Lockyer reveals teenager to revive woeful Broncos,Brisbane legend Darren Lockyer has tipped teenage hooker Blake Mozer to come in and make a difference next...
Lockyer reveals teenager to revive woeful Broncos
Brisbane legend Darren Lockyer has tipped teenage hooker Blake Mozer to come in and make a difference next…
Acceleration of 1I/鈥極umuamua from radiolytically produced H2 in H2O ice,In 2017, 1I/‘Oumuamua was identified as the first known interstellar object in the Solar System1. Although typical cometary activity tracers were not detected2–6, ‘Oumuamua showed a notable non-gravitational acceleration7. So far, there has been no explanation that can reconcile these constraints8. Owing to energetic considerations, outgassing of hyper-volatile molecules is favoured over heavier volatiles such as H2O and CO2 (ref. 9). However, there are theoretical and/or observational inconsistencies10 with existing models invoking the sublimation of pure H2 (ref. 9), N2 (ref. 11) and CO (ref. 12). Non-outgassing explanations require fine-tuned formation mechanisms and/or unrealistic progenitor production rates7,13–15. Here we report that the acceleration of ‘Oumuamua is due to the release of entrapped molecular hydrogen that formed through energetic processing of an H2O-rich icy body. In this model, ‘Oumuamua began as an icy planetesimal that was irradiated at low temperatures by cosmic rays during its interstellar journey, and experienced warming during its passage through the Solar System. This explanation is supported by a large body of experimental work showing that H2 is efficiently and generically produced from H2O ice processing, and that the entrapped H2 is released over a broad range of temperatures during annealing of the amorphous water matrix16–22. We show that this mechanism can explain many of ‘Oumuamua’s peculiar properties without fine-tuning. This provides further support3 that ‘Oumuamua originated as a planetesimal relic broadly similar to Solar System comets. Acceleration of ‘Oumuamua is due to the release of entrapped molecular hydrogen formed through energetic processing of an H2O-rich icy body, supporting the idea that it originated as a planetesimal relic similar to Solar System comets. Tags:asteroidsBergnercomets and Kuiper beltDarryl Z.humanities and social sciencesinterstellar mediumJennifer B.multidisciplinaryNaturenature.comscienceSeligman
Photosynthesis re-wired on the pico-second timescale,Photosystems II and I (PSII, PSI) are the reaction centre-containing complexes driving the light reactions of photosynthesis; PSII performs light-driven water oxidation and PSI further photo-energizes harvested electrons. The impressive efficiencies of the photosystems have motivated extensive biological, artificial and biohybrid approaches to ‘re-wire’ photosynthesis for higher biomass-conversion efficiencies and new reaction pathways, such as H2 evolution or CO2 fixation1,2. Previous approaches focused on charge extraction at terminal electron acceptors of the photosystems3. Electron extraction at earlier steps, perhaps immediately from photoexcited reaction centres, would enable greater thermodynamic gains; however, this was believed impossible with reaction centres buried at least 4 nm within the photosystems4,5. Here, we demonstrate, using in vivo ultrafast transient absorption (TA) spectroscopy, extraction of electrons directly from photoexcited PSI and PSII at early points (several picoseconds post-photo-excitation) with live cyanobacterial cells or isolated photosystems, and exogenous electron mediators such as 2,6-dichloro-1,4-benzoquinone (DCBQ) and methyl viologen. We postulate that these mediators oxidize peripheral chlorophyll pigments participating in highly delocalized charge-transfer states after initial photo-excitation. Our results challenge previous models that the photoexcited reaction centres are insulated within the photosystem protein scaffold, opening new avenues to study and re-wire photosynthesis for biotechnologies and semi-artificial photosynthesis. By using in vivo ultrafast TA spectroscopy, extraction of electrons directly from photoexcited PSI and PSII in cyanobacterial cells using exogenous electron mediators is demonstrated. Tags:BaikieBioenergeticsBiological physicsBiophysical chemistryElectron transferErwinHiteshhumanities and social sciencesJoshua M.Laura T.LawrenceMedipallymultidisciplinaryNaturenature.comPhotobiologyReisnerscienceTomi K.Wey
RHOJ controls EMT-associated resistance to chemotherapy,The resistance of cancer cells to therapy is responsible for the death of most patients with cancer1. Epithelial-to-mesenchymal transition (EMT) has been associated with resistance to therapy in different cancer cells2,3. However, the mechanisms by which EMT mediates resistance to therapy remain poorly understood. Here, using a mouse model of skin squamous cell carcinoma undergoing spontaneous EMT during tumorigenesis, we found that EMT tumour cells are highly resistant to a wide range of anti-cancer therapies both in vivo and in vitro. Using gain and loss of function studies in vitro and in vivo, we found that RHOJ—a small GTPase that is preferentially expressed in EMT cancer cells—controls resistance to therapy. Using genome-wide transcriptomic and proteomic profiling, we found that RHOJ regulates EMT-associated resistance to chemotherapy by enhancing the response to replicative stress and activating the DNA-damage response, enabling tumour cells to rapidly repair DNA lesions induced by chemotherapy. RHOJ interacts with proteins that regulate nuclear actin, and inhibition of actin polymerization sensitizes EMT tumour cells to chemotherapy-induced cell death in a RHOJ-dependent manner. Together, our study uncovers the role and the mechanisms through which RHOJ acts as a key regulator of EMT-associated resistance to chemotherapy. RHOJ regulates epithelial-to-mesenchymal-transition-associated resistance to chemotherapy by enhancing the response to replicative stress and activating the DNA damage response, enabling tumour cells to rapidly repair DNA lesions induced by chemotherapy. Tags:BlondeauCancer therapeutic resistanceDebaugnieshumanities and social sciencesjeremyManuelMarie AstridMaudmultidisciplinaryNaturenature.comparentRodr&237;guez AcebessarascienceTumour heterogeneityZocco
From primordial clocks to circadian oscillators,Circadian rhythms play an essential part in many biological processes, and only three prokaryotic proteins are required to constitute a true post-translational circadian oscillator1. The evolutionary history of the three Kai proteins indicates that KaiC is the oldest member and a central component of the clock2. Subsequent additions of KaiB and KaiA regulate the phosphorylation state of KaiC for time synchronization. The canonical KaiABC system in cyanobacteria is well understood3–6, but little is known about more ancient systems that only possess KaiBC. However, there are reports that they might exhibit a basic, hourglass-like timekeeping mechanism7–9. Here we investigate the primordial circadian clock in Rhodobacter sphaeroides, which contains only KaiBC, to elucidate its inner workings despite missing KaiA. Using a combination of X-ray crystallography and cryogenic electron microscopy, we find a new dodecameric fold for KaiC, in which two hexamers are held together by a coiled-coil bundle of 12 helices. This interaction is formed by the carboxy-terminal extension of KaiC and serves as an ancient regulatory moiety that is later superseded by KaiA. A coiled-coil register shift between daytime and night-time conformations is connected to phosphorylation sites through a long-range allosteric network that spans over 140 Å. Our kinetic data identify the difference in the ATP-to-ADP ratio between day and night as the environmental cue that drives the clock. They also unravel mechanistic details that shed light on the evolution of self-sustained oscillators. X-ray, cryo-EM and kinetic studies of the circadian oscillator KaiBC from the photosynthetic bacterium Rhodobacter sphaeroides shed light on the evolution of self-regulating oscillators. Tags:Enzyme mechanismsgrantHoembergerhumanities and social sciencesMarcmultidisciplinaryNaturenature.comottenP&225;duaPitsawongReneeRicardo A. P.scienceStructural biologytimothyWarintra
Structural and mechanistic insights into fungal 尾-1,3-glucan synthase FKS1,The membrane-integrated synthase FKS is involved in the biosynthesis of β-1,3-glucan, the core component of the fungal cell wall1,2. FKS is the target of widely prescribed antifungal drugs, including echinocandin and ibrexafungerp3,4. Unfortunately, the mechanism of action of FKS remains enigmatic and this has hampered development of more effective medicines targeting the enzyme. Here we present the cryo-electron microscopy structures of Saccharomyces cerevisiae FKS1 and the echinocandin-resistant mutant FKS1(S643P). These structures reveal the active site of the enzyme at the membrane–cytoplasm interface and a glucan translocation path spanning the membrane bilayer. Multiple bound lipids and notable membrane distortions are observed in the FKS1 structures, suggesting active FKS1–membrane interactions. Echinocandin-resistant mutations are clustered at a region near TM5–6 and TM8 of FKS1. The structure of FKS1(S643P) reveals altered lipid arrangements in this region, suggesting a drug-resistant mechanism of the mutant enzyme. The structures, the catalytic mechanism and the molecular insights into drug-resistant mutations of FKS1 revealed in this study advance the mechanistic understanding of fungal β-1,3-glucan biosynthesis and establish a foundation for developing new antifungal drugs by targeting FKS. Using cryo-electron microscopy, the molecular architecture and catalytic mechanism of action of the fungal β-1,3-glucan synthase FKS1 are determined. Tags:chaiChangdongCryoelectron microscopyFungiglycobiologyHuHuanhuanhumanities and social sciencesJiaLiumultidisciplinaryNaturenature.compingscienceSunXinlinYang
Quantum-enabled millimetre wave to optical transduction using neutral atoms,Early experiments with transiting circular Rydberg atoms in a superconducting resonator laid the foundations of modern cavity and circuit quantum electrodynamics1, and helped explore the defining features of quantum mechanics such as entanglement. Whereas ultracold atoms and superconducting circuits have since taken rather independent paths in the exploration of new physics, taking advantage of their complementary strengths in an integrated system enables access to fundamentally new parameter regimes and device capabilities2,3. Here we report on such a system, coupling an ensemble of cold 85Rb atoms simultaneously to an, as far as we are aware, first-of-its-kind optically accessible, three-dimensional superconducting resonator4 and a vibration-suppressed optical cavity in a cryogenic (5 K) environment. To demonstrate the capabilities of this platform, and with an eye towards quantum networking5, we leverage the strong coupling between Rydberg atoms and the superconducting resonator to implement a quantum-enabled millimetre wave (mmwave) photon to optical photon transducer6. We measured an internal conversion efficiency of 58(11)%, a conversion bandwidth of 360(20) kHz and added thermal noise of 0.6 photons, in agreement with a parameter-free theory. Extensions of this technique will allow near-unity efficiency transduction in both the mmwave and microwave regimes. More broadly, our results open a new field of hybrid mmwave/optical quantum science, with prospects for operation deep in the strong coupling regime for efficient generation of metrologically or computationally useful entangled states7 and quantum simulation/computation with strong non-local interactions8. We report an ensemble of cold 85Rb atoms strongly coupled to a superconducting resonator and optical cavity, resulting in the demonstration of quantum-enabled transduction of millimetre wave photons to optical photons. Tags:AishwaryaalexanderAnferovAtomic and molecular interactions with photonsAzizahumanities and social sciencesKumarLavanyamarkmultidisciplinaryNaturenature.comquantum informationquantum opticssciencestoneSuleymanzadeTaneja
CFTR function, pathology and pharmacology at single-molecule resolution,The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that regulates salt and fluid homeostasis across epithelial membranes1. Alterations in CFTR cause cystic fibrosis, a fatal disease without a cure2,3. Electrophysiological properties of CFTR have been analysed for decades4–6. The structure of CFTR, determined in two globally distinct conformations, underscores its evolutionary relationship with other ATP-binding cassette transporters. However, direct correlations between the essential functions of CFTR and extant structures are lacking at present. Here we combine ensemble functional measurements, single-molecule fluorescence resonance energy transfer, electrophysiology and kinetic simulations to show that the two nucleotide-binding domains (NBDs) of human CFTR dimerize before channel opening. CFTR exhibits an allosteric gating mechanism in which conformational changes within the NBD-dimerized channel, governed by ATP hydrolysis, regulate chloride conductance. The potentiators ivacaftor and GLPG1837 enhance channel activity by increasing pore opening while NBDs are dimerized. Disease-causing substitutions proximal (G551D) or distal (L927P) to the ATPase site both reduce the efficiency of NBD dimerization. These findings collectively enable the framing of a gating mechanism that informs on the search for more efficacious clinical therapies. A structure–function analysis of cystic fibrosis transmembrane conductance regulator shows its two nucleotide-binding domains dimerize before channel opening, and reveals a mechanism through which conformational changes in the channel regulate chloride conductance. Tags:blanchardChloride channelsCryoelectron microscopyDaniel S.Fitzgeraldgabrielhumanities and social sciencesJesperKilicKineticsLevringmembrane proteinsmultidisciplinaryNaturenature.comscienceScottSingle molecule biophysicsTerryzeliha
RBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer,Pancreatic ductal adenocarcinoma (PDA) is characterized by aggressive local invasion and metastatic spread, leading to high lethality. Although driver gene mutations during PDA progression are conserved, no specific mutation is correlated with the dissemination of metastases1–3. Here we analysed RNA splicing data of a large cohort of primary and metastatic PDA tumours to identify differentially spliced events that correlate with PDA progression. De novo motif analysis of these events detected enrichment of motifs with high similarity to the RBFOX2 motif. Overexpression of RBFOX2 in a patient-derived xenograft (PDX) metastatic PDA cell line drastically reduced the metastatic potential of these cells in vitro and in vivo, whereas depletion of RBFOX2 in primary pancreatic tumour cell lines increased the metastatic potential of these cells. These findings support the role of RBFOX2 as a potent metastatic suppressor in PDA. RNA-sequencing and splicing analysis of RBFOX2 target genes revealed enrichment of genes in the RHO GTPase pathways, suggesting a role of RBFOX2 splicing activity in cytoskeletal organization and focal adhesion formation. Modulation of RBFOX2-regulated splicing events, such as via myosin phosphatase RHO-interacting protein (MPRIP), is associated with PDA metastases, altered cytoskeletal organization and the induction of focal adhesion formation. Our results implicate the splicing-regulatory function of RBFOX2 as a tumour suppressor in PDA and suggest a therapeutic approach for metastatic PDA. Analysis of messenger RNA splicing in a large cohort of pancreatic ductal adenocarcinoma tumours identifies differential splicing correlating with disease progression, associated with the the splicing regulator RBFOX2. Tags:alternative splicingAminaChaniHayahumanities and social sciencesJbaraKuan TinglinMetastasismultidisciplinaryNaturenature.comRNAscienceShqeratSiegfriedStosselZahava
Former Bronco Milford a chance as Dolphins eye Brisbane,Former Bronco Anthony Milford, relegated to Queensland Cup feeder team Central Queensland Capras, is ready to make a statement if called upon for the Battle of Brisbane. Tags:Brisbane BroncosDolphinsNRLNRL 2023smh.com.auThe Sydney Morning Herald
Health fears lead Aussie star to quit surfing,Australian surfer Owen Wright will retire from World Surf League career after next month's Rip Curl Pro at ... Tags:cat1nine.com.auowen wrightSurfingWWOS9
Egyptian ref suspended over fake VAR scandal,A referee in an Egyptian football league has been suspended after he used a fan's phone to disallow a 90th ... Tags:cat1Footballnine.com.auWWOS9
'Horrendous': Aussie win marred by 'very bad' injury,Australia's Alexei Popyrin is through to the second round of the Miami Open after his opponent was forced ... Tags:Alexei Popyrincat1Miami Opennine.com.auTennisWWOS9
'Horrific': Schumacher's wife 'like a prisoner',Keeping Michael Schumacher's health a secret and upholding the family's privacy has an impact on his wife, ... Tags:cat1Michael SchumacherMotorsportnine.com.auWWOS9
Raider's perfect reply to 'weak-gutted dog' crack,Corey Horsburgh mocked rival Royce Hunt on social media after the latter labelled the Raiders player a "wea... Tags:Canberra Raiderscat1Cronulla Sharksnine.com.auNRLWWOS9
Pendlebury calls for AFL to bring in a sin bin,Scott Pendlebury would like to see the AFL trial a sin bin rule following a string of vicious head-high hit... Tags:aflcat1nine.com.auScott PendleburyWWOS9
Probe after ambulance causes terrifying race crash,Daniel Alexander survived a terrifying crash after an ambulance crossed a live track towards the end of a r... Tags:cat1Motorsportnine.com.auWWOS9
Teammate's telling reaction to Piastri team order,Having been ordered to let his young teammate past in the closing laps, Lando Norris gave a salty TV inter... Tags:cat1F1Lando NorrisMcLarennine.com.auOscar PiastriWWOS9
Three red cards in two minutes turn crazy match,Fulham had two players and manager Marco Silva sent off before quickly conceding twice against Manchester U... Tags:cat1FA CupFootballManchester Unitednine.com.auWWOS9
Three ways moving on from Aaron Rodgers impacts Packers
Three ways moving on from Aaron Rodgers impacts Packers,Moving on from a franchise quarterback is a challenging situation for any NFL team. Here are three ways the Packers will be impacted if Rodgers has indeed played his last game as a member of the
DOH warns vs eating seafood from oil spill areas
DOH warns vs eating seafood from oil spill areas,The Department of Health warned the public yesterday against eating fish and other seafood from areas affected by the oil spill.
The post DOH warns vs eating seafood from oil spill areas appeared first
Washington turns to Wall Street to help rescue dying bank
Washington turns to Wall Street to help rescue dying bank,In a scene reminiscent of the last financial crisis, the federal government turned to Wall Street this week for help with a blossoming emergency in the banking sector
Birds sometimes hitch rides on ships—and it's changing the way they migrate,Freighter crews have long told stories of sparrows and nightjars, owls, and herons settling on their boats’ decks. Tags:AnimalsBirdsEnvironmentpopsci.comPopular ScienceWildlife
What we know about hormonal birth control and breast cancer risk,Don't throw out your birth control pills just yet—studies show this risk disappears eventually after stopping hormonal birth control. Tags:CancerdiseasesHealthmedicinepopsci.comPopular ScienceScience
What ancient tsunamis can teach us about future disasters,Gigantic tsunamis have been decimating coastlines since time immemorial. We ignore these prehistoric warnings at our own peril. Tags:Environmentpopsci.comPopular ScienceScienceweather
