal damages will reduce the service life of the device. At present, the multi-physics coupling mechanism of pulsed high current linear driving device is still unclear, and the multi-parameter diagnosis method in the laboratory environment is limited. Therefore, it is urgent to clarify the evolution process of multiple physical parameters through numerical modeling methods, in order to guide the optimization of the overall performance and improve the service life of the device. In this work, mathematical and physical models of electromagnetic field, temperature field and structural field under dynamic conditions are established. The local solution is carried out by using the characteristics of rail reverse motion and the invariant physical quantities at the distal end of the contact. The constraint equations of the non-equipotential surface of the rail entrance and the armature-rail interface conditions under the technical framework are derived. The constraint equations are applied by the penalty function method. The model also takes into account the practical factors such as the temperature dependence of the material properties, thermal stresses, and the frictional heat of the contact surface. The finite element discrete format of the electromagnetic field and the temperature field is solved in the form of Euler’s backward differentiation, and the structural field is solved by the Newmark method. The reliability of the model is verified by comparing the calculation results with the numerical tools EMAP3D and Comsol under the same configuration and input conditions, as well as related experiments. Through the numerical simulation of the C-type armature, the typical evolution process of the corresponding multi-parameter is obtained. During sliding electrical contact, the velocity skin effect becomes more pronounced with velocity increasing. The current is gradually concentrated on the surface of the rail, and the highest current density is found at the rear edge of the contact surface and at the edge of the outer arm of the armature. Moreover, the magnetic induction intensity at the tail of the contact surface continues to shrink over time. The heat-concentrated region appears at the top edge of the contact surface, and with time going by, it extends along the sliding direction and bottom direction of the armature. In addition, there is peak stress in the front of the rail contact and significant stress at the armature throat. When the local stress at the throat of the armature exceeds the corresponding yield strength, it can cause serious deformation or even fracture of the armature.

Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment.

Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States, with an estimated 52,000 deaths in 2023. Though significant progress has been made in both diagnosis and treatment of CRC in recent years, genetic heterogeneity of CRC-the culprit for possible CRC relapse and drug resistance, is still an insurmountable challenge. Thus, developing more effective therapeutics to overcome this challenge in new CRC treatment strategies is imperative. Genetic and epigenetic changes are well recognized to be responsible for the stepwise development of CRC malignancy. In this review, we focus on detailed genetic alteration information about the nuclear factor (NF)-κB signaling, including both NF-κB family members, and their regulators, such as protein arginine methyltransferase 5 (PRMT5), and outer dynein arm docking complex subunit 2 (ODAD2, also named armadillo repeat-containing 4, ARMC4), etc., in CRC patients. Moreover, we provide deep insight into different CRC research models, with a particular focus on patient-derived xenografts (PDX) and organoid models, and their potential applications in CRC research. Genetic alterations on NF-κB signaling components are estimated to be more than 50% of the overall genetic changes identified in CRC patients collected by cBioportal for Cancer Genomics; thus, emphasizing its paramount importance in CRC progression. Consequently, various genetic alterations on NF-κB signaling may hold great promise for novel therapeutic development in CRC. Future endeavors may focus on utilizing CRC models (e.g., PDX or organoids, or isogenic human embryonic stem cell (hESC)-derived colonic cells, or human pluripotent stem cells (hPSC)-derived colonic organoids, etc.) to further uncover the underpinning mechanism of these genetic alterations in NF-κB signaling in CRC progression. Moreover, establishing platforms for drug discovery in dishes, and developing Biobanks, etc., may further pave the way for the development of innovative personalized medicine to treat CRC in the future.

A multiwavelength study of spiral structure in galaxies. II. Spiral arms in deep optical observations

ABSTRACT In this paper, we look to analyse the spiral features of grand-design, multiarmed, and flocculent spiral galaxies using deep optical imaging from DESI Legacy Imaging Surveys. We explore the resulting distributions of various characteristics of spiral structure beyond the optical radius, such as the distributions of azimuthal angle, the extent of spiral arms, and of the spiral arm widths for the aforementioned galaxy classes. We also compare the measured properties for isolated galaxies and galaxies in groups and clusters. We find that, on average, compared to multiarmed and flocculent spiral galaxies, the spiral arms of grand-design galaxies exhibit slightly larger azimuthal angles, greater extent, and larger widths in the periphery of the galaxy. Furthermore, on average, isolated galaxies tend to have slightly smaller widths of outer spiral arms compared to galaxies in tight environments, which is likely related to the tidally induced mechanism for generating wider outer spiral arms. We also report that breaks of the disc surface brightness profiles are often related to the truncation of spiral arms in galaxies.

