Thursday, July 31, 2008

Exciting and noteworthy in PLoS ONE: My picks

There are 62 brand new articles published at PLoS ONE this week which certainly reflects quite diverse food for thought. You can always join in discussion on interesting articles by creating an account on the journal site and posting your comments for others to read. Also, you may like to rate the articles. Ratings are the quickest and easiest way for users to indicate their support for the authors and to highlight which articles are of potential impact for the readers and the community. I suggest why not to begin with these exciting ones?

Dinosaurian Soft Tissues Interpreted as Bacterial Biofilms:

A scanning electron microscope survey was initiated to determine if the previously reported findings of "dinosaurian soft tissues" could be identified in situ within the bones. The results obtained allowed a reinterpretation of the formation and preservation of several types of these "tissues" and their content. Mineralized and non-mineralized coatings were found extensively in the porous trabecular bone of a variety of dinosaur and mammal species across time. They represent bacterial biofilms common throughout nature. Biofilms form endocasts and once dissolved out of the bone, mimic real blood vessels and osteocytes. Bridged trails observed in biofilms indicate that a previously viscous film was populated with swimming bacteria. Carbon dating of the film points to its relatively modern origin. A comparison of infrared spectra of modern biofilms with modern collagen and fossil bone coatings suggests that modern biofilms share a closer molecular make-up than modern collagen to the coatings from fossil bones. Blood cell size iron-oxygen spheres found in the vessels were identified as an oxidized form of formerly pyritic framboids. Our observations appeal to a more conservative explanation for the structures found preserved in fossil bone.

Remodeling of the Streptococcus agalactiae Transcriptome in Response to Growth Temperature

To act as a commensal bacterium and a pathogen in humans and animals, Streptococcus agalactiae (group B streptococcus, GBS) must be able to monitor and adapt to different environmental conditions. Temperature variation is a one of the most commonly encountered variables. To understand the extent to which GBS modify gene expression in response to temperatures encountered in the various hosts, we conducted a whole genome transcriptome analysis of organisms grown at 30°C and 40°C. We identified extensive transcriptome remodeling at various stages of growth, especially in the stationary phase (significant transcript changes occurred for 25% of the genes). A large proportion of genes involved in metabolism was up-regulated at 30°C in stationary phase. Conversely, genes up-regulated at 40°C relative to 30°C include those encoding virulence factors such as hemolysins and extracellular secreted proteins with LPXTG motifs. Over-expression of hemolysins was linked to larger zones of hemolysis and enhanced hemolytic activity at 40°C. A key theme identified by our study was that genes involved in purine metabolism and iron acquisition were significantly up-regulated at 40°C. Growth of GBS in vitro at different temperatures resulted in extensive remodeling of the transcriptome, including genes encoding proven and putative virulence genes. The data provide extensive new leads for molecular pathogenesis research.

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI). S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the ΔsimA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development. Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement. The M-like protein mutant created in this research holds promise as live-attenuated vaccine.

Effect of Attenuation of Treg during BCG Immunization on Anti-Mycobacterial Th1 Responses and Protection against Mycobacterium tuberculosis

The functional equilibrium between natural regulatory T cells (Treg) and effector T cells can affect the issue of numerous infections. In unvaccinated mice, the influence of Treg in the control of primary infection with mycobacteria remains controversial. Here, we evaluated the role of Treg during prophylactic vaccination with Mycobacterium bovis BCG (Bacillus Calmette-Guérin) on the induction of T cell responses and on the protective effect against subsequent M. tuberculosis challenge in mice. We demonstrated that, subsequent to BCG injection, Treg were recruited to the draining lymph nodes and negatively control anti-mycobacterial CD4+ — but not CD8+ — T-cell responses. Treatment of BCG-immunized mice with an anti-CD25 mAb (PC61) induced an increase IFN-γ response against both subdominant and immunodominant regions of the protective immunogen TB10.4. In Treg-attenuated, BCG-immunized mice, which were then infected with M. tuberculosis, the lung mycobacterial load was significantly, albeit moderately, reduced compared to the control mice. Our results provide the first demonstration that attenuation of Treg subset concomitant to BCG vaccination has a positive, yet limited, impact on the protective capacity of this vaccine against infection with M. tuberculosis. Thus, for rational design of improved BCG, it should be considered that, although the action of Treg does not represent the major cause of the limited efficiency of BCG, the impact of this cell population on the subsequent control of M. tuberculosis growth is significant and measurable.

Comparative Analysis of Human Gut Microbiota by Barcoded Pyrosequencing

Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.

Thursday, July 17, 2008

100th PLoS ONE article evaluated at Faculty of 1000 Biology

As a part of its thematic focus for the month of July, PLoS ONE announced a call for papers addressing gene expression studies. It appears that the gene expression community has already embraced PLoS ONE in a great style - here appears the authoritative and insightful review [by Charles Auffray] of one of the gene expression articles published by PLoS ONE: ‘High throughput gene expression measurement with real time PCR in a microfluidic dynamic array’. Interestingly, Auffray’s is the 100th evaluation of PLoSONE articles at the Faculty of 1000 Biology.

