Analysis of eys +/-; lrp5 +/- Zebrafish Reveals LRP5 as a Strong Candidate for the Receptor Of All- Trans Retinol in the Visual Cycle

2020 ◽  
Author(s):  
Shimpei Takita ◽  
Yuko Seko
Author(s):  
K.L. More ◽  
R.A. Lowden ◽  
T.M. Besmann

Silicon nitride possesses an attractive combination of thermo-mechanical properties which makes it a strong candidate material for many structural ceramic applications. Unfortunately, many of the conventional processing techniques used to produce Si3N4, such as hot-pressing, sintering, and hot-isostatic pressing, utilize significant amounts of densification aids (Y2O3, Al2O3, MgO, etc.) which ultimately lowers the utilization temperature to well below that of pure Si3N4 and also decreases the oxidation resistance. Chemical vapor deposition (CVD) is an alternative processing method for producing pure Si3N4. However, deposits made at temperatures less than ~1200°C are usually amorphous and at slightly higher temperatures, the deposition of crystalline material requires extremely low deposition rates (~5 μm/h). Niihara and Hirai deposited crystalline α-Si3N4 at 1400°C at a deposition rate of ~730 μm/h. Hirai and Hayashi successfully lowered the CVD temperature for the growth of crystalline Si3N4 by adding TiCl4 vapor to the SiCl4, NH3, and H2 reactants. This resulted in the growth of α-Si3N4 with small amounts of TiN at temperatures as low as 1250°C.


2020 ◽  
Vol 4 (s1) ◽  
pp. 50-50
Author(s):  
Robert Edward Freundlich ◽  
Gen Li ◽  
Jonathan P Wanderer ◽  
Frederic T Billings ◽  
Henry Domenico ◽  
...  

OBJECTIVES/GOALS: We modeled risk of reintubation within 48 hours of cardiac surgery using variables available in the electronic health record (EHR). This model will guide recruitment for a prospective, pragmatic clinical trial entirely embedded within the EHR among those at high risk of reintubation. METHODS/STUDY POPULATION: All adult patients admitted to the cardiac intensive care unit following cardiac surgery involving thoracotomy or sternotomy were eligible for inclusion. Data were obtained from operational and analytical databases integrated into the Epic EHR, as well as institutional and departmental-derived data warehouses, using structured query language. Variables were screened for inclusion in the model based on clinical relevance, availability in the EHR as structured data, and likelihood of timely documentation during routine clinical care, in the hopes of obtaining a maximally-pragmatic model. RESULTS/ANTICIPATED RESULTS: A total of 2325 patients met inclusion criteria between November 2, 2017 and November 2, 2019. Of these patients, 68.4% were male. Median age was 63.0. The primary outcome of reintubation occurred in 112/2325 (4.8%) of patients within 48 hours and 177/2325 (7.6%) at any point in the subsequent hospital encounter. Univariate screening and iterative model development revealed numerous strong candidate predictors (ANOVA plot, figure 1), resulting in a model with acceptable calibration (calibration plot, figure 2), c = 0.666. DISCUSSION/SIGNIFICANCE OF IMPACT: Reintubation is common after cardiac surgery. Risk factors are available in the EHR. We are integrating this model into the EHR to support real-time risk estimation and to recruit and randomize high-risk patients into a clinical trial comparing post-extubation high flow nasal cannula with usual care. CONFLICT OF INTEREST DESCRIPTION: REF has received grant funding and consulting fees from Medtronic for research on inpatient monitoring.


2000 ◽  
Vol 34 (1_suppl) ◽  
pp. A145-A149 ◽  
Author(s):  
Patrick D. McGorry

Objective The concept of duration of untreated psychosis or DUP has been a strong candidate for intervention as part of the early intervention paradigm. However, its importance has been questioned. This paper aims to present selected issues concerning attempts to reduce DUP and evaluate the impact of these attempts. Method Current research designs are critiqued and alternatives considered. Results Evidence suggests that it is difficult to design studies that are both ethical and potent enough to determine the contribution of treatment delay to outcome. Conclusions Further research is justified but this should not obstruct commonsense service reforms.


2008 ◽  
Vol 19 (5) ◽  
pp. 2154-2168 ◽  
Author(s):  
Corey L. Williams ◽  
Marlene E. Winkelbauer ◽  
Jenny C. Schafer ◽  
Edward J. Michaud ◽  
Bradley K. Yoder

Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and Joubert syndrome (JBTS) are a group of heterogeneous cystic kidney disorders with partially overlapping loci. Many of the proteins associated with these diseases interact and localize to cilia and/or basal bodies. One of these proteins is MKS1, which is disrupted in some MKS patients and contains a B9 motif of unknown function that is found in two other mammalian proteins, B9D2 and B9D1. Caenorhabditis elegans also has three B9 proteins: XBX-7 (MKS1), TZA-1 (B9D2), and TZA-2 (B9D1). Herein, we report that the C. elegans B9 proteins form a complex that localizes to the base of cilia. Mutations in the B9 genes do not overtly affect cilia formation unless they are in combination with a mutation in nph-1 or nph-4, the homologues of human genes (NPHP1 and NPHP4, respectively) that are mutated in some NPHP patients. Our data indicate that the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons. Together, these data suggest that the human homologues of the novel B9 genes B9D2 and B9D1 will be strong candidate loci for pathologies in human MKS, NPHP, and JBTS.


2021 ◽  
pp. 1-11
Author(s):  
Iris Cristina Maia Oliveira ◽  
Auriana Serra Vasconcelos Mallmann ◽  
Francisco Adelvane de Paula Rodrigues ◽  
Laura Maria Teodorio Vidal ◽  
Iardja Stéfane Lopes Sales ◽  
...  

<b><i>Background:</i></b> Depression is a common, chronic, and often recurrent serious mood disorder. Conventional antidepressants present limitations that stimulate the search for new drugs. Antioxidant and neuroprotective substances are potential antidepressant agents. In this context, riparin I (RIP I) has presented promising results, emerging as a potential source of a new therapeutic drug. In this study, the antidepressant effect of RIP I was evaluated in an animal model of depression induced by corticosterone (CORT). The involvement of neuroprotective and antioxidant mechanisms in the generation of this effect was also assessed. <b><i>Methods:</i></b> Female mice were submitted to CORT for 21 days and treated with RIP I in the last 7 days. Behavioral and neurochemical analyses were performed. <b><i>Results:</i></b> The administration of RIP I reversed the depressive and psychotic-like behavior, as well as the cognitive impairment caused by CORT, in addition to regulating oxidative stress parameters and BDNF levels in depression-related brain areas. <b><i>Conclusion:</i></b> These findings suggest that RIP I can be a strong candidate for drugs in the treatment of depression.


1991 ◽  
Vol 11 (9) ◽  
pp. 4591-4598 ◽  
Author(s):  
M R Mitts ◽  
J Bradshaw-Rouse ◽  
W Heideman

The adenylate cyclase system of the yeast Saccharomyces cerevisiae contains many proteins, including the CYR1 polypeptide, which is responsible for catalyzing the formation of cyclic AMP from ATP, RAS1 and RAS2 polypeptides, which mediate stimulation of cyclic AMP synthesis by guanine nucleotides, and the yeast GTPase-activating protein analog IRA1. We have previously reported that adenylate cyclase is only peripherally bound to the yeast membrane. We have concluded that IRA1 is a strong candidate for a protein involved in anchoring adenylate cyclase to the membrane. We base this conclusion on the following criteria: (i) a disruption of the IRA1 gene produced a mutant with very low membrane-associated levels of adenylate cyclase activity, (ii) membranes made from these mutants were incapable of binding adenylate cyclase in vitro, (iii) IRA1 antibodies inhibit binding of adenylate cyclase to the membrane, and (iv) IRA1 and adenylate cyclase comigrate on Sepharose 4B.


2016 ◽  
Vol 24 (1) ◽  
Author(s):  
Joshua C. Eby ◽  
Mary C. Gray ◽  
Jason M. Warfel ◽  
Tod J. Merkel ◽  
Erik L. Hewlett

ABSTRACT Adenylate cyclase toxin (ACT) is an essential virulence factor of Bordetella pertussis, and antibodies to ACT protect against B. pertussis infection in mice. The toxin is therefore a strong candidate antigen for addition to future acellular pertussis vaccines. In order to characterize the functionality of the immunologic response to ACT after infection, we developed an assay for testing the ability of serum samples from subjects infected with B. pertussis to neutralize ACT-induced cytotoxicity in J774 macrophage cells. Baboons develop neutralizing anti-ACT antibodies following infection with B. pertussis, and all sera from baboons with positive anti-ACT IgG enzyme-linked immunosorbent assay (ELISA) results neutralized ACT cytotoxicity. The toxin neutralization assay (TNA) was positive in some baboon sera in which ELISA remained negative. Of serum samples obtained from humans diagnosed with pertussis by PCR, anti-ACT IgG ELISA was positive in 72%, and TNA was positive in 83%. All samples positive for anti-ACT IgG ELISA were positive by TNA, and none of the samples from humans without pertussis neutralized toxin activity. These findings indicate that antibodies to ACT generated following infection with B. pertussis consistently neutralize toxin-induced cytotoxicity and that TNA can be used to improve understanding of the immunologic response to ACT after infection or vaccination.


1996 ◽  
Vol 13 (6) ◽  
pp. 595-604 ◽  
Author(s):  
David F. Barker ◽  
Eduardo R.A. Almeida ◽  
Graham Casey ◽  
Pamela R. Fain ◽  
Shu-Yuan Liao ◽  
...  

2015 ◽  
Vol 87 (4) ◽  
pp. 2335-2348 ◽  
Author(s):  
Bruno Milanez

ABSTRACT In this article, I argue that attempting to solve real problems is a possible approach to bring social and natural sciences together, and suggest that - as Environmental Impact Assessment necessarily brings together social and environmental issues - this debate is a strong candidate for such a task. The argument is based on a general discussion about the possibilities and limitations of Environmental Impact Assessments, the social-environmental impacts of mining activities and three case studies. The analysis of the cases indicates possibilities and limitations of the dialogue between scientists from various areas - and of the collaboration with social movements and affected communities - in avoiding negative impacts of mining projects and, eventually, increasing their sustainability.


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