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Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11–13, have recently been reported to cause Schaaf-Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties, and autism spectrum disorder. The causality of the reported variants in the context of the patients’ phenotypes was questioned, as MAGEL2 whole-gene deletions seem to cause little or no clinical phenotype. Here we report a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families, including 1 family with 3 individuals found to be affected with a truncating variant of MAGEL2, 11 individuals who are clinically affected but were not tested molecularly, and a presymptomatic fetal sibling carrying the pathogenic MAGEL2 variant. All cases harbor truncating mutations of MAGEL2, and nucleotides c.1990–1996 arise as a mutational hotspot, with 10 individuals and 1 fetus harboring a c.1996dupC (p.Q666fs) mutation and 2 fetuses harboring a c.1996delC (p.Q666fs) mutation. The phenotypic spectrum of Schaaf-Yang syndrome ranges from fetal akinesia to neurobehavioral disease and contractures of the small finger joints. This study provides strong evidence for the pathogenicity of truncating mutations of the paternal allele of MAGEL2, refines the associated clinical phenotypes, and highlights implications for genetic counseling for affected families.

MicroRNAs (miRNAs) are small non-coding RNAs that mediate post-transcriptional gene silencing. Over 700 human miRNAs have currently been identified, many of which are mutated or de-regulated in diseases. Here we report the identification of novel miRNAs through deep sequencing the small RNAome (<30 nt) of over 100 tissues or cell lines derived from human female reproductive organs in both normal and disease states. These specimens include ovarian epithelium and ovarian cancer, endometrium and endometriomas, and uterine myometrium and uterine smooth muscle tumors. Sequence reads not aligning with known miRNAs were each mapped to the genome to extract flanking sequences. These extended sequence regions were folded in silico to identify RNA hairpins. Sequences demonstrating the ability to form a stem loop structure with low minimum free energy (<-25 kcal) and predicted Drosha and Dicer cut sites yielding a mature miRNA sequence matching the actual sequence were considered putative novel miRNAs. Additional confidence was achieved when putative novel hairpins assembled a collection of sequences highly similar to the putative mature miRNA but with heterogeneous 3'-ends. A confirmed novel miRNA fulfilled these criteria and had its \"star\" sequence in our collection. We found 7 distinct confirmed novel miRNAs, and 51 additional novel miRNAs that represented highly confident predictions but without detectable star sequences. Our novel miRNAs were detectable in multiple samples, but expressed at low levels and not specific to any one tissue or cell type. To date, this study represents the largest set of samples analyzed together to identify novel miRNAs.

Caregivers of preschool and elementary school age children with Smith–Magenis syndrome (SMS), MBD5-associated neurodevelopmental disorder (MAND), and Pitt–Hopkins syndrome (PTHS) were surveyed to assess sleep disturbance and to identify disorder-specific sleep problems. Because of overlapping features of these rare genetic neurodevelopmental syndromes, data were compared to reports of sleep disturbance in children with autism spectrum disorder (ASD). While similarities were observed with ASD, specific concerns between disorders differed, including mean nighttime sleep duration, daytime sleepiness, night wakings, parasomnias, restless sleep, and bedwetting. Overall, sleep disturbance in PTHS is significant but less severe than in SMS and MAND. The complexity of these conditions and the challenges of underlying sleep disturbance indicate the need for more support, education, and ongoing management of sleep for these individuals.

Purpose Haploinsufficiency of USP7 , located at chromosome 16p13.2, has recently been reported in seven individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), seizures, and hypogonadism. Further, USP7 was identified to critically incorporate into the MAGEL2-USP7-TRIM27 (MUST), such that pathogenic variants in USP7 lead to altered endosomal F-actin polymerization and dysregulated protein recycling. Methods We report 16 newly identified individuals with heterozygous USP7 variants, identified by genome or exome sequencing or by chromosome microarray analysis. Clinical features were evaluated by review of medical records. Additional clinical information was obtained on the seven previously reported individuals to fully elucidate the phenotypic expression associated with USP7 haploinsufficiency. Results The clinical manifestations of these 23 individuals suggest a syndrome characterized by DD/ID, hypotonia, eye anomalies,feeding difficulties, GERD, behavioral anomalies, and ASD, and more specific phenotypes of speech delays including a nonverbal phenotype and abnormal brain magnetic resonance image findings including white matter changes based on neuroradiologic examination. Conclusion The consistency of clinical features among all individuals presented regardless of de novo USP7 variant type supports haploinsufficiency as a mechanism for pathogenesis and refines the clinical impact faced by affected individuals and caregivers.

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by neonatal hypotonia, developmental delay/intellectual disability, and characteristic feeding behaviors with failure to thrive during infancy; followed by hyperphagia and excessive weight gain later in childhood. Individuals with PWS also manifest complex behavioral phenotypes. Approximately 25% meet criteria for autism spectrum disorder (ASD). PWS is caused by the absence of paternally expressed, maternally silenced genes at chromosome 15q11-q13. MAGEL2 is one of five protein-coding genes in the PWS-critical domain. Truncating point mutations of the paternal allele of MAGEL2 cause Schaaf-Yang syndrome, which has significant phenotypic overlap with PWS, but is also clinically distinct; based on the presence of joint contractures, and a particularly high prevalence of autism spectrum disorder (up to 75% of affected individuals). The clinical and molecular overlap between PWS and Schaaf-Yang syndrome, but also their distinguishing features provide insight into the pathogenetic mechanisms underlying both disorders.

