Haut PDF Cell morphology and nucleoid dynamics in dividing Deinococcus radiodurans

Cell morphology and nucleoid dynamics in dividing Deinococcus radiodurans

Cell morphology and nucleoid dynamics in dividing Deinococcus radiodurans

Finally, we compared the number and distribution of the oriC and ter loci of chromosome 1 as a function of the cell cycle. As previously reported 25 , there were significantly more oriC foci in cells than ter sites irrespective of the stage of the cell cycle. This has been proposed to result from differences in the duration of periods of transient cohesion of the oriC and ter loci from the various copies of chromosome 1 after replication—this period being longer for ter—and/or a very late replication of ter com- pared with oriC 25 . Our cartography of the localizations of oriC and ter loci in D. radiodurans at each phase of the cell cycle also revealed very distinct distribution patterns for the two loci and allow us to propose a first model for nucleoid organization and choreography in a coccus bacterium possessing a complex, mul- ticopy genome (Fig. 7 ). Chromosome arrangement in D. radio- durans is neither longitudinal nor transversal, but instead radial with oriC sites distributed all around centrally located ter sites. The ter loci were clearly retained and clustered by a yet unknown mechanism in the central region of the cells until just before cytokinesis (Fig. 7 b, c). ter foci could indeed still be seen in the small gap formed by the closing septal doors in Phase 5 cells. Segregation of replicated ter loci occurred at a very late stage of the cell cycle (Phase 5; Fig. 7 c) and the duplicated ter loci then progressively migrated to the centre of the two new sister cells. In contrast, oriC loci localized throughout the cell, with the exclu- sion from membrane proximal regions, ruling out any direct anchoring of oriC loci to the cell walls as has been observed in some bacteria 51 – 53 . Further work will be needed to understand
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Variabilité génétique chez la bactérie radiorésistante Deinococcus radiodurans : la recombinaison entre séquences répétées et la transformation naturelle

Variabilité génétique chez la bactérie radiorésistante Deinococcus radiodurans : la recombinaison entre séquences répétées et la transformation naturelle

Summary The bacterium Deinococcus radiodurans is known for its ability to withstand a large number of genotoxic treatments, including exposure to ionizing or ultraviolet radiation, mitomycin C, desiccation, and oxidative stress. It is able, upon exposure to extreme doses of γ-radiation generating hundreds of DNA breaks, to reconstitute an intact genome in only 2 to 3 hours via an ESDSA mechanism, involving massive DNA synthesis during DNA double strand break repair. Together with efficient DNA repair mechanisms, D. radiodurans possesses a survival kit comprising significant compaction of its nucleoid, protection mechanisms against protein oxidation, an original response to DNA damage and specific proteins induced after irradiation. All of these contribute to the maintenance of genomic integrity and cell survival upon exposure to various genotoxic agents. In spite of the idea that D. radiodurans is an organism with outstanding genomic stability, this bacterium has in its genome a large number of repeat sequences and mobile elements and is also naturally competent. All these factors contribute to the genetic variability of species. I was interested in two processes that can play a role in genetic variability in D. radiodurans: recombination between repeated sequences and natural transformation.
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PprA Protein Is Involved in Chromosome Segregation via Its Physical and Functional Interaction with DNA Gyrase in Irradiated Deinococcus radiodurans Bacteria

PprA Protein Is Involved in Chromosome Segregation via Its Physical and Functional Interaction with DNA Gyrase in Irradiated Deinococcus radiodurans Bacteria

After irradiation, DNA is shattered into hundreds of fragments. Even after reconsti- tution of circular chromosomes, irradiated cells are expected to contain a large amount of relaxed DNA that might pointlessly recruit DNA gyrase. The PprA protein, by its localization through the septum after completion of DNA repair (21, 50), might facili- tate, by its interaction with GyrA, relocalization of the DNA gyrase at the septum. It has been shown that PprA polymerizes along dsDNA (23). Thus, we can also propose that PprA, like the MukB condensin in E. coli, may remodel the DNA and generate a preferred substrate for DNA gyrase and, thus, that the PprA-GyrA interaction might increase the effective rate of DNA decatenation. In nonirradiated cells, PprA is expressed at a low basal level and is not detected by immunofluorescence microscopy. Moreover, its absence has no effect on the viability and the morphology of cells that divide normally (21). Thus, we can imagine that, like E. coli Topo IV, whose decatenation activity is regulated through a physical interaction of the ParC subunit with FtsK, MreB, or MukB (51–53), the decatenation activity of deinococcal DNA gyrase could be regulated by its interaction with key proteins involved in chromosome segregation or cell division. FtsK and SMC (structural maintenance of chromosome), a functional analog of MukB, are present in D. radiodurans, but unlike the rod-shaped Deinococcus deserti bacteria,
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Nanoscale surface structures of DNA bound to Deinococcus radiodurans HU unveiled by atomic force microscopy.

Nanoscale surface structures of DNA bound to Deinococcus radiodurans HU unveiled by atomic force microscopy.

