Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Analyzing the impact of a dual lizard introduction on orbweaving spider communities in the Bahamas: an experimental approach

With the global increase in introduced species, it is important to understand the contexts in which these species negatively impact ecosystems. Species introductions are particularly important in structuring island ecosystems, which have high rates of disturbance and colonization (Tilman, 1997). Through a manipulative field experiment, I examined how two introduced lizards (the predatory Leiocephalus carinatus [curly-tailed lizard] and Anolis smaragdinus [green anole]) affected the native lizard (Anolis sagrei [brown anole]) and orbweaving spiders on small islands offshore from Staniel Cay, Bahamas. I showed that while the introduced species strongly affected brown anole height and weakly affected web spider height, they did not affect either brown anole density or web spider density. This suggests that behaviorally mediated interactions like predator avoidance are more important than consumptive interactions in structuring our island communities after the introductions. While many other studies have demonstrated the negative impacts of introduced species, in our system, the introduced species co-existed with native species without affecting population abundances (Towns, 2006; Gillespie et al, 2008)

Designing Business Case Writing As An Experiential Learning Project

The use of experiential learning approaches such as capstone seminars, simulations, case competitions, internships, service learning, and collaborative projects are all practices that are desirable and well documented in the teaching of business courses. Despite research that shows that business case writing can provide students with experiential learning that fosters the understanding of business challenges, ethical situations, and real-world decision-making processes, this pedagogical tool has gained little attention in the experiential learning curriculum (Vega, 2010). To demonstrate the effectiveness of business case writing as an experiential learning tool, we discuss the case writing experience and the learning outcomes for two undergraduate business students who participated in a summer case project at the David Berg Center of Ethics. This paper provides a model for integrating business case writing assignments into business experiential learning courses

Botox combined with myofascial release physical therapy as a treatment for myofascial pelvic pain

Purpose: To report the effects of combined onabotulinumtoxinA (Botox) injections and myofascial release physical therapy on myofascial pelvic pain (MFPP) by comparing pre- and posttreatment average pelvic pain scores, trigger points, and patient selfreported pelvic pain. Secondary outcomes were to examine posttreatment complications and determine demographic differences between patients with/without an improvement in pain. Materials and Methods: This was an Institutional Review Board approved retrospective case series on women over 18 years with MFPP who received Botox and physical therapy between July 2006 and November 2014. Presence of trigger points and pelvic pain scores were determined by digital palpation of the iliococcygeus, puborectalis, obturator internus, and rectus muscles. Average pelvic pain scores (0–10) reflected an average of the scores obtained from palpation of each muscle. Self-reported improvement in pain was recorded as yes/no. Results: Fifty women met the inclusion/exclusion criteria. Posttreatment, patients had lower average pelvic pain scores (3.7±4.0 vs. 6.4±1.8, p=0.005), and fewer trigger points (44% vs. 100%, p<0.001). Fifty-eight percent of patients (95% confidence interval, 44–72) noted an improvement in self-reported pain. Patients most likely to report no improvement in pain had chronic bowel disorders, while those most likely to report an improvement in pain had a history of past incontinence sling (p=0.03). Posttreatment complications included: constipation (8%), worsening urinary retention (2%), and urinary tract infection (4%). Conclusions: Botox combined with soft tissue myofascial release physical therapy under anesthesia can be effective in treating women with chronic pelvic pain secondary to MFPP

Epizootic to enzootic transition of a fungal disease in tropical Andean frogs: Are surviving species still susceptible?

<div><p>The fungal pathogen <i>Batrachochytrium dendrobatidis</i> (Bd), which causes the disease chytridiomycosis, has been linked to catastrophic amphibian declines throughout the world. Amphibians differ in their vulnerability to chytridiomycosis; some species experience epizootics followed by collapse while others exhibit stable host/pathogen dynamics where most amphibian hosts survive in the presence of Bd (e.g., in the enzootic state). Little is known about the factors that drive the transition between the two disease states within a community, or whether populations of species that survived the initial epizootic are stable, yet this information is essential for conservation and theory. Our study focuses on a diverse Peruvian amphibian community that experienced a Bd-caused collapse. We explore host/Bd dynamics of eight surviving species a decade after the mass extinction by using population level disease metrics and Bd-susceptibility trials. We found that three of the eight species continue to be susceptible to Bd, and that their populations are declining. Only one species is growing in numbers and it was non-susceptible in our trials. Our study suggests that some species remain vulnerable to Bd and exhibit ongoing population declines in enzootic systems where Bd-host dynamics are assumed to be stable.</p></div

Differences in survival and Bd infection intensity in two non-susceptible species of terrestrial-breeding frogs, <i>Pristimantis danae</i> and <i>Pristimantis pharangobates</i> (Craugastoridae).

<p>(A, B) Percentage survival, and (C, D) variation in log-transformed zoospore equivalents (Bd infection intensity) of Bd-exposed individuals of <i>Pristimantis danae</i> (left panels) and <i>P</i>. <i>pharangobates</i> (right panel). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186478#pone.0186478.g002" target="_blank">Fig 2</a> for caption details.</p

Variation in Bd infection prevalence for eight species of frogs in the montane forests of Manu National Park, Peru.

<p>Frogs were sampled during the dry season of 2012, approximately a decade after the Bd epizootic caused a collapse of montane amphibian communities.</p

Differences in survival and Bd infection intensity in two species of marsupial frogs <i>Gastrotheca</i> (Hemiphractidae).

<p>(A, B) Percentage survival, and (C, D) variation in log-transformed zoospore equivalents (Bd infection intensity) of Bd-exposed individuals of <i>Gastrotheca excubitor</i> (left panels) and <i>G</i>. <i>nebulanastes</i> (right panel). The shaded band represents the period of daily immersion in itraconazole solution to clear infection, while the shaded box represents the period of experimental exposure to Bd. Red lines represent individuals that died during the trial.</p

Differences in survival and Bd infection intensity in two susceptible species of terrestrial-breeding frogs, <i>Pristimantis platydactylus</i> and <i>Pristimantis toftae</i> (Craugastoridae).

<p>(A, B) Percentage survival, and (C, D) variation in log-transformed zoospore equivalents (Bd infection intensity) of Bd-exposed individuals of <i>Pristimantis platydactylus</i> (left panels) and <i>P</i>. <i>toftae</i> (right panel). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0186478#pone.0186478.g002" target="_blank">Fig 2</a> for caption details.</p