Effect of Lipid Characteristics on the Structure of Transmembrane Proteins

AbstractThe activity of embedded proteins is known to vary with lipid characteristics. Indeed, it has been shown that some cell-membrane proteins cannot function unless certain non-bilayer-forming lipids (i.e., nonzero spontaneous curvature) are present. In this paper we show that membranes exert a line tension on transmembrane proteins. The line tension, on the order of 1–100kT/protein, varies with the lipid properties and the protein configuration. Thus, membranes composed of different lipids favor different protein conformations. Model predictions are in excellent agreement with the data of Keller et al. (Biophys. J. 1993, 65:23–27) regarding the conductance of alamethicin channels

Membrane-protein interactions in mechanosensitive channels

In this paper, we examine the mechanical role of the lipid bilayer in ion channel conformation and function with specific reference to the case of the mechanosensitive channel of large conductance (MscL). In a recent paper (Wiggins and Phillips, 2004), we argued that mechanotransduction very naturally arises from lipid-protein interactions by invoking a simple analytic model of the MscL channel and the surrounding lipid bilayer. In this paper, we focus on improving and expanding this analytic framework for studying lipid-protein interactions with special attention to MscL. Our goal is to generate simple scaling relations which can be used to provide qualitative understanding of the role of membrane mechanics in protein function and to quantitatively interpret experimental results. For the MscL channel, we find that the free energies induced by lipid-protein interaction are of the same order as the free energy differences between conductance states measured by Sukharev et al. (1999). We therefore conclude that the mechanics of the bilayer plays an essential role in determining the conformation and function of the channel. Finally, we compare the predictions of our model to experimental results from the recent investigations of the MscL channel by Perozo et al. (2002), Powl et al. (2003), Yoshimura et al. (2004), and others and suggest a suite of new experiments

Scaling up Payments for Watershed Services: Recommendations for Increasing Participation in Watershed Conservation Among Non-Industrial Private Forest Landowners in the Sebago Lake Watershed, Maine

Payments for Watershed Services (PWS) programs are receiving attention throughout the U.S. as a policy option to secure water quality in a cost effective manner. PWS programs face many challenges in implementation; prominent among them is designing a program that generates interest and participation among the suppliers of water quality, upstream private landowners. This report seeks to inform the development of a PWS program in Southeast Maine by examining the system of incentives needed to encourage private forest owners to adopt conservation best management practices that enhance water quality downstream. While focused on the Sebago Lake watershed, which provides drinking water for the Greater Portland area, this project approaches the localized study as a specific case to identify biophysical, institutional, economic and social factors that favor or limit the scaling up of PWS schemes. This analysis combines a systematic review of literature on landowner preferences to existing incentive programs, interviews with program administrators from PWS schemes throughout the U.S., and interviews with key stakeholders in Southeast Maine. This report provides a set of recommendations organized around: segmentation of landowners; targeting and positioning PWS programs; selecting attractive program attributes; and leveraging effective outreach channels and tactics. Key recommendations include: co-create program attributes with landowners; encourage peer to peer communication to build support and awareness; provide a portfolio of financial and non-financial incentives to increase interest; and partner with existing conservation organizations to add capabilities and resources.Master of ScienceNatural Resources and EnvironmentUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/90874/1/scaling_up_watershed_services_2012.pd

The effect of osteopontin and osteopontin-derived peptides on preterm brain injury

Background: Osteopontin (OPN) is a highly phosphorylated sialoprotein and a soluble cytokine that is widely expressed in a variety of tissues, including the brain. OPN and OPN-derived peptides have been suggested to have potential neuroprotective effects against ischemic brain injury, but their role in preterm brain injury is unknown. Methods: We used a hypoxia-ischemia (HI)-induced preterm brain injury model in postnatal day 5 mice. OPN and OPN-derived peptides were given intracerebroventricularly and intranasally before HI. Brain injury was evaluated at 7 days after the insults. Results: There was a significant increase in endogenous OPN mRNA and OPN protein in the mouse brain after the induction of HI at postnatal day 5. Administration of full-length OPN protein and thrombin-cleaved OPN did not affect preterm brain injury. This was demonstrated with both intracerebroventricular and intranasal administration of OPN as well as in OPN-deficient mice. Interestingly, both N134–153 and C154–198 OPN-derived peptides increased the severity of brain injury in this HI-induced preterm brain injury model. Conclusions: The neuroprotective effects of OPN are age-dependent, and, in contrast to the more mature brain, OPN-derived peptides potentiate injury in postnatal day 5 mice. Intranasal administration is an efficient way of delivering drugs to the central nervous system (CNS) in neonatal mice and is likely to be an easy and noninvasive method of drug delivery to the CNS in preterm infants

