Connexons and cell adhesion: a romantic phase

Recent evidence indicates, that gap junction forming proteins do not only contribute to intercellular communication (Kanno and Saffitz in Cardiovasc Pathol 10:169-177, 2001; Saez et al. in Physiol Rev 83:1359-1400, 2003), ion homeostasis and volume control (Goldberg et al. in J Biol Chem 277:36725-36730, 2002; Saez et al. in Physiol Rev 83:1359-1400, 2003). They also serve biological functions in a mechanical sense, supporting adherent connections between neighbouring cells of epithelial and non-epithelial tissues (Clair et al. in Exp Cell Res 314:1250-1265, 2008; Shaw et al. in Cell 128:547-560, 2007), where they stabilize migratory pathways in the developing central nervous system (Elias et al. in Nature 448:901-907, 2007; Malatesta et al. in Development 127:5253-5263, 2000; Noctor et al. in Nature 409:714-720, 2001; Rakic in Brain Res 33:471-476, 1971; J Comp Neurol 145:61-83 1972; Science 241:170-176, 1988), or mediate polarized movements and directionality of neural crest cells during organogenesis (Kirby and Waldo in Circ Res 77:211-215, 1995; Xu et al. in Development 133:3629-3639, 2006). Since, most data describing adhesive properties of gap junctions delt with connexin 43 (Cx43) (Beardslee et al. in Circ Res 83:629-635, 1998), we will focus our brief review on this isoform.     

Analysis of avian bone response to mechanical loading—Part One: Distribution of bone fluid shear stress induced by bending and axial loading

Mechanical loading-induced signals are hypothesized to be transmitted and integrated by a bone-connected cellular network (CCN) before reaching the bone surfaces where adaptation occurs. Our objective is to establish a computational model to explore how bone cells transmit the signals through intercellular communication. In this first part of the study the bone fluid shear stress acting on every bone cell in a CCN is acquired as the excitation signal for the computational model. Bending and axial loading-induced fluid shear stress is computed in transverse sections of avian long bones for two adaptation experiments (Gross et al. in J Bone Miner Res 12:982-988, 1997 and Judex et al. in J Bone Miner Res 12:1737-1745, 1997). The computed fluid shear stress is found to be correlated with the radial strain gradient but not with bone formation. These results suggest that the radial strain gradient is the driving force for bone fluid flow in the radially distributed lacunar-canalicular system and that bone formation is not linearly related to the loading-induced local stimulus.     

Analysis of avian bone response to mechanical loading, Part Two: Development of a computational connected cellular network to study bone intercellular communication

Mechanical loading-induced signals are hypothesized to be transmitted and integrated by connected bone cells before reaching the bone surfaces where adaptation occurs. A computational connected cellular network (CCCN) model is developed to explore how bone cells perceive and transmit the signals through intercellular communication. This is part two of a two-part study in which a CCCN is developed to study the intercellular communication within a grid of bone cells. The excitation signal was computed as the loading-induced bone fluid shear stress in part one. Experimentally determined bone adaptation responses (Gross et al. in J Bone Miner Res 12:982-988, 1997 and Judex et al. in J Bone Miner Res 12:1737-1745, 1997) are correlated with the fluid shear stress by the CCCN, which adjusts cell sensitivities (loading and signal thresholds) and connection weights. Intercellular communication patterns extracted by the CCCN indicate the cell population responsible for perceiving the loading-induced signal, and loading threshold is shown to play an important role in regulating the bone response.     

Predicting genotoxicity of aromatic and heteroaromatic amines using electrotopological state indices

A quantitative structure-activity relationship (QSAR) model relating electrotopological state (E-state) indices and mutagenic potency was previously described by Cash [Mutat. Res. 491 (2001) 31-37] using a data set of 95 aromatic amines published by Debnath et al. [Environ. Mol. Mutagen. 19 (1992) 37-52]. Mutagenic potency was expressed as the number of Salmonella typhimurium TA98 revertants per nmol (LogR). Earlier work on the development of QSARs for the prediction of genotoxicity indicated that numerous methods could be effectively employed to model the same aromatic amines data set, namely, Debnath et al.; Maran et al. [Quant. Struct.-Act. Relat. 18 (1999) 3-10]; Basak et al. [J. Chem. Inf. Comput. Sci. 41 (2001) 671-678]; Gramatica et al. [SAR QSAR Environ. Res. 14 (2003) 237-250]. However, results obtained from external validations of those models revealed that the effective predictivity of the QSARs was well below the potential indicated by internal validation statistics (Debnath et al., Gramatica et al.). The purpose of the current research is to externally validate the model published by Cash using a data set of 29 aromatic amines reported by Glende et al. [Mutat. Res. 498 (2001) 19-37; Mutat. Res. 515 (2002) 15-38] and to further explore the potential utility of using E-state sums for the prediction of mutagenic potency of aromatic amines.     

