Effect of gonadotropin-releasing hormone on fertility in repeat-breeder California dairy cows

To assess the potential benefit to fertility from gonadotropin-releasing hormone (GnRH) administration to third service cows managed in typical California dairy systems, 963 cows were enlisted from 14 dairies served by 6 veterinary practices. The cows were randomly assigned to receive either GnRH (100 mug) or placebo at the time of the third artificial insemination. Fertility data were entered onto a proprietary microcomputer program common to all six practices, and collated independently by a third party. For the duration of the trial (1 yr), GnRH and placebo-treated cows had 43.2 and 39.3% conception rates, respectively (P=0.35). When treatments administered in summer months (July, August, September) were excluded, conception rates were 48.1 and 41.0%, respectively (P<0.1). The conception rates of cows treated with GnRH in August tended to be lower than those of placebo-treated cows (95% logarithmic confidence intervals of odds ratio = -1.139, 0.377). Between-herd variation in benefit from GnRH was evident, with two dairies showing no benefit, one dairy showing a negative effect, and four showing a range of effects from lightly beneficial to significantly beneficial. First-lactation cows did not benefit at any time from GnRH treatment. The data suggest that GnRH administered to third-service dairy cows under California conditions may result in increased conception rates in non-summer months, but that other unidentified variables may have important influence on the outcome of such treatment.     

Implementing team‐based learning in the life sciences: A case study in an online introductory level evolution and biodiversity course

Team‐Based Learning (TBL) is a pedagogical tool that has great potential to develop student engagement, accountability, and equity in the online classroom. TBL is rooted in evidence‐based educational theories and practices that underlie many active learning approaches such as self‐testing, team discussion, and application of knowledge. The use of these approaches is associated with better student performance, retention, and sense of belonging in the classroom, aspects that are often reported to be especially lacking in online courses. Here, we describe how we implemented TBL in a face‐to‐face and an online introductory level evolution and biodiversity course. We implemented TBL in the face‐to‐face course (~200 students) starting in 2018 and in the online course (~30 students) starting in the summer of 2019. We used several online applications to facilitate the transition to an online platform such as Simbio, Slack, VoiceThread, Articulate 360, and Teammates. Our experiences using TBL approaches in the online course have been rewarding, and students are engaged and accountable for their learning and performed well in the course. Our goal is to provide an example of how we designed a life science course using TBL approaches and transitioned the course to an online environment. With the current switch to remote instruction and online learning, we recommend the use of TBL as a course design approach that can improve the students’ online learning experience.     

The E46K mutation modulates α-synuclein prion replication in transgenic mice

In multiple system atrophy (MSA), the α-synuclein protein misfolds into a self-templating prion conformation that spreads throughout the brain, leading to progressive neurodegeneration. While the E46K mutation in α-synuclein causes familial Parkinson’s disease (PD), we previously discovered that this mutation blocks in vitro propagation of MSA prions. Recent studies by others indicate that α-synuclein adopts a misfolded conformation in MSA in which a Greek key motif is stabilized by an intramolecular salt bridge between residues E46 and K80. Hypothesizing that the E46K mutation impedes salt bridge formation and, therefore, exerts a selective pressure that can modulate α-synuclein strain propagation, we asked whether three distinct α-synuclein prion strains could propagate in TgM47^+/- mice, which express human α-synuclein with the E46K mutation. Following intracranial injection of these strains, TgM47^+/- mice were resistant to MSA prion transmission, whereas recombinant E46K preformed fibrils (PFFs) transmitted neurological disease to mice and induced the formation of phosphorylated α-synuclein neuropathology. In contrast, heterotypic seeding following wild-type (WT) PFF–inoculation resulted in preclinical α-synuclein prion propagation. Moreover, when we inoculated TgM20^+/- mice, which express WT human α-synuclein, with E46K PFFs, we observed delayed transmission kinetics with an incomplete attack rate. These findings suggest that the E46K mutation constrains the number of α-synuclein prion conformations that can propagate in TgM47^+/- mice, expanding our understanding of the selective pressures that impact α-synuclein prion replication.     

Does Respondent Driven Sampling Alter the Social Network Composition and Health-Seeking Behaviors of Illicit Drug Users Followed Prospectively?

Respondent driven sampling (RDS) was originally developed to sample and provide peer education to injection drug users at risk for HIV. Based on the premise that drug users'' social networks were maintained through sharing rituals, this peer-driven approach to disseminate educational information and reduce risk behaviors capitalizes and expands upon the norms that sustain these relationships. Compared with traditional outreach interventions, peer-driven interventions produce greater reductions in HIV risk behaviors and adoption of safer behaviors over time, however, control and intervention groups are not similarly recruited. As peer-recruitment may alter risk networks and individual risk behaviors over time, such comparison studies are unable to isolate the effect of a peer-delivered intervention. This analysis examines whether RDS recruitment (without an intervention) is associated with changes in health-seeking behaviors and network composition over 6 months. New York City drug users (N = 618) were recruited using targeted street outreach (TSO) and RDS (2006–2009). 329 non-injectors (RDS = 237; TSO = 92) completed baseline and 6-month surveys ascertaining demographic, drug use, and network characteristics. Chi-square and t-tests compared RDS- and TSO-recruited participants on changes in HIV testing and drug treatment utilization and in the proportion of drug using, sex, incarcerated and social support networks over the follow-up period. The sample was 66% male, 24% Hispanic, 69% black, 62% homeless, and the median age was 35. At baseline, the median network size was 3, 86% used crack, 70% used cocaine, 40% used heroin, and in the past 6 months 72% were tested for HIV and 46% were enrolled in drug treatment. There were no significant differences by recruitment strategy with respect to changes in health-seeking behaviors or network composition over 6 months. These findings suggest no association between RDS recruitment and changes in network composition or HIV risk, which supports prior findings from prospective HIV behavioral surveillance and intervention studies.     

A DExH/D-box protein coordinates the two steps of splicing in a group I intron

Proteins of the DExH/D family are ATPases that can unwind duplex RNA in vitro. Individual members of this family coordinate many steps in ribonucleoprotein enzyme assembly and catalysis in vivo, but it is largely unknown how the action of these co-factors is specified and precisely timed. As a first step to address this question biochemically, we describe the development of a new protein-dependent group I intron splicing system that requires such an ATPase for coordinating successive steps in splicing. While genetic analysis in yeast has shown that at least five nuclear-encoded proteins are required for splicing of the mitochondrial aI5β group I intron, we show that efficient in vitro splicing of aI5β occurs with only two of these co-factors and, furthermore, they fulfill distinct functions in vitro. The Mrs1p protein stabilizes RNA structure and promotes the first step in splicing. In contrast, a DExH/D protein, Mss116p, acts after the first step and, utilizing ATP hydrolysis, specifically enhances the efficiency of exon ligation. An analysis of Mss116p variants with mutations that impair its RNA-stimulated ATP hydrolysis activity or reduce its ability to unwind duplexes show that the efficiency of ATP hydrolysis is a major determinant in promoting exon ligation. These observations suggest that Mss116p acts in aI5β splicing by catalyzing changes in the structure of the RNA/protein splicing intermediate that promote the second step. More broadly, these observations are consistent with a model in which the “functional-timing” of DExH/D-box protein action can be specified by a specific conformation of its substrate due to the “upstream” activity of other co-factors.     

The oxidation of proline by mitochondrial preparations

The oxidation by mitochondria of various rat tissues of proline, pyrroline-5-carboxylate (P5C) and a number of aldehydes has been studied and ADP/O ratios determined for liver mitochondria. High oxidative activity for proline and P5C was found only in the liver and kidney. During the oxidation by liver and kidney mitochondria of proline and P5C; glutamate, ammonia, aspartate and some ornithine accumulated, thus suggesting that proline may normally be converted to ornithine by mitochondria. The oxidation of P5C (glutamic acid semialdehyde) by a mitochondrial dehydrogenase may be the same enzyme that oxidizes succinic acid semi-aldehyde but different from that oxidizing acetaldehyde.     

The importance of arginine in evolution

The special chemistry and metabolism of arginine has been considered in relation to the evolution of metabolic and structural features of animals. Arginine and compounds derived from it act in muscle as a major reserve of ATP and as a regulatory sink for phosphate. The metabolism of arginine in less complex animals has been extended to produce urea, firstly as an osmotic regulator and subsequently as a means for terrestrial animals to excrete surplus nitrogen. The ornithine component of arginine is metabolised to form important polyamines and also proline. It is also argued that the change from phosphoarginine to phosphocreatine was a permissive step in the development of the vertebrates which are rich in connective tissue.