OTUD7A Regulates Inflammation- and Immune-Related Gene Expression in Goose Fatty Liver

OTU deubiquitinase 7A (OTUD7A) can suppress inflammation signaling pathways, but it is unclear whether the gene can inhibit inflammation in goose fatty liver. In order to investigate the functions of OTUD7A and identify the genes and pathways subjected to the regulation of OTUD7A in the formation of goose fatty liver, we conducted transcriptomic analysis of cells, which revealed several genes related to inflammation and immunity that were significantly differentially expressed after OTUD7A overexpression. Moreover, the expression of interferon-induced protein with tetratricopeptide repeats 5 (IFIT5), tumor necrosis factor ligand superfamily member 8 (TNFSF8), sterile alpha motif domain-containing protein 9 (SAMD9), radical S-adenosyl methionine domain-containing protein 2 (RSAD2), interferon-induced GTP-binding protein Mx1 (MX1), and interferon-induced guanylate binding protein 1-like (GBP1) was inhibited by OTUD7A overexpression but induced by OTUD7A knockdown with small interfering RNA in goose hepatocytes. Furthermore, the mRNA expression of IFIT5, TNFSF8, SAMD9, RSAD2, MX1, and GBP1 was downregulated, whereas OTUD7A expression was upregulated in goose fatty liver after 12 days of overfeeding. In contrast, the expression patterns of these genes showed nearly the opposite trend after 24 days of overfeeding. Taken together, these findings indicate that OTUD7A regulates the expression of inflammation- and immune-related genes in the development of goose fatty liver.

Ablation of SAMD1 in Mice Causes Failure of Angiogenesis, Embryonic Lethality

Pathological retention of LDL in the intima is involved in atherosclerosis, although the retention mechanisms are not well-understood. Previously, we reported Sterile Alpha Motif Domain Containing 1 (SAMD1), a protein secreted by intimal smooth muscle cells in atherosclerotic lesions, appears to bind LDL in extracellular matrix around intimal cells. Fab-fragment inhibitors of apparently irreversible SAMD1/LDL binding reduced LDL retention in carotid injury models, but did not have a significant effect on early spontaneous lesion initiation. The normal function of SAMD1 is unknown, but it may have multiple epigenetic roles; our histology of mouse atherosclerosis models revealed extensive SAMD1 expression, possibly related to cell phenotype modulation and antigen presentation. For this report, we generated SAMD1-/-, SAMD1-/+, and SAMD1-/+ apoE-/- mice to further explore SAMD1's role in atherosclerosis. SAMD1 was found in tissues throughout the SAMD1+/+ and SAMD1-/+embryos. Homozygous loss of SAMD1 was embryonic lethal: at embryonic day 14, organs were partially developed and/or degraded; heads and brains were malformed; no blood vessels were observed; red blood cells were scattered and pooled, primarily near the embryo surface; and cell death was occurring. Development appeared normal in heterozygous SAMD1 embryos, but postnatal genotyping showed a reduced ability to thrive. Growth of atherosclerotic lesions in SAMD1-/+ apoE-/- after 35 weeks was not significantly less than in mice SAMD1+/+ apoE-/- mice.

SAMD3 expression associates with survival in triple negative breast cancer.

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of sterile alpha motif domain containing 3, encoded by SAMD3 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, SAMD3 expression was correlated with overall survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. SAMD3 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

Aberrant Visual-Related Networks in Familial Cortical Myoclonic Tremor with Epilepsy

In familial cortical myoclonic tremor with epilepsy, photic stimulation can trigger visual-related symptoms and induce a photoparoxysmal response on electroencephalography. This is known as photosensitivity. To explore the mechanism of prominent visual-related symptoms and photosensitivity in patients with genetically confirmed familial cortical myoclonic tremor with epilepsy type 1, resting-state functional magnetic resonance imaging data and electroencephalography data were collected from 31 patients carrying the heterozygous pathogenic intronic pentanucleotide (TTTCA)n insertion in the sterile alpha motif domain-containing 12 gene and from 52 age- and sex-matched healthy controls. Results: (1) Both regional homogeneity and degree centrality values in the bilateral calcarine sulcus were significantly increased in patients compared with HCs. (2) When the calcarine sulcus area with increased regional homogeneity was taken as a seed, increased functional connectivity values were observed in the right precentral gyrus, while decreased functional connectivity values were observed in the right superior frontal gyrus and right inferior parietal lobule. (3) independent component analysis showed increased connectivity in the left calcarine sulcus inside the medial visual network. (4) Correlation analysis revealed significant positive correlation between regional homogeneity values and frequency of seizure, and photoparoxysmal response grades were positively correlated with the severity of cortical tremor and duration of epilepsy. The findings provide strong evidence for the interpretation of visual-related symptoms and photosensitivity in familial cortical myoclonic tremor with epilepsy and may also relate to other epilepsy syndromes with photosensitivity. We speculate the significant functional change in primary visual cortex probably an imaging biomarker for the disease.

ENHANCED GRAVITROPISM 2 encodes a STERILE ALPHA MOTIVE containing protein that controls root growth angle in barley and wheat

The root growth angle defines how roots grow towards the gravity vector and is among the most important determinants of root system architecture. It controls water uptake capacity, nutrient use efficiency, stress resilience and as a consequence yield of crop plants. We demonstrated that the egt2 (enhanced gravitropism 2) mutant of barley exhibits steeper root growth of seminal and lateral roots and an auxin independent higher responsiveness to gravity compared to wild type plants. We cloned the EGT2 gene by a combination of bulked segregant analysis and whole genome sequencing. Subsequent validation experiments by an independent CRISPR/Cas9 mutant allele demonstrated that egt2 encodes a STERILE ALPHA MOTIF domain containing protein. In situ hybridization experiments illustrated that EGT2 is expressed from the root cap to the elongation zone. Subcellular localization experiments revealed that EGT2 localizes to the nucleus and cytoplasm. We demonstrated the evolutionary conserved role of EGT2 in root growth angle control between barley and wheat by knocking out the EGT2 orthologs in the A and B genomes of tetraploid durum wheat. By combining laser capture microdissection with RNA-seq, we observed that seven expansin genes were transcriptionally downregulated in the elongation zone. This is consistent with a role of EGT2 in this region of the root where the effect of gravity sensing is executed by differential cell elongation. Our findings suggest that EGT2 is an evolutionary conserved regulator of root growth angle in barley and wheat that could be a valuable target for root-based crop improvement strategies in cereals.Significance StatementTo date the potential of utilizing root traits in plant breeding remains largely untapped. In this study we cloned and characterized the ENHANCED GRAVITROPISM2 (EGT2) gene of barley that encodes a STERILE ALPHA MOTIF domain containing protein. We demonstrated that EGT2 is a key gene of root growth angle regulation in response to gravity which is conserved in barley and wheat and could be a promising target for crop improvement in cereals.

Involvement of natural killer cells in the pathogenesis of endometriosis in patients with pelvic pain

Objectives To detect the involvement of immune cells in the pathogenesis of endometriosis in patients with stable status or pelvic pain. Methods Blood was collected from patients with endometriosis with and without pelvic pain. Natural killer (NK) and Th17 cells were analyzed by flow cytometry, and secretion of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-7) was verified by enzyme-linked immunosorbent assay. We isolated immune cells from blood by density-gradient centrifugation to investigate the expression of functional molecules including sterile alpha motif domain-containing protein 9 (SAMD9), Ral guanine nucleotide dissociation stimulator-like 2 (RGL2), early growth response protein 1, and Akirin2. We also searched the BIOGPS database for protein expression profiles. Results SAMD9 and RGL2 expression levels were significantly upregulated in patients with pelvic pain. Furthermore, lysophosphatidic acid receptor 1 expression was higher in endometrial tissues from patients with pelvic pain, and was mainly localized in stromal and glandular epithelial cells in ectopic lesions. Conclusion NK cells play an important role in the pathogenesis of endometriosis in patients with pelvic pain. Suppressing the cytotoxic activity of NK cells may thus help to reduce the progression of pelvic pain in patients with endometriosis.

The Neuropathology of MIRAGE Syndrome

MIRAGE syndrome is a multisystem disorder characterized by myelodysplasia, infections, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. Mutations in the sterile alpha motif domain containing 9 (SAMD9) gene which encodes a protein involved in growth factor signal transduction are thought to cause MIRAGE syndrome. SAMD9 mutations lead to an antiproliferative effect resulting in a multisystem growth restriction disorder. Though rare, a few patients with SAMD9 mutations were reported to have hydrocephalus and/or cerebellar hypoplasia on imaging. The neuropathologic features of MIRAGE syndrome have not been previously described. Here, we describe the postmortem neuropathologic examinations of 2 patients with a clinical diagnosis of MIRAGE syndrome and confirmed SAMD9 mutations. Common features included microcephaly, hydrocephalus, white matter abnormalities, and perivascular calcifications. One of the 2 cases showed marked cerebellar hypoplasia with loss of Purkinje and granule neurons as well as multifocal polymicrogyria and severe white matter volume loss; similar findings were not observed in the second patient. These cases demonstrate the variation in neuropathologic findings in patients with MIRAGE syndrome. Interestingly, the findings are similar to those reported in ataxia-pancytopenia syndrome caused by mutations in SAMD9L, a paralogue of SAMD9.

Loss of a highly conserved sterile alpha motif domain gene (WEEP) results in pendulous branch growth in peach trees

Plant shoots typically grow upward in opposition to the pull of gravity. However, exceptions exist throughout the plant kingdom. Most conspicuous are trees with weeping or pendulous branches. While such trees have long been cultivated and appreciated for their ornamental value, the molecular basis behind the weeping habit is not known. Here, we characterized a weeping tree phenotype in Prunus persica (peach) and identified the underlying genetic mutation using a genomic sequencing approach. Weeping peach tree shoots exhibited a downward elliptical growth pattern and did not exhibit an upward bending in response to 90° reorientation. The causative allele was found to be an uncharacterized gene, Ppa013325, having a 1.8-Kb deletion spanning the 5′ end. This gene, dubbed WEEP, was predominantly expressed in phloem tissues and encodes a highly conserved 129-amino acid protein containing a sterile alpha motif (SAM) domain. Silencing WEEP in the related tree species Prunus domestica (plum) resulted in more outward, downward, and wandering shoot orientations compared to standard trees, supporting a role for WEEP in directing lateral shoot growth in trees. This previously unknown regulator of branch orientation, which may also be a regulator of gravity perception or response, provides insights into our understanding of how tree branches grow in opposition to gravity and could serve as a critical target for manipulating tree architecture for improved tree shape in agricultural and horticulture applications.