Avian proteomics: advances, challenges and new technologies

Proteomics is defined as an analysis of the full complement of proteins of a cell or tissue under given conditions. Avian proteomics, or more specifically chicken proteomics, has focussed on the study of individual tissues and organs of interest to specific researchers. Researchers have looked at skeletal muscle and growth, and embryonic development and have performed initial studies in avian disease. Traditional proteomics involves identifying and cataloguing proteins in a cell and identifying relative changes in populations between two or more states, be that physiological or disease-induced states. Recent advances in proteomic technologies have included absolute quantification, proteome simplification and the ability to determine the turnover of individual proteins in a global context. This review discusses the current developments in this relatively new field, new technologies and how they may be applied to biological questions, and the challenges faced by researchers in this ever-expanding and exciting field.     

Recent advances in obstructive sleep apnea pathophysiology and treatment

Obstructive sleep apnea (OSA) is a sleep disorder characterized by recurring collapse of the pharyngeal airway leading to restricted airflow. OSA is becoming increasingly common with at least moderate disease now evident in 17% of middle aged men and 9% of women. The list of recognized adverse health consequences associated with OSA is growing and includes daytime symptoms of sleepiness, impaired cognition and risk of motor vehicle accidents as well as associations with hypertension, cardiovascular morbidity, malignancy and all-cause mortality. In this context adequate treatment of OSA is imperative; however, there are well-recognized pitfalls in the uptake and usage of the standard treatment modality, Continuous Positive Airway Pressure (CPAP). A broad range of pathophysiological mechanisms are now recognized beyond an anatomically smaller pharyngeal airway and impaired compensatory pharyngeal muscle responsiveness. Perturbations in ventilatory control stability, low arousal threshold, sleep-related decrease in lung volume and fluid redistribution as well as upper airway surface tension have all been shown to variously contribute to sleep-disordered breathing. Many new therapies are emerging from these advances in understanding of the mechanisms of OSA. Although many may not be universally effective, the promise of phenotyping patients according to their individual pathophysiology in order to target one or more therapies may prove highly effective and allow the treatment of OSA towards a personalized medicine approach.

     

Recent advances in pathophysiology and treatment of spinal cord injury

Thirty years ago, patients with spinal cord injury (SCI) and their families were told "nothing can be done" to improve function. Since the SCI patient population is reaching normal life expectancy through better health care, it has become an obviously worthwhile enterprise to devote considerable research effort to SCI. Targets for intervention in SCI toward improved function have been identified using basic research approaches and can be simplified into a list: (1) reduction of edema and free-radical production, (2) rescue of neural tissue at risk of dying in secondary processes such as abnormally high extracellular glutamate concentrations, (3) control of inflammation, (4) rescue of neuronal/glial populations at risk of continued apoptosis, (5) repair of demyelination and conduction deficits, (6) promotion of neurite growth through improved extracellular environment, (7) cell replacement therapies, (8) efforts to bridge the gap with transplantation approaches, (9) efforts to retrain and relearn motor tasks, (10) restoration of lost function by electrical stimulation, and (11) relief of chronic pain syndromes. Currently, over 70 clinical trials are in progress worldwide. Consequently, in this millennium, unlike in the last, no SCI patient will have to hear "nothing can be done."     

Plant pan-genomics: recent advances,new challenges,and roads ahead

Pan-genomics can encompass most of the genetic diversity of a species or population and has proved to be a powerful tool for studying genomic evolution and the origin and domestication of species, and for providing information for plant improvement. Plant genomics has greatly progressed because of improvements in sequencing technologies and the rapid reduction of sequencing costs. Nevertheless, pan-genomics still presents many challenges, including computationally intensive assembly methods, high costs with large numbers of samples, ineffective integration of big data, and difficulty in applying it to downstream multi-omics analysis and breeding research. In this review, we summarize the definition and recent achievements of plant pan-genomics, computational technologies used for pan-genome construction, and the applications of pan-genomes in plant genomics and molecular breeding. We also discuss challenges and perspectives for future pan-genomics studies and provide a detailed pipeline for sample selection, genome assembly and annotation, structural variation identification, and construction and application of graph-based pan-genomes. The aim is to provide important guidance for plant pan-genome research and a better understanding of the genetic basis of genome evolution, crop domestication, and phenotypic diversity for future studies.     

The new era of Pompe disease: advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management

Pompe disease is an autosomal recessive neuromuscular disorder marked by progressive muscle weakness due to lysosomal buildup of glycogen. Presentation is described as a spectrum, varying by age of onset, organ involvement, and degree of myopathy. Given the phenotypic variability, Pompe disease is broadly classified into an infantile form and a late onset (juvenile, childhood, adult onset) form. Prior to the advent of enzyme replacement therapy (ERT) with alglucosidase alfa and approval for human use in 2006, the natural history was limited due to death before age 2 years for infantile onset cases and significant morbidity and early mortality for late onset Pompe disease (LOPD). ERT with alglucosidase alfa redefined the once fatal outcome in infantile Pompe, establishing an emergent phenotype. Treatment in late onset patients resulted in improved outcomes, enhancing understanding of the phenotype, presentation, and extent of organ involvement. This Issue of the Seminars seeks to enumerate the recent advancements in the field of Pompe disease, including newborn screening, novel therapeutic targets, new insights in the pathophysiology including role of autophagy, and impacts of long-term disease burden and CNS glycogen accumulation on cognition in infantile survivors. It also addresses immunological challenges and the critical role of immunomodulation in ERT treatment outcome. Other topics discussed include the role of biomarkers in monitoring disease progression and treatment responses, the role of genotype in defining phenotype and treatment response, better insights into the clinical presentations in LOPD and finally the importance of a multidisciplinary approach to care with the role of physical therapy as an example. Many gaps in our scientific understanding of this disease still remain; however, we hope the next decade will bring new knowledge and therapies to the horizon.     

Dirigent phenoxy radical coupling: advances and challenges

The past seven years have witnessed significant progress in the biochemical characterization of dirigent (monolignol radical binding) proteins in vitro, as well as in the delineation of their associated metabolic networks in planta. Interestingly, both the stereoselective and regiospecific control over phenoxy radical-radical coupling appears to have evolved during the transition of plants to a land base for lignan, norlignan and ellagitannin biosynthesis.     

Developmental psychopathology: recent advances and future challenges

The integrative field of developmental psychopathology is having a huge impact on our understanding of human health and behavior. In this paper, I use the example of children's early stress exposure to illustrate how developmental psychopathologists now tend to deemphasize diagnostic categories and, instead, emphasize the social and biological contexts, events and circumstances that have created opportunities for maladaptive responses and health problems in youth. This example shows that developmental psychopathology is increasing understanding of how children develop the abilities that allow them to cope effectively with challenges and what leads to failures in development of these abilities. Integrating research about the neurobiology of learning may prove to be a powerful future direction to understand how the environment regulates behavior. Learning processes become increasingly intricate and fine‐tuned as relevant neuroanatomical systems develop, and as the range, complexity and amount of environmental information increases for the developing child. A focus on these processes allows psychopathologists to formulate questions about which neural mechanisms children use to process information, how these mechanisms are themselves shaped by social context, why adverse social environments confer risk for children, and, perhaps, what sorts of neutrally informed interventions might remediate the deficits in self‐regulation that underlie common psychopathologies.     

Ocular herpes:the pathophysiology,management and treatment of herpetic eye diseases

Herpesviruses are a prominent cause of human viral disease, second only to the cold and influenza viruses. Most herpesvirus infections are mild or asymptomatic. However, when the virus invades the eye, a number of pathologies can develop and its associated sequelae have become a considerable source of ocular morbidity. The most common culprits of herpetic eye disease are the herpes simplex virus(HSV), varicella zoster virus(VZV), and cytomegalovirus(CMV). While primary infection can produce ocular disease, the most destructive manifestations tend to arise from recurrent infection. These recurrent infections can wreck devastating effects and lead to irreversible vision loss accompanied by a decreased quality of life, increased healthcare usage, and significant cost burden. Unfortunately, no method currently exists to eradicate herpesviruses from the body after infection. Treatment and management of herpes-related eye conditions continue to revolve around antiviral drugs, although corticosteroids, interferons, and other newer therapies may also be appropriate depending on the disease presentation. Ultimately, the advent of effective vaccines will be crucial to preventing herpesvirus diseases altogether and cutting the incidence of ocular complications.     

Ocular herpes: the pathophysiology,management and treatment of herpetic eye diseases

Herpesviruses are a prominent cause of human viral disease, second only to the cold and influenza viruses. Most herpesvirus infections are mild or asymptomatic. However, when the virus invades the eye, a number of pathologies can develop and its associated sequelae have become a considerable source of ocular morbidity. The most common culprits of herpetic eye disease are the herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV). While primary infection can produce ocular disease, the most destructive manifestations tend to arise from recurrent infection. These recurrent infections can wreck devastating effects and lead to irreversible vision loss accompanied by a decreased quality of life, increased healthcare usage, and significant cost burden. Unfortunately, no method currently exists to eradicate herpesviruses from the body after infection. Treatment and management of herpes-related eye conditions continue to revolve around antiviral drugs, although corticosteroids, interferons, and other newer therapies may also be appropriate depending on the disease presentation. Ultimately, the advent of effective vaccines will be crucial to preventing herpesvirus diseases altogether and cutting the incidence of ocular complications.     

Pantothenate biosynthesis in higher plants: advances and challenges

Pantothenate (vitamin B₅) is the precursor of the 4'-phosphopantetheine moiety of coenzyme A and acyl-carrier protein. Plants and microorganisms make the vitamin de novo, whereas animals must obtain it from their diet. Pantothenate is produced commercially by chemical synthesis for vitamin supplements, feed additives and cosmetics. An attractive alternative for production is biotransformation, which would avoid expensive procedures for separation of racemic intermediates. The biosynthetic pathway in bacteria, comprising four enzymic reactions, is well-established, and enzymes from Escherichia coli have been fully characterized including the overexpression and purification of recombinant enzymes and the determination of their X-ray crystal structures. Pantothenate biosynthesis in higher plants is beginning to be elucidated, and genes encoding the first and last enzymes have been identified and characterized in Arabidopsis thaliana and Oryza sativa (rice). This review describes our current understanding of the pathway in plants and the challenges that lie ahead in engineering plants to make increased amounts of the vitamin.     

Editing human hematopoietic stem cells: advances and challenges

Genome editing of hematopoietic stem and progenitor cells is being developed for the treatment of several inherited disorders of the hematopoietic system. The adaptation of CRISPR-Cas9-based technologies to make precise changes to the genome, and developments in altering the specificity and efficiency, and improving the delivery of nucleases to target cells have led to several breakthroughs. Many clinical trials are ongoing, and several pre-clinical models have been reported that would allow these genetic therapies to one day offer a potential cure to patients with diseases where limited options currently exist. However, there remain several challenges with respect to establishing safety, expanding accessibility and improving the manufacturing processes of these therapeutic products. This review focuses on some of the recent advances in the field of genome editing of hematopoietic stem and progenitor cells and illustrates the ongoing challenges.     

全基因组关联分析的进展与反思

全基因组关联分析(genomewide association study,GWAS)是应用人类基因组中数以百万计的单核苷酸多态性(single nucleotide polymorphism,SNP)为标记进行病例-对照关联分析,以期发现影响复杂性疾病发生的遗传特征的一种新策略。近年来,随着人类基因组计划和基因组单倍体图谱计划的实施,人们已通过GWAS方法发现并鉴定了大量与人类性状或复杂性疾病关联的遗传变异,为进一步了解控制人类复杂性疾病发生的遗传特征提供了重要的线索。然而,由于造成复杂性疾病/性状的因素较多,而且GWAS研究系统较为复杂,因此目前GWAS本身亦存在诸多的问题。本文将从研究方式、研究对象、遗传标记,以及统计分析等方面,探讨GWAS的研究现状以及存在的潜在问题,并展望GWAS今后的发展方向。     

Molecular pathogenesis of pancreatic cancer: advances and challenges

Pancreatic ductal adenocarcinoma (PDAC) is still a devastating and incurable disease with a median survival of 3-6 months and a 5-year survival rate of 1-4% when all stages are considered. Although crucial advances in our understanding of the molecular pathogenesis of the disease have been made, the exceptional aggressiveness of PDAC remains largely unexplained. Some key results will probably direct future PDAC research activities. For example, recent identification of pancreatic tumor stem cells has stimulated the debate over the cell of origin. Further, powerful new genetically engineered mouse models support the concept that stepwise progression of epithelial precursor lesions leads to invasive PDAC as a result of accumulating mutations in K-ras, INK4A/ARF, TP53 and DPC4; these models accentuate the initiating function of the K-ras mutation. Established PDAC exhibits all the classic hallmarks of cancer, including self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion, and metastasis. This review provides an overview of the molecular machinery that PDAC utilizes to acquire these tumorigenic capacities. Moreover, recent advances have identified essential elements of key pathways partly recapitulating developmental signals, and of the tumor microenvironment that promotes tumor growth through the complex interplay of its different cellular components. In spite of progress in molecular research, there is still a dichotomy between the encouraging results obtained with targeted interference of numerous oncogenic pathways in vitro and a lack of significant improvement in clinical detection and survival. Thus our primary challenge remains to translate the solid knowledge of genetic and epigenetic alterations in PDAC into clinical tools which can be used for early diagnosis and effective therapy.