Human-Mediated Emergence as a Weed and Invasive Radiation in the Wild of the CD Genome Allotetraploid Rice Species (Oryza, Poaceae) in the Neotropics

BACKGROUND: The genus Oryza is being used as a model in plant genomic studies although there are several issues still to be resolved regarding the spatio-temporal evolution of this ancient genus. Particularly contentious is whether undated transoceanic natural dispersal or recent human interference has been the principal agent determining its present distribution and differentiation. In this context, we studied the origin and distribution history of the allotetraploid CD rice genome. It is endemic to the Neotropics but the genus is thought to have originated in the Paleotropics, and there is relatively little genetic divergence between some orthologous sequences of the C genome component and their Old World counterparts. METHODOLOGY/PRINCIPAL FINDINGS: Because of its allotetraploidy, there are several potential pitfalls in trying to date the formation of the CD genome using molecular data and this could lead to erroneous estimates. Therefore, we rather chose to rely on historical evidence to determine whether or not the CD genome was present in the Neotropics before the arrival of Columbus. We searched early collections of herbarium specimens and studied the reports of explorers of the tropical Americas for references to rice. In spite of numerous collectors traveling inland and collecting Oryza, plants determined as CD genome species were not observed away from cultivated rice fields until 1869. Various arguments suggest that they only consisted of weedy forms until that time. CONCLUSIONS/SIGNIFICANCE: The spatio-temporal distribution of herbarium collections fits a simple biogeographical scenario for the emergence in cultivated rice fields followed by radiation in the wild of the CD genome in the Neotropics during the last four centuries. This probably occurred from species introduced to the Americas by humans and we found no evidence that the CD genome pre-existed in the Old World. We therefore propose a new evolutionary hypothesis for such a recent origin of the CD genome. Moreover, we exemplify how an historical approach can provide potentially important information and help to disentangle the timing of evolutionary events in the history of the Oryza genomes

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Interleukin-1 beta has atheroprotective effects in advanced atherosclerotic lesions of mice

Despite decades of research, our understanding of the processes controlling late-stage atherosclerotic plaque stability remains poor. A prevailing hypothesis is that reducing inflammation may improve advanced plaque stability, as recently tested in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, in which post-myocardial infarction subjects were treated with an IL-1β antibody. Here, we performed intervention studies in which smooth muscle cell (SMC) lineage-tracing Apoe-/- mice with advanced atherosclerosis were treated with anti-IL-1β or IgG control antibodies. Surprisingly, we found that IL-1β antibody treatment between 18 and 26 weeks of Western diet feeding induced a marked reduction in SMC and collagen content, but increased macrophage numbers in the fibrous cap. Moreover, although IL-1β antibody treatment had no effect on lesion size, it completely inhibited beneficial outward remodeling. We also found that SMC-specific knockout of Il1r1 (encoding IL-1 receptor type 1) resulted in smaller lesions nearly devoid of SMCs and lacking a fibrous cap, whereas macrophage-selective loss of IL-1R1 had no effect on lesion size or composition. Taken together, these results show that IL-1β has multiple beneficial effects in late-stage murine atherosclerosis, including promotion of outward remodeling and formation and maintenance of an SMC- and collagen-rich fibrous cap

Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers in the PPMI cohort

We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging, and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as <65% of age/sex-expected lowest putamen SBR) and 11% had hyposmia (defined as ≤15th percentile for age and sex). Only 5 of 176 LRRK2 NMCs developed PD during follow-up. Although NMCs scored significantly worse on numerous clinical scales at baseline than HCs, there was no longitudinal change in any clinical measures over 2 years or in DAT binding. There were no longitudinal differences in CSF and serum biomarkers between NMCs and HCs. Urinary BMP was significantly elevated in NMCs at all time points but did not change longitudinally. Neither baseline biofluid biomarkers nor the presence of DAT deficit correlated with 2-year change in clinical outcomes. We observed no significant 2-year longitudinal change in clinical or biomarker measures in LRRK2 G2019S NMCs in this large, well-characterized cohort even in the participants with baseline DAT deficit. These findings highlight the essential need for further enrichment biomarker discovery in addition to DAT deficit and longer follow-up to enable the selection of NMCs at the highest risk for conversion to enable future prevention clinical trials