Serine Metabolism Controls Dental Pulp Stem Cell Aging by Regulating the DNA Methylation of p16.

To investigate the characteristics and molecular events of dental pulp stem cells (DPSCs) for tissue regeneration with aging, we isolated and analyzed the stem cells from human exfoliated deciduous teeth (SHED) and permanent teeth of young (Y-DPSCs) and old (A-DPSCs) adults. Results showed that the stemness and osteogenic differentiation capacity of DPSCs decreased with aging. The RNA sequencing results showed that glycine, serine, and threonine metabolism was one of the most enriched gene clusters among SHED, Y-DPSCs, and A-DPSCs, according to analysis based on the Kyoto Encyclopedia of Genes and Genomes. The expression of serine metabolism-related enzymes phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate (PHGDH) decreased in A-DPSCs and provided less methyl donor S-adenosylmethionine (SAM) for DNA methylation, leading to the hypomethylation of the senescence marker p16 (CDNK2A). Furthermore, the proliferation and differentiation capacity of Y-DPSCs and SHED decreased after PHGDH siRNA treatment, which reduced the level of SAM. Convincingly, the ratios of PSAT1-, PHGDH-, or proliferating cell nuclear antigen-positive cells in the dental pulp of old permanent teeth were less than those in the dental pulp of deciduous teeth and young permanent teeth. In summary, the stemness and differentiation capacity of DPSCs decreased with aging. The decreased serine metabolism in A-DPSCs upregulated the expression of p16 via attenuating its DNA methylation, resulting in DPSC aging. Our finding indicated that serine metabolism and 1 carbon unit participated in stem cell aging, which provided new direction for stem cell aging study and intervention.

Accuracy of automated three-dimensional ultrasound imaging technique for fetal head biometry.

OBJECTIVES: To evaluate the accuracy of an automated three-dimensional (3D) ultrasound technique for fetal intracranial measurements compared with manual acquisition. METHODS: This was a prospective observational study of patients presenting for routine anatomical survey between 18 + 0 and 22 + 6 weeks' gestation. After providing informed consent, each patient underwent two consecutive ultrasound examinations of the fetal head, one by a sonographer and one by a physician. Each operator obtained manual measurements of the biparietal diameter (BPD), head circumference (HC), transcerebellar diameter (TCD), cisterna magna (CM) and posterior horn of the lateral ventricle (Vp), followed by automated measurements of these structures using an artificial intelligence-based tool, SonoCNS® Fetal Brain. Both operators repeated the automated approach until all five measurements were obtained in a single sweep, up to a maximum of three attempts. The accuracy of automated measurements was compared with that of manual measurements using intraclass correlation coefficients (ICC) by operator type, accounting for patient and ultrasound characteristics. RESULTS: One hundred and forty-three women were enrolled in the study. Median body mass index was 24.0 kg/m2 (interquartile range (IQR), 22.5-26.8 kg/m2 ) and median subcutaneous thickness was 1.6 cm (IQR, 1.3-2.0 cm). Fifteen (10%) patients had at least one prior Cesarean delivery, 17 (12%) had other abdominal surgery and 78 (55%) had an anterior placenta. Successful acquisition of the automated measurements was achieved on the first, second and third attempts in 70%, 22% and 3% of patients, respectively, by sonographers and in 76%, 16% and 3% of cases, respectively, by physicians. The automated algorithm was not able to identify and measure all five structures correctly in six (4%) and seven (5%) patients scanned by the sonographers and physicians, respectively. The ICCs reflected good reliability (0.80-0.88) of the automated compared with the manual approach for BPD and HC and poor to moderate reliability (0.23-0.50) for TCD, CM and Vp. Fetal lie, head position, placental location, maternal subcutaneous thickness and prior Cesarean section were not associated with the success or accuracy of the automated technique. CONCLUSIONS: Automated 3D ultrasound imaging of the fetal head using SonoCNS reliably identified and measured BPD and HC but was less consistent in accurately identifying and measuring TCD, CM and Vp. While these results are encouraging, further optimization of the automated technology is necessary prior to incorporation of the technique into routine sonographic protocols. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

ALK-positive anaplastic large-cell lymphoma with primary bone involvement: A rare case and review of the literature.

Primary bone lymphoma (PBL) is an uncommon type of extranodal lymphoma involvement. An anaplastic large-cell lymphoma (ALCL) is an extremely rare type of PBL, and it remains unclear whether ALCLs that primarily involve the bone exhibit favourable or unfavourable biological behaviour, and whether they are similar to ALCLs in general, or not. We reported a case of ALK-positive ALCL with primary bone involvement, and reviewed the clinicopathological features of 22 previously reported cases. An ALCL with primary bone involvement mostly affects younger patients with a preponderant towards the involvement of axial-bone. The prognosis of an ALCL that primarily involves bone is unfavourable, compared with PBL generally. The ALK-positive ALCLs in PBLs had less decedents than the ALK-negative ALCLs with a statistical non-significance (p=0.198).

Protein deprivation decreases male survival and the intensity of sexual antagonism in southern field crickets Gryllus bimaculatus.

Recent theory predicts that the magnitude of sexual antagonism should depend on how well populations are adapted to their environment. We tested this idea experimentally by comparing intersexual genetic correlations for adult survival in pedigreed populations of southern field crickets (Gryllus bimaculatus) raised on naturally balanced (free-choice) vs. imbalanced (protein-deprived) diets. We tested for (1) sex differences in nutritional intake and preference, (2) sex-specific effects of protein deprivation on survival and (3) diet dependence of the level of sexual antagonism. Adult males and females consumed a similar amount of protein, but protein deprivation decreased male survival but not female survival. Protein deprivation appeared to decrease the degree of sexual antagonism as intersexual genetic correlations were significantly lower than 1 only for the complementary free-choice diet group but close to 1 for the protein-deficient diet group. Our findings thereby implied that variation in nutritional environments can alter the magnitude of sexual antagonism. This research represents an important step towards understanding the relationship between sexual antagonism and adaptation in heterogeneous environments.

[(18)F] FP-CIT PET study in parkinsonian patients with leukoaraiosis.

BACKGROUNDS: Leukoaraiosis may present with slowly progressive parkinsonism indistinguishable from primary degenerative parkinsonism. Both leukoaraiosis and degenerative parkinsonism are an age-related disorder. Thus, comorbidity is expected to be common in elderly patients with parkinsonism. However, no systematic study has been reported on the clinical features indicating concomitant nigrostriatal dopaminergic denervation (NDD) in parkinsonian patients with leukoaraiosis. METHODS: We performed [(18)F] FP-CIT positron emission tomography studies in 42 consecutive parkinsonian patients with diffuse leukoaraiosis, but no basal ganglia vascular lesions. RESULTS: Twenty (48%) of the 42 patients had coexisting NDD. Compared to parkinsonian patients with isolated leukoaraiosis, those with coexisting NDD more frequently had asymmetric onset. They had similar degree of parkinsonian motor deficits in the legs, but greater rigidity and resting tremor in the arms. Consequently, they had less prominent lower body parkinsonism. They more frequently showed favorable response to levodopa treatment. They had similar burden of regional and total leukoaraiosis. Among a variety of clinical variables and MRI findings, only asymmetric onset and more than 30% improvement in UPDRS motor score by levodopa treatment were valuable indicators of coexisting NDD. CONCLUSIONS: We would like to recommend dopaminergic functional imaging studies for all parkinsonian patients with leukoaraiosis. Further studies are needed to confirm sensitivity and specificity of asymmetric onset and good levodopa response for the prediction of coexisting NDD in a different group of parkinsonian patients with leukoaraiosis.

Complete Genome Assemblies for Two Single-Chromosome Vibrio cholerae Isolates, Strains 1154-74 (Serogroup O49) and 10432-62 (Serogroup O27).

