Ultrasound effect on a biorefinery lignin-cellulose mixture.

Forest biorefineries provide multiple new avenues for applied research. The main concept lies in the malleability of the processes and their stepwise organization. The core element of the biorefinery concept addressed in the present study is the pretreatment step; here, wood biomass is converted into free hemicellulosic sugars, lignin and cellulose.

Translational control of MPS1 links protein synthesis with the initiation of cell division and spindle pole body duplication in Saccharomyces cerevisiae.

Protein synthesis underpins cell growth and controls when cells commit to a new round of cell division at a point in late G1 of the cell cycle called Start. Passage through Start also coincides with the duplication of the microtubule-organizing centers, the yeast spindle pole bodies, which will form the 2 poles of the mitotic spindle that segregates the chromosomes in mitosis. The conserved Mps1p kinase governs the duplication of the spindle pole body (SPB) in Saccharomyces cerevisiae.

CDK signaling via nonconventional CDK phosphorylation sites.

Since the discovery of cyclin-dependent kinases (CDKs), it has been perceived as a dogma that CDK signaling in the cell cycle is mediated via targeting the CDK consensus sites: the optimal and the minimal motifs S/T-P-x-K/R and S/T-P, respectively. However, more recent evidence suggests that often the CDK phosphorylation events of regulatory importance are mediated via nonconventional CDK sites that lack the required +1Pro of the consensus site motif. In these cases, the loss of specificity seems to be compensated via distant docking interactions facilitated by 1) phosphorylated priming sites binding to phospho-adaptor Cks1 and/or 2) cyclin-specific docking interactions via Short Linear Motifs (SLiMs) in substrates.

Ultrasound enhanced solubilization of forest biorefinery hydrolysis lignin in mild alkaline conditions.

In the forest biorefinery, hydrolysis lignin (HL) is often dissolved with high concentration NaOH solution, followed by acid precipitation to obtain purified HL. For the first time, this study evaluates the effect of ultrasound (US) on the dissolution of industrially produced HL in aqueous NaOH solutions and the acid precipitation yield of HL. The solubility of HL in mild aqueous NaOH solutions was studied with and without US treatment at 20 kHz concerning the solid-to-liquid ratio, molecular weight of dissolved fractions and structural changes in dissolved HL.

The Shape of Learning Curves: A Review.

Learning curves provide insight into the dependence of a learner's generalization performance on the training set size. This important tool can be used for model selection, to predict the effect of more training data, and to reduce the computational complexity of model training and hyperparameter tuning. This review recounts the origins of the term, provides a formal definition of the learning curve, and briefly covers basics such as its estimation.

Improved Generalization in Semi-Supervised Learning: A Survey of Theoretical Results.

Semi-supervised learning is the learning setting in which we have both labeled and unlabeled data at our disposal. This survey covers theoretical results for this setting and maps out the benefits of unlabeled data in classification and regression tasks. Most methods that use unlabeled data rely on certain assumptions about the data distribution.

Cdc6 is sequentially regulated by PP2A-Cdc55, Cdc14, and Sic1 for origin licensing in .

Cdc6, a subunit of the pre-replicative complex (pre-RC), contains multiple regulatory cyclin-dependent kinase (Cdk1) consensus sites, SP or TP motifs. In , Cdk1 phosphorylates Cdc6-T7 to recruit Cks1, the Cdk1 phospho-adaptor in S phase, for subsequent multisite phosphorylation and protein degradation. Cdc6 accumulates in mitosis and is tightly bound by Clb2 through N-terminal phosphorylation in order to prevent premature origin licensing and degradation.

Predicting patient response with models trained on cell lines and patient-derived xenografts by nonlinear transfer learning.

Preclinical models have been the workhorse of cancer research, producing massive amounts of drug response data. Unfortunately, translating response biomarkers derived from these datasets to human tumors has proven to be particularly challenging. To address this challenge, we developed TRANSACT, a computational framework that builds a consensus space to capture biological processes common to preclinical models and human tumors and exploits this space to construct drug response predictors that robustly transfer from preclinical models to human tumors.

Multisite phosphorylation by Cdk1 initiates delayed negative feedback to control mitotic transcription.

Cell-cycle progression is driven by the phosphorylation of cyclin-dependent kinase (Cdk) substrates. The order of substrate phosphorylation depends in part on the general rise in Cdk activity during the cell cycle, together with variations in substrate docking to sites on associated cyclin and Cks subunits. Many substrates are modified at multiple sites to provide more complex regulation.

Long-term maintenance of functional primary human hepatocytes in 3D gelatin matrices produced by solution blow spinning.

Solution blow spinning (SBS) has recently emerged as a novel method that can produce nano- and microfiber structures suitable for tissue engineering. Gelatin is an excellent precursor for SBS as it is derived mainly from collagens that are abundant in natural extracellular matrices. Here we report, for the first time the successful generation of 3D thermally crosslinked preforms by using SBS from porcine gelatin.

Resolution Learning in Deep Convolutional Networks Using Scale-Space Theory.

Resolution in deep convolutional neural networks (CNNs) is typically bounded by the receptive field size through filter sizes, and subsampling layers or strided convolutions on feature maps. The optimal resolution may vary significantly depending on the dataset. Modern CNNs hard-code their resolution hyper-parameters in the network architecture which makes tuning such hyper-parameters cumbersome.

Docking to a Basic Helix Promotes Specific Phosphorylation by G1-Cdk1.

Cyclins are the activators of cyclin-dependent kinase (CDK) complex, but they also act as docking scaffolds for different short linear motifs (SLiMs) in CDK substrates and inhibitors. According to the unified model of CDK function, the cell cycle is coordinated by CDK both via general CDK activity thresholds and cyclin-specific substrate docking. Recently, it was found that the G1-cyclins of have a specific function in promoting polarization and growth of the buds, making the G1 cyclins essential for cell survival.

