Spatiotemporal control of pattern formation during somitogenesis.

Spatiotemporal patterns widely occur in biological, chemical, and physical systems. Particularly, embryonic development displays a diverse gamut of repetitive patterns established in many tissues and organs. Branching treelike structures in lungs, kidneys, livers, pancreases, and mammary glands as well as digits and bones in appendages, teeth, and palates are just a few examples. A fascinating instance of repetitive patterning is the sequential segmentation of the primary body axis, which is conserved in all vertebrates and many arthropods and annelids. In these species, the body axis elongates at the posterior end of the embryo containing an unsegmented tissue. Meanwhile, segments sequentially bud off from the anterior end of the unsegmented tissue, laying down an exquisite repetitive pattern and creating a segmented body plan. In vertebrates, the paraxial mesoderm is sequentially divided into somites. In this review, we will discuss the most prominent models, the most puzzling experimental data, and outstanding questions in vertebrate somite segmentation.

Comparison of peripapillary vascular density as measured by optical coherence tomography angiography between various types of open-angle glaucoma.

PURPOSE: The purpose of this study is to compare the peripapillary vascular density in patients with various types of open-angle glaucoma (primary open-angle glaucoma, pseudoexfoliative glaucoma and pigmentary glaucoma) with healthy subjects by optic coherence tomography angiography (OCTA). METHODS: Twenty-seven eyes with diagnosed POAG, thirty-four eyes with diagnosed PXG, twenty eyes with diagnosed PG and thirty eyes of healthy individuals were included in our study. Peripapillary vessel density measurements were performed with all images; (AI-DD), intra-disc (ID-DD) and peripapillary (PP-DD); measurement of vascular density in the radial peripapillary capillary network was performed by OCTA. The Kruskal-Wallis test and post-hoc test were performed for statistical analysis. RESULTS: AI-DD was 50.76±2.07% in the healthy group, 47.12±2.57% in POAG, 39.71±6.64% in PXG, and 43.37±1.55% in PG. ID-DD was 50.49±3.74% in the healthy group, 49.51±6.83% in POAG, 38.42±13.46% in PXG, and 40.9±4.45% in PG. PP-DD was 51.26±3.12% in the healthy group, 50.13±3.04% in POAG, 42.31±7.31% in PXG, and 47.6±1.40% in PG. While it was found that all image and intra-disc vascular density measurements were statistically significantly lower in the PG and PXG group compared to the healthy group and the POAG (P<0.001), there was no significant difference between PXG and PG or between the control group and POAG. CONCLUSIONS: The lower radial peripapillary capillary density in PXG and PG compared to the POAG and healthy groups suggests that the blood flow around the optic disc is negatively affected in these patients.

Evaluation of the association between the optic nerve sheath diameter and extracorporeal life support time during cardiac surgery in newborns.

OBJECTIVE: Congenital heart disease (CHD), a birth defect, is a major cause of neonatal mortality; however, improvements in surgical procedures and medical treatments have resulted in decreased mortality rates. Nonetheless, postoperative morbidity, particularly cerebral dysfunction, remains an issue in patients receiving extracorporeal life support (ECLS) for cardiac surgeries. Herein, we aimed to assess the association between optic nerve sheath diameter (ONSD) and ECLS time in newborns receiving ECLS for cardiac surgery. PATIENTS AND METHODS: We enrolled 25 newborn patients who received ECLS for cardiac surgery at our hospital. ONSD was measured at four different time points during the surgery: baseline (T1), 15 min after cross-clamping (T2), after displacement of cross-clamping (T3) and at the end of the surgery (T4). Furthermore, the ECLS time, aortic cross-clamp time, and surgery time were recorded. RESULTS: The regression analysis revealed a significant association between ONSD and ECLS time, cross-clamp time and surgery time. The correlation analysis showed strong associations between baseline ONSD and ONSD at T2, T3, and T4. Moreover, ONSDs significantly increased at T2 compared with those at baseline during cardiac surgery. CONCLUSIONS: Our findings suggest an association between ONSD and ECLS time in newborns receiving ECLS for cardiac surgery. Monitoring ONSD may provide valuable information about intracranial pressure changes in these patients.

A design logic for sequential segmentation across organisms.

Multitudes of organisms display metameric compartmentalization of their body plan. Segmentation of these compartments happens sequentially in diverse phyla. In several sequentially segmenting species, periodically active molecular clocks and signaling gradients have been found. The clocks are proposed to control the timing of segmentation, while the gradients are proposed to instruct the positions of segment boundaries. However, the identity of the clock and gradient molecules differs across species. Furthermore, sequential segmentation of a basal chordate, Amphioxus, continues at late stages when the small tail bud cell population cannot establish long-range signaling gradients. Thus, it remains to be explained how a conserved morphological trait (i.e., sequential segmentation) is achieved by using different molecules or molecules with different spatial profiles. Here, we first focus on sequential segmentation of somites in vertebrate embryos and then draw parallels with other species. Thereafter, we propose a candidate design principle that has the potential to answer this puzzling question.

Human stem cell models unravel mechanisms of somite segmentation.

In vitro models to study human somitogenesis, the formation of the segmented body plan, have so far been limited.1 Two papers in Nature now report the creation of pluripotent stem cell (PSC)-derived 3D culture systems that recapitulate the formation of somite-like structures and help gain insights into this developmental process.2,3.

Periodic inhibition of Erk activity drives sequential somite segmentation.

Sequential segmentation creates modular body plans of diverse metazoan embryos1-4. Somitogenesis establishes the segmental pattern of the vertebrate body axis. A molecular segmentation clock in the presomitic mesoderm sets the pace of somite formation4. However, how cells are primed to form a segment boundary at a specific location remains unclear. Here we developed precise reporters for the clock and double-phosphorylated Erk (ppErk) gradient in zebrafish. We show that the Her1-Her7 oscillator drives segmental commitment by periodically lowering ppErk, therefore projecting its oscillation onto the ppErk gradient. Pulsatile inhibition of the ppErk gradient can fully substitute for the role of the clock, and kinematic clock waves are dispensable for sequential segmentation. The clock functions upstream of ppErk, which in turn enables neighbouring cells to discretely establish somite boundaries in zebrafish5. Molecularly divergent clocks and morphogen gradients were identified in sequentially segmenting species3,4,6-8. Our findings imply that versatile clocks may establish sequential segmentation in diverse species provided that they inhibit gradients.

COMPARISON OF C-PEPTIDE LEVELS IN MONOGENIC FORMS OF DIABETES WITH OTHER TYPES OF DIABETES: A SINGLE-CENTER STUDY.

Objective: This study aimed to evaluate the utility of C-peptide levels in the differentiation of monogenic forms of diabetes from type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in clinical practice. Subjects and Methods: A total of 104 patients aged >16 who visited the Dicle University's Faculty of Medicine between April 2011 and December 2020 and were diagnosed with monogenic diabetes by genetic analysis or with T1DM and T2DM were randomly selected for retrospective evaluation. The C-peptide levels of these patients at the time of diagnosis of diabetes were compared. Results: Of the 104 patients, 24 (23%) were diagnosed with maturity-onset diabetes of the young (MODY), 40 (38.5%) with T1DM, and 40 (38.5%) with T2DM. Median C-peptide levels (ng/mL) (interquartile range) were 1.78 (1.24-2.88) in MODY group, 0.86 (0.34-1.22) in T1DM group, and 2.38 (1.58-4.27) in T2DM group. Conclusions: There was a difference in C-peptide levels between MODY and T1DM groups but not between MODY and T2DM groups. As per clinical evaluations, although C-peptide levels of patients with MODY are similar to those of patients with T2DM patients, the possibility of C-peptide levels being similar to those required for T1DM diagnosis should also be considered.

Patterning principles of morphogen gradients.

Metazoan embryos develop from a single cell into three-dimensional structured organisms while groups of genetically identical cells attain specialized identities. Cells of the developing embryo both create and accurately interpret morphogen gradients to determine their positions and make specific decisions in response. Here, we first cover intellectual roots of morphogen and positional information concepts. Focusing on animal embryos, we then provide a review of current understanding on how morphogen gradients are established and how their spans are controlled. Lastly, we cover how gradients evolve in time and space during development, and how they encode information to control patterning. In sum, we provide a list of patterning principles for morphogen gradients and review recent advances in quantitative methodologies elucidating information provided by morphogens.

Muscle strength but not balance improves after arthroscopic biodegradable polyurethane meniscus scaffold application.

PURPOSE: This study aimed to assess the impact of biodegradable polyurethane meniscus scaffold implantation (BPMSI) on muscle strength and balance in comparison with the healthy contralateral knee in patients with irreparable medial meniscus defect. METHODS: This observational and prospective case-cohort study was conducted with patients who had irreparable meniscal defects and underwent arthroscopic meniscus scaffold implantation. Surgeries were carried out on the medial meniscus of 16 right and 4 left knees. Visual analog scale (VAS) was used to assess the degree of pain relief. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Lysholm (LYS) score were used to evaluate the functional improvement at weeks 12, 24 and 36. Concentric and eccentric quadriceps and hamstring peak torque (PT) as well as the peak torque-to-body weight (PTB) ratio, anterior-posterior, mediolateral and overall stability indexes were assessed at the same time points. RESULTS: Twenty male patients with a mean age and body mass index of 32.2 ± 8.8 years and 26.2 ± 4.2 kg/m2, respectively, were included in the study. The amount of pain decreased from 7.6 ± 1.5% to 2.9 ± 1.5% at postoperative week 36. Range of motion, Lysholm score and KOOS increased from 87.0ο ± 9.5ο to 115.0ο ± 15.1ο, 30.8 ± 4.3 to 81.5 ± 5.3 and 37.4 ± 5.3 to 74.1 ± 7.2, respectively. Concentric quadriceps and hamstring peak torque values and peak torque/body weight ratios were improved in the knees that received a meniscus scaffold implant. Anterior/posterior, medial/lateral, and overall stability indexes with or without biofeedback exhibited a slight improvement, which was not statistically significant. CONCLUSION: BPMSI led to decreased pain and improved function at postoperative week 36. Although muscle strength almost returned to normal, balance parameters did not recover within 36 weeks after the procedure.