Beyond homogeneity: Assessing the validity of the Michaelis-Menten rate law in spatially heterogeneous environments.

The Michaelis-Menten (MM) rate law has been a fundamental tool in describing enzyme-catalyzed reactions for over a century. When substrates and enzymes are homogeneously distributed, the validity of the MM rate law can be easily assessed based on relative concentrations: the substrate is in large excess over the enzyme-substrate complex. However, the applicability of this conventional criterion remains unclear when species exhibit spatial heterogeneity, a prevailing scenario in biological systems. Here, we explore the MM rate law's applicability under spatial heterogeneity by using partial differential equations. In this study, molecules diffuse very slowly, allowing them to locally reach quasi-steady states. We find that the conventional criterion for the validity of the MM rate law cannot be readily extended to heterogeneous environments solely through spatial averages of molecular concentrations. That is, even when the conventional criterion for the spatial averages is satisfied, the MM rate law fails to capture the enzyme catalytic rate under spatial heterogeneity. In contrast, a slightly modified form of the MM rate law, based on the total quasi-steady state approximation (tQSSA), is accurate. Specifically, the tQSSA-based modified form, but not the original MM rate law, accurately predicts the drug clearance via cytochrome P450 enzymes and the ultrasensitive phosphorylation in heterogeneous environments. Our findings shed light on how to simplify spatiotemporal models for enzyme-catalyzed reactions in the right context, ensuring accurate conclusions and avoiding misinterpretations in in silico simulations.

Beyond microtubules: The cellular environment at the endoplasmic reticulum attracts proteins to the nucleus, enabling nuclear transport.

All proteins are translated in the cytoplasm, yet many, including transcription factors, play vital roles in the nucleus. While previous research has concentrated on molecular motors for the transport of these proteins to the nucleus, recent observations reveal perinuclear accumulation even in the absence of an energy source, hinting at alternative mechanisms. Here, we propose that structural properties of the cellular environment, specifically the endoplasmic reticulum (ER), can promote molecular transport to the perinucleus without requiring additional energy expenditure. Specifically, physical interaction between proteins and the ER impedes their diffusion and leads to their accumulation near the nucleus. This result explains why larger proteins, more frequently interacting with the ER membrane, tend to accumulate at the perinucleus. Interestingly, such diffusion in a heterogeneous environment follows Chapman's law rather than the popular Fick's law. Our findings suggest a novel protein transport mechanism arising solely from characteristics of the intracellular environment.

Korean species of Hydrosmecta Thomson (Coleoptera: Staphylinidae: Aleocharinae) with descriptions of two new species.

A taxonomic study of the genus Hydrosmecta Thomson in Korea is presented. The genus is represented in Korea by three species including two new species, H. beolgokensis Lee & Ahn, sp. nov. and H. koreana Lee & Ahn, sp. nov. A key to Korean species, descriptions, and illustrations of habitus photographs and diagnostic characters are provided to facilitate identification.

Curvature-based interface restoration algorithm using phase-field equations.

In this study, we propose a restoration algorithm for distorted objects using a curvature-driven flow. First, we capture the convex-hull shaped contour of the distorted object using the mean curvature flow. With the supplemented mass on the captured feature, we evolve the constraint mean curvature flow to a steady state, preserving the non-distorted region. With respect to the mass, we select a restorative shape by considering the square of the curvature derivative. The Allen-Cahn and Cahn-Hilliard equations are applied to the generated restored image from the implicit curvature motions represented by the order parameter. We impose the Dirichlet boundary condition for the order parameter and the Neumann boundary for the chemical potential to fix the feature and to inherit the mass conservation, respectively. We provided examples of the restoration of half-circle and parentheses-shaped objects to reconstruct a circle shape.

Crossing fibers may underlie the dynamic pulling forces of muscles that attach to cartilage at the tip of the nose.

