Autosomal recessive primary microcephaly (MCPH) is a rare congenital disorder characterized by a below average brain volume at birth and is associated with neurodevelopmental disorders such as growth ...retardation and intellectual disability. Mutations in ANKLE2 have been identified as one of the causes of MCPH (MCPH16). ANKLE2 is a target molecule of the Zika virus NS4a protein that interferes with ANKLE2 function, resulting in severe microcephaly. ANKLE2 is essential for organizing the nuclear envelope and chromatin structures during the mitotic-end process via barrier to autointegration factor (BAF) dephosphorylation. However, the precise mechanism by which the loss of ANKLE2 function causes the pathogenesis of microcephaly remains unclear. In this study, we generated Ankle2-deficient zebrafish (ankle2−/−) with a significant reduction in brain size compared with that of their control siblings. The ankle2−/− brain showed a significant decrease in the number of radial glial progenitor cells, suggesting that Ankle2 deficiency in zebrafish causes neurogenesis defects. Furthermore, ankle2−/− male zebrafish showed infertility owing to defects in spermatogenesis. Notably, microcephaly was overcome by vrk1 morpholino knockdown or vrk1 heterozygous deletion. In addition, spermatogenesis in ankle2−/− zebrafish males was partially restored by the vrk1 heterozygous deletion, although infertility was not resolved. These results indicate that ANKLE2 and VRK1 coordinate with each other for BAF phosphorylation to maintain normal mitosis during neurogenesis and spermatogenesis.
•Ankle2−/− zebrafish displayed microcephaly.•Ankle2 plays an important role in nuclear envelope formation.•Ankle2−/− zebrafish showed spermatogenesis defects.•Morpholino knockdown or heterozygous deletion of vrk1 alleviated microcephaly.•Reduced expression of Vrk1 could not restore fertility in ankle2−/− zebrafish.
Organic amendments are important sources of nitrous oxide (N2O) emissions from agricultural soils. In 2020, the total amount of N in organic amendments applied to Japanese agricultural soils (440 ...ktN) was larger than that of synthetic fertilizer (374 ktN). However, N2O emissions from organic amendments were estimated by using the country-specific N2O emission factor (EF) for synthetic fertilizer (0.31 % for rice paddy, 2.9 % for tea, and 0.62 % for other crops) in the National Greenhouse Gas Inventory Report of Japan. Thus, we conducted a N2O flux measurement campaign at 12 different experimental sites across Japan to estimate fertilizer-induced N2O EFs for major organic amendments in Japan, that is, poultry manure compost, swine manure compost, cattle manure compost, and organic fertilizer pellets. In addition, we conducted systematic review of N2O emissions and EFs for organic amendments, including data from our measurement campaign and published data from peer-reviewed papers in Japan. The final dataset, including the field measurement campaign and published data, resulted in 404 observations (including synthetic fertilizer and zero-N control) in 29 sites. Results showed that soil type affected EFs, that is, the mean EF of Andosols was lower than that of non-Andosols, which is similar to the case of EFs for synthetic fertilizer. Mean EFs for poultry manure compost, swine manure compost, cattle manure (compost and slurry), and non-animal manure organic fertilizers were 0.83 % (uncertainty range of 2.5th and 97.5th percentile: 0.09 % to 3.46 %), 0.70 % (0.02 % to 2.45 %), 0.39 % (0.00 % to 1.62 %), and 1.16 % (0.41 % to 3.03 %), respectively, when weighted by area of soil types. The mean EF of all organic amendments was 0.84 % (0.00 % to 2.91 %), when the area of soil type and amount of organic amendment used in Japan were considered. Our study provides country-specific EFs to estimate N2O emission from organic amendments in Japan.
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•We estimated N2O emission factors (EFs) for organic amendments in Japan.•The mean EF of all organic amendments was 0.84 % in Japan.•The mean EF of Andosols was lower than that of non-Andosols.•Mean EFs for poultry, swine and cattle manures were 0.83 %, 0.70 % and 0.39 %.•The mean EF for non-animal manure organic fertilizers was 1.16 %.
Collagen XIX is a nonfibrillar collagen that localizes in restricted tissues at very low amounts. A previous study on
Col19a1
null mice revealed that collagen XIX is involved in esophageal muscle ...physiology and morphogenesis. Here, we use histological analysis to show that mice with a
Col19a1
mutant lacking the NC3 domain and seven collagen triplets display abnormal transition of smooth to striated muscle in the abdominal segment of esophagus, and a widened esophagus with age. With two newly prepared antibodies, we analyzed the expression of collagen XIX in the mouse esophagus and show that collagen XIX colocalizes with α-smooth muscle actin. By immunoelectron microscopy, we confirmed the localization of collagen XIX in esophageal smooth muscle cells.
Col19a1
mutant mice contained reduced levels of mutated
Col19a1
mRNA. Interestingly, hepatocyte growth factor, which has an important role in esophageal striated muscle development, was reduced in the esophagus of the
Col19a1
mutant mice. These findings suggest that collagen XIX may be critical for the function of esophageal smooth muscle cells as a scaffold for anteroposterior migration of esophagus-striated muscle cells.
Antidepressant‐induced jitteriness/anxiety syndrome is characterized as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, and (hypo)mania, ...which appear immediately after initiation or increased dosage of an antidepressant. This report describes a case of the jitteriness/anxiety syndrome caused by the coadministration of celecoxib with escitalopram and trazodone in a patient with depression and spondylolisthesis. The depression of a patient, a woman in her 60 s, had been in remission at least for 5 years under treatment using escitalopram and trazodone. Immediately after coadministration of celecoxib because of her buttock and limb pain, she showed anxiety, agitation, akathisia, insomnia, irritability, aggressiveness, impulsivity, and hypomania. These symptoms disappeared after the discontinuation of celecoxib. The present case suggests that coadministration of celecoxib with escitalopram and trazodone can cause the jitteriness/anxiety syndrome, presumably via a pharmacokinetic interaction of celecoxib with these antidepressants and/or the effects of celecoxib on serotonergic neurotransmission.
Human herpes virus 6 (HHV‐6) is known to cause primary encephalitis in the frontal lobes/cerebral hemisphere or reactivated encephalitis in the hippocampus, but the pathogenesis remains unclear. ...HHV‐6B has also been detected in hippocampal samples in patients with mesial temporal lobe epilepsy. A 1 year and 3 months old female, who had been clinically diagnosed with exanthema subitum and febrile convulsion, was found dead on the third day after onset. Macroscopic findings showed massive brain edema. Microscopic examination revealed gemistocytic astrocytes and ballooned oligodendrocytes in the frontal white matter, along with neuronal cell death with microglial infiltration in the frontal cortex. Polymerase chain reaction detected HHV‐6B in the cerebrospinal fluid and necropsy brain samples. The hippocampus showed a 4–5‐fold increase in virus copy number of HHV‐6B compared to samples from other brain sites. Immunostaining indicated that HHV‐6B had infected vascular endothelial cells, neurons and oligodendrocytes but not astrocytes or microglia. Hippocampal neurons were infected with highly concentrated HHV‐6B, but the hippocampus had neither neuronal loss nor reactive glial response. Silent and abundant HHV‐6B infection in the hippocampus might be associated with latent infection, reactivation and some hippocampus‐oriented disorders, including mesial temporal lobe epilepsy.
FixL is a heme-based oxygen-sensing histidine kinase that induces expression of nitrogen fixation genes under hypoxic conditions. Oxygen binding to heme iron in the sensor domain of FixL initiates ...protein conformational changes that are transmitted to the histidine kinase domain, inactivating autophosphorylation activity. Although FixL also can bind other diatomic ligands such as CO, the CO-bound FixL represents incomplete inhibition of kinase activity. Ultraviolet resonance Raman (UVRR) spectra revealed that oxygen binding to the truncated sensor domain of FixL markedly decreased the intensity of the Y8a band arising from Fα-10 Tyr. In contrast, no appreciable change in intensity of the Y8a band occurred after CO binding, and time-resolved UVRR spectra of the sensor domain of FixL upon O2 dissociation indicated that structural changes near Fα-10 Tyr occurred at ∼0.1 μs. These results suggest that O2 dissociation from FixL changes the protein conformation near the Fα-10 Tyr residue within a microsecond. The conformational changes of FixL upon O2 dissociation and the underlying sensing mechanism also are discussed.
Lanthanum carbonate (LaC) is used to prevent hyperphosphatemia in dialysis patients. It is commonly believed that there is little LaC absorption from the intestines. However, La deposition in the ...gastric mucosa, which we coined “gastric lanthanosis”, was recently reported. We describe here the clinicopathological features of and a possible mechanism for gastric lanthanosis. This study included 23 patients with definite gastric lanthanosis. We extracted characteristic clinicopathological features of gastric lanthanosis by computed tomography (CT) imaging and endoscopic, histologic, electron‐microscopic, and element analysis examinations. The Helicobacter pylori infection rate in the lanthanosis group was much lower than that among the general population. The clinicopathological features characteristic of gastric lanthanosis were mucosal high‐density linear appearance by CT, reflective bright‐white spots (BWS) by gastroscopy, eosinophilic histiocytes occasionally phagocytizing foreign materials by histology, and numerous electron‐dense particles in the histiocytes. The particles had burr‐like skeletons resembling La crystals. Gastric lanthanosis is an under‐reported, but not a rare lesion. It is characterized by endoscopic BWS and histologic eosinophilic histiocytes in dialysis patients treated with LaC. The proposed mechanism for gastric lanthanosis is that LaC is dissolved by gastric juice, crystallized within the mucosa and is phagocytized by histiocytes.
SMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations in SMG9 are associated with ...heart and brain malformation syndrome (HBMS). However, the molecular mechanism underlying HBMS remains unclear. We generated smg9 mutant zebrafish (smg9
) that have a lifespan of approximately 6 months or longer, allowing for analysis of the in vivo function of Smg9 in adults in more detail. smg9
zebrafish display congenital brain abnormalities and reduced cardiac contraction. Additionally, smg9
zebrafish exhibit a premature aging phenotype. Analysis of NMD target mRNAs shows a trend toward increased mRNA levels in smg9
zebrafish. Spermidine oxidase (Smox) is increased in smg9
zebrafish, resulting in the accumulation of byproducts, reactive oxygen species, and acrolein. The accumulation of smox mRNA due to NMD dysregulation caused by Smg9 deficiency leads to increased oxidative stress, resulting in premature aging.
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