Modulation of phrenic motoneuron excitability by ATP: consequences for respiratory-related output in vitro.

On the basis of the high level of P2X receptor expression found in phrenic motoneurons (MN) in rats (Kanjhan et al., J Comp Neurol 407: 11-32, 1999) and potentiation of hypoglossal MN inspiratory activity by ATP (Funk et al., J Neurosci 17: 6325-6337, 1997), we tested the hypothesis that ATP receptor activation also modulates phrenic MN activity. This question was examined in rhythmically active brain stem-spinal cord preparations from neonatal rats by monitoring effects of ATP on the activity of spinal C4 nerve roots and phrenic MNs. ATP produced a rapid-onset, dose-dependent, suramin- and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid 4-sodium-sensitive increase in C4 root tonic discharge and a 22 +/- 7% potentiation of inspiratory burst amplitude. This was followed by a slower, 10 +/- 5% reduction in burst amplitude. ATPgammaS, the hydrolysis-resistant analog, evoked only the excitatory response. ATP induced inward currents (57 +/- 39 pA) and increased repetitive firing of phrenic MNs. These data, combined with persistence of ATP currents in TTX and immunolabeling for P2X2 receptors in Fluoro-Gold-labeled C4 MNs, implicate postsynaptic P2 receptors in the excitation. Inspiratory synaptic currents, however, were inhibited by ATP. This inhibition differed from that seen in root recordings; it did not follow an excitation, had a faster onset, and was induced by ATPgammaS. Thus ATP inhibited activity through at least two mechanisms: 1) a rapid P2 receptor-mediated inhibition and 2) a delayed P1 receptor-mediated inhibition associated with hydrolysis of ATP to adenosine. The complex effects of ATP on phrenic MNs highlight the importance of ATP as a modulator of central motor outflows.     

Emergence of protocellular growth laws

Template-directed replication is known to obey a parabolic growth law due to product inhibition (Sievers & Von Kiedrowski 1994 Nature 369, 221; Lee et al. 1996 Nature 382, 525; Varga & Szathmáry 1997 Bull. Math. Biol. 59, 1145). We investigate a template-directed replication with a coupled template catalysed lipid aggregate production as a model of a minimal protocell and show analytically that the autocatalytic template-container feedback ensures balanced exponential replication kinetics; both the genes and the container grow exponentially with the same exponent. The parabolic gene replication does not limit the protocellular growth, and a detailed stoichiometric control of the individual protocell components is not necessary to ensure a balanced gene-container growth as conjectured by various authors (Gánti 2004 Chemoton theory). Our analysis also suggests that the exponential growth of most modern biological systems emerges from the inherent spatial quality of the container replication process as we show analytically how the internal gene and metabolic kinetics determine the cell population's generation time and not the growth law (Burdett & Kirkwood 1983 J. Theor. Biol. 103, 11-20; Novak et al. 1998 Biophys. Chem. 72, 185-200; Tyson et al. 2003 Curr. Opin. Cell Biol. 15, 221-231). Previous extensive replication reaction kinetic studies have mainly focused on template replication and have not included a coupling to metabolic container dynamics (Stadler et al. 2000 Bull. Math. Biol. 62, 1061-1086; Stadler & Stadler 2003 Adv. Comp. Syst. 6, 47). The reported results extend these investigations. Finally, the coordinated exponential gene-container growth law stemming from catalysis is an encouraging circumstance for the many experimental groups currently engaged in assembling self-replicating minimal artificial cells (Szostak 2001 et al. Nature 409, 387-390; Pohorille & Deamer 2002 Trends Biotech. 20 123-128; Rasmussen et al. 2004 Science 303, 963-965; Szathma ry 2005 Nature 433, 469-470; Luisi et al. 2006 Naturwissenschaften 93, 1-13).     

Sensitivity in horseradish peroxidase neurohistochemistry: a comparative and quantitative study of nine methods.

