The FHIT gene product: tumor suppressor and genome “caretaker”

The FHIT gene at FRA3B is one of the earliest and most frequently altered genes in the majority of human cancers. It was recently discovered that the FHIT gene is not the most fragile locus in epithelial cells, the cell of origin for most Fhit-negative cancers, eroding support for past claims that deletions at this locus are simply passenger events that are carried along in expanding cancer clones, due to extreme vulnerability to DNA damage rather than to loss of FHIT function. Indeed, recent reports have reconfirmed FHIT as a tumor suppressor gene with roles in apoptosis and prevention of the epithelial–mesenchymal transition. Other recent works have identified a novel role for the FHIT gene product, Fhit, as a genome “caretaker.” Loss of this caretaker function leads to nucleotide imbalance, spontaneous replication stress, and DNA breaks. Because Fhit loss-induced DNA damage is “checkpoint blind,” cells accumulate further DNA damage during subsequent cell cycles, accruing global genome instability that could facilitate oncogenic mutation acquisition and expedite clonal expansion. Loss of Fhit activity therefore induces a mutator phenotype. Evidence for FHIT as a mutator gene is discussed in light of these recent investigations of Fhit loss and subsequent genome instability.     

The building blocks of planets within the 'terrestrial' region of protoplanetary disks

Our Solar System was formed from a cloud of gas and dust. Most of the dust mass is contained in amorphous silicates, yet crystalline silicates are abundant throughout the Solar System, reflecting the thermal and chemical alteration of solids during planet formation. (Even primitive bodies such as comets contain crystalline silicates.) Little is known about the evolution of the dust that forms Earth-like planets. Here we report spatially resolved detections and compositional analyses of these building blocks in the innermost two astronomical units of three proto-planetary disks. We find the dust in these regions to be highly crystallized, more so than any other dust observed in young stars until now. In addition, the outer region of one star has equal amounts of pyroxene and olivine, whereas the inner regions are dominated by olivine. The spectral shape of the inner-disk spectra shows surprising similarity with Solar System comets. Radial-mixing models naturally explain this resemblance as well as the gradient in chemical composition. Our observations imply that silicates crystallize before any terrestrial planets are formed, consistent with the composition of meteorites in the Solar System.     

What was classical genetics?

I present an account of classical genetics to challenge theory-biased approaches in the philosophy of science. Philosophers typically assume that scientific knowledge is ultimately structured by explanatory reasoning and that research programs in well-established sciences are organized around efforts to fill out a central theory and extend its explanatory range. In the case of classical genetics, philosophers assume that the knowledge was structured by T. H. Morgan’s theory of transmission and that research throughout the later 1920s, 30s, and 40s was organized around efforts to further validate, develop, and extend this theory. I show that classical genetics was structured by an integration of explanatory reasoning (associated with the transmission theory) and investigative strategies (such as the ‘genetic approach’). The investigative strategies, which have been overlooked in historical and philosophical accounts, were as important as the so-called laws of Mendelian genetics. By the later 1920s, geneticists of the Morgan school were no longer organizing research around the goal of explaining inheritance patterns; rather, they were using genetics to investigate a range of biological phenomena that extended well beyond the explanatory domain of transmission theories. Theory-biased approaches in history and philosophy of science fail to reveal the overall structure of scientific knowledge and obscure the way it functions.     

The central dusty torus in the active nucleus of NGC 1068

Active galactic nuclei (AGNs) display many energetic phenomena--broad emission lines, X-rays, relativistic jets, radio lobes--originating from matter falling onto a supermassive black hole. It is widely accepted that orientation effects play a major role in explaining the observational appearance of AGNs. Seen from certain directions, circum-nuclear dust clouds would block our view of the central powerhouse. Indirect evidence suggests that the dust clouds form a parsec-sized torus-shaped distribution. This explanation, however, remains unproved, as even the largest telescopes have not been able to resolve the dust structures. Here we report interferometric mid-infrared observations that spatially resolve these structures in the galaxy NGC 1068. The observations reveal warm (320 K) dust in a structure 2.1 parsec thick and 3.4 parsec in diameter, surrounding a smaller hot structure. As such a configuration of dust clouds would collapse in a time much shorter than the active phase of the AGN, this observation requires a continual input of kinetic energy to the cloud system from a source coexistent with the AGN.     

Detection of carbonates in dust shells around evolved stars.

Carbonates on large Solar System bodies like Earth and Mars (the latter represented by the meteorite ALH84001) form through the weathering of silicates in a watery (CO3)2- solution. The presence of carbonates in interplanetary dust particles and asteroids (again, represented by meteorites) is not completely understood, but has been attributed to aqueous alteration on a large parent body, which was subsequently shattered into smaller pieces. Despite efforts, the presence of carbonates outside the Solar System has hitherto not been established. Here we report the discovery of the carbonates calcite and dolomite in the dust shells of evolved stars, where the conditions are too primitive for the formation of large parent bodies with liquid water. These carbonates, therefore, are not formed by aqueous alteration, but perhaps through processes on the surfaces of dust or ice grains or gas phase condensation. The presence of carbonates which did not form by aqueous alteration suggests that some of the carbonates found in Solar System bodies no longer provide direct evidence that liquid water was present on large parent bodies early in the history of the Solar System.     

Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome

3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome.     

70K heat shock related proteins stimulate protein translocation into microsomes

A yeast cytosol is shown to contain two distinct activities that stimulate protein translocation across microsomal membranes. One activity was purified. It consists of two constitutively expressed 70K heat shock related proteins that increase the rate of translocation. Possible mechanisms of action of these proteins are discussed.     

Geochronology: age of Mexican ash with alleged 'footprints'

A report of human footprints preserved in 40,000-year-old volcanic ash near Puebla, Mexico (http://www.royalsoc.ac.uk/exhibit.asp?id=3616&tip=1), was the subject of a press conference that stirred international media attention. If the claims (http://www.mexicanfootprints.co.uk) of Gonzalez et al. are valid, prevailing theories about the timing of human migration into the Americas would need significant revision. Here we show by 40Ar/39Ar dating and corroborating palaeomagnetic data that the basaltic tuff on which the purported footprints are found is 1.30+/-0.03 million years old. We conclude that either hominid migration into the Americas occurred very much earlier than previously believed, or that the features in question were not made by humans on recently erupted ash.