The ModelSEED Biochemistry Database for the integration of metabolic annotations and the reconstruction, comparison and analysis of metabolic models for plants, fungi and microbes

In the Abstract, the url https://modelseed.org has been replaced with https://modelseed.org/biochem

Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression

Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC

Analysis of genome-wide DNA arrays reveals the genomic population structure and diversity in autochthonous Greek goat breeds

Goats play an important role in the livestock sector in Greece. The national herd consists mainly of two indigenous breeds, the Eghoria and Skopelos. Here, we report the population structure and genomic profiles of these two native goat breeds using Illumina's Goat SNP50 BeadChip. Moreover, we present a panel of candidate markers acquired using different genetic models for breed discrimination. Quality control on the initial dataset resulted in 48,841 SNPs kept for downstream analysis. Principal component and admixture analyses were applied to assess population structure. The rate of inbreeding within breed was evaluated based on the distribution of runs of homozygosity in the genome and respective coefficients, the genomic relationship matrix, the patterns of linkage disequilibrium, and the historic effective population size. Results showed that both breeds exhibit high levels of genetic diversity. Level of inbreeding between the two breeds estimated by the Wright's fixation index FST was low (Fst = 0.04362), indicating the existence of a weak genetic differentiation between them. In addition, grouping of farms according to their geographical locations was observed. This study presents for the first time a genome-based analysis on the genetic structure of the two indigenous Greek goat breeds and identifies markers that can be potentially exploited in future selective breeding programs for traceability purposes, targeted genetic improvement schemes and conservation strategies

Influence of Retrograde Intramedullary Beam Position Within Talar Body on Radiographic Failure of Medial Column Fusion

Category: Midfoot/Forefoot; Diabetes Introduction/Purpose: Intramedullary fixation in the form of retrograde beam or bolt has developed as an intriguing treatment option for unstable midfoot collapse. This is particularly true when it is desired to minimize the length of incision or to avoid surface implants in a compromised soft tissue envelope. However, prior studies have demonstrated high rates of complications associated with intramedullary midfoot fusion constructs (Ford et al., Butt et al). The goal of this study was to create a reproducible convention of classifying position of the terminal implant within the talar body and to uncover an association of relative position of the implant at the time of surgery with an increased risk of failure. Methods: Consecutive patients treated surgically from January 2017 to September 2022 with retrograde intramedullary fusion beam were identified; 44 were included in the final analysis. Average age was 62.7 years and mean radiographic follow up measured 12.86 months. Figure 1 demonstrates our classification of relative talar position. First, a line was drawn along the axis of the talar neck and carried posteriorly dividing the talar body into dorsal and plantar hemispheres. Then, a line was drawn from the anterior articular margin of the talar body to the lateral talar process. Parallel lines were then created in an equidistant fashion to divide the talar body into equal relative quartiles. At the time of surgery, the tip of the intramedullary beam was classified into relative axial and coronal position by a single observer. Our primary outcomes were hardware failure defined by implant fracture or cutout from the bone or additional surgery. Results: Successful midfoot fusion with intramedullary beam was achieved in 77% of our cases. 10 cases demonstrated hardware failure or the need for additional surgery. Relative implant position was classified as dorsal in 43% of cases and plantar in 57% of cases. Talar quartile depth was classified as 1st in 6% cases, 2nd in 32% of cases, 3rd in 30% of cases, and 4th in 32% of cases. There was no clinical or statistically significant difference between rates of failure based on relative implant position. Conclusion: Retrograde intramedullary fusion for medial column collapse remains a viable treatment option and our data supports successful fusion in most patients but a risk of failure remains significant. In this study, the relative position of the terminal implant within the talar body did not correlate with an increased risk of failure. There are likely other patient specific, or biomechanical factors leading to hardware fracture, cut out, or return of deformity. Continued analysis as sample size increases remains paramount to forming additional conclusions

Predictors of Intraoperative and Early Complications in Total Ankle Replacement

Category: Ankle Arthritis; Ankle Introduction/Purpose: Predictors of intra operative and early complications following total ankle replacement (TAR) become more important as the incidence and indications for TAR continue to expand. Talar bone loss whether from avascular necrosis, osteoarthritis, or post traumatic arthritis can be a challenging problem to deal with in TAR. The aim of this study is to report predictors of complications in TAR with talar bone loss. Methods: A retrospective review using CPT codes for four surgeons over a three-year period at an academic institution was performed. A single surgeon reviewed the immediate preoperative plain radiographs for 200 consecutive patients for talar bone loss. The mortise and lateral views were used to calculate talar bone loss and then averaged (Fig 1). 37 patients were identified as having talar bone defects of greater than 20 percent when the two measurements were averaged. Our preoperative variables we looked at were size of talar defect, location, and cause of talar defect and postoperatively, the implant choice. Our primary outcomes were intraoperative fracture, reoperation, subsidence, and revision surgery. Results: The average follow up was 23 months. The average defect size was 54 percent with a range of 20 to 100 percent. Mann U Whitney tests were performed that showed a relationship between the lateral and overall percentage of talar bone loss being predictive of subsidence of the talar component. A Fischer exact test showed a that a chamfered talus cut was protective against subsidence. The mean of the talar bone loss for the chamfered components were 40% versus 58% in flat cut. There were no other significant differences when comparing complications, fracture, reoperation, or wound complications. Conclusion: While TAR for patients with talar bone loss can be a good option for the patient and surgeon it does have a higher complication rate than standard TARs. Careful attention should be given to the percentage of talar bone loss. Flat cut and revision style components were more likely to be used in worse situations, so it is not the authors belief that they are more prone to subsidence. All patients over 20% bone loss need extensive discussion regarding potential complications and additional procedures. Talar bone loss is a difficult problem to deal with but TAR is a viable option

Prophylactic Antibiotics After Stented, Distal Hypospadias Repair: Randomized Pilot Study

The usage of prophylactic oral antibiotics following distal hypospadias repair with stenting has been recently challenged. This study evaluated the incidence of symptomatic urinary tract infections (UTIs) following stented, distal hypospadias repair and the impact of prophylactic antibiotic therapy. Subjects 0 to 5 years of age with distal hypospadias were randomized to either Group 1 (antibiotics) or Group 2 (no prophylactic therapy). Urinalysis/urine culture was obtained intraoperatively with no preoperative antibiotics given. Phone interviews at 1 month and 3 months after surgery were done. Forty-eight patients were successfully randomized to either Group 1 (24) or Group 2 (24). The incidence of symptomatic UTI in this pilot study is low, and prophylactic antibiotic therapy does not appear to lower the incidence of symptomatic UTI. A larger, randomized, multicenter trial is needed to determine whether antibiotic prophylaxis reduces the risk of symptomatic UTIs following stented, distal hypospadias repair

A KBase Case Study on Genome-wide Transcriptomics and Plant Primary Metabolism in response to Drought Stress in Sorghum.

A better understanding of the genetic and metabolic mechanisms that confer stress resistance and tolerance in plants is key to engineering new crops through advanced breeding technologies. This requires a systems biology approach that builds on a genome-wide understanding of the regulation of gene expression, plant metabolism, physiology and growth. In this study, we examine the response to drought stress in Sorghum, as we leverage the tools for transcriptomics and plant metabolic modeling we have implemented at the U.S. Department of Energy Systems Biology Knowledgebase (KBase). KBase enables researchers worldwide to collaborate and advance research by uploading private or public data into the KBase Narrative Interface, analyzing it using a rich, extensible array of computational and data-analytics tools, and securely sharing scientific workflows and conclusions. We demonstrate how to use the current RNA-seq tools in KBase, applicable to both plants and microbes, to assemble and quantify long transcripts and identify differentially expressed genes effectively. More specifically, we demonstrate the utility of the platform by identifying key genes differentially expressed during drought-stress in Sorghum bicolor, an important sustainable production crop plant. We then show how we can use KBase tools to predict the membership of genes in metabolic pathways and examine expression data in the context of metabolic subsystems. We demonstrate the power of the platform by making the data, analysis and interpretation available to the biologists in the reproducible, re-usable, point-and-click format of a KBase Narrative thus promoting FAIR (Findable, Accessible, Interoperable and Reusable) guiding principles for scientific data management and stewardship