Energy functions in de novo protein design: current challenges and future prospects.
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ABSTRACT:
SUBMITTER: Li Z
PROVIDER: S-EPMC3851009 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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Project description:Five decades have passed since the first mumps vaccine was licensed. Over this period, a resurgence of mumps infections has been recorded worldwide. Although global mumps infections have been controlled through vaccination, outbreaks are still on the rise, including in populations with high vaccination coverage. Several epidemiological studies suggest that this infectious virus continues to be a worldwide public health threat. The development and deployment of an improved, prophylactic mumps vaccine that provides long-lasting protection is indeed a priority. The purpose of this review is to provide an immuno-biological perspective on mumps vaccines. Here, we review the virology of mumps, licensed mumps vaccines, and the typical immune responses elicited following mumps vaccination. Furthermore, we discuss the limitations and challenges of the currently licensed mumps vaccines and provide strategies for the development of an improved mumps vaccine.
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Project description:Hepatic encephalopathy (HE) is a common complication of liver dysfunction, including acute liver failure and liver cirrhosis. HE presents as a spectrum of neuropsychiatric symptoms ranging from subtle fluctuating cognitive impairment to coma. It is a significant contributor of morbidity in patients with liver disease. HE is observed in acute liver failure, liver bypass procedures, for example, shunt surgry and transjugular intrahepatic portosystemic shunt, and cirrhosis. These are classified as Type A, B and C HE, respectively. HE can also be classified according to whether its presence is overt or covert. The pathogenesis is linked with ammonia and glutamine production, and treatment is based on mechanisms to reduce the formation and/or removal of these compounds. There is no specific diagnostic test for HE, and diagnosis is based on clinical suspicion, excluding other causes and use of clinical tests that may support its diagnosis. Many tests are used in trials and experimentally, but have not yet gained universal acceptance. This review focuses on the definitions, pathogenesis and treatment of HE. Consideration will be given to existing treatment, including avoidance of precipitating factors and novel therapies such as prebiotics, probiotics, antibiotics, laxatives, branched-chain amino acids, shunt embolization and the importance of considering liver transplant in appropriate cases.
| S-EPMC5868572 | biostudies-literature
Project description:Diabetic gastroparesis (DMGP) is a condition of delayed gastric emptying after gastric outlet obstruction has been excluded. Symptoms of nausea, vomiting, early satiety, bloating, and abdominal pain are associated with DMGP. Uncontrolled symptoms can lead to overall poor quality of life and financial burdens on the healthcare system. A combination of antiemetics and prokinetics is used in symptom control; metoclopramide is the main prokinetic available for clinical use and is the only U.S. Food and Drug Administration-approved agent in the United States. However, a black box warning in 2009 reporting its association with tardive dyskinesia and recommending caution in chronically using this agent beyond 3 months has decreased its role in clinical practice. There is an unmet need for new prokinetics with good efficacy and safety profiles. Currently, there are several new drugs with different mechanisms of action in the pipeline that are under investigation and show promising preliminary results. Surgically combining gastric electrical stimulation with pyloroplasty is considered "gold" standard. Advances in therapeutic endoscopic intervention with gastric per-oral endoscopic pyloromyotomy have also been shown to improve gastric emptying and gastroparesis (GP) symptoms. In this review, we will comment on the challenges encountered when managing patients with DMGP and provide an update on advances in drug development and endoscopic and surgical interventions.
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Project description:Neurotrophic keratopathy (NK), or neurotrophic keratitis, is a degenerative condition that results from decreased innervation to the cornea. The cornea is innervated by the ophthalmic branch of the trigeminal nerve. Neurotrophic keratopathy is most commonly caused by herpes keratitis however, any condition that disrupts the normal corneal innervation can cause NK. Neurotrophic keratopathy is a clinical diagnosis and is classified into three stages based on the disease severity. Stage 1 has mild epithelial defects, such as punctate keratopathy, stage 2 disease has persistent epithelial defects, and stage 3 is defined by the presence of ulcers. Current treatment modalities consist of medical and surgical options. Stage 1 is treated with lubrication through artificial tears, eyelid taping, and punctal plug/cautery. Stage 2 treatment can involve therapeutic contact lenses, topical autologous or allogenic serum, tarsorrhaphy, botulinum toxin injections, and possibly anti-inflammatory medications. Stage 3 disease may require human nerve growth factor, amniotic membrane transplantation, conjunctival flap, or corneal neurotization. New therapies, such as matrix regenerating therapy, plasma rich in growth factors, Thymosin β4, Substance P/Insulin like growth factor-1, and nicergoline represent exciting future options.KEY MESSAGESNeurotrophic keratopathy is a rare degenerative disease defined by decreased innervation to the cornea that is associated with significant morbidity.Treatment options range from lubrication alone to various medical and surgical treatments.Matrix regenerating therapy, plasma rich in growth factors, Thymosin β4, Substance P/Insulin like growth factor-1, and nicergoline are exciting novel therapies that will influence how neurotrophic keratopathy is treated in the future.
| S-EPMC8903790 | biostudies-literature
Project description:Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The impairment of corneal sensory innervation causes the reduction of both protective reflexes and trophic neuromodulators that are essential for the vitality, metabolism, and wound healing of ocular surface tissues. A wide range of ocular and systemic conditions, including herpetic keratitis, ocular chemical burns, corneal surgery, diabetes, multiple sclerosis, and neurosurgical procedures, can cause NK by damaging trigeminal innervation. Diagnosis of NK requires careful investigation of any ocular and systemic condition associated with the disease, complete ocular surface examination, and quantitative measurement of corneal sensitivity. The clinical stages of NK range from corneal epithelial alterations (stage 1) to persistent epithelial defect (stage 2) and ulcer (stage 3), which may progress to corneal perforation. Management of NK is based on clinical severity, and the aim of the therapy is to halt the progression of corneal damage and promote epithelial healing. Although several medical and surgical treatments have been proposed, no therapies are currently available to restore corneal sensitivity, and thus, NK remains difficult and challenging to treat. The purpose of this review is to summarize available evidence on the pathogenesis, diagnosis, and treatment of NK. Novel medical and surgical therapies including the topical administration of nerve growth factor and corneal neurotization are also described.
| S-EPMC6029608 | biostudies-literature
Project description:BackgroundCurrent advancements in next-generation sequencing technology have made possible to sequence whole genome but assembling a large number of short sequence reads is still a big challenge. In this article, we present the comparative study of seven assemblers, namely, ABySS, Velvet, Edena, SGA, Ray, SSAKE, and Perga, using prokaryotic and eukaryotic paired-end as well as single-end data sets from Illumina platform.ResultsResults showed that in case of single-end data sets, Velvet and ABySS outperformed in all the seven assemblers with comparatively low assembling time and high genome fraction. Velvet consumed the least amount of memory than any other assembler. In case of paired-end data sets, Velvet consumed least amount of time and produced high genome fraction after ABySS and Ray. In terms of low memory usage, SGA and Edena outperformed in all the assemblers. Ray also showed good genome fraction; however, extremely high assembling time consumed by the Ray might make it prohibitively slow on larger data sets of single and paired-end data.ConclusionsOur comparison study will provide assistance to the scientists for selecting the suitable assembler according to their data sets and will also assist the developers to upgrade or develop a new assembler for de novo assembling.
| S-EPMC5826002 | biostudies-literature
Project description:Although anthropologists frequently report the centrality of odours in the daily lives and cultural beliefs of many small-scale communities, Western scholars have historically considered the sense of smell as minimally involved in human communication. Here, we suggest that the origin and persistence of this latter view might be a consequence of the fact that most research is conducted on participants from Western societies who, collectively, were rather old (adults), deodorized and desensitized (ODD) to various aspects of olfactory perception. The view is rapidly changing, however, and this themed issue provides a timely overview of the current state-of-the-art on human chemocommunication. Based on evolutionary models of communication, the papers cover both general mechanisms of odour production by 'senders' and odour perception by 'receivers'. Focus on specific functional contexts includes reciprocal impact of odours between infants and mothers, the role of odour in mate choice and how odours communicate emotion and disease. Finally, a position paper outlines pitfalls and opportunities for the future, against the context of the replication crisis in psychology. We believe a more nuanced view of human chemical communication is within our grasp if we can continue to develop inter-disciplinary insights and expand research activities beyond ODD people. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.
| S-EPMC7209938 | biostudies-literature
Project description:IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, exhibiting a variable clinical and pathological course and significantly contributing to the global burden of chronic kidney disease and end-stage renal disease. Current standards of care focus on optimization of antihypertensive and antiproteinuric therapies (typically renin- angiotensin system blockade) to reduce disease progression. Much recent attention has focused on whether additional immunosuppression confers better outcomes than supportive management alone, and indeed, several trials have demonstrated renoprotective effects following the use of oral corticosteroids. However, results have been inconsistent, and perceived benefits must be balanced against risks and adverse effects associated with generalized immunosuppression, as highlighted by the high-profile STOP-IgAN and TESTING clinical trials. Recent translational research in vitro and animal models of IgAN have generated greater insight into potential therapeutic targets for this complex autoimmune disease. Deeper understanding of the roles of the mucosal immune barrier, complement activation and deposition, T-cell dependent and independent mechanisms of B cell activation, and of the deposition and downstream inflammatory signaling pathways of nephritogenic polymeric IgA1 complexes (e.g., signaling of immune receptors via spleen tyrosine kinase) has formed the rationale for the development of novel agents and clinical trials of more targeted therapies. However, translating findings into clinical practice is challenging, with many immunopathological features of IgAN specific to humans. Recent comprehensive reviews outline current understanding of mechanisms of IgAN as well as ongoing and future clinical trials; it is not our aim to replicate this here. Instead, we take a mechanistic approach to current treatment strategies, outlining advantages and limitations of each before exploring ongoing research with potential translation into future targeted therapies for this complex disease.
| S-EPMC5905843 | biostudies-literature
Project description:Purpose:Incidence and mortality of biliary tract carcinoma (BTC) are increasing, especially in South America and Asia. Such a disease often bears a dismal prognosis because of diagnosis occurring at late stages and for the frequent relapses after surgery. The aims of this review were to summarize the state of the art of the treatment of BTC and give a view at possible future prospects linked with molecular profiling, immunotherapy, and targeted therapies. Design:We conducted a systematic literature search using MEDLINE and the 2018 ASCO Meeting abstract databases to identify published clinical trials, translational series, and meeting abstracts. All significant papers and abstracts available to date were included. Results:For resected BTC, thanks to the BILCAP study, adjuvant chemotherapy (CT) with capecitabine should be regarded as the new standard of care. For locally advanced inoperable and metastatic diseases, the use of chemoradiotherapy and radioembolization has not been supported by any randomized Phase III study. The standard of care remains the combination of CT with gemcitabine and cisplatin, as reported by the ABC-02 trial. All targeted therapies have failed to improve the survival outcomes, either in combination with CT or as single agents and are not recommended in the treatment of BTC. Whole-exome sequencing and molecular profiling have helped in identifying genetic signatures typical of different BTC subtypes. With this support, new trials with targeted agents and immunotherapy have been designed, and results are awaited. Conclusion:BTC still remains a disease with very few treatment options. Different BTC subtypes own peculiar gene mutations and pathways alterations. Therefore, molecular profiling may be the only key to enable new tailored strategies with targeted agents and immunotherapy.
| S-EPMC6314055 | biostudies-literature
Project description:Cold agglutinin disease (CAD) is a complement-dependent, classical pathway-mediated immune hemolytic disease, accounting for 15-25% of autoimmune hemolytic anemia, and at the same time, a distinct clonal B-cell lymphoproliferative disorder of the bone marrow. The disease burden is often high, but not all patients require pharmacological treatment. Several therapies directed at the pathogenic B-cells are now available. Rituximab plus bendamustine or rituximab monotherapy should be considered first-line treatment, depending on individual patient characteristics. Novel treatment options that target the classical complement pathway are under development and appear very promising, and the C1s inhibitor sutimlimab is currently being investigated in two clinical Phase II and III trials. These achievements have raised new challenges and further prospects, which are discussed. Patients with CAD requiring therapy should be considered for clinical trials.
| S-EPMC6497508 | biostudies-literature