Here, we report the completed genome sequences for two non-O1/non-O139 Vibrio cholerae isolates. Each isolate has only a single chromosome, as opposed to the normal paradigm of two chromosomes found in all other V. cholerae isolates.

Complete Genome Sequence of Anaeromyxobacter sp. Fw109-5, an Anaerobic, Metal-Reducing Bacterium Isolated from a Contaminated Subsurface Environment.

We report the genome sequence of Anaeromyxobacter sp. Fw109-5, isolated from nitrate- and uranium-contaminated subsurface sediment of the Oak Ridge Integrated Field-Scale Subsurface Research Challenge (IFC) site, Oak Ridge Reservation, TN. The bacterium's genome sequence will elucidate its physiological potential in subsurface sediments undergoing in situ uranium bioremediation and natural attenuation.

Variants of Monteggia Type Injury: Case Reports.

BACKGROUND: Monteggia fracture-dislocation is rare in children. Various reports attest to its rarity, while recording the many variant of this injury. It is, therefore, easy to miss the diagnosis in the absence of proper clinical examination and radiographs. CASE REPORT: This report highlights two rare variants of Monteggia fracture-dislocation seen in children. The first case was a 12-year old girl alleged to have fallen from a 15- feet tall tree and sustaining a combined type III Monteggia injury with ipsilateral Type II Salter-Harris injury of distal end radius with a metaphyseal fracture of the distal third of the ulna. The second case was a 13-year old who had sustained a closed fracture of atypical Type I Monteggia hybrid lesion, in a road traffic accident. CONCLUSION: This report highlights the rare variants of Monteggia fracture dislocation which could have been missed without proper clinical examinations and radiographs.

Single- and double-stranded viral RNA generate distinct cytokine and antiviral responses in human fetal membranes.

There has been growing interest in the role of viral infections and their association with adverse pregnancy outcomes. However, little is known about the impact viral infections have on the fetal membranes (FM). Toll-like receptors (TLR) are thought to play a role in infection-associated inflammation at the maternal-fetal interface. Therefore, the objective of this study was to characterize the cytokine profile and antiviral response in human FMs exposed to viral dsRNA, which activates TLR3, and viral ssRNA, which activates TLR8; and to determine the mechanisms involved. The viral dsRNA analog, Poly(I:C), induced up-regulated secretion of MIP-1α, MIP-1ß, RANTES and TNF-α, and down-regulated interleukin (IL)-2 and VEGF secretion. In contrast, viral ssRNA induced a broader panel of cytokines in the FMs by up-regulating the secretion of IL-1ß, IL-2, IL-6, G-CSF, MCP-1, MIP-1α, MIP-1ß, RANTES, TNF-α and GRO-α. Using inhibitory peptides against TLR adapter proteins, FM secretion of MIP-1ß and RANTES in response to Poly(I:C) was MyD88 dependent; MIP-1α secretion was dependent on MyD88 and TRIF; and TNF-α production was independent of MyD88 and TRIF. Viral ssRNA-induced FM secretion of IL-1ß, IL-2, IL-6, G-CSF, MIP-1α, RANTES and GRO-α was dependent on MyD88 and TRIF; MIP-1ß was dependent upon TRIF, but not MyD88; and TNF-α and MCP-1 secretion was dependent on neither. Poly(I:C), but not ssRNA, induced an FM antiviral response by up-regulating the expression of IFNß, myxovirus-resistance A, 2',5'-oligoadenylate synthetase and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G. These findings demonstrate that human FMs respond to two viral signatures by generating distinct inflammatory cytokine/chemokine profiles and antiviral responses through different mechanisms.

Correlational selection does not explain the evolution of a behavioural syndrome.

Correlated suites of behaviours, or behavioural syndromes, appear to be widespread, and yet few studies have explored how they arise and are maintained. One possibility holds that correlational selection can generate and maintain behavioural syndrome if certain behavioural combinations enjoy greater fitness than other combinations. Here we test this correlational selection hypothesis by comparing behavioural syndrome structure with a multivariate fitness surface based on reproductive success of male water striders. We measured the structure of a behavioural syndrome including dispersal ability, exploration behaviour, latency to remount and sex recognition sensitivity in males. We then measured the relationship between these behaviours and mating success in a range of sex ratio environments. Despite the presence of some significant correlational selection, behavioural syndrome structure was not associated with correlational selection on behaviours. Although we cannot conclusively reject the correlational selection hypothesis, our evidence suggests that correlational selection and resulting linkage disequilibrium might not be responsible for maintaining the strong correlations between behaviours. Instead, we suggest alternative ways in which this behavioural syndrome may have arisen and outline the need for physiological and quantitative genetic tests of these suggestions.

Evaluating the cost-effectiveness of prenatal surgery for myelomeningocele: a decision analysis.

OBJECTIVE: To determine whether prenatal myelomeningocele repair is a cost-effective strategy compared to postnatal repair. METHODS: Decision-analysis modeling was used to calculate the cumulative costs, effects and incremental cost-effectiveness ratio of prenatal myelomeningocele repair compared with postnatal repair in singleton gestations with a normal karyotype that were identified with myelomeningocele between T1 and S1. The model accounted for costs and quality-adjusted life years (QALYs) in three populations: (1) myelomeningocele patients; (2) mothers carrying myelomeningocele patients; and (3) possible future siblings of these patients. Sensitivity analysis was performed using one-way, two-way and Monte Carlo simulations. RESULTS: Prenatal myelomeningocele repair saves $ 2 066 778 per 100 cases repaired. Additionally, prenatal surgery results in 98 QALYs gained per 100 repairs with 42 fewer neonates requiring shunts and 21 fewer neonates requiring long-term medical care per 100 repairs. However, these benefits are coupled to 26 additional cases of uterine rupture or dehiscence and one additional case of neurologic deficits in future offspring per 100 repairs. Results were robust in sensitivity analysis. CONCLUSION: Prenatal myelomeningocele repair is cost effective and frequently cost saving compared with postnatal myelomeningocele repair despite the increased likelihood of maternal and future pregnancy complications associated with prenatal surgery.

Universal cervical-length screening to prevent preterm birth: a cost-effectiveness analysis.

OBJECTIVE: To determine whether routine measurement of second-trimester transvaginal cervical length by ultrasound in low-risk singleton pregnancies is a cost-effective strategy. METHODS: We developed a decision analysis model to compare the cost-effectiveness of two strategies for identifying pregnancies at risk for preterm birth: (1) no routine cervical length screening and (2) a single routine transvaginal cervical length measurement at 18-24 weeks' gestation. In our model, women identified as being at increased risk (cervical length < 1.5 cm) for preterm birth would be offered daily vaginal progesterone supplementation. We assumed that vaginal progesterone reduces preterm birth at < 34 weeks' gestation by 45%. We also assumed that a decreased cervical length could result in additional costs (ultrasound scans, inpatient admission) without significantly improved neonatal outcomes. The main outcome measure was incremental cost-effectiveness ratio. RESULTS: Our model predicts that routine cervical-length screening is a dominant strategy when compared to routine care. For every 100,000 women screened, $12,119,947 can be potentially saved (in 2010 US dollars) and 423.9 quality-adjusted life-years could be gained. Additionally, we estimate that 22 cases of neonatal death or long-term neurologic deficits could be prevented per 100,000 women screened. Screening remained cost-effective but was no longer the dominant strategy when cervical-length ultrasound measurement costs exceeded $187 or when vaginal progesterone reduced delivery risk at < 34 weeks by less than 20%. CONCLUSION: In low-risk pregnancies, universal transvaginal cervical length ultrasound screening appears to be a cost-effective strategy under a wide range of clinical circumstances (varied preterm birth rates, predictive values of a shortened cervix and costs).

Malignant myoepithelioma of the humerus with a satellite lesion: a case report and literature review.

We report an extremely rare case of malignant myoepithelioma presenting as a cortical osseous lesion on the humeral shaft with a satellite lesion. A 21-year-old man presented with persistent pain of the right upper arm after local trauma that had occurred 2 months earlier. Radiological examination revealed an expansile osseous tumour based on the cortex of the humeral shaft as well as a satellite lesion. En bloc resection was performed. Microscopic examination with immunohistochemical staining was used to establish a diagnosis of malignant myoepithelioma. Osseous malignant myoepithelioma occurring in long tubular bones rather than in bony structures with salivary tissue is extremely rare. Here, we demonstrate radiological and pathological features of a malignant myoepithelioma that developed in the cortex of the humeral shaft and review previously reported cases.

Brain-derived neurotrophic factor gene polymorphisms and mirtazapine responses in Koreans with major depression.

Brain-derived neurotrophic factor (BDNF) is a candidate molecule for influencing the clinical response to antidepressant treatment. The aims of this study were to determine the relationship between the Val66Met polymorphism in the BDNF gene and the response to mirtazapine in 243 Korean subjects with major depressive disorder (MDD). The reduction in the Hamilton Depression score over the 8-week treatment period was not influenced by BDNF V66M genotypes. A marginal effect of genotype on somatic anxiety score was observed at baseline (P = 0.047 in the dominant model). However, genotype-time interaction had no effect on somatic anxiety score after the 8-week a treatment period. Plasma BDNF levels tended to increase during mirtazapine treatment, although without statistical significance (P = 0.055). After 8 weeks of mirtazapine treatment, plasma BDNF levels were higher in Met allele homozygotes (1499.7 ± 370.6 ng/mL) than in Val allele carriers (649.7 ± 158.5 ng/mL, P = 0.049). Our results do not support the hypothesis that the Val66Met promoter polymorphism in the BDNF gene influences the therapeutic response to mirtazapine in Korean MDD patients. However, our data indicate that this polymorphism results in increased plasma BDNF after mirtazapine treatment.

Analysis of ten Brucella genomes reveals evidence for horizontal gene transfer despite a preferred intracellular lifestyle.

The facultative intracellular bacterial pathogen Brucella infects a wide range of warm-blooded land and marine vertebrates and causes brucellosis. Currently, there are nine recognized Brucella species based on host preferences and phenotypic differences. The availability of 10 different genomes consisting of two chromosomes and representing six of the species allowed for a detailed comparison among themselves and relatives in the order Rhizobiales. Phylogenomic analysis of ortholog families shows limited divergence but distinct radiations, producing four clades as follows: Brucella abortus-Brucella melitensis, Brucella suis-Brucella canis, Brucella ovis, and Brucella ceti. In addition, Brucella phylogeny does not appear to reflect the phylogeny of Brucella species' preferred hosts. About 4.6% of protein-coding genes seem to be pseudogenes, which is a relatively large fraction. Only B. suis 1330 appears to have an intact beta-ketoadipate pathway, responsible for utilization of plant-derived compounds. In contrast, this pathway in the other species is highly pseudogenized and consistent with the "domino theory" of gene death. There are distinct shared anomalous regions (SARs) found in both chromosomes as the result of horizontal gene transfer unique to Brucella and not shared with its closest relative Ochrobactrum, a soil bacterium, suggesting their acquisition occurred in spite of a predominantly intracellular lifestyle. In particular, SAR 2-5 appears to have been acquired by Brucella after it became intracellular. The SARs contain many genes, including those involved in O-polysaccharide synthesis and type IV secretion, which if mutated or absent significantly affect the ability of Brucella to survive intracellularly in the infected host.

Ultrasound in the evaluation of twin pregnancy.

