Search

Expectancy-value theory of motivation (EVT) suggests that student values influence their likelihood of putting in the effort required to learn, and these values can be shaped by student characteristics, such as their experiences, sociodemographics, and disciplinary norms. To understand the extent to which these characteristics relate to students' values, we surveyed 1162 graduating science, technology, engineering, and mathematics (STEM) students across four universities using the previously developed and validated Survey of Teaching Beliefs and Practices for Undergraduates (STEP-U). The STEP-U survey included Likert questions to capture students' values of 27 cross-disciplinary skills and the frequency with which they experienced 27 instructional methods thought to develop particular skills. Exploratory factor analyses (EFA) showed an understandable factor structure for both students' perceived value of cross-disciplinary skills and frequency of classroom experiences. Using multiple regression, we identified differences in values that were associated with classroom experiences, STEM discipline, participation in undergraduate research, and student sociodemographics. Findings were generalizable across institutions and disciplines. The theoretical framework (EVT), the broad data collection (four institutions with multiple disciplines), and the type of data analyses (e.g., EFA) used provide theoretical, methodological, and practical contributions and suggest additional directions for future research.

The New York State (NYS) Office of Mental Health created the NYS COVID-19 Emotional Support Helpline and enlisted graduate students to provide phone-based emotional support initially to the NYS community. This NYS-funded initiative transformed into providing psychosocial support for callers across the United States. Four NYS doctoral students acted as the helpline agents and received 251 individual calls from May-August 2020. The agents documented the calls with clinical notes which cannot be traced back to specific callers. The purpose of this retrospective qualitative study was to explore the themes that emerged from the calls to give voice to the trauma that callers were reporting during the early phases of the pandemic, and the resilience they demonstrated as they engaged with the Helpline. The agents' clinical transcripts were converted into codes using a critical-constructivist grounded theory approach (Levitt, 2021) with the NVIVO qualitative data analysis software. A second research team audited the initial codes for construct clarity. Emergent themes detailed the unique traumas that helpline callers divulged, how the agents provided support, and the callers' capacities for resilience. Recommendations are suggested to inform clinicians working with pandemic survivors, to offer guidance on providing distance or virtual interventions as well as to enhance policymakers' understanding of addressing mental health needs across populations served via the NYS COVID-19 Emotional Support Helpline.

Objective: To identify common causes of injury and liability claims related to cutaneous laser surgery from 2012 to 2020., Materials and Methods: Search of online national legal database of public legal documents regarding cutaneous laser surgery litigation., Results: From 2012 to 2020, 69 cases of liability claims due to a cutaneous laser surgery device were identified. Of these, 49 (71%) involved a nonphysician operator (NPO); 12 incidents (17%) involved non-core physician operators performing the procedure; 6 cases (9%) involved a plastic surgeon operator; and 2 cases (3%) involved a dermatologist operator. Laser hair removal was most litigated (44 cases, 64%), followed by laser skin rejuvenation (20 cases, 30%). Thirty-six of 69 cases had a discernible outcome, 53% (n = 19) rendered judgements in favor of the plaintiff, with a mean indemnity payment of $320,975 (range, $1,665-$1.5 million)., Conclusion: Previous work evaluating trends in laser surgery litigation from 1985 to 2012 identified increasing injury and legal action when performed by NPOs. Data from this study are consistent with these previous findings. Both studies demonstrate that NPOs account for most cases of legal action with an increasing proportion of cases being performed by NPOs. In this study, unsupervised NPOs comprise nearly three-quarters of laser surgery lawsuits, but the data may underestimate the frequency of injury and litigation caused by unsupervised NPOs., (Copyright © 2021 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Herein, we describe the discovery and optimization of a novel series that inhibits bacterial DNA gyrase and topoisomerase IV via binding to, and stabilization of, DNA cleavage complexes. Optimization of this series led to the identification of compound 25 , which has potent activity against Gram-positive bacteria, a favorable in vitro safety profile, and excellent in vivo pharmacokinetic properties. Compound 25 was found to be efficacious against fluoroquinolone-sensitive Staphylococcus aureus infection in a mouse thigh model at lower doses than moxifloxacin. An X-ray crystal structure of the ternary complex formed by topoisomerase IV from Klebsiella pneumoniae , compound 25 , and cleaved DNA indicates that this compound does not engage in a water-metal ion bridge interaction and forms no direct contacts with residues in the quinolone resistance determining region (QRDR). This suggests a structural basis for the reduced impact of QRDR mutations on antibacterial activity of 25 compared to fluoroquinolones.

