Current Issues in Molecular Biology

472 KiB

Open AccessReview

Insular Microbiogeography: Three Pathogens as Exemplars

by James H. Kaufman, Christopher A. Elkins, Matthew Davis, Allison M. Weis, Bihua C. Huang, Mark K. Mammel, Isha R. Patel, Kristen L. Beck, Stefan Edlund, David Chambliss, Judith Douglas, Simone Bianco, Mark Kunitomi and Bart C. Weimer

Curr. Issues Mol. Biol. 2020, 36(1), 89-108; https://doi.org/10.21775/cimb.036.089 - 09 Oct 2019

Cited by 4 | Viewed by 526

Abstract

Traditional taxonomy in biology assumes that life is organized in a simple tree. Attempts to classify microorganisms in this way in the genomics era led microbiologists to look for finite sets of 'core' genes that uniquely group taxa as clades in the tree. [...] Read more.

Traditional taxonomy in biology assumes that life is organized in a simple tree. Attempts to classify microorganisms in this way in the genomics era led microbiologists to look for finite sets of 'core' genes that uniquely group taxa as clades in the tree. However, the diversity revealed by large-scale whole genome sequencing is calling into question the long-held model of a hierarchical tree of life, which leads to questioning of the definition of a species. Large-scale studies of microbial genome diversity reveal that the cumulative number of new genes discovered increases with the number of genomes studied as a power law and subsequently leads to the lack of evidence for a unique core genome within closely related organisms. Sampling 'enough' new genomes leads to the discovery of a replacement or alternative to any gene. This power law behaviour points to an underlying self-organizing critical process that may be guided by mutation and niche selection. Microbes in any particular niche exist within a local web of organism interdependence known as the microbiome. The same mechanism that underpins the macro-ecological scaling first observed by MacArthur and Wilson also applies to microbial communities. Recent metagenomic studies of a food microbiome demonstrate the diverse distribution of community members, but also genotypes for a single species within a more complex community. Collectively, these results suggest that traditional taxonomic classification of bacteria could be replaced with a quasispecies model. This model is commonly accepted in virology and better describes the diversity and dynamic exchange of genes that also hold true for bacteria. This model will enable microbiologists to conduct population-scale studies to describe microbial behaviour, as opposed to a single isolate as a representative. Full article

436 KiB

Open AccessReview

Function of Prion Protein and the Family Member, Shadoo

by Takashi Onodera, Takuya Nishimura, Katsuaki Sugiura and Akikazu Sakudo

Curr. Issues Mol. Biol. 2020, 36(1), 67-88; https://doi.org/10.21775/cimb.036.067 - 27 Sep 2019

Cited by 7 | Viewed by 607

Abstract

Lowering cellular prion protein (PrP^C) levels in the brain is predicted to be a powerful therapeutic strategy for the prion disease. PrP^C may act as an antiapoptotic agent by blocking some of the internal environmental factors that initiate apoptosis. Prion [...] Read more.

Lowering cellular prion protein (PrP^C) levels in the brain is predicted to be a powerful therapeutic strategy for the prion disease. PrP^C may act as an antiapoptotic agent by blocking some of the internal environmental factors that initiate apoptosis. Prion protein (PrP)-knockout methods provide powerful indications on the neuroprotective function of PrP^C. Using PrP^C-knockout cell lines, the inhibition of apoptosis through stress inducible protein1 (STI1) is mediated by PrP^C-dependent superoxide dismutase (SOD) activation. Besides, PrP-knockout exhibited wide spread alterations of oscillatory activity in the olfactory bulb as well as altered paired-pulse plasticity at the dendrodendric synapse. Both the behavioural and electro-physiological phenotypes could be rescued by neuronal PrP^C expression. Neuprotein Shadoo (Sho), similarly to PrP^C, can prevent neuronal cell death induced by the expression of PrP△HD mutants, an artificial PrP mutant devoid of internal hydrophobic domain. Sho can efficiently protect cells against exito-toxin-induced cell death by glutamates. Sho and PrP seem to be dependent on similar domains, in particular N-terminal (N), and their internal hydrophobic domain. Sho△N and Sho△HD displayed a reduced stress-protective activity but are complex glycosylated and attached to the outer leaflet of the plasma membrane via glycosylphosphatidylinositol (GPI) anchor indicating that impaired activity is not due to incorrect cellular trafficking. In Sho, over-expressed mice showed large amyloid plaques not seen in wild-type mice. However, Shadoo is not a major modulator of abnormal prion protein (PrP^Sc) accumulation. Sho and PrP share a stress-protective activity. The ability to adopt a toxic conformation of PrP^Sc seems to be specific for PrP. Full article

