A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method ...reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ~90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a-regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2) as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4). Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division.
An iconoclast and best-selling author of both nonfiction and fiction, Elizabeth Marshall Thomas has spent a lifetime observing, thinking, and writing about the cultures of animals such as lions, ...wolves, dogs, deer, and humans. In this compulsively readable book, she provides a plainspoken, big-picture look at the commonality of life on our planet, from the littlest microbes to the largest lizards.
Inspired by the idea of symbiosis in evolution—that all living things evolve in a series of cooperative relationships—Thomas takes readers on a journey through the progression of life. Along the way she shares the universal likenesses, experiences, and environments of “Gaia’s creatures,” from amoebas in plant soil to the pets we love, from proud primates to Homo sapiens hunter-gatherers on the African savanna. Fervently rejecting “anthropodenial,” the notion that nonhuman life does not share characteristics with humans, Thomas instead shows that paramecia can learn, plants can communicate, humans aren’t really as special as we think we are—and that it doesn’t take a scientist to marvel at the smallest inhabitants of the natural world and their connections to all living things.
A unique voice on anthropology and animal behavior, Thomas challenges scientific convention and the jargon that prevents us all from understanding all living things better. This joyfully written book is a fascinating look at the challenges and behaviors shared by creatures from bacteria to larvae to parasitic fungi, a potted hyacinth to the author herself, and all those in between.
Health workers (HWs) in Africa face challenges accessing and learning from existing online training opportunities. To address these challenges, we developed a modular, self-paced, mobile-ready and ...work-relevant online course covering foundational infection prevention and control (IPC) concepts. Here, we evaluate the first pilot of this course, conducted with HWs in Nigeria.
We used a learner-centered design and prototyping process to create a new approach to delivering online training for HWs. The resulting course comprised 10 self-paced modules optimized for use on mobile devices. Modules presented IPC vignettes in which learning was driven by short assessment questions with feedback. Learners were recruited by distributing a link to the training through Nigeria-based email lists, WhatsApp groups and similar networks of HWs, managers and allied professionals. The course was open to learners for 8 weeks. We tracked question responses and time on task with platform analytics and assessed learning gains with pre- and post-testing. Significance was evaluated with the Wilcoxon signed-rank test, and effect size was calculated using Cohen's d.
Three hundred seventy-two learners, with roles across the health system, enrolled in the training; 59% completed all 10 modules and earned a certificate. Baseline knowledge of foundational IPC concepts was low, as measured by pre-test scores (29%). Post-test scores were significantly higher at 54% (effect size 1.22, 95% confidence interval 1.00-1.44). Learning gains were significant both among learners with low pre-test scores and among those who scored higher on the pre-test. We used the Net Promoter Score (NPS), a common user experience metric, to evaluate the training. The NPS was + 62, which is slightly higher than published scores of other self-paced online learning experiences.
High completion rates, significant learning gains and positive feedback indicate that self-paced, mobile-ready training that emphasizes short, low-stakes assessment questions can be an effective, scalable way to train HWs who choose to enroll. Low pre-test scores suggest that there are gaps in IPC knowledge among this learner population.
Advance directives guide healthcare providers to listen to and respect patients' wishes regarding their right to die in circumstances when cardiopulmonary resuscitation is required, and hospitals ...accredited by The Joint Commission are required to have a do-not-resuscitate (DNR) policy in place. However, when surgery and anesthesia are necessary for the care of the patient with a DNR order, this advance directive can create ethical dilemmas specifically involving patient autonomy and the physician's responsibility to do no harm.
This paper discusses the ethical considerations regarding perioperative DNR orders and provides guidance on how to handle situations that may arise in the conduct of perioperative care.
Because of the potential conflicts between ethical care and the restrictions of DNR orders, it is critically important to discuss the medical and ethical issues surrounding this clinical scenario with the patient or surrogate prior to any surgical intervention. However, many anesthesiologists do not adequately address this ethical dilemma prior to the procedure.
Practitioners are advised to first consider what is best for the patient and, when in doubt, to communicate with patients or surrogates and with colleagues to arrive at the most appropriate care plan. If irreconcilable conflicts arise, consultation with the institution's bioethics committee, if available, is beneficial to help reach a resolution.
FOREWORD ELIZABETH MARSHALL THOMAS
Among the Bone Eaters,
09/2015
Book Chapter
Ever since the Neolithic, we have left no stone unturned in distancing ourselves from other species, modifying our language, our laws, and our thoughts accordingly. A person is either he or she, an ...animal is it, we have thoughts, they have instincts, we have language, they have vocalizations, we have culture, they just run around in the woods, doing whatever it is they do, and so forth. During this time, anthropology was invented, as was zoology, and both had no choice but to continue the traditions. We mammals have evolved more than five thousand species, and zoology is concerned with
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