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A comprehensive characterization of key mechanisms underlying signal transmission within the human brain remains an unsolved problem. The neuronal surface, composed principally of phosphatidylcholine (POPC), has a known ordering effect on water. This produces highly organized water layers (OWLs) at the neuron-water interface--the neurochemical implications of which are not currently understood. The human brain is 75% water by volume, with folds and grooves to maximize surface area, suggesting that characterization of neuronal OWLs may contribute to an understanding of neuronal signal transmission. Previous experimental work has measured enhanced conductivity of POPC OWLs relative to bulk water. The mechanism underlying this conductivity is still debated. Using quantum chemical methods on a POPC-water interface model system, we present data characterizing OWL conductance. Non-equilibrium Green's function calculation results demonstrate that there is negligible electron transfer-based conductivity through the OWL at biological temperatures. This is consistent with existing studies suggesting the Grotthuss mechanism as the most likely explanation for experimentally observed enhanced conductivity at the POPC-water interface. The broader implications of enhanced proton conductivity at the neuron-water interface are discussed. Key words: interfacial water, organized water, conductance, neuronal lipid, quantum chemical, Introduction The main function of the brain is the transmission and processing of information. Traditionally this has been conceptualized within the context of synaptic transmission. However, the search for alternative [...]

Author(s): Ismail Tarhan [sup.1] , Seküre Çelikten [sup.1] , Hafize Merve Kestek [sup.1] , Murat Türkteki [sup.2] Author Affiliations: (1) grid.17242.32, 0000 0001 2308 7215, Selçuk University, Faculty of Science, [...], In this study, parameters of an acid-catalyzed direct extraction methylation method used for the determination of low-level lipid residues in the ceramic artifacts were investigated and optimized as a result of chemometric modeling techniques that enable comprehensive statistical data to be obtained with fewer analyses in the optimization studies. For this purpose, 25 amorphous unglazed ceramic artifacts found during the 1996-2021 excavations at the Küllüoba Höyük archaeological site were subjected to lipid residue determination. The ceramic samples extracted by the proposed method were analyzed by gas chromatography-mass spectrometry, and the lipid residues present in them were determined. According to the obtained fatty acid composition results, it can be said that the lipid residues in the analyzed ceramics are of both animal and plant origin. The ceramic artifact with the highest lipid residue concentration was selected, and the parameters of the extraction method were examined using the chemometric models. According to the response surface methodology, the extraction time and temperature should be high as long as the experimental conditions and environment allow for the extraction of the lipid residues in the ceramic artifacts, and the silylation process has a limited positive effect on the yield, but the extraction with methanol can be achieved successfully when the silylation process is not performed.

Long-term carbon (C) stabilisation in tropical and subtropical soils under no-tillage (NT) rests on the formation of mineral-organic associations (MOAs) that can be enriched with microbial metabolites. In this work, we assessed the role of long-term tillage and cropping systems and mineral N fertilisation in enriching MOAs with microbial metabolites in a subtropical soil. For this purpose, we sampled a sandy clay loam Acrisol up to 1 m depth involved in an ongoing 30-year-old experiment under two different tillage systems (conventional tillage and NT) in the presence and absence of legume cover crops and mineral nitrogen (N) fertilisation. The soil samples were subjected to particle size fractionation and n-alkane analysis. The NT and the presence of legume cover crops in the surface soil layer (0-5 cm) increased the abundance of plant-derived lipids (i.e. compounds with n-alkane chains of 25-33 C atoms) in the whole soil. Microbial-derived lipids (i.e. compounds with shorter n-alkane chains (15-24 C atoms)) were more abundant in the clay fraction of the surface (0-5 cm) and sub-surface soil layers (20-30 and 75-100 cm) in NT soil receiving high-quality residues of legume cover crops. However, N fertilisation decreased the abundance of microbial-derived lipids in the clay fraction of the 0-5 and 20-30 cm soil layers. Our findings highlight the role ofN-rich residues of legume cover crops, but not of mineral N fertilisation, in the long-term stabilisation of C in MOAs in NT soils through the action of microbial residues. Additional keywords: n-alkanes, no-tillage, soil carbon accumulation, soil lipids. Received 30 May 2019, accepted 13 August 2019, published online 19 September 2019, Introduction No-tillage (NT) is a widespread method of facilitating storage of organic carbon (C) in tropical and subtropical soils (Bayer et al. 2006; Veloso et al. 2018). Legume cover cropping [...]

Introduction Inflammatory bowel disease (IBD), inclusive of Crohn's disease (CD) and ulcerative colitis (UC), is a chronic and relapsing inflammatory disorder of the gastrointestinal tract. IBD consists of a dysregulated [...], Cyclooxygenase 2 (Cox2) total knockout and myeloid knockout (MKO) mice develop Crohn's-like intestinal inflammation when fed cholate-containing high-fat diet (CCHF). We demonstrated that CCHF impaired intestinal barrier function and increased translocation of endotoxin, initiating TLR/MyD88-dependent inflammation in Cox2-KO but not WT mice. Cox2MKO increased proinflammatory mediators in LPS-activated macrophages, and in the intestinal tissue and plasma upon CCHF challenge. Cox2-MKO also reduced inflammation resolving lipoxin A4 (LXA4) in intestinal tissue, whereas administration of an LXA4 analog rescued disease in Cox2-MKO mice fed CCHF. The apolipoprotein A-I (APOA1) mimetic 4F mitigated disease in both the Cox2-MKO/CCHF and piroxicam-accelerated [Il10.sup.-/-] models of inflammatory bowel disease (IBD) and reduced elevated levels of proinflammatory mediators in tissue and plasma. APOA1 mimetic Tg6F therapy was also effective in reducing intestinal inflammation in the Cox2-MKO/CCHF model. We further demonstrated that APOA1 mimetic peptides (a) inhibited LPS and oxidized 1-palmitoyl-2-arachidonoyl-sn-phosphatidylcholine-dependent (oxPAPC-dependent) proinflammatory responses in human macrophages and intestinal epithelium, and (b) directly cleared proinflammatory lipids from mouse intestinal tissue and plasma. Our results support a causal role for proinflammatory and inflammation-resolving lipids in IBD pathology and a translational potential for APOA1 mimetic peptides for the treatment of IBD.

The decline in physical activity (PA) from youth to young adulthood is evident, though limited research has addressed whether specific factors of K-12 physical education (PE) have any influence on outcomes during college years. This study examined the relationship between college students' physical fitness and PA behavior and their high school PE experiences. College student volunteers (n = 537) completed a fitness assessment examining aerobic endurance, muscular endurance, body composition, and blood glucose and lipids. A survey examined current PA and PE experience in high school (number of semesters, enjoyment, requirements). Analyses were conducted separately for males and females. Pearson correlations examined relationships between fitness, behavioral, and PE outcomes. Differences in behavioral and fitness outcomes were compared with t tests. The final sample was 56.6% male (n = 298) and 43.4% female (n = 227). For males, analyses revealed that PE enjoyment was significantly related to V[O.sub.2] max, curl-ups, and vigorous physical activity. Number of semesters of PE in high school was negatively associated with triglycerides and total cholesterol and positively associated with moderate physical activity. Those who took PE when it was not required were more vigorously active than those who did not. Males who had a waiver for PE had a lower body fat percentage, performed more curl-ups, and were more vigorously and moderately active compared with those who had no waiver. Number of semesters of PE in high school was negatively associated with triglycerides and total cholesterol. PE enjoyment was positively associated with V[O.sub.2] max and push-ups. For females, those who took PE when it wasn't required had a higher V[O.sub.2] max and vigorous physical activity compared with those who did not. Females with a waiver for PE class had higher triglycerides and total cholesterol compared with those who did not. Females in a coed PE class had a higher BMI and V[O.sub.2] max compared with those in a combination class. Effective PE programs that encourage participation and educate students on the benefits of physical activity have the capability to establish lifelong healthy and active habits that translate to the college years, and likely beyond. The main findings of this study have the potential to influence the policies regarding PE requirements for school-aged students in all states, such as possibly increasing PE requirements for all grades and discovering certain aspects of PE that could make it more enjoyable for a larger number of students., Physical education (PE) in schools is a cornerstone in the development of early physical activity (PA) habits, gross motor and movement skills, and personal and social character development in children [...]