Growing local arm inferred by the breathing motion

ABSTRACT Theoretical models of spiral arms suggest that the spiral arms provoke a vertical bulk motion in disc stars. By analysing the breathing motion, a coherent asymmetric vertical motion around the mid-plane of the Milky Way disc, with Gaia DR3, we found that a compressing breathing motion presents along the Local arm. On the other hand, with an N-body simulation of an isolated Milky Way-like disc galaxy, we found that the transient and dynamic spiral arms induce compressing breathing motions when the arms are in the growth phase, while the expanding breathing motion appears in the disruption phase. The observed clear alignment of the compressing breathing motion with the Local arm is similar to what is seen in the growth phase of the simulated spiral arms. Hence, we suggest that the Local arm’s compressing breathing motion can be explained by the Local arm being in the growth phase of a transient and dynamic spiral arm. We also identified the tentative signatures of the expanding breathing motion associated with the Perseus arm and also the Outer arm coinciding with the compressing breathing motion. This may infer that the Perseus and Outer arms are in the disruption and growth phases, respectively.

Achilles Tendon Ruptures: Limited Incision Repair

Achilles tendon ruptures are a common injury, and a steadily rising incidence has been noted since the middle of the 20th century. Conservative management is a recognized treatment method, but it bears a higher risk of tendon rerupture compared with surgical treatment. Standard open surgery, however, can lead to complications, such as wound complications and surgical site infection. Hence, efforts have been put into the development of alternative surgical techniques to lower the risk of complications. In the 1970s, Ma and Griffith introduced percutaneous tendon repair by limiting the incision to 6 stab wounds. Subsequently, the open and percutaneous approaches have been merged into limited incision procedures, which include the advantages of both: visual control as well as smaller incisions. The primary limited incision approach consisted in using twisted Kirschner wires as suture guides. They were replaced by specific guiding instruments, such as the Achillon and Percutaneous Achilles Repair System (PARS) device, which rendered the limited incision procedure safer and more standardized. The instruments consist of 4 arms: The outer arms facilitate needle introduction by predetermined holes, the inner arms allow for suture passage exclusively underneath the tendon sheath. The minimally invasive procedures may reduce complication rates, especially regarding wound healing and infection. Limited incision techniques also may reduce sural nerve injury. Level of Evidence: Diagnostic Level V—expert opinion. See Instructions for Authors for a complete description of levels of evidence.

The impact of contact and contactless interactions between the meta-atoms on terahertz bound states in the continuum

The excitation and manipulation of symmetry-protected bound states in the continuum (SP-BIC) is significantly valuable for metasurface-based biosensors. The interactions between adjacent meta-atoms determine the fundamental properties of SP-BIC; however, this topic has not been profoundly explored. In this work, we experimentally and numerically investigate the effects of contactless and contact interactions between adjacent dual-gap split-ring resonators (DSRRs) on the SP-BIC. We demonstrate that there is only one SP-BIC at 0.9 THz when the incident radiation polarization is parallel to the gap in both contactless and contact coupling conditions. When the polarization is vertical to the gap, the individual SP-BIC shifts the frequency to 0.8 THz under contactless coupling. Under contact coupling, the SP-BIC degrades to be an electromagnetically induced transparency (EIT) windows at 0.8 THz. We calculated a 3.6 ps group delay of slow light for EIT. Numerical simulations indicate that the combination of one magnetic dipole (MD) in the inner arm and another electric dipole in the outer arm of DSRR results in quasi-BIC at 0.9 THz and 0.8 THz under contactless coupling. Under contact coupling conditions, the formation of quasi-BIC at 0.9 THz is similar to contactless coupling. However, two MDs of opposite polarity results in the EIT windows at 0.8 THz. Our results reveal excitation and manipulation of terahertz SP-BIC via contactless and contact coupling, which is significant for the innovation of terahertz biosensors.

