Cell fate regulation during preimplantation development: A view of adhesion-linked molecular interactions

AbstractIn the developmental process of the early mammalian embryo, it is crucial to understand how the identical cells in the early embryo later develop different fates. Along with existing models, many recently discovered molecular, cellular and developmental factors play roles in cell position, cell polarity and transcriptional networks in cell fate regulation during preimplantation. A structuring process known as compaction provides the “start signal” for cells to differentiate and orchestrates the developmental cascade. The proper intercellular junctional complexes assembled between blastomeres act as a conducting mechanism governing cellular diversification. Here, we provide an overview of the diversification process during preimplantation development as it relates to intercellular junctional complexes. We also evaluate transcriptional differences between embryonic lineages according to cell- cell adhesion and the contributions of adhesion to lineage commitment. These series of processes indicate that proper cell fate specification in the early mammalian embryo depends on junctional interactions and communication, which play essential roles during early morphogenesis

BMP signalling is required for extra-embryonic ectoderm development during pre-to-post-implantation transition of the mouse embryo

At implantation, the mouse embryo undergoes a critical transformation which requires the precise spatiotemporal control of signalling pathways necessary for morphogenesis and developmental progression. The role played by such signalling pathways during this transition are largely unexplored, due to the inaccessibility of the embryo during the implantation when it becomes engulfed by uterine tissues. Genetic studies demonstrate that mutant embryos for BMPs die around gastrulation. Here we have aimed to dissect the role of BMPs during pre-to post-implantation transition by using a protocol permitting the development of the embryo beyond implantation stages in vitro and using stem cells to mimic post-implantation tissue organisation. By assessing both the canonical and non-canonical mechanisms of BMP, we show that the loss of canonical BMP activity compromises the extra-embryonic ectoderm development. Our analyses demonstrate that BMP signalling maintains stem cell populations within both embryonic/extra-embryonic tissues during pre-to post-implantation development. These results may provide insight into the role played by BMP signalling in controlling early embryogenesis

Podwójne znakowanie immunologiczne CD133 i Ki-67 wskazuje na ich istotną współlokalizację w podtypie włóknistym oponiaków

Background and purpose A unique molecular and/or cellular marker for meningiomas, the most common intracranial tumours, has not been identified yet. Material and methods We investigated the co-localization fraction of CD133/Ki-67 in meningioma tissue array slide composed of 80 meningioma tissue samples of various histological variants. CD133 – a cell membrane stem cell marker – was previously proved to be associated with the initiation and progression of intracerebral gliomas and medulloblastomas. Results Immunohistochemical co-localization of CD133/Ki-67 was significantly higher in fibroblastic variant than in meningothelial and transitional subtypes. However, since there were only 3 atypical and 1 malignant meningioma spots in the tumour tissue array slide, it is difficult to draw a firm conclusion regarding the actual co-localization percentage and persistence of CD133/Ki-67 in atypical and malignant meningiomas. Conclusions Far higher co-staining percentage of CD133/Ki-67 in fibroblastic meningioma samples compared to meningothelial subtype, a histological meningioma variant, architectonically resembling the non-neoplastic meningeal cells, gave us the impression that CD133 may play a role in the formation and progression of fibroblastic meningioma variants. The persistency and the validity of this finding need to be verified by further histopathological and molecular research in order to clarify the possible role of CD133 in meningiogenesis.Wstęp i cel pracy Nie określono dotąd unikalnego znacznika molekularnego lub komórkowego dla oponiaków, najczęstszych guzów wewnątrzczaszkowych. Wcześniej wykazano, że CD133 – znacznik błony komórkowej komórek macierzystych – jest związany z zapoczątkowaniem, a także wzrostem wewnątrzczaszkowych glejaków i rdzeniaków płodowych. Materiał i metody Zbadano odsetek współlokalizacji CD133/Ki-67 w zestawach macierzy tkankowych oponiaków, złożonych z próbek 80 rozmaitych odmian histologicznych oponiaków. Wyniki Immunohistochemiczna współlokalizacja CD133 i Ki-67 była stwierdzana istotnie częściej w podtypie włóknistym oponiaka niż w podtypach meningotelialnym lub przejściowym. Ze względu na małą liczbę preparatów opo-niaków atypowych (3) oraz złośliwych (1) w badanej macierzy tkankowej trudno wyciągnąć jednoznaczne wnioski dotyczące rzeczywistego odsetka współlokalizacji i utrzymywania się CD133/Ki-67 w oponiakach atypowych i złośliwych. Wnioski Znacząco większy odsetek wspólnie występującej reaktywności CD133/Ki-67 w preparatach oponiaka włóknistego w porównaniu z podtypem meningotelialnym, którego architektonika przypomina nienowotworowe komórki opon, sprawia wrażenie, że CD133 może odgrywać rolę w powstawaniu i rozwoju oponiaków włóknistych. Trafność tego spostrzeżenia wymaga weryfikacji w dalszych badaniach histopatologicznych i molekularnych w celu wyjaśnienia możliwej roli CD133 w powstawaniu oponiaków

Farede prematüre over yetmezliğinde mTERT telomeraz katalitik alt ünitesinin rolünün belirlenmesi

Memelilerde prenatal hayatta oluşan oosit rezervi, postnatal hayatta azalarak tükenmektedir. Foliküler atrezi olarak adlandırılan bu mekanizma ile ovariyal yaşlanma meydana gelmektedir. Primordiyal folikül havuzu tekrardan yenilenemediği için bu tükeniş sonucunda infertilite ya da Prematüre Over Yetmezliği (POY) ile karşı karşıya kalınmaktadır. Polisiklik aromatik hidrokarbon 7, 12-dimetilbenz (7,12-dimethylbenz-[a]anthracene (DMBA)), ovaryum da dahil olmak üzere pekçok tümörü tetikleyen ve günlük hayatta da sıklıkla maaruz kaldığımız bir çevresel karsinojendir. Telomeraz, hücrenin bölünmesi esnasında kromozomların kararlı yapılarının korunmasını sağlar ve fare telomeraz ters transkriptaz (mTERT), telomeraz kompleksinin gerekli bir bileşenidir. c-Abl protein tirozin kinaz, DNA çift sarmalında kırıkların oluşması ile aktive olan ve telomer kontrolü esnasında bu kırıkların tamir edilmesine katılan bir proteindir. Telomer kısalması, hücre bölünmesini zamanla durduran bir işlemdir. Bu nedenle çalışmamızda DMBA indüklü ovotoksisite sonucu oluşan POY’de c-Abl ve mTERT’in önemli bir role sahip olabileceğini düşünmekteyiz. Buradan yola çıkarak günlük yaşamda sürekli olarak maaruz kalınan DMBA’nın ovaryumdaki oosit rezervi, oosit kalitesi ve granuloza hücreleri üzerindeki etkisini c-Abl (Abelson Tirozin Kinaz) ve mTERT (telomeraz katalitik altünitesi) belirteçleri ile açıklamayı hedefledik. Çalışmamızda postnatal (PND) 28 günlük BalbC türü farelere 7 gün boyunca susam yağı içerisinde çözülen 1mg/kg DMBA uygulaması yapıldı. İzole edilen ovaryum dokularında Hematoksilen-Eozin boyama ile morfolojik değerlendirme ve folikül sayımı yapıldı. İmmünofloresan yöntemi ile c-Abl ve mTERT lokalizasyonları gösterildi. Ayrıca ELISA, western blot ve qRT-PCR yöntemleri kullanılarak fare ovaryumunda DMBA tedavisinin telomeraz aktivitesi üzerine olan etkisi gösterildi. Ayrıca, Transmisyon Elektron Mikroskobi yöntemi ile oosit-granuloza hücresi arasındaki ilişki ultrastrüktürel düzeyde incelendi. Çalışmamızda DMBA indüklü ovotoksisite sonucu oluşan POY’de c-Abl ve mTERT, ilk defa gösterilmiştir. Bu proje ile DMBA uygulanmış fare ovaryumunda c-Abl ve mTERT ekspresyonlarındaki değişimin gösterilmesiyle, projemizin sonuçlarının POY’de erken over yaşlanması ve kadın infertilitesine ilişkin sinyal mekanizmalarına ışık tutacağını düşünmekteyiz.(TÜBİTAK-215S867)

Effects of rosmarinic acid on cognitive and biochemical alterations in ovariectomized rats treated with D-galactose

Introduction. Animal models designed to mimic certain features of Alzheimer’s disease (AD) can help us to in­crease our understanding of the underlying mechanisms of disease. Previous studies have revealed that long-term D-galactose injection combined with ovariectomy results in pathophysiologic alterations associated with AD. Thus, the aim of the present study was to investigate the effects of rosmarinic acid (RA) administration on pathological changes associated with ovariectomy and D-galactose injection, which serve as a two-insult model for AD. Material and methods. One hundred female Wistar rats were divided into five equal groups: control (C), Sham (Sh), rosmarinic acid treated (R), ovariectomized rats treated with D-galactose (OD), ovariectomized rats treated with D-galactose and rosmarinic acid (ODR) groups. D-galactose (80 mg/kg/day) was administered by i.p. injection and RA (50 mg/kg/day) was given via gavage for 60 days. Open field and Y-maze tests were used to assess locomotor activity and short-term spatial memory, respectively. Biochemical and histopathological analyses of the brain tissue were performed. Results. Open field testing showed that the locomotor activity and exploratory behavior of rats were prominent­ly impaired in the OD group as compared to the other studied groups. Similarly, Y-maze test results revealed a decrease of short-term spatial memory in the OD rats. A concomitant treatment with RA significantly restored altered locomotor activity and cognitive functions in the ODR group. Lipid peroxidation levels, cyclooxygen­ase-2 expression and prostaglandin E2 levels in the brain tissue were higher in the OD group and RA treatment inhibited these changes. AD-like histopathological alterations and amyloid b peptide (Ab) depositions were observed in the OD group. Normal cell structure and lower Ab depositions were observed in the ODR group compared with the OD group. Conclusions. RA could have the potential to prevent some psychological and biochemical alterations of brain tissue found in a rat model of AD probably by attenuating lipid peroxidation and inflammatory response

The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder marked by cell death in the Substantia nigra (SN). Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the phospholipid fraction of the brain and is required for normal cellular function. Glial cell line derived neurotrophic factor (GDNF) and neurturin (NTN) are very potent trophic factors for PD. The aim of the study was to evaluate the neuroprotective effects of GDNF and NTN by investigating their immunostaining levels after administration of DHA in a model of PD. For this reason we hypothesized that DHA administration of PD might alter GDNF, NTN expression in SN. MPTP neurotoxin that induces dopaminergic neurodegeneration was used to create the experimental Parkinsonism model. Rats were divided into; control, DHA-treated (DHA), MPTP-induced (MPTP), MPTP-induced+DHA-treated (MPTP+DHA) groups. Dopaminergic neuron numbers were clearly decreased in MPTP, but showed an increase in MPTP+DHA group. As a result of this, DHA administration protected dopaminergic neurons as shown by tyrosine hydroxylase immunohistochemistry. In the MPTP+DHA group, GDNF, NTN immunoreactions in dopaminergic neurons were higher than that of the MPTP group. In conclusion, the characterization of GDNF and NTN will certainly help elucidate the mechanism of DHA action, and lead to better strategies for the use of DHA to treat neurodegenerative diseases

The Healing Effects of Autologous Mucosal Grafts in Experimentally Injured Rabbit Maxillary Sinuses

Objectives Healing processes of the nose and paranasal sinuses are quite complex, and poorly understood. In this study, we aimed to compare the effect of mucosal autologous grafts on the degenerated rabbit maxillary sinus mucosa with spontaneous wound healing. It is hypothesized that mucosal grafts will enhance ciliogenesis and improve the morphology of regenerated cilia. Methods Ten female New Zealand rabbits were included in the study. They underwent external maxillary sinus surgery through a transcutaneous approach. A total of 20 maxillary sinuses were randomly divided into 2 groups: ‘spontaneous healing group’ and ‘autologous graft group.’ The animals were sacrificed at the 14th day after the surgery. Scanning electron microscope (SEM), and light microscope were used for the evaluation. Results Cellular composition of the graft group is better than the spontaneous healing group. The graft group had larger areas covered with ciliary epithelium than the spontaneous healing group, and the mean length of the cilias were also longer. Additionally, there were wider cilia with abnormal morphology areas in the spontaneous healing group. Conclusion In our opinion, covering of the denuded areas with a graft improves re-epithelization, and may prevent the early complications after sinus surgeries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries