Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer

Prior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinogenesis, we measured genome-wide DNA methylation in breast milk from women with and without a diagnosis of breast cancer in two independent cohorts. DNA methylation was assessed using Illumina HumanMethylation450k in 87 breast milk samples. Through an epigenome-wide association study we explored CpG sites associated with a breast cancer diagnosis in the prospectively collected milk samples from the breast that would develop cancer compared with women without a diagnosis of breast cancer using linear mixed effects models adjusted for history of breast biopsy, age, RefFreeCellMix cell estimates, time of delivery, array chip and subject as random effect. We identified 58 differentially methylated CpG sites associated with a subsequent breast cancer diagnosis (q-value \u3c0.05). Nearly all CpG sites associated with a breast cancer diagnosis were hypomethylated in cases compared with controls and were enriched for CpG islands. In addition, inferred repeat element methylation was lower in breast milk DNA from cases compared to controls, and cases exhibited increased estimated epigenetic mitotic tick rate as well as DNA methylation age compared with controls. Breast milk has utility as a biospecimen for prospective assessment of disease risk, for understanding the underlying molecular basis of breast cancer risk factors and improving primary and secondary prevention of breast cancer

The Building Healthy Eating and Self-Esteem Together for University Students Mobile App to Treat Eating Disorders: User-Centered Research Design and Feasibility Study

Background: University students are an at-risk group for the development of eating disorders (EDs); however, many college campuses lack sufficient resources to provide ED specialty care. Students report unique reasons for not seeking ED treatment, including the desire to solve the problem on their own (eg, seeking help from friends, self-medicating, or waiting to see if their problems improve), inability to afford treatment, lack of time to participate in the treatment, fear of seeing their primary care physician, and lack of recognition of their issues as an ED. Mobile health (mHealth) apps may be a cost-effective, helpful adjunctive tool to overcome personal and systemic barriers and encourage help seeking. Objective: This paper describes the development, usability, and acceptability of the Building Healthy Eating and Self-Esteem Together for University Students (BEST-U) mHealth smartphone app, which is designed to fill critical gaps in access to ED treatment on college campuses. Methods: We undertook a 4-phase iterative development process that focused on user-centered design. The 4 phases included needs assessment based on literature reviews, prototype development and initial evaluation in a pilot trial, redesign, and further pilot-testing to assess the usability and acceptability of the final version of the mHealth app. Acceptability and user satisfaction were assessed using an ad hoc survey that ranged from 1 (strongly disagree) to 7 (strongly agree). Results: Our needs assessment identified a lack of accessible and affordable treatments for university students. To help meet this need, the BEST-U prototype was designed as an 11-week program that provided interactive, weekly modules that focused on second- and third-wave cognitive behavioral skills. The modules focused on topics such as psychoeducation, reducing thought distortions and body checking, improving body image, interpersonal effectiveness, and behavior chain analysis. The content included interactive quizzes, short answer questions, daily and weekly logs, and surveys completed in the app. BEST-U was paired with brief 25-30 minutes of weekly telehealth coaching sessions provided by a licensed provider or supervised trainee. Pilot-testing revealed minor issues with one module of the app content, which some participants viewed as having low relevance to their experience and therapist concerns about the organization of the app content. These issues were addressed through the removal, addition, and reorganization of BEST-U modules, with the help of therapists-in-training across 2 workshops. The revised version of the BEST-U app had a grand mean acceptability rating of 5.73 out of 7. The participants completed 90.1% (694/770) of the BEST-U modules, indicating high compliance. Conclusions: BEST-U is a new, acceptable, and user-friendly mHealth app to help therapists deliver brief, evidence-based cognitive behavioral interventions. Owing to its acceptability and user-friendly nature, BEST-U has high user compliance and holds promise for future implementation and dissemination in university mental health settings

Doubling the mobility of InAs/InGaAs selective area grown nanowires

Selective area growth (SAG) of nanowires and networks promise a route toward scalable electronics, photonics, and quantum devices based on III-V semiconductor materials. The potential of high-mobility SAG nanowires however is not yet fully realised, since interfacial roughness, misfit dislocations at the nanowire/substrate interface and nonuniform composition due to material intermixing all scatter electrons. Here, we explore SAG of highly lattice-mismatched InAs nanowires on insulating GaAs(001) substrates and address these key challenges. Atomically smooth nanowire/substrate interfaces are achieved with the use of atomic hydrogen (a-H) as an alternative to conventional thermal annealing for the native oxide removal. The problem of high lattice mismatch is addressed through an InxGa1-xAs buffer layer introduced between the InAs transport channel and the GaAs substrate. The Ga-In material intermixing observed in both the buffer layer and the channel is inhibited via careful tuning of the growth temperature. Performing scanning transmission electron microscopy and x-ray diffraction analysis along with low-temperature transport measurements we show that optimized In-rich buffer layers promote high-quality InAs transport channels with the field-effect electron mobility over 10 000 cm2 V-1 s-1. This is twice as high as for nonoptimized samples and among the highest reported for InAs selective area grown nanostructures.The project was supported by Microsoft Quantum, the European Research Council (ERC) under Grant No. 716655 (HEMs-DAM), and the European Union Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant No. 722176. The authors acknowledge Dr. Keita Ohtani for technical support and fruitful discussions. D.V.B. is grateful to Dr. Juan-Carlos Estrada Saldaña for careful reading of the manuscript. The authors thank Francesco Montalenti, Marco Albani and Leo Miglio for scientific discussions. ICN2 acknowledges funding from Generalitat de Catalunya 2017 SGR 327. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant No. SEV-2017-0706) and is funded by the CERCA Programme/Generalitat de Catalunya. Part of the present work has been performed in the framework of Universitat Autònoma de Barcelona Materials Science Ph.D. program. The HAADF-STEM microscopy was conducted in the Laboratorio de Microscopias Avanzadas at Instituto de Nanociencia de Aragon-Universidad de Zaragoza. M.C.S. has received funding from the European Unionâs Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 754510 (PROBIST). The funding agency is Consejo Superior de Investigaciones Científicas (CSIC) and the project reference is “Research Platform on Quantum Technologies PTI-001”

TESS Discovery of an ultra-short-period planet around the nearby M dwarf LHS 3844

Data from the newly-commissioned \textit{Transiting Exoplanet Survey Satellite} (TESS) has revealed a "hot Earth" around LHS 3844, an M dwarf located 15 pc away. The planet has a radius of $1.32\pm 0.02$ $R_\oplus$ and orbits the star every 11 hours. Although the existence of an atmosphere around such a strongly irradiated planet is questionable, the star is bright enough ($I=11.9$, $K=9.1$) for this possibility to be investigated with transit and occultation spectroscopy. The star's brightness and the planet's short period will also facilitate the measurement of the planet's mass through Doppler spectroscopy.Comment: 10 pages, 4 figures. Submitted to ApJ Letters. This letter makes use of the TESS Alert data, which is currently in a beta test phase, using data from the pipelines at the TESS Science Office and at the TESS Science Processing Operations Cente

TESS Discovery of a Transiting Super-Earth in the π\pi Mensae System

We report the detection of a transiting planet around $\pi$ Mensae (HD 39091), using data from the Transiting Exoplanet Survey Satellite (TESS). The solar-type host star is unusually bright (V=5.7) and was already known to host a Jovian planet on a highly eccentric, 5.7-year orbit. The newly discovered planet has a size of $2.04\pm 0.05$ $R_\oplus$ and an orbital period of 6.27 days. Radial-velocity data from the HARPS and AAT/UCLES archives also displays a 6.27-day periodicity, confirming the existence of the planet and leading to a mass determination of $4.82\pm 0.85$ $M_\oplus$. The star's proximity and brightness will facilitate further investigations, such as atmospheric spectroscopy, asteroseismology, the Rossiter--McLaughlin effect, astrometry, and direct imaging.Comment: Accepted for publication ApJ Letters. This letter makes use of the TESS Alert data, which is currently in a beta test phase. The discovery light curve is included in a table inside the arxiv submissio

Human milk-associated bacterial communities associate with the infant gut microbiome over the first year of life

IntroductionMicrobial communities inhabiting the human infant gut are important for immune system development and lifelong health. One critical exposure affecting the bacterial colonization of the infant gut is consumption of human milk, which contains diverse microbial communities and prebiotics. We hypothesized that human milk-associated microbial profiles are associated with those of the infant gut.MethodsMaternal–infant dyads enrolled in the New Hampshire Birth Cohort Study (n = 189 dyads) contributed breast milk and infant stool samples collected approximately at 6 weeks, 4 months, 6 months, 9 months, and 12 months postpartum (n = 572 samples). Microbial DNA was extracted from milk and stool and the V4-V5 region of the bacterial 16S rRNA gene was sequenced.ResultsClustering analysis identified three breast milk microbiome types (BMTs), characterized by differences in Streptococcus, Staphylococcus, Pseudomonas, Acinetobacter, and microbial diversity. Four 6-week infant gut microbiome types (6wIGMTs) were identified, differing in abundances of Bifidobacterium, Bacteroides, Clostridium, Streptococcus, and Escherichia/Shigella, while two 12-month IGMTs (12mIGMTs) differed primarily by Bacteroides presence. At 6 weeks, BMT was associated with 6wIGMT (Fisher’s exact test value of p = 0.039); this association was strongest among infants delivered by Cesarean section (Fisher’s exact test value of p = 0.0028). The strongest correlations between overall breast milk and infant stool microbial community structures were observed when comparing breast milk samples to infant stool samples collected at a subsequent time point, e.g., the 6-week breast milk microbiome associated with the 6-month infant gut microbiome (Mantel test Z-statistic = 0.53, value of p = 0.001). Streptoccous and Veillonella species abundance were correlated in 6-week milk and infant stool, and 4- and 6-month milk Pantoea species were associated with infant stool Lachnospiraceae genera at 9 and 12  months.DiscussionWe identified clusters of human milk and infant stool microbial communities that were associated in maternal–infant dyads at 6 weeks of life and found that milk microbial communities were more strongly associated with infant gut microbial communities in infants delivered operatively and after a lag period. These results suggest that milk microbial communities have a long-term effect on the infant gut microbiome both through sharing of microbes and other molecular mechanisms