The present study used microdissection, histology, and microcomputed tomography (micro-CT) with the aims of determining the prevalence and patterns of the depressor septi nasi (DSN) and orbicularis oris (OOr) muscles attached to the footplate of the medial crus (fMC) of the major alar cartilage, focusing on their crossing fibers. The DSN and OOr attached to the fMC of the major alar cartilage were investigated in 76 samples from 38 embalmed Korean adult cadavers (20 males, 18 females; mean age 70 years). The DSN, OOr, or both were attached to the fMC. When the DSN ran unilaterally or was absent, some OOr fibers ascended to attach to the fMC instead of the DSN in 20.6% of the samples. Crossing fibers of the DSN or OOr attached to the fMC were found in 82.4% of the samples. Bilateral and unilateral crossing fibers were found in 32.4% and 50.0%, respectively, and no crossing fibers were found in 17.6%. The DSN and OOr that attached to the fMC could be categorized into six types according to presence of the DSN and the crossing patterns of the DSN and OOr. Anatomical findings of the DSN and OOr that attached to the fMC were confirmed in histology and micro-CT images. These findings offer insights on anatomical mechanisms that may underlie the dynamic pulling forces generated by muscles that attach to the fMCs and on evolutionary variation observed in human facial expressions. They can also provide useful information for guiding rhinoplasty of the nasal tip.

Five new species of Bryaxis Kugelann (Coleoptera, Staphylinidae, Pselaphinae) from Korea and a nomenclatural note on Bryaxismahunkai Löbl.

The genus Bryaxis Kugelann (Goniaceritae: Bythinini) is the most species-rich genus of the subfamily Pselaphinae and is mainly distributed in the Palearctic region. Although previous studies have documented 14 species in the Korean Peninsula, the true diversity, ecology, and immature stages of the genus are still inadequately known. In this study, five new Korean species are described: B.grandinodussp. nov., B.uljinensissp. nov., B.fabaiformissp. nov., B.girinensissp. nov., and B.nemorosussp. nov. Illustrations of the habitus and other morphological details, and a distribution map are provided. In addition, Bryaxisleechanyoungi Nomura & Lee, 1993 is proposed as a new synonym of B.mahunkai Löbl, 1975 based on the original description and illustrations of diagnostic characters.

Spatially coordinated collective phosphorylation filters spatiotemporal noises for precise circadian timekeeping.

The circadian (∼24h) clock is based on a negative-feedback loop centered around the PERIOD protein (PER), translated in the cytoplasm and then enters the nucleus to repress its own transcription at the right time of day. Such precise nucleus entry is mysterious because thousands of PER molecules transit through crowded cytoplasm and arrive at the perinucleus across several hours. To understand this, we developed a mathematical model describing the complex spatiotemporal dynamics of PER as a single random time delay. We find that the spatially coordinated bistable phosphoswitch of PER, which triggers the phosphorylation of accumulated PER at the perinucleus, leads to the synchronous and precise nuclear entry of PER. This leads to robust circadian rhythms even when PER arrival times are heterogeneous and perturbed due to changes in cell crowdedness, cell size, and transcriptional activator levels. This shows how the circadian clock compensates for spatiotemporal noise.

Korean species of the genus Amischa Thomson (Coleoptera: Staphylinidae: Aleocharinae), with a description of new species.

A taxonomic study of the genus Amischa Thomson of Korea is presented. The genus is represented in Korea by three species, including A. koreana Lee & Ahn, sp. nov. Amischa analis (Gravenhorst) is reported for the first time in the Korean peninsula. A key to Korean species, descriptions, habitus photographs, and illustrations of the diagnostic characters are provided.

Korean species of the Atheta Thomson subgenus Dimetrota Mulsant amp; Rey (Coleoptera: Staphylinidae: Aleocharinae) with a description of new species.

A taxonomic review of the Atheta Thomson subgenus Dimetrota Mulsant Rey in the Korean Peninsula is presented. The subgenus is represented in Korea by 11 species including a new species, A. (D.) ovata Lee Ahn, sp. nov. and a new synonym [A. (Badura) tokiokai Sawada = A. (D.) chagangensis Panik syn. nov.]. Atheta (D.) yamamotoi Sawada is reported for the first time in the Korean Peninsula and A. (D.) machonryongica in South Korea. A key to Korean species and descriptions with illustrations of habitus photographs and diagnostic characters of three species new to Korea are provided.

