Evaluation of the Effect of Bacteriophages on Mosquito Larval Development

Mosquitoes are medically important arthropod vectors of arboviruses and Plasmodium parasites with half of the human population globally at risk of mosquito borne diseases. Due to the lack of efficient vaccines and the growing problem of insecticide resistance, alternative approaches to curb mosquito transmitted diseases are needed. An area of increased interest is the mosquito microbiome. Mosquitoes rely on microbes for larval development and the microbiome has also been shown to affect vector competence. In order to better understand the functions and effects of the microbiome, new tools must be developed to better target and investigate specific species of the mosquito microbiota. In this study, the potential use of bacteriophages as a tool to modulate the microbiota composition in Aedes aegypti larval breeding water was investigated. Mosquito larvae were placed in gnotobiotic conditions where different bacteria species were inoculated into the breeding water to study the effect that bacteriophage-mediated modulation of the microbiota had on time to pupation. Six bacteria species were used: E. coli W3110, Enterobacter spp., Serratia spp., two Microbacterium species, and Arthrobacter spp.. Larval development was first observed when only one of the six bacteria species was added to the breeding water and it was shown that in the E. coli W3110 and Enterobacter spp. treatments, larvae reached pupation the fastest with the highest survival rate of the six species. The two Microbacterium species mediated the slowest pupation rates and the lowest survival rates. The E. coli-infecting bacteriophage, T7, was then added to the breeding water in a separate E. coli treatment as a bacteria-bacteriophage proof of concept. Delays in larval pupation and lower survival rates were then observed in the bacteriophage treatment. Bacteriophages targeting Enterobacter spp. and Serratia spp. were then isolated and the Enterobacter spp. were sequenced. Sequencing revealed that the two isolated bacteriophages were induced from two prophage regions of the Enterobacter spp. genome

Contrast material–enhanced MRA overestimates severity of carotid stenosis, compared with 3D time-of-flight MRA

AbstractObjectiveNon–contrast-enhanced magnetic resonance angiography (MRA) carotid imaging with the time-of-flight (TOF) technique compares favorably with angiography, ultrasound, and excised plaques. However, gadolinium contrast-enhanced MRA (CE-MRA) has almost universally replaced TOF-MRA, because it reduces imaging time (25 seconds vs 10 minutes) and improves signal-to-noise ratio. In our practice we found alarming discrepancies between CE-MRA and TOF-MRA, which was the impetus for this study.Study designTo compare the two techniques, we measured stenosis, demonstrated on three-dimensional images obtained at TOF and CE-MRA, in 107 carotid arteries in 58 male patients. The measurements were made on a Cemax workstation equipped with enlargement and measurement tools. Measurements to 0.1 mm were made at 90 degrees to the flow channel at the area of maximal stenosis and distal to the bulb where the borders of the internal carotid artery lumen were judged to be parallel (North American Symptomatic Carotid Endarterectomy Trial criteria). Experiments with carotid phantoms were done to test the comtribution of imaging software to image quality.ResultsTwelve arteries were occluded. In the remaining 95 arteries, compared with TOF-MRA, CE-MRA demonstrated a greater degree of stenosis in 42 arteries, a lesser degree of stenosis in 14 arteries, and similar (±5%) stenosis in 39 arteries (P = .02, χ2 analysis). The largest discrepancies were arteries with 0% to 70% stenosis. In those arteries in which CE-MRA identified a greater degree of stenosis than shown with TOF-MRA, mean increase was 21% for 0% to 29% stenosis, 36% for 30% to 49% stenosis, and 38% for of 50% to 69% stenosis. The carotid phantom experiments showed that the imaging parameters of CE-MRA, particularly the plane on which frequency encoding gradients were applied, reduced signal acquisition at the area of stenosis.ConclusionsCollectively these data demonstrate that CE-MRA parameters must be retooled if the method is to be considered reliable for determination of severity of carotid artery stenosis. CE-MRA is an excellent screening technique, but only TOF-MRA should be used to determine degree of carotid artery stenosis

Discovery and Follow-up Observations of the Young Type Ia Supernova 2016coj

The Type~Ia supernova (SN~Ia) 2016coj in NGC 4125 (redshift $z=0.004523$) was discovered by the Lick Observatory Supernova Search 4.9 days after the fitted first-light time (FFLT; 11.1 days before $B$-band maximum). Our first detection (pre-discovery) is merely $0.6\pm0.5$ day after the FFLT, making SN 2016coj one of the earliest known detections of a SN Ia. A spectrum was taken only 3.7 hr after discovery (5.0 days after the FFLT) and classified as a normal SN Ia. We performed high-quality photometry, low- and high-resolution spectroscopy, and spectropolarimetry, finding that SN 2016coj is a spectroscopically normal SN Ia, but with a high velocity of \ion{Si}{2} $\lambda$6355 ($\sim 12,600$\,\kms\ around peak brightness). The \ion{Si}{2} $\lambda$6355 velocity evolution can be well fit by a broken-power-law function for up to a month after the FFLT. SN 2016coj has a normal peak luminosity ($M_B \approx -18.9 \pm 0.2$ mag), and it reaches a $B$-band maximum \about16.0~d after the FFLT. We estimate there to be low host-galaxy extinction based on the absence of Na~I~D absorption lines in our low- and high-resolution spectra. The spectropolarimetric data exhibit weak polarization in the continuum, but the \ion{Si}{2} line polarization is quite strong ($\sim 0.9\% \pm 0.1\%$) at peak brightness.Comment: Submitte