Whole ecosystem-based approaches are becoming increasingly common in pest management within agricultural systems. These strategies consider all trophic levels and abiotic processes within an ecosystem, including interactions between different factors. This review outlines a whole ecosystem approach to the integrated pest management of pear psyllid ( Cacopsylla pyri Linnaeus) within pear ( Pyrus communis L.) orchards, focusing on potential disruptions as a result of climate change. Pear psyllid is estimated to cost the UK pear industry £5 million per annum and has a significant economic impact on pear production globally. Pesticide resistance is well documented in psyllids, leading to many growers to rely on biological control using natural enemies during the summer months. In addition, multiple insecticides commonly used in pear psyllid control have been withdrawn from the UK and Europe, emphasising the need for alternative control methods. There is growing concern that climate change could alter trophic interactions and phenological events within agroecosystems. For example, warmer temperatures could lead to earlier pear flowering and pest emergence, as well as faster insect development rates and altered activity levels. If climate change impacts pear psyllid differently to natural enemies, then trophic mismatches could occur, impacting pest populations. This review aims to evaluate current strategies used in C. pyri management, discuss trophic interactions within this agroecosystem and highlight potential changes in the top-down and bottom-up control of C. pyri as a result of climate change. This review provides a recommended approach to pear psyllid management, identifies evidence gaps and outlines areas of future research.

In July 2015, the New Horizons spacecraft flew through the Pluto system at high speed, humanity's first close look at this enigmatic system on the outskirts of our solar system. In a series of papers, the New Horizons team present their analysis of the encounter data downloaded so far: Moore et al. present the complex surface features and geology of Pluto and its large moon Charon, including evidence of tectonics, glacial flow, and possible cryovolcanoes. Grundy et al. analyzed the colors and chemical compositions of their surfaces, with ices of H 2 O, CH 4 , CO, N 2 , and NH 3 and a reddish material which may be tholins. Gladstone et al. investigated the atmosphere of Pluto, which is colder and more compact than expected and hosts numerous extensive layers of haze. Weaver et al. examined the small moons Styx, Nix, Kerberos, and Hydra, which are irregularly shaped, fast-rotating, and have bright surfaces. Bagenal et al. report how Pluto modifies its space environment, including interactions with the solar wind and a lack of dust in the system. Together, these findings massively increase our understanding of the bodies in the outer solar system. They will underpin the analysis of New Horizons data, which will continue for years to come. Science , this issue pp. 1284 , 10.1126/science.aad9189 , 10.1126/science.aad8866 , 10.1126/science.aae0030 , & 10.1126/science.aad9045 Pluto’s atmosphere is cold, rarefied, and made mostly of nitrogen and methane, with layers of haze. Observations made during the New Horizons flyby provide a detailed snapshot of the current state of Pluto’s atmosphere. Whereas the lower atmosphere (at altitudes of less than 200 kilometers) is consistent with ground-based stellar occultations, the upper atmosphere is much colder and more compact than indicated by pre-encounter models. Molecular nitrogen (N 2 ) dominates the atmosphere (at altitudes of less than 1800 kilometers or so), whereas methane (CH 4 ), acetylene (C 2 H 2 ), ethylene (C 2 H 4 ), and ethane (C 2 H 6 ) are abundant minor species and likely feed the production of an extensive haze that encompasses Pluto. The cold upper atmosphere shuts off the anticipated enhanced-Jeans, hydrodynamic-like escape of Pluto’s atmosphere to space. It is unclear whether the current state of Pluto’s atmosphere is representative of its average state—over seasonal or geologic time scales.

Wild ground-nesting bees are key pollinators of apple (Malus domestica). We explored, (1) where they choose to nest, (2) what influences site selection and (3) species richness in orchards. Twenty-three orchards were studied over three years; twelve were treated with additional herbicide to increase bare ground with the remainder as untreated controls. Vegetation cover, soil type, soil compaction, nest number and location, and species were recorded. Fourteen species of ground-nesting solitary/eusocial bee were identified. Most nests were in areas free of vegetation and areas treated with additional herbicide were utilised by ground nesting bees within three years of application. Nests were also evenly distributed along the vegetation-free strips underneath the apple trees. This area was an important ground-nesting bee habitat with mean numbers of nests at peak nest activity of 873 per ha (range 44–5705), and 1153 per ha (range 0–4082) in 2018 and 2019, respectively. Increasing and maintaining areas of bare ground in apple orchards during peak nesting events could improve nesting opportunities for some species of ground-nesting bee and, combined with flowers strips, be part of a more sustainable pollinator management approach. The area under the tree row is an important contributor to the ground-nesting bee habitat and should be kept bare during peak nesting.

Pear psyllid (Cacopsylla pyri) is a persistent pest to the pear industry; with an estimated cost of £5 million per annum in the UK alone. This phloem feeding insect is resistant to a large proportion of approved pesticides, necessitating the use of alternative control strategies. Many pear growers practice integrated pest management (IPM) of pear psyllid, focusing on maximizing natural enemy populations, whilst minimizing the use of agrochemical sprays. The anthocorid Anthocoris nemoralis and the European earwig Forficula auricularia are particularly effective at controlling pear psyllid populations during the summer months. Despite the effectiveness of both natural enemies, there is a lack of understanding on whether both species should be promoted together or separately, due to the risk of intraguild predation (IGP) or interference competition. Furthermore, abiotic factors including temperature may influence both behaviors, altering activity level and niche overlap. Although IGP and interference competition have been documented between multiple species of natural enemies neither have been studied between these two specific predators. Using microcosm experiments, olfactometer assays and survival analyses this study demonstrated whether A. nemoralis and F. auricularia can be used in synchrony to control pear psyllid. Results indicated that IGP is present; F. auricularia will consume A. nemoralis when predators are not spatially separate and in absence of psyllid prey. There was no evidence for interference competition, although both predators consumed more prey at higher temperatures. This confirms that pear growers can encourage both predators for the control of pear psyllid without losing predation efficacy.