Genetics in Osteoarthritis Knee

Osteoarthritis (OA) is a debilitating joint disorder with a complex pathogeny wherein diverse factors interact, causing a process of deterioration of the articular cartilage and the subchondral bone. It can be primary or secondary but has common clinical, radiological, and pathological manifestations. Unfortunately, there are no curative or preventive options available for this disease. The knee is the most common site to develop OA among all synovial joints. Both environmental and genetic factors play an essential role in the initiation of the disease. Identifying the genes underlying the genetic background could give new insights into the pathophysiology of knee osteoarthritis (KOA) and could potentially lead to new drug targets. Several genes involving developmental processes or maintenance of cartilage and bone are found to be associated with KOA susceptibility and progression. Understanding the gene functions has improved the knowledge towards the disease pathogenesis. So, it will be of interest to investigate the role of gene-gene interaction in the disease

Spinal Cord Injury Prevalence and Treatment Modalities

Spinal cord injury (SCI) is a devasting neurological condition producing physical dependency, morbidity, psychological stress, and financial burden. During the last 30 years, its global prevalence has increased from 236 to 1298 cases per million populations. Two types of spinal cord injury are primary and secondary injury. Primary injury is mechanical damage to the cord itself whereas secondary injury results from one or more biochemical and cellular processes that are triggered by the primary lesion. In 1700 BC, in an Egyptian surgical papyrus, they describe the frustration of health care professionals in treating a severe spinal cord injury, the Papyrus reported spinal fractures as a “disease that should not be treated”. Most of these studies approach a patient with acute spinal cord injury (ASCI) in one of four manners: corrective surgery or a physical, biological, or pharmacological treatment method. Science is unraveling the mechanisms of cell protection and neuroregeneration, but clinically, we only provide supportive care for patients with spinal cord injuries. By combining these treatments, researchers attempt to enhance the functional recovery of patients with spinal cord injuries. Advances in the last decade have allowed us to encourage the development of experimental studies in the field of spinal cord regeneration. The combination of several therapeutic strategies should, at a minimum, allow for partial functional recoveries for these patients, which could improve their quality of life. More studies were done on spinalized animals that indicate that most of these pharmacological agents may act on receptors present in the spinal cord, thus facilitate to produce coordinated locomotor movement, whereas some other drugs used to improve the neuropathological changes caused because of spinal cord injury (SCI), such as spasticity or demyelination, to improve walking

Treatment Modalities of Ankylosing Spondylitis

Ankylosing spondylitis is a chronic inflammatory arthropathy of young adults which primarily affects the axial skeleton. The pathogenesis of AS is unclear, but it is thought to be caused by an early inflammatory phase followed by ossification that may induce local osteitis. It has also been linked to an increase in morbidity and mortality and is known to have a debilitating impact on QoL of the patients. Whereby, CRP and ESR are used for assessment of the disease activity and determination of treatment efficacy, HLA-B27 is considered the best biomarker for AS diagnosis. The conventional therapeutic regimen like NSAIDs and DMARDs alone are not effective in controlling symptoms and indicators of disease; however, when combined with the physical therapy, great improvement in the QoL of the patients has been observed. The outlook for AS has improved remarkably with the advent of biologics that blocks key inflammatory cytokines such as TNF inhibitors. Biologics aids in halting disease progression, and can be used concomitantly with other medications for pain management. In this chapter, barring surgical interventions, we will discuss about the non-pharmacological and pharmacological therapies routinely employed for the treatment of AS, as well as the novel therapeutics currently under study

Shifting the limits in wheat research and breeding using a fully annotated reference genome

