Mitochondrial biogenesis: An update

In response to the energy demand triggered by developmental signals and environmental stressors, the cells launch the mitochondrial biogenesis process. This is a self‐renewal route, by which new mitochondria are generated from the ones already existing. Recently, considerable progress has been made in deciphering mitochondrial biogenesis‐related proteins and genes that function in health and in pathology‐related circumstances. However, an outlook on the intracellular mechanisms shared by the main players that drive mitochondrial biogenesis machinery is still missing. Here, we provide such a view by focusing on the following issues: (a) the role of mitochondrial biogenesis in homeostasis of the mitochondrial mass and function, (b) the signalling pathways beyond the induction/promotion, stimulation and inhibition of mitochondrial biogenesis and (c) the therapeutic applications aiming the repair and regeneration of defective mitochondrial biogenesis (in ageing, metabolic diseases, neurodegeneration and cancer). The review is concluded by the perspectives of mitochondrial medicine and research.     

The influence of sexually active non-reproductive groups on persistent sexually transmitted diseases

We describe several population models exposed to a mild life-long sexually transmitted disease, i.e. without significant increased mortality among infected individuals and providing no immunity/recovery. We then modify these models to include non-reproductive groups consisting of those isolated from sexual contact and those who are sexually active but infertile due to choice, medical or other reasons. We analyse the potential effect on the dynamics of the population. We are interested in how the isolated class may curb the growth of the infected group while keeping the healthy population at acceptable levels. We also analyse the difference between being sexually active and abstained within the non-reproductive class and its impact on the epidemic reproductive number and the nature of the bifurcation around the disease-free equilibrium. We provide a comparison with our models introduced in a previous article, which include only the isolated from sexual contact class.     

A genome‐wide association study for the incidence of persistent bovine viral diarrhea virus infection in cattle

Bovine viral diarrhea viruses (BVDV) comprise a diverse group of viruses that cause disease in cattle. BVDV may establish both transient and persistent infections depending on the developmental stage of the animal at exposure. The objective was to determine whether genomic regions harboring single nucleotide polymorphisms (SNPs) could be associated with the presence or absence of persistent BVDV infection. A genome‐wide association approach based on 777 000 SNP markers was used. Samples of animals identified as positive (n = 1200) or negative (n = 1200) for the presence of BVDV in skin samples (n = 1200) were used. DNA samples were combined in 24 pools (100 animals per pool). One SNP, significant at the 5 percent genome‐wide level (P = 9.41 × 10^?8), was detected on chromosome 14, located at position 80 675 176 bp. Fifteen SNPs, residing on chromosomes 1, 2, 6, 8, 10, 15 and 18, were moderately associated (P < 1 × 10^?5) with persistent BVDV infection. Results show that genes harboring or neighboring significant SNPs are involved in leucopenia, signal transduction, RNA splicing and DNA methylation processes.     

The signal peptide as a new target for drug design

Many current and potential drug targets are membrane-bound or secreted proteins that are expressed and transported via the Sec61 secretory pathway. They are targeted to translocon channels across the membrane of the endoplasmic reticulum (ER) by signal peptides (SPs), which are temporary structures on the N-termini of their nascent chains. During translation, such proteins enter the lumen and membrane of the ER by a process known as co-translational translocation. Small molecules have been found that interfere with this process, decreasing protein expression by recognizing the unique structures of the SPs of particular proteins. The SP may thus become a validated target for designing drugs for numerous disorders, including certain hereditary diseases.     

A preliminary study on the relationships between diurnal melatonin secretion profile and sleep variables in patients emergently admitted to the coronary care unit

To clarify the significance of melatonin secretion under intensive care conditions, we investigated melatonin secretion profiles and sleep parameters of 23 patients just after admission to the coronary care unit (CCU) and 19 age-matched controls. Sleep parameters were evaluated by actigraphy, and melatonin secretion was assessed by measuring the urinary 6-sulphatoxy melatonin (6-SMT). 6-SMT secretion was lower and nocturnal sleep parameters were less satisfactory in the subjects than those in the controls, and there were positive correlations between these variables, particularly in the subject patients. The lowered melatonin secretion might be involved in the mechanism of insomnia in CCU patients.     

From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes

Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies. [BMB Reports 2015; 48(10): 549-558]     

Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis

Because protein variants play critical roles in many diseases including TDP-43 in Amyotrophic Lateral Sclerosis (ALS), alpha-synuclein in Parkinson’s disease and beta-amyloid and tau in Alzheimer’s disease, it is critically important to develop morphology specific reagents that can selectively target these disease-specific protein variants to study the role of these variants in disease pathology and for potential diagnostic and therapeutic applications. We have developed novel atomic force microscopy (AFM) based biopanning techniques that enable isolation of reagents that selectively recognize disease-specific protein variants. There are two key phases involved in the process, the negative and positive panning phases. During the negative panning phase, phages that are reactive to off-target antigens are eliminated through multiple rounds of subtractive panning utilizing a series of carefully selected off-target antigens. A key feature in the negative panning phase is utilizing AFM imaging to monitor the process and confirm that all undesired phage particles are removed. For the positive panning phase, the target antigen of interest is fixed on a mica surface and bound phages are eluted and screened to identify phages that selectively bind the target antigen. The target protein variant does not need to be purified providing the appropriate negative panning controls have been used. Even target protein variants that are only present at very low concentrations in complex biological material can be utilized in the positive panning step. Through application of this technology, we acquired antibodies to protein variants of TDP-43 that are selectively found in human ALS brain tissue. We expect that this protocol should be applicable to generating reagents that selectively bind protein variants present in a wide variety of different biological processes and diseases.     

The role of global trade and transport network topology in the human‐mediated dispersal of alien species

More people and goods are moving further and more frequently via many different trade and transport networks under current trends of globalisation. These networks can play a major role in the unintended introduction of exotic species to new locations. With the continuing rise in global trade, more research attention is being focused on the role of networks in the spread of invasive species. This represents an emerging field of research in invasion science and the substantial knowledge being generated within other disciplines can provide ecologists with new tools with which to study invasions. For the first time, we synthesise studies from several perspectives, approaches and disciplines to derive the fundamental characteristics of network topology determining the likelihood of spread of organisms via trade and transport networks. These characteristics can be used to identify critical points of vulnerability within these networks and enable the development of more effective strategies to prevent invasions.