Nodal signaling is required for closure of the anterior neural tube in zebrafish

Background: Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish

Circadian rhythms in the pineal organ persist in zebrafish larvae that lack ventral brain

<p>Abstract</p> <p>Background</p> <p>The mammalian suprachiasmatic nucleus (SCN), located in the ventral hypothalamus, is a major regulator of circadian rhythms in mammals and birds. However, the role of the SCN in lower vertebrates remains poorly understood. Zebrafish <it>cyclops </it>(<it>cyc</it>) mutants lack ventral brain, including the region that gives rise to the SCN. We have used <it>cyc </it>embryos to define the function of the zebrafish SCN in regulating circadian rhythms in the developing pineal organ. The pineal organ is the major source of the circadian hormone melatonin, which regulates rhythms such as daily rest/activity cycles. Mammalian pineal rhythms are controlled almost exclusively by the SCN. In zebrafish and many other lower vertebrates, the pineal has an endogenous clock that is responsible in part for cyclic melatonin biosynthesis and gene expression.</p> <p>Results</p> <p>We find that pineal rhythms are present in <it>cyc </it>mutants despite the absence of an SCN. The arginine vasopressin-like protein (Avpl, formerly called Vasotocin) is a peptide hormone expressed in and around the SCN. We find <it>avpl </it>mRNA is absent in <it>cyc </it>mutants, supporting previous work suggesting the SCN is missing. In contrast, expression of the putative circadian clock genes, <it>cryptochrome 1b (cry1b) </it>and <it>cryptochrome 3 (cry3)</it>, in the brain of the developing fish is unaltered. Expression of two pineal rhythmic genes, <it>exo-rhodopsin </it>(<it>exorh) </it>and <it>serotonin-N-acetyltransferase </it>(<it>aanat2</it>), involved in photoreception and melatonin synthesis, respectively, is also similar between <it>cyc </it>embryos and their wildtype (WT) siblings. The timing of the peaks and troughs of expression are the same, although the amplitude of expression is slightly decreased in the mutants. Cyclic gene expression persists for two days in <it>cyc </it>embryos transferred to constant light or constant dark, suggesting a circadian clock is driving the rhythms. However, the amplitude of rhythms in <it>cyc </it>mutants kept in constant conditions decreased more quickly than in their WT siblings.</p> <p>Conclusion</p> <p>Our data suggests that circadian rhythms can be initiated and maintained in the absence of SCN and other tissues in the ventral brain. However, the SCN may have a role in regulating the amplitude of rhythms when environmental cues are absent. This provides some of the first evidence that the SCN of teleosts is not essential for establishing circadian rhythms during development. Several SCN-independent circadian rhythms have also been found in mammalian species. Thus, zebrafish may serve as a model system for understanding how vertebrate embryos coordinate rhythms that are controlled by different circadian clocks.</p

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P \u3c 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension

#CDCGrandRounds and #VitalSigns : A Twitter Analysis

BACKGROUND: The CDC hosts monthly panel presentations titled 'Public Health Grand Rounds' and publishes monthly reports known as Vital Signs. Hashtags #CDCGrandRounds and #VitalSigns were used to promote them on Twitter. Objectives: This study quantified the effect of hashtag count, mention count, and URL count and attaching visual cues to #CDCGrandRounds or #VitalSigns tweets on their retweet frequency. METHODS: Through Twitter Search Application Programming Interface, original tweets containing the hashtag #CDCGrandRounds (n = 6,966; April 21, 2011-October 25, 2016) and the hashtag #VitalSigns (n = 15,015; March 19, 2013-October 31, 2016) were retrieved respectively. Negative binomial regression models were applied to each corpus to estimate the associations between retweet frequency and three predictors (hashtag count, mention count, and URL link count). Each corpus was sub-set into cycles (#CDCGrandRounds: n = 58, #VitalSigns: n = 42). We manually coded the 30 tweets with the highest number of retweets for each cycle, whether it contained visual cues (images or videos). Univariable negative binomial regression models were applied to compute the prevalence ratio (PR) of retweet frequency for each cycle, between tweets with and without visual cues. FINDINGS: URL links increased retweet frequency in both corpora; effects of hashtag count and mention count differed between the two corpora. Of the 58 #CDCGrandRounds cycles, 29 were found to have statistically significantly different retweet frequencies between tweets with and without visual cues. Of these 29 cycles, one had a PR estimate &lt; 1; twenty-four, PR &gt; 1 but &lt; 3; and four, PR &gt; 3. Of the 42 #VitalSigns cycles, 19 were statistically significant. Of these 19 cycles, six were PR &gt; 1 and &lt; 3; and thirteen, PR &gt; 3. Conclusions: The increase of retweet frequency through attaching visual cues varied across cycles for original tweets with #CDCGrandRounds and #VitalSigns. Future research is needed to determine the optimal choice of visual cues to maximize the influence of public health tweets

Disparities in the survivorship experience among Latina survivors of breast cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144236/1/cncr31342_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144236/2/cncr31342.pd

A case-control study of the joint effect of reproductive factors and radiation treatment for first breast cancer and risk of contralateral breast cancer in the WECARE study.

OBJECTIVE: To examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC). METHODS: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity). RESULTS: Nulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast. CONCLUSION: Among young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman's risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC

#Globalhealth Twitter Conversations on #Malaria, #HIV, #TB, #NCDS, and #NTDS: a Cross-Sectional Analysis

BackgroundAdvocates use the hashtag #GlobalHealth on Twitter to draw users' attention to prominent themes on global health, to harness their support, and to advocate for change.ObjectivesWe aimed to describe #GlobalHealth tweets pertinent to given major health issues.MethodsTweets containing the hashtag #GlobalHealth (N = 157,951) from January 1, 2014, to April 30, 2015, were purchased from GNIP Inc. We extracted 5 subcorpora of tweets, each with 1 of 5 co-occurring disease-specific hashtags (#Malaria, #HIV, #TB, #NCDS, and #NTDS) for further analysis. Unsupervised machine learning was applied to each subcorpus to categorize the tweets by their underlying topics and obtain the representative tweets of each topic. The topics were grouped into 1 of 4 themes (advocacy; epidemiological information; prevention, control, and treatment; societal impact) or miscellaneous. Manual categorization of most frequent users was performed. Time zones of users were analyzed.FindingsIn the entire #GlobalHealth corpus (N = 157,951), there were 40,266 unique users, 85,168 retweets, and 13,107 unique co-occurring hashtags. Of the 13,087 tweets across the 5 subcorpora with co-occurring hashtag #malaria (n = 3640), #HIV (n = 3557), #NCDS (noncommunicable diseases; n = 2373), #TB (tuberculosis; n = 1781), and #NTDS (neglected tropical diseases; n = 1736), the most prevalent theme was prevention, control, and treatment (4339, 33.16%), followed by advocacy (3706, 28.32%), epidemiological information (1803, 13.78%), and societal impact (1617, 12.36%). Among the top 10 users who tweeted the highest number of tweets in the #GlobalHealth corpus, 5 were individual professionals, 3 were news media, and 2 were organizations advocating for global health. The most common users' time zone was Eastern Time (United States and Canada).ConclusionsThis study highlighted the specific #GlobalHealth Twitter conversations pertinent to malaria, HIV, tuberculosis, noncommunicable diseases, and neglected tropical diseases. These conversations reflect the priorities of advocates, funders, policymakers, and practitioners of global health on these high-burden diseases as they presented their views and information on Twitter to their followers

Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women's Environmental Cancer and Radiation Epidemiology Study.

Purpose The Women's Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2 mutations. With the completion of WECARE II, updated risk estimates are reported. Additional analyses that exclude women negative for deleterious mutations in ATM, CHEK2*1100delC, and PALB2 were performed. Patients and Methods The WECARE Study is a population-based case-control study that compared 1,521 CBC cases with 2,212 individually matched unilateral breast cancer (UBC) controls. Participants were younger than age 55 years when diagnosed with a first invasive breast cancer between 1985 and 2008. Women were interviewed about breast cancer risk factors, including family history. A subset of women was screened for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2. Rate ratios (RRs) were estimated using multivariable conditional logistic regression. Cumulative absolute risks (ARs) were estimated by combining RRs from the WECARE Study and population-based SEER*Stat cancer incidence data. Results Women with any first-degree relative with breast cancer had a 10-year AR of 8.1% for CBC (95% CI, 6.7% to 9.8%). Risks also were increased if the relative was diagnosed at an age younger than 40 years (10-year AR, 13.5%; 95% CI, 8.8% to 20.8%) or with CBC (10-year AR, 14.1%; 95% CI, 9.5% to 20.7%). These risks are comparable with those seen in BRCA1/2 deleterious mutation carriers (10-year AR, 18.4%; 95% CI, 16.0% to 21.3%). In the subset of women who tested negative for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2, estimates were unchanged. Adjustment for known breast cancer single-nucleotide polymorphisms did not affect estimates. Conclusion Breast cancer family history confers a high CBC risk, even after excluding women with deleterious mutations. Clinicians are urged to use detailed family histories to guide treatment and future screening decisions for young women with breast cancer

#CDCGrandRounds and #VitalSigns: A Twitter Analysis

Background: The CDC hosts monthly panel presentations titled ‘Public Health Grand Rounds’ and publishes monthly reports known as Vital Signs. Hashtags #CDCGrandRounds and #VitalSigns were used to promote them on Twitter. Objectives: This study quantified the effect of hashtag count, mention count, and URL count and attaching visual cues to #CDCGrandRounds or #VitalSigns tweets on their retweet frequency. Methods: Through Twitter Search Application Programming Interface, original tweets containing the hashtag #CDCGrandRounds (n = 6,966; April 21, 2011–October 25, 2016) and the hashtag #VitalSigns (n = 15,015; March 19, 2013–October 31, 2016) were retrieved respectively. Negative binomial regression models were applied to each corpus to estimate the associations between retweet frequency and three predictors (hashtag count, mention count, and URL link count). Each corpus was sub-set into cycles (#CDCGrandRounds: n = 58, #VitalSigns: n = 42). We manually coded the 30 tweets with the highest number of retweets for each cycle, whether it contained visual cues (images or videos). Univariable negative binomial regression models were applied to compute the prevalence ratio (PR) of retweet frequency for each cycle, between tweets with and without visual cues. Findings: URL links increased retweet frequency in both corpora; effects of hashtag count and mention count differed between the two corpora. Of the 58 #CDCGrandRounds cycles, 29 were found to have statistically significantly different retweet frequencies between tweets with and without visual cues. Of these 29 cycles, one had a PR estimate 1 but 3. Of the 42 #VitalSigns cycles, 19 were statistically significant. Of these 19 cycles, six were PR > 1 and 3. Conclusions: The increase of retweet frequency through attaching visual cues varied across cycles for original tweets with #CDCGrandRounds and #VitalSigns. Future research is needed to determine the optimal choice of visual cues to maximize the influence of public health tweets