Early stone technology on Flores and its implications for Homo floresiensis

In the Soa Basin of central Flores, eastern Indonesia, stratified archaeological sites, including Mata Menge, Boa Lesa and Kobatuwa (Fig. 1), contain stone artefacts associated with the fossilized remains of Stegodon florensis, Komodo dragon, rat and various other taxa. These sites have been dated to 840-700 kyr bp (thousand years before present). The authenticity of the Soa Basin artefacts and their provenance have been demonstrated by previous work, but to quell lingering doubts, here we describe the context, attributes and production modes of 507 artefacts excavated at Mata Menge. We also note specific similarities, and apparent technological continuity, between the Mata Menge stone artefacts and those excavated from Late Pleistocene levels at Liang Bua cave, 50 km to the west. The latter artefacts, dated to between 95-74 and 12 kyr ago, are associated with the remains of a dwarfed descendent of S. florensis, Komodo dragon, rat and a small-bodied hominin species, Homo floresiensis, which had a brain size of about 400 cubic centimetres. The Mata Menge evidence negates claims that stone artefacts associated with H. floresiensis are so complex that they must have been made by modern humans (Homo sapiens).     

Future fitness and helping in social queues

Helpers in primitively eusocial and cooperatively breeding animal societies forfeit their own reproduction to rear the offspring of a queen or breeding pair, but may eventually attain breeding status themselves. Kin selection provides a widely accepted theoretical framework for understanding these societies, but differences in genetic relatedness do not explain a universal societal feature: the huge variation between individuals in helping effort. An alternative explanation for this variation lies in a fundamental trade-off faced by helpers: by working harder, they increase the indirect component of their fitness, but simultaneously decrease their own future survival and fecundity. Here, we show that individuals work less hard when they stand to lose more future fitness through working. We experimentally manipulated two components of future fitness in social queues of hover wasps (Stenogastrinae): a helper's chance of inheriting an egg-laying position, and the workforce available to rear her offspring should she inherit. After each manipulation, helpers increased or decreased their effort as appropriate to the change in expected future fitness that they experienced. Although helping provides significant indirect fitness benefits for hover wasps, our study shows that variation in the costs associated with helping is the major determinant of helping effort.     

Myocardial infarction accelerates atherosclerosis

During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.     

Catalysis for fluorination and trifluoromethylation

Recent advances in catalysis have made the incorporation of fluorine into complex organic molecules easier than ever before, but selective, general and practical fluorination reactions remain sought after. Fluorination of molecules often imparts desirable properties, such as metabolic and thermal stability, and fluorinated molecules are therefore frequently used as pharmaceuticals or materials. But the formation of carbon-fluorine bonds in complex molecules is a significant challenge. Here we discuss reactions to make organofluorides that have emerged within the past few years and which exemplify how to overcome some of the intricate challenges associated with fluorination.     

Embracing the quantum limit in silicon computing

Quantum computers hold the promise of massive performance enhancements across a range of applications, from cryptography and databases to revolutionary scientific simulation tools. Such computers would make use of the same quantum mechanical phenomena that pose limitations on the continued shrinking of conventional information processing devices. Many of the key requirements for quantum computing differ markedly from those of conventional computers. However, silicon, which plays a central part in conventional information processing, has many properties that make it a superb platform around which to build a quantum computer.     

Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.