A Role for Proapoptotic BID in the DNA-Damage Response

SummaryThe BCL-2 family of apoptotic proteins encompasses key regulators proximal to irreversible cell damage. The BH3-only members of this family act as sentinels, interconnecting specific death signals to the core apoptotic pathway. Our previous data demonstrated a role for BH3-only BID in maintaining myeloid homeostasis and suppressing leukemogenesis. In the absence of Bid, mice accumulate chromosomal aberrations and develop a fatal myeloproliferative disorder resembling chronic myelomonocytic leukemia. Here, we describe a role for BID in preserving genomic integrity that places BID at an early point in the path to determine the fate of a cell. We show that BID plays an unexpected role in the intra-S phase checkpoint downstream of DNA damage distinct from its proapoptotic function. We further demonstrate that this role is mediated through BID phosphorylation by the DNA-damage kinase ATM. These results establish a link between proapoptotic Bid and the DNA-damage response

Effects of weight on osmoregulatory ability of Salmo trutta caspius juveniles

Salmo trutta caspius is a commercial migratory fish species in the Caspian Sea. Over fishing and deterioration of natural spawning grounds of the species are two major causes depressing stocks of the fish in the Sea. Thus, artificial breeding and release of salmon juveniles into the Caspian Sea is now considered an urgent need towards the rehabilitation of the stocks of the fish. This study was conducted in early 2004 to determine the ideal weight for the release of salmon fry in order to increase fishery return coefficients in the species. For this research, we used facilities of the Marine Fisheries Breeding and Research Center in Ghazian, along the coastal areas of the Bandar Anzali. Salmon juveniles used in this study belonged to the same generation. Fishes belongirig to different weight classes (5, 10, 15 and 20g) were selected in a random design and stocked in two groups of sea water at 7% salinity and freshwater. Osmosis was studied using blood samples collected at 0, 3, 6, 12, 24, 72, 168 and 240 hours. Heparin tubes were used for sampling blood which was centrifuged to separate blood plasma. Osmotic pressure was determined using osmometer. Statistical analysis of the results on variations in osmotic pressure showed that after 10 days of stocking fish in seawater (7%), fishes in all weight classes were capable of osmoregulation. Also fishes in weight classes 10, 15 and 20g were capable of osmore-gulation in the Caspian Sea water

Conceptualising the more knowledgeable other within a multi-directional ZPD:

From a Marxian/Vygotskian perspective, learning is social in origin and it happens in the presence of others that are more knowledgeable. Extending this view to the learning of mathematics, such learning also becomes inseparable from the presence of others (people and artefacts). Researchers over decades have studied different interactions to see how such learning with others occurs, what is the role of the (more knowledgeable) other, and if at all this role alternates between the participants. In this paper, we looked at a 5-year-old’s (Lila) interaction with her mother (Mellony) and a television remote control as Lila attempted to count in threes using the three by three physical layout of the numbered buttons 1–9 on the remote control. We specifically looked at the emergence of the Zone of Proximal Development (ZPD) as Lila’s attention was caught by the properties of the remote control and by her mother’s questions. We also pay attention to how the role of the more knowledgeable other alternates among the participants. Our findings suggest that Lila, at times, used resources provided by the physical properties of the remote control and sometimes, used resources provided by Mellony to think about the task of counting in threes. In Lila’s interaction, we interpreted a multi-directional ZPD as the role of the more knowledgeable other alternated between Mellony, Lila and the remote control

\u3ci\u3en\u3c/i\u3e-Type Charge Transport in Heavily \u3ci\u3ep\u3c/i\u3e-Doped Polymers

It is commonly assumed that charge-carrier transport in doped π-conjugated polymers is dominated by one type of charge carrier, either holes or electrons, as determined by the chemistry of the dopant. Here, through Seebeck coefficient and Hall effect measurements, we show that mobile electrons contribute substantially to charge-carrier transport in π-conjugated polymers that are heavily p-doped with strong electron acceptors. Specifically, the Seebeck coefficient of several p-doped polymers changes sign from positive to negative as the concentration of the oxidizing agents FeCl3 or NOBF4 increase, and Hall effect measurements for the same p-doped polymers reveal that electrons become the dominant delocalized charge carriers. Ultraviolet and inverse photoelectron spectroscopy measurements show that doping with oxidizing agents results in elimination of the transport gap at high doping concentrations. This approach of heavy p-type doping is demonstrated to provide a promising route to high-performance n-type organic thermoelectric materials

Early effects of parathyroid hormone on bisphosphonate/steroid-associated compromised osseous wound healing

Summary: Administration of intermittent parathyroid hormone (PTH) promoted healing of tibial osseous defects and tooth extraction wounds and prevented the development of necrotic lesions in rats on a combined bisphosphonate and steroid regimen. Introduction: Osteonecrosis of the jaw (ONJ) has emerged in association with antiresorptive therapies. The pathophysiology of ONJ is unknown and no established cure currently exists. Our objective was to determine the effect of intermittent PTH administration on early osseous healing in the jaw and long bones of rats receiving bisphosphonate and steroid treatment. Methods: Ovariectomized rats received the combination therapy of alendronate and dexamethasone (ALN/DEX) for 12 weeks. Osseous wounds were created in the jaw and tibia. PTH was administered intermittently and healing at 2 weeks post-op was compared between the jaw and tibia by microcomputed tomography and histomorphometric analyses. Results: ALN/DEX treatment was associated with necrotic open wounds in the jaw but had no negative effects on healing and promoted bone fill in tibial defects. PTH therapy prevented the development of necrotic lesions in the jaw and promoted healing of the tibial defects. PTH therapy was associated with the promotion of osteocyte survival in osseous wounds both in the jaw and tibia. Conclusions: Wound healing was impaired in the jaw in rats on a combined bisphosphonate and steroid regimen, and PTH therapy rescued necrotic lesions. These findings suggest that PTH therapy could be utilized to prevent ONJ from occurring in patients on combination antiresorptive and steroid therapy

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.</p

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.</p

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.</p