Assessing “Dangerous Climate Change”: Required Reduction of Carbon Emissions to Protect Young People,Future Generations and Nature

We assess climate impacts of global warming using ongoing observations and paleoclimate data. We use Earth’s measured energy imbalance, paleoclimate data, and simple representations of the global carbon cycle and temperature to define emission reductions needed to stabilize climate and avoid potentially disastrous impacts on today’s young people, future generations, and nature. A cumulative industrial-era limit of ∼500 GtC fossil fuel emissions and 100 GtC storage in the biosphere and soil would keep climate close to the Holocene range to which humanity and other species are adapted. Cumulative emissions of ∼1000 GtC, sometimes associated with 2°C global warming, would spur “slow” feedbacks and eventual warming of 3–4°C with disastrous consequences. Rapid emissions reduction is required to restore Earth’s energy balance and avoid ocean heat uptake that would practically guarantee irreversible effects. Continuation of high fossil fuel emissions, given current knowledge of the consequences, would be an act of extraordinary witting intergenerational injustice. Responsible policymaking requires a rising price on carbon emissions that would preclude emissions from most remaining coal and unconventional fossil fuels and phase down emissions from conventional fossil fuels.     

Evolutionary relationships of <Emphasis Type="Italic">Fusobacterium nucleatum</Emphasis> based on phylogenetic analysis and comparative genomics

Background  

The phylogenetic position and evolutionary relationships of Fusobacteria remain uncertain. Especially intriguing is their relatedness to low G+C Gram positive bacteria (Firmicutes) by ribosomal molecular phylogenies, but their possession of a typical gram negative outer membrane. Taking advantage of the recent completion of the Fusobacterium nucleatum genome sequence we have examined the evolutionary relationships of Fusobacterium genes by phylogenetic analysis and comparative genomics tools.     

The Neolithic revolution of bacterial genomes

Current human activities undoubtedly impact natural ecosystems. However, the influence of Homo sapiens on living organisms must have also occurred in the past. Certain genomic characteristics of prokaryotes can be used to study the impact of ancient human activities on microorganisms. By analyzing DNA sequence similarity features of transposable elements, dramatic genomic changes have been identified in bacteria that are associated with large and stable human communities, agriculture and animal domestication: three features unequivocally linked to the Neolithic revolution. It is hypothesized that bacteria specialized in human-associated niches underwent an intense transformation after the social and demographic changes that took place with the first Neolithic settlements. These genomic changes are absent in related species that are not specialized in humans.     

Comparative genomics of gene-family size in closely related bacteria

Background  

The wealth of genomic data in bacteria is helping microbiologists understand the factors involved in gene innovation. Among these, the expansion and reduction of gene families appears to have a fundamental role in this, but the factors influencing gene family size are unclear.     

Comparison of prokaryotic diversity at offshore oceanic locations reveals a different microbiota in the Mediterranean Sea

The bacterial and archaeal assemblages at two offshore sites located in polar (Greenland Sea; depth: 50 and 2000 m) and Mediterranean (Ionian Sea; depth 50 and 3000 m) waters were studied by PCR amplification and sequencing of the last 450-500 bp of the 16S rRNA gene. A total of 1621 sequences, together with alignable 16S rRNA gene fragments from the Sargasso Sea metagenome database, were analysed to ascertain variations associated with geographical location and depth. The Ionian 50 m sample appeared to be the most diverse and also had remarkable differences in terms of the prokaryotic groups retrieved; surprisingly, however, many similarities were found at the level of large-scale diversity between the Sargasso database fragments and the Greenland 50 m sample. Most sequences with more than 97% sequence similarity, a value often taken as indicative of species delimitation, were only found at a single location/depth; nevertheless, a few examples of cosmopolitan sequences were found in all samples. Depth was also an important factor and, although both deep-water samples had overall similarities, there were important differences that could be due to the warmer waters at depth of the Mediterranean Sea.     

IWoCS: analyzing ribosomal intergenic transcribed spacers configuration and taxonomic relationships

MOTIVATION: Lately the use of 16S-23S Intergenic Transcribed Spacer (ITS) sequences for bacterial typing purposes has increased. The presence of conserved regions like tRNA genes or boxes together with hypervariable regions allows performing intraspecific discrimination of very close bacterial strains. On the other hand this mosaic of variability makes the ITS a sequence difficult to analyze and compare. RESULTS: A software to study ITSs by a Word Count based System (IWoCS) is proposed. A large dataset of ITS was created (comprising 7355 sequences). A database indicating all the occurrences of possible n-mers (tags), describing each ITS sequence, was created (with n going from 5 to 13) including 32 061 819 entries. The database allows to analyze ITS sequences submitted by users using a web-based interface. The abundance in the database of each n-mer is given in a one-base sliding frame. A dominance plot reflects how common the tags are within different taxonomic levels. The obtained profile identifies highly repeated tags as evolutionarily conserved regions (like tRNA or boxes) or low frequency tags as regions specifically associated to taxonomic groups. The study of the dominance and abundance profiles combined with the taxonomy reports provides a novel tool for the use of the ITS in bacteria typing and identification. AVAILABILITY: The database is freely accessible at http://egg.umh.es/iwocs/.     

Meta-Analysis To Test the Association of HIV-1 nef Amino Acid Differences and Deletions with Disease Progression

