Collective nuclear behavior shapes bilateral nuclear symmetry for subsequent left-right asymmetric morphogenesis in Drosophila.

Proper organ development often requires nuclei to move to a specific position within the cell. To determine how nuclear positioning affects left-right (LR) development in the Drosophila anterior midgut (AMG), we developed a surface-modeling method to measure and describe nuclear behavior at stages 13-14, captured in three-dimensional time-lapse movies. We describe the distinctive positioning and a novel collective nuclear behavior by which nuclei align LR symmetrically along the anterior-posterior axis in the visceral muscles that overlie the midgut and are responsible for the LR-asymmetric development of this organ. Wnt4 signaling is crucial for the collective behavior and proper positioning of the nuclei, as are myosin II and the LINC complex, without which the nuclei fail to align LR symmetrically. The LR-symmetric positioning of the nuclei is important for the subsequent LR-asymmetric development of the AMG. We propose that the bilaterally symmetrical positioning of these nuclei may be mechanically coupled with subsequent LR-asymmetric morphogenesis.

Temporomandibular Joint Space in Mandibular Prognathism.

This study compared the temporomandibular joint (TMJ) space between patients with normal and prognathic mandibles. The study included a total of 68 Korean individuals, and the TMJ space was measured using computed tomography. Patients with normal SNB values (normal mandible) were classified into Group 1. Patients with high SNB values (prognathic mandibles) were categorized into Group 2. The TMJ space was defined as the distance between the condylar process and the mandibular fossa, and it was significantly different between Groups 1 and 2 (1.94±0.07 mm versus 1.50±0.05 mm, P< 0.01). This study confirmed that the TMJ space in patients with prognathic mandibles is narrower than that in patients with normal mandibles.

Structure-Guided Engineering of Thermodynamically Enhanced SaCas9 for Improved Gene Suppression.

Proteins with multiple domains play pivotal roles in various biological processes, necessitating a thorough understanding of their structural stability and functional interplay. Here, a structure-guided protein engineering approach is proposed to develop thermostable Cas9 (CRISPR-associated protein 9) variant for CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) interference applications. By employing thermodynamic analysis, combining distance mapping and molecular dynamics simulations, deletable domains are identified to enhance stability while preserving the DNA recognition function of Cas9. The resulting engineered Cas9, termed small and dead form Cas9, exhibits improved thermostability and maintains target DNA recognition function. Cryo-electron microscopy analysis reveals structural integrity with reduced atomic density in the deleted domain. Fusion with functional elements enables intracellular delivery and nuclear localization, demonstrating efficient gene suppression in diverse cell types. Direct delivery in the mouse brain shows enhanced knockdown efficiency, highlighting the potential of structure-guided engineering to develop functional CRISPR systems tailored for specific applications. This study underscores the significance of integrating computational and experimental approaches for protein engineering, offering insights into designing tailored molecular tools for precise biological interventions.

Proper direction of male genitalia is prerequisite for copulation in Drosophila, implying cooperative evolution between genitalia rotation and mating behavior.

Animal morphology and behavior often appear to evolve cooperatively. However, it is difficult to assess how strictly these two traits depend on each other. The genitalia morphologies and courtship behaviors in insects, which vary widely, may be a good model for addressing this issue. In Diptera, phylogenetic analyses of mating positions suggested that the male-above position evolved from an end-to-end one. However, with this change in mating position, the dorsoventral direction of the male genitalia became upside down with respect to that of the female genitalia. It was proposed that to compensate for this incompatibility, the male genitalia rotated an additional 180° during evolution, implying evolutionary cooperativity between the mating position and genitalia direction. According to this scenario, the proper direction of male genitalia is critical for successful mating. Here, we tested this hypothesis using a Drosophila Myosin31DF (Myo31DF) mutant, in which the rotation of the male genitalia terminates prematurely, resulting in various deviations in genitalia direction. We found that the proper dorsoventral direction of the male genitalia was a prerequisite for successful copulation, but it did not affect the other courtship behaviors. Therefore, our results suggested that the male genitalia rotation and mating position evolved cooperatively in Drosophila.

