A newly discovered species of living baleen whale

In the late 1970s eight Balaenoptera specimens of unknown identity were caught in the lower latitudinal Indo-Pacific waters by Japanese research whaling vessels. The combination of the allozyme patterns and physical maturity of the eight specimens separated them from all acknowledged Balaenoptera species. In September 1998 we collected a medium-sized baleen whale carcass on a coastal island in the Sea of Japan. This specimen and the previously collected eight specimens resembled Balaenoptera physalus (fin whale) in external appearance but were much smaller. Comparison of external morphology, osteology and mitochondrial DNA data grouped the nine specimens as a single species but separated them from all known baleen whale species. Therefore, here we describe a new species of Balaenoptera, which is characterized by its unique cranial morphology, its small number of baleen plates, and by its distant molecular relationships with all of its congeners. Our analyses also separated Balaenoptera brydei (Bryde's whale) and Balaenoptera edeni (Eden's whale) into two distinct species, raising the number of known living Balaenoptera species to eight.     

Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease

Camurati-Engelmann disease (CED, MIM 131300) is an autosomal dominant, progressive diaphyseal dysplasia characterized by hyperosteosis and sclerosis of the diaphyses of long bones. We recently assigned the CED locus to an interval between D19S422 and D19S606 at chromosome 19q13.1-q13.3, which two other groups confirmed. As the human transforming growth factor-1 gene (TGFB1) is located within this interval, we considered it a candidate gene for CED.     

Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1

Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection.     

A signature of cosmic-ray increase in AD 774-775 from tree rings in Japan

Increases in (14)C concentrations in tree rings could be attributed to cosmic-ray events, as have increases in (10)Be and nitrate in ice cores. The record of the past 3,000 years in the IntCal09 data set, which is a time series at 5-year intervals describing the (14)C content of trees over a period of approximately 10,000 years, shows three periods during which (14)C increased at a rate greater than 3‰ over 10 years. Two of these periods have been measured at high time resolution, but neither showed increases on a timescale of about 1 year (refs 11 and 12). Here we report (14)C measurements in annual rings of Japanese cedar trees from ad 750 to ad 820 (the remaining period), with 1- and 2-year resolution. We find a rapid increase of about 12‰ in the (14)C content from ad 774 to 775, which is about 20 times larger than the change attributed to ordinary solar modulation. When averaged over 10 years, the data are consistent with the decadal IntCal (14)C data from North American and European trees. We argue that neither a solar flare nor a local supernova is likely to have been responsible.     

Enterotypes of the human gut microbiome

Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.     

Structure and mechanism of the chromatin remodelling factor ISW1a

Site-specific recognition of DNA in eukaryotic organisms depends on the arrangement of nucleosomes in chromatin. In the yeast Saccharomyces cerevisiae, ISW1a and related chromatin remodelling factors are implicated in establishing the nucleosome repeat during replication and altering nucleosome position to affect gene activity. Here we have solved the crystal structures of S. cerevisiae ISW1a lacking its ATPase domain both alone and with DNA bound at resolutions of 3.25?? and 3.60??, respectively, and we have visualized two different nucleosome-containing remodelling complexes using cryo-electron microscopy. The composite X-ray and electron microscopy structures combined with site-directed photocrosslinking analyses of these complexes suggest that ISW1a uses a dinucleosome substrate for chromatin remodelling. Results from a remodelling assay corroborate the dinucleosome model. We show how a chromatin remodelling factor could set the spacing between two adjacent nucleosomes acting as a 'protein ruler'.     

Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model

Spinal muscular atrophy (SMA) is a motor neuron disease and the leading genetic cause of infant mortality; it results from loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Humans have a paralogue, SMN2, whose exon 7 is predominantly skipped, but the limited amount of functional, full-length SMN protein expressed from SMN2 cannot fully compensate for a lack of SMN1. SMN is important for the biogenesis of spliceosomal small nuclear ribonucleoprotein particles, but downstream splicing targets involved in pathogenesis remain elusive. There is no effective SMA treatment, but SMN restoration in spinal cord motor neurons is thought to be necessary and sufficient. Non-central nervous system (CNS) pathologies, including cardiovascular defects, were recently reported in severe SMA mouse models and patients, reflecting autonomic dysfunction or direct effects in cardiac tissues. Here we compared systemic versus CNS restoration of SMN in a severe mouse model. We used an antisense oligonucleotide (ASO), ASO-10-27, that effectively corrects SMN2 splicing and restores SMN expression in motor neurons after intracerebroventricular injection. Systemic administration of ASO-10-27 to neonates robustly rescued severe SMA mice, much more effectively than intracerebroventricular administration; subcutaneous injections extended the median lifespan by 25 fold. Furthermore, neonatal SMA mice had decreased hepatic Igfals expression, leading to a pronounced reduction in circulating insulin-like growth factor 1 (IGF1), and ASO-10-27 treatment restored IGF1 to normal levels. These results suggest that the liver is important in SMA pathogenesis, underscoring the importance of SMN in peripheral tissues, and demonstrate the efficacy of a promising drug candidate.