75 KiB

Open AccessEditorial

Introduction to Current Progress in Advanced Research on Prions

by Takashi Onodera and Akikazu Sakudo

Curr. Issues Mol. Biol. 2020, 36(1), 63-66; https://doi.org/10.21775/cimb.036.063 - 27 Sep 2019

Cited by 5 | Viewed by 1819

Abstract

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurological diseases that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, camel spongiform encephalopathy (CSE) in camels and chronic wasting disease (CWD) in cervids. A [...] Read more.

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurological diseases that include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle, camel spongiform encephalopathy (CSE) in camels and chronic wasting disease (CWD) in cervids. A key event in prion diseases is the conversion of the cellular, host-encoded prion protein (PrP^C) to its abnormal isoform (PrP^Sc) predominantly in the central nervous system of the infected host (Aguzzi et al., 2004). These diseases are transmissible under some circumstances, but unlike other transmissible disorders, prion diseases can also be caused by mutations in the host gene. The mechanism of prion spread among sheep and goats that develop natural scrapie is unknown. CWD, transmissible mink encephalopathy (TME), BSE, feline spongiform encephalopathy (FSE), and exotic ungulate encephalopathy (EUE) are all thought to occur after the consumption of prion-infected material. Most cases of human prion disease occur from unknown reasons, and greater than 20 mutations in the prion protein (PrP) gene may lead to inherited prion disease. In other instances, prion diseases are contracted by exposure to prion infectivity. These considerations raise the question of how a mere protein aggregate can bypass mucosal barriers, circumvent innate and adoptive immunity, and traverse the blood-brain barrier to give rise to brain disease. Here, we will briefly introduce a few topics in current prion studies. Full article

1067 KiB

Open AccessReview

Microbiome: Effects of Ageing and Diet

by Nuria Salazar, Sonia González, Alicja M. Nogacka, David Rios-Covián, Silvia Arboleya, Miguel Gueimonde and Clara G. de los Reyes-Gavilán

Curr. Issues Mol. Biol. 2020, 36(1), 33-62; https://doi.org/10.21775/cimb.036.033 - 27 Sep 2019

Cited by 43 | Viewed by 2548

Abstract

The microbial community inhabiting our intestine, known as 'microbiota', and the ensemble of their genomes (microbiome) regulate important functions of the host, being essential for health maintenance. The recent development of next-generation sequencing (NGS) methods has greatly facilitated the study of the microbiota [...] Read more.

The microbial community inhabiting our intestine, known as 'microbiota', and the ensemble of their genomes (microbiome) regulate important functions of the host, being essential for health maintenance. The recent development of next-generation sequencing (NGS) methods has greatly facilitated the study of the microbiota and has contributed to evidence of the strong influence exerted by age and diet. However, the precise way in which the diet and its components modify the functionality of the intestinal microbiome is far from being completely known. Changes in the intestinal microbiota occur during ageing, frequently accompanied by physiological changes of the digestive tract, modification of dietary patterns and impairment of the immune system. Establishing nutritional strategies aiming to counterbalance the specific alterations taking place in the microbiota during ageing would contribute to improved health status in the elderly. This review will analyse changes appearing in the intestinal microbiota from adulthood to old age and their association with dietary patterns and lifestyle factors. Full article

157 KiB

Open AccessReview

Inactivation Methods for Prions

by Akikazu Sakudo

Curr. Issues Mol. Biol. 2020, 36(1), 23-32; https://doi.org/10.21775/cimb.036.023 - 11 Sep 2019

Cited by 12 | Viewed by 1320

Abstract

Incidences of iatrogenic Creutzfeldt-Jakob disease (iCJD) are caused by transplantation of prion-contaminated hormones, cornea and dura mater as well as contact with prion- contaminated medical devices, such as stereotactic electrodes, used in neurosurgery. Because prions are highly resistant and difficult to inactivate, prion [...] Read more.

