Downregulation of Yap1 during limb regeneration results in defective bone formation in axolotl

The Hippo pathway plays an imperative role in cellular processes such as differentiation, regeneration, cell migration, organ growth, apoptosis, and cell cycle. Transcription coregulator component of Hippo pathway, YAP1, promotes transcription of genes involved in cell proliferation, migration, differentiation, and suppressing apoptosis. However, its role in epimorphic regeneration has not been fully explored. The axolotl is a well-established model organism for developmental biology and regeneration studies. By exploiting its remarkable regenerative capacity, we investigated the role of Yap1 in the early blastema stage of limb regeneration. Depleting Yap1 using gene-specific morpholinos attenuated the competence of axolotl limb regeneration evident in bone formation defects. To explore the affected downstream pathways from Yap1 down-regulation, the gene expression profile was examined by employing LC-MS/MS technology. Based on the generated data, we provided a new layer of evidence on the putative roles of increased protease inhibition and immune system activities and altered ECM composition in diminished bone formation capacity during axolotl limb regeneration upon Yap1 deficiency. We believe that new insights into the roles of the Hippo pathway in complex structure regeneration were granted in this study.Science Academ

Managing health and safety risks in restoration/renovation of historic buildings

Restoration and renovation of historic buildings aim to preserve and sustain those buildings with their original state. This fact is important to conserve historical values for a society as well as for sustainable city planning. Restoration projects have their own occupational health and safety risks and differ from ordinary construction projects. Additionally, implementation of safety measures according to the current regulations are very difficult due to geometrical structure, type of material used and preservation consideration for the structural and architectural elements of the historic buildings. Since the risks as well as mitigation and abatement techniques differ from conventional buildings, restoration projects require paying attention to establish safety and health plan and risk management system to implement safety and health measures. In this paper, different health and safety risks of the restoration projects are discussed. Different safety and health practices are dealt with ordinary structures, risk assessment is made according to specific risks, findings are revealed in some certain restoration projects in Turkey and a new approach for health and safety management in restoration projects is introduced.Publisher's Versio