Justice derailed : the uncertain fate of Haitian migrants and Dominicans of Haitian descent in the Dominican Republic

Over time, the Dominican Republic formalized a more restrictive definition of citizenship by birth. By expanding the interpretation of what it means to be “in transit,” the Dominican Republic began to chip away at its jus soli (right of soil) regime. Given the long history of migration from Haiti to the Dominican Republic and demographic realities, this shift has had a disproportionate impact on individuals of Haitian descent. The redefinition of the jus soli basis for citizenship reached its peak in the now infamous sentence of the Constitutional Tribunal of the Dominican Republic, 168-13. In September 2013, the Constitutional Tribunal issued Sentence 168-13, which retroactively denationalized and effectively rendered stateless many Dominicans of Haitian descent by establishing that children born in the Dominican Republic to those illegally residing in the country were not entitled to citizenship by birth, as their parents were considered to be “in transit.” The Sentence further called for a national regularization plan. In an effort to implement Sentence 168-13, the Dominican government established the National Plan for the Regularization of Foreigners (PNRE). The PNRE is a plan to regularize the status of undocumented migrants in the Dominican Republic, which most notably impacts Haitian migrants. Following international backlash over Sentence 168-13, Dominican Republic President Danilo Medina issued Law 169-14 (Naturalization Law), which provides a pathway to naturalization for those effectively left stateless by the Sentence. This report will detail the problems in the implementation of the PNRE and the Naturalization Law, how various actors were involved in or impacted by the regularization and naturalization processes, and finally, will outline the constraints that may inhibit the work of policy makers and human rights defenders in addressing immigration and citizenship issues going forward

Preferences for HIV prevention strategies among newly arrived Asian-born men who have sex with men living in Australia: A discrete choice experiment.

The HIV epidemic in Australia is changing with higher risk for HIV among newly-arrived Asian-born men who have sex with men (MSM) compared to Australian-born MSM. We evaluated the preferences for HIV prevention strategies among 286 Asian-born MSM living in Australia for <5 years. A latent class analysis uncovered three classes of respondents who were defined by their preferences: "PrEP" (52%), "Consistent condoms" (31%), and "No strategy" (17%). Compared to the "No strategy" class, men in the "PrEP" class were less likely to be a student or ask their partner for their HIV status. Men in the "Consistent condoms" class were more likely to get information about HIV from online, and less likely to ask their partner for their HIV status. Overall, PrEP was the preferred HIV prevention strategy for newly arrived migrants. Removing structural barriers to access PrEP can accelerate progress toward ending HIV transmission

PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery.

We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI\u27s Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples across 308 patients, which are hosted on the Cancer Genomics Cloud powered by Seven Bridges and the NCI Cancer Data Service for long-term storage and access with dbGaP permissions. The portal includes results from freely available, robust, validated and standardized analysis workflows on PDXNet sequencing files and PDMR data (3857 samples from 629 patients across 85 disease types). The PDXNet portal is continuously updated with new data and is of significant utility to the cancer research community as it provides a centralized location for PDXNet resources, which support multi-agent treatment studies, determination of sensitivity and resistance mechanisms, and preclinical trials

Reactive Oxygen Species Hydrogen Peroxide Mediates Kaposi's Sarcoma-Associated Herpesvirus Reactivation from Latency

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the host following an acute infection. Reactivation from latency contributes to the development of KSHV-induced malignancies, which include Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients, primary effusion lymphoma and multicentric Castleman's disease. However, the physiological cues that trigger KSHV reactivation remain unclear. Here, we show that the reactive oxygen species (ROS) hydrogen peroxide (H2O2) induces KSHV reactivation from latency through both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic replication, and KSHV reactivation from latency induced by oxidative stress, hypoxia, and proinflammatory and proangiogenic cytokines are mediated by H2O2. Mechanistically, H2O2 induction of KSHV reactivation depends on the activation of mitogen-activated protein kinase ERK1/2, JNK, and p38 pathways. Significantly, H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase and glutathione inhibit KSHV lytic replication in culture. In a mouse model of KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and significantly prolongs the lifespan of the mice. These results directly relate KSHV reactivation to oxidative stress and inflammation, which are physiological hallmarks of KS patients. The discovery of this novel mechanism of KSHV reactivation indicates that antioxidants and anti-inflammation drugs could be promising preventive and therapeutic agents for effectively targeting KSHV replication and KSHV-related malignancies

Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing

INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality