A Broad Requirement for TLS Polymerases η and κ, and Interacting Sumoylation and Nuclear Pore Proteins, in Lesion Bypass during C. elegans Embryogenesis

Translesion synthesis (TLS) polymerases are specialized DNA polymerases capable of inserting nucleotides opposite DNA lesions that escape removal by dedicated DNA repair pathways. TLS polymerases allow cells to complete DNA replication in the presence of damage, thereby preventing checkpoint activation, genome instability, and cell death. Here, we characterize functional knockouts for polh-1 and polk-1, encoding the Caenorhabditis elegans homologs of the Y-family TLS polymerases η and κ. POLH-1 acts at many different DNA lesions as it protects cells against a wide range of DNA damaging agents, including UV, γ-irradiation, cisplatin, and methyl methane sulphonate (MMS). POLK-1 acts specifically but redundantly with POLH-1 in protection against methylation damage. Importantly, both polymerases play a prominent role early in embryonic development to allow fast replication of damaged genomes. Contrary to observations in mammalian cells, we show that neither POLH-1 nor POLK-1 is required for homologous recombination (HR) repair of DNA double-strand breaks. A genome-wide RNAi screen for genes that protect the C. elegans genome against MMS–induced DNA damage identified novel components in DNA damage bypass in the early embryo. Our data suggest SUMO-mediated regulation of both POLH-1 and POLK-1, and point towards a previously unrecognized role of the nuclear pore in regulating TLS

Неустойчивость двухслойных течений в проливах Черного моря

Рассмотрена плоская задача о прогрессивных гравитационных внутренних волнах в горизонтальном двухслойном течении Кельвина-Гельмгольца. Найдено аналитическое решение задачи и условия существования внутренних волн. Для течений с параметрами, типичными для пролива Босфор и Керченского пролива, рассчитаны характеристики бароклинных волн. В пространстве волновых чисел определены диапазоны устойчивости и неустойчивости двухслойных течений с характерными для этих проливов параметрами относительно малых возмущений в форме прогрессивных волн.Розглянуто плоску задачу про прогресивні гравітаційні внутрішні хвилі у горизонтальній двошаровій течії Кельвіна-Гельмгольца. Знайдено аналітичне рішення задачі та умови існування внутрішніх хвиль. Для течій з параметрами, типовими для протоки Босфор і Керченської протоки, розраховані характеристики бароклінних хвиль. У просторі хвильових чисел визначені діапазони стійкості і нестійкості двошарових течій з характерними для цих проток параметрами відносно малих збурень у формі прогресивних хвиль.The plane problem of the progressive internal gravity waves in a horizontal two-layer Kelvin-Helmholtz flow is considered. The analytical solution of the problem and the conditions of existence of internal waves are found. For the flows with the typical parameters for the Bosphorus Strait and the Strait of Kerch, characteristics of baroclinic waves are calculated. The stability and instability regimes of two-layer currents with characteristic parameters of these straits with respect to small wave disturbances are found in the space of wave numbers

FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Introduction Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort. Methods Protein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation. Results FGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member proteins. FGFR1 protein was more frequently highly expressed in human papillomavirus (HPV)-negative OPSCC than HPV-positive OPSCC (82 vs. 65 %; p = 0.008). Furthermore, protein expression of FGFR family members was not related to overall survival in OCSCC or OPSCC (p . 0.05). Conclusion FGFR family members are frequently highly expressed in OCSCC and OPSCC. These FGFR family member proteins are therefore potential targets for novel therapies that are urgently required to improve survival of OCSCC and OPSCC patients

Cell-Based Bone Tissue Engineering

The authors review the available data on bone tissue engineering and discuss possible new research areas that could help to make bone tissue engineering a clinical success

Implants in the severely resorbed mandibles: whether or not to augment? What is the clinician’s preference?

Contains fulltext : 96000.pdf (publisher's version ) (Open Access)INTRODUCTION: The aim of this study is to inventory in the Netherlands which therapy is the clinician's first choice when restoring the edentulous mandible. MATERIAL AND METHODS: A questionnaire was sent to all Dutch Oral and Maxillofacial surgeons. As part of this, the surgeons were invited to treat five virtual edentulous patients, differing only in mandibular residual height. RESULTS: In cases of a sufficient residual height of 15 mm, all surgeons were in favour to insert solely two implants to anchor an overdenture. In case of a residual height of 12 mm, 10% of the surgeons choose for an augmentation procedure. If a patient was presented with a mandibular height of 10 mm, already 40% of the OMF surgeons executed an augmentation procedure. Most (80%) surgeons prefer the (anterior) iliac crest as donor site. The choice of 'whether or not to augment' was not influenced by the surgeon's age; however, the hospital, where he was trained, did. Surgeons trained in Groningen were more in favour of installing short implants in mandibles with reduced vertical height. DISCUSSION: As the option overdenture supported on two interforaminal implants is reimbursed by the Dutch health assurance, this treatment modality is very popular in the Netherlands. From a point of costs and to minimize bypass comorbidity, surgeons should be more reluctant in executing augmentation procedures to restore the resorbed edentulous mandible as it is dated in literature that also in mandibles with a residual height of 10 mm or less, solely placing implants, thus without an augmentation procedure in advance, is a reliable treatment option

Naar landelijke learning communities: Leerervaringen uit twee jaar learing community logistiek in de leefbare stad

Learning communities kunnen een middel zijn om bij vraagstukken zoals logistiek in de leefbare stad, in een publiek-privaat samenwerkingsverband te leren, problemen op te lossen en te innoveren. Vanuit het CoE KennisDC Logistiek is door vier hogescholen de Learning Community Logistiek in de Leefbare Stad uitgevoerd. Op basis van het Conceptueel raamwerk Publiek-Private Learning Communities wordt gereflecteerd hierop. Hieruit zijn inzichten gekomen voor de verdere uitrol van het concept learning communities binnen het CoE KennisDC Logistiek. De learning community logistiek in de leefbare stad heeft een mooie rijkheid aan hedendaags praktijkgericht onderzoek en praktijkcases laat zien en heeft partijen bij elkaar gebracht. De meerwaarde is mede erkend doordat tijdens de Pareltjesdag van het CoE KennisDC Logistiek, de learning community de publieksprijs 2023 in ontvangst heeft mogen neme

Cell based bone tissue engineering in jaw defects

In 6 patients the potency of bone tissue engineering to reconstruct jaw defects was tested. After a bone marrow aspirate was taken, stem cells were cultured, expanded and grown for 7 days on a bone substitute in an osteogenic culture medium to allow formation of a layer of extracellular bone matrix. At the end of the procedure, this viable bone substitute was not only re-implanted in the patient, but also simultaneously subcutaneously implanted in mice to prove its osteogenic potency. In all patients, a viable bone substitute was successfully constructed, which was proven by bone formation after subcutaneous implantation in mice (ectopic bone formation). However, the same construct was reluctant to form bone in patients with intra-oral osseous defects (orthotopic bone formation). Although biopsies, taken 4 months after reconstructing the intra-oral bone defect, showed bone formation in 3 patients, only in 1 patient bone formation was induced by the tissue-engineered construct. Although bone tissue engineering has proven its value in animal studies, extra effort is needed to make it a predictable method for reconstruction jaw defects in humans. To judge its benefit, it is important to differentiate between bone formation induced by cells from the border of the osseous defect (osteoconduction) in relation to bone matrix produced by the implanted cells (osteogenesis)

Factors influencing neck and shoulder function after oral oncology treatment: a five-year prospective cohort study in 113 patients

Contains fulltext : 204583.pdf (publisher's version ) (Open Access