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Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer(1-3). However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer.

Observed reversals in GNSS surface motions suggests greatly enhanced slab pull in the months preceding the great subduction earthquakes in Maule (Chile, 2010) and Tohoku-oki (Japan, 2011) of moment magnitudes 8.8 and 9.0.

Megathrust earthquakes are responsible for some of the most devastating natural disasters(1). To better understand the physical mechanisms of earthquake generation, subduction zones worldwide are continuously monitored with geophysical instrumentation. One key strategy is to install stations that record signals from Global Navigation Satellite Systems(2,3) (GNSS), enabling us to track the non-steady surface motion of the subducting and overriding plates before, during and after the largest events(4-6). Here we use a recently developed trajectory modelling approach(7) that is designed to isolate secular tectonic motions from the daily GNSS time series to show that the 2010 Maule, Chile (moment magnitude 8.8) and 2011 Tohoku-oki, Japan (moment magnitude 9.0) earthquakes were preceded by reversals of 4-8 millimetres in surface displacement that lasted several months and spanned thousands of kilometres. Modelling of the surface displacement reversal that occurred before the Tohoku-oki earthquake suggests an initial slow slip followed by a sudden pulldown of the Philippine Sea slab so rapid that it caused a viscoelastic rebound across the whole of Japan. Therefore, to understand better when large earthquakes are imminent, we must consider not only the evolution of plate interface frictional processes but also the dynamic boundary conditions from deeper subduction processes, such as sudden densification of metastable slab.

After severe brain injury, it can be difficult to determine the state of consciousness of a patient, to determine whether the patient is unresponsive or perhaps minimally conscious(1), and to predict whether they will recover. These diagnoses and prognoses are crucial, as they determine therapeutic strategies such as pain management, and can underlie end-of-life decisions(2,3). Nevertheless, there is an error rate of up to 40% in determining the state of consciousness in patients with brain injuries(4,5). Olfaction relies on brain structures that are involved in the basic mechanisms of arousal(6), and we therefore hypothesized that it may serve as a biomarker for consciousness(7). Here we use a non-verbal non-task-dependent measure known as the sniff response(8-11) to determine consciousness in patients with brain injuries. By measuring odorant-dependent sniffing, we gain a sensitive measure of olfactory function(10-15). We measured the sniff response repeatedly over time in patients with severe brain injuries and found that sniff responses significantly discriminated between unresponsive and minimally conscious states at the group level. Notably, at the single-patient level, if an unresponsive patient had a sniff response, this assured future regaining of consciousness. In addition, olfactory sniff responses were associated with long-term survival rates. These results highlight the importance of olfaction in human brain function, and provide an accessible tool that signals consciousness and recovery in patients with brain injuries.

Odorant-dependent sniff responses predicted the long-term survival rates of patients with severe brain injury, and discriminated between individuals who were unresponsive and in minimally conscious states.

A microscopy system that enables simultaneous recording from hundreds of neurons in the mouse visual cortex reveals that the brain enhances its coding capacity by representing visual inputs in dimensions perpendicular to correlated noise.

Apoptotic cells communicate with neighbouring cells by the regulated release of specific metabolites, and a cocktail of select apoptotic metabolites reduces disease severity in mouse models of inflammatory arthritis and lung transplant rejection.