Introduction Pulmonary surfactant is a complex mixture of lipids and associated proteins synthesized by alveolar type 2 (AT2) cells in the peripheral lung. Surfactant is required at birth and throughout [...], Adaptation to respiration at birth depends upon the synthesis of pulmonary surfactant, a lipid-protein complex that reduces surface tension at the air-liquid interface in the alveoli and prevents lung collapse during the ventilatory cycle. Herein, we demonstrated that the gene encoding a subunit of the endoplasmic reticulum membrane complex, EMC3, also known as TMEM111 (Emc3/Tmem111), was required for murine pulmonary surfactant synthesis and lung function at birth. Conditional deletion of Emc3 in murine embryonic lung epithelial cells disrupted the synthesis and packaging of surfactant lipids and proteins, impaired the formation of lamellar bodies, and induced the unfolded protein response in alveolar type 2 (AT2) cells. EMC3 was essential for the processing and routing of surfactant proteins, SP-B and SP-C, and the biogenesis of the phospholipid transport protein ABCA3. Transcriptomic, lipidomic, and proteomic analyses demonstrated that EMC3 coordinates the assembly of lipids and proteins in AT2 cells that is necessary for surfactant synthesis and function at birth.

In Canada, over half of children between 6 months and 5 years of age spend close to 30 hours a week in childcare centres (CCs). (1) Children attending these centres [...], OBJECTIVES: Childcare centres (CCs) typically offer one meal and snacks daily. This study compared what is served in CCs with what the nutriti recommendations are; described and compared the nutritional composition of lunches served in CCs in New Brunswick and Saskatchewan; and examin differences between French and English, and urban and rural centres. METHODS: The study involved 61 randomly selected CCs in New Brunswick and Saskatchewan, Canada. Lunch content was measured on two consecutive days by weighing each food item served to children and by visually documenting the food items using digital photography. Food items were categ into food groups according to Health Canada's Eating Well with Canada's Food Guide, and nutrients were analyzed using a nutritional analysis s sample t tests compared lunch content with nutritional recommendations. Independent t tests compared the nutrient and food group content of lu New Brunswick and Saskatchewan, French and English, and urban and rural CCs. RESULTS: On average, CCs did not meet provincial recommendations. Lunches in both provinces were low in calories ( CONCLUSIONS: Few CC lunches met nutritional recommendations. Interventions are required to improve the quality of foods offered in CCs. Review developing comprehensive nutrition guidelines is warranted. KEY WORDS: Child day care centers; food quality; lunch; nutritional value OBJECTIFS : Les centres de la petite enfance (CPE) offrent generalement un repas par jour et des collations. Dans cette etude, nous avons : compare ce qui est servi dans les CPE aux recommandations nutritionnelles; decrit et compare la composition nutritionnelle des dejeuners servis dans les CPE au Nouveau-Brunswick et en Saskatchewan; et examine les differences entre les centres francophones et anglophones, urbains et ruraux. METHODE : Ont participe a l'etude 61 CPE selectionnes au hasard au Nouveau-Brunswick et en Saskatchewan, au Canada. Le contenu des dejeuners a ete mesure deux jours de suite en pesant chaque produit alimentaire servi aux enfants et en consignant visuellement les produits alimentaires a l'aide de photographies numeriques. Les produits alimentaires ont ete classes en groupes d'aliments conformement au document Bien manger avec le Cuide alimentaire canadien de Sante Canada, et les nutriments ont ete analyses a l'aide d'un logiciel d'analyse nutritionnelle. Des tests t a echantillon unique ont permis de comparer le contenu des dejeuners aux recommandations nutritionnelles. Des tests t independants ont permis de comparer le contenu nutritionnel et les groupes d'aliments des dejeuners servis dans les CPE francophones et anglophones, urbains et ruraux du Nouveau-Brunswick et de la Saskatchewan. RESULTATS : En moyenne, les CPE ne respectaient pas les recommandations provinciales. Dans les deux provinces, les dejeuners etaient faibles en calories ( CONCLUSIONS : Peu de dejeuners offerts dans les CPE respectaient les recommandations nutritionnelles. Il faudrait intervenir pour ameliorer la qualite des aliments offerts dans les CPE. La revision ou l'elaboration de directives nutritionnelles completes s'impose. MOTS CLES : garderies d'enfants; qualite alimentaire; dejeuner; valeur nutritionnelle

The focus of this review is the application of infrared (IR) spectroscopy to study human lens and tear lipids with minimal discussion of the role of lipids and the complex [...]

