FA Components Research Articles

Defining the Ceramide Composition of Bovine and Human Milk Gangliosides by Direct Infusion ESI-CID Tandem Mass Spectrometry of Native and Permethylated Molecular Species.

Gangliosides are glycosphingolipids composed of an oligosaccharide that contains one or more sialic acid residues and is linked to a ceramide, a lipid composed of a long chain base (LCB) that bears an amide-linked fatty acyl group (FA). The ceramide portions of gangliosides are embedded in cell membranes; the exposed glycans interact with the extracellular environment. Gangliosides play a myriad of roles in activities such as cell-cell communication, formation of lipid rafts, cellular adhesion, calcium homeostasis, host-pathogen interaction, and viral invasion. Although the epitopes responsible for the interactions of gangliosides are located in the glycan, the epitope presentation is strongly influenced by the orientation of the attached ceramide within the lipid membrane, a feature that depends on the details of its structure, that is, the specific LCB and FA. Since the identities of both the glycan and the ceramide affect the activity of gangliosides, it is important to characterize the individual intact molecular forms. We report here a mass spectrometry-based method that combines the information gained from low-energy collision-induced dissociation (CID) measurements for the determination of the glycan with tandem mass spectra obtained at stepped higher-energy CID for the detailed characterization of the LCB and FA components of intact gangliosides. We provide results from applications of this method to the analysis of gangliosides present in bovine and human milk in order to demonstrate the assignment of LCB and FA for intact gangliosides and differential detection of isomeric ceramide structures.

Myocardin-related transcription factor contributes to renal fibrosis through the regulation of extracellular microenvironment surrounding fibroblasts.

Fibroblast accumulation and extracellular matrix (ECM) deposition are common critical steps for the progression of organ fibrosis, but the precise molecular mechanisms remain to be fully investigated. We have previously demonstrated that lysophosphatidic acid contributes to organ fibrosis through the production of connective tissue growth factor (CTGF) via actin cytoskeleton-dependent signaling, myocardin-related transcription factor family (MRTF) consisting of MRTF-A and MRTF-B-serum response factor (SRF) pathway. In this study, we investigated the role of the MRTF-SRF pathway in the development of renal fibrosis, focusing on the regulation of ECM-focal adhesions (FA) in renal fibroblasts. Here we showed that both MRTF-A and -B were required for the expressions of ECM-related molecules such as lysyl oxidase family members, type I procollagen and fibronectin in response to transforming growth factor (TGF)-β1 . TGF-β1 -MRTF-SRF pathway induced the expressions of various components of FA such as integrin α subunits (αv , α2 , α11 ) and β subunits (β1 , β3 , β5 ) as well as integrin-linked kinase (ILK). On the other hand, the blockade of ILK suppressed TGF-β1 -induced MRTF-SRF transcriptional activity, indicating a mutual relationship between MRTF-SRF and FA. Myofibroblast differentiation along with CTGF expression was also dependent on MRTF-SRF and FA components. Finally, global MRTF-A deficient and inducible fibroblast-specific MRTF-B deficient mice (MRTF-AKO BiFBKO mice) are protected from renal fibrosis with adenine administration. Renal expressions of ECM-FA components and CTGF as well as myofibroblast accumulation were suppressed in MRTF-AKO BiFBKO mice. These results suggest that the MRTF-SRF pathway might be a therapeutic target for renal fibrosis through the regulation of components forming ECM-FA in fibroblasts.

Modelling of the Face-Milling Process by Toroidal Cutter

When face milling using a toroidal cutter, with a change in the depth of the cut, the entering angle varies as well. An experimental test of the influence of cutting parameters, such as the depth of the cut and the feed per tooth on the cutting force components and surface roughness parameters, was conducted. The experimental test was carried out using a DMU 100 monoBLOCK CNC machine with registration of cutting force components and surface roughness parameters Ra, Rz, and RSm. FEM analysis of the face-milling process was also carried out and compared with the experimental results. The average deviation of the FEM values for cutting force components does not exceed 12%. Experimental models were established for each force component. It was shown that the depth of the cut has the strongest influence on each force component. The feed per tooth has a little impact on the cutting force. The obtained model of the feed force component is the most complex, and the model of the Fa component is only linear. The influence of the ap parameter on the surface roughness parameters is nonlinear and nonmonotonic. In the range of approx. ap = 2 mm, there is a maximum surface roughness.