ODAD1 variants resulting from splice-site mutations retain partial function and cause primary ciliary dyskinesia with outer dynein arm defects.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder caused by defects in motile ciliary function and/or structure. Outer dynein arm docking complex subunit 1 (ODAD1) is an important component of the outer dynein arm docking complex (ODA-DC). To date, 13 likely pathogenic mutations of ODAD1 have been reported. However, the pathogenesis of ODAD1 mutations remains elusive. To investigate the pathogenesis of splice-site mutations in ODAD1 discovered in this study and those reported previously, molecular and functional analyses were performed. Whole-exome sequencing revealed a compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) in a patient with PCD, with c.598-2A>C being a novel mutation that resulted in two mutant transcripts. The compound mutation in ODAD1 (c.71-2A>C; c.598-2A>C) led to aberrant splicing that resulted in the absence of the wild-type ODAD1 and defects of the outer dynein arm in ciliary axonemes, causing a decrease in ciliary beat frequency. Furthermore, we demonstrated that the truncated proteins resulting from splice-site mutations in ODAD1 could retain partial function and inhibit the interaction between wild-type ODAD1 and ODAD3. The results of this study expand the mutational and clinical spectrum of PCD, provide more evidence for genetic counseling, and offer new insights into gene-based therapeutic strategies for PCD.

N-Terminal Processing and Modification of Ciliary Dyneins.

Axonemal dyneins are highly complex microtubule motors that power ciliary motility. These multi-subunit enzymes are assembled at dedicated sites within the cytoplasm. At least nineteen cytosolic factors are specifically needed to generate dynein holoenzymes and/or for their trafficking to the growing cilium. Many proteins are subject to N-terminal processing and acetylation, which can generate degrons subject to the AcN-end rule, alter N-terminal electrostatics, generate new binding interfaces, and affect subunit stoichiometry through targeted degradation. Here, we have used mass spectrometry of cilia samples and electrophoretically purified dynein heavy chains from Chlamydomonas to define their N-terminal processing; we also detail the N-terminal acetylase complexes present in this organism. We identify four classes of dynein heavy chain based on their processing pathways by two distinct acetylases, one of which is dependent on methionine aminopeptidase activity. In addition, we find that one component of both the outer dynein arm intermediate/light chain subcomplex and the docking complex is processed to yield an unmodified Pro residue, which may provide a setpoint to direct the cytosolic stoichiometry of other dynein complex subunits that contain N-terminal degrons. Thus, we identify and describe an additional level of processing and complexity in the pathways leading to axonemal dynein formation in cytoplasm.

Outer dynein arm docking complex subunit 2 polymorphism rs7893462 modulates hepatocellular carcinoma susceptibility and can serve as an overall survival biomarker for hepatitis B virus-related hepatocellular carcinoma after hepatectomy: a cohort study with a long-term follow-up

BackgroundGenetic variants of outer dynein arm docking complex subunit 2 (ODAD2) have been reported to be closely associated with primary ciliary dyskinesia and colorectal cancer in previous studies, but the association of genetic variants of ODAD2 with hepatocellular carcinoma (HCC) has not been reported.MethodsWe enrolled 80 healthy subjects and 468 Guangxi hepatitis B virus (HBV)-related HCC patients in this study. A case–control study method was used to explore the association of different ODAD2-rs7893462 genotypes with hepatocarcinogenesis. A comprehensive survival analysis was used to explore the association of rs7893462 with the prognosis of HBV-related HCC in Guangxi.ResultsThrough a case–control study, we observed that patients carrying the G allele of rs7893462 had a markedly increased susceptibility to hepatocarcinogenesis (odds ratio = 1.712, 95% confidence interval = 1.032–2.839, P = 0.037). We found that there were significant prognosis differences among three different genotypes of rs7893462. Nomogram analysis suggested that the contribution of rs7893462 polymorphisms to the prognosis of HBV-related HCC was second only to the BCLC stage. Stratified survival analysis suggested that the AG genotype of rs7893462 was an independent prognostic risk factor for HBV-related HCC. Joint effect survival analysis also observed that the AG genotype of rs7893462 combined with clinical parameters could significantly identify HBV-related HCC patients with different prognostic outcomes more accurately, and the AG genotype was also observed to be independent of clinical factors in HBV-related HCC survival.ConclusionThe ODAD2-rs7893462 polymorphisms can be used as an independent prognostic indicator of HBV-related HCC overall survival and are significantly associated with susceptibility to hepatocarcinogenesis.

