Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signaling in The Prefrontal Cortex Modulates Cued Fear Learning, But Not Spatial Working Memory, in Female Rats

A genetic polymorphism within the gene encoding the pituitary adenylate cyclase- activating polypeptide (PACAP) receptor type I (PAC1R) has recently been associated with hyper-reactivity to threat-related cues in women, but not men, with post-traumatic stress disorder (PTSD). PACAP is a highly conserved peptide, whose role in mediating adaptive physiological stress responses is well established. Far less is understood about the contribution of PACAP signaling in emotional learning and memory, particularly the encoding of fear to discrete cues. Moreover, a neurobiological substrate that may account for the observed link between PAC1R and PTSD in women, but not men, has yet to be identified. Sex differences in PACAP signaling during emotional learning could provide novel targets for the treatment of PTSD. Here we investigated the contribution of PAC1R signaling within the prefrontal cortex to the acquisition of cued fear in female and male rats. We used a variant of fear conditioning called trace fear conditioning, which requires sustained attention to fear cues and depends on working-memory like neuronal activity within the prefrontal cortex. We found that cued fear learning, but not spatial working memory, was impaired by administration of a PAC1R antagonist directly into the prelimbic area of the prefrontal cortex. This effect was specific to females. We also found that levels of mRNA for the PAC1R receptor in the prelimbic cortex were greater in females compared with males, and were highest during and immediately following the proestrus stage of the estrous cycle. Together, these results demonstrate a sex-specific role of PAC1R signaling in learning about threat-related cues

Planetary Construction Zones in Occultation: Discovery of an Extrasolar Ring System Transiting a Young Sun-like Star and Future Prospects for Detecting Eclipses by Circumsecondary and Circumplanetary Disks

The large relative sizes of circumstellar and circumplanetary disks imply that they might be seen in eclipse in stellar light curves. We estimate that a survey of ~10^4 young (~10 Myr old) post-accretion pre-MS stars monitored for ~10 years should yield at least a few deep eclipses from circumplanetary disks and disks surrounding low mass companion stars. We present photometric and spectroscopic data for a pre-MS K5 star (1SWASP J140747.93-394542.6), a newly discovered ~0.9 Msun member of the ~16 Myr-old Upper Cen-Lup subgroup of Sco-Cen at a kinematic distance of 128 pc. SuperWASP and ASAS light curves for this star show a remarkably long, deep, and complex eclipse event centered on 29 April 2007. At least 5 multi-day dimming events of >0.5 mag are identified, with a >3.3 mag deep eclipse bracketed by two pairs of ~1 mag eclipses symmetrically occurring +-12 days and +-26 days before and after. Hence, significant dimming of the star was taking place on and off over at least a ~54 day period in 2007, and a strong >1 mag dimming event occurred over a ~12 day span. We place a firm lower limit on the period of 850 days (i.e. the orbital radius of the eclipser must be >1.7 AU and orbital velocity must be <22 km/s). The shape of the light curve is similar to the lop-sided eclipses of the Be star EE Cep. We suspect that this new star is being eclipsed by a low-mass object orbited by a dense inner disk, girded by at least 3 dusty rings of lower optical depth. Between these rings are at least two annuli of near-zero optical depth (i.e. gaps), possibly cleared out by planets or moons, depending on the nature of the secondary. For possible periods in the range 2.33-200 yr, the estimated total ring mass is ~8-0.4 Mmoon (if the rings have optical opacity similar to Saturn's rings), and the edge of the outermost detected ring has orbital radius ~0.4-0.09 AU.Comment: Astronomical Journal, in press, 13 figure

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC)