Properties of the fluoroacrylate and methacryloxypropyl-trimethoxysilane applied to a layer of Cu2O on bronze as either single or multi-component coatings

Various coatings have been developed and explored to protect bronze surfaces against the uncontrolled formation of different corrosion products when exposed to outdoor environments.In this research, the surfaces of artificially-formed oxidized bronze patinas (OB), consisting of Cu2O, were covered with either a single-component (fluoroacrylate, FA or methacryloxypropyl-trimethoxysilane, MS) or multi-component (a mixture of FA and MS, FA-MS) fluoropolymer coating and investigated. Variations in the concentration of each component in the coating were studied. Electrochemical tests were performed to determine the corrosion protection efficiency, followed by detailed surface analyses of the OBs, both uncoated and covered with single and multi-component coatings. A variety of investigative methods were used, including focused ion beam scanning electron microscopy (FIB-SEM), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and time-of-flight secondary ion mass spectrometry (ToF-SIMS).The coating made from a combination of FA and MS resulted in a very high protection efficiency. Despite the increased hydrophilicity of the single MS component, however, it was shown to efficiently protect the oxidized bronze surface. The FA-MS systems showed high hydrophobicity, but no improvement was measured in the efficiency of the corrosion protection when it was compared to the coating that contained 10% MS. According to XPS and ToF-SIMS imaging, the FA component of the FA-MS coating was not present only on the uppermost surface of the coating but throughout the whole coating, which could affect its corrosion protection efficiency.

Body shape and fluctuating asymmetry following different feeding sources and feeding time in a triatomine, Triatoma pallidipennis (Stål, 1892).

Even when an animal has a generalist diet, different food sources can impact its body shape and fluctuating asymmetry (a stress indicator; FA). To test this, we varied the food source (mammalian, avian or defibrinated mammalian blood; and control animals - ad libitum feeding) and the time of feeding (every 8days, 45days and ad libitum) having the Chagas triatomine vector, Triatoma pallidipennis (Stål, 1892), as a study animal which has presumable generalist feeding habits. This factorial design was applied since first instar animals until adulthood. As response variables, we measured body shape and FA in adults of both sexes, using a two-dimensional geometric morphometrics protocol. The highest variance in body shape was explained by diet (17%), followed by sex nested within diet (12%). Males had less morphological differentiation than females: females with defibrinated blood provided every 45days differentiated more, while those that fed on mammalian blood every 8days differed less. Distances among the averages of the FA component related to shape indicated greater distances between avian blood provided every 45days and mammalian blood provided every 8days, as well as between the two groups fed on avian blood (feeding every 8 and 45days), followed by avian and defibrinated blood, both fed every 8days. These results indicate that blood source and feeding time have significant effects on the body shape, and FA in females and both sexes. Thus, despite general feeding habits, avian blood showed a greater impact on shape and FA in triatomines. This may select for triatomines to use mammal blood rather than avian blood if they have the chance to do so.

Discrimination between the Two Closely Related Species of the Operational Group B. amyloliquefaciens Based on Whole-Cell Fatty Acid Profiling.

(1) Background: Bacillus velezensis and Bacillus amyloliquefaciens are closely related members of the “operational group B. amyloliquefaciens”, a taxonomical unit above species level within the ”Bacillus subtilis species complex”. They have similar morphological, physiological, biochemical, phenotypic, and phylogenetic characteristics. Thus, separating these two taxa from each another has proven to be difficult to implement and could not be pushed easily into the line of routine analyses. (2) Methods: The aim of this study was to determine whether whole FAME profiling could be used to distinguish between these two species, using both type strains and environmental isolates. Initially, the classification was determined by partial sequences of the gyrA and rpoB genes and the classified isolates and type strains were considered as samples to develop the identification method, based on FAME profiles. (3) Results: The dissimilarities in 16:0, 17:0 iso, and 17:0 FA components have drawn a distinction between the two species and minor differences in FA 14:0, 15:0 iso, and 16:0 iso were also visible. The statistical analysis of the FA profiles confirmed that the two taxa can be distinguished into two separate groups, where the isolates are identified without misreading. (4) Conclusions: Our study proposes that the developed easy and fast-automated identification tool based on cellular FA profiles can be routinely applied to distinguish B. velezensis and B. amyloliquefaciens.

Effect of vernalisation on the diurnal changes in fatty acid profile and nutrient composition of chicory in response to defoliation frequency

ABSTRACT The effect of defoliation frequency and severity on FA and nutrient composition of forage chicory (Cichorium intybus L.) before and after vernalisation were compared. Before vernalisation, the FA and nutrient components exhibited little variation with defoliation frequency and severity irrespective of the time of day. After vernalisation, total FA more than halved compared with pre vernalisation levels (52.2 versus 19.2 mg/g DM). Concentrations of total FA and polyunsaturated FA: linoleic and linolenic declined by 63%, 50%, and 74%, respectively. Furthermore, extending the defoliation frequency from 300 to 600 growing degree-days after vernalisation caused a decline of 28% of linoleic, 40% of linolenic and 33% of total FA concentrations. Diurnal fluctuations were detected for linoleic and oleic acids after vernalisation (P < 0.01). In terms of nutrient composition, vernalisation decreased CP, digestibility and ME, while fibre contents increased. Between morning and afternoon, there were general declines in CP and fibre contents as well as increases in soluble sugars the herbage regardless of vernalisation. Overall, the feeding value and the concentration of FA were greater on chicory herbage managed under shorter regrowth intervals than that under longer regrowth intervals, which is likely to favour animal production and the concentration of the desirable FA in ruminant products.

Lipids and Free Fatty Acids of Red Sea Avrainvillea amadelpha, Holothuria atra, and Sarcocornia fruticosa Inhibit Marine Bacterial Biofilms

This study aimed at evaluating the antibiofilm activity of the Red Sea metabolites from green alga Avrainvillea amadelpha, sea cucumber Holothuria atra and costal plant Sarcocornia fruticosa against three biofilm bacterial strains isolated from Jeddah coast. Free fatty acids (FFAs) and other lipoidal matters were extracted from these organisms and analyzed by GC-MS. The composition of lipoidal fractions showed that A. amadelpha is rich by 74% saturated FAs, while sea cucumber H. atra revealed high content (60%) of unsaturated FAs. Palmitic acid is the major FA component in all species ranging from 14.5 to 26.7%. Phytol, sterols and hydrocarbons (C8-C29) were represented in the alga A. amadelpha as high contents with values 25.8, 21.9 and 18.5%, respectively. The extracts and lipoidal contents showed biofilm inhibitory activity against the isolated bacterial strains, where the unsaponified lipoidal fraction of S. fruticosa exhibited highest inhibitory activity against Planomicrobium sp. at concentration of 200 &amp;#181;g/mL.

Consumption of the fish oil high fat diet uncouples obesity and tumor growth through induction of reactive oxygen species in pro-tumor macrophages