Previous relatively small studies have associated particular amino acid replacements and deletions in the HIV-1 nef gene with differences in the rate of HIV disease progression. We tested more rigorously whether particular nef amino acid differences and deletions are associated with HIV disease progression. Amino acid replacements and deletions in patients'' consensus sequences were investigated for 153 progressor (P), 615 long-term nonprogressor (LTNP), and 2,311 unknown progressor sequences from 582 subtype B HIV-infected patients. LTNPs had more defective nefs (interrupted by frameshifts or stop codons), but on a per-patient basis there was no excess of LTNP patients with one or more defective nef sequences compared to the Ps (P = 0.47). The high frequency of amino acid replacement at residues S⁸, V¹⁰, I¹¹, A¹⁵, V⁸⁵, V¹³³, N¹⁵⁷, S¹⁶³, V¹⁶⁸, D¹⁷⁴, R¹⁷⁸, E¹⁸², and R¹⁸⁸ in LTNPs was also seen in permuted datasets, implying that these are simply rapidly evolving residues. Permutation testing revealed that residues showing the greatest excess over expectation (A¹⁵, V⁸⁵, N¹⁵⁷, S¹⁶³, V¹⁶⁸, D¹⁷⁴, R¹⁷⁸, and R¹⁸⁸) were not significant (P = 0.77). Exploratory analysis suggested a hypothetical excess of frameshifting in the regions ⁹SVIG and ¹¹⁸QGYF among LTNPs. The regions V¹⁰ and ¹⁵²KVEEA of nef were commonly deleted in LTNPs. However, permutation testing indicated that none of the regions displayed significantly excessive deletion in LTNPs. In conclusion, meta-analysis of HIV-1 nef sequences provides no clear evidence of whether defective nef sequences or particular regions of the protein play a significant role in disease progression.HIV-infected people can be categorized according to the number of years in which they progress to AIDS. Long-term nonprogressors (LTNPs) do not progress to AIDS even after more than 10 years of infection, and they maintain stable CD4 lymphocyte counts (5, 8). Nonprogression status may reflect differences in either in the host, in viral genetics, or in environmental factors. Within the virus, R⁷⁷Q, a mutation in the HIV-1 vpr gene, was associated with both LTNP infection and impaired induction of apoptosis (38). However, this mutation was not statistically significant, and no other clearly attenuating mutations or deletions were detected (20). Most attention, however, has focused on role of the viral nef protein.In rhesus monkeys infected with simian immunodeficiency virus (SIV), a model for studying AIDS pathogenesis (37), animals infected with nef-deficient SIV showed an attenuated course of infection (17, 30, 31, 51). nef was also a major determinant of pathogenicity in transgenic mice with AIDS-like symptoms induced by HIV-1 (27). Some patients with LTNP strains of HIV were found to have gross deletions in the nef gene (16, 33, 49), suggesting the importance of nef for HIV-1 progression in humans.Previous studies related to phylogenetic analysis have reported that nef sequences from patients with different rates of progression do not form distinct clusters (28, 29, 40, 43). Each patient had sequences that clustered together and could be differentiated from those of the other patients, supporting the monophyletic origin of the infections. The absence of intragroup clustering suggested that no correlation existed between the phylogenetic relationship of the nef sequences and the progression rate in the patients (10). The differences in genetic distance between LTNP and progressors (Ps) were not statistically significant, suggesting that the degree of sequence variation in nef is unlikely to reflect the stage of HIV-1 disease (4).Amino acids 25 to 36 in HIV-1 nef are important both for several well-defined in vitro functions of nef and for the pathogenicity of HIV-1 in humans, and nef''s ability to enhance virion infectivity was fully restored when the deletion was repaired by the insertion of that region (8). Nef proteins derived from LTNPs and slow progressors (SPs) were found to be defective or far less capable of enhancing viral replication and/or viral infectivity in herpesvirus saimiri-transformed human T cells and peripheral blood mononuclear cells (PBMC) (24). The sizes of the deletions in the nef/LTR (long terminal repeat) region increased progressively from 84 to 1,400 bp during the 5-year follow-up period in one case of a SP (35). Gross defects were also present in the RNA-derived sequences of an LTNP individual because of a frameshift and the premature termination of the protein (4). HIV-1 sequences from the isolates or patient PBMC had similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the LTR (16). There was a 36-bp deletion close to the 5′ end of nef that impaired nef function in an LTNP (8).Many studies not only have described nef as carrying large deletions in LTNPs (16, 33) but also found a higher proportion of disrupted nef gene sequences in LTNPs. A study of six HIV patients who reached at least 11 years of age without or with mild symptoms revealed that LTNPs had higher proportions of disrupted nef sequences (10). Seven LTNPs, all belonging to the same cohort of infected hemophiliacs, had more defective nef sequences than in progressors; the number of disrupted nef sequences within each individual was significantly higher in LTNPs than in progressors (4).The nef amino acid sequence has been reported to be highly polymorphic even within a particular subtype (4, 22, 28, 29, 40, 42, 53). Single amino acid deletions have been found predominantly at three locations that are structurally less defined loop regions: positions 8 to 11, 49 to 51, and 155 to 162 (25). Five variants (T¹⁵, N⁵¹, H¹⁰², L¹⁷⁰, and E¹⁸²) have been noted among LTNPs, whereas nine variants (N-terminal PxxP motif; A¹⁵, R³⁹, T⁵¹, T¹⁵⁷, C¹⁶³, N¹⁶⁹, Q¹⁷⁰, and M¹⁸²) have been noted among progressors (32). nef has been often changed at residues localized in the folded core domain at cytotoxic-T-lymphocyte epitopes (E¹⁰⁵, K¹⁰⁶, E¹¹⁰, Y¹³², K¹⁶⁴, and R²⁰⁰); moreover, LTNP-associated variations occur in the core domain of nef. Recently, nef sequence variations have been found in the WL motif of the CD4 binding site, as well as a premature stop codon in infected LTNPs that could potentially contribute to the attenuation of the virus; however, these deletions were found to be insignificant (13).There has been a broad agreement that grossly defective nefs are associated with an attenuated course of infection (17, 30, 31, 51) but rare in HIV-1 infection (32). Grossly defective nef genes or significant changes from relevant clade reference sequences were not identified in a study of 32 LTNP children (13). One study noted that the proportion of disrupted nef sequences within each patient was significantly higher in LTNPs compared to Ps; however, the proportions of individuals with nef defects (in LTNPs, 5 of 7, and in Ps, 6 of 8) were similar (4). No major defects have been reported in a few other studies (28, 39, 40). Another study of a small number of patients does not indicate that gross deletions play any major role in delaying or halting disease progression in infected drug abusers in Italy (11), and premature stop codons were observed at equivalent, yet low, frequencies among the different clinical groups (41). In addition, disease progression has been reported in a HIV patient with a virus grossly deleted of nef (26).Thus, overall, most of these studies were based on observation or case study rather than systematic scientific evaluation (11). The objective of the present study was to determine in a substantially larger sample than investigated to date whether there is any association between disease progression and particular nef amino acid differences or deletions.     

Micro-Mar: a database for dynamic representation of marine microbial biodiversity

Background  

The cataloging of marine prokaryotic DNA sequences is a fundamental aspect for bioprospecting and also for the development of evolutionary and speciation models. However, large amount of DNA sequences used to quantify prokaryotic biodiversity requires proper tools for storing, managing and analyzing these data for research purposes.