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Unlabelled: Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students' interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training., Importance: Engagement of undergraduate students in scientific research at early stages in their careers presents an opportunity to excite students about science, technology, engineering, and mathematics (STEM) disciplines and promote continued interests in these areas. Many excellent course-based undergraduate research experiences have been developed, but scaling these to a broader impact with larger numbers of students is challenging. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunting Advancing Genomics and Evolutionary Science (SEA-PHAGES) program takes advantage of the huge size and diversity of the bacteriophage population to engage students in discovery of new viruses, genome annotation, and comparative genomics, with strong impacts on bacteriophage research, increased persistence in STEM fields, and student self-identification with learning gains, motivation, attitude, and career aspirations.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.

Sixteen squirrel monkey mother and infant dyads were housed in groups of two. They were separated and then immediately reunited in their familiar home cage or in a novel environment, either in conjunction with the second mother-infant dyad, or as a single manipulated pair. Behavioral observations of both dyads were made during the 30-min period following these manipulations; blood samples were then taken for cortisol assay. Mothers' locomotor activity increased when a single dyad was manipulated in the home cage and decreased in the novel environment where proximity between the pairs increased. Cortisol levels varied significantly across conditions, with mothers and infants responding to different stimuli. Mothers responded primarily to social disruption, including separation from the other dyad, and infants responded most clearly to novelty and separation from the other dyad. No significant differences were observed over base levels when both mother and infant pairs were reunited in the home cage, indicating that changes were not due to the disturbance involved in the separation procedure.

A modification of the histochemical method for myosin ATPase was used to determine the myofibril complement, mean myofibril size and myofibrillar packing of defined muscle fibre types in rat skeletal muscle. Fast muscle fibres (Types IIA and IIB) were found to have smaller myofibrils and a lower packing density than slower (Type I) fibres. These findings were discussed with respect to their relevance in estimations of muscle strength from histological and histochemical preparations of muscle cross-sections.

The possibility of a "hippocampal syndrome' was investigated in mature animals whose mothers had received a period of undernutrition during pregnancy and throughout lactation. Spontaneous alternation behaviour was abolished, and performance was found to be at chance level. Significant depletions in cell numbers were found throughout the hippocampal region; however, hippocampal theta rhythm remained and threshold levels for theta driving appeared normal. It was concluded that the behavioural differences observed did no arise from some simple deficit in the circuitry controlling hippocampal theta rhythm and that it was more likely due to an impairment at the synaptic level. The similarity of these, and other recent behavioural observations, to those of animals with hippocampal damage may provide a reasonable basis for investigating a number of learning deficits induced by early undernutrition.

Recent studies have shown that rats have a remarkable ability to keep track of their spatial location. Explanations stress the involvement of a form of short-term (working) memory in which the hippocampus appears to play a major role. The hippocampus appears to be vulnerable to early undernutrition and preliminary investigations indicate that Areas CA3 and CA4 suffer the most. Ninety-day-old rats, previously undernourished prenatally and throughout lactation, were tested in an 8- and, then, a 16-arm radial maze. Significant differences were observed between the experimental and control groups on both tests, especially in the 16-arm maze. Error distributions were also significantly different with experimental animals tending to perseverate in 1 area of the maze. Differences were also observed in the time taken to make the choices and in exploratory behavior. We conclude that early undernutrition affected the spatial learning ability of the animals and that this may be due to the distortions observed in the normal growth pattern of the hippocampus.

Early undernutrition of male and female rats was effected by limiting the mothers' food supply by 40% during pregnancy and lactation. The rats were killed at the age of 20 weeks and physiologically fast and slow skeletal muscles were prepared for histochemical demonstration of muscle fibre types. In the fast extensor digitorum longus (EDL) and the slow soleus (SOL) significant decreases in muscle weight were seen only in male experimental animals. Decreases in muscle fibre type cross-sectional area were found in the EDL in both males and females. In SOL, both fibre types showed evidence of fibre hypertrophy, and this was statistically significant in male animals. No changes were seen in the proportions present of the fibre types in either of the muscles.

Following high-frequency stimulation of hippocampal dentate granule cells, potentiation was difficult to achieve in undernourished animals, showed a significant decline within 3 to 6 hr, and was completely absent at 24 hr. Further trains of stimulation resulted in only small benefits in undernourished animals. Coupled with previously reported morphological and behavioral deficits, these findings indicate a marked hippocampal dysfunction resulting from early undernutrition and provide a potentially valuable approach for relating nutritionally induced behavioral impairments to brain function.

Male rats were subjected to early undernutrition by limiting the mothers' food supply by 50% during pregnancy and lactation. At age 36 weeks, quantitative cytochemical determinations of succinic dehydrogenase activity were made in muscle fibres from the anterior tibialis and soleus muscles. Marked decreases were found in the former muscle but relatively little decrease was seen in the latter. This response of the muscles to early undernutrition was discussed with reference to other studies on pre and post-natal starvation.

Twelve elderly and 12 young subjects were tested on a series of experiments with increasing complexity of perceptual-response mapping. As task complexity increased the differential slowing in performance between young and old increased and an ageXtask complexity interaction was observed. However, with practice this phenomenon disappeared leaving an apparent age lag constant. This slowing was due to increased central processing time rather than peripheral factors. No major differences in strategies were observed between the groups, though the old subjects tended to be less able to extract critical (useful) features from the display. Stimulus repetitions of a new kind were found where all characteristics of the stimulus (relevant and irrelevant) were important. Repetitions of coding rules rather than of particular signals or responses also facilitated RT. It was also found that later in practice old subjects were making fewer errors than the young, reversing earlier observations.

Pre and perinatal malnutrition of rats was effected by means of limiting the mothers' food intake by 50% during pregnancy and lactation. Male offspring were sacrificed at 36 weeks of age and the anterior tibialis (ANTIB) and soleus (SOL) muscles were prepared for histochemical demonstration of Type I, IIA and IIB muslce fibre types using myosin ATPase and succinic dehydrogenase activity. Muscle weights and mean muscle fibre area determinations showed greater decreases in ANTIB than SOL, SOL muscle fibre areas being relatively unaffected by the undernutrition regimen. The proportions present of the muscle fibre types differed in ANTIB and to a small extent on SOL. In the former muscle, some decreases in area in certain of the fibres were associated with increases in the percentages present, showing a tendency to maintain the physiological cross-sectional area of the muscle.

Twelve infant squirrel monkeys were separated from their mothers once every 48 hr for a total of 20 separations. Half of the infants experienced separations for a fixed interval (FI) of 30 min. The remaining 6 infants experienced separations for a variable interval (VI) which averaged 30 min. During the separation periods, movement and vocalizations were recorded. Blood was sampled for later cortisol assay after the 1st, 5th, 10th, 15th, and final separation. The FI group showed increased levels of movement and vocalization over repeated separations when compared with the VI group. Cortisol showed significant increases over basal levels and remained elevated throughout the entire period in both groups. These findings suggest that predictability may be more stressful than unpredictability when organisms cannot control the predicted event.