Abstract It is clear that obesity is associated with increased risk of many types of cancer. However, obesity can be induced by various high fat diets (HFDs) from different fat sources. It remains unknown whether fatty acid composition in different HFDs influences obesity-associated tumor development. Herein we report that consumption of either a cocoa butter or fish oil HFD induced similar obesity in mouse models. While obesity induced by the cocoa butter HFD was associated with accelerated tumor growth, consumption of the fish oil HFD uncoupled obesity from increased tumor growth and exhibited a decrease in pro-tumor macrophages. Interestingly, compared to FA components in both HFDs, n-3 FAs rich in the fish oil HFD induced significant production of reactive oxygen species (ROS) and macrophage cell death. Moreover, we found that A-FABP expression in the pro-tumor macrophages facilitated n-3 FA intracellular transportation and mitochondrial FA oxidation. A-FABP deficiency diminished n-3 FA-mediated ROS production and macrophage cell death both in vitro and in vivo. Altogether, our results demonstrate a novel mechanism by which n-3 FAs induce ROS-mediated pro-tumor macrophage cell death in an A-FABP dependent manner. This study provides mechanistic insights into dietary supplementation with fish oil for cancer prevention and puts forwards a new concept that not all HFDs leading to obesity are tumorigenic.

Thermal Degradation of p‐Hydroxybenzoic Acid in Macadamia Nut Oil, Olive Oil, and Corn Oil

Abstractp‐Hydroxybenzoic acid (PHBA) plays a significant role in sustaining the oxidative stability of macadamia nut oil (MNO). However, PHBA undergoes thermal decarboxylation and loses its bioactive antioxidant properties. In this study, we determine PHBA degradation kinetics in oils at various heating temperatures, which provides fundamental understanding of PHBA thermal degradation in oils and oil quality changes during high‐temperature processing. PHBA degradation kinetics in MNO, olive oil, and corn oil were evaluated at temperatures typical for cooking and frying. PBHA headspace concentration was measured using selected ion flow tube mass spectrometry. PHBA decarboxylation followed a zero‐order reaction, where degradation could be affected by factors such as the type of oil matrix having different FA compositions, antioxidants, and component interactions. PHBA degradation activation energies (E a) showed that PHBA was more stable against thermal decarboxylation in MNO (85 kJ mol–1) than in olive oil (40 kJ mol−1) or corn oil (22 kJ mol−1). The higher enthalpy () of decarboxylation in MNO (82 kJ mol−1) indicates that PHBA is more inhibited from decomposition than olive oil (37 kJ mol−1) or corn oil (19 kJ mol−1). Moreover, the negative entropy values () of PHBA degradation from MNO (−192 J mol−1 K−1), olive oil (−277 J mol−1 K−1), and corn oil (−325 J mol−1 K−1) indicates that these oils impart some inhibitory properties against PHBA thermal decarboxylation.

SPINMELT-2.0: Simulation of Spinel–Melt Equilibrium in Basaltic Systems under Pressures up to 15 Kbar: III. The Effects of Major Components in the Melt on the Chrome-Spinel Stability and a Possible Solution of the Problem of Origin of Chromitites

The effect of variations in the fo, fa, en, fs, di, an and ab components in high-Mg basaltic melts on the topology of the spinel liquidus was quantified by conducting simulations with the new SPINMELT-2.0 model for the spinel–melt equilibrium. It has been established that enrichment of the melt in pyroxene components leads to an increase, and conversely, enrichment in plagioclase and olivine components, to a decrease in the solubility of chromite. This effect can be important at the gravitational compaction of cumulates accompanied by the extraction of intercumulus melt and its infiltration upward. In this case, it is reasonable to expect sequential reequilibration of the infiltrating melt with cumulate piles of different composition. This suggests that Cr-spinel can be transferred and concentrated again during the postcumulus solidification stage of layered intrusions. The concentrating process involves Cr-spinel extraction into the melt enriched in pyroxene components and the subsequent redeposition of the mineral during when this melt reacts with the feldspar-rich matrix of proto-anorthosite layers or horizons enriched in olivine. Some of these layers and horizons may be produced by additional injections of more primitive magma. The realism of the proposed mechanism is evident from the well-known spatial relations between the chromite layers with anorthosites and dunite–harzburgites of the Bushveld complex.