Nine currently available methods for HRP neurohistochemistry have been compared with each other on matching tissue sections from four rats and four rhesus monkeys. The nine methods investigated in this report are the diaminobenzidine (DAB) procedures of LaVail JH and LaVail MM (J Comp Neurol 157:303, 1974), of Adams JC (Neuroscience 2:141, 1977) and of Streit P and Reubi JC (Brain Res 126:530, 1977); the benzidine dihydrochloride (BDHC) procedures of Mesulam M-M (J Histochem Cytochem 24:1273, 1976) and of De Olmos J and Heimer L (Neurosci Lett 6:107, 1977); the o-dianisidine (O-D) procedure of De Olmos J (Exp Brain Res 29:541, 1977); the p-phenylenediamine dihydrochloride and pyrocatechol (PPD-PC) procedure of Hanker JS et al., (Histochem J 9:789, 1977) and the tetramethyl benzidine (TMB) procedures of Mesulam M-M (J Histochem Cytochem 26:106, 1978) and of De Olmos J et al. (J Comp Neurol 181:213, 1978). Quantitative comparisons were based on counts of retrogradely labeled perikarya. The extent of anterograde transport and the size of the injection site were also compared at a more qualitative level. The results indicate that one TMB procedure (Mesulam M-M, J Histochem Cytochem 26:106, 1978) is distinctly superior to each of the other eight procedures in the number of labeled perikarya that it can demonstrate. Furthermore, these differences are statistically significant at better than the 0.05 level of confidence. Differences in sensitivity are most evident when the perikarya contain small quantities of transported HRP. The same TMB method also demonstrates more anterograde transport and a larger injection site than all the other procedures. If less sensitive procedures are employed, afferent or efferent connections that are clearly demonstrated by this TMB procedure are either underestimated or completely overlooked. It is suggested that sensitivity in HRP neurohistochemistry is determined by multiple factors which include the method of fixation, post-fixation storage, the choice of chromogen, the incubation parameters, the type of HRP enzyme that is administered, and the postreaction treatment.     

Unrestrained stochastic dynamics simulations of the UUCG tetraloop using an implicit solvation model.

Three unrestrained stochastic dynamics simulations have been carried out on the RNA hairpin GGAC[UUCG] GUCC, using the AMBER94 force field (Cornell et al., 1995. J. Am. Chem. Soc. 117:5179-5197) in MacroModel 5.5 (Mohamadi et al., 1990. J. Comp. Chem. 11:440-467) and either the GB/SA continuum solvation model (Still et al., 1990. J. Am. Chem. Soc. 112:6127-6129) or a linear distance-dependent dielectric (1/R) treatment. The linear distance-dependent treatment results in severe distortion of the nucleic acid structure, restriction of all hydroxyl dihedrals, and collapse of the counterion atmosphere over the course of a 5-ns simulation. An additional vacuum simulation without counterions shows somewhat improved behavior. In contrast, the two GB/SA simulations (1.149 and 3.060 ns in length) give average structures within 1.2 A of the initial NMR structure and in excellent agreement with results of an earlier explicit solvent simulation (Miller and Kollman, 1997. J. Mol. Biol. 270:436-450). In a 3-ns GB/SA simulation starting with the incorrect UUCG tetraloop structure (Cheong et al., 1990. Nature. 346:680-682), this loop conformation converts to the correct loop geometry (Allain and Varani, 1995. J. Mol. Biol. 250:333-353), suggesting enhanced sampling relative to the previous explicit solvent simulation. Thermodynamic effects of 2'-deoxyribose substitutions of loop nucleotides were experimentally determined and are found to correlate with the fraction of time the ribose 2'-OH is hydrogen bonded and the distribution of the hydroxyl dihedral is observed in the GB/SA simulations. The GB/SA simulations thus appear to faithfully represent structural features of the RNA without the computational expense of explicit solvent.     

Effects of heterogeneities on the partitioning of airway and tissue properties in normal mice.

