Strongly asymmetric hybridization barriers shape the origin of a new polyploid species and its hybrid ancestor

PREMISE OF THE STUDY: Hybridization between diploids and tetraploids can lead to new allopolyploid species, often via a triploid intermediate. Viable triploids are often produced asymmetrically, with greater success observed for maternal-excess crosses where the mother has a higher ploidy than the father. Here we investigated the evolutionary origins of Mimulus peregrinus, an allohexaploid recently derived from the triploid M. xrobertsii, to determine whether reproductive asymmetry has shaped the formation of this new species. METHODS: We used reciprocal crosses between the diploid (M. guttatus) and tetraploid (M. luteus) progenitors to determine the viability of triploid M. xrobertsii hybrids resulting from paternal-vs. maternal-excess crosses. To investigate whether experimental results predict patterns seen in the field, we performed parentage analyses comparing natural populations of M. peregrinus to its diploid, tetraploid, and triploid progenitors. Organellar sequences obtained from pre-existing genomic data, supplemented with additional genotyping was used to establish the maternal ancestry of multiple M. peregrinus and M. xrobertsii populations. KEY RESULTS: We found strong evidence for asymmetric origins of M. peregrinus, but opposite to the common pattern, with paternal-excess crosses significantly more successful than maternal-excess crosses. These results successfully predicted hybrid formation in nature: 111 of 114 M. xrobertsii individuals, and 27 of 27 M. peregrinus, had an M. guttatus maternal haplotype. CONCLUSION: This study, which includes the first Mimulus chloroplast genome assembly, demonstrates the utility of parentage analysis through genome skimming. We highlight the benefits of complementing genomic analyses with experimental approaches to understand asymmetry in allopolyploid speciation

Strongly asymmetric hybridization barriers shape the origin of a new polyploid species and its hybrid ancestor

PREMISE OF THE STUDY:Hybridization between diploids and tetraploids can lead to new allopolyploid species, often via a triploid intermediate. Viable triploids are often produced asymmetrically, with greater success observed for “maternal-excess” crosses where the mother has a higher ploidy than the father. Here we investigated the evolutionary origins ofMimulus peregrinus, an allohexaploid recently derived from the triploidM. ×robertsii, to determine whether reproductive asymmetry has shaped the formation of this new species.  METHODS:We used reciprocal crosses between the diploid (M. guttatus) and tetraploid (M. luteus) progenitors to determine the viability of triploidM. ×robertsiihybrids resulting from paternal- vs. maternal-excess crosses. To investigate whether experimental results predict patterns seen in the field, we performed parentage analyses comparing natural populations ofM. peregrinusto its diploid, tetraploid, and triploid progenitors. Organellar sequences obtained from pre-existing genomic data, supplemented with additional genotyping was used to establish the maternal ancestry of multipleM. peregrinusandM. ×robertsiipopulations.  KEY RESULTS:We found strong evidence for asymmetric origins ofM. peregrinus, but opposite to the common pattern, with paternal-excess crosses significantly more successful than maternal-excess crosses. These results successfully predicted hybrid formation in nature: 111 of 114M. ×robertsiiindividuals, and 27 of 27M. peregrinus, had anM. guttatusmaternal haplotype.  CONCLUSION:This study, which includes the firstMimuluschloroplast genome assembly, demonstrates the utility of parentage analysis through genome skimming. We highlight the benefits of complementing genomic analyses with experimental approaches to understand asymmetry in allopolyploid speciation

Morphine Attenuates fNIRS Signal Associated With Painful Stimuli in the Medial Frontopolar Cortex (medial BA 10)

Functional near infrared spectroscopy (fNIRS) is a non-invasive optical imaging method that provides continuous measure of cortical brain functions. One application has been its use in the evaluation of pain. Previous studies have delineated a deoxygenation process associated with pain in the medial anterior prefrontal region, more specifically, the medial Brodmann Area 10 (BA 10). Such response to painful stimuli has been consistently observed in awake, sedated and anesthetized patients. In this study, we administered oral morphine (15 mg) or placebo to 14 healthy male volunteers with no history of pain or opioid abuse in a crossover double blind design, and performed fNIRS scans prior to and after the administration to assess the effect of morphine on the medial BA 10 pain signal. Morphine is the gold standard for inhibiting nociceptive processing, most well described for brain effects on sensory and emotional regions including the insula, the somatosensory cortex (the primary somatosensory cortex, S1, and the secondary somatosensory cortex, S2), and the anterior cingulate cortex (ACC). Our results showed an attenuation effect of morphine on the fNIRS-measured pain signal in the medial BA 10, as well as in the contralateral S1 (although observed in a smaller number of subjects). Notably, the extent of signal attenuation corresponded with the temporal profile of the reported plasma concentration for the drug. No clear attenuation by morphine on the medial BA 10 response to innocuous stimuli was observed. These results provide further evidence for the role of medial BA 10 in the processing of pain, and also suggest that fNIRS may be used as an objective measure of drug-brain profiles independent of subjective reports

Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer

PURPOSE: Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM). PATIENTS AND METHODS: A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading. RESULTS: Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. CONCLUSION: GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety

Early patient and liver allograft outcomes from donation after circulatory death donors using thoracoabdominal normothermic regional: a multi-center observational experience

BackgroundDonation after circulatory death (DCD) liver allografts are associated with higher rates of primary non-function (PNF) and ischemic cholangiopathy (IC). Advanced recovery techniques, including thoracoabdominal normothermic regional perfusion (TA-NRP), may improve organ utilization and patient and allograft outcomes. Given the increasing US experience with TA-NRP DCD recovery, we evaluated outcomes of DCD liver allografts transplanted after TA-NRP.MethodsLiver allografts transplanted from DCD donors after TA-NRP were identified from 5/1/2021 to 1/31/2022 across 8 centers. Donor data included demographics, functional warm ischemic time (fWIT), total warm ischemia time (tWIT) and total time on TA-NRP. Recipient data included demographics, model of end stage liver disease (MELD) score, etiology of liver disease, PNF, cold ischemic time (CIT), liver function tests, intensive care unit (ICU) and hospital length of stay (LOS), post-operative transplant related complications.ResultsThe donors' median age was 32 years old and median BMI was 27.4. Median fWIT was 20.5 min; fWIT exceeded 30 min in two donors. Median time to initiation of TA-NRP was 4 min and median time on bypass was 66 min. The median recipient listed MELD and MELD at transplant were 22 and 21, respectively. Median allograft CIT was 292 min. The median length of follow up was 257 days. Median ICU and hospital LOS were 2 and 7 days, respectively. Three recipients required management of anastomotic biliary strictures. No patients demonstrated IC, PNF or required re-transplantation.ConclusionLiver allografts from TA-NRP DCD donors demonstrated good early allograft and recipient outcomes

Hepatitis C Virus (HCV) Evades NKG2D-Dependent NK Cell Responses through NS5A-Mediated Imbalance of Inflammatory Cytokines

Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4) promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5.1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention

Gestational diabetes mellitus, prenatal maternal depression, and risk for postpartum depression: an Environmental influences on Child Health Outcomes (ECHO) Study

Background Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. Methods Participants in the current analysis included 5,822 women from the National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) Research Program: N = 4,606 with Neither GDM nor Prenatal Maternal Depression (Reference Category); N = 416 with GDM only; N = 689 with Prenatal Maternal Depression only; and N = 111 with Comorbid GDM and Prenatal Maternal Depression. The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. Results A higher proportion of women with GDM were classified as having prenatal depression (N = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression (N = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. Conclusions Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation

Quantifying sources of variability in infancy research using the infant-directed-speech preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure. (This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 798658.

SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States

This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe