Evolutionarily labile dispersal behavior and discontinuous habitats enhance population differentiation in island versus continentally distributed swallows.

The causes of population divergence in vagile groups remain a paradox in evolutionary biology: dispersive species should be able to colonize new areas, a prerequisite for allopatric speciation, but dispersal also facilitates gene flow, which erodes population differentiation. Strong dispersal ability has been suggested to enhance divergence in patchy habitats and inhibit divergence in continuous landscapes, but empirical support for this hypothesis is lacking. Here we compared patterns of population divergence in a dispersive clade of swallows distributed across both patchy and continuous habitats. The Pacific Swallow (Hirundo tahitica) has an insular distribution throughout Southeast Asia and the Pacific, while its sister species, the Welcome Swallow (H. neoxena), has a continental distribution in Australia. We used whole-genome data to demonstrate strong genetic structure and limited introgression among insular populations, but not among continental populations. Demographic models show that historic changes in habitat connectivity have contributed to population structure within the clade. Swallows appear to exhibit evolutionarily labile dispersal behavior in which they reduce dispersal propensity after island colonization despite retaining strong flight ability. Our data support the hypothesis that fragmented habitats enhance population differentiation in vagile groups, and suggest that labile dispersal behavior is a key mechanism underlying this pattern.

Sampling affects population genetic inference: A case study of the Allen's (Selasphorus sasin) and rufous hummingbird (Selasphorus rufus).

Gene flow can affect evolutionary inference when species are undersampled. Here, we evaluate the effects of gene flow and geographic sampling on demographic inference of 2 hummingbirds that hybridize, Allen's hummingbird (Selasphorus sasin) and rufous hummingbird (Selasphorus rufus). Using whole-genome data and extensive geographic sampling, we find widespread connectivity, with introgression far beyond the Allen's × rufous hybrid zone, although the Z chromosome resists introgression beyond the hybrid zone. We test alternative hypotheses of speciation history of Allen's, rufous, and Calliope (S. calliope) hummingbird and find that rufous hummingbird is the sister taxon to Allen's hummingbird, and Calliope hummingbird is the outgroup. A model treating the 2 subspecies of Allen's hummingbird as a single panmictic population fit observed genetic data better than models treating the subspecies as distinct populations, in contrast to morphological and behavioral differences and analyses of spatial population structure. With additional sampling, our study builds upon recent studies that came to conflicting conclusions regarding the evolutionary histories of these 2 species. Our results stress the importance of thorough geographic sampling when assessing demographic history in the presence of gene flow.

Surgeon Strategies to Patient-Centered Decision-making in Cancer Care: Validation and Applications of a Conceptual Model.

We sought to construct and validate a model of cancer surgeon approaches to patient-centered decision-making (PCDM) and compare applications of that model relative to surgical specialties. Ten PCDM strategies were assessed using a cross-sectional survey administered online to 295 board-certified cancer surgeons. Structural equation modeling was used to empirically validate and compare approaches to PCDM. Within the full sample, 7 strategies comprised a latent construct labeled, "physical & emotional accessibility," associated with surgeon approaches to PCDM (ß = 0.37, p < .05). Three individual strategies were included: "expectations (Q4)" (ß = 0.52, p < .05), "decision preferences (Q5) (ß = 0.47, p < .05), and "access medical information (Q3)" (ß = 0.75). Surgical specialties for subgroup analysis were classified as general/other (67.6%) or hepato-pancreato-biliary and upper gastrointestinal (HPB/UGI) (34.2%). For general/other surgeons, 7 individual strategies composed the model of surgeon approaches to PCDM, with "time (Q6) (ß = 0.70, p < .001) and "therapeutic relationship building (Q9)" (ß = 0.69, p < .001) being the strongest predictors. The HPB/UGI model included 2 latent constructs labeled "physical accessibility" (ß = 0.72, p < .05) and "creating a decision-making dialogue" (ß = 0.62) as well as the individual strategy, "effective communication (Q8)" (ß = 0.51, p < .05). Although models of surgeon PCDM varied, there were 4 overlapping strategies, including effective communication. Tailoring models of PCDM may improve surgeon uptake and thus, overall patient satisfaction with their cancer care.

Spiritual Motivations to Practice Medicine: A Survey of Cancer Care Providers.

BACKGROUND: There is increased interest in the role of spirituality in the cancer care context, but how it may inspire individuals to pursue a career as a healthcare provider is unknown. We sought to determine the relationship between intrinsic religiosity, religious identity, provider role, and spiritual motivations to practice medicine. METHODS: A cross-sectional survey was administered to healthcare providers at a large, Midwest Comprehensive Cancer Center. The relationship between provider type, intrinsic religiosity, religious identity, and spiritual motivations to practice medicine was assessed with binary logistic regression. RESULTS: Among 340 participants, most were female (82.1%) or Caucasian (82.6%) and identified as being religious (57.5%); median age was 35 years (IQR: 31-48). Providers included nurses (64.7%), physicians (17.9%), and "other" (17.4%). Compared with physicians, nurses were less likely to agree that they felt responsible for reducing pain and suffering in the world (OR: 0.12, p = 0.03). Similarly, "other" providers were less likely than physicians to believe that the practice of medicine was a calling (OR: 0.28, p = 0.02). Providers with a high self-reported intrinsic religiosity demonstrated a much greater likelihood to believe that the practice of medicine is a calling (OR:1.75, p = 0.001), as well as believe that personal R&S beliefs influence the practice of medicine (OR:3.57, p < 0.001). Provider religious identity was not associated with spiritual motivations to practice medicine (all p > 0.05). CONCLUSION: Intrinsic religiosity had the strongest relationship with spiritual motivations to practice medicine. Understanding these motivations may inform interventions to avoid symptoms of provider burnout in cancer care.

The Influence of Patient and Provider Religious and Spiritual Beliefs on Treatment Decision Making in the Cancer Care Context.

BACKGROUND: Providers often underestimate the influence of patient religious and spiritual (R&S) needs. The current study sought to determine the influence of R&S beliefs on treatment decision making among patients and providers in the context of cancer care. METHODS: We conducted a systematic review of the literature using web-based search engines and discipline-specific databases. Search terms included a combination of the following Medical Subject Headings and key terms: "cancer,""spirituality,""religion," and "decision making." We used Covidence to screen relevant studies and extracted data into Microsoft Excel. RESULTS: Among 311 screened studies, 32 met inclusion/exclusion criteria. Most studies evaluated the patient perspective (n = 29), while 2 studies evaluated the provider perspective and 1 study examined both. In assessing patient R&S relative to treatment decision making, we thematically characterized articles according to decision-making contexts, including general (n = 11), end-of-life/advance care planning (n = 13), and other: specific (n = 8). Specific contexts included, but were not limited to, clinical trial participation (n = 2) and use of complementary and alternative medicine (n = 4). Within end-of-life/advance care planning, there was a discrepancy regarding how R&S influenced treatment decision making. The influence of R&S on general treatment decision making was both active and passive, with some patients wanting more direct integration of their R&S beliefs in treatment decision making. In contrast, other patients were less aware of indirect R&S influences. Patient perception of the impact of R&S on treatment decision making varied relative to race/ethnicity, being more pronounced among Black patients. CONCLUSION: Most articles focused on R&S relative to treatment decision making at the end of life, even though R&S appeared important across the care continuum. To improve patient-centered cancer care, providers need to be more aware of the impact of R&S on treatment decision making.

Wild-type FUS corrects ALS-like disease induced by cytoplasmic mutant FUS through autoregulation.

Mutations in FUS, an RNA-binding protein involved in multiple steps of RNA metabolism, are associated with the most severe forms of amyotrophic lateral sclerosis (ALS). Accumulation of cytoplasmic FUS is likely to be a major culprit in the toxicity of FUS mutations. Thus, preventing cytoplasmic mislocalization of the FUS protein may represent a valuable therapeutic strategy. FUS binds to its own pre-mRNA creating an autoregulatory loop efficiently buffering FUS excess through multiple proposed mechanisms including retention of introns 6 and/or 7. Here, we introduced a wild-type FUS gene allele, retaining all intronic sequences, in mice whose heterozygous or homozygous expression of a cytoplasmically retained FUS protein (Fus∆NLS) was previously shown to provoke ALS-like disease or postnatal lethality, respectively. Wild-type FUS completely rescued the early lethality caused by the two Fus∆NLS alleles, and improved the age-dependent motor deficits and reduced lifespan caused by heterozygous expression of mutant FUS∆NLS. Mechanistically, wild-type FUS decreased the load of cytoplasmic FUS, increased retention of introns 6 and 7 in the endogenous mouse Fus mRNA, and decreased expression of the mutant mRNA. Thus, the wild-type FUS allele activates the homeostatic autoregulatory loop, maintaining constant FUS levels and decreasing the mutant protein in the cytoplasm. These results provide proof of concept that an autoregulatory competent wild-type FUS expression could protect against this devastating, currently intractable, neurodegenerative disease.

The population genetics of nonmigratory Allen's Hummingbird (Selasphorus sasin sedentarius) following a recent mainland colonization.

Allen's Hummingbird comprises two subspecies, one migratory (Selasphorus sasin sasin) and one nonmigratory (S. s. sedentarius). The nonmigratory subspecies, previously endemic to the California Channel Islands, apparently colonized the California mainland on the Palos Verdes Peninsula some time before 1970 and now breeds throughout coastal southern California. We sequenced and compared populations of mainland nonmigratory Allen's Hummingbird to Channel Island populations from Santa Catalina, San Clemente, and Santa Cruz Island. We found no evidence of founder effects on the mainland population. Values of nucleotide diversity on the mainland were higher than on the Channel Islands. There were low levels of divergence between the Channel Islands and the mainland, and Santa Cruz Island was the most genetically distinct. Ecological niche models showed that rainfall and temperature variables on the Channel Islands are similar in the Los Angeles basin and predicted continued expansion of nonmigratory Allen's Hummingbird north along the coast and inland. We also reviewed previous genetic studies of vertebrate species found on the Channel Islands and mainland and showed that broad conclusions regarding island-mainland patterns remain elusive. Challenges include the idiosyncratic nature of colonization itself as well as the lack of a comprehensive approach that incorporates similar markers and sampling strategies across taxa, which, within the context of a comparative study of island-mainland relationships, may lead to inconsistent results.

Do Religious/Spiritual Preferences and Needs of Cancer Patients Vary Based on Clinical- and Treatment-Level Factors?

BACKGROUND: The objective of this study is to characterize the religion and spiritual (R&S) needs of patients who undergo cancer-directed surgery. In addition, we seek to examine how R&S needs vary based on R&S identity and clinical and surgical treatment characteristics. PATIENTS AND METHODS: A cross-sectional survey was administered to potential participants who were recruited through outpatient clinics and online. Respondent desires for R&S resources and engagement with the healthcare team  around R&S topics were assessed. RESULTS: Among 383 potential participants who were identified, 236 respondents were included in the analytic cohort. Mean age was 58.8 (SD 12.10) years, and most participants were female (75.8%) and White/Caucasian (94.1%). The majority (78.4%) identified as currently cancer free. Commonly treated malignancies included breast (43.2%), male reproductive (8.9%), skin (8.5%), and gastrointestinal (GI) (7.2%). Two-thirds of the respondents indicated a desire to have R&S incorporated into their cancer treatment (63.3%). Patients who identified as highly/moderately religious reported wanting R&S more often (highly religious: 95.2% versus moderately religious: 71.4% vs. nonreligious but spiritual: 4.5%). On multivariable analysis, patients who believed their health would improve in the future were more likely to report wanting R&S service (OR 2.2, 95% CI 1.0-4.7) as well as wanting to engage their healthcare providers on R&S topics (OR 2.4, 95% CI 1.2-4.7). In contrast, perception of current or future health status was not associated with patient desire for the actual surgeon/doctor him/herself to be involved in R&S activities (OR 1.83, 95% CI 0.97-3.45). CONCLUSIONS: Two-thirds of patients undergoing cancer-directed surgery expressed a desire to have R&S incorporated into their cancer treatment. Incorporating R&S into cancer treatment can help a subset of patients throughout their cancer experience.

ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS.

Through the generation of humanized FUS mice expressing full-length human FUS, we identify that when expressed at near endogenous murine FUS levels, both wild-type and ALS-causing and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels and transporters essential for synaptic function, and reduced synaptic activity without loss of nuclear FUS or its cytoplasmic aggregation. Most strikingly, accumulation of mutant human FUS is shown to activate an integrated stress response and to inhibit local, intra-axonal protein synthesis in hippocampal neurons and sciatic nerves. Collectively, our evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain of toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs. VIDEO ABSTRACT.

Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs.

Hexanucleotide expansions in C9ORF72 are the most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Disease mechanisms were evaluated in mice expressing C9ORF72 RNAs with up to 450 GGGGCC repeats or with one or both C9orf72 alleles inactivated. Chronic 50% reduction of C9ORF72 did not provoke disease, while its absence produced splenomegaly, enlarged lymph nodes, and mild social interaction deficits, but not motor dysfunction. Hexanucleotide expansions caused age-, repeat-length-, and expression-level-dependent accumulation of RNA foci and dipeptide-repeat proteins synthesized by AUG-independent translation, accompanied by loss of hippocampal neurons, increased anxiety, and impaired cognitive function. Single-dose injection of antisense oligonucleotides (ASOs) that target repeat-containing RNAs but preserve levels of mRNAs encoding C9ORF72 produced sustained reductions in RNA foci and dipeptide-repeat proteins, and ameliorated behavioral deficits. These efforts identify gain of toxicity as a central disease mechanism caused by repeat-expanded C9ORF72 and establish the feasibility of ASO-mediated therapy.

Potentiation of Ecstasy-induced hyperthermia and FAT/CD36 expression in chronically exercised animals.

Fatal hyperthermia as a result of 3,4-methylenedioxymethamphetamine (MDMA) use involves non-esterified free fatty acids (NEFA) and the activation of mitochondrial uncoupling proteins (UCP). NEFA gain access into skeletal muscle via specific transport proteins, including fatty acid translocase (FAT/CD36). FAT/CD36 expression is known to increase following chronic exercise. Previous studies have demonstrated the essential role of NEFA and UCP3 in MDMA-induced hyperthermia. The aims of the present study were to use a chronic exercise model (swimming for two consecutive hours per day, five days per wk for six wk) to increase FAT/CD36 expression in order to: 1) determine the contribution of FAT/CD36 in MDMA (20 mg/kg, s.c.)-mediated hyperthermia; and 2) examine the effects of the FAT/CD36 inhibitor, SSO (sulfo-N-succinimidyl oleate), on MDMA-induced hyperthermia in chronic exercise and sedentary control rats. MDMA administration resulted in hyperthermia in both sedentary and chronic exercise animals. However, MDMA-induced hyperthermia was significantly potentiated in the chronic exercise animals compared to sedentary animals. Additionally, chronic exercise significantly reduced body weight, increased FAT/CD36 protein expression levels and reduced plasma NEFA levels. The FAT/CD36 inhibitor, SSO (40 mg/kg, ip), significantly attenuated the hyperthermia mediated by MDMA in chronic exercised but not sedentary animals. Plasma NEFA levels were elevated in sedentary and exercised animals treated with SSO prior to MDMA suggesting attenuation of NEFA uptake into skeletal muscle. Chronic exercise did not alter skeletal muscle UCP3 protein expression levels. In conclusion, chronic exercise potentiates MDMA-mediated hyperthermia in a FAT/CD36 dependent fashion.

The Synthesis of a New Class of Highly Fluorescent Chromones via an Inverse-Demand Hetero-Diels-Alder Reaction.

A new class of fluorophores has been developed utilizing an inverse-demand hetero-Diels-Alder reaction with silyl enol ethers and substituted 3-formylchromones. These compounds yield blue to green fluorescence with quantum yields up to 73%. They also exhibit good potential for use as fluorescent probes in biological systems, as they are cell membrane permeable with low cytotoxicity.

Profiles in chemistry: a historical perspective on the national organic symposium.

This perspective delineates the history of the National Organic Chemistry Symposium (NOS) and, in doing so, traces the development of organic chemistry over the past 88 years. The NOS is the premier event sponsored by the ACS Division of Organic Chemistry (ORGN) and has been held in odd-numbered years since 1925, with the exceptions of 1943 and 1945. During the 42 symposia, 332 chemists have given 549 plenary lectures. The role the NOS played in the launch of The Journal of Organic Chemistry and Organic Reactions and the initiation of the Roger Adams Award are discussed. Representative examples highlighting the chemistry presented in each era are described, and the evolution of the field is examined by assigning each NOS talk to one of seven subdisciplines and analyzing how the number of talks in each subdiscipline has changed over time. Comparisons of the demographics of speakers, attendees, and ORGN members are made, and superlatives are noted. Personal interest stories of the speakers are discussed, along with the relationships among them, especially their academic lineage. Logistical aspects of the NOS and their historical trends are reviewed. Finally, the human side of science is examined, where over the past century, the NOS has been intertwined with some of the most heated debates in organic chemistry. Conflicts and controversies involving free radicals, reaction mechanisms, and nonclassical carbocations are discussed.

Studies for the total synthesis of amphidinolide P.

A convergent, enantiocontrolled total synthesis of the 15-membered macrolide, amphidinolide P, is described. The synthesis utilizes three nonracemic components for an efficient assembly of the macrolactone in 12 steps via the longest linear pathway. Key developments include studies of the Hosomi-Sakurai reaction for the formation of the C6-C7 bond, a "ligandless" palladium-mediated Stille cross-coupling of the vinylic stannane 4 and the alkenyl bromide 5 to produce a highly functionalized dienol, and a thermally induced, intramolecular lactonization via the late-stage formation of an intermediate α-acylketene.

Sodium intake and intraventricular hemorrhage in the preterm infant.

OBJECTIVE: Hypernatremia is associated with intracranial hemorrhage in term infants. The etiology of intraventricular hemorrhage in preterm infants is multifactorial. We aimed to characterize the associations between sodium intake, hypernatremia, and intraventricular hemorrhage in preterm infants. METHODS: The charts of 722 preterm infants with a birth weight

Sodium bicarbonate administration and outcome in preterm infants.

The short-term outcomes of sodium bicarbonate therapy in preterm infants were investigated by retrospective analysis of 165 of 984 infants who received sodium bicarbonate. The infants treated with sodium bicarbonate were more immature and had greater severity of illness and more adverse outcomes. Sodium bicarbonate therapy did not improve the blood pH.

Insecticidal anthranilic diamides: a new class of potent ryanodine receptor activators.

A novel class of anthranilic diamides has been discovered with exceptional insecticidal activity on a range of Lepidoptera. These compounds have been found to exhibit their action by release of intracellular Ca2+ stores mediated by the ryanodine receptor. The discovery, synthesis, structure-activity, and biological results are presented.