Multiple gestations account for approximately 3% of all live births, but contribute to a disproportionate 15% of the overall perinatal mortality. Ultrasound evaluation of twin pregnancies serves an important role in surveillance, early detection, and invasive treatment of complications in twin pregnancies, including spontaneous abortion, abnormalities in placentation, preterm labor, growth restriction, congenital abnormalities, fetal demise, fetal mal-presentation, and twin-to-twin transfusion syndrome. A review of literature regarding the indications and use of ultrasound in twin pregnancy is presented.

Titin-cap (TCAP) polymorphisms associated with marbling score of beef.

Marbling score (MS) is the major qualitative trait that affects carcass quality in beef cattle. In this study, we examined the association between genetic polymorphisms of the titin-cap gene (TCAP) and carcass traits in Korean native cattle (also known as Hanwoo). By direct DNA sequencing in 24 unrelated Korean cattle, we identified five sequence variants in 1.2kb of TCAP. Among them, four common polymorphic sites were selected for genotyping in the beef cattle (n=437). Pair-wise linkage analysis with four polymorphisms showed strong linkage disequilibrium (LD), and three major haplotypes (freq.>0.1) were constructed. Statistical analysis revealed that polymorphisms in intron1 (g.346G>A) and exon2 (g.592-597CTGCAG[Leu-Gln]insdel) showed significant association with marbling score (P(cor.)=0.003 and 0.02, respectively). One haplotype, ht2[C-G-G-del], also showed significant association with MS (P(cor.)=0.0004). Our findings suggest that polymorphisms in TCAP might be among the important genetic factors involved in carcass quality in beef cattle.

Germ cell apoptosis induced by experimental cryptorchidism is mediated by multiple molecular pathways in Cynomolgus Macaque.

Experimental cryptorchidism is a common model for examining the expression and function of heat-sensitive spermatogenesis-related genes in testis. Previous studies have shown that germ cells in cryptorchid testis die mainly in an apoptotic way. The molecular mechanism, however, is still unclear. We have established unilateral cryptorchid monkey model (Cynomolgus Macaque) to identify possible molecules involved in the germ cell apoptosis. The degree of germ cell apoptosis, the morphology of the cryptorchid testis, and the changes in the serum concentration of FSH, LH and testosterone after cryptorchid surgery were analyzed. Sertoli cell marker molecule vimentin, the orphan receptor LRH-1, as well as the mitochondria-related protein HSP60 and Bcl-2 were examined. Our results showed that the weight of the cryptorchid testis decreased in a time-dependent manner started from day 7 after the surgery, while the weight of the scrotal testis had no obvious change. HE staining showed that from day 5, some germ cells were detached from the epithelium. A massive degeneration of the seminiferous epithelium characteristic of epithelial structural disorganization and the formation of multinucleated giant cells as well as vacuoles was observed on day 10 and 15. The cryptorchidism induced a marked germ cell apoptosis on day 3 after the operation, reaching a peak level on day 7.

VEGF, bFGF and their receptors at the fetal-maternal interface of the rhesus monkey.

Placental development involves trophoblast outgrowth and a coordinated angiogenesis in the implantation site. In this study, expression of angiogenic factors, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), VEGF receptors, kinase insert domain-containing region (KDR), and bFGF receptor Flg was characterized at the maternal-embryonic boundary of the rhesus monkey on Day 17, 19, 28 and 34 of pregnancy. Immunohistochemistry and in situ hybridization showed that VEGF mRNA and protein were both strongly expressed in the cytotrophoblast, the blood vessels and certain immunocytes. These sites were also immunopositive for KDR. In addition to the vascular endothelial cells and the vascular smooth muscle cells, the protein and mRNA for bFGF were also detected in cyto/syncytiotrophoblast bilayer, whereas the staining for Flg protein was mainly localized in the cytotrophoblast cells. The staining degree of VEGF and bFGF in the villi gradually decreased with the development of placenta. Strong expression of bFGF, Flg and KDR was also detected in the decidual cells. These data suggest that VEGF and bFGF may be involved in angiogenesis, cytotrophoblast proliferation and migration during early stage of placentation in the rhesus monkey.