Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers.

The human mitotic spindle is made of microtubules nucleated at centrosomes, at kinetochores, and from pre-existing microtubules by the augmin complex. However, it is unknown how the augmin-mediated nucleation affects distinct microtubule classes and thereby mitotic fidelity. Here, we use superresolution microscopy to analyze the previously indistinguishable microtubule arrangements within the crowded metaphase plate area and demonstrate that augmin is vital for the formation of uniformly arranged parallel units consisting of sister kinetochore fibers connected by a bridging fiber.

Meeting report - Mitotic spindle: from living and synthetic systems to theory.

Leading scientists from the field of mitotic spindle research gathered from 24-27 March 2019 to participate in the first 'Mitotic spindle: From living and synthetic systems to theory' conference. This meeting was held in Split, Croatia, organized by Nenad Pavin (Faculty of Science, University of Zagreb) and Iva Tolić (Ruđer Bošković Institute, Zagreb). Around 75 participants presented the latest advances in mitotic spindle research, ranging from live-cell imaging, reconstitution experiments and theoretical models of spindle assembly.

Maximum Entropy Production Theorem for Transitions between Enzyme Functional States and Its Applications.

Transitions between enzyme functional states are often connected to conformational changes involving electron or proton transport and directional movements of a group of atoms. These microscopic fluxes, resulting in entropy production, are driven by non-equilibrium concentrations of substrates and products. Maximal entropy production exists for any chosen transition, but such a maximal transitional entropy production (MTEP) requirement does not ensure an increase of total entropy production, nor an increase in catalytic performance.

Design of α-helical antimicrobial peptides with a high selectivity index.

: Low-molecular-weight antibiotics are gradually rendered ineffective by multidrug-resistant bacteria. Promising replacements are fast-acting antimicrobial peptides, either found as host defense peptides or designed, but their main weakness in applications is low selectivity for bacterial cells. : This paper explores how much human design has improved the evolutionary design for linear alpha-class antimicrobial peptides with a selective antibacterial activity.

Meiotic Spindle Has a Soft Spot.

The spindle relies on forces exerted by microtubules and motor proteins to align and segregate chromosomes. In this issue of Developmental Cell, Takagi et al. (2019) show that meiotic spindle microtubules respond differently to forces at different spindle locations, depending on microtubule organization and motor proteins that crosslink them.

The maximum entropy production requirement for proton transfers enhances catalytic efficiency for β-lactamases.

Movement of charges during enzyme catalytic cycle may be due to conformational changes, or to fast electron or proton transfer, or to both events. In each case, entropy production can be calculated using Terrel L. Hill's method, if relevant microscopic rate constants are known.

The mitotic spindle is chiral due to torques within microtubule bundles.

Mitosis relies on forces generated in the spindle, a micro-machine composed of microtubules and associated proteins. Forces are required for the congression of chromosomes to the metaphase plate and their separation in anaphase. However, besides forces, torques may exist in the spindle, yet they have not been investigated.

PGLa-H tandem-repeat peptides active against multidrug resistant clinical bacterial isolates.

Antimicrobial peptides (AMPs) are promising candidates for new antibiotic classes but often display an unacceptably high toxicity towards human cells. A naturally produced C-terminal fragment of PGLa, named PGLa-H, has been reported to have a very low haemolytic activity while maintaining a moderate antibacterial activity. A sequential tandem repeat of this fragment, diPGLa-H, was designed, as well as an analogue with a Val to Gly substitution at a key position.

Mitotic Spindle Assembly: Building the Bridge between Sister K-Fibers.

The mitotic spindle performs the task of physically dividing the genetic material between the newly formed daughter cells. To achieve this, bundles of microtubules and associated proteins orchestrate forces that spatially organize and then separate the chromosomes. In the classic view of the spindle, the kinetochore microtubules (k-fibers) are tensed and, thus, straight, whereas interpolar bundles are curved and do not interact with k-fibers close to the spindle equator.

Predicting the Minimal Inhibitory Concentration for Antimicrobial Peptides with Rana-Box Domain.

The global spreading of multidrug resistance has motivated the search for new antibiotic classes including different types of antimicrobial peptides (AMPs). Computational methods for predicting activity in terms of the minimal inhibitory concentration (MIC) of AMPs can facilitate "in silico" design and reduce the cost of synthesis and testing. We have used an original method for separating training and test data sets, both of which contain the sequences and measured MIC values of non-homologous anuran peptides having the Rana-box disulfide motif at their C-terminus.

Trichoplaxin - a new membrane-active antimicrobial peptide from placozoan cDNA.

A method based on the use of signal peptide sequences from antimicrobial peptide (AMP) precursors was used to mine a placozoa expressed sequence tag database and identified a potential antimicrobial peptide from Trichoplax adhaerens. This peptide, with predicted sequence FFGRLKSVWSAVKHGWKAAKSR is the first AMP from a placozoan species, and was named trichoplaxin. It was chemically synthesized and its structural properties, biological activities and membrane selectivity were investigated.

Evidence for distinct functions of MRE11 in Arabidopsis meiosis.

The evolutionary conserved Mre11/Rad50/Nbs1 complex functions as one of the guardians of genome integrity in eukaryotes; it is required for the double-strand break repair, meiosis, DNA checkpoint, and telomere maintenance. To better understand the role of the MRE11 gene in Arabidopsis, we performed comparative analysis of several mre11 alleles with respect to genome stability and meiosis. The mre11-4 and mre11-2 alleles presumably produce truncated MRE11 proteins composed of the first 499 and 529 amino acids, respectively.

Improving the selectivity of antimicrobial peptides from anuran skin.

Anuran skin is known to be a rich source of antimicrobial peptides although their therapeutic potential is often limited due to their toxicity against mammalian cells. The analysis of structure-activity relationships among anuran antimicrobial peptides provided the parameters to construct the "Mutator" tool for improving their selectivity for bacterial cells, by suggesting appropriate point substitutions. Double substitution analogues [K2, K16] of the Xenopus tropicalis peptide XT-7 and [I2, K19] of the Ascaphus truei peptide ascaphin-8 were predicted by this tool to have an increased 'therapeutic index' (TI = HC(50)/MIC for erythrocytes with respect to bacteria) > 80.

DADP: the database of anuran defense peptides.

Anuran tissues, and especially skin, are a rich source of bioactive peptides and their precursors. We here present a manually curated database of antimicrobial and other defense peptides with a total of 2571 entries, most of them in the precursor form with demarcated signal peptide (SP), acidic proregion(s) and bioactive moiety(s) corresponding to 1923 non-identical bioactive sequences. Search functions on the corresponding web server facilitate the extraction of six distinct SP classes.

Characterization of a membrane-bound angiotensin-converting enzyme isoform in crayfish testis and evidence for its release into the seminal fluid.

In the present study, an isoform of angiotensin-converting enzyme was characterized from the testis of a decapod crustacean, the crayfish Astacus leptodactylus. Angiotensin-converting enzyme cDNA, obtained by 3'- to 5' RACE of testis RNAs, codes for a predicted one-domain protein similar to the mammalian germinal isoform of angiotensin-converting enzyme. All amino acid residues involved in enzyme activity are highly conserved, and a potential C-terminus transmembrane anchor may be predicted from the sequence.

Evidence for an angiotensin-converting enzyme (ACE) polymorphism in the crayfish Astacus leptodactylus.

The present study was initiated to characterize angiotensin-converting enzyme (ACE) in Crustaceans. Using degenerate DNA primers deduced from consensus sequences located upward and downward from the active site of ACEs from different arthropod species, several tissues from the crayfish Astacus leptodactylus were screened by RT-PCR. Amplicons were obtained from hepatopancreas, testis and hemocytes.