Starting in the early 2000's, several reports were released recognizing the convergence of mathematics, biology and computer science, and calling for a rethinking of how undergraduates are prepared for careers in research and the science and technology workforce. This call for change requires careful consideration of the mathematical biology education system to identify key components and leverage points for change. This paper demonstrates the wide range of resources and approaches available to the mathematical biology education community to create systemic change by highlighting the efforts of four community-based education reform organizations. A closer look at these organizations provides an opportunity to examine how to leverage components of the education system including faculty, academic institutions, students, access to resources, and the power of community.

Since their discovery over 5 decades ago, quinolone antibiotics have found enormous success as broad spectrum agents that exert their activity through dual inhibition of bacterial DNA gyrase and topoisomerase IV. Increasing rates of resistance, driven largely by target-based mutations in the GyrA/ParC quinolone resistance determining region, have eroded the utility and threaten the future use of this vital class of antibiotics. Herein we describe the discovery and optimization of a series of 4-(aminomethyl)quinolin-2(1 H )-ones, exemplified by 34 , that inhibit bacterial DNA gyrase and topoisomerase IV and display potent activity against ciprofloxacin-resistant Gram-negative pathogens. X-ray crystallography reveals that 34 occupies the classical quinolone binding site in the topoisomerase IV-DNA cleavage complex but does not form significant contacts with residues in the quinolone resistance determining region.

Upregulated expression of efflux pumps, lpxC target mutations, LpxC protein overexpression, and mutations in fabG were previously shown to mediate single-step resistance to the LpxC inhibitor CHIR-090 in P. aeruginosa Single-step selection experiments using three recently described LpxC inhibitors (compounds 2, 3, and 4) and mutant characterization showed that these mechanisms affect susceptibility to additional novel LpxC inhibitors. Serial passaging of P. aeruginosa wild-type and efflux pump-defective strains using the LpxC inhibitor CHIR-090 or compound 1 generated substantial shifts in susceptibility and underscored the interplay of efflux and nonefflux mechanisms. Whole-genome sequencing of CHIR-090 passage mutants identified efflux pump overexpression, fabG mutations, and novel mutations in fabF1 and in PA4465 as determinants of reduced susceptibility. Two new lpxC mutations, encoding A214V and G208S, that reduce susceptibility to certain LpxC inhibitors were identified in these studies, and we show that these and other target mutations differentially affect different LpxC inhibitor scaffolds. Lastly, the combination of target alteration (LpxC A214V ) and upregulated expression of LpxC was shown to be tolerated in P. aeruginosa and could mediate significant decreases in susceptibility., (Copyright © 2019 American Society for Microbiology.)

The Gram-negative cell envelope presents a formidable barrier to xenobiotics, and achieving sufficient compound exposure inside the cell is a key challenge for the discovery of new antibiotics. To provide insight on the molecular determinants governing compound exposure in Gram-negative bacteria, we developed a methodology leveraging a cyclooctyne-based bioorthogonal probe to assess compartment-specific compound exposure. This probe can be selectively localized to the periplasmic or cytoplasmic compartments of Gram-negative bacteria. Once localized, the probe is used to test azide-containing compounds for exposure within each compartment by quantifying the formation of click-reaction products by mass spectrometry. We demonstrate this approach is an accurate and sensitive method of determining compartment-specific compound exposure profiles. We then apply this technology to study the compartment-specific exposure profiles of a small panel of azide-bearing compounds with known permeability characteristics in Gram-negative bacteria, demonstrating the utility of the system and the insight it is able to provide regarding compound exposure within intact bacteria.

Tightly synchronized reproduction in vast wildebeest herds underpins the keystone role this iconic species plays in the Serengeti. However, despite decades of study, the proximate synchronizing mechanism remains unknown. Combining a season-long field experiment with simple stochastic process models, we show that females exposed to playback of male rutting vocalizations are over three times more synchronous in their expected time to mating than a control group isolated from all male stimuli. Additionally, predictions of both mating and calving synchrony based on the playback group were highly consistent with independent data on wildebeest mating and calving synchrony, while control-based predictions were inconsistent with the data. Taken together, our results provide the first experimental evidence that male rutting vocalizations alone could account for the highly synchronized reproduction observed in Serengeti wildebeest. Given anthropogenically driven losses in many areas, a mechanistic understanding of synchrony can highlight additional risks declining wildebeest populations may face.

