THE NEW FEDERALISM: WHAT IT MEANS FOR MINNESOTANS

Public Economics,

THE NEW FEDERALISM: HOW WOULD IT AFFECT MINNESOTA?

Community/Rural/Urban Development, Political Economy,

Artificial escape from XCI by DNA methylation editing of the CDKL5 gene.

A significant number of X-linked genes escape from X chromosome inactivation and are associated with a distinct epigenetic signature. One epigenetic modification that strongly correlates with X-escape is reduced DNA methylation in promoter regions. Here, we created an artificial escape by editing DNA methylation on the promoter of CDKL5, a gene causative for an infantile epilepsy, from the silenced X-chromosomal allele in human neuronal-like cells. We identify that a fusion of the catalytic domain of TET1 to dCas9 targeted to the CDKL5 promoter using three guide RNAs causes significant reactivation of the inactive allele in combination with removal of methyl groups from CpG dinucleotides. Strikingly, we demonstrate that co-expression of TET1 and a VP64 transactivator have a synergistic effect on the reactivation of the inactive allele to levels >60% of the active allele. We further used a multi-omics assessment to determine potential off-targets on the transcriptome and methylome. We find that synergistic delivery of dCas9 effectors is highly selective for the target site. Our findings further elucidate a causal role for reduced DNA methylation associated with escape from X chromosome inactivation. Understanding the epigenetics associated with escape from X chromosome inactivation has potential for those suffering from X-linked disorders

Polarized XANES of iron porphyrins

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27901/1/0000321.pd

Identification of G α 11 as the phospholipase C-activating G-protein of turkey erythrocytes

A 43 kDa phospholipase C-activating protein has been purified previously from turkey erythrocytes and shown to express immunological properties expected of that of the Gq family of G-protein alpha-subunits [Waldo, Boyer, Morris and Harden (1991) J. Biol. Chem. 266, 14217-14225]. Internal amino acid sequence has now been obtained from this protein which shares 50-100% sequence identity with sequences encoded by mammalian G alpha 11 and G alpha q cDNAs. To identify the purified protein unambiguously, it was necessary to compare its amino acid sequence with the sequence encoded by avian G-protein alpha-subunit cDNA. As such, mouse G alpha q was used as a probe to screen turkey brain and fetal-turkey blood cDNA libraries. A full-length cDNA was identified that encodes avian G alpha 11, on the basis of its 96-98% amino acid identity with mammalian G alpha 11. All eight peptides sequenced from the turkey erythrocyte phospholipase C-activating protein are completely contained within the deduced amino acid sequence of the avian G alpha 11 cDNA. Expression of this cDNA in Sf9 cells by using a baculovirus expression system resulted in the production of a 43 kDa protein that reacts strongly with antisera to the Gq family of G-protein alpha-subunits and activated purified avian phospholipase C in an AlF4(-)-dependent manner. Taken together, these results unambiguously identify the protein purified from turkey erythrocytes, on the basis of its capacity to activate avian phospholipase C, as G alpha 11

URBAN TERRAIN CLIMATOLOGY AND REMOTE SENSING *

. Urban areas have been conceived of as monolithic heat islands because traditional ground observation techniques do not lend themselves to more specific analyses. Observations of urban energy-exchange obtained from calibrated electro-optical scanners combined with energy budget simulation techniques provide tools to relate the urban land use mosaic to the heat island phenomenon. Maps of surface energy-related phenomena were made from airborne scanner outputs for selected flightpaths across the city of Baltimore, Maryland. Conditions for the flight time were simulated according to the various types of land use using an energy budget simulation model which lends itself to extrapolation of simulated grid-point conditions into a map form. Maps made by simulation compare sufficiently well with those made by aerial observation to encourage further refinement of the simulation approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72392/1/j.1467-8306.1976.tb01110.x.pd

3-D struktura serumske paraoksonaze 1 objašnjava njezinu aktivnost, stabilnost, topljivost i kristalizaciju

Serum paraoxonases (PONs) exhibit a wide range of physiologically important hydrolytic activities, including drug metabolism and detoxification of nerve gases. PON1 and PON3 reside on high-density lipoprotein (HDL) (the “good cholesterol”), and are involved in the alleviation of atherosclerosis. Members of the PON family have been identified not only in mammals and other vertebrates, but also in invertebrates. We earlier described the first crystal structure of a PON family member, a directly-evolved variant of PON1, at 2.2 Å resolution. PON1 is a 6-bladed beta-propeller with a unique active-site lid which is also involved in binding to HDL. The 3-D structure, taken together with directed evolution studies, permitted analysis of mutations which enhanced the stability, solubility and crystallizability of this PON1 variant. The structure permits a detailed description of PON1’s active site and suggests possible mechanisms for its catalytic activity on certain substrates.Serumske paraoksonaze (PONs) imaju široki raspon fiziološki važnih hidrolitičkih aktivnosti uključujući metabolizam lijekova i detoksikaciju nervnih plinova. PON1 i PON3 smještene su na lipoproteinima visoke gustoće (engl. high-density lipoprotein; HDL - “dobri kolesterol”) i uključene su u ublažavanje ateroskleroze. Članovi skupine PON identificirani su ne samo u sisavaca i drugih kralježnjaka već i kod beskralješnjaka. Prije smo opisali prvu kristalnu strukturu člana PON skupine, direktno razrađenu varijantu PON1 pri rezoluciji 2,2 Å. PON1 je beta-propeler sa šest lopatica s jedinstvenim poklopcem aktivnog mjesta, koji je tako|er uključen u vezanje na HDL. 3-D struktura, gledana zajedno s direktnim razvojnim istraživanjima, omogućila je analizu mutacija koje povećavaju stabilnost, topljivost i kristalizaciju te PON1 varijante. Struktura dopušta detaljan opis aktivnog mjesta PON1 i sugerira moguće mehanizme za njezinu katalitičku aktivnost prema odre|enim supstratima

Levels of resilience and delivery of HIV care in response to urban violence and crime

Aims To understand the impact of urban violence and crime on HIV care delivery. Background Urban violence and crime can put pressure on the health care system and on nursing staff. Whilst the impact this has at the individual level has been researched, there is less research that places this within the context of the overall social eco system. Design A qualitative design using inductive thematic analysis. Methods Between July 2016 February 2017, in‐depth interviews were conducted with 10 nurses working in two neighbourhoods with high levels of violence in Cape Town, South Africa. Results The effects of crime and violence were evident at multiple levels resulting in participants feeling ‘safe and unsafe’ in a context where crime is viewed as endemic. Resilience emerged as a key concept in the findings. Resilience was apparent at individual, community and organizational levels and enabled continued delivery of HIV care. Conclusion The findings demonstrate the potential role of resilience within the social eco‐health system required to sustain delivery of HIV care in the midst of urban violence and gangsterism. Impact This study examined the impact of and response to urban violence on HIV care delivery. The findings indicate that resilience manifests at all levels of the social eco‐system. Understanding the mechanisms employed to cope with endemic violence helps to address these challenges in the study setting, but also has a much wider application to other areas with endemic urban violence and crime