We measured the mechanical properties of the respiratory system of C57BL/6 mice using the optimal ventilation waveform method in closed- and open-chest conditions at different positive end-expiratory pressures. The tissue damping (G), tissue elastance (H), airway resistance (Raw), and hysteresivity were obtained by fitting the impedance data to three different models: a constant-phase model by Hantos et al. (Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ. J Appl Physiol 72: 168-178, 1992), a heterogeneous Raw model by Suki et al. (Suki B, Yuan H, Zhang Q, Lutchen KR. J Appl Physiol 82: 1349-1359, 1997), and a heterogeneous H model by Ito et al. (Ito S, Ingenito EP, Arold SP, Parameswaran H, Tgavalekos NT, Lutchen KR, Suki B. J Appl Physiol 97: 204-212, 2004). Both in the closed- and open-chest conditions, G and hysteresivity were the lowest and Raw the highest in the heterogeneous Raw model, and G and H were the largest in the heterogeneous H model. Values of G, Raw, and hysteresivity were significantly higher in the closed-chest than in the open-chest condition. However, H was not affected by the conditions. When the tidal volume of the optimal ventilation waveform was decreased from 8 to 4 ml/kg in the closed-chest condition, G and hysteresivity significantly increased, but there were smaller changes in H or Raw. In summary, values of the obtained mechanical properties varied among these models, primarily due to heterogeneity. Moreover, the mechanical parameters were significantly affected by the chest wall and tidal volume in mice. Contribution of the chest wall and heterogeneity to the mechanical properties should be carefully considered in physiological studies in which partitioning of airway and tissue properties are attempted.     

Assessing model accuracy using the homology modeling automatically software

Homology modeling is a powerful technique that greatly increases the value of experimental structure determination by using the structural information of one protein to predict the structures of homologous proteins. We have previously described a method of homology modeling by satisfaction of spatial restraints (Li et al., Protein Sci 1997;6:956-970). The Homology Modeling Automatically (HOMA) web site, , is a new tool, using this method to predict 3D structure of a target protein based on the sequence alignment of the target protein to a template protein and the structure coordinates of the template. The user is presented with the resulting models, together with an extensive structure validation report providing critical assessments of the quality of the resulting homology models. The homology modeling method employed by HOMA was assessed and validated using twenty-four groups of homologous proteins. Using HOMA, homology models were generated for 510 proteins, including 264 proteins modeled with correct folds and 246 modeled with incorrect folds. Accuracies of these models were assessed by superimposition on the corresponding experimentally determined structures. A subset of these results was compared with parallel studies of modeling accuracy using several other automated homology modeling approaches. Overall, HOMA provides prediction accuracies similar to other state-of-the-art homology modeling methods. We also provide an evaluation of several structure quality validation tools in assessing the accuracy of homology models generated with HOMA. This study demonstrates that Verify3D (Luthy et al., Nature 1992;356:83-85) and ProsaII (Sippl, Proteins 1993;17:355-362) are most sensitive in distinguishing between homology models with correct or incorrect folds. For homology models that have the correct fold, the steric conformational energy (including primarily the Van der Waals energy), MolProbity clashscore (Word et al., Protein Sci 2000;9:2251-2259), and the PROCHECK G-factors (Laskowski et al., J Biomol NMR 1996;8:477-486) provide sensitive and consistent methods for assessing accuracy and can distinguish between homology models of higher and lower accuracy. As demonstrated in the accompanying paper (Bhattacharya et al., accompanying paper), combinations of these scores for models generated with HOMA provide a basis for distinguishing low from high accuracy models.     

Sensorimotor development in neonatal progesterone receptor knockout mice

Early exposure to steroid hormones can permanently and dramatically alter neural development. This is best understood in the organizational effects of hormones during development of brain regions involved in reproductive behaviors or neuroendocrine function. However, recent evidence strongly suggests that steroid hormones play a vital role in shaping brain regions involved in cognitive behavior such as the cerebral cortex. The most abundantly expressed steroid hormone receptor in the developing rodent cortex is the progesterone receptor (PR). In the rat, PR is initially expressed in the developmentally‐critical subplate at E18, and subsequently in laminas V and II/III through the first three postnatal weeks (Quadros et al. [2007] J Comp Neurol 504:42–56; Lopez & Wagner [2009]: J Comp Neurol 512:124–139), coinciding with significant periods of dendritic maturation, the arrival of afferents and synaptogenesis. In the present study, we investigated PR expression in the neonatal mouse somatosensory cortex. Additionally, to investigate the potential role of PR in developing cortex, we examined sensorimotor function in the first two postnatal weeks in PR knockout mice and their wildtype (WT) and heterozygous (HZ) counterparts. While the three genotypes were similar in most regards, PRKO and HZ mice lost the rooting reflex 2–3 days earlier than WT mice. These studies represent the first developmental behavioral assessment of PRKO mice and suggest PR expression may play an important role in the maturation of cortical connectivity and sensorimotor integration. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 16–24, 2014     

Helical growth of stage-IVb sporangiophores of <Emphasis Type="Italic">Phycomyces blakesleeanus</Emphasis>: the relationship between rotation and elongation growth rates

