65 research outputs found
The ABCs of the Atypical Fam20 Secretory Pathway Kinases
The study of extracellular phosphorylation was initiated in late 19th century when the secreted milk protein, casein, and egg-yolk protein, phosvitin, were shown to be phosphorylated. However, it took more than a century to identify Fam20C, which phosphorylates both casein and phosvitin under physiological conditions. This kinase, along with its family members Fam20A and Fam20B, defined a new family with altered amino acid sequences highly atypical from the canonical 540 kinases comprising the kinome. Fam20B is a glycan kinase that phosphorylates xylose residues and triggers peptidoglycan biosynthesis, a role conserved from sponges to human. The protein kinase, Fam20C, conserved from nematodes to humans, phosphorylates well over 100 substrates in the secretory pathway with overall functions postulated to encompass endoplasmic reticulum homeostasis, nutrition, cardiac function, coagulation, and biomineralization. The preferred phosphorylation motif of Fam20C is SxE/pS, and structural studies revealed that related member Fam20A allosterically activates Fam20C by forming a heterodimeric/tetrameric complex. Fam20A, a pseudokinase, is observed only in vertebrates. Loss-of-function genetic alterations in the Fam20 family lead to human diseases such as amelogenesis imperfecta, nephrocalcinosis, lethal and nonlethal forms of Raine syndrome with major skeletal defects, and altered phosphate homeostasis. Together, these three members of the Fam20 family modulate a diverse network of secretory pathway components playing crucial roles in health and disease. The overarching theme of this review is to highlight the progress that has been made in the emerging field of extracellular phosphorylation and the key roles secretory pathway kinases play in an ever-expanding number of cellular processes
Single stage electrochemical exfoliation method for the production of few-layer graphene via intercalation of tetraalkylammonium cations
We present a non-oxidative production route to few layer graphene via the electrochemical intercalation of tetraalkylammonium cations into pristine graphite. Two forms of graphite have been studied as the source material with each yielding a slightly different result. Highly orientated pyrolytic graphite (HOPG) offers greater advantages in terms of the exfoliate size but the source electrode set up introduces difficulties to the procedure and requires the use of sonication. Using a graphite rod electrode, few layer graphene flakes (2 nm thickness) are formed directly although the flake diameters from this source are typically small (ca. 100–200 nm). Significantly, for a solvent based route, the graphite rod does not require ultrasonication or any secondary physical processing of the resulting dispersion. Flakes have been characterized using Raman spectroscopy, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS)
Mechanical Relaxation in Glasses and at the Glass Transition
The Gilroy-Phillips model of relaxational jumps in asymmetric double-well
potentials, developed for the Arrhenius-type secondary relaxations of the glass
phase, is extended to a formal description of the breakdown of the shear
modulus at the glass transition, the flow process.Comment: 13 pages, 11 figures, 49 ref
Energy landscape - a key concept for the dynamics of glasses and liquids
There is a growing belief that the mode coupling theory is the proper
microscopic theory for the dynamics of the undercooled liquid above a critical
temperature T_c. In addition, there is some evidence that the system leaves the
saddlepoints of the energy landscape to settle in the valleys at this critical
temperature. Finally, there is a microscopic theory for the entropy at the
calorimetric glass transition T_g by Mezard and Parisi, which allows to
calculate the Kauzmann temperature from the atomic pair potentials.
The dynamics of the frozen glass phase is at present limited to
phenomenological models. In the spirit of the energy landscape concept, one
considers an ensemble of independent asymmetric double-well potentials with a
wide distribution of barrier heights and asymmetries (ADWP or Gilroy-Phillips
model). The model gives an excellent description of the relaxation of glasses
up to about T_g/4. Above this temperature, the interaction between different
relaxation centers begins to play a role. One can show that the interaction
reduces the number of relaxation centers needed to bring the shear modulus down
to zero by a factor of three.Comment: Contribution to the III Workshop on Nonequilibrium Phenomena in
Supercooled Fluids, Glasses and Amorphous Materials, 22-27 September 2002,
Pisa; 14 pages, 3 figures; Version 3 takes criticque at Pisa into account;
final version 4 will be published in J.Phys.: Condens.Matte
Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.
The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP
Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses
To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely
Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials
An amendment to this paper has been published and can be accessed via the original article
A secretory pathway kinase regulates sarcoplasmic reticulum Ca2+ homeostasis and protects against heart failure.
Phosphorylation of serine96 of histidine-rich calcium-binding protein by the Fam20C kinase functions to prevent cardiac arrhythmia.
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