A novel deconvolution method for modeling UDP-N-acetyl-D-glucosamine biosynthetic pathways based on 13C mass isotopologue profiles under non-steady-state conditions

This article is a response to Wang and Luo. See correspondence article http://www.biomedcentral.com/1741-7007/10/30/ [WEBCITE] and the original research article http://www.biomedcentral.com/1741-7007/9/24 [WEBCITE].     

Proteasome inhibition,the pursuit of new cancer therapeutics,and the adaptor molecule p130Cas

Current interest in proteasome inhibitors for cancer therapy has stimulated considerable research efforts to identify the molecular pathway to their cytotoxicity with a view to identifying the mechanisms of sensitivity and resistance as well as informing the development of new drugs. Zhao and Vuori describe this month in BMC Biology experiments indicating a novel role of the adaptor protein p130Cas in sensitivity to apoptosis induced not only by proteasome inhibitors but also by the unrelated drug doxorubicin.See research article: http://www.biomedcentral.com/1741-7007/9/73     

Tackling thermosensation with multidimensional phenotyping

Ring species, in which two different forms coexist in one region while being connected by a long chain of interbreeding populations encircling a geographic barrier, provide clear demonstrations of the evolution of one species into two. Known ring species are rare, but now Monahan et al. propose an intriguing new approach to discovering them: focus first on geography to find potential barriers. See research article http://www.biomedcentral.com/1741-7007/10/20     

The Rabs: A family at the root of metazoan evolution

This paper is a response to Pecinka A, Fang W, Rehmsmeier M, Levy AA, Mittelsten Scheid, O: Polyploidization increases meiotic recombination frequency in Arabidopsis. BMC Biology 2011, 9:24. See research article at http://www.biomedcentral.com/1741-7007/9/24     

Difficult phylogenetic questions: more data, maybe; better methods, certainly

The combination of molecular sequence data and bioinformatics has revolutionized phylogenetic inference over the past decade, vastly increasing the scope of the evolutionary trees that we are able to infer. A recent paper in BMC Biology describing a new phylogenomic pipeline to help automate the inference of evolutionary trees from public sequence databases provides another important tool in our efforts to derive the Tree of Life. See research article: http://www.biomedcentral.com/1741-7007/9/55     

Opening a can of centipedes: new insights into mechanisms of body segmentation

The search for a common developmental genetic mechanism of body segmentation appears to become more difficult, and more interesting, as new segmented organisms are added to the roster. Recent work in this journal by Brena and Akam on segmentation of the geophilomorph centipede Strigamia maritima, an arthropod distantly related to the standard insect models, contains developmental and evolutionary surprises that highlight the importance of a wider sampling of phyla.See research article: http://www.biomedcentral.com/1741-7007/11/112     

Frugal fat or munificent muscle: genomic imprinting and metabolism

Variation in body composition is a popular obsession. The culturally ‘ideal’ body type is light on fat and heavy on muscle but the human population is collectively laying on fat. A new study finds antagonistic effects of two imprinted genes, Grb10 and Dlk1, on body composition in mice. These findings pose the question whether there is an evolutionary conflict between genes of maternal and paternal origin over the optimal proportions of body fat and lean muscle mass.See research article: http://www.biomedcentral.com/1741-7007/12/771     

Segmental structure in banded mongoose calls

In complex animal vocalizations, such as bird or whale song, a great variety of songs can be produced via rearrangements of a smaller set of 'syllables', known as 'phonological syntax' or 'phonocoding' However, food or alarm calls, which function as referential signals, were previously thought to lack such combinatorial structure. A new study of calls in the banded mongoose Mungos mungo provides the first evidence of phonocoding at the level of single calls. The first portion of the call provides cues to the identity of the caller, and the second part encodes its current activity. This provides the first example known in animals of something akin to the consonants and vowels of human speech.See research article http://www.biomedcentral.com/1741-7007/10/97     

Modeling the epidemiological history of plague in Central Asia: Palaeoclimatic forcing on a disease system over the past millennium

Background

Human cases of plague (Yersinia pestis) infection originate, ultimately, in the bacterium's wildlife host populations. The epidemiological dynamics of the wildlife reservoir therefore determine the abundance, distribution and evolution of the pathogen, which in turn shape the frequency, distribution and virulence of human cases. Earlier studies have shown clear evidence of climatic forcing on contemporary plague abundance in rodents and humans.