Overexpression of two plastidial fatty acid desaturase genes from tree peony affects the ratio of α-linolenic acid to linoleic acid in Arabidopsis seeds

ABSTRACTTree peony (Paeonia section Moutan DC.) has recently been recognised as an important woody oil plant of high economic value, with its seeds containing high levels of α-linolenic acids (ALA, C18:3). Here, we identified two novel FA desaturase genes from Paeonia. rockii, designated PrFAD6 and PrFAD7. Sequence, structure, and phylogenetic analyses revealed that they share high similarity with ω-6 and ω-3 plastidial FA desaturases. qRT-PCR showed that PrFAD6 and PrFAD7 were expressed in all studied tissues, particularly high in stamen, pistil, seed and leaf. Heterologous expression of PrFAD6 in Arabidopsis resulted in a 2.3–2.9% reduction in the ratio of ALA to linoleic acid (LA, C18:2), whilst overexpression of PrFAD7 increased the ALA/LA ratio by 7.0–9.9%. Moreover, the transgenic Arabidopsis plants overexpressing PrFAD6 and PrFAD7 exhibited varied abundances of a few FA components, particularly increased C18:2 and C18:3 levels, respectively. These results support the biological role of PrFAD6 and PrFAD7 in the biosynthesis of ALA and LA in tree peony seeds. Our study is the first attempt to verify the functions of plastidial FA desaturases in tree peony and will facilitate future research and industrial utilisation of tree peony as an important oil plant.

Effect of amphiphilic PCL-PEG nano-micelles on HepG2 cell migration.

Uptake of nanoparticles (NPs) affects cell migration but the mechanism remains poorly understood. In this study, the amphiphilic block PCL-PEG nano-micelles with well-controlled hydrophilic/hydrophobic chains were used to investigate the effect of internalized nano-micelles on cancer cell migration. Our results indicated that the nano-micelles with medium PCL and PEG chains increased expression of Rho GTPases and impeded focal adhesion components. This could enhance Hep G2 cell motility. The nano-micelles with large PCL and PEG chains showed lower Rho GTPase levels and higher FA components. This is consistent with slower cell migration. Understanding the mechanism of NPs regulating cell behaviors may help the design of efficient drug delivery systems based on polymer micelles.

Motion Technology for FA Components and Industrial Machinery Systems

Motion Technology for FA Components and Industrial Machinery Systems

Compositional and structural studies of the oils from two edible seeds: Tiger nut, Cyperus esculentum, and asiato, Pachira insignis, from Ghana

A comprehensive lipid profiling has been carried out on the seed oils of tiger nut, Cyperus esculentum, and asiato, Pachira insignis, from Ghana in order to evaluate their potential uses for the region. Composition of FAs and phytosterols were determined using GC–MS, while tocol composition was determined with HPLC. TAG composition and regiochemistry were determined using ES-FTICR-MS and 13C NMR, respectively. The major FA components in asiato seed oil were palmitic acid (56.58%) and sterculic and dihydrosterculic acids (20.06% combined). The major FA components in tiger nut oil were oleic (65.55%), palmitic (16. 32%), and linoleic (12.13%) acids. Asiato seed oil had 18 major TAG classes, dominated by, C51:1 (38.45%) and C50:1 (13.941%). Tiger nut oil had 7 major TAG classes, with C54:3 (29.00%) and C52:2 (27.82%) dominating. The sn-1/3 and sn-2 positions in the TAGS for asiato oil were predominantly occupied by saturated acyl chains (87.25%) and cyclic acyl chains (71.44%), respectively. Oleoyl chain primarily occupied both sn-1/3 (52.68%) and sn-2 (77.62%) positions in the tiger nut oil. Total tocol content in asiato oil was 200.31μg/g, with γ-tocopherol (182.99μg/g) dominating. Tiger nut oil had a total tocol content of 120.10μg/g, dominated by α-tocopherol (86.73) and β-tocopherol (33.37μg/g).Tiger nut oil had total 4-desmethylsterol content of 986μg/g, dominated by β-sitosterol (517.25μg/g) and stigmasterol (225.25μg/g), while asiato oil had total desmethylsterol content of 590.24μg/g, dominated by β-sitosterol (518.91μg/g). The presence of cyclopropenoid FAs in asiato oil makes it unsuitable for food uses. Tiger nut oil can replace imported olive oil in food products in the West African region.

The effect of temperature and dietary fat level on tissue lipid composition in Atlantic salmon (Salmo salar) fed wax ester-rich oil from Calanus finmarchicus

Copepod oil (CO) from the marine zooplankton, Calanus finmarchicus, is a potential alternative to fish oils (FOs) for inclusion in aquafeeds. The oil is composed mainly of wax esters (WE) containing high levels of saturated fatty acids (SFAs) and monounsaturated fatty alcohols that are poorly digested by fish at low temperatures. Consequently, tissue lipid compositions may be adversely affected in salmon-fed CO at low temperatures. This study examined the lipid and FA compositions of muscle and liver of Atlantic salmon reared at two temperatures (3 and 12 °C) and fed diets containing either FO or CO, supplying 50% of dietary lipid as WE, at two fat levels (∼330 g kg−1, high; ∼180 g kg−1, low). Fish were acclimatized to rearing temperature for 1 month and then fed one of four diets: high-fat fish oil (HFFO), high-fat Calanus oil (HFCO), low-fat fish oil (LFFO) and low-fat Calanus oil (LFCO). The fish were grown to produce an approximate doubling of initial weight at harvest (220 days at 3 °C and 67 days at 12 °C), and lipid content, lipid class composition and FA composition of liver and muscle were determined. The differences in tissue lipid composition between dietary groups were relatively small. The majority of FA in triacylglycerols (TAG) in both tissues were monounsaturated, and their levels were generally higher at 3 °C than 12 °C. Polyunsaturated fatty acids (PUFA), particularly (n-3) PUFA, predominated in the polar lipids, and their level was not significantly affected by temperature. The PUFA content of TAG was highest (∼26%) in the muscle of fish fed the HFCO diet at both temperatures. Tissue levels of SFAs were lower in fish-fed diets containing HFCO than those fed HFFO, LFFO or LFCO, particularly at 3 °C. The results are consistent with Atlantic salmon being able to incorporate both the FA and fatty alcohol components of WE into tissue lipids but, overall, the effects of environmental temperature on tissue lipids were more pronounced in fish fed the CO diets than FO diets.

S2046 Reducing Tumor Growth On Stents Using Nanorods: Nanotechnology for the Prevention of Cell Adhesion and Migration

Src activity might induce the recruitment of Dyn2, we first tested the role of the adaptor protein Grb2 which is known to bind to the proline-rich domain (PRD) of Dyn2 at the plasma membrane during endocytosis. Surprisingly, Grb2 was also recruited to FAs following Src activation, and knockdown of Grb2 inhibited Dyn2's FA targeting. To test if Src might activate Dyn2 to alter FA dynamics, we mutated specific Src substrates on Dyn2 to mimic either phosph-active Dyn2 (Dyn2 Y231, 597E), or phospho-defective Dyn2 (Dyn2 Y231, 597F). Interestingly, expression of the Dyn2 YE form greatly increased internalization of an FA component β1-integrin (compared to WT cells) that potentiated the neoplastic potential of these cells as they became substantially more rounded and poorly adherent with more dynamic FAs. Together, we conclude that Src kinase acts to regulate FA dynamics in two related but distinct ways; first, by increasing Dyn2 recruitment to adhesion sites via the Grb2 adaptor, and second, via phospho-activation of Dyn2 leading to increased endocytic turnover of FA components. These findings provide a novel mechanistic insight into how EGFR/Src signaling promotes pancreatic cancer cell migration and metastasis.

S2043 Anticancer Effects of Astaxanthin in Stomach Cancer Cell Lines

Src activity might induce the recruitment of Dyn2, we first tested the role of the adaptor protein Grb2 which is known to bind to the proline-rich domain (PRD) of Dyn2 at the plasma membrane during endocytosis. Surprisingly, Grb2 was also recruited to FAs following Src activation, and knockdown of Grb2 inhibited Dyn2's FA targeting. To test if Src might activate Dyn2 to alter FA dynamics, we mutated specific Src substrates on Dyn2 to mimic either phosph-active Dyn2 (Dyn2 Y231, 597E), or phospho-defective Dyn2 (Dyn2 Y231, 597F). Interestingly, expression of the Dyn2 YE form greatly increased internalization of an FA component β1-integrin (compared to WT cells) that potentiated the neoplastic potential of these cells as they became substantially more rounded and poorly adherent with more dynamic FAs. Together, we conclude that Src kinase acts to regulate FA dynamics in two related but distinct ways; first, by increasing Dyn2 recruitment to adhesion sites via the Grb2 adaptor, and second, via phospho-activation of Dyn2 leading to increased endocytic turnover of FA components. These findings provide a novel mechanistic insight into how EGFR/Src signaling promotes pancreatic cancer cell migration and metastasis.

Building Developmental Integration into Functional Systems: Function-Induced Integration of Mandibular Shape

The mammalian mandible is a developmentally modular but functionally integrated system. Whether morphological integration can evolve to match the optimal pattern of functional integration may depend on the developmental origin of integration, specifically, on the role that direct epigenetic interactions play in shaping integration. These interactions are hypothesized to integrate modules and also to be highly conservative, potentially constraining the evolution of integration. Using the fox squirrel (Sciurus niger) mandible as a model system, we test five a priori developmental hypotheses that predict mandibular integration and we also explore for correlations between shapes of mandibular regions not anticipated by any of the developmental models. To determine whether direct epigenetic interactions are highly conserved in rodents, we examine the correlation structure of fluctuating asymmetry, and compare integration patterns between fox squirrels and prairie deer mice (Peromyscus maniculatus bairdii). In fox squirrels, we find a correlation structure unanticipated by all a priori developmental models: adjacent parts along the proximodistal jaw axis are correlated whereas more distant ones are not. The most notable exception is that the shape of the anterior incisor alveolus is correlated with the shape of the ramus (FA component) or coronoid (symmetric component). Those exceptions differ between species; in prairie deer mice, the molar alveolus is connected to more parts, and the incisor alveolus to fewer, than in fox squirrels. The structure of integration suggests that the mandible cannot be decomposed into parts but rather is a single connected unit, a result consistent with its functional integration. That match between functional and developmental integration may arise, at least in part, from function-induced growth, building developmental integration into the functional system and enabling direct epigenetic interactions to evolve when function does.

DOG-1 Is the Caenorhabditis elegans BRIP1/FANCJ Homologue and Functions in Interstrand Cross-Link Repair

Fanconi anemia (FA) is a cancer susceptibility syndrome characterized by defective DNA interstrand cross-link (ICL) repair. Here, we show that DOG-1 is the Caenorhabditis elegans homologue of FANCJ, a helicase mutated in FA-J patients. DOG-1 performs a conserved role in ICL repair, as dog-1 mutants are hypersensitive to ICL-inducing agents, but not to UVC irradiation or X rays. Genetic analysis indicated that dog-1 is epistatic with fcd-2 (C. elegans FANCD2) but is nonepistatic with brc-1 (C. elegans BRCA1), thus establishing the existence of two distinct pathways of ICL repair in worms. Furthermore, DOG-1 is dispensable for FCD-2 and RAD-51 focus formation, suggesting that DOG-1 operates downstream of FCD-2 and RAD-51 in ICL repair. DOG-1 was previously implicated in poly(G)/poly(C) (G/C) tract maintenance during DNA replication. G/C tracts remain stable in the absence of ATL-1, CLK-2 (FA pathway activators), FCD-2, BRC-2, and MLH-1 (associated FA components), implying that DOG-1 is the sole FA component required for G/C tract maintenance in a wild-type background. However, FCD-2 is required to promote deletion-free repair at G/C tracts in dog-1 mutants, consistent with a role for FA factors at the replication fork. The functional conservation between DOG-1 and FANCJ suggests a possible role for FANCJ in G/C tract maintenance in human cells.