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of all cases. Until recently, chemotherapy – characterized by some benefit but only rare durable responses – was the only treatment option for patients with NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated distinctly durable responses and represent the advent of a new treatment approach for patients with NSCLC. Three immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab, are now approved for use in first- and/or second-line settings for selected patients with advanced NSCLC, with promising benefit also seen in patients with stage III NSCLC. Additionally, durvalumab following chemoradiation has been approved for use in patients with locally advanced disease. Due to the distinct features of cancer immunotherapy, and rapid progress in the field, clinical guidance is needed on the use of these agents, including appropriate patient selection, sequencing of therapies, response monitoring, adverse event management, and biomarker testing. The Society for Immunotherapy of Cancer (SITC) convened an expert Task Force charged with developing consensus recommendations on these key issues. Following a systematic process as outlined by the National Academy of Medicine, a literature search and panel voting were used to rate the strength of evidence for each recommendation. This consensus statement provides evidence-based recommendations to help clinicians integrate immune checkpoint inhibitors into the treatment plan for patients with NSCLC. This guidance will be updated following relevant advances in the field

The Impact of HIV, an Antiretroviral Programme and Tuberculosis on Mortality in South African Platinum Miners, 1992–2010

HIV and tuberculosis (TB) are the most common causes of death in South Africa. Antiretroviral therapy (ART) programmes should have had an impact on mortality rates. This study describes the impact of HIV, a Wellness (HIV/ART) programme and TB on population-wide trends in mortality and causes of death among South African platinum miners, from before the HIV epidemic into the ART era

Loss of Cytoplasmic CDK1 Predicts Poor Survival in Human Lung Cancer and Confers Chemotherapeutic Resistance

The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery

Differential Pathogenesis of Lung Adenocarcinoma Subtypes Involving Sequence Mutations, Copy Number, Chromosomal Instability, and Methylation

Lung adenocarcinoma (LAD) has extreme genetic variation among patients, which is currently not well understood, limiting progress in therapy development and research. LAD intrinsic molecular subtypes are a validated stratification of naturally-occurring gene expression patterns and encompass different functional pathways and patient outcomes. Patients may have incurred different mutations and alterations that led to the different subtypes. We hypothesized that the LAD molecular subtypes co-occur with distinct mutations and alterations in patient tumors.The LAD molecular subtypes (Bronchioid, Magnoid, and Squamoid) were tested for association with gene mutations and DNA copy number alterations using statistical methods and published cohorts (n = 504). A novel validation (n = 116) cohort was assayed and interrogated to confirm subtype-alteration associations. Gene mutation rates (EGFR, KRAS, STK11, TP53), chromosomal instability, regional copy number, and genomewide DNA methylation were significantly different among tumors of the molecular subtypes. Secondary analyses compared subtypes by integrated alterations and patient outcomes. Tumors having integrated alterations in the same gene associated with the subtypes, e.g. mutation, deletion and underexpression of STK11 with Magnoid, and mutation, amplification, and overexpression of EGFR with Bronchioid. The subtypes also associated with tumors having concurrent mutant genes, such as KRAS-STK11 with Magnoid. Patient overall survival, cisplatin plus vinorelbine therapy response and predicted gefitinib sensitivity were significantly different among the subtypes.The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response. These results advance the understanding of lung adenocarcinoma etiology and nominate patient subgroups for future evaluation of treatment response

Synopsis of the pelidnotine scarabs (Coleoptera, Scarabaeidae, Rutelinae, Rutelini) and annotated catalog of the species and subspecies

The pelidnotine scarabs (Scarabaeidae: Rutelinae: Rutelini) are a speciose, paraphyletic assemblage of beetles that includes spectacular metallic species (“jewel scarabs”) as well as species that are ecologically important as herbivores, pollinators, and bioindicators. These beetles suffer from a complicated nomenclatural history, due primarily to 20th century taxonomic and nomenclatural errors. We review the taxonomic history of the pelidnotine scarabs, present a provisional key to genera with overviews of all genera, and synthesize a catalog of all taxa with synonyms, distributional data, type specimen information, and 107 images of exemplar species. As a result of our research, the pelidnotine leaf chafers (a paraphyletic group) include 27 (26 extant and 1 extinct) genera and 420 valid species and subspecies (419 extant and 1 extinct). Our research makes biodiversity research on this group tractable and accessible, thus setting the stage for future studies that address evolutionary and ecological trends. Based on our research, 1 new species is described, 1 new generic synonym and 12 new species synonyms are proposed, 11 new lectotypes and 1 new neotype are designated, many new or revised nomenclatural combinations, and many unavailable names are presented. The following taxonomic changes are made: New generic synonym: The genus Heteropelidnota Ohaus, 1912 is a new junior synonym of Pelidnota MacLeay, 1819. New species synonyms: Plusiotis adelaida pavonacea Casey, 1915 is a syn. n. of Chrysina adelaida (Hope, 1841); Odontognathus gounellei Ohaus, 1908 is a revised synonym of Pelidnota ebenina (Blanchard, 1842); Pelidnota francoisgenieri Moore & Jameson, 2013 is a syn. n. of Pelidnota punctata (Linnaeus, 1758); Pelidnota genieri Soula, 2009 is a syn. n. of Pelidnota punctata (Linnaeus, 1758); Pelidnota lutea (Olivier, 1758) is a revised synonym of Pelidnota punctata (Linnaeus, 1758); Pelidnota (Pelidnota) texensis Casey, 1915 is a revised synonym of Pelidnota punctata (Linnaeus, 1758); Pelidnota (Strigidia) zikani (Ohaus, 1922) is a revised synonym of Pelidnota tibialis tibialis Burmeister, 1844; Pelidnota ludovici Ohaus, 1905 is a syn. n. of Pelidnota burmeisteri tricolor Nonfried, 1894; Rutela fulvipennis Germar, 1824 is syn. n. of Pelidnota cuprea (Germar, 1824); Pelidnota pulchella blanda Burmeister, 1844 is a syn. n. of Pelidnota pulchella pulchella (Kirby, 1819); Pelidnota pulchella scapularis Burmeister, 1844 is a syn. n. of Pelidnota pulchella pulchella (Kirby, 1819); Pelidnota xanthogramma Perty, 1830 is a syn. n. of Pelidnota pulchella pulchella (Kirby, 1819). New or revised statuses: Pelidnota fabricelavalettei Soula, 2009, revised status, is considered a species; Pelidnota rioensis Soula, 2009, stat. n., is considered a species; Pelidnota semiaurata semiaurata Burmeister, 1844, stat. rev., is considered a subspecies. New or comb. rev. and revised status: Plusiotis guaymi Curoe, 2001 is formally transferred to the genus Chrysina (C. guaymi (Curoe, 2001), comb. n.); Plusiotis transvolcanica Morón & Nogueira, 2016 is transferred to the genus Chrysina (C. transvolcanica (Morón & Nogueira, 2016), comb. n.). Heteropelidnota kuhnti Ohaus, 1912 is transferred to the genus Pelidnota (P. kuhnti (Ohaus, 1912), comb. n.); Odontognathus riedeli Ohaus, 1905 is considered a subspecies of Pelidnota rubripennis Burmeister, 1844 (Pelidnota rubripennis riedeli (Ohaus, 1905), revised status and comb. rev.); Pelidnota (Strigidia) acutipennis (F. Bates, 1904) is transferred to the genus Sorocha (Sorocha acutipennis (F. Bates, 1904), comb. rev.); Pelidnota (Odontognathus) nadiae Martínez, 1978 is transferred to the genus Sorocha (Sorocha nadiae (Martínez, 1978), comb. rev.); Pelidnota (Ganonota) plicipennis Ohaus, 1934 is transferred to the genus Sorocha (Sorocha plicipennis (Ohaus, 1934), comb. rev.); Pelidnota similis Ohaus, 1908 is transferred to the genus Sorocha (Sorocha similis (Ohaus, 1908), comb. rev.); Pelidnota (Ganonota) yungana Ohaus, 1934 is transferred to Sorocha (Sorocha yungana (Ohaus, 1934), comb. rev.); Pelidnota malyi Soula, 2010: 58, revised status; Xenopelidnota anomala porioni Chalumeau, 1985, revised subspecies status. To stabilize the classification of the group, a neotype is designated for the following species: Pelidnota thiliezi Soula, 2009. Lectotypes are designated for the following names (given in their original combinations): Pelidnota brevicollis Casey, 1915, Pelidnota brevis Casey, 1915, Pelidnota debiliceps Casey, 1915, Pelidnota hudsonica Casey, 1915, Pelidnota oblonga Casey, 1915, Pelidnota pallidipes Casey, 1915, Pelidnota ponderella Casey, 1915, Pelidnota strenua Casey, 1915, Pelidnota tarsalis Casey, 1915, Pelidnota texensis Casey, 1915, and Scarabaeus punctatus Linnaeus, 1758. The following published infrasubspecific names are unavailable per ICZN Article 45.6.1: Pelidnota (Odontognathus) cuprea var. coerulea Ohaus, 1913; Pelidnota (Odontognathus) cuprea var. rufoviolacea Ohaus, 1913; Pelidnota (Odontognathus) cuprea var. nigrocoerulea Ohaus, 1913; Pelidnota pulchella var. fulvopunctata Ohaus, 1913; Pelidnota pulchella var. sellata Ohaus, 1913; Pelidnota pulchella var. reducta Ohaus, 1913; Pelidnota unicolor var. infuscata Ohaus, 1913. The following published species name is unavailable per ICZN Article 11.5: Neopatatra synonyma Moore & Jameson, 2013. The following published species name is unavailable per application of ICZN Article 16.1: Parhoplognathus rubripennis Soula, 2008. Synopsis of the pelidnotine scarabs (Coleoptera, Scarabaeidae, Rutelinae, Rutelini) 3 The following published species name is unavailable per application of ICZN Article 16.4.1: Strigidia testaceovirens argentinica Soula, 2006, Pelidnota (Strigidia) testaceovirens argentinica (Soula, 2006), and Pelidnota testaceovirens argentinica (Soula, 2006). The following published species names are unavailable per application of ICZN Article 16.4.2: Homonyx digennaroi Soula, 2010; Homonyx lecourti Soula, 2010; Homonyx mulliei Soula, 2010; Homonyx simoensi Soula, 2010; Homonyx wagneri Soula, 2010; Homonyx zovii Demez & Soula, 2011; Pelidnota arnaudi Soula, 2009; Pelidnota brusteli Soula, 2010; Pelidnota chalcothorax septentrionalis Soula, 2009; Pelidnota degallieri Soula, 2010; Pelidnota lavalettei Soula, 2008; Pelidnota lavalettei Soula, 2009; Pelidnota dieteri Soula, 2011; Strigidia gracilis decaensi Soula, 2008, Pelidnota (Strigidia) gracilis decaensi (Soula, 2008), and Pelidnota gracilis decaensi (Soula, 2008); Pelidnota halleri Demez & Soula, 2011; Pelidnota injantepalominoi Demez & Soula, 2011; Pelidnota kucerai Soula, 2009; Pelidnota malyi Soula, 2010: 36-37; Pelidnota mezai Soula, 2009; Pelidnota polita darienensis Soula, 2009; Pelidnota polita orozcoi Soula, 2009; Pelidnota polita pittieri Soula, 2009; Pelidnota punctulata decolombia Soula, 2009; Pelidnota punctulata venezolana Soula, 2009; Pelidnota raingeardi Soula, 2009; Pelidnota schneideri Soula, 2010; Pelidnota simoensi Soula, 2009; Pelidnota unicolor subandina Soula, 2009; Sorocha carloti Demez & Soula, 2011; Sorocha castroi Soula, 2008; Sorocha fravali Soula, 2011; Sorocha jeanmaurettei Demez & Soula, 2011; Sorocha yelamosi Soula, 2011; Xenopelidnota bolivari Soula, 2009; Xenopelidnota pittieri pittieri Soula, 2009. Due to unavailability of the name Pseudogeniates cordobaensis Soula 2009, we describe the species as intentionally new (Pseudogeniates cordobaensis Moore, Jameson, Garner, Audibert, Smith, and Seidel, sp. n.)

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world\u27s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world’s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications