Status of Divisions of the International Geologic Time Scale

Each chronostratigraphic unit of the International Geologic Time Scale will be defined at its base by a Global Stratotype Section and Point (GSSP) or Global Standard Stratigraphic Age (GSSA). Nearly 50 GSSPs and 10 GSSAs have now been ratified. Ideally, the GSSP coincides with events having a global correlation potential. The international stage divisions of some systems, such as the Jurassic or Neogene, are similar to traditional usage in European geology. However, in order to utilize global correlation horizons, the international stage divisions of other systems, such as the Ordovician or Permian, have required assembling new stage nomenclatures or hybrids of different regional stages. A reference table by the International Commission on Stratigraphy itemizes the current or potential GSSP and GSSA definitions of all international geologic time units.     

Pseudouridine in RNA: what, where, how, and why

Pseudouridine (5-ribosyluracil) is a ubiquitous yet enigmatic constituent of structural RNAs (transfer, ribosomal, small nuclear, and small nucleolar). Although pseudouridine (psi) was the first modified nucleoside to be discovered in RNA, and is the most abundant, its biosynthesis and biological roles have remained poorly understood since its identification as a "fifth nucleoside" in RNA. Recently, a combination of biochemical, biophysical, and genetic approaches has helped to illuminate the structural consequences of psi in polyribonucleotides, the biochemical mechanism of U-->psi isomerization in RNA, and the role of modification enzymes (psi synthases) and box H/ACA snoRNAs, a class of eukaryotic small nucleolar RNAs, in the site-specific biosynthesis of psi. Through its unique ability to coordinate a structural water molecule via its free N1-H, psi exerts a subtle but significant "rigidifying" influence on the nearby sugar-phosphate backbone and also enhances base stacking. These effects may underlie the biological role of most (but perhaps not all) of the psi residues in RNA. Certain genetic mutants lacking specific psi residues in tRNA or rRNA exhibit difficulties in translation, display slow growth rates, and fail to compete effectively with wild-type strains in mixed culture. In particular, normal growth is severely compromised in an Escherichia coli mutant deficient in a pseudouridine synthase responsible for the formation of three closely spaced psi residues in the mRNA decoding region of the 23S rRNA. Such studies demonstrate that pseudouridylation of RNA confers an important selective advantage in a natural biological context.     

Visual attention: the where,what, how and why of saliency

Attention influences the processing of visual information even in the earliest areas of primate visual cortex. There is converging evidence that the interaction of bottom-up sensory information and top-down attentional influences creates an integrated saliency map, that is, a topographic representation of relative stimulus strength and behavioral relevance across visual space. This map appears to be distributed across areas of the visual cortex, and is closely linked to the oculomotor system that controls eye movements and orients the gaze to locations in the visual scene characterized by a high salience.     

Oscillatory signaling processes: the how, the why and the where

Oscillatory processes in biological signal transduction have come under progressively increasing scrutiny in terms of their functional significance and mechanisms of emergence and regulation. Since oscillatory processes can be a by-product of rapid adaptation and can also easily emerge if the feedback underlying adaptive processes is inadvertently artificially enhanced, one needs to exercise caution in both claiming the existence of in vivo oscillations and seeking to assign to them a specific functional significance. Nevertheless, oscillations can be a powerful means of encoding and transferring information both in time and in space, thus possessing important potential advantages for evolutionary selection and stabilization. Thus periodicity in the cell responses to diverse persistent external stimuli might become a more recognized and even expected feature of signaling processes.     

The what, where, how and why of gene ontology--a primer for bioinformaticians

With high-throughput technologies providing vast amounts of data, it has become more important to provide systematic, quality annotations. The Gene Ontology (GO) project is the largest resource for cataloguing gene function. Nonetheless, its use is not yet ubiquitous and is still fraught with pitfalls. In this review, we provide a short primer to the GO for bioinformaticians. We summarize important aspects of the structure of the ontology, describe sources and types of functional annotations, survey measures of GO annotation similarity, review typical uses of GO and discuss other important considerations pertaining to the use of GO in bioinformatics applications.     

Caveolin‐1 as a promoter of tumour spreading: when,how, where and why

Caveolae are non‐clathrin invaginations of the plasma membrane in most cell types; they are involved in signalling functions and molecule trafficking, thus modulating several biological functions, including cell growth, apoptosis and angiogenesis. The major structural protein in caveolae is caveolin‐1, which is known to act as a key regulator in cancer onset and progression through its role as a tumour suppressor. Caveolin‐1 can also promote cell proliferation, survival and metastasis as well as chemo‐ and radioresistance. Here, we discuss recent findings and novel concepts that support a role for caveolin‐1 in cancer development and its distant spreading. We also address the potential application of caveolin‐1 in tumour therapy and diagnosis.     