Results

We find that high-resolution palaeoclimatic indices correlate with plague prevalence and population density in a major plague host species, the great gerbil (Rhombomys opimus), over 1949-1995. Climate-driven models trained on these data predict independent data on human plague cases in early 20th-century Kazakhstan from 1904-1948, suggesting a consistent impact of climate on large-scale wildlife reservoir dynamics influencing human epidemics. Extending the models further back in time, we also find correspondence between their predictions and qualitative records of plague epidemics over the past 1500 years.

Conclusions

Central Asian climate fluctuations appear to have had significant influences on regional human plague frequency in the first part of the 20th century, and probably over the past 1500 years. This first attempt at ecoepidemiological reconstruction of historical disease activity may shed some light on how long-term plague epidemiology interacts with human activity. As plague activity in Central Asia seems to have followed climate fluctuations over the past centuries, we may expect global warming to have an impact upon future plague epidemiology, probably sustaining or increasing plague activity in the region, at least in the rodent reservoirs, in the coming decades. See commentary: http://www.biomedcentral.com/1741-7007/8/108     

Tracking down the sources of experimental contamination in microbiome studies

A recent report warns that DNA extraction kits and other laboratory reagents are considerable sources of contamination in microbiome experiments. The issue of contamination is particularly problematic for samples of low biomass.See related research, http://www.biomedcentral.com/1741-7007/12/87High-throughput sequencing has revolutionized our understanding of the microbial world, providing a means by which we can characterize microbial communities in considerable detail without being affected by biases introduced by culture-based protocols that might reveal only a small fraction of the community. We have learned that, although humans share over 99.9% of their genomic DNA sequence with one another, they might share as little as 10% of their microbes at a given body site. Therefore, an intriguing hypothesis is that some aspects of the human phenotype might be determined more by microbial DNA than human DNA. Over the past five years, an enormous push in microbiome research has elucidated many of the factors that can affect this microbial individuality – the human microbiome is affected by diet, culture, geography, age and antibiotic use, among other factors [1]. Importantly, the microbiome has been implicated in numerous health conditions through correlative studies in humans and experimental research in mouse models. These conditions range from obesity [2] to multiple sclerosis [3]. However, if samples are not collected, processed, and analyzed properly, this may lead to erroneous conclusions.     

Single-nucleotide polymorphism,linkage disequilibrium and geographic structure in the malaria parasite <Emphasis Type="Italic">Plasmodium vivax</Emphasis>: prospects for genome-wide association studies

Background

The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized.

Results

We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for ~40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance.

Conclusion

These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.See commentary: http://www.biomedcentral.com/1741-7007/8/90

     

A central role for p38 MAPK in the early transcriptional response to stress

A study using phylogenetic hypothesis testing, published in BMC Evolutionary Biology, suggests that non-mimetic forms of the North American white admiral butterfly evolved from a mimetic ancestor. This case might provide one of the first examples in which mimicry was gained and then lost again, emphasizing the evolutionary lability of Batesian mimicry. See research article http://www.biomedcentral.com/1471-2148/10/239     

Darcin: a male pheromone that stimulates female memory and sexual attraction to an individual male's odour

Background

Among invertebrates, specific pheromones elicit inherent (fixed) behavioural responses to coordinate social behaviours such as sexual recognition and attraction. By contrast, the much more complex social odours of mammals provide a broad range of information about the individual owner and stimulate individual-specific responses that are modulated by learning. How do mammals use such odours to coordinate important social interactions such as sexual attraction while allowing for individual-specific choice? We hypothesized that male mouse urine contains a specific pheromonal component that invokes inherent sexual attraction to the scent and which also stimulates female memory and conditions sexual attraction to the airborne odours of an individual scent owner associated with this pheromone.