To test whether the lysosomal localization is crucial for the reported ability of Hsp70 to stabilize lysosomal membranes (1), we took advantage of the endocytic machinery of cells to target [...], Heat shock protein 70 (Hsp70) is an evolutionarily highly conserved molecular chaperone that promotes the survival of stressed cells by inhibiting lysosomal membrane permeabilization (1-5),a hallmark of stress-induced cell death (6-10). Clues to its molecular mechanism of action may lay in the recently reported stress- and cancer-associated translocation of a small portion of Hsp70 to the lysosomal compartment (1,11). Here we show that Hsp70 stabilizes lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential co-factor for lysosomal sphingomyelin metabolism (12-14). In acidic environments Hsp70 binds with high affinity and specificity to BMP, thereby facilitating the BMP binding and activity of acid sphingomyelinase (ASM). The inhibition of the Hsp70-BMP interaction by BMP antibodies or a point mutation in Hsp70 (Trp90Phe), as well as the pharmacological and genetic inhibition of ASM, effectively revert the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann-Pick disease (NPD) A and B--severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1) encoding for ASM (15)--is also associated with a marked decrease in lysosomal stability, and this phenotype can be effectively corrected by treatment with recombinant Hsp70. Taken together, these data open exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2009.11.003 Byline: Harry H. Low (1), Carsten Sachse (1), Linda A. Amos (1), Jan Lowe (1) Keywords: CELLBIO Abstract: Proteins of the dynamin superfamily mediate membrane fission, fusion, and restructuring events by polymerizing upon lipid bilayers and forcing regions of high curvature. In this work, we show the electron cryomicroscopy reconstruction of a bacterial dynamin-like protein (BDLP) helical filament decorating a lipid tube at [approximately equal to]11 A resolution. We fitted the BDLP crystal structure and produced a molecular model for the entire filament. The BDLP GTPase domain dimerizes and forms the tube surface, the GTPase effector domain (GED) mediates self-assembly, and the paddle region contacts the lipids and promotes curvature. Association of BDLP with GMPPNP and lipid induces radical, large-scale conformational changes affecting polymerization. Nucleotide hydrolysis seems therefore to be coupled to polymer disassembly and dissociation from lipid, rather than membrane restructuring. Observed structural similarities with rat dynamin 1 suggest that our results have broad implication for other dynamin family members. Author Affiliation: (1) MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK Article History: Received 24 April 2009; Revised 17 August 2009; Accepted 2 November 2009 Article Note: (miscellaneous) Published: December 24, 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2009.02.014 Byline: Chan Young Park (1), Paul J. Hoover (2), Franklin M. Mullins (2)(3), Priti Bachhawat (2)(4), Elizabeth D. Covington (2), Stefan Raunser (5), Thomas Walz (5)(6), K. Christopher Garcia (2)(4), Ricardo E. Dolmetsch (1), Richard S. Lewis (2) Keywords: CELLBIO Abstract: Store-operated Ca.sup.2+ channels activated by the depletion of Ca.sup.2+ from the endoplasmic reticulum (ER) are a major Ca.sup.2+ entry pathway in nonexcitable cells and are essential for T cell activation and adaptive immunity. After store depletion, the ER Ca.sup.2+ sensor STIM1 and the CRAC channel protein Orai1 redistribute to ER-plasma membrane (PM) junctions, but the fundamental issue of how STIM1 activates the CRAC channel at these sites is unresolved. Here, we identify a minimal, highly conserved 107-aa CRAC activation domain (CAD) of STIM1 that binds directly to the N and C termini of Orai1 to open the CRAC channel. Purified CAD forms a tetramer that clusters CRAC channels, but analysis of STIM1 mutants reveals that channel clustering is not sufficient for channel activation. These studies establish a molecular mechanism for store-operated Ca.sup.2+ entry in which the direct binding of STIM1 to Orai1 drives the accumulation and the activation of CRAC channels at ER-PM junctions. Author Affiliation: (1) Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA (2) Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA (3) Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA (4) Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA (5) Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA (6) Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA Article History: Received 24 September 2008; Revised 6 January 2009; Accepted 9 February 2009 Article Note: (miscellaneous) Published online: February 26, 2009