An understanding of the relationship between the two components of helical growth (rotation rate and elongation rate) is fundamental to understanding the biophysical and molecular mechanism(s) of cell wall extension in algal cells, fungal cells, and plant stems and roots. Helical growth occurs throughout development of the sporangiophores of Phycomyces blakesleeanus. Previous studies within the growth zone of stage-IVb sporangiophores have reported conflicting conclusions. An implicit assumption in the previous studies [E.S. Castle (1937) J Cell Comp Physiol 9:477-489; R. Cohen and M. Delbruck (1958) J Cell Comp Physiol 52:361-388; J.K.E. Ortega et al. (1974) Plant Physiol 53:485-490] was that the relationship between rotation rate and elongation rate was independent of the magnitude of the elongation rate. In the present study, for stage-IVb sporangiophores growing at a steady rate, it is shown that the ratio of rotation rate and elongation rate decreases as the elongation rate increases. Previously proposed biophysical and molecular mechanisms cannot account for the observed behavior. The previously postulated fibril-reorientation mechanism [J.K.E. Ortega and R.I. Gamow (1974) J Theor Biol 47:317-332; J.K.E. Ortega et al. (1974) Plant Physiol 53:485-490] is modified to accommodate this new finding. Other experiments were conducted to determine how the ratio of rotation rate and elongation rate behaves during a pressure response (a transient decrease in elongation rate produced by a large step-up in turgor pressure using the pressure probe). Results of these experiments indicate that this ratio increases during the pressure response.     

Molecular evolution of human immunodeficiency virus env in humans and monkeys: similar patterns occur during natural disease progression or rapid virus passage

Neonatal rhesus macaque 95-3 was inoculated with nonpassaged simian-human immunodeficiency virus strain SHIV-vpu(+), which encodes env of the laboratory-adapted human immunodeficiency virus (HIV) strain IIIB and is considered nonpathogenic. CD4(+) T-cell counts dropped to <200 cells/microl within 4.6 years, and monkey 95-3 died with opportunistic infections 5.9 years postinoculation. Transfer of blood from 95-3 to two naive adult macaques resulted in high peak viral loads and rapid, persistent T-cell depletion. Progeny virus evolved in 95-3 despite high SHIV-vpu(+) neutralizing antibody titers and still used CXCR4 but, in contrast to parental SHIV-vpu(+), productively infected macrophages and resisted neutralization. Sequence analysis revealed three new potential glycosylation sites in gp120; another two were lost. Strikingly similar mutations were detected in a laboratory worker who progressed to AIDS after accidental HIV-IIIB infection (T. Beaumont et al., J. Virol. 75:2246-2252, 2001), thus supporting the SHIV-vpu(+)/rhesus macaque system as a relevant model. Similar mutations were also described after rapid passage of chimeric viruses encoding IIIB env in rhesus and pig-tailed macaques (M. Cayabyab et al., J. Virol. 73:976-984, 1999; Z. Q. Liu et al., Virology 260:295-307, 1999; S. V. Narayan et al., Virology 256:54-63, 1999; R. Raghavan et al., Brain Pathol. 7:851-861, 1997; E. B. Stephens et al., Virology 231:313-321, 1997). Thus, HIV-IIIB env evolved similarly in three different species; this selection occurred in chronically infected individuals during disease progression as well as after rapid virus passage. We postulate that evolutionary pressure led to the outgrowth of more aggressive viral variants in all three species.     

Buckling of adaptive elastic bone-plate: theoretical and numerical investigation

During day-to-day activities, many bones in the axial and appendicular skeleton are subjected to repetitive, cyclic loading that often results directly in an increased risk of bone fracture. In clinical orthopedics, trabecular fatigue fractures are observed as compressive stress fractures in the proximal femur, vertebrae, calcaneus and tibia, that are often preceded by buckling and bending of microstructural elements (Müller et al. in J Biomechanics 31:150 1998; Gibson in J Biomechanics 18:317-328 1985; Gibson and Ashby in Cellular solids 1997; Lotz et al. in Osteoporos Int 5:252-261 1995; Carter and Hayes in Science 194:1174-1176 1976). However, the relative importance of bone density and architecture in the etiology of these fractures are poorly understood and consequently not investigated from a biomechanical point of view. In the present contribution, an attempt is made to formulate a bone-plate buckling theory using Cowin's concepts of adaptive elasticity (Cowin and Hegedus in J Elast 6:313-325 1976; Hegedus and Cowin J Elast 6:337-352 1976). In particular, the buckling problem of a Kirchhoff-Love bone plate is investigated numerically by using the finite difference method and an iterative solving approach (Chen in Comput Methods Appl Mech Eng 167:91-99 1998; Hildebland in Introduction to numerical analysis 1974; Richtmyer and Morton in Difference methods for initial-value problems 1967).     

The density and strength of proteoglycan-proteoglycan interaction sites in concentrated solutions.

Rheological flow properties of link-stable and link-free proteoglycan (PG) aggregates in concentrated solutions were measured using a cone-on-plate viscometer. A second-order constitutive model, based upon the statistical-network theories of Lodge, [Rheol. Acta 7, 379-392 (1968)] and De Kee and Carreau [J. Non-Newtonian Fluid Mech. 6, 127-143 (1979)], was developed to describe the measured steady and transient flow responses exhibited by the PG solutions. Our measurements confirmed previous experimental findings that the complex shear modulus of PG solutions depends on the frequency of the imposed small-amplitude oscillatory shear, and the apparent viscosity and primary normal-stress difference depend nonlinearly on the shear rate under steady-shear flow conditions [Mow et al., J. Biomechanics 17, 325-338 (1984b); Hardingham et al., J. orthop. Res. 5, 36-46 (1987)]. In the present study, we found that PG solutions exhibit pronounced stress overshoot responses and large hysteresis loop effects. These transient responses were shown to be sensitive to acceleration strain (i.e. the second rate of strain) as well as PG structure (i.e. link-protein stabilization). The model parameters were determined by curvefitting of the second-order constitutive model and experimental data from steady, oscillatory and transient shear flow measurements. Using this network model, we calculated the density of the idealized interaction sites existing in the PG network, and the average strength of these interaction sites. The results indicate that link-protein stabilization of PG aggregates does not change the density of interaction sites formed in the PG network, rather, it increases the average strength of these interaction sites.     

Comparative models for human apolipoprotein A-I bound to lipid in discoidal high-density lipoprotein particles

We have constructed a series of models for apolipoprotein A-I (apo A-I) bound to discoidal high-density lipoprotein (HDL) particles, based upon the molecular belt model [Segrest, J. P., et al. (1999) J. Biol. Chem. 274, 31755-31758] and helical hairpin models [Rogers, D. P., et al. (1998) Biochemistry 37, 11714-11725], and compared these with picket fence models [Phillips, J. C., et al. (1997) Biophys. J. 73, 2337-2346]. Molecular belt models for discoidal HDL particles with differing diameters are presented, illustrating that the belt model can explain the discrete changes in HDL particle size observed experimentally. Hairpin models are discussed for the binding of apo A-I to discoidal HDL particles with diameters identical to those for the molecular belt model. Two models are presented for the binding of three monomers of apo A-I to a 150 A diameter discoidal HDL particle. In one model, two monomers of apo A-I bind to the exterior of the HDL particle in an antiparallel belt, with a third monomer of apo A-I bound to the disk in a hairpin conformation. In the second model, all three monomers of apo A-I are bound to the discoidal HDL particle in a hairpin conformation. Previously published experimental data for each model are reviewed, with FRET favoring either the belt or hairpin models over the picket fence models for HDL particles with diameters of 105 A. Naturally occurring mutations appear to favor the belt model for the 105 A particles, while the 150 A HDL particles favor the presence of at least one hairpin.     

Maternal and fetal antibrain antibodies in development and disease

Recent evidence has emerged indicating that the maternal immune response can have a substantial deleterious impact on prenatal development (Croen et al., [2008]: Biol Psychiatry 64:583-588). The maternal immune response is largely sequestered from the fetus. Maternal antibodies, specifically immunoglobulin G (IgG), are passed to the fetus to provide passive immunity throughout much of pregnancy. However, both protective and pathogenic autoantibodies have equal access to the fetus (Goines and Van de Water [2010]: Curr Opin Neurol 23:111-117). If the mother has an underlying autoimmune disease or has reactivity to fetal antigens, autoantibodies produced before or during pregnancy can target tissues in the developing fetus. One such tissue is the fetal brain. The blood brainbarrier (BBB) is developing during the fetal period allowing maternal antibodies to have direct access to the brain during gestation (Diamond et al. [2009]: Nat Rev Immunol; Braunschweig et al. [2011]; Neurotoxicology 29:226-231). It has been proposed that brain injury by circulating brain-specific maternal autoantibodies might underlie multiple congenital, developmental disorders (Lee et al. [2009]: Nat Med 15:91-96). In this review, we will discuss the current state of research in the area of maternal autoantibodies and the development of autism. ? 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2012.