F1000Prime Reports

The nucleolus is a non-membrane-bound nuclear organelle found in all eukaryotes. It is the quintessential 'RNA-seeded' nuclear body, forming around specific chromosomal features called nucleolar organizing regions that contain arrays of ribosomal DNA. Assembly is triggered by activation of RNA polymerase I-mediated transcription and regulated in mammalian cells in a cell cycle-dependent manner. Although the nucleolus is best known for its role in coordinating ribosome biogenesis, biochemical and proteomic analyses have revealed a much wider functional complexity than previously appreciated, including roles in cell cycle regulation, DNA damage sensing and repair, pre-mRNA processing, telomere metabolism, processing of non-coding RNAs, and coordination of the cellular response to various stresses...

Invasions by non-native species have caused many extinctions and greatly modified many ecosystems and are among the major anthropogenic global changes transforming the earth. Beginning in the mid-1980s, a dramatic burst of research in invasion biology has revealed a plethora of previously unrecognized impacts and laid bare the scope of the phenomenon. Similarly, research on various methods of managing invasions has expanded enormously, yielding incremental improvements in traditional methods and the advent of several new approaches, including the use of species-specific genetic and pheromonal methods...

The entirely subcutaneous implantable cardioverter defibrillator (S-ICD(®)) is emerging as a widely accepted therapeutic alternative to a conventional implantable cardioverter defibrillator (ICD) for prevention of sudden cardiac death. Essentially, the S-ICD(®) is promising in terms of reduction of electrode-related complications such as lead failure and infections. The conventional transvenous ICD has proven efficacy in various randomized clinical trials. The first results of S-ICD(®) studies confirm efficacy and safety in primary and secondary prevention as well...

Cochlear implants are a medical prosthesis used to treat sensorineural deafness, and one of the greatest advances in modern medicine. The following article is an overview of cochlear implant technology. The history of cochlear implantation and the development of modern implant technology will be discussed, as well as current surgical techniques. Research regarding expansion of candidacy, hearing preservation cochlear implantation, and implantation for unilateral deafness are described. Lastly, innovative technology is discussed, including the hybrid cochlear implant and the totally implantable cochlear implant...

Significant progress in our understanding of Crohn's disease (CD), an archetypal common, complex disease, has now been achieved. Our ability to interrogate the deep complexities of the biological processes involved in maintaining gut mucosal homeostasis is a major over-riding factor underpinning this rapid progress. Key studies now offer many novel and expansive insights into the interacting roles of genetic susceptibility, immune function, and the gut microbiota in CD. Here, we provide overviews of these recent advances and new mechanistic themes, and address the challenges and prospects for translation from concept to clinic...

Understanding of posttraumatic stress disorder (PTSD) has increased substantially in the past several decades. There is now more awareness of the many different types of trauma that can lead to PTSD, greater refinement of diagnostic criteria, and the development and testing of various treatments for it. As implementation of PTSD therapies has increased, there is also increased attention to the key issues of retention and dropout. Retention refers to the percentage of patients who stay in a treatment for its intended dose, and dropout is the opposite (the percentage who leave prior to the intended dose); both of which have major implications for treatment outcomes...

As mitochondria are the powerhouses of the cell, their damage during the cell suicide process of apoptosis is essentially responsible for cellular demise in most cells. A key family of proteins, the B-cell lymphoma-2 (BCL-2) family, determines the integrity of mitochondria in the face of apoptotic insult. A comprehensive understanding of the molecular details of how apoptosis is initiated and how it culminates is essential if apoptosis is to fulfil its undoubted potential as a therapeutic target to treat diseases ranging from cancer to neurodegenerative conditions...

Compared with normal cells, cancer cells show alterations in many cellular processes, including energy metabolism. Studies on cancer metabolism started with Otto Warburg's observation at the beginning of the last century. According to Warburg, cancer cells rely on glycolysis more than mitochondrial respiration for energy production. Considering that glycolysis yields much less energy compared with mitochondrial respiration, Warburg hypothesized that mitochondria must be dysfunctional and this is the initiating factor for cancer formation...

The management of preterm birth has seen major transformations in the last few decades with increasing interest worldwide, due to the impact of preterm birth on neonatal morbidity and mortality. The prevention strategies currently available for asymptomatic women at risk of preterm birth include progesterone, cervical cerclage and cervical pessary. Each approach has varying effects depending on the patient's prior history of preterm birth, cervical length and the presence of multiple gestations. There is a shift in the focus of antenatal treatment, with the use of prenatal magnesium sulphate and corticosteroids, to reduce neonatal intensive care admissions and longer-term disabilities associated with preterm birth, consequently relieving emotional and economical burden...

Memory CD8 T cells generated after acute viral infections or live vaccines can persist for extended periods, in some instances for life, and play an important role in protective immunity. This long-lived immunity is achieved in part through cytokine-mediated homeostatic proliferation of memory T cells while maintaining the acquired capacity for rapid recall of effector cytokines and cytolytic molecules. The ability of memory CD8 T cells to retain their acquired properties, including their ability to remain poised to recall effector functions, is a truly impressive feat given that these acquired properties can be maintained for decades without exposure to cognate antigen...

The development of the ventral midbrain is orchestrated by a number of cell-extrinsic and -intrinsic factors that control critical processes, such as the patterning of the neural tube along the main body axis and the specification of diverse neuronal cell types in distinct positions of the neural tube. Subsequently, the regulation of neurogenesis and survival- acquire particular relevance in order to define the final size of diverse neuronal populations. In a series of studies during the last few years, we have identified liver X receptors (LXRs) as critical regulators of ventral midbrain development...

Primary ciliary dyskinesia (PCD) is a ciliopathy, but represents the sole entity from this class of disorders that results from the dysfunction of motile cilia. Characterized by respiratory problems appearing in childhood, infertility, and situs defects in ~50% of individuals, PCD has an estimated prevalence of approximately 1 in 10,000 live births. The diagnosis of PCD can be prolonged due to a lack of disease awareness, coupled with the fact that symptoms can be confused with other more common genetic disorders, such as cystic fibrosis, or environmental insults that result in frequent respiratory infections...

Food allergy is a common problem in childhood. The term is used to include both immunoglobulin E (IgE)-mediated and non-IgE-mediated food allergies, which have a significant effect on the quality of life of patients and their families. In this report, we aim to discuss recent advances in the diagnosis, management, and treatment modalities of food allergy in children.

Drug-induced liver injury (DILI) is a potentially fatal adverse event with significant medical and economic impact. Many drugs, especially anti-infective, neurologic or pain-modifying substances, act as hepatotoxins. With cardiovascular toxicity, liver toxicity is one of the two leading causes for drug withdrawal from the market. The liver can be affected directly, in a predictable and dose-dependent manner, or idiosyncratically, independent of the dose and therefore unpredictable. Currently DILI is a diagnosis of exclusion that physicians have to bear in mind in patients with an unexplained increase of liver enzymes...

Menstrual disorders are a major reason for gynaecological consultations worldwide and, unfortunately there are many different definitions and classifications of this condition. Clear definitions and terminology are necessary for scientific literature, particularly for clinicians, and for clinical trials comparing two treatments. The International Federation of Gynaecology and Obstetrics (FIGO) Menstrual Disorders Working Group has proposed abandoning the use of one common term, dysfunctional uterine bleeding (DUB), while continuing to use the terms abnormal uterine bleeding (AUB) and heavy menstrual bleeding (HMB)...

Osmotically driven turgor pressure of plant cells can be higher than that of a car tire. It puts tremendous forces onto cell walls and drives cell growth and changes in cell shape. This has given rise to unique mechanisms to control organ formation compared to metazoans. The fascinating interplay between forces and local cellular reorganization is still poorly understood. Growth of lateral roots is a prominent example of a developmental process in which mechanical forces between neighboring cells are generated and must be dealt with...

Gene expression is controlled by diverse mechanisms before, during, and after transcription. Chromatin modification factors as well as transcriptional repressors, silencers, and enhancers all feed into how eukaryotes transcribe RNA in the nucleus. However, there is increasing evidence that post-transcriptional regulation of gene expression is as widespread as transcriptional control if not more so. Studies of specific transcripts in oocytes and embryos are at the core of our mechanistic understanding of many post-transcriptional events...

Origins of DNA replication (ORIs) occur at defined regions in the genome. Although DNA sequence defines the position of ORIs in budding yeast, the factors for ORI specification remain elusive in metazoa. Several methods have been used recently to map ORIs in metazoan genomes with the hope that features for ORI specification might emerge. These methods are reviewed here with analysis of their advantages and shortcomings. The various factors that may influence ORI selection for initiation of DNA replication are discussed...

Lipid mediators play an important role in infection- and tissue injury-driven inflammatory responses and in the subsequent inhibition and resolution of the response. Here, we discuss recent findings that substantiate how Mycobacterium tuberculosis promotes its survival in the host by dysregulation of lipid mediator balance. By inhibiting prostaglandin E2 (PGE2) and enhancing lipoxin production, M. tuberculosis induces necrotic death of the macrophage, an environment that favors its growth. These new findings provide opportunities for developing and repurposing therapeutics to modulate lipid mediator balance and enhance M...

Non-alcoholic steatohepatitis (NASH) can lead to advanced fibrosis, hepatocellular carcinoma, and end-stage liver disease requiring liver transplantation. A myriad of pathways and genetic influence contribute to NASH pathogenesis and liver disease progression. Diagnosing patients with NASH and advanced fibrosis is critical prior to treatment and prognostication. There has been ongoing interest in developing non-invasive biomarkers and tools for identifying NASH and advanced fibrosis. To date, there has been no approved therapy for NASH...