Kinetic modeling of electron transfer reactions in photosystem I complexes of various structures with substituted quinone acceptors

The reduction kinetics of the photo-oxidized primary electron donor P₇₀₀ in photosystem I (PS I) complexes from cyanobacteria Synechocystis sp. PCC 6803 were analyzed within the kinetic model, which considers electron transfer (ET) reactions between P₇₀₀, secondary quinone acceptor A₁, iron-sulfur clusters and external electron donor and acceptors – methylviologen (MV), 2,3-dichloro-naphthoquinone (Cl₂NQ) and oxygen. PS I complexes containing various quinones in the A₁-binding site (phylloquinone PhQ, plastoquinone-9 PQ and Cl₂NQ) as well as F _X-core complexes, depleted of terminal iron–sulfur F _A/F _B clusters, were studied. The acceleration of charge recombination in F _X-core complexes by PhQ/PQ substitution indicates that backward ET from the iron–sulfur clusters involves quinone in the A₁-binding site. The kinetic parameters of ET reactions were obtained by global fitting of the P₇₀₀ ⁺ reduction with the kinetic model. The free energy gap ΔG ₀ between F _X and F _A/F _B clusters was estimated as ?130 meV. The driving force of ET from A₁ to F _X was determined as ?50 and ?220 meV for PhQ in the A and B cofactor branches, respectively. For PQ in A_1A-site, this reaction was found to be endergonic (ΔG ₀?=?+75 meV). The interaction of PS I with external acceptors was quantitatively described in terms of Michaelis–Menten kinetics. The second-order rate constants of ET from F _A/F _B, F _X and Cl₂NQ in the A₁-site of PS I to external acceptors were estimated. The side production of superoxide radical in the A₁-site by oxygen reduction via the Mehler reaction might comprise ≥0.3% of the total electron flow in PS I.     

Infant sitting postural control appears robust across changes in surface context

Aim of the study: Independent sitting requires the control of the involved body segments over the base of support using information obtained from the three sensory systems (visual, vestibular, and somatosensory). The contribution of somatosensory information in infant sitting has not been explored. To address this gap, we altered the context of the sitting support surface and examined the infants’ immediate postural responses.

Materials and methods: Ten 7-month-old typically developing infants sat on compliant and firm surfaces in one session. Spatial, frequency, and temporal measures of postural control were obtained using center of pressure data.

Results Our results suggest that infants’ postural sway is not immediately affected by the different types of foam surface while sitting.

Conclusions: It seems that mature sitter infants are able to adapt to different environmental constraints by disregarding the distorted somatosensory information from the support surface and relying more on their remaining senses (visual and vestibular) to control their sitting posture.     

Microbial cyclophilins: specialized functions in virulence and beyond

Cyclophilins belong to the superfamily of peptidyl-prolyl cis/trans isomerases (PPIases, EC: 5.2.1.8), the enzymes that catalyze the cis/trans isomerization of peptidyl-prolyl peptide bonds in unfolded and partially folded polypeptide chains and native state proteins. Cyclophilins have been extensively studied, since they are involved in multiple cellular processes related to human pathologies, such as neurodegenerative disorders, infectious diseases, and cancer. However, the presence of cyclophilins in all domains of life indicates a broader biological importance. In this mini-review, we summarize current advances in the study of microbial cyclophilins. Apart from their anticipated role in protein folding and chaperoning, cyclophilins are involved in several other biological processes, such as cellular signal transduction, adaptation to stress, control of pathogens virulence, and modulation of host immune response. Since many existing family members do not have well-defined functions and novel ones are being characterized, the requirement for further studies on their biological role and molecular mechanism of action is apparent.     

Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures

Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions across diverse cancer types. These patterns are suggestive of conserved selection pressures during tumor evolution but cannot be fully explained by known oncogenes and tumor suppressor genes. Using a pan‐cancer analysis of CNA data from patient tumors and experimental systems, here we show that principal component analysis‐defined CNA signatures are predictive of glycolytic phenotypes, including ¹⁸F‐fluorodeoxy‐glucose (FDG) avidity of patient tumors, and increased proliferation. The primary CNA signature is enriched for p53 mutations and is associated with glycolysis through coordinate amplification of glycolytic genes and other cancer‐linked metabolic enzymes. A pan‐cancer and cross‐species comparison of CNAs highlighted 26 consistently altered DNA regions, containing 11 enzymes in the glycolysis pathway in addition to known cancer‐driving genes. Furthermore, exogenous expression of hexokinase and enolase enzymes in an experimental immortalization system altered the subsequent copy number status of the corresponding endogenous loci, supporting the hypothesis that these metabolic genes act as drivers within the conserved CNA amplification regions. Taken together, these results demonstrate that metabolic stress acts as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution.     

Identifying Morphological and Mechanical Traits Associated with Stem Lodging in Bioenergy Sorghum (<Emphasis Type="Italic">Sorghum bicolor</Emphasis>)

Stem lodging in Sorghum is a major agronomic problem that has far-reaching economic consequences. More rapid and reliable advances in stem lodging resistance could be achieved through development of selective breeding tools that are not dependent on post hoc data or dependent on abiotic or biotic environmental factors. Our objective was to use sorghum to examine how mechanical stability is achieved and lost, and to provide insights into the development of a rapid and reliable phenotyping approach. The biomechanical properties of the stems of six bioenergy sorghum genotypes were investigated using a three-point bending test protocol. Important morphometric data were also collected, and previously collected lodging scores were used to associate with morphological and mechanical traits. Nodes were two to three-folds stronger, stiffer, and more rigid than internodes. In general, internodes were numerically weakest and more rigid between internodes 3 and 6, corresponding to the area where higher stem lodging is observed. Internode strength was negatively correlated with diameter (r = ?0.77, P < 0.05) and volume (r = 0.96, P < 0.01), while stem lodging was positively correlated with flexural rigidity (r = 0.85, P < 0.05) and volume (r = 0.78, P < 0.05). The analysis revealed key functional traits that influence the mode and location of stem lodging. Moreover, these results indicate the potential of these methods as a selective breeding tool for indirect selection of stem lodging resistance in bioenergy sorghum.     

Detection of IgG and IgM to meningococcal outer membrane proteins in relation to carriage of Neisseria meningitidis or Neisseria lactamica

Carriage of non-serogroupable Neisseria meningitidis or Neisseria lactamica induces antibodies protective against meningococcal disease. Antibodies directed against outer membrane proteins are bactericidal and the serotype and subtype outer membrane protein antigens are being examined for their value as vaccine candidates for serogroup B disease. The aim of this study was to examine the effect of carriage of these two Neisseria species among children and young adults on induction of antibodies to outer membrane components from strains causing disease in Greece. Among 53 patients with meningococcal disease, IgG or IgM antibodies were detected by ELISA in 9 of 13 (69%) from whom the bacteria were isolated and 27 of 40 (67%) who were culture-negative. For military recruits (n = 604), the proportion of carriers of meningococci with IgM or IgG to outer membrane proteins was higher than non-carriers, P < 0.05 and P = 0.000000, respectively. Among school children (n = 319), the proportion with IgM or IgG to outer membrane proteins for carriers of meningococci was higher compared with non-carriers, P = 0.000000 and P = 0000043, respectively. Carriage of N. lactamica was not associated with the presence of either IgM or IgG to the outer membrane proteins in the children. The higher proportion of children (50%) with IgM to outer membrane proteins compared with recruits (10%) might reflect more recent exposure and primary immune responses to the bacteria. The lack of association between antibodies to outer membrane proteins and carriage of N. lactamica could reflect observations that the majority of N. lactamica isolates from Greece and other countries do not react with monoclonal typing reagents. Bactericidal antibodies to meningococci associated with high levels of IgG to N. lactamica were found in a previous study; these are thought to be directed to antigens other than outer membrane proteins or capsules and imply antigens such as lipo-oligosaccharide are involved in induction of antibodies cross-reactive with meningococci.     

Synthesis of (E)-9-(1-pyrenyl)-4-hydroxynon-2-enal, a fluorescent probe of the (E)-4-hydroxynon-2-enal with retained biological properties

(E)-9-(1-pyrenyl)-4-hydroxynon-2-enal (FHNE), a fluorescent probe of (E)-4-hydroxynon-2-enal (HNE) is synthesised in seven steps and in 35% overall yield, starting from commercially available 1-pyrencarboxyaldehyde. When incubated with cultured HeLa cells this fluorescent probe penetrates cells and particularly concentrates in the region surrounding the nucleus. As the parent compound, HNE it is able to induce the activation of heat shock factor (HSF) and it is able to induce the binding of HSF to heat shock element (HSE).     

CRISPR–Cas9 gRNA efficiency prediction: an overview of predictive tools and the role of deep learning

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has become a successful and promising technology for gene-editing. To facilitate its effective application, various computational tools have been developed. These tools can assist researchers in the guide RNA (gRNA) design process by predicting cleavage efficiency and specificity and excluding undesirable targets. However, while many tools are available, assessment of their application scenarios and performance benchmarks are limited. Moreover, new deep learning tools have been explored lately for gRNA efficiency prediction, but have not been systematically evaluated. Here, we discuss the approaches that pertain to the on-target activity problem, focusing mainly on the features and computational methods they utilize. Furthermore, we evaluate these tools on independent datasets and give some suggestions for their usage. We conclude with some challenges and perspectives about future directions for CRISPR–Cas9 guide design.     

Acute and long-term effects of two different static stretching training protocols on range of motion and vertical jump in preadolescent athletes

This study examined the acute and long-term effects of two static stretching protocols of equal duration, performed either as a single stretch or multiple shorter duration repetitions on hip hyperextension range of motion (ROM) and single leg countermovement jump height (CMJ). Thirty female gymnasts were randomly assigned to stretching (SG) or control groups (CG). The SG performed two different protocols of static stretching, three times per week for 9 weeks. One leg performed repeated stretching (3 × 30 s with 30 s rest) while the other leg performed a single stretch (90 s). The CG continued regular training. ROM and CMJ were measured pre- and 2 min post-stretching on weeks 0, 3, 6, 9, and 3 weeks into detraining. CMJ height increased over time irrespective of group (main effect time, p = 0.001), with no statistical difference between groups (main effect group, p = 0.272). Three-way ANOVA showed that, CMJ height after stretching was not affected by either stretching protocol at any time point (p = 0.503 to 0.996). Both stretching protocols equally increased ROM on weeks 6 (10.9 ± 13.4%, p < 0.001, d = 0.42), and 9 (21.5 ± 13.4%, p < 0.001, d = 0.78), and this increase was maintained during detraining (17.0 ± 15.0%, p < 0.001, d = 0.68). No increase in ROM was observed in the CG (p > 0.874). Static stretching of long duration applied either as single or multiple bouts of equal duration, results in similar acute and long-term improvements in ROM. Furthermore, both stretching protocols do not acutely affect subsequent CMJ performance, and this effect is not influenced by the large increase in ROM and CMJ overtime.