AGL1-AGL6, an Arabidopsis gene family with similarity to floral homeotic and transcription factor genes

The predicted products of floral homeotic genes, AGAMOUS (AG) from Arabidopsis thaliana and DEFICIENS A (DEF A) from Antirrhinum majus, have been shown previously to share strong sequence similarity with transcription factors from humans (SRF) and yeast (MCM1). The conserved sequence between these proteins is localized within a domain known to be necessary for the DNA binding and for the dimerization of SRF. We have isolated six new genes from A. thaliana, AGL1-AGL6, which also have this conserved sequence motif. On the basis of the sequence comparison between the AG and AGL genes, they can be assigned to two subfamilies of a large gene family. RNA dot blot analysis indicates that five of these genes (AGL1, AGL2, AGL4, AGL5, and AGL6) are preferentially expressed in flowers. In addition, in situ RNA hybridization experiments with AGL1 and AGL2 show that their mRNAs are detected in some floral organs but not in others. Our results suggest that these genes may act to control many steps of Arabidopsis floral morphogenesis. In contrast, the AGL3 gene is expressed in vegetative tissues as well as in flowers, suggesting that it functions in a broader range of tissues. We discuss possible roles of this gene family during the evolution of flowers

Multiple Imputation Method for High-Dimensional Neuroimaging Data

Missingness is a common issue for neuroimaging data, and neglecting it in downstream statistical analysis can introduce bias and lead to misguided inferential conclusions. It is therefore crucial to conduct appropriate statistical methods to address this issue. While multiple imputation is a popular technique for handling missing data, its application to neuroimaging data is hindered by high dimensionality and complex dependence structures of multivariate neuroimaging variables. To tackle this challenge, we propose a novel approach, named High Dimensional Multiple Imputation (HIMA), based on Bayesian models. HIMA develops a new computational strategy for sampling large covariance matrices based on a robustly estimated posterior mode, which drastically enhances computational efficiency and numerical stability. To assess the effectiveness of HIMA, we conducted extensive simulation studies and real-data analysis using neuroimaging data from a Schizophrenia study. HIMA showcases a computational efficiency improvement of over 2000 times when compared to traditional approaches, while also producing imputed datasets with improved precision and stability.Comment: 13 pages, 5 figure

The Replicative Consequences of Papillomavirus E2 Protein Binding to the Origin Replication Factor ORC2.

The origin recognition complex (ORC) coordinates a series of events that lead to initiation of DNA strand duplication. As a nuclear double stranded DNA plasmid, the papillomavirus (PV) genome resembles a mini-chromosome in infected cells. To initiate its replication, the viral E2 protein binds to and recruits the E1 DNA helicase at the viral origin. PV genome replication program exhibits three stages: initial amplification from a single genome upon infection to a few copies per cell, a cell cycle linked maintenance phase, and a differentiation dependent late stage where the genome is amplified to thousands of copies. Involvement of ORC or other pre-replication complex (pre-RC) factors has not been described. We report that human PV (HPV) and bovine PV (BPV-1) E2 proteins bind to ORC2, however, ORC2 was not detected at the viral origin. Depletion of ORC2 enhanced PV replication in a transient replication model and in keratinocytes stably maintaining viral episomes, while there was no effect on copy number in a cell line with integrated HPV genomes. Consistent with this, occupancy of E1 and E2 at the viral origin increased following ORC2 silencing. These data imply that ORC2 is not necessary for activation of the PV origin by E1 and E2 but instead suppresses E2 replicative function. Furthermore, we observed that over-expression of HPV E2 decreased ORC2 occupation at two known mammalian origins of replication, suggesting that E2 restricts pre-ORC assembly that could otherwise compete for host replication complexes necessary for viral genome amplification. We infer that the ORC2 complex with E2 restricts viral replication in the maintenance phase of the viral replication program and that elevated levels of E2 that occur during the differentiation dependent amplification stage subvert ORC loading and hence DNA synthesis at cellular origins

Evaluating the effects of high-throughput structural neuroimaging predictors on whole-brain functional connectome outcomes via network-based vector-on-matrix regression

The joint analysis of multimodal neuroimaging data is critical in the field of brain research because it reveals complex interactive relationships between neurobiological structures and functions. In this study, we focus on investigating the effects of structural imaging (SI) features, including white matter micro-structure integrity (WMMI) and cortical thickness, on the whole brain functional connectome (FC) network. To achieve this goal, we propose a network-based vector-on-matrix regression model to characterize the FC-SI association patterns. We have developed a novel multi-level dense bipartite and clique subgraph extraction method to identify which subsets of spatially specific SI features intensively influence organized FC sub-networks. The proposed method can simultaneously identify highly correlated structural-connectomic association patterns and suppress false positive findings while handling millions of potential interactions. We apply our method to a multimodal neuroimaging dataset of 4,242 participants from the UK Biobank to evaluate the effects of whole-brain WMMI and cortical thickness on the resting-state FC. The results reveal that the WMMI on corticospinal tracts and inferior cerebellar peduncle significantly affect functional connections of sensorimotor, salience, and executive sub-networks with an average correlation of 0.81 (p<0.001).Comment: 20 pages, 5 figures, 2 table

AGL1-AGL6, an Arabidopsis gene family with similarity to floral homeotic and transcription factor genes

The predicted products of floral homeotic genes, AGAMOUS (AG) from Arabidopsis thaliana and DEFICIENS A (DEF A) from Antirrhinum majus, have been shown previously to share strong sequence similarity with transcription factors from humans (SRF) and yeast (MCM1). The conserved sequence between these proteins is localized within a domain known to be necessary for the DNA binding and for the dimerization of SRF. We have isolated six new genes from A. thaliana, AGL1-AGL6, which also have this conserved sequence motif. On the basis of the sequence comparison between the AG and AGL genes, they can be assigned to two subfamilies of a large gene family. RNA dot blot analysis indicates that five of these genes (AGL1, AGL2, AGL4, AGL5, and AGL6) are preferentially expressed in flowers. In addition, in situ RNA hybridization experiments with AGL1 and AGL2 show that their mRNAs are detected in some floral organs but not in others. Our results suggest that these genes may act to control many steps of Arabidopsis floral morphogenesis. In contrast, the AGL3 gene is expressed in vegetative tissues as well as in flowers, suggesting that it functions in a broader range of tissues. We discuss possible roles of this gene family during the evolution of flowers

A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier

Schizophrenia (SZ) is one of the most severe forms of mental illness, yet mechanisms remain unclear. A widely established brain finding in SZ is hippocampal atrophy, and a coherent explanation similarly is lacking. Epidemiological evidence suggests increased cerebrovascular and cardiovascular complications in SZ independent of lifestyle and medication, pointing to disease-specific pathology. Endothelial cell contributions to blood-brain barrier (BBB) compromise may influence neurovascular unit and peripheral vascular function, and we hypothesize that downstream functional and structural abnormalities may be explained by impaired BBB

Sedimentology of Acid Saline Lakes in Southern Western Australia: Newly Described Processes and Products of an Extreme Environment

Naturally acid saline systems with pH values between 1.7 and 4 are common on the Yilgarn Craton of southern Western Australia. a combination of physical and chemical processes here yield a previously undescribed type of modern sedimentary environment. Flooding, evapoconcentration, desiccation, and eolian transport at the surface, as well as influx of acid saline groundwaters, strongly influence these lakes. Halite, gypsum, kaolinite, and iron oxides precipitate from acid hypersaline lake waters. Shallow acid saline groundwaters affect the sediments of the lakes and associated mudflats, sandflats, channels, and dunes by precipitating early diagenetic halite, gypsum, iron oxides, clays, jarosite, and alunite. These modern environments would likely yield a rock record composed mostly of bedded red siliciclastic and reworked gypsum sand, alternating with less common beds of bottom-growth gypsum and halite, with alteration by early diagenetic features diagnostic of acid saline waters. This documentation of sedimentary processes and products of modern acid saline environments is an addition to the comparative sedimentology knowledge base and an expansion of the traditional models for classifying brines. Implications include better interpretations of terrestrial redbeds and lithified martian strata, improved acid remediation methods, new models for the formation and occlusion of pores, and the new setting for finding previously undescribed extremophiles

Lack of association between COMT gene and deficit/nondeficit schizophrenia

BACKGROUND: The dopamine dysregulation hypothesis of schizophrenia posits that positive, negative and cognitive symptoms correlate with cortical/subcortical imbalances in dopaminergic transmission. A functional polymorphism (Val(158)Met) in the catechol-O-methyltransferase (COMT) gene is implicated in the pathophysiology of schizophrenia by its effect on prefrontal dopamine transmission, and its unique impact on prefrontal cognitive and behavioral phenotypes. Cognitive impairments and negative symptoms in schizophrenia have been hypothesized to be associated with hypodopaminergic states. Schizophrenia patients with the deficit syndrome are characterized by primary enduring negative symptoms, impairment on neurocognitive tasks sensitive to frontal and parietal cortical functioning, and poorer functional outcome compared to non-deficit patients. METHODS: Eighty-six schizophrenia cases that met DSM-IV criteria for schizophrenia were recruited. Additional categorization into deficit and nondeficit syndrome was performed using the Schedule for the Deficit Syndrome (SDS). A healthy comparison group (n = 50) matched to cases on age and ethnicity was recruited. Allele and genotype frequencies of the Val(158)Met polymorphism were compared among healthy controls, and schizophrenia cases with the deficit (n = 21), and nondeficit syndrome (n = 65). RESULTS: There was a significant difference in Val/Val genotype frequencies between schizophrenia cases (combined deficit/nondeficit) and healthy controls (p = 0.004). No significant differences in allele or genotype frequencies were observed between deficit and nondeficit cases. CONCLUSION: Results from this preliminary analysis failed to show an effect of COMT gene on deficit schizophrenia

Interaction between alpha-COP and SMN ameliorates disease phenotype in a mouse model of spinal muscular atrophy

We report that expression of the α-COP protein rescues disease phenotype in a severe mouse model of Spinal Muscular Atrophy (SMA).. Lentiviral particles expressing α-COP were injected directly into the testes of genetically pure mouse strain of interest resulting in infection of the spermatagonial stem cells. α-COP was stably expressed in brain, skeletal muscle, and spinal cord without altering SMN protein levels. SMA mice transgenic for α-COP live significantly longer than their non-transgenic littermates, and showed increased body mass and normal muscle morphology at postnatal day 15. We previously reported that binding between SMN and α-COP is required for restoration of neurite outgrowth in cells lacking SMN, and we report similar finding here. Lentiviral-mediated transgenic expression of SMN where the dilysine domain in exon 2b was mutated was not able to rescue the SMA phenotype despite robust expression of the mutant SMN protein in brain, muscle and spinal cord. These results demonstrate that α-COP is a validated modifier of SMA disease phenotype in a mammalian, vertebrate model and is a potential target for development of future SMN-independent therapeutic interventions

Multi-visceral resection of pancreatic VIPoma in a patient with sinistral portal hypertension

BACKGROUND: VIPomas are rare neuroendocrine tumors poorly described in the literature. Aggressive resection of patients with advanced VIPoma neuroendocrine tumors has rarely been reported. CASE PRESENTATION: A 46 year old women presented with abdominal pain and diarrhea. A three-dimensional (3-D) pancreas protocol computed tomography scan revealed an 18 × 12 cm pancreatic VIPoma abutting the liver, stomach, spleen, left adrenal, colon that also invaded the distal duodenum – proximal jejunum at the ligament of Treitz in association with sinistral portal hypertension. Following preoperative proximal splenic artery embolization, the patient with underwent successful en bloc resection of the locally advanced VIPoma in conjunction with a diaphragmatic resection, total gastrectomy, splenectomy, left adrenalectomy, as well as small and large bowel resection. The estimated blood loss was 500 ml. All margins were negative (R0 resection). The patient is alive and disease-free. CONCLUSION: This case illustrates the role of aggressive resection of pancreatic neuroendocrine tumors and highlights several key technical points that allowed for successful resection