421 research outputs found
Recommended from our members
The Effects of Carbohydrate, Unsaturated Fat, and Protein Intake on Measures of Insulin Sensitivity: Results from the OmniHeart Trial
OBJECTIVE Impaired insulin sensitivity increases the risk of cardiovascular disease. Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain. The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate-rich diet (CARB; similar to the Dietary Approaches to Stop Hypertension [DASH] diet), a protein-rich diet (PROT; protein predominantly from plant sources), and an unsaturated fatârich diet (UNSAT; predominantly monounsaturated). RESEARCH DESIGN AND METHODS This study was a randomized, controlled, three-period, crossover feeding study. The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes. Diets were administered for 6 weeks each, with a washout period between diets of 2â4 weeks. Weight was held constant throughout the study. For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin. QUICKI is a validated measure of insulin sensitivity. The primary analyses used generalized estimating equations. RESULTS At baseline, mean (SD) BMI was 30.2 (6.1) kg/m2, and mean (SD) QUICKI was 0.35 (0.04). The UNSAT diet increased QUICKI by 0.005, more than the CARB diet (P = 0.04). PROT had no significant effect compared with CARB. CONCLUSIONS A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease. Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity
'The world is full of big bad wolves': investigating the experimental therapeutic spaces of R.D. Laing and Aaron Esterson
In conjunction with the recent critical assessments of the life and work of R.D. Laing, this paper seeks to demonstrate what is revealed when Laingâs work on families and created spaces of mental health care are examined through a geographical lens. The paper begins with an exploration of Laingâs time at the Tavistock Clinic in London during the 1960s, and of the co-authored text with Aaron Esterson entitled, Sanity, Madness and the Family (1964). The study then seeks to demonstrate the importance Laing and his colleague placed on the time-space situatedness of patients and their worlds. Finally, an account is provided of Laingâs and Estersonâs spatial thinking in relation to their creation of both real and imagined spaces of therapeutic care
TetR-Based Gene Regulation Systems for Francisella tularensis
ABSTRACT There are a number of genetic tools available for studying Francisella tularensis , the etiological agent of tularemia; however, there is no effective inducible or repressible gene expression system. Here, we describe inducible and repressible gene expression systems for F. tularensis based on the Tet repressor, TetR. For the inducible system, a tet operator sequence was cloned into a modified F. tularensis groESL promoter sequence and carried in a plasmid that constitutively expressed TetR. To monitor regulation the luminescence operon, luxCDABE , was cloned under the hybrid Francisella tetracycline-regulated promoter ( FTRp ), and transcription was initiated with addition of anhydrotetracycline (ATc), which binds TetR and alleviates TetR association with tetO. Expression levels measured by luminescence correlated with ATc inducer concentrations ranging from 20 to 250 ng ml â1 . In the absence of ATc, luminescence was below the level of detection. The inducible system was also functional during the infection of J774A.1 macrophages, as determined by both luminescence and rescue of a mutant strain with an intracellular growth defect. The repressible system consists of FTRp regulated by a reverse TetR mutant (revTetR), TetR r1.7. Using this system with the lux reporter, the addition of ATc resulted in decreased luminescence, while in the absence of ATc the level of luminescence was not significantly different from that of a construct lacking TetR r1.7. Utilizing both systems, the essentiality of SecA, the protein translocase ATPase, was confirmed, establishing that they can effectively regulate gene expression. These two systems will be invaluable in exploring F. tularensis protein function
Extragenic suppressor mutations in ÎripA disrupt stability and function of LpxA
Abstract
Background
Francisella tularensis is a Gram-negative bacterium that infects hundreds of species including humans, and has evolved to grow efficiently within a plethora of cell types. RipA is a conserved membrane protein of F. tularensis, which is required for growth inside host cells. As a means to determine RipA function we isolated and mapped independent extragenic suppressor mutants in âripA that restored growth in host cells. Each suppressor mutation mapped to one of two essential genes, lpxA or glmU, which are involved in lipid A synthesis. We repaired the suppressor mutation in lpxA (S102, LpxA T36N) and the mutation in glmU (S103, GlmU E57D), and demonstrated that each mutation was responsible for the suppressor phenotype in their respective strains. We hypothesize that the mutation in S102 altered the stability of LpxA, which can provide a clue to RipA function. LpxA is an UDP-N-acetylglucosamine acyltransferase that catalyzes the transfer of an acyl chain from acyl carrier protein (ACP) to UDP-N-acetylglucosamine (UDP-GlcNAc) to begin lipid A synthesis.
Results
LpxA was more abundant in the presence of RipA. Induced expression of lpxA in the ÎripA strain stopped bacterial division. The LpxA T36N S102 protein was less stable and therefore less abundant than wild type LpxA protein.
Conclusion
These data suggest RipA functions to modulate lipid A synthesis in F. tularensis as a way to adapt to the host cell environment by interacting with LpxA.http://deepblue.lib.umich.edu/bitstream/2027.42/110509/1/12866_2014_Article_336.pd
Recommended from our members
Manticore and CS mode : parallelizable encryption with joint cipher-state authentication.
We describe a new mode of encryption with inexpensive authentication, which uses information from the internal state of the cipher to provide the authentication. Our algorithms have a number of benefits: (1) the encryption has properties similar to CBC mode, yet the encipherment and authentication can be parallelized and/or pipelined, (2) the authentication overhead is minimal, and (3) the authentication process remains resistant against some IV reuse. We offer a Manticore class of authenticated encryption algorithms based on cryptographic hash functions, which support variable block sizes up to twice the hash output length and variable key lengths. A proof of security is presented for the MTC4 and Pepper algorithms. We then generalize the construction to create the Cipher-State (CS) mode of encryption that uses the internal state of any round-based block cipher as an authenticator. We provide hardware and software performance estimates for all of our constructions and give a concrete example of the CS mode of encryption that uses AES as the encryption primitive and adds a small speed overhead (10-15%) compared to AES alone
Considering sex as a biological variable in preclinical research
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154390/1/fsb2fj201600781r.pd
Examining the Role of Marine Mammals and Seabirds in Southeast Alaskaâs Marine Ecosystem Dynamics
Primary producers are the foundation of marine food webs and require reliable nutrient sources to maintain their
important role with ecosystems. While marine mammals and seabirds can play critical roles in marine nutrient
cycling, their contributions are often overlooked. The fjord systems of Southeast Alaska support a high diversity of
marine mammals and seabirds in addition to some of the most valuable fisheries in the US. Nonetheless, there is
still relatively little known about nutrient sources and fluxes in this region which is a critical component of fisheries
management. The goal of our study was to advance knowledge of the role of mammals and seabirds in marine
nutrient cycling and to understand how changing marine mammal and seabird populations may alter ecosystem
dynamics. We analyzed nutrient levels in marine mammal scat, seabird guano, and seawater samples collected in
Berners Bay, Southeast Alaska, to determine the influence of marine mammals and seabirds on nearshore nutrient
concentrations. Utilizing qualitative network models (QNMs), we then examined how a simulated Berners Bay
ecosystem would respond to an increase in marine mammals, seabirds, and nutrients. Researchers are
increasingly utilizing QNMs as a first step in the development of ecosystem-based fisheries management plans as
their adaptable nature is well suited to address rapidly changing climatic conditions. Our direct nutrient
measurements and QNM results indicate that marine mammals and seabirds have the potential to provide
substantial contributions to marine nutrient concentrations in the region and that these valuable ecosystem
services should not be overlooked.We sincerely thank the reviewers for their suggestions and feedbackYe
The Circadian Rhythm of Blood Pressure During Pregnancy
To review the literature on the circadian rhythm of blood pressure during pregnancy. Data Sources : Computerized searches on MEDLINE, CINAHL, and MIRLYN. Study Selection : Selected studies from 1969 to 1997 were evaluated. Data Extraction : Data were extracted and information was organized under the following areas: definition of and the interconnection between circadian rhythm and blood pressure; the circadian variability of blood pressure throughout the trimesters; the patterns of the circadian rhythm of blood pressure in pregnancies defined as normal and those complicated by chronic hypertension and preeclampsia; and clinical implications. Data Synthesis : The circadian rhythm of blood pressure in pregnancy is the same as in the nonpregnant state, with a nocturnal decrease, especially during sleep. In patients with chronic hypertension, the nocturnal fall in blood pressure may be steeper. Patients with mild preeclampsia may experience a less pronounced nocturnal decrease in blood pressure. Patients with severe preeclampsia may display a reversed circadian rhythm, with no decrease and/or an increase in nocturnal blood pressure. Conclusions : The patterns of the circadian rhythm of blood pressure during normal pregnancy and pregnancies complicated by chronic hypertension and preeclampsia warrant consideration when monitoring patients and implementing management plans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71412/1/j.1552-6909.2000.tb02771.x.pd
When to update COVID-19 vaccine composition
Vaccines against different SARS-CoV-2 variants have been approved, but continued surveillance is needed to determine when the antigen composition of vaccines should be updated, together with clinical studies to assess vaccine efficacy
Validation of spinal motion with the spine reposition sense device
© 2009 Petersen and Rundquist; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
- âŠ