Effects of an easy neuroanatomy book with schematics on student learning / Efectos de un libro sencillo de neuroanatomía con esquemas sobre el aprendizaje de los estudiantes

SUMMARY: Numerous students perceive neuroanatomy as a particularly difficult subject due to its overwhelming complexity. Therefore, a neuroanatomy book that concentrates on easy-to-read stories with schematics rather than exhaustive details has been published. This study evaluates the effect of a trial of the new neuroanatomy book on student learning. From the book, a printout on the brainstem and cranial nerve was extracted. Medical students read the printout, and subsequently were examined on their knowledge of and interest in neuroanatomy. Students who read the extract answered examination questions relatively well and were more interested in neuroanatomy. The printout seemed to enhance the knowledge and concentration of the students. After grasping the fundamental information in the book, students are expected to be able to learn advanced concepts comfortably and confidently. In addition, the book with its concise and simple content is suitable not only for short- duration neuroanatomy courses but also for self-learning.

Muchos estudiantes perciben la neuroanatomía como un tema particularmente difícil debido a su abrumadora complejidad. Por lo tanto, se ha publicado un libro de neuroanatomía que se concentra en historias fáciles de leer con esquemas en lugar de detalles exhaustivos. Este estudio evalúa el efecto de una prueba del nuevo libro de neuroanatomía en el aprendizaje de los estudiantes. Del libro, se extrajo una impresión sobre el tronco encefálico y los nervios craneales. Los estudiantes de medicina leyeron la copia impresa y, posteriormente, se les examinó su conocimiento e interés por la neuroanatomía. Los estudiantes que leyeron el extracto respondieron relativamente bien a las preguntas del examen y estaban más interesados en la neuroanatomía. La impresión parecía mejorar el conocimiento y la concentración de los estudiantes. Después de comprender la información fundamental del libro, se espera que los estudiantes puedan aprender conceptos avanzados con comodidad y confianza. Además, el libro con su contenido conciso y simple es adecuado no solo para cursos de neuroanatomía de corta duración, sino también, para el autoaprendizaje.

Inhibition of infection of the rice blast fungus by halisulfate 1, an isocitrate lyase inhibitor.

Halisulfate 1, a sesterterpene sulfate and an isocitrate lyase (ICL) inhibitor that is isolated from tropical sponge Hippospongia spp., reduces both appressorium formation and infection of rice plants by the fungus Magnaporthe grisea. Rice plants infected with wild-type M. grisea Guy 11 exhibited significantly lower disease severity after halisulfate 1 treatment than without, and the treatment effect was comparable to the behavior of the Delta icl knockout mutant I-10. The protection observed upon applying halisulfate 1 to rice plants suggests that the ICL inhibitor may be a promising candidate for crop protection, particularly to protect rice plants against M. grisea.

Inhibition of the pathogenicity of Magnaporthe grisea by bromophenols, isocitrate lyase inhibitors, from the red alga Odonthalia corymbifera.

Magnaporthe grisea is a fungal pathogen of rice that forms appressoria that penetrate the outer cuticle of the rice plant. Data from recent studies indicate that M. grisea isocitrate lyase (ICL), a key enzyme in the glyoxylate cycle, is highly expressed during appressorium-mediated plant infection. Bromophenols isolated from the red alga Odonthalia corymbifera exhibited potent ICL inhibitory activity and blocked appressoria formation by M. grisea in a concentration-dependent manner. In addition, these compounds protected the rice plants from infection by M. grisea. Rice plants infected with wild-type M. grisea Guy 11 exhibited significantly lower disease severity with bromophenol treatment than without, and the treatment effect was comparable to the behavior of the Deltaicl knockout mutant I-10. The protective effect of bromophenols and their strong inhibition of appressorium formation on rice plants suggest that ICL inhibitors may be promising candidates for crop protection, particularly to protect rice plants against M. grisea.

Synthesis and evaluation of hydroquinone derivatives as inhibitors of isocitrate lyase.

Isocitrate lyase (ICL) is envisaged as an attractive drug target for the development of antimicrobial agents. We have prepared a series of hydroquinone derivatives on the basis of the structure of halisulfates, a naturally occurring inhibitor of ICL. The obtained derivatives were evaluated against ICL of C. albicans. The preliminary structure-activity relationships and the minimal structural requirements for potency were established through structural modifications.

Antibacterial compounds from the leaves of Acanthopanax senticosus.

Chiisanogenin (1), hyperin (2) and chiisanoside (3) were isolated from the leaves of Acanthopanax senticosus, and were tested for their inhibitory activities against 6 strains of bacteria. Among them, chiisanogenin (1) revealed broad but moderate antibacterial activities against G (+) and G (-) bacteria, the minimum inhibitory concentration (MIC) being in the range of 50-100 microg/ml.

Antibacterial coumarins from Angelica gigas roots.

Systematic fractionation of Angelica gigas roots led to the isolation of linear furano(pyrano)coumarins such as bergapten (1), decursinol angelate (2), decursin (3), nodakenetin (4) and nodakenin (5). The antibacterial activities of those compounds against pathogenic bacteria were investigated. Among the compounds tested, decursinol angelate (2) and decursin (3) exhibited significant antibacterial activity against Bacillus subtilis with the minimum inhibitory concentrations (MICs) of 50 and 12.5 microg/mL, respectively.

Inhibition of sortase-mediated Staphylococcus aureus adhesion to fibronectin via fibronectin-binding protein by sortase inhibitors.

The sortase enzymes are a family of Gram-positive transpeptidases responsible for anchoring surface protein virulence factors to the peptidoglycan cell wall layer. In Staphylococcus aureus, deletion of the sortase isoforms results in marked reduction in virulence and infection potential, making it an important antivirulence target. Recombinant sortase A (SrtA) and sortase B (SrtB) were incubated with peptide substrate containing either the LPETG or NPQTN motifs. (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile, beta-sitosterol-3-O-glucopyranoside, berberine chloride, and psammaplin A1 showed potent inhibitory activity against SrtA and SrtB. These compounds also exhibited potent inhibitory activity against S. aureus cell adhesion to fibronectin. The fibronectin-binding activity data highlight the potential of these compounds for the treatment of S. aureus infections via inhibition of sortase activity.

Periconicins, two new fusicoccane diterpenes produced by an endophytic fungus Periconia sp. with antibacterial activity.

Two new fusicoccane diterpenes, named periconicins A (1) and B (2), with antibacterial activities have been isolated by bioassay-guided fractionation from an endophytic fungus Periconia sp., collected from small branches of Taxus cuspidata. The structures of the new compounds were determined by combined spectroscopic methods.

Inhibition of the bacterial surface protein anchoring transpeptidase sortase by isoquinoline alkaloids.

The inhibitory activity of Coptis chinensis rhizome-derived material was evaluated against sortase, a bacterial surface protein anchoring transpeptidase, from Staphylococcus aureus ATCC 6538p and compared to that of four commercially available isoquinoline alkaloids. The biologically active constituent of C. chinensis extract was characterized as the isoquinoline alkaloid, berberine chloride, by spectral analysis. The isolate was a potent inhibitor of sortase, with an IC50 value of 8.7 microg/ml and had antibacterial activity against Gram-positive bacteria with a minimum inhibitory concentration (MIC) in the range of 50-400 microg/ml. Among the four isoquinoline alkaloids tested, berberine chloride had strong inhibitory activity. These results indicate that berberine is a possible candidate for the development of a bacterial sortase inhibitor.

Inhibition of sortase, a bacterial surface protein anchoring transpeptidase, by beta-sitosterol-3-O-glucopyranoside from Fritillaria verticillata.

A glucosylsterol, beta-sitosterol-3-O-glucopyranoside, has been isolated as an active principle with sortase inhibitory effect from the bulbs of Fritillaria verticillata by bioassay-guided chromatographic fractionation. The isolate was a potent inhibitor of sortase, with an IC(50) value of 18.3 microg/ml and had antibacterial activity against Bacillus subtilis, Staphylococcus aureus, and Micrococcus leuteus with MIC values of 50, 200, and 400 microg/ml, respectively, indicating that this compound is a possible candidate for the development of a bacterial sortase inhibitor. In addition, sitosterol was found to be inactive upon sortase and bacterial cell growth. These results suggest that the inhibitory potency of beta-sitosterol-3-O-glucopyranoside is sensitively dependent upon the glucopyranoside side chain moiety.