Results

Using wild-stock house mice to ensure natural responses that generalize across individual genomes, we identify a single atypical male-specific major urinary protein (MUP) of mass 18893Da that invokes a female's inherent sexual attraction to male compared to female urinary scent. Attraction to this protein pheromone, which we named darcin, was as strong as the attraction to intact male urine. Importantly, contact with darcin also stimulated a strong learned attraction to the associated airborne urinary odour of an individual male, such that, subsequently, females were attracted to the airborne scent of that specific individual but not to that of other males.

Conclusions

This involatile protein is a mammalian male sex pheromone that stimulates a flexible response to individual-specific odours through associative learning and memory, allowing female sexual attraction to be inherent but selective towards particular males. This 'darcin effect' offers a new system to investigate the neural basis of individual-specific memories in the brain and give new insights into the regulation of behaviour in complex social mammals.See associated Commentary http://www.biomedcentral.com/1741-7007/8/71

     

Appetite for destruction: the inhibition of glycolysis as a therapy for tuberous sclerosis complex-related tumors

Rule-based modeling has become a powerful approach for modeling intracellular networks, which are characterized by rich molecular diversity. Truly comprehensive models of cell behavior, however, must address spatial complexity at both the intracellular level and at the level of interacting populations of cells, and will require richer modeling languages and tools. A recent paper in BMC Systems Biology represents a signifcant step toward the development of a unified modeling language and software platform for the development of multi-level, multiscale biological models. See research article: http://www.biomedcentral.com/1752-0509/5/166     

The small protein floodgates are opening; now the functional analysis begins

Aside from a few serendipitous discoveries, small proteins of less than 50 amino acids in bacteria and 100 amino acids in eukaryotes were largely ignored due to challenges in their genetic and biochemical detection. However, with the ever-increasing availability of completed genome sequences and deep sequencing, which allows analysis of genome-wide ribosome occupancy, hundreds of small proteins are now being identified. This brings to the forefront the challenges and opportunities associated with the characterization of these proteins.See research article: http://www.biomedcentral.com/1471-2164/15/946.     

Is sex necessary?

Fungal sexual reproductive modes have markedly high diversity and plasticity, and asexual species have been hypothesized to arise frequently from sexual fungal species. A recent study on the red yeasts provides further support for the notion that sexual ancestors may give rise to shorter-lived asexual species. However, presumed asexual species may also be cryptically sexual, as revealed by other recent studies.See research article: http://www.biomedcentral.com/1471-2148/11/249     

Optimization and control in bacterial Lag phase

The lag phase of bacterial growth is important from a medical and food safety perspective, but difficult to study due to the low density and metabolic rate of cells. A new study by Alon and colleagues reveals that the gene expression program during early lag phase prioritizes carbon source utilization enzymes over genes responsible for biomass accumulation. This cellular strategy ultimately maximizes growth, making the best long-term use of the new nutrient-rich environment.See research article: http://www.biomedcentral.com/1752-0509/7/136     

The Year of the Wisent

Delving into European prehistory, two recent studies analyze ancient DNA from bison species depicted by our ancestors on the walls of their caves. The DNA tells a story of migrations driven by climate change but leaves some mystery clouding the genetic descent and climate preference of the still-extant wisent, otherwise known as the European bison.See research articles: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0317-7 http://www.nature.com/articles/ncomms13158     

In search of noise-induced bimodality

Many biological studies are carried out on large populations of cells, often in order to obtain enough material to make measurements. However, we now know that noise is endemic in biological systems and this results in cell-to-cell variability in what appears to be a population of identical cells. Although often neglected, this noise can have a dramatic effect on system responses to environmental cues with significant and often counter-intuitive biological outcomes. A recent study in BMC Systems Biology provides an example of this, documenting a bimodal distribution of activated extracellular signal-regulated kinase in a population of cells exposed to epidermal growth factor and demonstrating that the observed bimodality of the response is induced purely by noise.See research article: http://www.biomedcentral.com/1752-0509/6/109     

Signal peptide cleavage site prediction

A series of reports - and extracts of reports - from the Freedom of Information Conference, 6-7 July, 2000, New York Academy of Medicine. The conference was sponsored by BioMed Central, to promote debate about the communication and validation of biomedical research published on the internet. Details of the meeting and all presentations are available in full online at http://biomedcentral.com/info/conference.asp