Misconceptions, also known as alternate conceptions, about key concepts often hinder the ability of students to learn new knowledge. Concept inventories (CIs) are designed to assess students' understanding of key concepts, especially those prone to misconceptions. Two-tiered CIs include prompts that ask students to explain the logic behind their answer choice. Such two-tiered CIs afford an opportunity for faculty to explore the student thinking behind the common misconceptions represented by their choice of a distractor. In this study, we specifically sought to probe the misconceptions that students hold prior to beginning an introductory microbiology course (i.e., preconceptions). Faculty-learning communities at two research-intensive universities used the validated Host-Pathogen Interaction Concept Inventory (HPI-CI) to reveal student preconceptions. Our method of deep analysis involved communal review and discussion of students' explanations for their CI answer choice. This approach provided insight valuable for curriculum development. Here the process is illustrated using one question from the HPI-CI related to the important topic of antibiotic resistance. The frequencies with which students chose particular multiple-choice responses for this question were highly correlated between institutions, implying common underlying misconceptions. Examination of student explanations using our analysis approach, coupled with group discussions within and between institutions, revealed patterns in student thinking to the participating faculty. Similar application of a two-tiered concept inventory by general microbiology instructors, either individually or in groups, at other institutions will allow them to better understand student thinking related to key concepts in their curriculum.

We present a novel assessment tool for measuring biology students' values and experiences across their undergraduate degree program. Our Survey of Teaching Beliefs and Practices for Undergraduates (STEP-U) assesses the extent to which students value skills needed for the workplace (e.g., ability to work in groups) and their experiences with teaching practices purported to promote such skills (e.g., group work). The survey was validated through factor analyses in a large sample of biology seniors (n = 1389) and through response process analyses (five interviewees). The STEP-U skills items were characterized by two underlying factors: retention (e.g., memorization) and transfer (e.g., knowledge application). Multiple linear regression models were used to examine relationships between classroom experiences, values, and student characteristics (e.g., gender, cumulative grade point average [GPA], and research experience). Student demographic and experiential factors predicted the extent to which students valued particular skills. Students with lower GPAs valued retention skills more than those with higher GPAs. Students with research experience placed greater value on scientific writing and interdisciplinary understanding. Greater experience with specific teaching practices was associated with valuing the corresponding skills more highly. The STEP-U can provide feedback vital for designing curricula that better prepare students for their intended postgraduate careers., (© 2016 G. Marbach-Ad et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

This study investigated the impact of three commonly used cardiovascular model-assisted activities on student learning and student attitudes and perspectives about science. College students enrolled in a Human Anatomy and Physiology course were randomly assigned to one of three experimental groups (organ dissections, virtual dissections, or plastic models). Each group received a 15-min lecture followed by a 45-min activity with one of the treatments. Immediately after the lesson and then 2 mo later, students were tested on anatomy and physiology knowledge and completed an attitude survey. Students who used plastic models achieved significantly higher overall scores on both the initial and followup exams than students who performed organ or virtual dissections. On the initial exam, students in the plastic model and organ dissection treatments scored higher on anatomy questions than students who performed virtual dissections. Students in the plastic model group scored higher than students who performed organ dissections on physiology questions. On the followup exam, when asked anatomy questions, students in the plastic model group scored higher than dissection students and virtual dissection students. On attitude surveys, organ dissections had higher perceived value and were requested for inclusion in curricula twice as often as any other activity. Students who performed organ dissections were more likely than the other treatment groups to agree with the statement that "science is fun," suggesting that organ dissections may promote positive attitudes toward science. The findings of this study provide evidence for the importance of multiple types of hands-on activities in anatomy laboratory courses.

The National Experiment in Undergraduate Science Education project funded by the Howard Hughes Medical Institute is a direct response to the Scientific Foundations for Future Physicians report, which urged a shift in premedical student preparation from a narrow list of specific course work to a more flexible curriculum that helps students develop broad scientific competencies. A consortium of four universities is working to create, pilot, and assess modular, competency-based curricular units that require students to use higher-order cognitive skills and reason across traditional disciplinary boundaries. Purdue University; the University of Maryland, Baltimore County; and the University of Miami are each developing modules and case studies that integrate the biological, chemical, physical, and mathematical sciences. The University of Maryland, College Park, is leading the effort to create an introductory physics for life sciences course that is reformed in both content and pedagogy. This course has prerequisites of biology, chemistry, and calculus, allowing students to apply strategies from the physical sciences to solving authentic biological problems. A comprehensive assessment plan is examining students' conceptual knowledge of physics, their attitudes toward interdisciplinary approaches, and the development of specific scientific competencies. Teaching modules developed during this initial phase will be tested on multiple partner campuses in preparation for eventual broad dissemination.

High-throughput phenotypic screening against the yeast Saccharomyces cerevisiae revealed a series of triazolopyrimidine-sulfonamide compounds with broad-spectrum antifungal activity, no significant cytotoxicity, and low protein binding. To elucidate the target of this series, we have applied a chemogenomic profiling approach using the S. cerevisiae deletion collection. All compounds of the series yielded highly similar profiles that suggested acetolactate synthase (Ilv2p, which catalyzes the first common step in branched-chain amino acid biosynthesis) as a possible target. The high correlation with profiles of known Ilv2p inhibitors like chlorimuron-ethyl provided further evidence for a similar mechanism of action. Genome-wide mutagenesis in S. cerevisiae identified 13 resistant clones with 3 different mutations in the catalytic subunit of acetolactate synthase that also conferred cross-resistance to established Ilv2p inhibitors. Mapping of the mutations into the published Ilv2p crystal structure outlined the chlorimuron-ethyl binding cavity, and it was possible to dock the triazolopyrimidine-sulfonamide compound into this pocket in silico. However, fungal growth inhibition could be bypassed through supplementation with exogenous branched-chain amino acids or by the addition of serum to the medium in all of the fungal organisms tested except for Aspergillus fumigatus. Thus, these data support the identification of the triazolopyrimidine-sulfonamide compounds as inhibitors of acetolactate synthase but suggest that targeting may be compromised due to the possibility of nutrient bypass in vivo.

Mycograb C28Y is a recombinant human antibody fragment thought to target HSP-90 and potentiate amphotericin B (AMB). Absence of in vivo efficacy led us to reevaluate its in vitro activity. Interactions between AMB and Mycograb were investigated using a checkerboard design. Addition of Mycograb or various unrelated proteins, including human serum, resulted in similar decreases in the MIC of AMB. Potentiation of AMB by Mycograb appears to be a nonspecific protein effect.

This essay describes how the use of a concept inventory has enhanced professional development and curriculum reform efforts of a faculty teaching community. The Host Pathogen Interactions (HPI) teaching team is composed of research and teaching faculty with expertise in HPI who share the goal of improving the learning experience of students in nine linked undergraduate microbiology courses. To support evidence-based curriculum reform, we administered our HPI Concept Inventory as a pre- and postsurvey to approximately 400 students each year since 2006. The resulting data include student scores as well as their open-ended explanations for distractor choices. The data have enabled us to address curriculum reform goals of 1) reconciling student learning with our expectations, 2) correlating student learning with background variables, 3) understanding student learning across institutions, 4) measuring the effect of teaching techniques on student learning, and 5) demonstrating how our courses collectively form a learning progression. The analysis of the concept inventory data has anchored and deepened the team's discussions of student learning. Reading and discussing students' responses revealed the gap between our understanding and the students' understanding. We provide evidence to support the concept inventory as a tool for assessing student understanding of HPI concepts and faculty development.

There is widespread agreement within the scientific and education communities that undergraduate biology curricula fall short in providing students with the quantitative and interdisciplinary problem-solving skills they need to obtain a deep understanding of biological phenomena and be prepared fully to contribute to future scientific inquiry. MathBench Biology Modules were designed to address these needs through a series of interactive, Web-based modules that can be used to supplement existing course content across the biological sciences curriculum. The effect of the modules was assessed in an introductory biology course at the University of Maryland. Over the course of the semester, students showed significant increases in quantitative skills that were independent of previous math course work. Students also showed increased comfort with solving quantitative problems, whether or not they ultimately arrived at the correct answer. A survey of spring 2009 graduates indicated that those who had experienced MathBench in their course work had a greater appreciation for the role of mathematics in modern biology than those who had not used MathBench. MathBench modules allow students from diverse educational backgrounds to hone their quantitative skills, preparing them for more complex mathematical approaches in upper-division courses.

Despite the importance of the western white-bearded wildebeest (Connochaetes taurinus mearnsi) to the Serengeti-Mara ecosystem, surprisingly little is known about the reproductive physiology of this keystone species. A longitudinal, non-invasive endocrine study was conducted on female wildebeest captured from the Serengeti-Mara migration and maintained for approximately 16 months in large fenced enclosures within the species' natural range. An intact bull was introduced to a female subgroup (n=5), while remaining females (n=10) were unexposed to a male. Fecal progestagen patterns reflected ovarian activity and pregnancy. In non-pregnant animals, luteal and inter-luteal baseline progestagen values differed (p<0.001) over time, thereby allowing identification of recurrent estrous cycles. The average durations of the luteal phase, estrous cycle, gestation, and post-partum anestrus were 14.3+/-0.5, 22.6+/-1.0, 240.8+/-11.7, and 104.1+/-15.6 d, respectively. Annual reproductive patterns indicated a distinctive period of ovarian activity that extended from 13 May through 3 December (203.5+/-29.9 d) with all unmated females displaying from one to 14 estrous cycles. Progestagens were higher (p <0.001) in pregnant (n=4) than non-pregnant (n=10) cows. These data (1) reveal the value of fecal hormone monitoring for establishing the first ever endocrine profiles of female wildebeest in semi-free-living conditions in their native range, and (2) indicate that the species is a seasonal breeder that is polyestrous and a spontaneous ovulator., ((c) 2009 Elsevier Inc. All rights reserved.)

As research faculty with expertise in the area of host-pathogen interactions (HPI), we used a research group model to effect our professional development as scientific educators. We have established a working hypothesis: The implementation of a curriculum that forms bridges between our seven HPI courses allows our students to achieve deep and meaningful learning of HPI concepts. Working collaboratively, we identified common learning goals, and we chose two microorganisms to serve as anchors for student learning. We instituted variations of published active-learning methods to engage students in research-oriented learning. In parallel, we are developing an assessment tool. The value of this work is in the development of a teaching model that successfully allowed faculty who already work collaboratively in the research area of HPI to apply a "research group approach" to further scientific teaching initiatives at a research university. We achieved results that could not be accomplished by even the most dedicated instructor working in isolation.

Techniques for manipulating the oestrous cycle of sable antelope, Hippotragus niger, were evaluated in a captive population of 24 females maintained at the Smithsonian Institution's Conservation and Research Center in Front Royal, VA, USA. A secondary objective was to demonstrate the effectiveness of fecal steroid monitoring techniques as a non-invasive method of tracking experimental manipulations. Controlled Internal Drug Releasing (CIDR) devices designed for cattle (type B, reduced in length by 5 cm to fit the sable antelope's smaller reproductive tract) were more effective than CIDR devices designed for goats (type G) at delivering progesterone into circulation, and maintained serum progesterone at levels up to 86.1+/-7.8% of normal luteal concentrations in females whose spontaneous ovarian activity had been inhibited with melengestrol acetate. Serum progesterone and fecal progestagen measurements were highly correlated (P<0.05). Synchronization treatments of prostaglandin (PG) F2alpha alone and in combination with modified CIDR-B devices (12-day insertion interval) were both effective in inducing synchronized ovulation, however the PGF2alpha/modified CIDR-B treatment resulted in more precise synchrony and a shorter latency to ovulation than did PGF2alpha alone. In a separate experiment to characterize the temporal relationship between synchronization treatment, behavioral oestrus and ovulation, onset of behavioral oestrus occurred 34.1+/-5.7 h following PGF2alpha/modified CIDR-B treatment. Mean duration of the induced oestrus was 24.9+/-4.3 h. The first detectable rise in fecal progestagens occurred 5.1+/-1.0 and 4.1+/-1.0 days following PGF2alpha/modified CIDR-B treatment in groups of females housed with and without an adult male, respectively, indicating that the presence of a male did not accelerate the onset of the induced cycle.

Fecal progesterone metabolite monitoring techniques were validated for the sable antelope and used to characterize ovarian cycle dynamics and reproductive seasonality in a captive population at the National Zoological Park's Conservation and Research Center. Hormone was homogeneously distributed within fecal samples. Longitudinal fluctuations in fecal progesterone metabolites were consistent with typical luteal phase patterns and corresponded closely with changes in serum progesterone. The lag time from an im injection of progesterone to peak excretion in feces was 16 h. The pattern of births showed a slight peak in the summer (May-July), but year-round endocrine monitoring of six nonpregnant females showed no evidence of seasonality in ovarian activity. Females exhibited 11-14 estrous cycles per year, averaging 24.2 +/- 0.9 days in length. Luteal and interluteal phases were 18.4 +/- 0.9 and 5.8 +/- 0.4 days in length, respectively. Although only a small number of hippotragine antelope species have been studied, data indicate that they exhibit considerable interspecific variability in estrous cycle length and reproductive seasonality and thus may be a useful group for further investigation of factors regulating fertility., (Copyright 1998 Academic Press.)

I studied the relationship between the timing of birth relative to other births in the social group, and the rate of spatial integration into the herd in six cohorts of semi-free-ranging infant sable antelope at the National Zoological Park's Conservation and Research Center near Front Royal, Virginia. All calves spent the initial few days of life resting in seclusion ('hiding'), and interacted with mothers and other conspecifics only during activity bouts. With time, calves became increasingly likely to rest apart from the herd with other calves in crèches, and by 6 weeks of age, calves remained with the herd throughout all resting and activity bouts. The rate of spatial integration for individual calves depended upon the calf's birth date and the availability of peers of similar age (birth clustering). Only the first few calves born in each cohort were observed in crèches, and crèche groups synchronized their entry into the herd. First-born calves remained in crèches longer and began resting with the herd later in life than calves born later in the cohort. Last-born calves typically did not form crèches, but instead rested with the herd from an early age. Other infants may serve as social cover during the time that infants form crèches and when they first begin to accompany the herd. The observed individual differences in the rate of spatial integration may represent individual adjustments in response to the varying degrees of protection offered by the spatial environment. Copyright 1998 The Association for the Study of Animal Behaviour.

Trios of prairie voles (Microtus ochrogaster) composed of either two estrous sibling or nonsibling females and one male were monitored via time-lapse videotaping over 72 hr. Social and sexual behaviors were analyzed as a function of trio type (sibling or nonsibling) and fate (survivor or nonsurvivor) across 12-h time blocks. Within nonsibling trios, females that were able to maintain prolonged physical contact with the male within the first 3 days of trio formation later survived and successfully produced litters; females that did not maintain male contact later died of undetermined causes, presumably related to social stress. Frequencies of sexual behavior were similar in both trio types and both surviving and nonsurviving females received equivalent amounts of copulatory stimulation from the male. Sibling groups exhibited higher levels of female-female side-by-side contact; nonsibling groups exhibited greater amounts of female-initiated anogenital sniffing, and female-initiated aggression. Female-female social interactions may be determined by prior familiarity and/or relatedness and may play a dominant role in determining the social organization and mating system of this species.

The level of heat-labile glucose-6-phosphate dehydrogenase (G6PD) has been measured in skin fibroblast cultures from premature ageing or DNA repair deficient genetic syndromes. The short in vitro longevity of Werner's syndrome, progeria, Cockayne's syndrome, ataxia telangiectasia, Fanconi's anaemia, and Bloom's syndrome cultures was correlated with the appearance of a significant fraction of heat-labile enzyme. Long-lived control cultures contain a low level of altered enzyme until they become senescent. The evidence that heat-labile G6PD molecules are derived from errors in synthesis, or from other causes, is critically assessed. It is shown that normal cells grown in medium containing the antibiotic, paromomycin, which is known to reduce the fidelity of ribosomal translation, produce a significant fraction of altered G6PD.

In attempts to transform and immortalize human cell cultures, skin fibroblasts from normal donors of different ages, from patients with the premature ageing diseases Werner's syndrome (WS) and progeria (PR), and from donors with the cancer-prone diseases ataxia telangiectasia (AT), Bloom's syndrome (BS) and Fanconi's anaemia (FA), were infected with SV40 virus and their growth monitored thereafter. Lesch-Nyhan (LN) fibroblasts were also infected. SV40-infected cultures from two normal and from WS, AT and LN donors attained a spectrum of transformed properties, high mitotic activity at confluence, presence of T-antigen, anchorage independence and altered morphology. Most of these pretransformed cultures died in the crisis period. However, two cultures from the WS and LN patients survived the crisis period and have now been grown to more than 200 passages. For the LN culture the crisis period was at least 200 days. Both permanent lines retain the properties of pretransformed cells, but differ in their modal chromosome number and ability to grow in methionine-free medium. It can be concluded from these experiments that transformation by SV40 to permanent lines is a rare event in human skin fibroblasts, even when these cells were taken from patients predisposed to form cancers.