Autophagy in DNA Damage Response

DNA damage response (DDR) involves DNA repair, cell cycle regulation and apoptosis, but autophagy is also suggested to play a role in DDR. Autophagy can be activated in response to DNA-damaging agents, but the exact mechanism underlying this activation is not fully understood, although it is suggested that it involves the inhibition of mammalian target of rapamycin complex 1 (mTORC1). mTORC1 represses autophagy via phosphorylation of the ULK1/2–Atg13–FIP200 complex thus preventing maturation of pre-autophagosomal structures. When DNA damage occurs, it is recognized by some proteins or their complexes, such as poly(ADP)ribose polymerase 1 (PARP-1), Mre11–Rad50–Nbs1 (MRN) complex or FOXO3, which activate repressors of mTORC1. SQSTM1/p62 is one of the proteins whose levels are regulated via autophagic degradation. Inhibition of autophagy by knockout of FIP200 results in upregulation of SQSTM1/p62, enhanced DNA damage and less efficient damage repair. Mitophagy, one form of autophagy involved in the selective degradation of mitochondria, may also play role in DDR. It degrades abnormal mitochondria and can either repress or activate apoptosis, but the exact mechanism remains unknown. There is a need to clarify the role of autophagy in DDR, as this process may possess several important biomedical applications, involving also cancer therapy

Heavy ion collisions in the used nucleon model

It is shown that recently proposed by R.J. Glauber the used nucleon model combined with the assumption that the nucleon consists of two constituents (a quark and a diquark) describes well the PHOBOS data on particle production at midrapidity.Comment: 5 pages, 2 figure

Kaon and Φ\Phi production vs Participants in Nuclear Collisions

Data on kaon and $\Phi$ production in nuclear collisions as a function of centrality are analysed both at AGS and SPS energy range. We compare the results of several experiments, looking for common trend in `participant scaling' of production yields. We find a smooth description of scaled kaon and $\Phi$ yields as a function of participant density. We also show a participant density dependence of kaons and $\Phi$ produced in the forward hemisphere for proton-nucleus collisions.Comment: Proceedings of the International Conference on Strangeness in Quark Matter, 20-25 July 2000, Berkeley, CA. To appear in Journal of Physics G: Nuclear and Particle Physic

Improved tagging strategy for protein identification in mammalian cells

BACKGROUND: The tagging strategy enables full-length endogenous proteins in mammalian cells to be expressed as green fluorescent fusion proteins from their authentic promoters. RESULTS: We describe improved genetic tools to facilitate protein tagging in mammalian cells based on a mobile genetic element that harbors an artificial exon encoding a protein tag. Insertion of the artificial exon within introns of cellular genes results in expression of hybrid proteins consisting of the tag sequence fused in-frame to sequences of a cellular protein. We have used lentiviral vectors to stably introduce enhanced green fluorescent protein (EGFP) tags into expressed genes in target cells. The data obtained indicate that this strategy leads to bona fide tripartite fusion proteins and that the EGFP tag did not affect the subcellular localization of such proteins. CONCLUSION: The tools presented here have the potential for protein discovery, and subsequent investigation of their subcellular distribution and role(s) under defined physiological conditions, as well as for protein purification and protein-protein interaction studies

Locating suitable habitats for West Nile Virus-infected mosquitoes through association of environmental characteristics with infected mosquito locations: a case study in Shelby County, Tennessee

<p>Abstract</p> <p>Background</p> <p>Since its first detection in 2001, West Nile Virus (WNV) poses a significant health risk for residents of Shelby County in Tennessee. This situation forced public health officials to adopt efficient methods for monitoring disease spread and predicting future outbreaks. Analyses that use environmental variables to find suitable habitats for WNV-infected mosquitoes have the potential to support these efforts. Using the Mahalanobis Distance statistic, we identified areas of Shelby County that are ecologically most suitable for sustaining WNV, based on similarity of environmental characteristics to areas where WNV was found. The environmental characteristics in this study were based on Geographic Information Systems (GIS) data, such as elevation, slope, land use, vegetation density, temperature, and precipitation.</p> <p>Results</p> <p>Our analyses produced maps of likely habitats of WNV-infected mosquitoes for each week of August 2004, revealing the areas that are ecologically most suitable for sustaining WNV within the core of the Memphis urban area. By comparing neighbourhood social characteristics to the environmental factors that contribute to WNV infection, potential social drivers of WNV transmission were revealed in Shelby County. Results show that human population characteristics and housing conditions such as a high percentage of black population, low income, high rental occupation, old structures, and vacant housing are associated with the focal area of WNV identified for each week of the study period.</p> <p>Conclusion</p> <p>We demonstrated that use of the Mahalanobis Distance statistic as a similarity index to assess environmental characteristics is a potential raster-based approach to identify areas ecologically most suitable for sustaining the virus. This approach was also useful to monitor changes over time for likely locations of infected mosquito habitats. This technique is very helpful for authorities when making decisions related to an integrated mosquito management plan and targeted health education outreach.</p

Paraplegic Wakeboard Suspension Design and Testing

Abstract The Paraplegic Wakeboard Suspension provides paraplegics with a comfortable and safe environment as wakeboard riders. Due to their disabilities, people with paraplegia either are not able to enjoy standard wakeboarding, or cannot afford it due to the high prices the current market holds. The current market for suspension attachments for wakeboards is very limited and costly for those looking to get into the sport. Our competitors, such as Swaik, have accomplished the task of distributing the oscillatory loading produced by the waves and transmitted to the rider via their full-flex suspension system. Although their design is costly, starting around $2000, the cost of our suspension, wakeboard, and seat altogether will be less than$1000. Additionally, the major improvement in our suspension system is the addition of two DNM adjustable air shock absorbers to allow precise control for multiple wakeboarding scenarios. The design is also modular in that it can be placed on any standard sized wakeboard via M6 bolts. The prototype of the suspension is made with 2xs4 wood and 1x3 wood, and will undergo structural testing before the final suspension can be built using aluminum. The final suspension will undergo testing that validates the initial design requirements. Keywords: Paraplegic, Suspension, Wakeboard, Shocks

Wounded quarks and diquarks in heavy ion collisions

A model in which the soft collisions of the nucleon are described in terms of interactions of its two constituents (a quark and a diquark) is proposed. When adjusted to describe precisely the elastic proton-proton scattering data and supplemented with the idea of wounded constituents, the model accounts rather well for the centrality dependence of particle production in the central rapidity region at RHIC energies.Comment: 8 pages, 4 figures, added references; corrected typo in Eq. (15

Usoda skrb vzbujajočih onesnaževal v jezerih, nastalih v vrtačah, Florida, ZDA

Zakrasele karbonatne platforme, kot je Florida, zaznamujejo hitra stopnja infiltracije, visoka prepustnost podlage in neposredna povezava z vodonosniki prek številnih vrtač. Kombinacija teh fizikalnih lastnosti prispeva k visoki občutljivosti podtalnice in vodonosnikov na kontaminacijo s skrb vzbujajočimi sintetičnimi kemikalijami. Uporaba greznic spodbuja vnos teh onesnaževal v okolje. Da bi proučili vpliv kemikalij na kraško pokrajino, so bili vzorci vode, sedimenta in vegetacije odvzeti v jezeru, nastalem v vrtači in obdanem s stanovanji, ki so opremljena z greznicami. Glavno vprašanje tega raziskovalnega projekta je, kaj se dogaja z onesnaževali iz grezničnih odplak v vodnem zajetju vrtače. Za analizo vzorcev je bila izvedena masna spektrometrija s tekočinsko kromatografijo. Ugotovljeno je bilo, da je sorazmerna količina kemikalij odvisna od 1) hidrofobnosti in polarnosti spojine, 2) mesta vzorčenja, 3) topografskega gradienta in 4) za vegetacijo, povezanosti vrste vzorca s sedimentom. Hidrogeološke študije so pokazale, da so vrtače na tem območju povezane z vodonosnikom, ki je pod njimi. Posledično skrb vzbujajoča onesnaževala predstavljajo tveganje za onesnaženje podtalnice. Ta študija je prikaz razmer v sušni sezoni Floride, to je najverjetneje obdobje z najmanjšo kontaminacijo. Vzorčenje bi bilo treba opraviti v tudi deževnem obdobju, ko izpiranje onesnaževal iz greznic lahko poveča koncentracije onesnaževal, tako v jezeru kot v vodonosnikih, kar je posebno problematično zaradi uporabnosti vode iz vodnjaka v prehranske namene. Čeprav je bila študija izvedena na Floridi, verjamemo, da so naše ugotovitve in priporočila splošno uporabni, saj se greznice uporabljajo v številnih kraških predelih sveta.Highly karstified carbonate platforms such as Florida are characterized by rapid infiltration rates, highly permeable bedrock and the direct connection to the below aquifer through the high density of sinkholes. This combination of physical features makes the groundwater and aquifers highly vulnerable to contamination from synthetic chemicals commonly referred to as contaminants of emerging concern (CECs). The use of septic tanks, otherwise referred to as onsite water treatment systems (OWTS), promotes the introduction of CECs into the environment. In order to study the impacts of CECs from OWTS on a karst landscape, water, sediment, and vegetation samples were collected in a sinkhole lake surrounded by residential housing using this waste disposal method. The main question of this research project is what is the fate of CECs from OWTSs effluent within the catchment of a sinkhole lake? Liquid chromatograph mass spectrometry was used to analyze the samples for the presence of CECs. It was found that the relative quantity of CECs in the individual constituents is dependent upon 1) the hydrophobicity and polarity of the individual compound, 2) the specific sampling site, 3) the topography gradient, and 4) for vegetation, the connectedness of the sample type to the sediment. Hydrogeological studies have found that the sinkholes of the area are all connected to the below aquifer. Consequently, these CECs pose a risk of the contamination of the groundwater. This study is a temporal snapshot, that being the dry season of Florida which is most likely the time of lowest CEC contamination. It is imperative that sampling extend into the wet season when flushing of CECs from the OWTS may increase their concentrations in both the lake but also the aquifers especially since residents use well water as their source of potable water. While this study is based in Florida, we strongly suspect that our findings and recommendations are applicable more generally as OWTS are used throughout the many karst regions of the world

Reply to Comment of Gazdzicki and Heinz on Strangeness Enhancement in p+Ap+A and S+AS+A

The Comment of Gazdzicki and Heinz is flawed because their assumed baryon stopping power in $pA$ is inconsistent with data and because they ignored half the analysis based on the VENUS model. The Comment continues the misleading presentation of strangeness enhancement by focusing on ratios of integrated yields. Those ratios discard essential experimental information on the rapidity dependence of produced $\Lambda$ and obscure discrepancies between different data sets. Our conclusion remains that the NA35 minimum bias data on $p+S\rightarrow\Lambda +X$ indicate an anomalous enhancement of central rapidity strangeness in few nucleon reactions that points to non-equilibrium dynamics as responsible for strangeness enhancement in nuclear reactions.Comment: revtex file, 6 pages, submitted to Phys. Rev.