Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.
Centrioles/genetics* ; Homozygote ; Humans ; Infertility, Male/genetics* ; Male ; Mutation ; Spermatogenesis/genetics* ; Spermatozoa

Animals ; Biological Transport, Active/physiology* ; Centrioles/metabolism* ; Cilia/metabolism* ; Mice ; Mice, Mutant Strains ; N-Acetylglucosaminyltransferases/metabolism*

This article reviews the historical development and up-to-date state of thermometric technologies for measuring human body temperature (BT) from two aspects: measurement methodology and signifi cance interpretation. Since the fi rst systematic and comprehensive study on BT and its relation to human diseases was conducted by Wunderlich in the late 19th century, BT has served as one of the most fundamental vital signs for clinical diagnosis and daily healthcare. The physiological implication of BT set point and thermoregulatory mechanisms are briefl y outlined. Infl uential determinants of BT measurement are investigated thoroughly. Three types of BT measurement, i.e., core body temperature, surface body temperature and basal body temperature, are categorized according to its measurement position and activity level. With the comparison of temperature measurement in industrial fi elds, specialties in technological and biological aspects in BT measurement are mentioned. Methodologies used in BT measurement are grouped into instrumental methods and mathematical methods. Instrumental methods utilize results of BT measurements directly from temperature-sensitive transducers and electronic instrumentations by the combination of actual and predictive measurement, invasive and noninvasive measurement. Mathematical methods use several numerical models, such as multiple regression model, autoregressive model, thermoregulatory mechanism-based model and the Kalman fi lter-based method to estimate BT indirectly from some relevant vital signs and environmental factors. Thermometry modalities are summarized on the dichotomies into invasive and noninvasive, contact and noncontact, direct and indirect, free and restrained, 1-D and n-D. Comprehensive interpretation of BT has an equal importance as the measurement of BT. Two modes to apply BT are classifi ed into real-time applications and long-term applications. With rapid advancement in IoT infrastructure, big data analytics and AI platforms, prospects for future development in thermometry and interpretation of BT are discussed.
Basal Bodies ; Body Temperature ; Delivery of Health Care ; Diagnosis ; Human Body ; Humans ; Methods ; Thermometers ; Thermometry ; Transducers ; Vital Signs

Somatic cell nuclear transfer (SCNT) has various applications in research, as well as in the medical field and animal husbandry. However, the efficiency of SCNT is low and the accurate mechanism of SCNT in murine embryo development is unreported. In general, the developmental rate of SCNT murine embryos is lower than in vivo counterparts. In previous studies, polo-like kinase 1 (Plk1) was reported to be a crucial element in cell division including centrosome maturation, cytokinesis, and spindle formation. In an initial series of experiments in this study, BI2536, a Plk1 inhibitor, was treated to in vivo-fertilized embryos and the embryos failed to develop beyond the 2-cell stage. This confirmed previous findings that Plk1 is crucial for the first mitotic division of murine embryos. Next, we investigated Plk1's localization and intensity by immunofluorescence analysis. In contrast to normally developed embryos, SCNT murine embryos that failed to develop exhibited two types of Plk1 expressions; a low Plk1 expression pattern and ectopic expression of Plk1. The results show that Plk1 has a critical role in SCNT murine embryos. In conclusion, this study demonstrated that the SCNT murine embryos fail to develop beyond the 2-cell stage, and the embryos show abnormal Plk1 expression patterns, which may one of the main causes of developmental failure of early SCNT murine embryos.
Animal Husbandry ; Cell Division ; Centrosome ; Cytokinesis ; Ectopic Gene Expression ; Embryonic Development ; Embryonic Structures ; Female ; Fluorescent Antibody Technique ; Nuclear Transfer Techniques ; Phosphotransferases ; Pregnancy

Obesity has become a common healthcare problem worldwide. Cilia are tiny hair-like organelles on the cell surface that are generated and anchored by the basal body. Non-motile primary cilia have been considered to be evolutionary rudiments until a few decades, but they are now considered as important signaling organelles because many receptors, channels, and signaling molecules are highly expressed in primary cilia. A potential role of primary cilia in metabolic regulation and body weight maintenance has been suspected based on rare genetic disorders termed as ciliopathy, such as Bardet-Biedl syndrome and Alström syndrome, which manifest as obesity. Recent studies have demonstrated involvement of cilia-related cellular signaling pathways in transducing metabolic information in hypothalamic neurons and in determining cellular fate during adipose tissue development. In this review, we summarize the current knowledge about cilia and cilia-associated signaling pathways in the regulation of body metabolism.
Adipose Tissue ; Alstrom Syndrome ; Bardet-Biedl Syndrome ; Basal Bodies ; Body Weight Maintenance ; Cilia* ; Delivery of Health Care ; Energy Metabolism* ; Hedgehogs ; Metabolism ; Neurons ; Obesity ; Organelles ; Wnt Signaling Pathway

BACKGROUND: Autoantibodies have been detected in patients with psychiatric disorders. However, there is no standard test for the detection of these autoantibodies. In this study, we analyzed autoimmune target (AIT) test results in patients with psychiatric disorders and investigated the clinical utility of the AIT test for psychiatric disorders. METHODS: We retrospectively analyzed data from patients diagnosed with psychiatric disorders between August 1995 and May 2015. Of these, 100 patients assessed using the AIT test were enrolled in this study. Data regarding positive rates, immunofluorescent patterns of AIT results, and the presence of autoimmune diseases in patients with psychiatric disorders were retrospectively collected and analyzed. RESULTS: The autoantibody-positive rate was high in patients with psychiatric disorders (70.0%, 70/100). The positive rates in patients with schizophrenia, depressive disorders, bipolar and related disorders, adjustment disorders, anxiety disorders, and others were 82.9%, 64.7%, 88.9%, 57.1%, 66.7%, and 53.8%, respectively. The most frequent pattern of immunofluorescence was a speckled pattern in 30 cases, followed by microtubule organizing center with microtubule (MTOC-MT) in 17 cases. Twenty-one patients were diagnosed with autoimmune diseases. CONCLUSIONS: In this study, the incidence of autoantibodies was high in patients with psychiatric disorders not specific to schizophrenia. This suggests that the AIT test may therefore have the potential to be a screening test for psychiatric disorders. Further, additional AIT tests in patients with psychiatric disorders may help to clarify the relationships between psychiatric disorders and autoimmune disease.
Adjustment Disorders ; Anxiety Disorders ; Autoantibodies ; Autoimmune Diseases ; Bipolar and Related Disorders ; Depressive Disorder ; Fluorescent Antibody Technique ; Humans ; Incidence ; Mass Screening ; Microtubule-Organizing Center ; Microtubules ; Retrospective Studies ; Schizophrenia

In recent years, several radiotracers that selectively bind to pathological tau proteins have been developed. Evidence is emerging that binding patterns of in vivo tau positron emission tomography (PET) studies in Alzheimer's disease (AD) patients closely resemble the distribution patterns of known neurofibrillary tangle pathology, with the extent of tracer binding reflecting the clinical and pathological progression of AD. In Lewy body diseases (LBD), tau PET imaging has clearly revealed cortical tau burden with a distribution pattern distinct from AD and increased cortical binding within the LBD spectrum. In progressive supranuclear palsy, the globus pallidus and midbrain have shown increased binding most prominently. Tau PET patterns in patients with corticobasal syndrome are characterized by asymmetrical uptake in the motor cortex and underlying white matter, as well as in the basal ganglia. Even in the patients with multiple system atrophy, which is basically a synucleinopathy, ¹⁸F-flortaucipir, a widely used tau PET tracer, also binds to the atrophic posterior putamen, possibly due to off-target binding. These distinct patterns of tau-selective radiotracer binding in the various degenerative parkinsonisms suggest its utility as a potential imaging biomarker for the differential diagnosis of parkinsonisms.
Alzheimer Disease ; Basal Ganglia ; Diagnosis, Differential ; Electrons ; Globus Pallidus ; Humans ; Lewy Bodies ; Mesencephalon ; Motor Cortex ; Multiple System Atrophy ; Neurofibrillary Tangles ; Parkinsonian Disorders ; Pathology ; Positron-Emission Tomography ; Putamen ; Supranuclear Palsy, Progressive ; tau Proteins ; White Matter

Previously, we have reported that CKAP2 is involved in the maintenance of centrosome integrity, thus allowing for proper mitosis in primary hepatocytes. To understand this biological process, we identified the mitosis-specific phosphorylation sites in mouse CKAP2 and investigated CKAP’s possible role in cell cycle progression. Because we observed mouse CKAP2 depletion in amplified centrosomes and aberrant chromosomal segregation, which was rescued by ectopic expression of wild-type CKAP2, we focused on the centrosome duplication process among the various aspects of the cell cycle. Among the identified phosphorylation sites, T603 and possibly S608 were phosphorylated by CDK1–cyclin B1 during mitosis, and the ectopic expression of both T603A and S608A mutants was unable to restore the centrosomal abnormalities in CKAP2-depleted cells. These results indicated that the phosphorylation status of CKAP2 during mitosis is critical for controlling both centrosome biogenesis and bipolar spindle formation.
Animals ; Biological Processes ; Cell Cycle ; Centrosome* ; Ectopic Gene Expression ; Hepatocytes ; Mice ; Mitosis ; Phosphorylation*

Here we present an autopsy case of chronic traumatic encephalopathy (CTE) in a 36-year-old man. He had a history of febrile seizures at the age of four and was severely demented at age 10 when he was admitted to a mental hospital. He had suffered repetitive self-harm, such as frequent banging of the head on the wall in his hospital record, but he had no clear history between the ages of four and ten. Autopsy revealed global cerebral atrophy, including the basal ganglia, thalamus, hippocampus, amygdala, mammilary bodies and lateral geniculate bodies. This case showed typical pathological features of CTE. Phosphorylated tau (p-tau)-positive neurofibrillary tangles (NFTs) and neuropil threads (NT) we are widely distributed in the brain, especially in the depth of the cerebral sulci. NFT and NT were also found in the basal ganglia, thalamus, amygdala and brainstem. Scanty β-amyloid deposits were found in the motor and sensory cortices, but α-synuclein was completely negative in the brain. This example showed that CTE can occur in young ages and that even children can experience CTE dementia.
Adult ; Amygdala ; Atrophy ; Autopsy* ; Basal Ganglia ; Brain ; Brain Injuries ; Brain Injury, Chronic* ; Brain Stem ; Child* ; Dementia ; Geniculate Bodies ; Head ; Hippocampus ; Hospital Records ; Hospitals, Psychiatric ; Humans ; Neurofibrillary Tangles ; Neuropil Threads ; Pathology ; Seizures, Febrile ; Thalamus

Oligoasthenozoospermia, teratozoospermia or low sperm motility is the main cause of male infertility. Low sperm motility can be induced by abnormalities of the sperm tail structure and sperm function. The outer dense fiber protein 2 (ODF2) is a protein fiber maintaining cytoskeleton, as a major component of the mammalian sperm tail and centrosome, and its abnormality is closely related to asthenospermia. Recent studies indicate that ODF2 includes many proteins of the same name and homologous splices located in the sperm centrosomes and spindles of cleaved-embryos, necessary for animal ciliogenesis and associated with sperm capacitation. The features of ODF2 indicate that it is not a single-structural protein. This paper reviews the known functions of ODF2, paving a ground for further studies of the relationship between the ODF2 protein and fertilization.
Animals ; Asthenozoospermia ; complications ; Azoospermia ; complications ; Centrosome ; chemistry ; Cytoskeleton ; chemistry ; Heat-Shock Proteins ; physiology ; Humans ; Infertility, Male ; etiology ; Male ; Sperm Motility ; physiology ; Sperm Tail ; Spermatozoa ; physiology