PIH1D3-knockout rats exhibit full ciliopathy features and dysfunctional pre-assembly and loading of dynein arms in motile cilia.

Background: Recessive mutation of the X-linked gene, PIH1 domain-containing protein 3 (PIH1D3), causes familial ciliopathy. PIH1D3 deficiency is associated with the defects of dynein arms in cilia, but how PIH1D3 specifically affects the structure and function of dynein arms is not understood yet. To gain insights into the underlying mechanisms of the disease, it is crucial to create a reliable animal model. In humans, rats, and mice, one copy of the PIH1D3 gene is located on the X chromosome. Interestingly, mice have an additional, intronless copy of the Pih1d3 gene on chromosome 1. To develop an accurate disease model, it is best to manipulate the X-linked PIH1D3 gene, which contains essential regulatory sequences within the introns for precise gene expression. This study aimed to develop a tailored rat model for PIH1D3-associated ciliopathy with the ultimate goal of uncovering the intricate molecular mechanisms responsible for ciliary defects in the disease. Methods: Novel Pih1d3-knockout (KO) rats were created by using TALEN-mediated non-homologous DNA recombination within fertilized rat eggs and, subsequently, underwent a comprehensive characterization through a battery of behavioral and pathological assays. A series of biochemical and histological analyses were conducted to elucidate the identity of protein partners that interact with PIH1D3, thus shedding light on the intricate molecular mechanisms involved in this context. Results: PIH1D3-KO rats reproduced the cardinal features of ciliopathy including situs inversus, defects in spermatocyte survival and mucociliary clearance, and perinatal hydrocephalus. We revealed the novel function of PIH1D3 in cerebrospinal fluid circulation and elucidated the mechanism by which PIH1D3 deficiency caused communicating hydrocephalus. PIH1D3 interacted with the proteins required for the pre-assembly and uploading of outer (ODA) and inner dynein arms (IDA), regulating the integrity of dynein arm structure and function in cilia. Conclusion: PIH1D3-KO rats faithfully reproduced the cardinal features of ciliopathy associated with PIH1D3 deficiency. PIH1D3 interacted with the proteins responsible for the pre-assembly and uploading of dynein arms in cilia, and its deficiency led to dysfunctional cilia and, thus, to ciliopathy by affecting the pre-assembly and uploading of dynein arms. The resultant rat model is a valuable tool for the mechanistic study of PIH1D3-caused diseases.

Morphological Decomposition of the Early-type Spiral Galaxy M81 (NGC 3031)

This paper presents a morphological investigation of the early-type spiral galaxy M81 (NGC 3031) through decomposition by fitting radial profiles of surface brightness using the software GALFIT, aimed at exploring structural components of M81 and quantifying their morphology. In this work, we adopt 6 types of decompositions with different numbers of morphological components, among which the most complicated one contains 5 components such as a bulge, a disk, a pair of outer spiral arms, a pair of inner spiral arms, and a galactic nucleus. The results show that, M81 hosts a classical bulge with the Sérsic index ∼ 5.0; the morphology and the luminosity for the bulge are almost constant in the different decomposition types. The disk of M81 has the Sérsic index ∼ 1.2 but the morphology and the luminosity are found sensitive to the inclusion of the inner spiral arms in the decomposition or not. The results of this work indicate that the combination of individual substructures has a considerable impact on the morphology of the galaxy as a mixture. On the basis of the results, the usability of the different types of decomposition is suggested in this work. The three-component decomposition, i.e., bulge + disk + nucleus, is applicable to statistics of large samples of galaxies; more complicated decomposition with spiral arms taken into account is suitable for precise measurements of individual galaxies in small samples. This work is based on the single-band Spitzer-The Infrared Array Camera (IRAC) 4.5 μm image. In the future, we will carry out multi-wavelength decomposition, for the purpose of investigating spectral energy distributions and stellar population properties for the galactic substructures, and thereby deduce their formation history and evolution processes.