Cdc4 phospho-degrons allow differential regulation of Ame1 protein stability across the cell cycle.

Kinetochores are multi-subunit protein assemblies that link chromosomes to microtubules of the mitotic and meiotic spindle. It is still poorly understood how efficient, centromere-dependent kinetochore assembly is accomplished from hundreds of individual protein building blocks in a cell cycle-dependent manner. Here, by combining comprehensive phosphorylation analysis of native Ctf19 subunits with biochemical and functional assays in the model system budding yeast, we demonstrate that Cdk1 phosphorylation activates phospho-degrons on the essential subunit Ame1, which are recognized by the E3 ubiquitin ligase complex SCF-Cdc4.

SLiMs in intrinsically disordered protein regions regulate the cell cycle dynamics of ORC1-CDC6 interaction and pre-replicative complex assembly.

Hossain et al. (2021) show that human origin recognition complex subunit ORC1 and licensing factor CDC6 interact when the pre-replicative complex forms in G1. Short linear motifs (SLiMs) in intrinsically disordered regions (IDRs) mediate this interaction and its regulation by CDKs.

Regulation of trehalase activity by multi-site phosphorylation and 14-3-3 interaction.

Protein phosphorylation enables a rapid adjustment of cellular activities to diverse intracellular and environmental stimuli. Many phosphoproteins are targeted on more than one site, which allows the integration of multiple signals and the implementation of complex responses. However, the hierarchy and interplay between multiple phospho-sites are often unknown.

A new linear cyclin docking motif that mediates exclusively S-phase CDK-specific signaling.

Cyclin-dependent kinases (CDKs), the master regulators of cell division, are activated by different cyclins at different cell cycle stages. In addition to being activators of CDKs, cyclins recognize various linear motifs to target CDK activity to specific proteins. We uncovered a cyclin docking motif, NLxxxL, that contributes to phosphorylation-dependent degradation of the CDK inhibitor Far1 at the G1/S stage in the yeast Saccharomyces cerevisiae.

The sequence at Spike S1/S2 site enables cleavage by furin and phospho-regulation in SARS-CoV2 but not in SARS-CoV1 or MERS-CoV.

The Spike protein of the novel coronavirus SARS-CoV2 contains an insertion SPRRAR↓SV forming a cleavage motif RxxR for furin-like enzymes at the boundary of S1/S2 subunits. Cleavage at S1/S2 is important for efficient viral entry into target cells. The insertion is absent in other CoV-s of the same clade, including SARS-CoV1 that caused the 2003 outbreak.

Comprehensive Analysis of G1 Cyclin Docking Motif Sequences that Control CDK Regulatory Potency In Vivo.

Many protein-modifying enzymes recognize their substrates via docking motifs, but the range of functionally permissible motif sequences is often poorly defined. During eukaryotic cell division, cyclin-specific docking motifs help cyclin-dependent kinases (CDKs) phosphorylate different substrates at different stages, thus enforcing a temporally ordered series of events. In budding yeast, CDK substrates with Leu/Pro-rich (LP) docking motifs are recognized by Cln1/2 cyclins in late G1 phase, yet the key sequence features of these motifs were unknown.

Detection of Multisite Phosphorylation of Intrinsically Disordered Proteins Using Quantitative Mass-Spectrometry.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) within proteins have attracted considerable attention in recent years. Several important biological signaling mechanisms including protein-protein interactions and post-translational modifications can be easily mediated by IDPs and IDRs due to their flexible structure. These regions can encode linear sequences that are indispensable in cell-signaling networks and circuits.

Detection of Multisite Phosphorylation of Intrinsically Disordered Proteins Using Phos-tag SDS-PAGE.

Phos-tag SDS-PAGE is a method that enables electrophoretic separation of proteins based on their phosphorylation status. With Phos-tag SDS-PAGE, it is possible to discriminate between different phosphoforms of proteins based on their phosphorylation level and the number of phosphorylated sites, and to determine the stoichiometry of different phosphorylation products. Phos-tag SDS-PAGE is useful for analyzing disordered proteins with multiple phosphorylation sites and can be used for any of the downstream applications used in combination with conventional SDS-PAGE, for example, Western blotting and mass-spectrometry.

Proline-Rich Motifs Control G2-CDK Target Phosphorylation and Priming an Anchoring Protein for Polo Kinase Localization.

The hydrophobic patch (hp), a docking pocket on cyclins of CDKs (cyclin-dependent kinases), has been thought to accommodate a single short linear motif (SLiM), the "RxL or Cy" docking motif. Here we show that hp can bind different motifs with high specificity. We identify a PxxPxF motif that is necessary for G2-cyclin Clb3 function in S.

A processive phosphorylation circuit with multiple kinase inputs and mutually diversional routes controls G1/S decision.

Studies on multisite phosphorylation networks of cyclin-dependent kinase (CDK) targets have opened a new level of signaling complexity by revealing signal processing routes encoded into disordered proteins. A model target, the CDK inhibitor Sic1, contains linear phosphorylation motifs, docking sites, and phosphodegrons to empower an N-to-C terminally directed phosphorylation process. Here, we uncover a signal processing mechanism involving multi-step competition between mutually diversional phosphorylation routes within the S-CDK-Sic1 inhibitory complex.

A Review of Domain Adaptation without Target Labels.

Domain adaptation has become a prominent problem setting in machine learning and related fields. This review asks the question: How can a classifier learn from a source domain and generalize to a target domain? We present a categorization of approaches, divided into, what we refer to as, sample-based, feature-based, and inference-based methods. Sample-based methods focus on weighting individual observations during training based on their importance to the target domain.