Sedum survival and ramification patterns under different pedoclimatic conditions

This article explores the use of Sedum species in landscape design, focusing on their adaptability to different pedoclimatic conditions and their ability to thrive in conditions of neglect. The article discusses the importance of understanding a plant's place of origin and natural habitat when considering its cultivation in a different area and the benefits and drawbacks associated with different types of substrates. Sedums are identified as an excellent choice for those who want to enjoy the aesthetic value of plants without the hassle of regular upkeep. The study investigates the growth and survival patterns of three Sedum cultivars in different growth media without additional watering or fertilization. The findings have the potential to provide insights into landscaping solutions and the evolution of these succulent species in arduous conditions. The study also explores Romanian identity and tradition by incorporating traditional motifs and patterns as mosaics into the landscape, creating a new style of landscaping. In addition to our main objective, we were interested in displaying an intricate landscape design to further illustrate the negative visual impact an un-cared-for outdoor environment can have

The immune response after hypoxia-ischemia in a mouse model of preterm brain injury

Background: Preterm brain injury consists primarily of periventricular leukomalacia accompanied by elements of gray-matter injury, and these injuries are associated with cerebral palsy and cognitive impairments. Inflammation is believed to be an important contributing factor to these injuries. The aim of this study was to examine the immune response in a postnatal day (PND) 5 mouse model of preterm brain injury induced by hypoxia-ischemia (HI) that is characterized by focal white and gray-matter injury. Methods: C57Bl/6 mice at PND 5 were subjected to unilateral HI induced by left carotid artery ligation and subsequent exposure to 10% O2 for 50 minutes, 70 minutes, or 80 minutes. At seven days post-HI, the white/gray-matter injury was examined. The immune responses in the brain after HI were examined at different time points after HI using RT-PCR and immunohistochemical staining. Results: HI for 70 minutes in PND 5 mice induced local white-matter injury with focal cortical injury and hippocampal atrophy, features that are similar to those seen in preterm brain injury in human infants. HI for 50 minutes resulted in a small percentage of animals being injured, and HI for 80 minutes produced extensive infarction in multiple brain areas. Various immune responses, including changes in transcription factors and cytokines that are associated with a T-helper (Th)1/Th17-type response, an increased number of CD4+ T-cells, and elevated levels of triggering receptor expressed on myeloid cells 2 (TREM-2) and its adaptor protein DNAX activation protein of 12 kDa (DAP12) were observed using the HI 70 minute preterm brain injury model. Conclusions: We have established a reproducible model of HI in PND 5 mice that produces consistent local white/gray-matter brain damage that is relevant to preterm brain injury in human infants. This model provides a useful tool for studying preterm brain injury. Both innate and adaptive immune responses are observed after HI, and these show a strong pro-inflammatory Th1/Th17-type bias. Such findings provide a critical foundation for future studies on the mechanism of preterm brain injury and suggest that blocking the Th1/Th17-type immune response might provide neuroprotection after preterm brain injury

Gauss Composition for P^1, and the universal Jacobian of the Hurwitz space of double covers

We investigate the universal Jacobian of degree n line bundles over the Hurwitz stack of double covers of P^1 by a curve of genus g. Our main results are: the construction of a smooth, irreducible, universally closed (but not separated) moduli compactification of this universal Jacobian; a description of the global geometry and moduli properties of these stacks; and a computation of the Picard groups of these stacks in the cases when n-g is even. An important ingredient of our work is the parametrization of line bundles on double covers by binary quadratic forms. This parametrization generalizes the classical number theoretic correspondence between ideal classes of quadratic rings and integral binary quadratic forms, which in particular gives the group law on integral binary quadratic forms first discovered by Gauss.Comment: mathematical and expositional updates and improvements, 29 pages, 5 figure

Primary cilia signaling mediates intraocular pressure sensation

Lowe syndrome is a rare X-linked congenital disease that presents with congenital cataracts and glaucoma, as well as renal and cerebral dysfunction. OCRL, an inositol polyphosphate 5-phosphatase, is mutated in Lowe syndrome. We previously showed that OCRL is involved in vesicular trafficking to the primary cilium. Primary cilia are sensory organelles on the surface of eukaryotic cells that mediate mechanotransduction in the kidney, brain, and bone. However, their potential role in the trabecular meshwork (TM) in the eye, which regulates intraocular pressure, is unknown. Here, we show that TM cells, which are defective in glaucoma, have primary cilia that are critical for response to pressure changes. Primary cilia in TM cells shorten in response to fluid flow and elevated hydrostatic pressure, and promote increased transcription of TNF-α, TGF-β, and GLI1 genes. Furthermore, OCRL is found to be required for primary cilia to respond to pressure stimulation. The interaction of OCRL with transient receptor potential vanilloid 4 (TRPV4), a ciliary mechanosensory channel, suggests that OCRL may act through regulation of this channel. A novel disease-causing OCRL allele prevents TRPV4-mediated calcium signaling. In addition, TRPV4 agonist GSK 1016790A treatment reduced intraocular pressure in mice; TRPV4 knockout animals exhibited elevated intraocular pressure and shortened cilia. Thus, mechanotransduction by primary cilia in TM cells is implicated in how the eye senses pressure changes and highlights OCRL and TRPV4 as attractive therapeutic targets for the treatment of glaucoma. Implications of OCRL and TRPV4 in primary cilia function may also shed light on mechanosensation in other organ systems