Hymenocallis littoralis ameliorates inflammatory responses in LPS-stimulated RAW264.7 cells and HCl/EtOH-induced gastric mucosal injury via targeting the MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenocallis littoralis (Jacq.) Salisb. Also known as Pancratium littorale Jacq. And Hymenocallis panamensis Lindl., is a medicinal plant from the family Amarylideceae used for emetic and wound healing and has manifested anti-neoplastic, anti-oxidant, and anti-viral properties. AIM OF THE STUDY: The aim of this paper is to investigate the anti-inflammatory potential and molecular mechanism of H. littoralis against lipopolysaccharide (LPS)-induced macrophages and in vivo HCl/EtOH-induced gastritis mucosal injury models. MATERIALS AND METHODS: The production of pro-inflammatory cytokines and mediators was evaluated by Griess assay, RT-PCR, and real-time PCR. Moreover, the relevant proteins of mitogen-activated protein kinases (MAPKs) including ERK, JNK, p38, c-Jun, and c-Fos were detected using immunoblotting. RESULTS: We demonstrated that H. littoralis prominently dampened production of nitric oxide (NO) in LPS-, poly I:C-, or pam3CSK-stimulated RAW264.7 cells; down-regulated the expression levels of interleukin 6 (IL-6) and inducible nitric oxide synthase; and markedly attenuated the luciferase activities of AP-1 reporter promoters. Moreover, H. littoralis administration prominently downregulated c-Fos and c-Jun phosphorylation as well as JNK1, ERK2, and MKK7 overexpression in HEK 293T cells. Furthermore, H. littoralis displayed anti-inflammatory effects in the HCl/EtOH-induced gastritis mice model. CONCLUSIONS: Cumulatively, these results demonstrated that H. littoralis exerts eminently anti-inflammatory activities in LPS-stimulated RAW264.7 cells in vitro and in HCl/EtOH-induced gastritis mice models in vivo. These activities could be attributed to its modulatory effects on the MAPK signaling pathway.

Review of the Korean Species of the Genus Edaphus Motschulsky (Coleoptera, Staphylinidae) with Description of Four New Species.

The cosmopolitan euaesthetine genus, Edaphus Motschulsky, 1857, with about 90 Palaearctic species, was formerly known by a single species, E. koreanus Puthz, 2011, of which 2 specimens were collected in the southern part of the Korean Peninsula. In this paper, the knowledge of the Korean Edaphus fauna is expanded to include six species, including four described here based on a rich material collected in recent years. A key to all six species of Korean Edaphus, illustration of the habitus and diagnostic characters, and a distribution map are provided.

Anatomical connections among the depressor supercilii, levator labii superioris alaeque nasi, and inferior fibers of orbicularis oculi: Implications for variation in human facial expressions.

The aim of this study was to determine how the depressor supercilii (DS) connects to the levator labii superioris alaeque nasi (LLSAN) and inferior fibers of the orbicularis oculi (OOc INF) in the human midface. While grimacing, contraction of the DS with fibers connecting to the LLSAN and OOc INF can assist in pulling the medial eyebrow downward more than when these connecting fibers are not present. Contraction of these distinct connecting fibers between the DS and the LLSAN can also slightly elevate the nasal ala and upper lip. The DS was examined in 44 specimens of embalmed adult Korean cadavers. We found that the DS connected to the LLSAN or the OOc INF by muscle fibers or thin aponeuroses in 33 (75.0%) of the 44 specimens. The DS was connected to both the LLSAN and OOc INF by muscle fibers or aponeuroses and had no connection to either in 5 (11.4%) and 11 (25.0%) specimens, respectively. The DS was connected to the LLSAN by the muscle fibers and thin aponeuroses in 6 (13.6%) and 4 (9.1%) specimens, respectively. The DS was connected to the OOc INF by the muscle fibers and thin aponeuroses in 5 (11.4%) and 23 (52.3%) specimens, respectively. Our findings regarding the anatomical connections of the glabellar region DS to the midface LLSAN and OOc INF provide insights on the dynamic balance between the brow depressors such as the DS and brow-elevating muscle and contribute to understanding the anatomical origins of individual variation in facial expressions. These results can also improve the safety, predictability, and aesthetics of treatments for the glabellar region with botulinum toxin type A and can be helpful when performing electromyography.

The three muscle layers in the pyloric sphincter and their possible function during antropyloroduodenal motility.

This study was conducted to determine the muscular arrangement of the human pyloric sphincter using a comprehensive approach that involved microdissection, histology, and microcomputed tomography (micro-CT). The stomachs of 80 embalmed Korean adult cadavers were obtained. In all specimens, loose muscular tissue of the innermost aspect of the sphincter wall ran aborally, forming the newly found inner longitudinal muscle bundles, entered the duodenum, and connected with the nearby circular bundles. In all specimens, approximately one-third of the outer longitudinal layer of the sphincter entered its inner circular layer, divided the circular layer into several parts, and finally connected with the circular bundles. Anatomical findings around the sphincter were confirmed in micro-CT images. The sphincter wall comprised three layers: an inner layer of longitudinal bundles, a middle layer of major circular and minor longitudinal bundles, and an outer layer of longitudinal bundles. The stomach outer longitudinal bundles were connected to the sphincter circular bundles. The inner longitudinal bundles of the sphincter were connected to the adjacent circular bundles of the duodenum.

Current Advances in Wearable Devices and Their Sensors in Patients With Depression.

In this study, a literature survey was conducted of research into the development and use of wearable devices and sensors in patients with depression. We collected 18 studies that had investigated wearable devices for assessment, monitoring, or prediction of depression. In this report, we examine the sensors of the various types of wearable devices (e.g., actigraphy units, wristbands, fitness trackers, and smartwatches) and parameters measured through sensors in people with depression. In addition, we discuss future trends, referring to research in other areas employing wearable devices, and suggest the challenges of using wearable devices in the field of depression. Real-time objective monitoring of symptoms and novel approaches for diagnosis and treatment using wearable devices will lead to changes in management of patients with depression. During the process, it is necessary to overcome several issues, including limited types of collected data, reliability, user adherence, and privacy concerns.

Historical review and occurrence records of Callipogon relictus Semenov, 1899 (Coleoptera, Cerambycidae) in Gwangneung Forest, South Korea with suggestions for species conservation.

Biodiversity has been declining and extinction rates have been exponentially increasing because of land use changes, invasion of exotic species, nutrient enrichment and climate change. In this scenario, many international networks such as the International Union for the Conservation of Nature have been making efforts to raise conservation awareness and preserve species and their habitats in many countries. The relict longhorn beetle Callipogon relictus Semenov, 1899 (Coleoptera: Cerambycidae) is the largest coleopteran species in the Palearctic region and has a unique distribution compared to its congeneric species. Callipogon relictus has been protected by two Korean laws since it was designated as a Korean Natural Monument and an Endangered Species in 1968 and 2012, respectively. To improve the conservation of this species, ecological and biological data were obtained from studies performed during the last 12 years on its populations in Gwangneung Forest, the fourth UNESCO biosphere reserve in South Korea. Previously scattered distribution records of C. relictus from South Korea from 1932 to 2007 are therefore summarized and ecological features of adults observed during fields studies performed from 2008 to 2019 are presented. Based on the summarized data, we suggest different management measures and conservation efforts to maintain the size of C. relictus populations in South Korea, which can also be further used in the restoration of other endangered insects.

Newly-found channels in the interatrial septum of the heart by dissection, histologic evaluation, and three-dimensional microcomputed tomography.

A minute thrombus can pass through a small type of interatrial communication, which can result in a stroke or transient ischemic attack and several associated symptoms. This study sought to investigate a new type of interatrial communication. Thirty-one hearts from embalmed adult cadavers were investigated. Each interatrial channels (IACs) was classified as either an open or obstructed channel according to the connection of each hole on the right and left surfaces of the interatrial septum. Open channels were found in two specimens (6.5%). Both open and obstructed IACs followed tortuous courses through the interatrial septum. On the right surface of the interatrial septum, the hole was usually found adjacent to the left border of the interatrial septum between the opening of the superior vena cava into the right atrium and the superior margin of the fossa ovalis. Conversely, holes on the left surface of the interatrial septum were usually found in the upper and middle parts adjacent to the left border of the interatrial septum. This novel finding is expected to support our understanding of the onset of possible symptoms such as stroke in the absence of classical atrial septal defects.

Genome Size Estimation of Callipogon relictus Semenov (Coleoptera: Cerambycidae), an Endangered Species and a Korea Natural Monument.

We estimated the genome size of a relict longhorn beetle, Callipogon relictus Semenov (Cerambycidae: Prioninae)-the Korean natural monument no. 218 and a Class I endangered species-using a combination of flow cytometry and k-mer analysis. The two independent methods enabled accurate estimation of the genome size in Cerambycidae for the first time. The genome size of C. relictus was 1.8 ± 0.2 Gb, representing one of the largest cerambycid genomes studied to date. An accurate estimation of genome size of a critically endangered longhorned beetle is a major milestone in our understanding and characterization of the C. relictus genome. Ultimately, the findings provide useful insight into insect genomics and genome size evolution, particularly among beetles.

Heights and spatial relationships of the facial muscles acting on the nasolabial fold by dissection and three-dimensional microcomputed tomography.

The aim of this study was to clarify the heights and spatial relationships of the facial muscles acting on the nasolabial fold (NLF) by dissection and three-dimensional microcomputed tomography for use in aesthetic treatments. This study used 56 specimens from 34 embalmed adult Korean. A reference line (RF) was set to imitate the NLF after removing the skin, from the superior point of the alar facial crease to the lateral point of the orbicularis oris muscle at the level of the corner of the mouth. The heights and spatial relationships of the facial muscles along the RF could be categorized into five main patterns. The dominant pattern was that the levator labii superioris alaeque nasi muscle (LLSAN), levator labii superioris muscle (LLS), zygomaticus minor muscle (Zmi), and zygomaticus major muscle (Zmj) were on the medial third, medial half, middle third, and lateral third of the RF, respectively. In micro-CT imaging, beneath the skin of the medial half of the NLF, the LLSAN and Zmi fibers inserted into the dermis of the NLF and adjacent to the NLF. Beneath the skin of the middle third of the NLF, the Zmi fibers were found before the muscle inserted into the dermis of the NLF and adjacent to the NLF. Beneath the skin of the lateral third of the NLF, the lateral margin of the orbicularis oris muscle and some Zmj fibers were found at the location of the NLF. The present study utilized dissections and micro-CT to reveal the general pattern and variations of heights and spatial relationships of the facial muscles passing beneath the NLF. These findings will be useful for understanding which muscles affect specific parts of NLFs with various contours, for reducing the NLF in aesthetic treatments, and for reconstructing the NLF in cases of facial paralysis.

Longitudinal muscular column in the prostatic urethral wall: Its form, shape, and possible function based on mathematical simulation in ejaculation.

BACKGROUND: The shape and function of the longitudinal muscular column (LMC) of the prostate have not been established in detail. The present study was undertaken to elucidate the roles of the LMC of the posterior wall of the prostatic urethra (PSU) in the emission phase of ejaculation by investigating the form and muscular arrangement of the LMC. METHODS: Prostates and urinary bladders were obtained from 14 Korean adult cadavers. Nine specimens were histologically analyzed using hematoxylin and eosin, Masson's trichrome, and Verhoeff-van Gieson staining. Two specimens were scanned using microcomputed tomography (micro-CT), and all scanned images were reconstructed into a three-dimensional model. RESULTS: At the proximal level of the prostate, the ejaculatory ducts (EDs) and prostatic utricle (PU) together were surrounded by circular smooth-muscle fibers. However, at the seminal colliculus (SC) where the EDs and PU opened, they were mainly surrounded by an abundance of longitudinal fibers. The longitudinal fibers posterior to the EDs and PU formed a distinctive LMC in the posterior urethral wall. In histologic sections and micro-CT images, the LMC extended distally from the level of the SC to the level of the membranous urethra (MBU). We simulated a potential mechanism of LMC using a mathematical model of its movements. CONCLUSIONS: Comprehensive analyses based on in-depth assessment of histologic characteristics and micro-CT images demonstrated extension of the LMC from the level of the SC to the level of the MBU, enabling a better understanding of ejaculation physiology involving the LMC. These results suggest that the LMC in the posterior wall of the PSU is a critical component of ejaculation by facilitating the ejection of seminal vesicle fluid into the PSU via well-coordinated contractions.

A taxonomic review of Korean Atheta Thomson subgenus Atheta Thomson (Coleoptera, Staphylinidae, Aleocharinae), with descriptions of two new species.

A taxonomic review of Atheta Thomson subgenus Atheta Thomson in the Korean Peninsula is presented. The subgenus is represented in Korea by eight species including two new species, A. (A.) prolixa Lee Ahn, sp. nov. and A. (A.) vegrandis Lee Ahn, sp. nov. Atheta (A.) sauteri Bernhauer is reported for the first time in South Korea. A key, descriptions, habitus photographs and illustrations of the diagnostic characters are provided.