A common deep source for upper-mantle upwellings below the Ibero-western Maghreb region from teleseismic P-wave travel-time tomography

Upper-mantle upwellings are often invoked as the cause of Cenozoic volcanism in the Ibero-western Maghreb region. However, their nature, geometry and origin are unclear. This study takes advantage of dense seismic networks, which cover an area extending from the Pyrenees in the north to the Canaries in the south, to provide a new high-resolution P-wave velocity model of the upper-mantle and topmost lower-mantle structure. Our images show three subvertical upper-mantle upwellings below the Canaries, the Atlas Ranges and the Gibraltar Arc, which appear to be rooted beneath the upper-mantle transition zone (MTZ). Two other mantle upwellings beneath the eastern Rif and eastern Betics surround the Gibraltar subduction zone. We propose a new geodynamic model in which narrow upper-mantle upwellings below the Canaries, the Atlas Ranges and the Gibraltar Arc rise from a laterally-propagating layer of material below the MTZ, which in turn is fed by a common deep source below the Canaries. In the Gibraltar region, the deeply rooted upwelling interacts with the Gibraltar slab. Quasi-toroidal flow driven by slab rollback induces the hot mantle material to flow around the slab, creating the two low-velocity anomalies below the eastern Betics and eastern Rif. Our results suggest that the Central Atlantic plume is a likely source of hot mantle material for upper-mantle upwellings in the Ibero-western Maghreb region

Annual Ryegrass Pasture for Dairy Cows Receiving Total Mixed Ration

The inclusion of herbage in the diet of medium yielding dairy cows offered a total mixed ration (TMR) may be beneficial. This study, which involved mid lactation dairy cows, examined the effect of partial replacement of a TMR with annual temperate pasture. Treatments were ad libitum TMR (TMR100), 75% ad libitum TMR + ryegrass (Lolium multiflorum ‘Maximus’) (TMR75), and 50% ad libitum TMR + ryegrass (TMR50). Twelve multiparous Holstein and F1 Jersey × Holstein cows were divided into six homogeneous groups, taking account of milk production (26.6 ± 4.5 kg/day), days in milk (128 ± 50) and body weight (546 ± 31 kg). Treatments were compared in a replicated 3×3 Latin square design, comprising three 21-day periods (measurements during final 5 days). Cows on TMR75 and TMR50 strip grazed between morning and afternoon milking (7 h/day), with a target pre- and post-grazing sward height of 24 and 12 cm, respectively. Herbage DM intake was estimated as the difference between pre- and post-grazing herbage mass. The TMR and herbage had a crude protein content of 150 and 303 g/kg DM, and a NDF content of 366 and 495 g/kg DM, respectively. Herbage DM intake increased from 4.8 kg/day in TMR75 to 6.7 kg/day on TMR50. Total DM intake decreased from 19.4 kg/day (TMR100), to 18.1 and 15.9 kg/day (TMR75 and TMR50, respectively). Milk production, milk fat and milk protein content were similar between treatments, averaging 25.6 kg/day, 44.6 g/kg and 33.7 g/kg, respectively. The net energy for lactation (NEL) supply was 113, 104 and 92% of NEL requirements, for cows receiving TMR100, TMR75 and TMR50, respectively. Ryegrass pastures were able to replace up to 50% of TMR offered to mid lactation dairy cows without any adverse effects on milk production and milk composition

The seismic signature of Upper‐Mantle Plumes: application to the Northern East African Rift

Several seismic and numerical studies proposed that below, some hotspots upper‐mantle plumelets rise from a thermal boundary layer below 660 km depth, fed by a deeper plume source. We recently found tomographic evidence of multiple upper‐mantle upwellings, spaced by several 100 km, rising through the transition zone below the northern East African Rift. To better test this interpretation, we run 3‐D numerical simulations of mantle convection for Newtonian and non‐Newtonian rheologies, for both thermal instabilities rising from a lower boundary layer, and the destabilization of a thermal anomaly placed at the base of the box (700–800 km depth). The thermal structures are converted to seismic velocities using a thermodynamic approach. Resolution tests are then conducted for the same P and S data distribution and inversion parameters as our traveltime tomography. The Rayleigh Taylor models predict simultaneous plumelets in different stages of evolution rising from a hot layer located below the transition zone, resulting in seismic structure that looks more complex than the simple vertical cylinders that are often anticipated. From the wide selection of models tested, we find that the destabilization of a 200 °C, 100 km thick thermal anomaly with a non‐Newtonian rheology, most closely matches the magnitude and the spatial and temporal distribution of the anomalies below the rift. Finally, we find that for reasonable upper‐mantle viscosities, the synthetic plume structures are similar in scale and shape to the actual low‐velocity anomalies, providing further support for the existence of upper‐mantle plumelets below the northern East African Rift

PAK6 Phosphorylates 14-3-3 gamma to Regulate Steady State Phosphorylation of LRRK2

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson’s disease (PD) and, as such, LRRK2 is considered a promising therapeutic target for age-related neurodegeneration. Although the cellular functions of LRRK2 in health and disease are incompletely understood, robust evidence indicates that PD-associated mutations alter LRRK2 kinase and GTPase activities with consequent deregulation of the downstream signaling pathways. We have previously demonstrated that one LRRK2 binding partner is P21 (RAC1) Activated Kinase 6 (PAK6). Here, we interrogate the PAK6 interactome and find that PAK6 binds a subset of 14-3-3 proteins in a kinase dependent manner. Furthermore, PAK6 efficiently phosphorylates 14-3-3γ at Ser59 and this phosphorylation serves as a switch to dissociate the chaperone from client proteins including LRRK2, a well-established 14-3-3 binding partner. We found that 14-3-3γ phosphorylated by PAK6 is no longer competent to bind LRRK2 at phospho-Ser935, causing LRRK2 dephosphorylation. To address whether these interactions are relevant in a neuronal context, we demonstrate that a constitutively active form of PAK6 rescues the G2019S LRRK2-associated neurite shortening through phosphorylation of 14-3-3γ. Our results identify PAK6 as the kinase for 14-3-3γ and reveal a novel regulatory mechanism of 14-3-3/LRRK2 complex in the brain

GTP binding controls complex formation by the human ROCO protein MASL1.

The human ROCO proteins are a family of multi-domain proteins sharing a conserved ROC-COR supra-domain. The family has four members: leucine-rich repeat kinase 1 (LRRK1), leucine-rich repeat kinase 2 (LRRK2), death-associated protein kinase 1 (DAPK1) and malignant fibrous histiocytoma amplified sequences with leucine-rich tandem repeats 1 (MASL1). Previous studies of LRRK1/2 and DAPK1 have shown that the ROC (Ras of complex proteins) domain can bind and hydrolyse GTP, but the cellular consequences of this activity are still unclear. Here, the first biochemical characterization of MASL1 and the impact of GTP binding on MASL1 complex formation are reported. The results demonstrate that MASL1, similar to other ROCO proteins, can bind guanosine nucleotides via its ROC domain. Furthermore, MASL1 exists in two distinct cellular complexes associated with heat shock protein 60, and the formation of a low molecular weight pool of MASL1 is modulated by GTP binding. Finally, loss of GTP enhances MASL1 toxicity in cells. Taken together, these data point to a central role for the ROC/GTPase domain of MASL1 in the regulation of its cellular function

Multiple mantle upwellings in the transition zone beneath the northern East-African Rift system from relative P-wave travel-time tomography

Mantle plumes and consequent plate extension have been invoked as the likely cause of East African Rift volcanism. However, the nature of mantle upwelling is debated, with proposed configurations ranging from a single broad plume connected to the large low-shear-velocity province beneath Southern Africa, the so-called African Superplume, to multiple lower-mantle sources along the rift. We present a new P-wave travel-time tomography model below the northern East-African, Red Sea, and Gulf of Aden rifts and surrounding areas. Data are from stations that span an area from Madagascar to Saudi Arabia. The aperture of the integrated data set allows us to image structures of 100 km length-scale down to depths of 700– 800 km beneath the study region. Our images provide evidence of two clusters of low-velocity structures consisting of features with diameter of 100–200 km that extend through the transition zone, the first beneath Afar and a second just west of the Main Ethiopian Rift, a region with off-rift volcanism. Considering seismic sensitivity to temperature, we interpret these features as upwellings with excess temperatures of 100 6 50 K. The scale of the upwellings is smaller than expected for lower mantle plume sources. This, together with the change in pattern of the low-velocity anomalies across the base of the transition zone, suggests that ponding or flow of deep-plume material below the transition zone may be spawning these upper mantle upwellings

Thermal Nature of Mantle Upwellings Below the Ibero-Western Maghreb Region Inferred From Teleseismic Tomography

©2019. American Geophysical Union. All Rights Reserved. Independent models of P wave and S wave velocity anomalies in the mantle derived from seismic tomography help to distinguish thermal signatures from those of partial melt, volatiles, and compositional variations. Here we use seismic data from SW Europe and NW Africa, spanning the region between the Pyrenees and the Canaries, in order to obtain a new S-SKS relative arrival-time tomographic model of the upper mantle below Iberia, Western Morocco, and the Canaries. Similar to previous P wave tomographic results, the S wave model provides evidence for (1) subvertical upper-mantle low-velocity structures below the Canaries, Atlas Ranges, and Gibraltar Arc, which are interpreted as mantle upwellings fed by a common lower-mantle source below the Canaries; and (2) two low-velocity anomalies below the eastern Rif and Betics that we interpret as the result of the interaction between quasi-toroidal mantle flow induced by the Gibraltar slab and the mantle upwelling behind it. The analysis of teleseismic P wave and S wave arrival-time residuals and the conversion of the low-velocity anomalies to temperature variations suggest that the upwellings in the upper mantle below the Canaries, Atlas Ranges, and Gibraltar Arc system may be solely thermal in nature, with temperature excesses in the range ~100–350 °C. Our results also indicate that local partial melting can be present at lithospheric depths, especially below the Atlas Ranges. The locations of thermal mantle upwellings are in good agreement with those of thinned lithosphere, moderate to high heat-flow measurements, and recent magmatic activity at the surface

The LRRK2 signalling system

The LRRK2 gene is a major contributor to genetic risk for Parkinson's disease and understanding the biology of the leucine-rich repeat kinase 2 (LRRK2, the protein product of this gene) is an important goal in Parkinson's research. LRRK2 is a multi-domain, multi-activity enzyme and has been implicated in a wide range of signalling events within the cell. Because of the complexities of the signal transduction pathways in which LRRK2 is involved, it has been challenging to generate a clear idea as to how mutations and disease associated variants in this gene are altered in disease. Understanding the events in which LRRK2 is involved at a systems level is therefore critical to fully understand the biology and pathobiology of this protein and is the subject of this review

LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same

Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at the trans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places