Introduction: Wheat (Triticum aestivum L.) is the most widely cultivated crop on Earth, contributing about a fifth of the total calories consumed by humans. Consequently, wheat yields and production affect the global economy, and failed harvests can lead to social unrest. Breeders continuously strive to develop improved varieties by fine-tuning genetically complex yield and end-use quality parameters while maintaining stable yields and adapting the crop to regionally specific biotic and abiotic stresses. Rationale: Breeding efforts are limited by insufficient knowledge and understanding of wheat biology and the molecular basis of central agronomic traits. To meet the demands of human population growth, there is an urgent need for wheat research and breeding to accelerate genetic gain as well as to increase and protect wheat yield and quality traits. In other plant and animal species, access to a fully annotated and ordered genome sequence, including regulatory sequences and genome-diversity information, has promoted the development of systematic and more time-efficient approaches for the selection and understanding of important traits. Wheat has lagged behind, primarily owing to the challenges of assembling a genome that is more than five times as large as the human genome, polyploid, and complex, containing more than 85% repetitive DNA. To provide a foundation for improvement through molecular breeding, in 2005, the International Wheat Genome Sequencing Consortium set out to deliver a high-quality annotated reference genome sequence of bread wheat. Results: An annotated reference sequence representing the hexaploid bread wheat genome in the form of 21 chromosome-like sequence assemblies has now been delivered, giving access to 107,891 high-confidence genes, including their genomic context of regulatory sequences. This assembly enabled the discovery of tissue- and developmental stage–related gene coexpression networks using a transcriptome atlas representing all stages of wheat development. The dynamics of change in complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. Aspects of the future value of the annotated assembly for molecular breeding and research were exemplarily illustrated by resolving the genetic basis of a quantitative trait locus conferring resistance to abiotic stress and insect damage as well as by serving as the basis for genome editing of the flowering-time trait. Conclusion: This annotated reference sequence of wheat is a resource that can now drive disruptive innovation in wheat improvement, as this community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding. Importantly, the bioinformatics capacity developed for model-organism genomes will facilitate a better understanding of the wheat genome as a result of the high-quality chromosome-based genome assembly. By necessity, breeders work with the genome at the whole chromosome level, as each new cross involves the modification of genome-wide gene networks that control the expression of complex traits such as yield. With the annotated and ordered reference genome sequence in place, researchers and breeders can now easily access sequence-level information to precisely define the necessary changes in the genomes for breeding programs. This will be realized through the implementation of new DNA marker platforms and targeted breeding technologies, including genome editing

Stock Price Prediction Website Using Linear Regression - A Machine Learning Algorithm

The most valuable indicator of a company’s success is its stock price, which can rise in tandem with the price of a single share. For that reason, businesses advertise their stocks to their customers in an effort to get them to buy them. The volatility of stock prices makes it difficult for clients or stockholding companies to forecast the future value of a single stock. Therefore, stock market forecasting has emerged as the most well-liked topic in the corporate sector, and hence solving this problem has become so important for the betterment of the investors and buyers as many a times they have to face loss in their investment and this problem can be solve by various Machine learning algorithms. To solve this problem we are developing one stock price prediction website using Python and Linear Regression which is one of the best Machine Learning statistical method for predictive analysis. We are using historical Data for the prediction. Finding a method to use linear regression models to obtain more precise values is the major goal. To acquire more precise results from the linear regression models, it is possible to change the dataset that will be used to train the models. The purpose of this paper is to demonstrate that linear regression is the most appropriate and effective method for forecasting stock market analysis

Rapid Development and Characterization of Chromosome Specific Translocation Line of Thinopyrum elongatum with Improved Dough Strength

The protein content and its type are principal factors affecting wheat (Triticum aestivum) end product quality. Among the wheat proteins, glutenin proteins, especially, high molecular weight glutenin subunits (HMW-GS) are major determinants of processing quality. Wheat and its primary gene pool have limited variation in terms of HMW-GS alleles. Wild relatives of wheat are an important source of genetic variation. For improvement of wheat processing quality its wild relative Thinopyrum elongatum with significant potential was utilized. An attempt was made to replace Th. elongatum chromosome long arm (1EL) carrying HMW-GS genes related to high dough strength with chromosome 1AL of wheat with least or negative effect on dough strength while retaining the chromosomes 1DL and 1BL with a positive effect on bread making quality. To create chromosome specific translocation line [1EL(1AS)], double monosomic of chromosomes 1E and 1A were created and further crossed with different cultivars and homoeologous pairing suppressor mutant line PhI. The primary selection was based upon glutenin and gliadin protein profiles, followed by sequential genomic in situ hybridization (GISH) and fluorescent in situ hybridization (FISH). These steps significantly reduced time, efforts, and economic cost in the generation of translocation line. In order to assess the effect of translocation on wheat quality, background recovery was carried out by backcrossing with recurrent parent for several generations and then selfing while selecting in each generation. Good recovery of parent background indicated the development of almost near isogenic line (NIL). Morphologically also translocation line was similar to recipient cultivar N61 that was further confirmed by seed storage protein profiles, RP-HPLC and scanning electron microscopy. The processing quality characteristics of translocation line (BC4F6) indicated significant improvement in the gluten performance index (GPI), dough mixing properties, dough strength, and extensibility. Our work aims to address the challenge of limited genetic diversity especially at chromosome 1A HMW-GS locus. We report successful development of chromosome 1A specific translocation line of Th. elongatum in wheat with improved dough strength