The influence of species diversity on ecosystem productivity: how,where, and why?

The effect of species diversity on ecosystem productivity is controversial, in large part because field experiments investigating this relationship have been fraught with difficulties. Unfortunately, there are few guidelines to aid researchers who must overcome these difficulties and determine whether global species losses seriously threaten the ecological and economic bases of terrestrial ecosystems. In response, I offer a set of hypotheses that describe how diversity might influence productivity in plant communities based on three well-known mechanisms: complementarity, facilitation, and the sampling effect. Emphasis on these mechanisms reveals the sensitivity of any diversity-productivity relationship to ecological context (i.e., where this relationship should be found); ecological context includes characteristics of the surrounding environment, temporal and spatial scales of observation, and the intensity of human management. In particular, the legitimacy of the sampling effect as a mechanism of productivity enhancement is dependent upon the degree to which stochastic events influence immigration and extinction processes in a given ecosystem. A mechanistic approach also requires that the three mechanisms be separated and quantified in diversity experiments, and I examine the most appropriate analyses for doing so, focusing on the overyielding technique. Finally, I question why productivity per se is a relevant management concern in non-agricultural systems once relationships among diversity, productivity, and the qualities of the surrounding environment are considered.     

The why,what, where,when and how of goal-directed choice: neuronal and computational principles

The central problems that goal-directed animals must solve are: ‘What do I need and Why, Where and When can this be obtained, and How do I get it?'' or the H4W problem. Here, we elucidate the principles underlying the neuronal solutions to H4W using a combination of neurobiological and neurorobotic approaches. First, we analyse H4W from a system-level perspective by mapping its objectives onto the Distributed Adaptive Control embodied cognitive architecture which sees the generation of adaptive action in the real world as the primary task of the brain rather than optimally solving abstract problems. We next map this functional decomposition to the architecture of the rodent brain to test its consistency. Following this approach, we propose that the mammalian brain solves the H4W problem on the basis of multiple kinds of outcome predictions, integrating central representations of needs and drives (e.g. hypothalamus), valence (e.g. amygdala), world, self and task state spaces (e.g. neocortex, hippocampus and prefrontal cortex, respectively) combined with multi-modal selection (e.g. basal ganglia). In our analysis, goal-directed behaviour results from a well-structured architecture in which goals are bootstrapped on the basis of predefined needs, valence and multiple learning, memory and planning mechanisms rather than being generated by a singular computation.     

The what,how and why of doing macroecology

Macroecology is a growing and important subdiscipline of ecology, but it is becoming increasingly diffuse, without an organizing principle that is widely agreed upon. I highlight two main current views of macroecology: as the study of large‐scale systems and as the study of emergent systems. I trace the history of both these views through the writings of the founders of macroecology. I also highlight the transmutation principle that identifies serious limitations to the study of large‐scale systems with reductionist approaches. And I suggest that much of the underlying goal of macroecology is the pursuit of general principles and the escape from contingency. I highlight that there are many intertwined aspects of macroecology, with a number of resulting implications. I propose that returning to a focus on studying assemblages of a large number of particles is a helpful view. I propose defining macroecology as “the study at the aggregate level of aggregate ecological entities made up of large numbers of particles for the purposes of pursuing generality”.     

Integron-bearing methicillin-resistant coagulase-negative staphylococci in South China, 2001–2004

A total of 53 methicillin-resistant coagulase-negative staphylococci strains isolated in a hospital in Guangzhou, China, were analyzed to detect class 1 integrons and SCC mec typing. Thirty strains had the class 1 integrase ( intI1 ) gene and 26 strains possessed the 3' conserved region of qacE Δ 1 - sul1 . Four different types of gene cassette arrays were found and a highly prevalent array of dfrA12-orfF-aadA2 gene cassettes was observed. Thirty class 1 integron-positive coagulase-negative staphylococci strains were subjected to Southern hybridization analysis; the result showed that class 1 integrons were located on chromosome, not plasmid. According to the results of SCC mec typing for 30 integron-bearing MRCNS strains, five, 15 and five strains belonged to type I, II and III SCC mec , respectively, and five strains were untypeable. For 23 non-integron-bearing methicillin-resistant coagulase-negative staphylococci strains, four, nine and seven strains belonged to type I, II and III SCC mec , respectively, and three strains were untypeable. None of the strains belonged to type IV or V. Twenty-three coagulase-negative staphylococci isolates of three Staphylococcal species that contained the dfrA12-orfF-aadA2 gene cassette array were phylogenetically unrelated to each other by randomly amplified polymorphic DNA, indicating that the gene cassettes might be disseminated in the clinical strains by a horizontal gene transfer.     

mRNA vaccines for COVID-19: what,why and how

The Coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2), has impacted human lives in the most profound ways with millions of infections and deaths. Scientists and pharmaceutical companies have been in race to produce vaccines against SARS-CoV-2. Vaccine generation usually demands years of developing and testing for efficacy and safety. However, it only took less than one year to generate two mRNA vaccines from their development to deployment. The rapid production time, cost-effectiveness, versatility in vaccine design, and clinically proven ability to induce cellular and humoral immune response have crowned mRNA vaccines with spotlights as most promising vaccine candidates in the fight against the pandemic. In this review, we discuss the general principles of mRNA vaccine design and working mechanisms of the vaccines, and provide an up-to-date summary of pre-clinical and clinical trials on seven anti-COVID-19 mRNA candidate vaccines, with the focus on the two mRNA vaccines already licensed for vaccination. In addition, we highlight the key strategies in designing mRNA vaccines to maximize the expression of immunogens and avoid intrinsic innate immune response. We also provide some perspective for future vaccine development against COVID-19 and other pathogens.     

Sculpture and vascularization of dermal bones,and the implications for the physiology of basal tetrapods

Sculpture of dermal bones and their vascularization in basal tetrapods are closely connected. Ontogenetic data suggest that the large vessels that coursed to the superficial bone surface induced the formation of sculptural ridges and tubercles around their openings. Imprints show that the vessels continued on the bone surface and coursed within furrows or pits, where they were protected by the sculpture from mechanical damage. Dermal bone histology indicates a consolidation of the integument in basal tetrapods by strong, mineralized Sharpey's fibres in the sculptural ridges and tubercles, and by the presence of metaplastic tissue in several taxa. Because of the tight integration of bone and dermis, the large vessels were not able to spread over the sculptural elements, but instead had to pass interosseously. The diverse sculptural morphologies depend on the variation in height and width of the ‘nodal points’ and their connecting ridges, and in the size and shape of the enclosed cells and furrows. A principal component analysis (PCA) and discriminant function analysis (DFA) of 47 basal tetrapod taxa with 12 discrete characters shows that dermal sculpture is suited for distinguishing some main basal tetrapod lineages. Taxa that are interpreted as being largely aquatic have generally a more regular sculpture than presumably terrestrial ones. © 2010 The Linnean Society of London, Zoological Journal of the Linnean Society, 2010, 160 , 302–340.     

Historical review and surveillance of Japanese encephalitis, Republic of Korea, 2002–2004

Japanese encephalitis virus (JEV), transmitted by culicine mosquitoes, is endemic throughout much of South‐East Asia, extending to the Korean Peninsula. The zoonotic cycle is from large water birds to culicine mosquitoes, with swine as an amplifying host and man as an incidental host. Culex tritaeniorhynchus, the primary JEV vector in the Republic of Korea, populations peak in late August through to early September when most cases of Japanese encephalitis (JE) are reported. Cx. tritaeniorhynchus were observed near the Demilitarized Zone in each of the years that mosquitoes were assayed for JEV. Each year that vector mosquitoes were assayed for JEV, minimum field infection rates (number of JEV positive mosquites/1000 Cx. tritaeniorhynchus assayed) ranged from 0.31 to 3.27. The epidemiology of JE has been recorded in Korea for more than half a century, from 1949 to 2005. During a major epidemic in 1949, there were 5616 cases and 2729 deaths reported, with levels persisting near epidemic levels of 1000 cases annually thereafter until 1969. Following the introduction and government mandated mass immunization in 1971, JE decreased dramatically. Since 1984, 0–6 cases of JE have been reported each year. However, continued evidence of mosquitoes positive for JEV indicates that JE continues to be a civilian and military health threat to immunocompromised persons in Korea, as well as non‐immune US soldiers, civilians and their family members.     

Inhibition of a mitotic motor protein: where, how, and conformational consequences

We report here the first inhibitor-bound structure of a mitotic motor protein. The 1.9 A resolution structure of the motor domain of KSP, bound with the small molecule monastrol and Mg2+ x ADP, reveals that monastrol confers inhibition by "induced-fitting" onto the protein some 12 A away from the catalytic center of the enzyme, resulting in the creation of a previously non-existing binding pocket. The structure provides new insights into the biochemical and mechanical mechanisms of the mitotic motor domain. Inhibition of KSP provides a novel mechanism to arrest mitotic spindle formation, a target of several approved and investigative anti-cancer agents. The structural information gleaned from this novel pocket offers a new angle for the design of anti-mitotic agents.