Nuclear Factor I-C acts as a regulator of hepatocyte proliferation at the onset of liver regeneration

BACKGROUND & AIMS: Knockout studies of the murine Nuclear Factor I-C (NFI-C) transcription factor revealed abnormal skin wound healing and growth of its appendages, suggesting a role in controlling cell proliferation in adult regenerative processes. Liver regeneration following partial hepatectomy (PH) is a well-established regenerative model whereby changes elicited in hepatocytes lead to their rapid and phased proliferation. Although NFI-C is highly expressed in the liver, no hepatic function was yet established for this transcription factor. This study aimed to determine whether NFI-C may play a role in hepatocyte proliferation and liver regeneration. METHODS: Liver regeneration and cell proliferation pathways following two-thirds PH were investigated in NFI-C knockout (ko) and wild-type (wt) mice. RESULTS: We show that the absence of NFI-C impaired hepatocyte proliferation because of plasminogen activator I (PAI-1) overexpression and the subsequent suppression of urokinase plasminogen activator (uPA) activity and hepatocyte growth factor (HGF) signalling, a potent hepatocyte mitogen. This indicated that NFI-C first acts to promote hepatocyte proliferation at the onset of liver regeneration in wt mice. The subsequent transient down regulation of NFI-C, as can be explained by a self-regulatory feedback loop with transforming growth factor beta 1 (TGF-ß1), may limit the number of hepatocytes entering the first wave of cell division and/or prevent late initiations of mitosis. CONCLUSION: NFI-C acts as a regulator of the phased hepatocyte proliferation during liver regeneration.

The Efficacy of a Novel Microbial 6-Phytase Expressed in Aspergillus oryzae on the Performance and Phosphorus Utilization of Cold- and Warm-Water Fish: Rainbow Trout, Oncorhynchus mykiss , and Nile Tilapia, Oreochromis niloticus

The efficacy and tolerance of a novel microbial 6-phytase were investigated in rainbow trout, Oncorhynchus mykiss, and Nile tilapia, Oreochromis niloticus. Reference diets were sufficient in available phosphorus (P). The test diet limiting in available P was supplemented with phytase at 500, 1000, or 2000 phytase units/kg feed. The enzyme was effective in increasing total P apparent digestibility coefficient in relation to increasing the dose of phytase in rainbow trout and Nile tilapia. Zinc apparent digestibility improved in relation to phytase supplementation in rainbow trout. P release due to phytase supplementation ranged from 0.06 to 0.18% P/kg feed in rainbow trout and from 0.13 to 0.26% P/kg feed in Nile tilapia. A 58-d performance trial was conducted to evaluate tolerance of fish to phytase supplementation. Dietary treatments consisted of a basal diet without phytase or supplemented with 2000 and 200,000 phytase units/kg feed. Results indicate that this novel microbial 6-phytase is well tolerated by fish. Significant improvements for growth as well as feed conversion ratio were observed when the phytase was fed at 2000 phytase units/kg feed. This phytase is proven efficient in releasing P from phytate and could be added when plants are used for fish meal replacement in diets for salmonid and omnivorous fish.

Forest regeneration capacity and its enhancement by forest management and silviculture in Cabo Delgado

SDC has been involved in rural development in Cabo Delgado for more than 30 years. Shortly after the independence of Mozambique, projects in water supply and integrated rural development were initiated. The silvoagropastoral project FO9 based in Mueda was a very early experience in forestry in Cabo Delgado. Andreas Kläy was responsible for the forestry sector in FO9 for 3 years in the early 1980s and had an opportunity to initiate an exchange of ideas and experience in rural development theory and approaches with Yussuf Adam, who was doing research in human anthropology and history in the province. 25 years later, the current situation of forest management in Cabo Delgado was reassessed, with a specific focus on concessions in the North. The opportunity for a partnership between the MITI SA, the University of Eduardo Mondlane, and CDE was created on the basis of this preliminary study1. The aim of this partnership is to generate knowledge and develop capacity for sustainable forest management. The preliminary study showed that “…we have to face weaknesses and would like to start a learning process with the main institutions, organisations, and stakeholder groups active in forest management and research in the North of Cabo Delgado. This learning process will involve studies supported by competent research institutions and workshops …” The specific objectives of ESAPP project Q804 are the following: 1. Contribute to understanding of the forestry sector; 2. Capacity development for professionals and academics; 3. Support for the private sector and the local forest service; 4. Support data generation at Cabo Delgado's Provincial Service; 5. Capacity development for Swiss academic institutions (CDE and ETHZ). A conceptual planning platform was elaborated as a basis for cooperation and research in the partnership (cf. Annex 1). The partners agreed to work on two lines of research: biophysical and socio-economic. In order to ensure a transdisciplinary approach, disciplinary research is anchored in common understanding in workshops based on the LforS methods. These workshops integrate the main stakeholders in the local context of the COMADEL concession in Nangade District managed by MITI SA, and take place in the village of Namiune. The research team observed that current management schemes consist mainly of strategies of nature mining by most stakeholders involved. Institutional settings - formal and informal - have little impact due to weak capacity at the local level and corruption. Local difficulties in a remote rural area facilitate external access to resources and are perpetuated by the loss of benefits. The benefits of logging remain at the top level (economic and political elites). The interests of the owners of the concession in stopping the loss of resources caused by this regime offers a unique opportunity to intervene in the logic of resource degradation and agony in rural development and forest management.

Cell-to-cell communication--periodontal regeneration.

BACKGROUND Although regenerative treatment options are available, periodontal regeneration is still regarded as insufficient and unpredictable. AIM This review article provides scientific background information on the animated 3D film Cell-to-Cell Communication - Periodontal Regeneration. RESULTS Periodontal regeneration is understood as a recapitulation of embryonic mechanisms. Therefore, a thorough understanding of cellular and molecular mechanisms regulating normal tooth root development is imperative to improve existing and develop new periodontal regenerative therapies. However, compared to tooth crown and earlier stages of tooth development, much less is known about the development of the tooth root. The formation of root cementum is considered the critical element in periodontal regeneration. Therefore, much research in recent years has focused on the origin and differentiation of cementoblasts. Evidence is accumulating that the Hertwig's epithelial root sheath (HERS) has a pivotal role in root formation and cementogenesis. Traditionally, ectomesenchymal cells in the dental follicle were thought to differentiate into cementoblasts. According to an alternative theory, however, cementoblasts originate from the HERS. What happens when the periodontal attachment system is traumatically compromised? Minor mechanical insults to the periodontium may spontaneously heal, and the tissues can structurally and functionally be restored. But what happens to the periodontium in case of periodontitis, an infectious disease, after periodontal treatment? A non-regenerative treatment of periodontitis normally results in periodontal repair (i.e., the formation of a long junctional epithelium) rather than regeneration. Thus, a regenerative treatment is indicated to restore the original architecture and function of the periodontium. Guided tissue regeneration or enamel matrix proteins are such regenerative therapies, but further improvement is required. As remnants of HERS persist as epithelial cell rests of Malassez in the periodontal ligament, these epithelial cells are regarded as a stem cell niche that can give rise to new cementoblasts. Enamel matrix proteins and members of the transforming growth factor beta (TGF-ß) superfamily have been implicated in cementoblast differentiation. CONCLUSION A better knowledge of cell-to-cell communication leading to cementoblast differentiation may be used to develop improved regenerative therapies to reconstitute periodontal tissues that were lost due to periodontitis.

Alveolar bone regeneration in response to local application of calcitriol in vitamin D deficient rats

AIM Vitamin D deficiency is considered to diminish bone regeneration. Yet, raising the serum levels takes months. A topic application of the active vitamin D metabolite, calcitriol, may be an effective approach. Thus, it becomes important to know the effect of vitamin D deficiency and local application on alveolar bone regeneration. MATERIAL AND METHODS Sixty rats were divided into three groups; two vitamin depletion groups and a control group. Identical single defects (2 mm diameter) were created in the maxilla and mandible treated with calcitriol soaked collagen in one deficiency group while in the other two groups not. Histomorphometric analysis and micro CTs were performed after 1 and 3 weeks. Serum levels of 25(OH)D3 and PTH were determined. RESULTS Bone formation rate significantly increased within the observation period in all groups. Bone regeneration was higher in the maxilla than in the mandible. However, bone regeneration was lower in the control group compared to vitamin depletion groups, with no significant effects by local administration of calcitriol (micro CT mandible p = 0.003, maxilla p < 0.001; histomorphometry maxilla p = 0.035, mandible p = 0.18). CONCLUSION Vitamin D deficiency not necessarily impairs bone regeneration in the rat jaw and a single local calcitriol application does not enhance healing.

Efficiency of In Vitro Regeneration is Dependent on the Genotype and Size of Explant in Tef [Eragrostis tef (Zucc.) Trotter]

Tef [Eragrostis tef (Zucc.) Trotter] is the major cereal crop in the Horn of Africa particularly in Ethiopia where it is staple food for about 50 million people. Its resilience to extreme environmental conditions and high in nutrition makes tef the preferred crop among both farmers and consumers. The efficiency of in vitro regeneration plays significant role in the improvement of crops. We investigated the efficiency of regeneration in 18 tef genotypes (15 landraces and three improved varieties) using three sizes of immature embryos (small, intermediate and large) as an explant. In vitro regeneration was significantly affected by the genotype and the size of the immature embryo used as a donor. Intermediate-size immature embryos which were 101-350 µm long led to the highest percentage of regeneration. Interestingly, the three improved varieties presented very low regeneration efficiencies whereas the landrace Manyi resulted in consistently superior percentage of in vitro regeneration from all three sizes of explants. The findings of this work provide useful insight into the tef germplasm amenable for the regeneration technique which has direct application in techniques such as transformation. It also signifies the importance of using tef landraces instead of improved varieties for in vitro regeneration.

Plant regeneration directs changes in grassland composition after extreme drought: a 13-year study in southern Switzerland

1. The cover of plant species was recorded annually from 1988 to 2000 in nine spatially replicated plots in a species-rich, semi-natural meadow at Negrentino (southern Alps). This period showed large climatic variation and included the centennial maximum and minimum frequency of days with ≥ 10 mm of rain. 2. Changes in species composition were compared between three 4-year intervals characterized by increasingly dry weather (1988–91), a preceding extreme drought (1992–95), and increasingly wet weather (1997–2000). Redundancy analysis and anova with repeated spatial replicates were used to find trends in vegetation data across time. 3. Recruitment capacity, the potential for fast clonal growth and seasonal expansion rate were determined for abundant taxa and tested in general linear models (GLM) as predictors for rates of change in relative cover of species across the climatically defined 4-year intervals. 4. Relative cover of the major growth forms present, graminoids and forbs, changed more in the period following extreme drought than at other times. Recruitment capacity was the only predictor of species’ rates of change. 5. Following perturbation, re-colonization was the primary driver of vegetation dynamics. The dominant grasses, which lacked high recruitment from seed, therefore decreased in relative abundance. This effect persisted until the end of the study and may represent a lasting response to an extreme climatic event.

Enamel matrix derivative and bone grafts for periodontal regeneration of intrabony defects. A systematic review and meta-analysis

OBJECTIVE The aim of the present systematic review and meta-analysis was to assess the clinical efficacy of regenerative periodontal surgery of intrabony defects using a combination of enamel matrix derivative (EMD) and bone graft compared with that of EMD alone. MATERIALS AND METHODS The Cochrane Oral Health Group specialist trials, MEDLINE, and EMBASE databases were searched for entries up to February 2014. The primary outcome was gain of clinical attachment (CAL). Weighted means and forest plots were calculated for CAL gain, probing depth (PD), and gingival recession (REC). RESULTS Twelve studies reporting on 434 patients and 548 intrabony defects were selected for the analysis. Mean CAL gain amounted to 3.76 ± 1.07 mm (median 3.63 95 % CI 3.51-3.75) following treatment with a combination of EMD and bone graft and to 3.32 ± 1.04 mm (median 3.40; 95 % CI 3.28-3.52) following treatment with EMD alone. Mean PD reduction measured 4.22 ± 1.20 mm (median 4.10; 95 % CI 3.96-4.24) at sites treated with EMD and bone graft and yielded 4.12 ± 1.07 mm (median 4.00; 95 % CI 3.88-4.12) at sites treated with EMD alone. Mean REC increase amounted to 0.76 ± 0.42 mm (median 0.63; 95 % CI 0.58-0.68) at sites treated with EMD and bone graft and to 0.91 ± 0.26 mm (median 0.90; 95 % CI 0.87-0.93) at sites treated with EMD alone. CONCLUSIONS Within their limits, the present results indicate that the combination of EMD and bone grafts may result in additional clinical improvements in terms of CAL gain and PD reduction compared with those obtained with EMD alone. The potential influence of the chosen graft material or of the surgical procedure (i.e., flap design) on the clinical outcomes is unclear. CLINICAL RELEVANCE The present findings support the use of EMD and bone grafts for the treatment of intrabony periodontal defects.

Biomaterials for promoting periodontal regeneration in human intrabony defects: a systematic review

Intrabony periodontal defects are a frequent complication of periodontitis and, if left untreated, may negatively affect long-term tooth prognosis. The optimal outcome of treatment in intrabony defects is considered to be the absence of bleeding on probing, the presence of shallow pockets associated with periodontal regeneration (i.e. formation of new root cementum with functionally orientated inserting periodontal ligament fibers connected to new alveolar bone) and no soft-tissue recession. A plethora of different surgical techniques, often including implantation of various types of bone graft and/or bone substitutes, root surface demineralization, guided tissue regeneration, growth and differentiation factors, enamel matrix proteins or various combinations thereof, have been employed to achieve periodontal regeneration. Despite positive observations in animal models and successful outcomes reported for many of the available regenerative techniques and materials in patients, including histologic reports, robust information on the degree to which reported clinical improvements reflect true periodontal regeneration does not exist. Thus, the aim of this review was to summarize, in a systematic manner, the available histologic evidence on the effect of reconstructive periodontal surgery using various types of biomaterials to enhance periodontal wound healing/regeneration in human intrabony defects. In addition, the inherent problems associated with performing human histologic studies and in interpreting the results, as well as certain ethical considerations, are discussed. The results of the present systematic review indicate that periodontal regeneration in human intrabony defects can be achieved to a variable extent using a range of methods and materials. Periodontal regeneration has been observed following the use of a variety of bone grafts and substitutes, guided tissue regeneration, biological factors and combinations thereof. Combination approaches appear to provide the best outcomes, whilst implantation of alloplastic material alone demonstrated limited, to no, periodontal regeneration.

Wound models for periodontal and bone regeneration: the role of biologic research

The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal-regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase.