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Parasite-mediated selection is potentially of great importance in modulating genetic diversity. Genetic variation for resistance, the fuel for natural selection, appears to be common in host-parasite interactions, but responses to selection are rarely observed. In the present study, we tested whether environmental variation could mediate infection and determine evolutionary outcomes. Temperature was shown to dramatically alter the potential for parasite-mediated selection in two independent laboratory infection experiments at four temperatures. The bacterial parasite, Pasteuria ramosa, was extremely virulent at 20°C and 25°C, sterilizing its host, Daphnia magna, so that females often never produced a single brood. However, at 10°C and 15°C, the host-parasite interaction was much more benign, as nearly all females produced broods before becoming sterile. This association between virulence and temperature alone could stabilize coexistence and lead to the maintenance of diversity, because it would weaken parasite-mediated selection during parts of the season. Additionally, highly significant genotype-by-environment interactions were found, with changes in clone rank order for infection rates at different temperatures. Our results clearly show that the outcome of parasite-mediated selection in this system is strongly context dependent.

Historic, wide-spread destruction of native prairies in Minnesota was caused by conversion to agricultural land, disruption of disturbance regimes, and loss of key species. Attempts to restore tall-grass prairies have resulted in a new ecosystem type on the Midwestern landscape, with novel assemblages of both plant and animal species. The mammalian herbivore community, once dominated by bison, is now primarily comprised of white-tailed deer (Odocoileus virginianus), Eastern cottontail rabbits (Sylvilagus floridanus), and small mammals such as meadow voles (Microtus pennsylvanicus). The role of this assemblage of herbivores in restored prairies is not well understood. This study characterizes patterns of mammalian herbivory on five legume species in restored prairie in southern Minnesota. Legumes were sampled along transects that varied in their distance from the prairie-forest boundary and time since prescribed burning. Herbivore selectivity was determined for each legume species using an electivity index based on the total number of stems of each species and the percent of stems grazed. Herbivory was highly variable among legume species: Desmodium canadense was strongly preferred, Dalea candida and Dalea purpurea were moderately preferred, and Amorpha canescens and Lespedeza capitata were avoided. Both Dalea species and Lespedeza experienced increased rates of herbivory in burned sites. Avoided species were characterized by either low tissue nitrogen content or a high proportion of recalcitrant carbon relative to preferred species. These results suggest mammalian herbivores have an important functional role in prairie communities with potential consequences for community dynamics and the success of prairie restorations.

Parasite‐mediated selection is potentially of great importance in modulating genetic diversity. Genetic variation for resistance, the fuel for natural selection, appears to be common in host‐parasite interactions, but responses to selection are rarely observed. In the present study, we tested whether environmental variation could mediate infection and determine evolutionary outcomes. Temperature was shown to dramatically alter the potential for parasite‐mediated selection in two independent laboratory infection experiments at four temperatures. The bacterial parasite, Pasteuria ramosa, was extremely virulent at 20d̀C and 25d̀C, sterilizing its host, Daphnia magna, so that females often never produced a single brood. However, at 10d̀C and 15d̀C, the host‐parasite interaction was much more benign, as nearly all females produced broods before becoming sterile. This association between virulence and temperature alone could stabilize coexistence and lead to the maintenance of diversity, because it would weaken parasite‐mediated selection during parts of the season. Additionally, highly significant genotype‐by‐environment interactions were found, with changes in clone rank order for infection rates at different temperatures. Our results clearly show that the outcome of parasite‐mediated selection in this system is strongly context dependent.

Parasite-mediated selection is potentially of great importance in modulating genetic diversity. Genetic variation for resistance, the fuel for natural selection, appears to be common in host-parasite interactions, but responses to selection are rarely observed. In the present study, we tested whether environmental variation could mediate infection and determine evolutionary outcomes. Temperature was shown to dramatically alter the potential for parasite-mediated selection in two independent laboratory infection experiments at four temperatures. The bacterial parasite, Pasteuria ramosa, was extremely virulent at 20 degrees C and 25 degrees C, sterilizing its host, Daphnia magna, so that females often never produced a single brood. However, at 10 degrees C and 15 degrees C, the host-parasite interaction was much more benign, as nearly all females produced broods before becoming sterile. This association between virulence and temperature alone could stabilize coexistence and lead to the maintenance of diversity, because it would weaken parasite-mediated selection during parts of the season. Additionally, highly significant genotype-by-environment interactions were found, with changes in clone rank order for infection rates at different temperatures. Our results clearly show that the outcome of parasite-mediated selection in this system is strongly context dependent. [PUBLICATION ABSTRACT]

Light-driven [2+2] cycloaddition is the most direct strategy to build tetrasubstituted cyclobutanes, core components of many lead compounds for drug development. Significant advances in the chemoselectivity and enantioselectivity of [2+2] photocycloadditions have been made, but exceptional and tunable diastereoselectivity and regioselectivity (head-to-head versus head-to-tail adducts) is required for the synthesis of bioactive molecules. Here we show that colloidal quantum dots serve as visible-light chromophores, photocatalysts and reusable scaffolds for homo- and hetero-intermolecular [2+2] photocycloadditions of 4-vinylbenzoic acid derivatives, including aryl-conjugated alkenes, with up to 98% switchable regioselectivity and 98% diastereoselectivity for the previously minor syn -cyclobutane products. Transient absorption spectroscopy confirms that our system demonstrates catalysis triggered by triplet–triplet energy transfer from the quantum dot. The precisely controlled triplet energy levels of the quantum dot photocatalysts facilitate efficient and selective heterocoupling, a major challenge in direct cyclobutane synthesis. Tuning the selectivity for [2+2] photocycloadditions remains challenging. Now, triplet–triplet energy transfer from CdSe quantum dots enables the homo- and heterocouplings of 4-vinylbenzoic acid derivatives via [2+2] photocycloaddition. Preorganization of substrates on the quantum dots reverses intrinsic stereoelectronic preferences to yield cyclobutane products with unprecedented diastereo- and regioselectivity.

Background Frailty is increasingly recognized as an important construct which has health implications for older adults. The Clinical Frailty Scale (CFS) is a judgement-based frailty tool that evaluates specific domains including comorbidity, function, and cognition to generate a frailty score ranging from 1 (very fit) to 9 (terminally ill). The aim of this scoping review is to identify and document the nature and extent of research evidence related to the CFS. Methods We performed a comprehensive literature search to identify original studies that used the Clinical Frailty Scale. Medline OVID, Scopus, Web of Science, CINAHL, PsycINFO, Cochrane Library and Embase were searched from January 2005 to March 2017. Articles were screened by two independent reviewers. Data extracted included publication date, setting, demographics, purpose of CFS assessment, and outcomes associated with CFS score. Results Our search yielded 1688 articles of which 183 studies were included. Overall, 62% of studies were conducted after 2015 and 63% of the studies measured the CFS in hospitalized patients. The association of the CFS with an outcome was examined 526 times; CFS was predictive in 74% of the cases. Mortality was the most common outcome examined with CFS being predictive 87% of the time. CFS was associated with comorbidity 73% of the time, complications 100%, length of stay 75%, falls 71%, cognition 94%, and function 91%. The CFS was associated with other frailty scores 94% of the time. Conclusions This scoping review revealed that the CFS has been widely used in multiple settings. The association of CFS score with clinical outcomes highlights its utility in the care of the aging population.

Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology. Pacing tools that support small animals and can serve as models for pathogenesis of cardiovascular diseases are currently not available. Here, the authors report a miniaturized wireless battery-free implantable multimodal and multisite pacemaker that provides unlimited stimulation to test subjects.

In August 2013, the National Institutes of Health sponsored a conference to address major gaps in our understanding of the epidemiology, pathophysiology, and management of fecal incontinence (FI) and to identify topics for future clinical research. This article is the first of a two-part summary of those proceedings. FI is a common symptom, with a prevalence that ranges from 7 to 15% in community-dwelling men and women, but it is often underreported, as providers seldom screen for FI and patients do not volunteer the symptom, even though the symptoms can have a devastating impact on the quality of life. Rough estimates suggest that FI is associated with a substantial economic burden, particularly in patients who require surgical therapy. Bowel disturbances, particularly diarrhea, the symptom of rectal urgency, and burden of chronic illness are the strongest independent risk factors for FI in the community. Smoking, obesity, and inappropriate cholecystectomy are emerging, potentially modifiable risk factors. Other risk factors for FI include advanced age, female gender, disease burden (comorbidity count, diabetes), anal sphincter trauma (obstetrical injury, prior surgery), and decreased physical activity. Neurological disorders, inflammatory bowel disease, and pelvic floor anatomical disturbances (rectal prolapse) are also associated with FI. The pathophysiological mechanisms responsible for FI include diarrhea, anal and pelvic floor weakness, reduced rectal compliance, and reduced or increased rectal sensation; many patients have multifaceted anorectal dysfunctions. The type (urge, passive or combined), etiology (anorectal disturbance, bowel symptoms, or both), and severity of FI provide the basis for classifying FI; these domains can be integrated to comprehensively characterize the symptom. Several validated scales for classifying symptom severity and its impact on the quality of life are available. Symptom severity scales should incorporate the frequency, volume, consistency, and nature (urge or passive) of stool leakage. Despite the basic understanding of FI, there are still major knowledge gaps in disease epidemiology and pathogenesis, necessitating future clinical research in FI.

The gut microbiome is an established regulator of aspects of host metabolism, such as glucose handling. Despite the known impacts of the gut microbiota on host glucose homeostasis, the underlying mechanisms are unknown. The gut microbiome is also a potent mediator of gut-derived serotonin synthesis, and this peripheral source of serotonin is itself a regulator of glucose homeostasis. Here, we determined whether the gut microbiome influences glucose homeostasis through effects on gut-derived serotonin. Using both pharmacological inhibition and genetic deletion of gut-derived serotonin synthesis, we find that the improvements in host glucose handling caused by antibiotic-induced changes in microbiota composition are dependent on the synthesis of peripheral serotonin.

In vivo optogenetics and photopharmacology are two techniques for controlling neuronal activity that have immense potential in neuroscience research. Their applications in tether-free groups of animals have been limited in part due to tools availability. Here, we present a wireless, battery-free, programable multilateral optofluidic platform with user-selected modalities for optogenetics, pharmacology and photopharmacology. This system features mechanically compliant microfluidic and electronic interconnects, capabilities for dynamic control over the rates of drug delivery and real-time programmability, simultaneously for up to 256 separate devices in a single cage environment. Our behavioral experiments demonstrate control of motor behaviors in grouped mice through in vivo optogenetics with co-located gene delivery and controlled photolysis of caged glutamate. These optofluidic systems may expand the scope of wireless techniques to study neural processing in animal models. Wireless delivery of both light and pharmacological agents is important for optogenetic and other mechanistic experiments in the brain. Here the authors present a wireless real-time programmable optofluidic platform that enables optogenetics and photopharmacology experiments that require real-time precise control of light and drug delivery.