Incidences of iatrogenic Creutzfeldt-Jakob disease (iCJD) are caused by transplantation of prion-contaminated hormones, cornea and dura mater as well as contact with prion- contaminated medical devices, such as stereotactic electrodes, used in neurosurgery. Because prions are highly resistant and difficult to inactivate, prion contamination is a severe risk when medical instruments are reused after surgical procedures involving suspicious and confirmed cases of patients with prion diseases. Therefore, when high-risk procedures such as cerebral surgery, craniotomy surgery, orthopaedic spinal surgery and ophthalmic surgery are performed for high-risk patients or individuals with prion diseases, it is neces- sary to appropriately treat the medical devices using scientifically proven prion inactivation methods. In this chapter, we introduce fundamental aspects of prion inactivation methods, looking specifically at the practical issues involved in their implementation. Full article

154 KiB

Open AccessReview

Chronic Wasting Disease: Current Assessment of Transmissibility

by Akikazu Sakudo

Curr. Issues Mol. Biol. 2020, 36(1), 13-22; https://doi.org/10.21775/cimb.036.013 - 09 Sep 2019

Cited by 8 | Viewed by 959

Abstract

Chronic wasting disease (CWD) is a prion disease of cervids characterized by clini- cal symptoms of progressive weight loss, abnormal behaviour and excessive salivation. Incidents have been reported in North America and Korea as well as in Europe. Current knowledge, based on in [...] Read more.

Chronic wasting disease (CWD) is a prion disease of cervids characterized by clini- cal symptoms of progressive weight loss, abnormal behaviour and excessive salivation. Incidents have been reported in North America and Korea as well as in Europe. Current knowledge, based on in vitro and in vivo experiments, suggests direct CWD transmis- sion to humans is unlikely. Nonetheless, humans may consume CWD-infected materials, which presents a potential risk. Studies indicate that transmission by horizontal infection of cervids probably occurs via saliva, faeces, and urine as well as from environmental res- ervoirs of prions found in soil and water. In addition, infectivity in the skeletal muscle of infected deer has been observed. These findings suggest that direct contact with infected animals and indirect contact with prion-contaminated materials are potential sources of infection. However, recent studies on the detection of pregnancy-related prion infectivity imply the potential transmission of CWD from mother to offspring. In this review, fundamental aspects of CWD are reviewed. Full article

420 KiB

Open AccessReview

Effect of Microglial Inflammation in Prion Disease

by Yasuhisa Ano, Akikazu Sakudo and Takashi Onodera

Curr. Issues Mol. Biol. 2020, 36(1), 1-12; https://doi.org/10.21775/cimb.036.001 - 05 Sep 2019

Cited by 2 | Viewed by 530

Abstract

Prion diseases are a group of transmissible fatal neurodegenerative disorders. Neuropatho- logical features of prion diseases include neuroinflammation featuring the infiltration of activated microglia in affected brain areas as well as the accumulation of an abnormal isoform of the cellular prion protein and [...] Read more.

Prion diseases are a group of transmissible fatal neurodegenerative disorders. Neuropatho- logical features of prion diseases include neuroinflammation featuring the infiltration of activated microglia in affected brain areas as well as the accumulation of an abnormal isoform of the cellular prion protein and neuronal loss. Recent studies have elucidated that inflammation in the brain induced by microglia plays an important role in the pathogenesis of neurodegenerative disorders including prion disease. Thus, the regulation of neuroin- flammation is key in terms of therapeutic and preventative approaches. The functions of neuroinflammation and microglia in this disease are discussed in this article. Full article

Journal Menu

Journal Browser

Curr. Issues Mol. Biol., Volume 36, Issue 1 (April 2020) – 7 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI