Conventional Synapses for Unconventional Cells

Powerful synapses between climbing fibers (CF) and Purkinje cells are crucial to cerebellar motor learning. In this issue of Neuron, Lin and colleagues provide compelling evidence for the existence of direct synaptic contacts between CFs and NG2-expressing glia cells, adding to the intrigue of neuro-glial interactions

Quo Vadis Kinesiology

Iʼd like to thank Gil Reeve, the organizer of the Academy program, for asking me to attempt a "wrap up" of the presentations at this the 2006 Academy meeting. This has been a comprehensive program that has encompassed important topics including (again) the name of our fi eld and the implications that has for both the short-and long-term development of our fi eld. Contributors have focused on a breadth of content, including undergraduate and graduate degree programs, as well professional content issues related to degrees in the physical activity sciences and important challenges such as accreditation. All of the presentations at this yearʼs meeting covered a wide range of important issues that pose a challenge to the individual tasked to provide a comprehensive summary. My remarks focus primarily on the comments raised by our keynote speaker Karl Newell that address the future of our fi eld (which we at least tentatively have agreed to call kinesiology). This topic continues as the proverbial "300 pound gorilla in the room" simply because we have yet to arrive at a consensus as to what to call our fi eld of study. The presentations on knowledge, content, professional issues, and accreditation were all timely and provided important "updates" of program content direction in our different subfi elds. Not in any way to undermine those presentations, my comments will focus more on what, in my judgment, is the major constraint facing the Academy and the physical activity sciences, namely the necessity to create a unifi ed body of scientists and professionals organized under an umbrella (big tent) that we call kinesiology. After 75 years of existence, the AAKPE still lacks that one single voice whereby both scholars and professionals can comment or pass judgment on the plethora of health and wellness issues related to sport, physical activity, aging, and a host of topics yet to be addressed. As I write this summary for Quest, I note in the press today (October 10, 2006), the American Academy of Pediatrics issued a statement recommending "less participation in organized sports for young children in their developing years" and urging that "more time be set aside for recreation and free play." I would submit that experts in our fi eld (kinesiology) are as well qualifi ed or better qualifi ed to comment on the role of sport and participation in play (both organized and voluntary) and recreational activities than pediatricians! Yet we have no organized mouthpiece by which we can speak and make recommendations about such societal issues that impact the well-being of our nationʼs youth! This is a serious barrier and constraint to the development of our fi eld. We need an American College of Kinesiology

Subjective Reports and Postural Performance Among Older Adult Passengers on a Sea Voyage

We sought to evaluate changes in subjective experience and postural performance among older adult passengers during the first 2 days of a sea voyage. On a vacation cruise, volunteer passengers gave verbal ratings of subjective bodily stability and awareness of ship motion followed by performance on the tandem Romberg test while facing fore-aft and athwartship. Data were collected when the ship was at the dock and on each of the first 2 full days at sea. Ship motion reduced subjective bodily stability and performance on the Romberg test and increased awareness of ship motion. On the first day at sea, Romberg performance was more strongly impacted by motion of the ship in roll (i.e., when facing fore-aft) than in pitch (i.e., when facing athwartship). Also on the first day at sea, subjective bodily stability was correlated with Romberg performance when facing fore-aft but not when facing athwart. In summary, at the beginning of the voyage older adult passengers on a sea voyage exhibited consistent changes in subjective awareness and postural performance. Subjective reports were correlated with postural performance in ways that appeared to be functional. We suggest that this finding may help to illuminate the role of conscious awareness within ecological analyses of perception and action

The Rim and the Ancient Mariner: The Nautical Horizon Affects Postural Sway in Older Adults

On land, the spatial magnitude of postural sway (i.e., the amount of sway) tends to be greater when participants look at the horizon than when they look at nearby targets. By contrast, on ships at sea, the spatial magnitude of postural sway in young adults has been greater when looking at nearby targets and less when looking at the horizon. Healthy aging is associated with changes in the movement patterns of the standing body sway, and these changes typically are interpreted in terms of age-related declines in the ability to control posture. To further elucidate the mechanisms associated with these changes we investigated control of posture in a setting that poses substantial postural challenges; standing on a ship at sea. In particular, we explored postural sway on a ship at sea when older adults looked at the horizon or at nearby targets. We evaluated the kinematics of the center of pressure in terms of spatial magnitude (i.e., the amount of sway) and multifractality (a measure of temporal dynamics). We found that looking at the horizon significantly affected the multifractality of standing body, but did not systematically influence the spatial magnitude of sway. We discuss the results in terms of age-related changes in the perception and control of dynamic body orientation

A Model for Simulating the Response of Aluminum Honeycomb Structure to Transverse Loading

A 1-dimensional material model was developed for simulating the transverse (thickness-direction) loading and unloading response of aluminum honeycomb structure. The model was implemented as a user-defined material subroutine (UMAT) in the commercial finite element analysis code, ABAQUS(Registered TradeMark)/Standard. The UMAT has been applied to analyses for simulating quasi-static indentation tests on aluminum honeycomb-based sandwich plates. Comparison of analysis results with data from these experiments shows overall good agreement. Specifically, analyses of quasi-static indentation tests yielded accurate global specimen responses. Predicted residual indentation was also in reasonable agreement with measured values. Overall, this simple model does not involve a significant computational burden, which makes it more tractable to simulate other damage mechanisms in the same analysis

The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing

Kinetoplastid parasites—trypanosomes and leishmanias—infect millions of humans and cause economically devastating diseases of livestock, and the few existing drugs have serious deficiencies. Benzoxaborole-based compounds are very promising potential novel anti-trypanosomal therapies, with candidates already in human and animal clinical trials. We investigated the mechanism of action of several benzoxaboroles, including AN7973, an early candidate for veterinary trypanosomosis. In all kinetoplastids, transcription is polycistronic. Individual mRNA 5'-ends are created by trans splicing of a short leader sequence, with coupled polyadenylation of the preceding mRNA. Treatment of Trypanosoma brucei with AN7973 inhibited trans splicing within 1h, as judged by loss of the Y-structure splicing intermediate, reduced levels of mRNA, and accumulation of peri-nuclear granules. Methylation of the spliced leader precursor RNA was not affected, but more prolonged AN7973 treatment caused an increase in S-adenosyl methionine and methylated lysine. Together, the results indicate that mRNA processing is a primary target of AN7973. Polyadenylation is required for kinetoplastid trans splicing, and the EC50 for AN7973 in T. brucei was increased three-fold by over-expression of the T. brucei cleavage and polyadenylation factor CPSF3, identifying CPSF3 as a potential molecular target. Molecular modeling results suggested that inhibition of CPSF3 by AN7973 is feasible. Our results thus chemically validate mRNA processing as a viable drug target in trypanosomes. Several other benzoxaboroles showed metabolomic and splicing effects that were similar to those of AN7973, identifying splicing inhibition as a common mode of action and suggesting that it might be linked to subsequent changes in methylated metabolites. Granule formation, splicing inhibition and resistance after CPSF3 expression did not, however, always correlate and prolonged selection of trypanosomes in AN7973 resulted in only 1.5-fold resistance. It is therefore possible that the modes of action of oxaboroles that target trypanosome mRNA processing might extend beyond CPSF3 inhibition

Complexity of childhood sexual abuse: predictors of current post-traumatic stress disorder, mood disorders, substance use, and sexual risk behavior among adult men who have sex with men

Men who have sex with men (MSM) are the group most at risk for HIV and represent the majority of new infections in the United States. Rates of childhood sexual abuse (CSA) among MSM have been estimated as high as 46 %. CSA is associated with increased risk of HIV and greater likelihood of HIV sexual risk behavior. The purpose of this study was to identify the relationships between CSA complexity indicators and mental health, substance use, sexually transmitted infections, and HIV sexual risk among MSM. MSM with CSA histories (n = 162) who were screened for an HIV prevention efficacy trial completed comprehensive psychosocial assessments. Five indicators of complex CSA experiences were created: CSA by family member, CSA with penetration, CSA with physical injury, CSA with intense fear, and first CSA in adolescence. Adjusted regression models were used to identify relationships between CSA complexity and outcomes. Participants reporting CSA by family member were at 2.6 odds of current alcohol use disorder (OR 2.64: CI 1.24–5.63), two times higher odds of substance use disorder (OR 2.1: CI 1.02–2.36), and 2.7 times higher odds of reporting an STI in the past year (OR 2.7: CI 1.04–7.1). CSA with penetration was associated with increased likelihood of current PTSD (OR 3.17: CI 1.56–6.43), recent HIV sexual risk behavior (OR 2.7: CI 1.16–6.36), and a greater number of casual sexual partners (p = 0.02). Both CSA with Physical Injury (OR 4.05: CI 1.9–8.7) and CSA with Intense Fear (OR 5.16: CI 2.5–10.7) were related to increased odds for current PTSD. First CSA in adolescence was related to increased odds of major depressive disorder. These findings suggest that CSA, with one or more complexities, creates patterns of vulnerabilities for MSM, including post-traumatic stress disorder, substance use, and sexual risk taking, and suggests the need for detailed assessment of CSA and the development of integrated HIV prevention programs that address mental health and substance use comorbidities.This study was supported by a Grant from the NIMH (R01 MH095624) PI: O'Cleirigh; Author time (Safren) was supported, in part, by Grant 5K24MH094214. (R01 MH095624 - NIMH; 5K24MH094214)Accepted manuscrip

Synthesis of β,β-Disubstituted Styrenes via Trimethylsilyl Trifluoromethanesulfonate-Promoted Aldehyde-Aldehyde Aldol Addition-Deformylative Elimination.

In the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,6-lutidine, α,α-disubstituted aldehydes condense with electron-rich aromatic aldehydes to yield β, β- disubstituted styrenes. More electron-rich aromatic aldehydes react more rapidly and in higher yield. Preliminary results suggest that the reaction may proceed via the ionization and formal deformylation of an aldol intermediate