Biology subjects

Keller, J.

Publications and source records attributed to Keller, J..

39 records · Page 3Linked to original sources

bioRxiv2019

Genome sequence of the cluster root forming white lupin

White lupin (Lupinus albus L.) is a legume that produces seeds recognized for their high protein content and good nutritional value (lowest glycemic index of all grains, high dietary fiber content, and zero gluten or starch)1-5. White lupin can form nitrogen-fixing nodules but has lost the ability to form mycorrhizal symbiosis with fungi6. Nevertheless, its root system is well adapted to poor soils: it produces cluster roots, constituted of dozens of determinate lateral roots that improve soil exploration and phosphate remobilization7. As phosphate is a limited resource that comes from rock reserves8, the production of cluster roots is a trait of interest to improve fertilizers efficiency. Using long reads sequencing technologies, we provide a high-quality genome sequence of a modern variety of white lupin (2n=50, 451 Mb), as well as de novo assemblies of a landrace and a wild relative. We describe how domestication impacted soil exploration capacity through the early establishment of lateral and cluster roots. We identify the APETALA2 transcription factor LaPUCHI-1, homolog of the Arabidopsis morphogenesis coordinator9, as a potential regulator of this trait. Our high-quality genome and companion genomic and transcriptomic resources enable the development of modern breeding strategies to increase and stabilize yield and to develop new varieties with reduced allergenic properties (caused by conglutins10), which would favor the deployment of this promising culture.

genomics↗

bioRxiv2019

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD).

BackgroundCurrent treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment that is FDA-approved for treatment-resistant depression (TRD). Recent methodological advancements suggest iTBS could be improved through 1) treating with multiple sessions per day at optimally-spaced intervals, 2) applying a higher overall pulse-dose of stimulation and 3) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. We examined the feasibility, tolerability, and preliminary efficacy of an accelerated, high-dose, resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for TRD termed Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT). MethodsTwenty-one participants with TRD received open-label SAINT. FcMRI was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. ResultsNineteen of 21 participants (90.48%) met criteria for remission ([≤]10 on the Montgomery-[A]sberg Depression Rating Scale) immediately after SAINT. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events. DiscussionOur accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatment-resistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study. Trial registrationClinicalTrials.gov NCT03240692

clinical trials↗

bioRxiv2018

Dynamic Kinetochore Size Regulation Promotes Microtubule Capture And Chromosome Biorientation In Mitosis

Faithful chromosome segregation depends on the ability of sister kinetochores to attach to spindle microtubules. An outer layer of the kinetochore known as the fibrous corona transiently expands in early mitosis and disassembles upon microtubule capture. Neither the functional importance nor the mechanistic basis for this are known. Here we show that the dynein adaptor Spindly and the RZZ kinetochore complex drive fibrous corona formation in a dynein-independent manner. C-terminal farnesylation and MPS1 kinase activity cause conformational changes of Spindly that promote oligomerization of RZZ:Spindly complexes into a corona-like meshwork in cells and in vitro. Concurrent with corona expansion, Spindly potentiates corona shedding by recruiting dynein via three conserved short linear motifs. Expanded, non-sheddable fibrous coronas engage in extensive, long-lived lateral microtubule interactions that persist to metaphase and result in fused sister kinetochores, formation of merotelic attachments and chromosome segregation errors in anaphase. Thus, dynamic kinetochore size regulation in mitosis is coordinated by a single, Spindly-based mechanism that promotes initial microtubule capture and subsequent correct maturation of attachments.

cell biology↗