On the impacts of preferential trade agreements on Turkeys's foreign trade

Eine große Anzahl von Faktoren wie Verbraucherpräferenzen, Technologie und Beschäftigungsmerkmalen fördert den Außenhandel zwischen den Ländern. Die globalen wirtschaftlichen Entwicklungen, die zu Beginn des 20. Jahrhunderts entstanden und sich Mitte der gleichen Epoche beschleunigten, sowie die Vernetzung zwischen den Ländern erhöhten das Handelsvolumen zwischen den Ländern. Parallel zu dem steigenden Handelsvolumen wurden neue ökonomische Theorien und Modelle entwickelt, um die Ursachen und Folgen des internationalen Handels zu erklären. Eines dieser bedeutenden Modelle ist das Gravitationsmodell, welches das Ausmaß des Handels zwischen Ländern als eine Funktion der wirtschaftlichen Größe eines Landes, dessen Entfernung zu Partnerländern sowie anderen kulturellen und wirtschaftlichen Beziehungen (z.B. angeschlossene Organisationen, gemeinsame Grenzen, Visumfreiheit, etc.) berechnet. In dieser Studie werden mithilfe des Gravitationsmodells Auswirkungen der Mitgliedschaft der Türkei in der Zollunion auf deren Außenhandel untersucht. Für die Berechnung mit dem Gravitationsmodell zieht die vorliegende Studie jährlich erhobene Daten von Handelspartnern der Türkei heran, da die Studie ihren Fokus auf die Auswirkungen des türkischen Beitritts in die Zollunion (CU) der Europäischen Union (EU) und anderer präferenzielle Handelsabkommen (PTA) auf den türkischen Ex- und Import legt. Die Auswirkungen der Zollunion und präferenziellen Handelsabkommen auf den Außenhandel der Türkei werden verglichen. Die Studie besteht aus sechs Kapiteln. Das erste Kapitel stellt das Thema vor. Das zweite Kapitel beschreibt den Außenhandel und die Faktoren, welche den internationalen Handel beeinflussen. Kapitel drei diskutiert präferenzielle Handelsabkommen und Zollunionen und beschreibt kurz die Vorteile von Freihandelsabkommen. Die historische Entwicklung des Beitrittsprozess der Türkei in die Zollunion, das Konzept der Zollunion und die Auswirkungen von Zollunionen auf die Volkswirtschaften der Mitgliedsländer werden in diesem Kapitel ebenso genauer beleuchtet. Das vierte Kapitel beschreibt das Gravitationsmodell. Die Beiträge anderer Forscher und eine Literaturübersicht über das Gravitationsmodell werden hier vorgestellt. Darüber hinaus sind in diesem Kapitel die Variablen, die das Gravitationsmodell verwendet, und die Definitionen dieser Variablen angegeben. Schließlich stellt dieses Kapitel eine Überprüfung der Literatur über das Gravitationsmodell an, welches den türkischen Außenhandel erklärt. Das fünfte Kapitel befasst sich mit der Anwendung des Gravitationsmodells auf den Außenhandel der Türkei. Nach Erläuterung der Grundlagen der Regressionsanalyse werden die Auswirkungen von Zollunionen und präferenziellen Handelsabkommen auf den Außenhandel der Türkei analysiert. Die Ergebnisse dieser Analyse werden anschließend im Detail diskutiert. Das abschließende Kapitel - Kapitel Sechs – ist die Schlussfolgerung dieser Studie.A large number of factors such as consumer preferences, technology and labour characteristics encourage international trade between countries. The global economic developments, which emerged at the beginning of the 20th century and accelerated towards the middle of the same era and integration between countries, have increased the volume of trade between countries. In parallel with the increasing volume of trade new economic theories and models have emerged to explain the causes and consequences of international trade. The Gravity Model is one such model that has been important in explaining the structure and direction of international trade. The gravity model estimates the extent of trade flows between countries as a function of country’s economic size, their distance to trade partners as well as other cultural and economic links between pairs of countries (such as affiliated organizations, common borders, visa exemptions, etc). In this study, the effects of Customs Union (CU) membership on Turkey's foreign trade are examined using the Gravity Model. The Gravity Model is estimated using annual data on a large sample of Turkey’s trade partners, with the focus of the study being on the effects of a CU with the European Union (EU) and other Preferential Trade Agreements (PTAs) on Turkey’s exports and imports. The effects of CUs and PTAs on Turkey´s foreign trade are then compared. The study consists of six main chapters. The first chapter introduces the topic. The second chapter discusses foreign trade and the factors affecting international trade in a theoretical way. Chapter three discusses PTAs and CUs and briefly describes the benefits of FTAs. A discussion of the historical development of Turkey's CU accession process, the concept of the CU and the impacts of CU on economies of member countries is also provided in this chapter. The fourth chapter describes the Gravity Model. The contributions of other researchers and a literature review on Gravity Model are presented here. Furthermore, the variables used in the gravity model and the definitions of these variables are stated here. Finally, this chapter presents a review of literature using the gravity model to explain Turkey's foreign trade. The fifth chapter presents an application of the gravity model on Turkey's foreign trade. After explaining the basics about regression analysis, the impacts of CUs and PTAs on Turkey´s foreign trade are analyzed. The results of this analysis are then discussed in detail. The final chapter – Chapter Six – concludes

Consequences of neurite transection in vitro

WOS: 000309967300004PubMed ID: 20121423In order to quantify degenerative and regenerative changes and analyze the contribution of multiple factors to the outcome after neurite transection, we cultured adult mouse dorsal root ganglion neurons, and with a precise laser beam, we transected the nerve fibers they extended. Cell preparations were continuously visualized for 24 h with time-lapse microscopy. More distal cuts caused a more elongated field of degeneration, while thicker neurites degenerated faster than thinner ones. Transected neurites degenerated more if the uncut neurites of the same neuron simultaneously degenerated. If any of these uncut processes regenerated, the transected neurites underwent less degeneration. Regeneration of neurites was limited to distal cuts. Unipolar neurons had shorter regeneration than multipolar ones. Branching slowed the regenerative process, while simultaneous degeneration of uncut neurites increased it. Proximal lesions, small neuronal size, and extensive and rapid neurite degeneration were predictive of death of an injured neuron, which typically displayed necrotic rather than apoptotic form. In conclusion, this in vitro model proved useful in unmasking many new aspects and correlates of mechanically-induced neurite injury.Yuzuncu Yil University Directorate of Scientific Research Projects [TF073]This study was supported by the Yuzuncu Yil University Directorate of Scientific Research Projects (grant no. TF073)

Longitudinal metabolomics analysis reveals the acute effect of cysteine and NAC included in the combined metabolic activators

Growing evidence suggests that the depletion of plasma NAD+ and glutathione (GSH) may play an important role in the development of metabolic disorders. The administration of Combined Metabolic Activators (CMA), consisting of GSH and NAD+ precursors, has been explored as a promising therapeutic strategy to target multiple altered pathways associated with the pathogenesis of the diseases. Although studies have examined the therapeutic effect of CMA that contains N-acetyl-L-cysteine (NAC) as a metabolic activator, a system-wide comparison of the metabolic response to the administration of CMA with NAC and cysteine remains lacking. In this placebo-controlled study, we studied the acute effect of the CMA administration with different metabolic activators, including NAC or cysteine with/without nicotinamide or flush free niacin, and performed longitudinal untargeted-metabolomics profiling of plasma obtained from 70 well-characterized healthy volunteers. The time-series metabolomics data revealed the metabolic pathways affected after the administration of CMAs showed high similarity between CMA containing nicotinamide and NAC or cysteine as metabolic activators. Our analysis also showed that CMA with cysteine is well-tolerated and safe in healthy individuals throughout the study. Last, our study systematically provided insights into a complex and dynamics landscape involved in amino acid, lipid and nicotinamide metabolism, reflecting the metabolic responses to CMA administration containing different metabolic activators.PoLiMeR Innovative Training Network ; SNIC ; ScandiBio Therapeutics ; U.S. Food and Drug Administration ; H2020 Marie Skłodowska-Curie Actions ; National Arts Council - Singapore ; Knut och Alice Wallenbergs Stiftelse ; Chinese Medical Association ; Horizon 202

Sabit Tahar Planı Ile Değişik Dokuma Örgüleri Türetme Yöntemi Geliştirme

Dokuma işleminde kumaş örgüsünü oluşturmanın temel araçları, ağızlık açma mekanizması diye bilinen desenlendirme donanımının yeteneği (örneğin kamlı, armürlü) ve uygulanan tahar planıdır. Bunlardan birinde yapılan bir değişiklik kumaşın örgü yapısında da kendisini gösterecektir. Kullanılan dokuma makinası özelliklerine göre çerçeve hareketlerini değiştirmenin zorluk derecesi ve süresi de değişecektir. Diğer taraftan tahar planı değişikliği genel olarak benzer özellikler gösterir. Çerçeve hareketini değiştirmenin daha kolay olduğu tezgah tiplerinde, örneğin armürlü, desen değişimlerinde tahar planı değişikliği yerine çerçeve hareketlerinin yani bunu belirleyen armür raporunun değiştirilmesi tercih edilir. Bu projenin amacı da bu tür tezgahlarda farklı örgülerin dokunmasına olanak sağlayacak ortak tahar planları belirleyebilecek yöntemleri geliştirmek olacaktır. Böylece bu tür makinalarda, aynı tahar planı kullanarak farklı kumaş görünümleri ya da desenleri elde etmenin daha pratik ve sistematik bir yöntemi ortaya konulacaktır. Dokuma kumaşları desenlendirme sürecinde ortak tahar planları bazında, farklı örgüler geliştirme sistematiği ele alınacak ve buna yönelik modelleme çalışmaları yapılmıştır. Günümüzde genellikle sıra tahar yöntemi kullanarak basit değişiklikler ile farklılaşma yapılmaktadır. Rekabetin ve ürün çeşitliliğin arttığı bir dönemde, daha kısa bir hazırlık süresiyle dolayısıyla bir maliyet avantajıyla farklı kumaş ürünleri geliştirip dokuyabilmek büyük avantaj sağlayacaktır. Bu projede hedeflenen çıktılar hem akademik hem de endüstriyel nitelik taşımaktadır. Dokuma kumaş desenlendirmesinde örgü, tahar ve çerçeve hareket planları birbirleriyle bağlantılı sistemlerdir. Herhangi ikisinin belirlenmesinden sonra üçüncü plan da bunların birleşimi olarak kendiliğinden ortaya çıkar. Dolayısıyla bu ilişkiyi modellemek ve sabit tahar planı üzerinden farklı çerçeve hareket planı geliştirme yöntemleri uygulayarak, değişik örgü planları ortaya çıkarmanın sistematiğini araştırmak özgün bir akademik çalışma olmuştur. Bu alanda yapılmış çalışma ve araştırma sayısı da, eski dönemlerde yapılmış çok az sayıda çalışmalarla sınırlıdır. Proje çalışması endüstriyel açıdan da önemli bir çıktı sağlama potansiyeli vardır. Armürlü dokuma makinalarında, daha sistematik ve ekonomik bir örgü geliştirme yöntemine yönelik ip uçları içermektedir. 12, 18 ve 20 çerçeve üzerinden yapılan sıra taharlar en üretken çözüm seçeneği olarak öne çıkmaktadır.Basic means of patterning in weaving are the capability and setting of shedding mechanism (eg. tappet, cam , dobby) and warp draft plan. Any change in one of them will result in variation of the woven fabric. Depending on the type of the weaving machine, the difficulty and set-up period of heald frames lifting plan would vary. On the other hand change of draft plan in any looms would be approximately similar. In the case of looms where changing the dobby plan (based on heald frames lifting plan) is much easier than changing the draft plan such as dobby looms, shifting of the dobby plan is preferred. The purpose of this project is to examine the potential of common draft plans which would enable to weave a variety of different weaves. By developing common draft plans for such looms, an easy and systematic method of woven fabric patterning would be possible. A systematic approach based on a common and fixed draft plan for developing different patterns in woven fabrics is analysed and new models are introduced. Currently, straight draft technique is widely used in order to apply variation in patterning. As the competition and product diversification are fiercely increasing, varied product development with a shorter preparation period and cost gain would be very advantageous. The outcomes of this project have both academic and industrial importance. In design of woven fabrics, weave report, draft plan and frame lifting plan are dependent on each other. Having defined any two, the third one is generated as the resultant of the two plans. Modelling of this relationship and applying different warp lifting plans on the base of constant draft plan so as to develop varied weaves appears to be an original academic research. The research work carried out on this topic is very few and limited with very earlier works. The outputs of this project may have an impact on industrial practices. The principles and important clues towards systematic and more economical weave developments in dobby weaving are introduced. It appears that straight draft with 12, 18 and 20 frames are the most productive settings

Development of a chemogenetic approach to manipulate intracellular pH

Chemogenetic Operation of iNTRacellular prOton Levels(pH-Control)is a novel substrate-based enzymatic method that enables precise spatiotemporalcontrol of ultralocal acidification in cultured cell lines and primaryneurons. The genetically encoded biosensor SypHer3s showed that pH-Controleffectively acidifies cytosolic, mitochondrial, and nuclear pH exclusivelyin the presence of beta-chloro-d-alanine in living cellsin a concentration-dependent manner. The pH-Control approach is promisingfor investigating the ultralocal pH imbalance associated with manydiseases.CE254SWXHI ; NN254SWPZX ; CP254SWT2