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Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N2 gas. Anaerobic metabolism has not yet been observed in SAR11, and it remains unknown how these bacteria contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells from the world's largest OMZ revealed previously uncharacterized SAR11 lineages with adaptations for life without oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalysing the nitrite-producing first step of denitrification and constituted ~40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of maximum nitrate reduction activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth's most abundant organismal group.

KRAS is the most frequently mutated oncogene in cancer and encodes a key signalling protein in tumours.sup.1,2. The KRAS(G12C) mutant has a cysteine residue that has been exploited to design covalent inhibitors that have promising preclinical activity.sup.3-5. Here we optimized a series of inhibitors, using novel binding interactions to markedly enhance their potency and selectivity. Our efforts have led to the discovery of AMG 510, which is, to our knowledge, the first KRAS(G12C) inhibitor in clinical development. In preclinical analyses, treatment with AMG 510 led to the regression of KRAS.sup.G12C tumours and improved the anti-tumour efficacy of chemotherapy and targeted agents. In immune-competent mice, treatment with AMG 510 resulted in a pro-inflammatory tumour microenvironment and produced durable cures alone as well as in combination with immune-checkpoint inhibitors. Cured mice rejected the growth of isogenic KRAS.sup.G12D tumours, which suggests adaptive immunity against shared antigens. Furthermore, in clinical trials, AMG 510 demonstrated anti-tumour activity in the first dosing cohorts and represents a potentially transformative therapy for patients for whom effective treatments are lacking. Treatment of KRAS.sup.G12C-mutant cancer cells with the KRAS(G12C) inhibitor AMG 510 leads to durable response in mice, and anti-tumour activity in patients suggests that AMG 510 could be effective in patients for whom treatments are currently lacking., Author(s): Jude Canon [sup.1] , Karen Rex [sup.1] , Anne Y. Saiki [sup.1] , Christopher Mohr [sup.1] , Keegan Cooke [sup.1] , Dhanashri Bagal [sup.2] , Kevin Gaida [sup.1] , [...]

Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron- based screening, we developed a family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice invivo. In layer 2/3 pyramidal neurons ofthe mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5-40- µm long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales., Neural activity causes rapid changes in intracellular free calcium (1-4). Calcium imaging experiments have relied on this principle to track the activity of neuronal populations (5,6) and to probe excitation [...]

Chemical ozone destruction occurs over both polar regions in local winter-spring. In the Antarctic, essentially complete removal of lower-stratospheric ozone currently results in an ozone hole every year, whereas in the Arctic, ozone loss is highly variable and has until now been much more limited. Here we demonstrate that chemical ozone destruction over the Arctic in early 2011 was--for the first time in the observational record--comparable to that in the Antarctic ozone hole. Unusually long-lasting cold conditions in the Arctic lower stratosphere led to persistent enhancement in ozone-destroying forms of chlorine and to unprecedented ozone loss, which exceeded 80 per cent over 18-20 kilometres altitude. Our results show that Arctic ozone holes are possible even with temperatures much milder than those in the Antarctic. We cannot at present predict when such severe Arctic ozone depletion may be matched or exceeded., Since the emergence of the Antarctic 'ozone hole' in the 1980s (1) and elucidation of the chemical mechanisms (2-5) and meteorological conditions (6) involved in its formation, the likelihood of [...]

The crisis that swept across the world's financial markets this autumn is widely regarded as the worst since the 1930s. The global economic downturn that helped precipitate the crash, and [...]

Author(s): B. Scott Gaudi (corresponding author) [1]; Keivan G. Stassun [2, 3]; Karen A. Collins [2]; Thomas G. Beatty [4, 5]; George Zhou [6]; David W. Latham [6]; Allyson Bieryla [...]

In a canyon just outside Kabul, the rocky terrain is strewn with debris symbolizing the troubled past and tenuous future of war-torn Afghanistan. Exploratory cores, drilled decades ago by Soviets [...]

Author(s): Chen Chen [1]; Wenjun Ouyang [4]; Vadim Grigura [1]; Qing Zhou [5]; Kay Carnes [6]; Hyunjung Lim [3]; Guang-Quan Zhao [7]; Silvia Arber [8, 9]; Natasza Kurpios [10]; Theresa [...]

Author(s): Rex Dalton San Francisco An ecologist at the University of California, Berkeley, best known for his outspoken criticism of genetically modified crops and of the university's links with the [...]

Author(s): Steven A. Harich [1]; Dongxu Dai [1, 2]; Chia C. Wang [1, 3]; Xueming Yang (corresponding author) [1, 2, 4]; Sheng Der Chao [5, 6]; Rex T. Skodje (corresponding [...]

Scientific fraud has become increasingly common as the world of scientific research becomes more competitive. In many cases, scientists do not seek to deliberately falsify their findings, but fail to follow accepted practice in order to come more rapidly to a conclusion they genuinely believe to be true. It is very hard to obtain reliable information about scientific fraud, and there are therefore very mixed views about the extent of this problem. There are also mixed views about how far investigations into scientific fraud should be taken.