Modeling polar marine ecosystem functions guided by bacterial physiological and taxonomic traits

Heterotrophic marine bacteria utilize organic carbon for growth and biomass synthesis. Thus, their physiological variability is key to the balance between the production and consumption of organic matter and ultimately particle export in the ocean. Here we investigate a potential link between bacterial traits and ecosystem functions in the rapidly warming West Antarctic Peninsula (WAP) region based on a bacteria-oriented ecosystem model. Using a data assimilation scheme, we utilize the observations of bacterial groups with different physiological traits to constrain the group-specific bacterial ecosystem functions in the model. We then examine the association of the modeled bacterial and other key ecosystem functions with eight recurrent modes representative of different bacterial taxonomic traits. Both taxonomic and physiological traits reflect the variability in bacterial carbon demand, net primary production, and particle sinking flux. Numerical experiments under perturbed climate conditions demonstrate a potential shift from low nucleic acid bacteria to high nucleic acid bacteria-dominated communities in the coastal WAP. Our study suggests that bacterial diversity via different taxonomic and physiological traits can guide the modeling of the polar marine ecosystem functions under climate change

12-h clock regulation of genetic information flow by XBP1s

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pan, Y., Ballance, H., Meng, H., Gonzalez, N., Kim, S., Abdurehman, L., York, B., Chen, X., Schnytzer, Y., Levy, O., Dacso, C. C., McClung, C. A., O'Malley, B. W., Liu, S., & Zhu, B. 12-h clock regulation of genetic information flow by XBP1s. Plos Biology, 18(1), (2020): e3000580, doi:10.1371/journal.pbio.3000580.Our group recently characterized a cell-autonomous mammalian 12-h clock independent from the circadian clock, but its function and mechanism of regulation remain poorly understood. Here, we show that in mouse liver, transcriptional regulation significantly contributes to the establishment of 12-h rhythms of mRNA expression in a manner dependent on Spliced Form of X-box Binding Protein 1 (XBP1s). Mechanistically, the motif stringency of XBP1s promoter binding sites dictates XBP1s’s ability to drive 12-h rhythms of nascent mRNA transcription at dawn and dusk, which are enriched for basal transcription regulation, mRNA processing and export, ribosome biogenesis, translation initiation, and protein processing/sorting in the Endoplasmic Reticulum (ER)-Golgi in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). We further identified GA-binding proteins (GABPs) as putative novel transcriptional regulators driving 12-h rhythms of gene expression with more diverse phases. These 12-h rhythms of gene expression are cell autonomous and evolutionarily conserved in marine animals possessing a circatidal clock. Our results demonstrate an evolutionarily conserved, intricate network of transcriptional control of the mammalian 12-h clock that mediates diverse biological pathways. We speculate that the 12-h clock is coopted to accommodate elevated gene expression and processing in mammals at the two rush hours, with the particular genes processed at each rush hour regulated by the circadian and/or tissue-specific pathways.This study was supported by the American Diabetes Association junior faculty development award 1-18-JDF-025 to B.Z., by funding from National Institute of Health HD07879 and 1P01DK113954 to B.W.O, by funding from National Science Foundation award 1703170 to C.C.D. and B.Z., and by funding from Brockman Foundation to C.C.D and B.W.O. This work was further supported by the UPMC Genome Center with funding from UPMC’s Immunotherapy and Transplant Center. This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. Research reported in this publication was further supported by the National Institute of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under award number P30DK120531 to Pittsburgh Liver Research Center, in which both S.L. and B.Z. are members. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Dissemination of information to General Practitioners: a questionnaire survey

BACKGROUND: Early identification of permanent hearing impairment in children enables appropriate intervention which reduces adverse developmental outcomes. The UK Government has introduced a universal hearing screening programme for neonates. All involved health professionals, including those in Primary Care, need to be aware of the service to enable them to offer appropriate support to their patients. A programme of information dissemination within Primary Care was therefore undertaken. The aim of the current study was to determine the extent to which the information had reached General Practitioners (GPs), the GPs' preferred mode of dissemination and the sources from which GPs accessed information METHODS: Postal questionnaire survey of a randomised sample of 1000 GPs in the Phase I pilot sites of the Neonatal Hearing Screening Programme (NHSP). RESULTS: Responses were received from 54.2% of the sample. Just under 50% of those responding had received information, 62.2% of respondents said they would like to receive more information and the preferred methods of dissemination were the written word and web-sites to allow access when needed. Few GPs perceive themselves to have a core role in the delivery of the NHSP and thence a need for knowledge in the subject. Many are keen to delegate detail to a third party, usually the health visitor, who has traditionally had responsibility for hearing screening. CONCLUSIONS: Dissemination efforts for service developments of relevance to GPs should concentrate on advertising a website address via brief but memorable posted literature and/or articles in relevant journals and magazines. The website should be GP-friendly, and have a dedicated area for GPs including information of specific relevance and downloadable information sheets

HPV31 utilizes the ATR-Chk1 pathway to maintain elevated RRM2 levels and a replication-competent environment in differentiating Keratinocytes

Productive replication of human papillomaviruses (HPV) is restricted to the uppermost layers of the differentiating epithelia. How HPV ensures an adequate supply of cellular substrates for viral DNA synthesis in a differentiating environment is unclear. Here, we demonstrate that HPV31 positive cells exhibit increased dNTP pools and levels of RRM2, a component of the ribonucleotide reductase (RNR) complex, which is required for de novo synthesis of dNTPs. RRM2 depletion blocks productive replication, suggesting RRM2 provides dNTPs for viral DNA synthesis in differentiating cells. We demonstrate that HPV31 regulates RRM2 levels through expression of E7 and activation of the ATR-Chk1-E2F1 DNA damage response, which is essential to combat replication stress upon entry into S-phase, as well as for productive replication. Our findings suggest a novel way in which viral DNA synthesis is regulated through activation of ATR and Chk1 and highlight an intriguing new virus/host interaction utilized for viral replication

Centennial Challenges Program Update: From Humanoids to 3D-Printing Houses on Mars, How the Public Can Advance Technologies for NASA and the Nation

The Centennial Challenges (CC) program, part of NASA's Space Technology Mission Directorate (STMD), was founded upon the principle that engaging the public at large was a very important part of garnering the true magnitude of grassroots American innovation and ingenuity. The program uses a focused problem-statement approach to obtain solutions and/or stimulate innovation in key NASA technology gaps by catalyzing sources outside of the traditional aerospace community. The CC program announced the first two challenge competitions in 2005 incentivizing the public to participate using a congressionally authorized prize purse. Since then, the program has developed and executed more than 18 competitions and has awarded over $9 million in prize money. The challenges have covered a variety of technology areas, including propulsion, robotics, communications and navigation, human health, science instrumentation, nanotech, materials and structures, and aerodynamics. Centennial Challenges' accomplishments from October 2016 to December 2017--including significant increases in the amount and diversity of participants; increase in prize purse awards; strong alignments with NASA missions; and partnerships with industry, academia, and other government agencies-are summarized in this paper. Technological advancements, communication strategies, and legal authority are also discussed. NASA is leading the government agencies in the area of prizes and competitions to push technologies, and the CC program is one powerful example of NASA's continuing commitment to technological advancement and innovation through non-traditional programs. Currently, the Agency has in place the proven infrastructure, policies, and people needed to enable the successful use of competition tools, including the ones used as part of the CC program

Aptamer-Phage Reporters for Ultrasensitive Lateral Flow Assays

We introduce the modification of bacteriophage particles with aptamers for use as bioanalytical reporters, and demonstrate the use of these particles in ultrasensitive lateral flow assays. M13 phage displaying an in vivo biotinylatable peptide (AviTag) genetically fused to the phage tail protein pIII were used as reporter particle scaffolds, with biotinylated aptamers attached via avidin朾iotin linkages, and horseradish peroxidase (HRP) reporter enzymes covalently attached to the pVIII coat protein. These modified viral nanoparticles were used in immunochromatographic sandwich assays for the direct detection of IgE and of the penicillin-binding protein from Staphylococcus aureus (PBP2a). We also developed an additional lateral flow assay for IgE, in which the analyte is sandwiched between immobilized anti-IgE antibodies and aptamer-bearing reporter phage modified with HRP. The limit of detection of this LFA was 0.13 ng/mL IgE, ?100 times lower than those of previously reported IgE assays

The Nihoku Ecosystem Restoration Project: A case study in predator exclusion fencing, ecosystem restoration, and seabird translocation

Reports were scanned in black and white at a resolution of 600 dots per inch and were converted to text using Adobe Paper Capture Plug-in.Newell’s Shearwater (Puffinus auricularis newelli; NESH) and Hawaiian Petrel (Pterodroma sandwichensis; HAPE) are both listed under the Endangered Species Act of 1973 and are declining due to collisions with power lines and structures, light attraction, predation by feral cats, pigs, rats, and introduced Barn Owls, habitat degradation by feral ungulates (pigs, goats) and invasive exotic plants. Protection of NESH and HAPE on their nesting grounds and reduction of collision and lighting hazards are high priority recovery actions for these species. Given the challenges in protecting nesting birds in their rugged montane habitats, it has long been desirable to also create breeding colonies of both species in more accessible locations that offer a higher level of protection. Translocation of birds to breeding sites within predator exclusion fences was ranked as priority 1 in the interagency 5-year Action Plan for Newell’s Shearwater and Hawaiian Petrel. In 2012, funding became available through several programs to undertake this action at Kilauea Point National Wildlife Refuge (KPNWR), which is home to one of the largest seabird colonies in the main Hawaiian Islands. The project was named the “Nihoku Ecosystem Restoration Project” after the area on the Refuge where the placement of the future colony was planned. The Nihoku Ecosystem Restoration Project is a result of a large partnership between multiple government agencies and non-profit groups who have come together to help preserve the native species of Hawaii. There were four stages to this multi-faceted project: permitting and biological monitoring, fence construction, restoration and predator eradication, followed by translocation of the birds to the newly secured habitat. The translocation component is expected to last five years and involve up to 90 individuals each of NESH and HAPE. Prior to fence construction, baseline monitoring data were collected in order to provide a record of initial site conditions and species diversity. Surveys were conducted quarterly from 2012-2014, investigating diversity and richness of plant, invertebrate, mammalian, and avian species. A 650 m (2130 ft) long predator proof fence was completed at Nihoku in September 2014, enclosing 2.5 ha (6.2 ac), and all mammalian predators were eradicated by March 2015. From 2015-2017, approximately 40% of the fenced area (~1 ha) was cleared of non-native vegetation using heavy machinery and herbicide application. A water catchment and irrigation system was installed, and over 18,000 native plants representing 37 native species were outplanted in the restoration area. The plant species selected are low-in-stature, making burrow excavation easier for seabirds while simultaneously providing forage for Nene (Branta sandvicensis). Habitat restoration was done in phases (10-15% of the project per year) and will be continued until the majority of the area has been restored. In addition to habitat restoration, 50 artificial burrows were installed in the restoration to facilitate translocation activities. From 2012-2017 potential source colonies of NESH and HAPE were located by the Kauai Endangered Seabird Recovery Project (KESRP) with visual, auditory, and ground searching methods at locations around Kauai. The sites that were selected as source colonies for both species were Upper Limahuli Preserve (owned by the National Tropical Botanical Garden; NTBG) and several sites within the Hono o Na Pali Natural Area Reserve system. These sites had high call rates, high burrow densities to provide an adequate source of chicks for the translocation, and had active predator control operations in place to offset any potential impacts of the monitoring. Translocation protocols were developed based on previous methods developed in New Zealand; on the ground training was done by the translocation team by visiting active projects in New Zealand. In year one, 10 HAPE and eight NESH were translocated, and the goal is to translocate up to 20 in subsequent years for a cohort size of 90 birds of each species over a five year period. Post-translocation monitoring has been initiated to gauge the level of success, and social attraction has been implemented in an attempt to attract adults to the area. It is anticipated that the chicks raised during this project will return to breed at Nihoku when they are 65-6 years old; for the first cohort released in 2015 this would be starting in 2020. Once this occurs, Nihoku will be the first predator-free breeding area of both species in Hawaii.This project and manuscript are part of a large collaboration that spans beyond the agencies mentioned. Many individuals were consulted for advice and input along the way. For botanical and invertebrate advice, we thank: David Burney, Lida Burney, Natalia Tangalin, Emory Griffin‐Noyes, Kawika Winter, Kim Starr, Forest Starr, Sheldon Plentovich and Keren Gunderson. For assistance with translocation training and predator exclusion fence technical advice we thank Helen Gummer, John McLennan, Lindsay Wilson, and Darren Peters. For reviewing documents related to this project, and for feedback on techniques we thank the seabird hui, particularly Fern Duvall, Jay Penniman, Megan Laut, Darcy Hu and Cathleen Bailey. For their on the ground assistance at KPNWR, we thank: Shannon Smith, Chadd Smith, Warren Madeira, Rob Petersen, Jennifer Waipa, Padraic Gallagher, Carolyn Rushforth, Kristina Macaulay, Jimmy Macaulay, and Jillian Cosgrove. We would also like to thank Chris Mottley, Kyle Pias and the entire predator control team in Hono o Na Pali NAR and Kawika Winter, Chiemi Nagle, Merlin Edmonds and the entire predator control team in Upper Limahuli Preserve. We would also like to thank the Kaua‘i Island Utility Co‐operative (KIUC) for the funding that they provide – through a Habitat Conservation Plan – to provide predator control and seabird monitoring at several of the sites used for translocation. Lastly, we would like to thank all of the endangered seabird technicians within the Kauaʻi Endangered Seabird Recovery Project for all of their hard work in montane colonies. Mahalo

Home Blood Pressure Telemonitoring Technology for Patients With Asymptomatic Elevated Blood Pressure Discharged From the Emergency Department: Pilot Study

BACKGROUND: Hypertension affects 1 in 5 Canadians and is the leading cause of morbidity and mortality globally. Hypertension control is declining due to multiple factors including lack of access to primary care. Consequently, patients with hypertension frequently visit the emergency department (ED) due to high blood pressure (BP). Telehealth for Emergency-Community Continuity of Care Connectivity via Home-Telemonitoring Blood Pressure is a pilot project that implements and evaluates a comprehensive home blood pressure telemonitoring (HBPT) and physician case management protocol designed as a postdischarge management strategy to support patients with asymptomatic elevated BP as they transition from the ED to home. OBJECTIVE: Our objective was to conduct a feasibility study of an HBPT program for patients with asymptomatic elevated BP discharged from the ED. METHODS: Patients discharged from an urban, tertiary care hospital ED with asymptomatic elevated BP were recruited in Vancouver, British Columbia, Canada, and provided with HBPT technology for 3 months of monitoring post discharge and referred to specialist hypertension clinics. Participants monitored their BP twice in the morning and evenings and tele-transmitted readings via Bluetooth Sensor each day using an app. A monitoring clinician received these data and monitored the patient\u27s condition daily and adjusted antihypertensive medications. Feasibility outcomes included eligibility, recruitment, adherence to monitoring, and retention rates. Secondary outcomes included proportion of those who were defined as having hypertension post-ED visits, changes in mean BP, overall BP control, medication adherence, changes to antihypertensive medications, quality of life, and end user experience at 3 months. RESULTS: A total of 46 multiethnic patients (mean age 63, SD 17 years, 69%, n=32 women) found to have severe hypertension (mean 191, SD 23/mean 100, SD 14 mm Hg) in the ED were recruited, initiated on HBPT with hypertension specialist physician referral and followed up for 3 months. Eligibility and recruitment rates were 40% (56/139) and 88% (49/56), respectively. The proportion of participants that completed ≥80% of home BP measurements at 1 and 3 months were 67% (31/46) and 41% (19/46), respectively. The proportion of individuals who achieved home systolic BP and diastolic BP control at 3 months was 71.4% (30/42) and 85.7% (36/42) respectively. Mean home systolic and diastolic BP improved by -13/-5 mm Hg after initiation of HBPT to the end of the study. Patients were prescribed 1 additional antihypertensive medication. No differences in medication adherence from enrollment to 3 months were noted. Most patients (76%, 25/33) were highly satisfied with the HBPT program and 76% (25/33) found digital health tools easy to use. CONCLUSIONS: HBPT intervention is a feasible postdischarge management strategy and can be beneficial in supporting patients with asymptomatic elevated BP from the ED. A randomized trial is underway to evaluate the efficacy of this intervention on BP control