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.

Prevalence of odontogenic cysts and tumors on turkish sample according to latest classification of world health organization: A 10-year retrospective study.

AIM: The aims of this study are to investigate the prevalence of odontogenic cysts and tumors occurred in a sample of Turkish population in the last 10 years and to compare the data with latest reports. METHODS AND MATERIAL: The present retrospective study was carried out at Gazi University, School of Dentistry (GUSD) in Ankara, Turkey. All the data was retrieved from the GUSD archive on patients treated for various oral and maxillofacial lesions between 2008 and 2018. Patients' demographical data, main clinical features of the lesions along with histopathological findings were retrieved from the dental files of the patients. The type of lesions was evaluated according to the latest Head and Neck Tumor (HNT) classification published by the World Health Organization (WHO) in 2017. Data was analyzed by descriptive statistics and Chi-square test using SPSS version 21.0 software. RESULTS: Among a total of 739 biopsy-conducted lesions, 467 (63.19%) were odontogenic cysts, 43 (5.82%) were benign odontogenic tumors, and 7 (0.95%) were malignant tumors. The rest of 222 cases were defined as others. CONCLUSIONS: The present study assessed the demographic and clinico-pathological characteristics of odontogenic cysts/tumors in a group of Turkish people, who visited GUSD for therapeutic purpose in the past 10 years. Results showed that male patients in their 5th-6th decades have the highest risk of odontogenic cyst/tumor, especially in the mandibular posterior region.

Quantifying spatial and temporal variations of the cell membrane ultra-structure by bimFCS.

It has been long recognized that the cell membrane is heterogeneous on scales ranging from a couple of molecules to micrometers in size and hence diffusion of receptors is length scale dependent. This heterogeneity modulates many cell-membrane-associated processes requiring transient spatiotemporal separation of components. The transient increase in local concentration of interacting signal components enables robust signaling in an otherwise thermally noisy system. Understanding how lipids and proteins self-organize and interact with the cell cortex requires quantifying the motion of the components. Multi-length scale diffusion measurements by single particle tracking, fluorescence correlation spectroscopy (FCS) or related techniques are able to identify components being transiently trapped in nanodomains, from freely moving one and from ones with reduced long-scale diffusion due to interaction with the cell cortex. One particular implementation of multi-length scale diffusion measurements is the combination of FCS with a spatially resolved detector, such as a camera and two-dimensional extended excitation profile. The main advantages of this approach are that all length scales are interrogated simultaneously, uniquely permits quantifying changes to the membrane structure caused by extrenal or internal perturbations. Here, we review how combining total internal reflection microscopy (TIRF) with FC resolves the membrane organization in living cells. We show how to implement the method, which requires only a few seconds of data acquisition to quantify membrane nanodomains, or the spacing of membrane fences caused by the actin cortex. The choice of diffusing fluorescent probe determines which membrane heterogeneity is detected. We review the instrument, sample preparation, experimental and computational requirements to perform such measurements, and discuss the potential and limitations. The discussion includes examples of spatial and temporal comparisons of the membrane structure in response to perturbations demonstrating the complex cell physiology.

Determination of the antibiotic resistance rates of Serratia marcescens isolates obtained from various clinical specimens.

AIM: Serratia marcescens clinical isolates are increasingly resistant to antibiotics. Therefore, the treatment of infections caused by S. marcescens becomes difficult. The aim of this study was to examine the antimicrobial resistance profiles of S. marcescens bacteria isolated from various clinical specimens according to body regions and clinics and to evaluate for enzyme production rates associated with antibiotic resistance of these isolates. MATERIALS AND METHODS: Blood culture samples were incubated in a fully automated BACTEC-FX system. Identification and antibiogram processing was carried out by fully automated VITEK 2 identification and antibiogram system. The obtained results were retrospectively screened. RESULTS: S. marcescens was identified in a total of 158 clinical specimens. The departments where S. marcescens was most commonly identified were the Anesthesia Intensive Care Unit (25.9%), followed by Chest Diseases (19.6%). Serratia isolates were most commonly determined in blood culture (35.4%) and sputum culture (24.6%). Resistance rates to ceftriaxone and ceftazidime were 22.7% and 19.6%, respectively. However, the rate of resistance detected to cefotaxime and gentamicin (0.6%) was very low. CONCLUSION: Clinical isolates of Serratia exhibited highest resistance to ceftriaxone, ceftazidime, and piperacillin/tazobactam. However, it was found that the tested Serratia strains did not exhibit high resistance to other antibiotics. Our results suggest that cefotaxime and gentamicin are the most suitable antibiotics for treatment. The extended-spectrum ß-lactamase and inducible ß-lactamase ratios were found to be decreased by 6%-7%. Although different results may be obtained from different hospitals and regions, it should not be forgotten that Serratia strains may be resistant to many antibiotics and that the results of antibiotic susceptibility testing may help plan antibiotic treatment.

PRENATAL DIAGNOSIS OF DE NOVO SUPERNUMERARY MARKER CHROMOSOME ORIGINATED FROM CHROMOSOME 16 BY ARRAY-CGH.

A 33 years-old pregnant woman was referred for amniocentesis at 19 weeks of gestation due to abnormal serum biochemistry. A non-satellited, monocentric marker chromosome was observed with a frequency of 50% in cultured amniocytes. Parental karyotypes were normal. The marker chromosome was found to be derived from chromosome 16 by FISH and array-CGH analysis. Genetic counseling was given to parents and the family decided to terminate the pregnancy. Dysmorphic findings including; low set ears, exophtalmos depressed nasal bridge, large mouth and lips, posture anomalies at the extremities were detected at autopsy.

The association between ischaemia-modified albumin levels in umbilical vein and intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is one of the most common problems in obstetrics. Ischaemia-modified albumin (IMA), a product deriving from albumin as a result of the modification by oxidative free radicals in response to hypoxia, was previously used as a marker of ischaemia in acute coronary syndrome. We performed this study to determine whether umbilical venous IMA levels are associated with IUGR. A total of 40 pregnancies with IUGR were compared with 40 of normal fetal development. Blood samples were obtained from the umbilical vein after delivery. IMA levels in the IUGR group were higher than in the control group (78.74 ± 6.87 vs 74.43 ± 7.84 U/ml, respectively, p = 0.011). An elevated IMA level was associated with IUGR (OR: 1.079, 95% CI: 1.000-1.163, p = 0.049). We suggest that IMA, which was formerly proved to arise in ischaemic conditions, may also be a valuable marker in perinatal hypoxia and IUGR detection.

Effect of a re-wetting agent on bond strength of an adhesive to primary and permanent teeth dentin after different etching techniques.

OBJECTIVE: This study investigated the effect of a re-wetting agent on the microtensile bond strengths (mTBS) of primary and permanent dentin after acid or laser etching. MATERIALS AND METHODS: Twelve permanent and 12 primary molar teeth were ground to expose an occlusal dentin surface. Each group teeth were randomly divided into groups; I-II: 37% phosphoric acid etching with/without re-wetting agent, III-IV: Erbium: Yttrium aluminium garnet laser etching with/without re-wetting agent. An etch-and-rinse adhesive was used, and vertical sticks were obtained for the microtensile test. RESULTS: mTBS of permanent teeth was higher than that of primary teeth (P < 0.05). Re-wetting agent groups were similar with control groups in both etching groups in the permanent teeth (P > 0.05). Re-wetting agent group was similar with the control group in acid etch group (P > 0.05) and lower than the control group in laser etch group in primary teeth (P < 0.05). CONCLUSION: Acid etching in permanent teeth; laser etching in primary teeth was found more successful. The use of re-wetting agent did not provide an advance on bond strength of the adhesive in both primary and permanent teeth after acid-etch or laser-etch.

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.

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.

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.

Association of first trimester low PAPP-A levels with adverse pregnancy outcomes.

OBJECTIVE: To investigate whether first trimester low PAPP-A levels are associated with adverse pregnancy outcomes. METHODS: A case control retrospective study including 663 pregnant women whose gestational age ranged between 11 and 14 weeks attending prenatal care at Akdeniz University Hospital was carried out. Chromosomal abnormalities, spontaneous abortions, and multiple pregnancies were excluded from the study. Finally 318 singleton pregnancies were included in this study. Pregnant women whose PAPP-A levels were < or =10th percentile were compared with PAPP-A levels > 10'h percentile for the frequency of pregnancy complications such as SGA, preeclampsia, preterm delivery, gestational diabetes mellitus and gestational hypertension. RESULTS: The most common complication of pregnancy was SGA (9.4%, n=30). There was no significant association between low PAPP-A levels and incidence of subsequent pregnancy outcomes. Maternal age was found to be a risk factor for gestational diabetes (p = 0.00). Small for gestational age was significantly associated with nulliparity and smoking during pregnancy (p = 0.03 and p = 0.01, respectively). CONCLUSION: First trimester of low PAPP-A level (< or = 10th percentile) was not associated with SGA, preeclampsia, preterm delivery, gestational hypertension or gestational diabetes mellitus.

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.

Apoptosis and expression of Bcl-2, Bax, p53, caspase-3, and Fas, Fas ligand in placentas complicated by preeclampsia.

AIM: To determine whether preeclampsia is associated with an increase in placental apoptosis and altered expression of mediators of apoptosis such as Fas, Fas ligand, caspase-3, p53, Bcl-2 and Bax. METHODS: Placental samples obtained from 20 women with preeclampsia and 14 normal women were analyzed using the Klenow, Frag-EL DNA fragmentation detection kit for apoptosis. Expression of Fas, Fas ligand, caspase-3, p53 Bcl-2, and Bax was assessed using immunohistochemistry. RESULTS: The median percentage of apoptotic nuclei in trophoblasts was significantly higher for the preeclampsia group than for the controls (6.9 vs 0.25; p =.001). Fas ligand expression was significantly higher in the decidua among the subjects with preeclampsia compared with controls (1.2 vs 0; p = .023). Otherwise no difference was observed in the expression of Bax , Bcl-2, p53, caspase-3, and Fas between groups. CONCLUSION: Increased apoptosis in preeclampsia may not be associated with significant alterations in Fas, Fas ligand, caspase-3, p53, Bcl-2 and Bax expression.

A 3-D Tail Explant Culture to Study Vertebrate Segmentation in Zebrafish.

Vertebrate embryos pattern their major body axis as repetitive somites, the precursors of vertebrae, muscle, and skin. Somites progressively segment from the presomitic mesoderm (PSM) as the tail end of the embryo elongates posteriorly. Somites form with regular periodicity and scale in size. Zebrafish is a popular model organism as it is genetically tractable and has transparent embryos that allow for live imaging. Nevertheless, during somitogenesis, fish embryos are wrapped around a large, rounding yolk. This geometry limits live imaging of PSM tissue in zebrafish embryos, particularly at higher resolutions that require a close objective working distance. Here, we present a flattened 3-D tissue culture method for live imaging of zebrafish tail explants. Tail explants mimic intact embryos by displaying a proportional slowdown of axis elongation and shortening of rostrocaudal somite lengths. We are further able to stall axis elongation speed through explant culture. This, for the first time, enables us to untangle the chemical input of signaling gradients from the mechanistic input of axial elongation. In future studies, this method can be combined with a microfluidic setup to allow time-controlled pharmaceutical perturbations or screening of vertebrate segmentation without any drug penetration concerns.

The effect of adenosine triphosphate on sunitinib-induced cardiac injury in rats.

In this study, we aimed to show the effect of adenosine 5'-triphosphate (ATP) on sunitinib-induced cardiac injury in rats. The rats (n = 30) were divided equally into three groups as sunitinib group (SG), sunitinib plus ATP group (SAG), and healthy group (HG); 2 mg/kg ATP was injected intraperitoneally (ip) to the SAG group. Same volume normal saline as solvent was administered ip to the other two groups. After 1 h, 25 mg/kg sunitinib was applied orally via catheter to stomach in the SAG and SG groups. This procedure was repeated once daily for 5 weeks. At the end of this period, all animals were sacrificed and their cardiac tissue was removed. Malondialdehyde (MDA), total glutathione (tGSH), tumor necrosis factor α (TNF-α), and nuclear factor κB (NF-κB) levels in rats' cardiac tissues and troponin I (Tp-I) levels in rats' blood samples were evaluated. Histopathological analysis was also performed in cardiac tissues of the animals. MDA, TNF-α, NF-κB, and Tp-I levels were higher in the SG group compared to the SAG and HG groups (p < 0.001). tGSH levels of the SG group were lower than the SAG and HG groups (p < 0.001). The structure and morphology of cardiac muscle fibers and blood vessels were normal in the control group. In the SG group, obvious cardiac muscle tissue damage with dilated myofibers, locally atrophic myofibers, and congested blood vessels were observed. In the SAG group, marked amelioration in these findings was observed. We showed this for the first time that ATP administration exerts a protective effect against cardiac effects of sunitinib.

Prenatal diagnosis of a de novo supernumerary marker chromosome originating from chromosome 16.

Prenatal diagnosis of a de novo supernumerary marker chromosome originating from chromosome 16: A 37 year old pregnant woman was referred for amniocentesis at 18 weeks of gestation due to advanced maternal age and abnormal serum biochemistry. A nonsatellited, monocentric marker chromosome was observed with a frequency of 57% in cultured amniocytes. Parental karyotypes were normal. The marker chromosome was found to be derived from chromosome 16 by FISH using CEP16 and WCP16 probes. Marker chromosomes were not painted with M-FISH probe mixture, indicating an exclusively heterochromatin nature. CGH analysis using genomic DNA isolated from uncultured amniocytes also supported the M-FISH results. Genetic counseling was given to parents and the family decided to continue the pregnancy to term. The baby was born at 36 weeks of gestation without any dysmorphic features. Follow-up at 7 months of age revealed no developmental abnormalities.