Crystal structure of archaeal RNase HII: a homologue of human major RNase H

AbstractBackground: RNases H are present in all organisms and cleave RNAs in RNA/DNA hybrids. There are two major types of RNases H that have little similarity in sequence, size and specificity. The structure of RNase HI, the smaller enzyme and most abundant in bacteria, has been extensively studied. However, no structural information is available for the larger RNase H, which is most abundant in eukaryotes and archaea. Mammalian RNase H participates in DNA replication, removal of the Okazaki fragments and possibly DNA repair.Results: The crystal structure of RNase HII from the hypothermophile Methanococcus jannaschii, which is homologous to mammalian RNase H, was solved using a multiwavelength anomalous dispersion (MAD) phasing method at 2 Å resolution. The structure contains two compact domains. Despite the absence of sequence similarity, the large N-terminal domain shares a similar fold with the RNase HI of bacteria. The active site of RNase HII contains three aspartates: Asp7, Asp112 and Asp149. The nucleotide-binding site is located in the cleft between the N-terminal and C-terminal domains.Conclusions: Despite a lack of any detectable similarity in primary structure, RNase HII shares a similar structural domain with RNase HI, suggesting that the two classes of RNases H have a common catalytic mechanism and possibly a common evolutionary origin. The involvement of the unique C-terminal domain in substrate recognition explains the different reaction specificity observed between the two classes of RNase H

Boys in care: How social workers interpret deviant adolescent behaviour.

The purpose of this thesis is to offer an ethnomethodological analysis of institutional life at St. Nicholas', a community home for deviant adolescent boys. I have been particularly concerned to examine the therapeutic mode of reasoning which the staff so often employed in interpreting the boys' behaviour as the surface manifestation of their underlying emotional disturbance. This constitutes the main focus of chapters three and four. The psychological problems from which the boys were typically seen to suffer were routinely attributed to their past, punctuated as it was by a variety of deprivations. I examine the construction of such historical links in chapters five to eight. To procure the material necessary for a detailed empirical exploration of institutional discourse I spent a year and a quarter "in the field" at St. Nicholas'. In addition to my everyday observation of myriad institutional routines and practices I also recorded the vast majority of staff meetings and case conferences, and photocopied dozens of case histories. This form of data collection provided the empirical precision necessary for the methodological purpose in hand. I attempted to bring to the data an anthropological sensitivity. This involved the partial suspension of my normal, practical orientation to the world. By dint of this distancing process one is able to identify and analyze the common sense methods through which institutional realities are accomplished. These are usually concealed by their very proximity. By subjecting the empirical material to such close methodological scrutiny, "children with problems", or "disturbed adolescents" emerge not as the starting point, but the product of the social knowledge and discursive procedures through which staff called their environment to account

Migration Tactics Of A Long-Distance Migratory Songbird From Across A Continental Breeding Range

Migration strategies in the avian world are often compared at the species level and evaluated relative to general ecology and constraints such as molting and breeding timetables. The advancement of tracking technology provides an opportunity to explore variation in more specific migration tactics within species and their populations as it relates to demographic and environmental factors throughout the annual cycle. We compare migration timing among 4 populations of Bobolink (Dolichonyx oryzivorus) from across the breeding range using data from light-level geolocators. The date of departure from the breeding grounds and the duration of southbound migration differed among breeding populations, and were more variable for eastern breeding populations compared to western populations farther from the main migration corridor. Despite variation in both timing and distance from the corridor among breeding populations, date of arrival at the major southbound stop in the Llanos of South America remained synchronous, but less so than previously described. Weekly flight distances were highly variable and did not differ among populations. Duration of northbound migration did not differ among populations and was half as long as the southbound migration. Our findings show Bobolink populations breeding near the species’ relatively narrow migration corridor in the southeastern United States were more variable in terms of how they reached the first lengthy stop in the Llanos, suggesting more flexibility in migration tactics. Breeding locations were not associated, however, with the timing or duration of the remainder of their migratory schedule. Our findings support the hypothesis that food resources, both historical and present, drive and also modify the endogenous migration schedule of this flocking species with a split migration

Multipar-T: Multiparty-Transformer for Capturing Contingent Behaviors in Group Conversations

As we move closer to real-world AI systems, AI agents must be able to deal with multiparty (group) conversations. Recognizing and interpreting multiparty behaviors is challenging, as the system must recognize individual behavioral cues, deal with the complexity of multiple streams of data from multiple people, and recognize the subtle contingent social exchanges that take place amongst group members. To tackle this challenge, we propose the Multiparty-Transformer (Multipar-T), a transformer model for multiparty behavior modeling. The core component of our proposed approach is the Crossperson Attention, which is specifically designed to detect contingent behavior between pairs of people. We verify the effectiveness of Multipar-T on a publicly available video-based group engagement detection benchmark, where it outperforms state-of-the-art approaches in average F-1 scores by 5.2% and individual class F-1 scores by up to 10.0%. Through qualitative analysis, we show that our Crossperson Attention module is able to discover contingent behavior.Comment: 7 pages, 4 figures, IJCA

Aphasia Treatment over the Internet: A Randomized Placebo-Controlled Clinical Trial

We report results of a randomized placebo-controlled clinical trial evaluating an aphasia treatment provided over the internet. Thirty-two persons with aphasia were randomized to receive 6 weeks of practice with Oral Reading for Language in Aphasia (ORLA) (N=19) or a commercial computer game (N=13). Results indicated significant changes on WAB-R subtests (AQ, reading and writing) with web-based ORLA; changes were maintained for six weeks. There was no significant difference between ORLA versus the placebo computer program.  Findings support the feasibility and efficacy of providing ORLA over the internet. Reasons for improvements with the commercial computer program are discussed

Local Parasite Lineage Sharing In Temperate Grassland Birds Provides Clues About Potential Origins Of Galapagos Avian Plasmodium

Oceanic archipelagos are vulnerable to natural introduction of parasites via migratory birds. Our aim was to characterize the geographic origins of two Plasmodium parasite lineages detected in the Galapagos Islands and in North American breeding bobolinks (Dolichonyx oryzivorus) that regularly stop in Galapagos during migration to their South American overwintering sites. We used samples from a grassland breeding bird assemblage in Nebraska, United States, and parasite DNA sequences from the Galapagos Islands, Ecuador, to compare to global data in a DNA sequence registry. Homologous DNA sequences from parasites detected in bobolinks and more sedentary birds (e.g., brown-headed cowbirds Molothrus ater, and other co-occurring bird species resident on the North American breeding grounds) were compared to those recovered in previous studies from global sites. One parasite lineage that matched between Galapagos birds and the migratory bobolink, Plasmodium lineage B, was the most common lineage detected in the global MalAvi database, matching 49 sequences from unique host/site combinations, 41 of which were of South American origin. We did not detect lineage B in brown-headed cowbirds. The other Galapagos-bobolink match, Plasmodium lineage C, was identical to two other sequences from birds sampled in California. We detected a close variant of lineage C in brown-headed cowbirds. Taken together, this pattern suggests that bobolinks became infected with lineage B on the South American end of their migratory range, and with lineage C on the North American breeding grounds. Overall, we detected more parasite lineages in bobolinks than in cowbirds. Galapagos Plasmodium had similar host breadth compared to the non-Galapagos haemosporidian lineages detected in bobolinks, brown-headed cowbirds, and other grassland species. This study highlights the utility of global haemosporidian data in the context of migratory bird–parasite connectivity. It is possible that migratory bobolinks bring parasites to the Galapagos and that these parasites originate from different biogeographic regions representing both their breeding and overwintering sites

Expression and Characterization of Recombinant Rat Acyl-CoA Synthetases 1, 4, and 5: SELECTIVE INHIBITION BY TRIACSIN C AND THIAZOLIDINEDIONES

Inhibition by triacsins and troglitazone of long chain fatty acid incorporation into cellular lipids suggests the existence of inhibitor-sensitive and -resistant acyl-CoA synthetases (ACS, EC ) that are linked to specific metabolic pathways. In order to test this hypothesis, we cloned and purified rat ACS1, ACS4, and ACS5, the isoforms present in liver and fat cells, expressed the isoforms as ACS-Flag fusion proteins in Escherichia coli, and purified them by Flag affinity chromatography. The Flag epitope at the C terminus did not alter the kinetic properties of the enzyme. Purified ACS1-, 4-, and 5-Flag isoforms differed in their apparent K(m) values for ATP, thermolability, pH optima, requirement for Triton X-100, and sensitivity to N-ethylmaleimide and phenylglyoxal. The ACS inhibitor triacsin C strongly inhibited ACS1 and ACS4, but not ACS5. The thiazolidinedione (TZD) insulin-sensitizing drugs and peroxisome proliferator-activated receptor gamma (PPARgamma) ligands, troglitazone, rosiglitazone, and pioglitazone, strongly and specifically inhibited only ACS4, with an IC(50) of less than 1.5 microm. Troglitazone exhibited a mixed type inhibition of ACS4. alpha-Tocopherol, whose ring structure forms the non-TZD portion of troglitazone, did not inhibit ACS4, indicating that the thiazolidine-2,4-dione moiety is the critical component for inhibition. A non-TZD PPARgamma ligand, GW1929, which is 7-fold more potent than rosiglitazone, inhibited ACS1 and ACS4 poorly with an IC(50) of greater than 50 microm, more than 100-fold higher than was required for rosiglitazone, thereby demonstrating the specificity of TZD inhibition. Further, the PPARalpha ligands, clofibrate and GW4647, and various xenobiotic carboxylic acids known to be incorporated into complex lipids had no effect on ACS1, -4, or -5. These results, together with previous data showing that triacsin C and troglitazone strongly inhibit triacylglycerol synthesis compared with other metabolic pathways, suggest that ACS1 and ACS4 catalyze the synthesis of acyl-CoAs used for triacylglycerol synthesis and that lack of inhibition of a metabolic pathway by triacsin C does not prove lack of acyl-CoA involvement. The results further suggest the possibility that the insulin-sensitizing effects of the thiazolidinedione drugs might be achieved, in part, through direct interaction with ACS4 in a PPARgamma-independent manner

Centennial Challenges Program Update: From Humanoids to 3D-Printing Houses on Mars, How the Public Can Advance Technologies for NASA and the Nation

The Centennial Challenges (CC) program, part of NASA's Space Technology Mission Directorate (STMD), was founded upon the principle that engaging the public at large was a very important part of garnering the true magnitude of grassroots American innovation and ingenuity. The program uses a focused problem-statement approach to obtain solutions and/or stimulate innovation in key NASA technology gaps by catalyzing sources outside of the traditional aerospace community. The CC program announced the first two challenge competitions in 2005 incentivizing the public to participate using a congressionally authorized prize purse. Since then, the program has developed and executed more than 18 competitions and has awarded over $9 million in prize money. The challenges have covered a variety of technology areas, including propulsion, robotics, communications and navigation, human health, science instrumentation, nanotech, materials and structures, and aerodynamics. Centennial Challenges' accomplishments from October 2016 to December 2017--including significant increases in the amount and diversity of participants; increase in prize purse awards; strong alignments with NASA missions; and partnerships with industry, academia, and other government agencies-are summarized in this paper. Technological advancements, communication strategies, and legal authority are also discussed. NASA is leading the government agencies in the area of prizes and competitions to push technologies, and the CC program is one powerful example of NASA's continuing commitment to technological advancement and innovation through non-traditional programs. Currently, the Agency has in place the proven infrastructure, policies, and people needed to enable the successful use of competition tools, including the ones used as part of the CC program