Mosquito Infection Responses to Developing Filarial Worms

Human lymphatic filariasis is a mosquito-vectored disease caused by the nematode parasites Wuchereria bancrofti, Brugia malayi and Brugia timori. These are relatively large roundworms that can cause considerable damage in compatible mosquito vectors. In order to assess how mosquitoes respond to infection in compatible mosquito-filarial worm associations, microarray analysis was used to evaluate transcriptome changes in Aedes aegypti at various times during B. malayi development. Changes in transcript abundance in response to the different stages of B. malayi infection were diverse. At the early stages of midgut and thoracic muscle cell penetration, a greater number of genes were repressed compared to those that were induced (20 vs. 8). The non-feeding, intracellular first-stage larvae elicited few differences, with 4 transcripts showing an increased and 9 a decreased abundance relative to controls. Several cecropin transcripts increased in abundance after parasites molted to second-stage larvae. However, the greatest number of transcripts changed in abundance after larvae molted to third-stage larvae and migrated to the head and proboscis (120 induced, 38 repressed), including a large number of putative, immunity-related genes (∼13% of genes with predicted functions). To test whether the innate immune system of mosquitoes was capable of modulating permissiveness to the parasite, we activated the Toll and Imd pathway controlled rel family transcription factors Rel1 and Rel2 (by RNA interference knockdown of the pathway's negative regulators Cactus and Caspar) during the early stages of infection with B. malayi. The activation of either of these immune signaling pathways, or knockdown of the Toll pathway, did not affect B. malayi in Ae. aegypti. The possibility of LF parasites evading mosquito immune responses during successful development is discussed

Characteristics of Kepler Planetary Candidates Based on the First Data Set: The Majority are Found to be Neptune-Size and Smaller

In the spring of 2009, the Kepler Mission commenced high-precision photometry on nearly 156,000 stars to determine the frequency and characteristics of small exoplanets, conduct a guest observer program, and obtain asteroseismic data on a wide variety of stars. On 15 June 2010 the Kepler Mission released data from the first quarter of observations. At the time of this publication, 706 stars from this first data set have exoplanet candidates with sizes from as small as that of the Earth to larger than that of Jupiter. Here we give the identity and characteristics of 306 released stars with planetary candidates. Data for the remaining 400 stars with planetary candidates will be released in February 2011. Over half the candidates on the released list have radii less than half that of Jupiter. The released stars include five possible multi-planet systems. One of these has two Neptune-size (2.3 and 2.5 Earth-radius) candidates with near-resonant periods.Comment: Paper to accompany Kepler's June 15, 2010 data release; submitted to Astrophysical Journal Figures 1,2,& 3 revised. Improved labeling on all figures. Slight changes to planet frequencies in result

Planet Occurrence within 0.25 AU of Solar-type Stars from Kepler

We report the distribution of planets as a function of planet radius (R_p), orbital period (P), and stellar effective temperature (Teff) for P < 50 day orbits around GK stars. These results are based on the 1,235 planets (formally "planet candidates") from the Kepler mission that include a nearly complete set of detected planets as small as 2 Earth radii (Re). For each of the 156,000 target stars we assess the detectability of planets as a function of R_p and P. We also correct for the geometric probability of transit, R*/a. We consider first stars within the "solar subset" having Teff = 4100-6100 K, logg = 4.0-4.9, and Kepler magnitude Kp < 15 mag. We include only those stars having noise low enough to permit detection of planets down to 2 Re. We count planets in small domains of R_p and P and divide by the included target stars to calculate planet occurrence in each domain. Occurrence of planets varies by more than three orders of magnitude and increases substantially down to the smallest radius (2 Re) and out to the longest orbital period (50 days, ~0.25 AU) in our study. For P < 50 days, the radius distribution is given by a power law, df/dlogR= k R^\alpha. This rapid increase in planet occurrence with decreasing planet size agrees with core-accretion, but disagrees with population synthesis models. We fit occurrence as a function of P to a power law model with an exponential cutoff below a critical period P_0. For smaller planets, P_0 has larger values, suggesting that the "parking distance" for migrating planets moves outward with decreasing planet size. We also measured planet occurrence over Teff = 3600-7100 K, spanning M0 to F2 dwarfs. The occurrence of 2-4 Re planets in the Kepler field increases with decreasing Teff, making these small planets seven times more abundant around cool stars than the hottest stars in our sample. [abridged]Comment: Submitted to ApJ, 22 pages, 10 figure