Cellular Mechanisms of Mammalian Liver Regeneration

ABSTRACT CELLULAR MECHANISMS OF MAMMALIAN LIVER REGENERATION Kilangsungla Yanger Ben Z. Stanger The liver is an essential organ that aids in metabolic processes, protein synthesis and detoxification of harmful substances. As the centre for detoxification, the liver is able to compensate for this routine damage with its robust regenerative ability. All vertebrate livers, for example, can make up for tissue mass loss (via surgical excision of a portion of the liver) by replication of their differentiated cells within the remnant lobes. These differentiated cells include parenchymal cells such as the hepatocytes and biliary epithelial cells (BECs) and also non-parenchymal cells. Despite the proliferative capacity exhibited by hepatocytes, the mechanism for how the liver regenerates after toxin injuries is debated. The liver is thought to utilize facultative stem cells (FSCs) originating from the BECs, often referred to as oval cells, for regeneration following toxin-based injury. However, the notion that oval cells act as stem cells has been based largely on in vitro studies and transplantation models; where lineage tracing has been employed, results have been conflicting. This thesis work employs multiple genetic tools to lineage trace the origin and contribution of various cell populations to liver regeneration in vivo. The findings reveal that contrary to stem cell-based models of regeneration, virtually all new hepatocytes come from pre-existing hepatocytes with no evidence of BECs functioning as FSCs. Instead, hepatocyte lineage tracing reveals in addition to replication, they can function as FSCs. Upon perturbations including toxin injuries, they undergo a hepatocyte-to-BEC reprogramming process in vivo. Cellular reprogramming is the ability to interconvert distinct cell types with defined factors. This phenomenon has rarely been observed in vivo without exogenous factors. However, a detailed in vivo analysis reveals hepatocytes undergoing this cellular reprogramming process in a robust and step-wise manner involving both morphological and transcriptional changes. This hepatocyte-to-BEC reprogramming requires Notch signalling, similar to how the pathway functions in BEC-specification during liver development. These results provide direct evidence that mammalian regeneration prompts extensive and dramatic changes in cellular identity under various perturbations and thus can also serve as a cellular source for various diseases and potentially for therapy involving BEC paucity and dysfunction

Extending a Helping Hand in Child- Centered Disaster Preparedness

Eastern Visayas State University (EVSU), Tacloban City, Philippines has a strong formal partnership with Save the Children, an International non- government organization, in technical assistance and capability building program for Local Disaster Risk Reduction Management Officers (LDRRMO’s) to help communities avert loss of lives during the occurrence of natural hazards. This study employed a descriptive research design to determine the usefulness and applicability of the EVSU-initiated extension activity on mentors’ capability building on comprehensive Community-Based Disaster Risk Reduction Management (CBDRRM) which highlighted the role of children in Barangay DRRM plans. Through a survey questionnaire it was found out that 71% of the respondents strongly agree that the approach was useful in understanding the situation of the children during emergencies, 62% strongly agree that they understood the basic rights of a child anchored on the United Nations Convention on the Rights of Children (UNCRC) and how this can be protected during disasters, while 57 % strongly believe that they can apply what they have learned.. Therefore, the mentors’ capability building initiative is useful and applicable but there is a need to generate more resources to be effective in their ability to mentor LDRRMOs in CBDRRM Planning.

Experimental Restoration of Mesic and Wet Forests in Former Pastureland, Kahuku Unit, Hawai`i Volcanoes National Park

Reports were scanned in black and white at a resolution of 600 dots per inch and were converted to text using Adobe Paper Capture Plug-in.The Kahuku unit of Hawaii Volcanoes National Park (HAVO) contains seven thousand acres of former forest that was converted to pasture for grazing cattle. There were several phases of forest clearing and pasture development (Parker Ranch 1912-1947, James Glover 1947-1958, and Damon Estate 1958-2000) creating an open pasture with scattered native trees and small remnant stands of native species. In 2005, methods to facilitate forest recovery were tested in four ungulate-proof exclosures (four hectares each). Within the exclosures, three temporary grass removal treatments (herbicide, soil turnover, and herbicide/soil turnover) were tested with the objective of finding a method that best promoted native forest recovery in conjunction with ungulate exclusion. In addition to monitoring plant recruitment from the natural seed bank in the soil, establishment by direct seeding and planting of native species in the different treatments was evaluated. By year one, rapid re-establishment of alien grasses occurred in all removal treatments, but was slowest in plots that received a combination of soil turnover and herbicide. Natural native plant recovery was evident in all grass removal treatments with a limited number of seedlings in the untreated grass control. Plant establishment from direct seeding for koa and pilo was highest in the combination soil turnover and herbicide treatment. No seedlings of Pipturus albidus (māmaki), Cheirodendron trigynum (‘ōlapa), Coprosma pubens (pilo), Myoporum sandwicense (naio) and very few Acacia koa (koa) and Metrosideros polymorpha (‘ōhi‘a) were observed outside of ungulate-proof exclosures. Planted seedling survival was moderate to high with no significant differences among sites and treatments (57-70%). Based on these results, temporary suppression of alien grasses in conjunction with ungulate exclusion can facilitate recovery of native species once abundant in the Kahuku region

Tratamiento quirúrgico de una perforación radicular como complicación endodóntica. Presentación de un caso

RESUMEN Introducción: durante el tratamiento endodóntico existe la posibilidad de que ocurran accidentes y complicaciones por lo que el profesional debe tener el máximo cuidado y concentración, además de una sólida base de conocimientos y un buen manejo clínico durante el procedimiento endodóntico. Objetivo: determinar la efectividad del tratamiento quirúrgico de un falso conducto radicular en un diente con pronóstico desfavorable. Caso clínico: se presenta el caso de una paciente de 31 años de edad con antecedentes de necrosis pulpar en el 21, al cual se le realizó un tratamiento pulporradicular hace 3 años aproximadamente. Acude a consulta con un proceso fistuloso a nivel de tercio medio radicular de dicho diente y discromía de la corona. A los rayos X se observó presencia de falso conducto a nivel de tercio cervical radicular. Se realizó una técnica quirúrgica, obturación retrógrada del falso conducto con amalgama de plata y retratamiento del conducto principal. Luego se aplicó la técnica de peróxido de hidrógeno activado con calor combinado con perborato de sodio para la recromia, se obtuvieron resultados favorables. Conclusiones: la técnica aplicada ofrece ampliar el arsenal terapéutico del estomatólogo para la conservación de unidades dentarias destinadas a perderse por los criterios de tratamiento convencional. ABSTRACT Introduction: during the endodontic treatment there is the possibility that accidents and complications occur so the professional must have the utmost care and concentration, as well as a solid base of knowledge and good clinical management during the endodontic procedure. Objective: to determine the effectiveness of the surgical treatment of a false root canal in a tooth with an unfavourable prognosis. Clinical case: we present the case of a 31-year-old patient with a history of pulpal necrosis in year 21, who underwent pulporradicular treatment approximately 3 years ago. The patient comes to consultation with a fistulous process at the level of the middle third of the tooth and crown dyschromia. X-rays showed the presence of a false duct at the level of the third cervical root. A surgical technique was performed, retrograde obturation of the false canal with silver amalgam and retreatment of the main canal. Then applied the technique of activated hydrogen peroxide with heat combined with sodium perborate for rejection, favourable results were obtained. Conclusions: the applied technique offers to extend the therapeutic arsenal of the stomatologist for the conservation of dental units destined to be lost by the criteria of conventional treatment

Hippo Pathway Activity Influences Liver Cell Fate

SummaryThe Hippo-signaling pathway is an important regulator of cellular proliferation and organ size. However, little is known about the role of this cascade in the control of cell fate. Employing a combination of lineage tracing, clonal analysis, and organoid culture approaches, we demonstrate that Hippo pathway activity is essential for the maintenance of the differentiated hepatocyte state. Remarkably, acute inactivation of Hippo pathway signaling in vivo is sufficient to dedifferentiate, at very high efficiencies, adult hepatocytes into cells bearing progenitor characteristics. These hepatocyte-derived progenitor cells demonstrate self-renewal and engraftment capacity at the single-cell level. We also identify the NOTCH-signaling pathway as a functional important effector downstream of the Hippo transducer YAP. Our findings uncover a potent role for Hippo/YAP signaling in controlling liver cell fate and reveal an unprecedented level of phenotypic plasticity in mature hepatocytes, which has implications for the understanding and manipulation of liver regeneration