LIM Kinase Regulation of Cytoskeletal Dynamics is Required for Salivary Gland Branching Morphogenesis

Coordinated actin microfilament and microtubule dynamics is required for salivary gland development, although the mechanisms by which they contribute to branching morphogenesis are not defined. Because LIM kinase (LIMK) regulates both actin and microtubule organization, we investigated the role of LIMK signaling in mouse embryonic submandibular salivary glands using ex vivo organ cultures. Both LIMK 1 and 2 were necessary for branching morphogenesis and functioned to promote epithelial early- and late-stage cleft progression through regulation of both microfilaments and microtubules. LIMK-dependent regulation of these cytoskeletal systems was required to control focal adhesion protein– dependent fibronectin assembly and integrin β1 activation, involving the LIMK effectors cofilin and TPPP/p25, for assembly of the actin- and tubulin-based cytoskeletal systems, respectively. We demonstrate that LIMK regulates the early stages of cleft formation—cleft initiation, stabilization, and progression—via establishment of actin stability. Further, we reveal a novel role for the microtubule assembly factor p25 in regulating stabilization and elongation of late-stage progressing clefts. This study demonstrates the existence of multiple actin- and microtubule-dependent stabilization steps that are controlled by LIMK and are required in cleft progression during branching morphogenesis

Multiband Comparative Study of Optical Microvariability in RL vs. RQ Quasars

We present the results of an optical multi-band (BVR) photometric monitoring program of 22 core-dominated radio-loud quasars (CRLQs) and 22 radio-quiet quasars (RQQs). The aim was to compare the properties of microvariability in both types of quasars. We detected optical microvariability in 5 RQQs and 4 CRLQs. Our results confirm that microvariability in RQQs may be as frequent as in CRLQs. In addition we compare microvariability duty cycles in different bands. Finally, the implications for the origin of the microvariations are briefly discussed.Comment: 17 pages, 14 figures, Accepted for publication in the Astronomical Journa

Proof of concept study on coronary microvascular function in low flow low gradient aortic stenosis

ObjectivesWe hypothesised that low flow low gradient aortic stenosis (LFLGAS) is associated with more severe coronary microvascular dysfunction (CMD) compared with normal-flow high-gradient aortic stenosis (NFHGAS) and that CMD is related to reduced cardiac performance. MethodsInvasive CMD assessment was performed in 41 consecutive patients with isolated severe aortic stenosis with unobstructed coronary arteries undergoing transcatheter aortic valve implantation (TAVI). The index of microcirculatory resistance (IMR), resistive reserve ratio (RRR) and coronary flow reserve (CFR) were measured in the left anterior descending artery before and after TAVI. Speckle tracking echocardiography was performed to assess cardiac function at baseline and repeated at 6 months. ResultsIMR was significantly higher in patients with LFLGAS compared with patients with NFHGAS (24.1 (14.6 to 39.1) vs 12.8 (8.6 to 19.2), p=0.002), while RRR was significantly lower (1.4 (1.1 to 2.1) vs 2.6 (1.5 to 3.3), p=0.020). No significant differences were observed in CFR between the two groups. High IMR was associated with low stroke volume index, low cardiac output and reduced peak atrial longitudinal strain (PALS). TAVI determined no significant variation in microvascular function (IMR: 16.0 (10.4 to 26.1) vs 16.6 (10.2 to 25.6), p=0.403) and in PALS (15.9 (9.9 to 26.5) vs 20.1 (12.3 to 26.7), p=0.222). Conversely, left ventricular (LV) global longitudinal strain increased after TAVI (-13.2 (8.4 to 16.6) vs -15.1 (9.4 to 17.8), p=0.047). In LFLGAS, LV systolic function recovered after TAVI in patients with preserved microvascular function but not in patients with CMD. ConclusionsCMD is more severe in patients with LFLGAS compared with NFHGAS and is associated with low-flow state, left atrial dysfunction and reduced cardiac performance

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements