Biological functions of CDK5 and potential CDK5 targeted clinical treatments.

Cyclin dependent kinases are proline-directed serine/threonine protein kinases that are traditionally activated upon association with a regulatory subunit. For most CDKs, activation by a cyclin occurs through association and phosphorylation of the CDK\u27s T-loop. CDK5 is unusual because it is not typically activated upon binding with a cyclin and does not require T-loop phosphorylation for activation, even though it has high amino acid sequence homology with other CDKs. While it was previously thought that CDK5 only interacted with p35 or p39 and their cleaved counterparts, Recent evidence suggests that CDK5 can interact with certain cylins, amongst other proteins, which modulate CDK5 activity levels. This review discusses recent findings of molecular interactions that regulate CDK5 activity and CDK5 associated pathways that are implicated in various diseases. Also covered herein is the growing body of evidence for CDK5 in contributing to the onset and progression of tumorigenesis

Controlled conversion approaches to selective laser sintering (SLS) printing of high Tg thermosets

Thermoset materials display superior physical and mechanical properties as compared to commonly printed semi-crystalline thermoplastics, yet they typically are not printed by selective laser sintering (SLS). This is because these materials require a post-print thermal cure above Tg to achieve maximal properties. However, such thermal treatment typically results in re-melting of the printed part. Current approaches to printing thermoset materials by this technique have largely relied on infiltrating a porous thermoplastic printed object with a low viscosity reactive resin which is then cured. More recently, direct printing of thermoset materials was also demonstrated, but these approaches require very rapid curing which is often also associated with reduced shelf-life and/or high filler content which may not be desired. Other higher temperature thermoplastics with superior properties (PPS and PEEK) have also been printed using this technique, but the printing of these requires specially designed high-temperature (200-300°C) printing chambers. Please click Additional Files below to see the full abstract

Acute military psychiatric casualties from the war in Iraq

Background: The view that most military personnel evacuated from war zones are suffering from combat stress reactions, or are otherwise traumatised by the horrors of war, has an impact on all aspects of military psychiatry. Aims: To delineate the reasons for psychiatric aeromedical evacuation from Iraq from the start of build-up of UK forces in January 2003 until the end of October that year, 6 months after the end of formal hostilities. Method: A retrospective study was conducted of field and in-patient psychiatric assessments of 116 military personnel evacuated to the UK military psychiatric in-patient facility in Catterick Garrison. Results: Evacuees were mainly non-combatants (69%). A significant proportion were in reserve service (21%) and had a history of contact with mental health services (37%). Only 3% had a combat stress reaction. In over 85% of cases evacuation was for low mood attributed to separation from friends or family, or difficulties adjusting to the environment. Conclusions: These findings have implications especially for screening for suitability for deployment, and for understanding any longer-term mental health problems arising in veterans from Iraq

Phomopsis Stem Canker of Sunflower in North America: Correlation with Climate and Solutions Through Breeding and Management

Climate change is occurring in the central US and is interacting with agroecological factors to increase biotic stress in sunflower. Certain species of Diaporthe cause Phomopsis stem canker in sunflower and other dicotyledonous weeds and crops. The increase in precipitation already observed in the states of North Dakota, South Dakota, and Minnesota have increased the chances of outbreaks of necrotrophic pathogens, like Diaporthe. We discuss how climate trends, combined with technological, management, and economic interactions, are correlated with increasing incidence of Phomopsis stem canker in these and adjacent areas in North America. Further, we discuss management options and the role of improved sunflower genetics in reducing Phomopsis stem canker outbreak risk

Effect of reduced salinity on the initial mortality of Sprat, Spratelloides delicatulus (Bennett), in captivity

The effect of exposure to different concentrations of sea water on the initial mortality of Spratelloides delicatulus, the common tuna-live-bait fish of Lakshadweep, was experimented. The shock mortality of the fish due to stress of capture was found to be greatly! reduced by introducing them at once in 50% sea water. However, the aggregate mortality from the time of capture to the end of the second day was least among the fish exposed to 75% sea water, being about three-fourth of the mortality in 100% sea water

Observations on certain environmental parameters in relation to surface tuna fishery at Minicoy Island, Lakshadweep

Environmental parameters viz. surface temperature, salinity, dissolved oxygen, zooplankton biomass and availability of forage fishes were studied in relation to surface tuna fishery at Minicoy Island. A surface temperature range of 28°C to 31 °C and salinity around 34 %o were found to be optimum for tuna schools. Dissolved oxygen was not found to act as a limiting factor. Zooplankton biomass was found to influence the tuna catch indirectly through the abundance of forage fishes

Trends in secondary production in the inshore waters of the seas around India

CMFRI has been monitoring the microscopic organisms which belong to the categories of phyto and zooplanktons, being a reliable tool for the identification of areas prone to industrial and natural pollution and for understanding its extent and intensity, especially in the inshore areas selected centres along the Indian coasts.These studies assist in foretelling any alarming situations developed in the living environment that may affect the commercially important resources adversely. The pattern of the occurrence and abundance of zooplankton along the Indian coasts from Bombay on the west coast upto Madras on the east coast were described.The samples were collected from Bombay, Karwar, Calicut, Vizhinjam, Tuticorin, Mandapam and Madras. In conclusion,the rate of secondary production on the west as well as on the east coasts during the 1981-82 period was comparatively lesser than during the previous year

Cyclin D1-mediated microRNA expression signature predicts breast cancer outcome

Background: Genetic classification of breast cancer based on the coding mRNA suggests the evolution of distinct subtypes. Whether the non-coding genome is altered concordantly with the coding genome and the mechanism by which the cell cycle directly controls the non-coding genome is poorly understood. Methods: Herein, the miRNA signature maintained by endogenous cyclin D1 in human breast cancer cells was defined. In order to determine the clinical significance of the cyclin D1-mediated miRNA signature, we defined a miRNA expression superset from 459 breast cancer samples. We compared the coding and non-coding genome of breast cancer subtypes. Results: Hierarchical clustering of human breast cancers defined four distinct miRNA clusters (G1-G4) associated with distinguishable relapse-free survival by Kaplan-Meier analysis. The cyclin D1-regulated miRNA signature included several oncomirs, was conserved in multiple breast cancer cell lines, was associated with the G2 tumor miRNA cluster, ERα+ status, better outcome and activation of the Wnt pathway. The coding and non-coding genome were discordant within breast cancer subtypes. Seed elements for cyclin D1-regulated miRNA were identified in 63 genes of the Wnt signaling pathway including DKK. Cyclin D1 restrained DKK1 via the 3\u27UTR. In vivo studies using inducible transgenics confirmed cyclin D1 induces Wnt-dependent gene expression. Conclusion: The non-coding genome defines breast cancer subtypes that are discordant with their coding genome subtype suggesting distinct evolutionary drivers within the tumors. Cyclin D1 orchestrates expression of a miRNA signature that induces Wnt/β-catenin signaling, therefore cyclin D1 serves both upstream and downstream of Wnt/β-catenin signaling