Below is the simplified version of Charles Auffray’s evaluation of the article. Full evaluation can be read at F1000Biology website.

‘The novel microfluidic device described in this paper transforms real-time quantitative PCR into a much higher throughput technology for gene expression measurement. The authors have used a dynamic array of microfluidic channels, valves and nanoliter reaction chambers to perform simultaneously 2304 real-time qPCR assays, monitoring expression of 45 human genes in 18 tissues with very high sensitivity (down to <10 RNA molecules). The results presented compare very well with those obtained with conventional microliter RT-PCR, outperforming DNA microarrays. Miniaturization and parallelization result in faster delivery of results with much less reagents and handling. This technological advance should prove useful for validation of expression profile signatures obtained with microarrays, and their extensive use for diagnosis and prognosis. In order to compete directly with microarrays for transcriptome analysis, the number of genes that can be assayed in parallel would have to be increased by at least two orders of magnitude’.

Of its 2600 articles in PubMED, one hundred (4%) articles have been already evaluated and commented upon by F1000 Members. For a broad based and high volume journal such as PLoS ONE, the F1000 evaluations constitute important quality indexes for individual articles apart from hundreds of articles already reviewed through PLoS ONE’s unique rating and discussion tools and journal clubs which are fully compliant to the cutting edge concepts of Science 2.0. Such 'article level metrics' are especially relevant when the significance of a popular bibliometric index, the 'impact factor' is increasingly being questioned.

Conflict of interest: I volunteer as Section Editor of PLoS ONE and as a Faculty Member at F1000 Biology and F1000 Medicine.

Thursday, July 10, 2008

Birds are singing again!

PLoS ONE had a thematic focus last month on avian research. Several high profile papers related to birds were highlighted and discussed also through an avian journal club. This week again 2 more bird articles have been published; both the articles are being quite enthusiastically discussed in popular media as well as on science channels. While the first article deals with how superfast muscle movements are harnessed by birds to produce their tunes, the other one describes bird’s behavior and personality exhibition during singing and that only high-quality individuals can afford to display attractive songs, and they will necessarily be risk takers:

Superfast Vocal Muscles Control Song Production in Songbirds

Birdsong is a widely used model for vocal learning and human speech, which exhibits high temporal and acoustic diversity. Rapid acoustic modulations are thought to arise from the vocal organ, the syrinx, by passive interactions between the two independent sound generators or intrinsic nonlinear dynamics of sound generating structures. Additionally, direct neuromuscular control could produce such rapid and precisely timed acoustic features if syringeal muscles exhibit rare superfast muscle contractile kinetics. However, no direct evidence exists that avian vocal muscles can produce modulations at such high rates. Here, we show that 1) syringeal muscles are active in phase with sound modulations during song over 200 Hz, 2) direct stimulation of the muscles in situ produces sound modulations at the frequency observed during singing, and that 3) syringeal muscles produce mechanical work at the required frequencies and up to 250 Hz in vitro. The twitch kinematics of these so-called superfast muscles are the fastest measured in any vertebrate muscle. Superfast vocal muscles enable birds to directly control the generation of many observed rapid acoustic changes and to actuate the millisecond precision of neural activity into precise temporal vocal control. Furthermore, birds now join the list of vertebrate classes in which superfast muscle kinetics evolved independently for acoustic communication.

Birds Reveal their Personality when Singing

Individual differences in social behaviour may have consequences for mate choice and sexual signalling, because partners should develop preferences for personalities that maximize reproductive output. Here we propose that behavioural traits involved in sexual advertisement may serve as good indicators of personality, which is fundamental for sexual selection to operate on temperament. Bird song has a prominent and well-established role in sexual selection, and it displays considerable variation among individuals with a potentially strong personality component. Therefore, we predicted that features of song would correlate with estimates of personality. In a field study of free-living male collared flycatchers, Ficedula albicollis, we characterised personality based on the exploration of an altered breeding environment, and based on the risk taken when a potential predator was approaching during a simulated territorial interaction. We found that explorative and risk-taker individuals consistently sang at lower song posts than shy individuals in the presence of a human observer. Moreover, males from lower posts established pair-bonds relatively faster than males from higher posts. Our results may demonstrate that risk taking during singing correlates with risk taking during aggression and with exploration, thus personality may be manifested in different contexts involving sexual advertisement. These findings are in accordance with the hypothesis that the male's balance between investment in reproduction and risk taking is reflected in sexual displays, and it may be important information for choosy females that seek partners with personality traits enhancing breeding success.

Tuesday, July 8, 2008

Thematic Journal Clubs at PLoS ONE

I liked the idea at PLoS ONE to have a thematic focus each month to assess how well the journal is doing in that particular area. This is gauged most often with the help of statistics obtained from Google Analytics on page views related to each article in that category and the most accessed article is highlighted on the main page of the journal. At this stage PLoS ONE receives from the authors of the article their comments on the editorial processes and their feelings on seeing the article fetching community attention/response. Also, the article receives at this occasion additional comments from experts and young scientists in the academia through PLoS ONE's unique discussion and response forum with ratings and annotations. This can effectively catalyze community engagement through PLoS ONE Journal Clubs (JCs). Such JCs involve groups of scientists, post docs and graduate students who volunteer to discuss PLoS ONE articles and post their discussions as a series of questions, comments, annotations, and ratings eventually triggering discussions within a broader scientific community.

Sunday, July 6, 2008

The ‘threatening’ success of PLoS; now heard aloud!

I was so happy to have published in May this year an invited perspectives article in a Nature Reviews journal. I considered Nature a prestigious place to publish and that they are highly organized and professional. However, sadly, this belief stand shaken after reading a slanted story in the recent issue of Nature, apparently attacking PLoS (that Nature sees as competitor!). I am kinda surprised; sometime back a similar slang on PLoS was passed by another group, although it was not heard aloud. Well that means PLoS is fast becoming a threatening success! Thanks to the cause that it bolsters and the public support that it enjoys globally.

As the matter currently dominantes blogosphere (see links below), I think I am not alone with my shaken belief; this should be sorrowfully the case of many who proudly published in journals of both Nature and PLoS. I wonder, if Nature risks alienating many of its well-wishers with such a stand it has taken against PLoS and Open Access.

I found the overall tone and spirit of the news article quite disturbing and distasteful. Especially, their painting of PLoS ONE journal as a ‘dumping ground’ and mention of its peer review process as ‘light’ is not at all correct and ignores facts. I see it as an unsuccessful attempt to dump all the ground-breaking work that PLoS ONE has been publishing since its launch in 2006 (see these posts for exmple; here, here and here). As I said in my response to the story, it is a simple fact that the ~300 scientists who publish in PLoS ONE every month and the 500 Editors who devote their time on rounds of peer reviewing are certainly not the fools out there.

The story referred PLoS as resorting to ‘bulk and cheap publishing’; what a slang! Apparently, however, the "bulk, cheap and lower quality papers" published by PLoS are not going unnoticed by Nature. Three of the ‘Research Highlights’ articles in the same issue report on articles published in PLoS journals (two from PLoS ONE! and one from PLoS Genetics). And I quote Scott Ramsey: ‘If it (the research that PLoS published) is not interesting enough to publish in Nature, at least it provides enough free copy to help round out an issue’!

Finally, I do not want to add more on my own perspective here as it is no different than what many others have already rolled out. There has been tremendous outrage to Nature’s self serving article (apparently all going in favor of PLoS!) in the blogosphere, as well as in the comments thread of the article itself. A summary of the relevant posts on the article can be found at:

Links to other related posts are here:

Conflict of interest statement: I volunteer as Section Editor for PLoS ONE.

Wednesday, July 2, 2008

New in PLoS ONE: Genetic structure of Adi tribes of North-East India

PLoS ONE today published a crop of 60 brand new articles, several of them are hitting the headlines. An interesting article from India by TS Vasulu and colleagues is also being talked about a lot since this morning (see below). The paper discusses 'Microsatellite based analysis of the genetic status of Adi tribes of Northeast India'.

Population biologists and anthropologists have been traditionally interested in aspects of human history and population migration in India -a homeland of a large number of genetic lineages of tribals and mainstream populations which speak 1600 different languages and dialects.

The article by Vasulu presents important genetic data from a number of closely related Tibeto-Burman speaking tribes from north-east India. The authors correctly present this region of India of utmost importance with respect to ancient human migration processes. In addition, the novel results obtained from these populations are compared with similar data from a range of other populations obtained from the literature.

Based on 15 autosomal microsatellite (STR) markers, the authors studied the genetic affinity, differentiation and sub-structuring among six Adi subgroups, as well as their genetic affinity with other neighbouring, Tibeto-Burman-speaking, tribes of India and with the linguistically divergent east and south-east Asian populations, with whom they share common ethno-historical and cultural attributes. The researchers investigated to what extent the six Adi subgroups are genetically divergent or affiliated. A comparison with the 16 Tibeto-Burman-speaking tribes of the neighbouring region in northern and north-eastern parts of the country as revealed by the cluster analyses indicates geographically proximate populations forming a close cluster. This is to be expected if these populations have indeed diverged from a common source after their settlement in different regions of the country in the recent past. In a comparison of the 50 populations (including populations from east and south-east Asia) for genetic diversity based on the autosomal loci, the resultant clustering tree showed some of the Tibeto-Burman tribes clustering with the populations from Tibet and China and whereas other Tibeto-Burman tribes of India cluster with linguistically different Southeast Asian populations. These results support the possibility that Tibeto-Burman populations were derived from more than one common source. Overall, the Adi and other Tibeto-Burman speaking populations of India are regionally well differentiated and exhibit genetic affinity with the neighboring populations of East/Southeast Asia, based on their shared ethno-history. However, a clearer picture may well emerge from the analysis of increased number of informative genetic markers and from the uniparental markers like mitochondrial DNA and Y chromosome.

You can read the news coverage about this study here and you may post your own reactions and comments directly on the article of Vasulu and colleagues by creating an account on the PLoS ONE website.

[Source: Press release of T S Vasulu, Indian Statistical Institute, Kolkata, India]