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2007.10.025 Byline: R. Luke Wiseman (1)(2), Evan T. Powers (1)(2), Joel N. Buxbaum (3), Jeffery W. Kelly (1)(2), William E. Balch (4)(5) Keywords: CELLBIO; PROTEINS; HUMDISEASE Abstract: To provide an integrated view of endoplasmic reticulum (ER) function in protein export, we have described the interdependence of protein folding energetics and the adaptable biology of cellular protein folding and transport through the exocytic pathway. A simplified treatment of the protein homeostasis network and a formalism for how this network of competing pathways interprets protein folding kinetics and thermodynamics provides a framework for understanding cellular protein trafficking. We illustrate how folding and misfolding energetics, in concert with the adjustable biological capacities of the folding, degradation, and export pathways, collectively dictate an adaptable standard for protein export from the ER. A model of folding for export (FoldEx) establishes that no single feature dictates folding and transport efficiency. Instead, a network view provides insight into the basis for cellular diversity, disease origins, and protein homeostasis, and predicts strategies for restoring protein homeostasis in protein-misfolding diseases. Author Affiliation: (1) Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA (2) The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA (3) Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA (4) Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA (5) The Institute for Childhood and Neglected Diseases, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA Article History: Received 9 March 2007; Revised 31 July 2007; Accepted 10 October 2007 Article Note: (miscellaneous) Published: November 15, 2007

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2007.10.018 Byline: David Reczek (1), Michael Schwake (2), Jenny Schroder (2), Heather Hughes (1), Judith Blanz (2), Xiaoying Jin (1), William Brondyk (1), Scott Van Patten (1), Tim Edmunds (1), Paul Saftig (2) Keywords: CELLBIO; HUMDISEASE Abstract: [beta]-glucocerebrosidase, the enzyme defective in Gaucher disease, is targeted to the lysosome independently of the mannose-6-phosphate receptor. Affinity-chromatography experiments revealed that the lysosomal integral membrane protein LIMP-2 is a specific binding partner of [beta]-glucocerebrosidase. This interaction involves a coiled-coil domain within the lumenal domain. [beta]-glucocerebrosidase activity and protein levels were severely decreased in LIMP-2-deficient mouse tissues. Analysis of fibroblasts and macrophages isolated from these mice indicated that the majority of [beta]-glucocerebrosidase was secreted. Missorting of [beta]-glucocerebrosidase was also evident in vivo, as protein and activity levels were significantly higher in sera from LIMP-2-deficient mice compared to wild-type. Reconstitution of LIMP-2 in LIMP-2-deficient fibroblasts led to a rescue of [beta]-glucocerebrosidase levels and distribution. LIMP-2 expression also led to lysosomal transport of a [beta]-glucocerebrosidase endoplasmic reticulum retention mutant. These data support a role for LIMP-2 as the mannose-6-phosphate-independent trafficking receptor for [beta]-glucocerebrosidase. Author Affiliation: (1) Genzyme Corporation, 1 Mountain Road, Framingham, MA 01701, USA (2) Biochemical Institute, Christians-Albrechts University Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany Article History: Received 15 May 2007; Revised 5 September 2007; Accepted 8 October 2007 Article Note: (miscellaneous) Published: November 15, 2007

High intakes of whole grain foods are inversely related to the incidence of coronary heart diseases and type 2 diabetes, but the mechanisms remain unclear. Our study aimed to evaluate the effects of a diet rich in whole grains compared with a diet containing the same amount of refined grains on insulin sensitivity and markers of lipid peroxidation and inflammation. In a randomized crossover study, 22 women and 8 men (BMI 28 [+ or -] 2) were given either whole-grain or refined-grain products (3 bread slices, 2 crisp bread slices, 1 portion muesli, and 1 portion pasta) to include in their habitual daily diet for two 6-wk periods. Peripheral insulin sensitivity was determined by euglycemic hyperinsulinemic clamp tests. 8-Iso-prostaglandin [F.sub.2[alpha]] (8-iso PG[F.sub.2[alpha]]), an [F.sub.2]-isoprostane, was measured in the urine as a marker of lipid peroxidation, and highly sensitive C-reactive protein and IL-6 were analyzed in plasma as markers of inflammation. Peripheral insulin sensitivity [mg glucose * kg body [wt.sup.-1] * [min.sup.-1] per unit plasma insulin (mU/L) x 100] did not improve when subjects consumed whole-grain products (6.8 [+ or -] 3.0 at baseline and 6.5 [+ or -] 2.7 after 6 wk) or refined products (6.4 [+ or -] 2.9 and 6.9 [+ or -] 3.2, respectively) and there were no differences between the 2 periods. Whole-grain consumption also did not affect 8-iso-PG[F.sub.2[alpha]] in urine, IL-6 and C-reactive protein in plasma, blood pressure, or serum lipid concentrations. In conclusion, substitution of whole grains (mainly based on milled wheat) for refined-grain products in the habitual daily diet of healthy moderately overweight adults for 6-wk did not affect insulin sensitivity or markers of lipid peroxidation and inflammation.

Marine hydrocarbonoclastic bacteria, like Alcanivorax borkumensis, play a globally important role in bioremediation of petroleum oil contamination in marine ecosystems. Accumulation of storage lipids, serving as endogenous carbon and energy sources during starvation periods, might be a potential adaptation mechanism for coping with nutrient limitation, which is a frequent stress factor challenging those bacteria in their natural marine habitats. Here we report on the analysis of storage lipid biosynthesis in A. borkumensis strain SK2. Triacylglycerols (TAGs) and wax esters (WEs), but not poly(hydroxyalkanoic acids), are the principal storage lipids present in this and other hydrocarbonoelastie bacterial species. Although so far assumed to be a characteristic restricted to gram-positive actinomycetes, substantial accumulation of TAGs corresponding to a fatty acid content of more than 23% of the cellular dry weight is the first characteristic of large-scale de novo TAG biosynthesis in a gram-negative bacterium. The acyltransferase AtfA1 (ABO_2742) exhibiting wax ester synthase/acyl-coenzyme A'diacylglycerol acyltransferase (WS/DGAT) activity plays a key role in both TAG and WE biosynthesis, whereas AtfA2 (ABO_1804) was dispensable for storage lipid formation. However, reduced but still substantial residual TAG levels in atfA1 and atfA2 knockout mutants compellingly indicate the existence of a yet unknown WS/DGAT-independent alternative TAG biosynthesis route. Storage lipids of A. borkumensis were enriched in saturated fatty acids and accumulated as insoluble intracytoplasmic inclusions exhibiting great structural variety. Storage lipid accumulation provided only a slight growth advantage during short-term starvation periods but was not required for maintaining viability and long-term persistence during extended starvation phases.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.11.040 Byline: Kezhong Zhang (1), Xiaohua Shen (2), Jun Wu (1), Kenjiro Sakaki (1), Thomas Saunders (3), D. Thomas Rutkowski (2), Sung Hoon Back (2), Randal J. Kaufman (1)(2) Abstract: Regulated intramembrane proteolysis (RIP) of endoplasmic reticulum (ER) membrane-anchored transcription factors is known to maintain sterol homeostasis and to mediate the unfolded protein response (UPR). Here, we identified CREBH as a RIP-regulated liver-specific transcription factor that is cleaved upon ER stress and required to activate expression of acute phase response (APR) genes. Proinflammatory cytokines increase expression of ER membrane-anchored CREBH. In response to ER stress, CREBH is cleaved by site-1 and site-2 proteases to liberate an amino-terminal fragment that transits to the nucleus to activate transcription of the genes encoding serum amyloid P-component (SAP) and C-reactive protein (CRP). Proinflammatory cytokines and lipopolysaccharide activate the UPR and induce cleavage of CREBH in the liver in vivo. Together, our studies delineate a molecular mechanism for activation of an ER-localized transcription factor, CREBH, and reveal an unprecedented link by which ER stress initiates an acute inflammatory response. Author Affiliation: (1) Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, USA (2) Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109, USA (3) Transgenic Animal Model Core, University of Michigan Medical Center, Ann Arbor, MI 48109, USA Article History: Received 9 May 2005; Revised 8 September 2005; Accepted 11 November 2005 Article Note: (miscellaneous) Published: February 9, 2006

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.08.031 Byline: Maya Schuldiner (1), Sean R. Collins (1), Natalie J. Thompson (2), Vladimir Denic (1), Arunashree Bhamidipati (1), Thanuja Punna (2), Jan Ihmels (1), Brenda Andrews (2)(3), Charles Boone (2)(3), Jack F. Greenblatt (2)(3), Jonathan S. Weissman (1), Nevan J. Krogan (2)(3) Abstract: We present a strategy for generating and analyzing comprehensive genetic-interaction maps, termed E-MAPs (epistatic miniarray profiles), comprising quantitative measures of aggravating or alleviating interactions between gene pairs. Crucial to the interpretation of E-MAPs is their high-density nature made possible by focusing on logically connected gene subsets and including essential genes. Described here is the analysis of an E-MAP of genes acting in the yeast early secretory pathway. Hierarchical clustering, together with novel analytical strategies and experimental verification, revealed or clarified the role of many proteins involved in extensively studied processes such as sphingolipid metabolism and retention of HDEL proteins. At a broader level, analysis of the E-MAP delineated pathway organization and components of physical complexes and illustrated the interconnection between the various secretory processes. Extension of this strategy to other logically connected gene subsets in yeast and higher eukaryotes should provide critical insights into the functional/organizational principles of biological systems. Author Affiliation: (1) Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94143 (2) Banting and Best Department of Medical Research, University of Toronto, 112 College Street, Toronto, Ontario M5G 1L6, Canada (3) Department of Medical Genetics and Microbiology, University of Toronto, 1 Kings College Circle, Toronto, Ontario M5S 1A8, Canada Article History: Received 12 July 2005; Revised 12 August 2005; Accepted 22 August 2005 Article Note: (miscellaneous) Published: November 3, 2005

Research has been conducted on the Mucor circinelloides and Mortierella alpina. The use of these bacteria as the principle model for the oleaginous filamentous fungi is described and the results indicate the difference in the biochemistry of lipid accumulation between oleaginous yeasts and oleaginous filamentous fungi.

Research has been conducted on the Golgi complex functions. The regulation of the cargo protein inclusion and vesicle budding by the Golgi complex has been investigated.

The synthesis and fluorescence analysis of metal-chelating lipids, incorporating fluorophores pyrene, rhodamine B, coumarin, and disperse orange, are described. The lipid are reconstituted into liposomes and polymerized to demonstrate their use as membrane probes for studying the polymerizable liposomes in the unpolymerized state and lipid redistribution during polymerization.

A study was conducted to analyze the influence of alcohols on well-defined lipid bilayers. Isothermal titration calorimetry was utilized to determine the excess partial molar enthalpy of alcohol in liposome suspensions. Calorimetric data were then used to examine molecular interactions. Results indicated a maximum in partitioning coefficients in the transition region resulting from the formation of heterogenous lateral bilayers characterized by fluctuating lipid domains and interfacial regions acting as adsorption sites.

The structural properties of the palmitoyl and dodecyl chains as well as of the headgroups of POPC and C12E4, respectively, were obtained at 25 degrees C in the pure and mixed membranes hydrated at the same relative humidity of 97% by deuterium NMR utilizing partially deuterated lipids and surfactants. Results showed a thickening of the bilayer and its hydrophobic core because of the stretching of the surfactant dodecyl chain which is mainly due to the reduction of the surfactant headgroup repulsions.

Apolipophorin III (apoLp-III) from the sphinx moth, Manduca sexta, is a helix bundle protein that interacts reversibly with lipoproteins. Its five elongated amphipathic [Alpha]-helices are organized in an antiparallel fashion, with helices 3 and 4 connected by a short 6-residue (PDVEKE) linker helix, termed helix 3[prime]. Upon interaction with lipoproteins, apoLp-III opens to expose a continuous hydrophobic interior. It was postulated that helix bundle opening is preceded by an initiation step wherein helix 3[prime] serves to recognize available lipoprotein surface binding sites. To test this hypothesis, helix 3[prime] was replaced by residues that have a propensity to form a type I [Beta]-turn, NPNG. This mutant apoLp-III was defective in lipoprotein binding assays. To define a more precise mode of interaction, the relevance of the presence of the hydrophobic Val-97 flanked by Asp-96 and Glu-98 was investigated by site-directed mutagenesis. V97N and D96N//V97N/E98Q apoLp-III were unable to compete with wild-type apoLp-III to initiate an interaction with lipoproteins, whereas D96N//E98Q apoLp-III was as competent as wild-type apoLp-III. The results suggest that Val-97 is critical, whereas Asp-96 and Glu-98 are irrelevant for initiating binding to lipoproteins. A model of binding is presented wherein apoLp-III is oriented with the helix 3[prime] end of the molecule juxtaposed to the lipoprotein surface. Recognition of lipoprotein surface hydrophobic defects by Val-97 triggers opening of the helix bundle and facilitates formation of a stable binding interaction.

A study was conducted to analyze closed form results associated with shape transitions in lipid monolayer domains. Asymptotic behavior was determined in different limits of interest. A general closed form expression was then obtained for the critical domain radii. Results indicated that lipid monolayers establish two-dimensional domains because of the competition between line-tension and long-range repulsive interactions.