Disruption of FEM1C-W gene in zebra finch: evolutionary insights on avian ZW genes

Sex chromosome genes control sex determination and differentiation, but the mechanisms of sex determination in birds are unknown. In this study, we analyzed the gene FEM1C which is highly conserved from Caenorhabditis elegans to higher vertebrates and interacts with the sex determining pathway in C. elegans. We found that FEM1C is located on the Z and W chromosome of zebra finches and probably other Passerine birds, but shows only Z linkage in other avian orders. In the zebra finch, FEM1C-W is degraded because of a point mutation and possibly because of loss of the first exon containing the start methionine. Thus, FEM1C-W appears to have degenerated or been lost from most bird species. FEM1C-Z is expressed in a cytoplasmic location in zebra finch fibroblast cells, as in C. elegans. FEM1C represents an interesting example of evolutionary degradation of a W chromosome gene

Zebra finch cell lines from naturally occurring tumors

The zebra finch (Taeniopygia guttata) has been intensively studied in many research fields including neuroscience, behavioral neurobiology, and evolution of the genome. Although numerous molecular and genomic resources are available for this model species, immortalized cell lines have been lacking. We have established two zebra finch cell lines derived from spontaneous tumors. ZFTMA is a tetraploid female cell line and G266 as a diploid male cell line. These first zebra finch cell lines should facilitate development of research on this model species

Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes.

Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune encephalomyelitis (EAE). Astrocyte-specific RNAs from various neuroanatomic regions were attained using RiboTag technology. Sequencing and bioinformatics analyses showed that EAE-induced gene expression changes differed between neuroanatomic regions when comparing astrocytes from spinal cord, cerebellum, cerebral cortex, and hippocampus. The top gene pathways that were changed in astrocytes from spinal cord during chronic EAE involved decreases in expression of cholesterol synthesis genes while immune pathway gene expression in astrocytes was increased. Optic nerve from EAE and optic chiasm from MS also showed decreased cholesterol synthesis gene expression. The potential role of cholesterol synthesized by astrocytes during EAE and MS is discussed. Together, this provides proof-of-concept that a cell-specific and region-specific gene expression approach can provide potential treatment targets in distinct neuroanatomic regions during multifocal neurological diseases

Cell-autonomous sex determination outside of the gonad

The classic model of sex determination in mammals states that the sex of the individual is determined by the type of gonad that develops, which in turn determines the gonadal hormonal milieu that creates sex differences outside of the gonads. However, XX and XY cells are intrinsically different because of the cell-autonomous sex-biasing action of X and Y genes. Results: Recent studies of mice, in which sex chromosome complement is independent of gonadal sex, reveal that sex chromosome complement has strong effects contributing to sex differences in phenotypes such as metabolism. Adult mice with two X chromosomes (relative to mice with one X chromosome) show dramatically greater increases in body weight and adiposity after gonadectomy, irrespective of their gonadal sex. When fed a high-fat diet, XX mice develop striking hyperinsulinemia and fatty liver, relative to XY mice. The sex chromosome effects are modulated by the presence of gonadal hormones, indicating an interaction of the sex-biasing effects of gonadal hormones and sex chromosome genes. Conclusions: Other cell-autonomous sex chromosome effects are detected in mice in many phenotypes. Birds (relative to eutherian mammals) are expected to show more widespread cell-autonomous sex determination in non-gonadal tissues, because of ineffective sex chromosome dosage compensation mechanisms

Sex differences in the neuronal transcriptome and synaptic mitochondrial function in the cerebral cortex of a multiple sclerosis model

IntroductionMultiple sclerosis (MS) affects the cerebral cortex, inducing cortical atrophy and neuronal and synaptic pathology. Despite the fact that women are more susceptible to getting MS, men with MS have worse disability progression. Here, sex differences in neurodegenerative mechanisms are determined in the cerebral cortex using the MS model, chronic experimental autoimmune encephalomyelitis (EAE).MethodsNeurons from cerebral cortex tissues of chronic EAE, as well as age-matched healthy control, male and female mice underwent RNA sequencing and gene expression analyses using RiboTag technology. The morphology of mitochondria in neurons of cerebral cortex was assessed using Thy1-CFP-MitoS mice. Oxygen consumption rates were determined using mitochondrial respirometry assays from intact as well as permeabilized synaptosomes.ResultsRNA sequencing of neurons in cerebral cortex during chronic EAE in C57BL/6 mice showed robust differential gene expression in male EAE compared to male healthy controls. In contrast, there were few differences in female EAE compared to female healthy controls. The most enriched differential gene expression pathways in male mice during EAE were mitochondrial dysfunction and oxidative phosphorylation. Mitochondrial morphology in neurons showed significant abnormalities in the cerebral cortex of EAE males, but not EAE females. Regarding function, synaptosomes isolated from cerebral cortex of male, but not female, EAE mice demonstrated significantly decreased oxygen consumption rates during respirometry assays.DiscussionCortical neuronal transcriptomics, mitochondrial morphology, and functional respirometry assays in synaptosomes revealed worse neurodegeneration in male EAE mice. This is consistent with worse neurodegeneration in MS men and reveals a model and a target to develop treatments to prevent cortical neurodegeneration and mitigate disability progression in MS men

Identifying Suspicious Regions of Covid-19 by Abnormality-Sensitive Activation Mapping

This paper presents a fully-automated method for the identification of suspicious regions of a coronavirus disease (COVID-19) on chest CT volumes. One major role of chest CT scanning in COVID-19 diagnoses is identification of an inflammation particular to the disease. This task is generally performed by radiologists through an interpretation of the CT volumes, however, because of the heavy workload, an automatic analysis method using a computer is desired. Most computer-aided diagnosis studies have addressed only a portion of the elements necessary for the identification. In this work, we realize the identification method through a classification task by using a 2.5-dimensional CNN with three-dimensional attention mechanisms. We visualize the suspicious regions by applying a backpropagation based on positive gradients to attention-weighted features. We perform experiments on an in-house dataset and two public datasets to reveal the generalization ability of the proposed method. The proposed architecture achieved AUCs of over 0.900 for all the datasets, and mean sensitivity $0.853 \pm 0.036$ and specificity $0.870 \pm 0.040$. The method can also identify notable lesions pointed out in the radiology report as suspicious regions.Comment: 10 pages, 3 figure

Karyotypic polymorphism of the zebra finch Z chromosome

We describe a karyotypic polymorphism on the zebra finch Z chromosome. This polymorphism was discovered because of a difference in the position of the centromere and because it occurs at varying frequencies in domesticated colonies in the USA and Germany and among two zebra finch subspecies. Using DNA fluorescent in situ hybridization to map specific Z genes and measurements of DNA replication, we show that this polymorphism is the result of a large pericentric inversion involving the majority of the chromosome. We sequenced a likely breakpoint for the inversion and found many repetitive sequences. Around the breakpoint, there are numerous repetitive sequences and several copies of PAK3 (p21-activated kinase 3)-related sequences (PAK3Z) which showed testes-specific expression by RT-PCR. Our findings further suggest that the sequenced genome of the zebra finch may be derived from a male heterozygote for the Z chromosome polymorphism. This finding, in combination with regional differences in the frequency of the polymorphism, has important consequences for future studies using zebra finches

Subaru Hyper Suprime-Cam Survey for An Optical Counterpart of GW170817

We perform a $z$-band survey for an optical counterpart of a binary neutron star coalescence GW170817 with Subaru/Hyper Suprime-Cam. Our untargeted transient search covers $23.6$ deg$^2$ corresponding to the $56.6\%$ credible region of GW170817 and reaches the $50\%$ completeness magnitude of $20.6$ mag on average. As a result, we find 60 candidates of extragalactic transients, including J-GEM17btc (a.k.a. SSS17a/DLT17ck). While J-GEM17btc is associated with NGC 4993 that is firmly located inside the 3D skymap of GW170817, the other 59 candidates do not have distance information in the GLADE v2 catalog or NASA/IPAC Extragalactic Database (NED). Among 59 candidates, 58 are located at the center of extended objects in the Pan-STARRS1 catalog, while one candidate has an offset. We present location, $z$-band apparent magnitude, and time variability of the candidates and evaluate the probabilities that they are located inside of the 3D skymap of GW170817. The probability for J-GEM17btc is $64\%$ being much higher than those for the other 59 candidates ($9.3\times10^{-3}-2.1\times10^{-1}\%$). Furthermore, the possibility, that at least one of the other 59 candidates is located within the 3D skymap, is only $3.2\%$. Therefore, we conclude that J-GEM17btc is the most-likely and distinguished candidate as the optical counterpart of GW170817.Comment: 14 pages, 9 figures. Accepted for publication in PASJ (Publications of the Astronomical Society of Japan

The importance of having two X chromosomes

Historically, it was thought that the number of X chromosomes plays little role in causing sex differences in traits. Recently, selected mouse models have been used increasingly to compare mice with the same type of gonad but with one versus two copies of the X chromosome. Study of these models demonstrates that mice with one X chromosome can be strikingly different from those with two X chromosomes, when the differences are not attributable to confounding group differences in gonadal hormones. The number of X chromosomes affects adiposity and metabolic disease, cardiovascular ischaemia/reperfusion injury and behaviour. The effects of X chromosome number are likely the result of inherent differences in expression of X genes that escape inactivation, and are therefore expressed from both X chromosomes in XX mice, resulting in a higher level of expression when two X chromosomes are present. The effects of X chromosome number contribute to sex differences in disease phenotypes, and may explain some features of X chromosome aneuploidies such as in Turner and Klinefelter syndromes