The Deinococcus radiodurans protein HU (DrHU) was shown to be critical for nucleoid activities, yet its functional and structural properties remain largely unexplored. We have applied atomic force microscopy (AFM) imaging to study DrHU binding to pUC19-DNA in vitro and analyzed the topographic structures formed at the nanoscale. At the single-molecule level, AFM imaging allows visualization of super-helical turns on naked DNA surfaces and characterization of free DrHU molecules observed as homodimers. When enhancing the molecular surface structures of AFM images by the Laplacian weight filter, the distri- bution of bound DrHUs was visibly varied as a function of the DrHU/DNA molar ratio. At a low molar ratio, DrHU binding was found to reduce the volume of condensed DNA con figuration by about 50%. We also show that DrHU is capable of bridging distinct DNA segments. Moreover, at a low molar ratio, the binding orientation of individual DrHU dimers could be perceived on partially “open” DNA configuration. At a high molar ratio, DrHU sti ffened the DNA molecule and enlarged the spread of the open DNA configuration. Furthermore, a lattice-like pattern could be seen on the surface of DrHU –DNA complex, indicating that DrHU multimerization had occurred leading to the formation of a higher order architecture. Together, our results show that the functional plasticity of DrHU in mediating DNA organization is subject to both the conformational dynamics of DNA molecules and protein abundance.
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PprA : une protéine clé dans la radiorésistance chez Deinococcus radiodurans

PprA : une protéine clé dans la radiorésistance chez Deinococcus radiodurans

a b s t r a c t Deinococcus radiodurans, one of the most radioresistant organisms known to date is able to reconstruct an intact genome from hundreds of DNA fragments. Here, we investigate the in vivo role of PprA, a radiation- induced Deinococcus specific protein. We report that DNA double strand break repair in cells devoid of PprA and exposed to 3800 Gy ␥-irradiation takes place efficiently with a delay of only 1 h as compared to the wild type, whereas massive DNA synthesis begins 90 min after irradiation as in the wild type, a phenotype insufficient to explain the severe radiosensitivity of the pprA mutant. We show that the slow kinetics of reassembly of DNA fragments in a pprA recA double mutant was the same as that observed in a recA single mutant demonstrating that PprA does not play a major role in DNA repair through RecA- independent pathways. Using a tagged PprA protein and immunofluorescence microscopy, we show that PprA is recruited onto the nucleoid after ␥-irradiation before DNA double strand break repair completion, and then is found as a thread across the septum in dividing cells. Moreover, whereas untreated cells devoid of PprA displayed a wild type morphology, they showed a characteristic cell division abnormality after irradiation not found in other radiosensitive mutants committed to die, as DNA is present equally in the two daughter cells but not separated at the division septum. We propose that PprA may play a crucial role in the control of DNA segregation and/or cell division after DNA double strand break repair.
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Stability of the cell dynamics in acute myeloid leukemia

Stability of the cell dynamics in acute myeloid leukemia

In this paper we analyze the global asymptotic stability of the trivial solution for a multi-stage maturity acute myeloid leukemia model. By employing the positivity of the corresponding nonlinear time-delay model, where the nonlin- earity is locally Lipschitz, we establish the global exponential stability under the same conditions that are necessary for the local exponential stability. The result is derived for the multi-stage case via a novel construction of linear Lyapunov functionals. In a simpler model of hematopoiesis (without fast self-renewal) our conditions guarantee also global exponential stability with a given decay rate. Moreover, in this simpler case the analysis of the PDE model is presented via novel Lyapunov functionals for the transport equations.
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Live-Cell Chromosome Dynamics and Outcome of X Chromosome Pairing Events during ES Cell Differentiation

Live-Cell Chromosome Dynamics and Outcome of X Chromosome Pairing Events during ES Cell Differentiation

This hemizygous PGKT1 clone was then used to generate ES cells in which both Xic loci were tagged for visualization. Initially, targeting of the second Xic locus was attempted using a targeting construct containing a Lac operator (LacO) array. However, this failed despite repeated attempts. Instead, we generated Xic TetO homozygous cells by treating the hemizygous PGKT1 cells using increased G418 selection ( Figure 1 B) ( Mortensen et al., 1992 ). One of the clones obtained (PGKT2) was found to have two X chromosomes, each of which carried a TetO-tagged Xic locus based on Southern blotting and DNA FISH on metaphase spreads ( Figures S1 B–S1D). A TetR-mCherry fusion protein construct was introduced into the PGKT2 cell line as a stable transgene to enable visualization of the two Xic TetO loci ( Fig- ure 1 B). In this clone (PGKT2-TetR), two TetR-mCherry foci could be readily detected by fluorescence microscopy ( Fig- ure S1 E and Movie S1 ). The two TetR-mCherry foci corre- sponded to the TetO-tagged Xics as they systematically colocal- ized with punctate Xist/Tsix RNA FISH signals in undifferentiated ES cells ( Figure S1 E). Upon differentiation of PGKT2-TetR cells, monoallelic Xist RNA accumulation was observed with similar kinetics to the parental line ( Figure 1 D). We conclude that the presence of the TetO tag within each of the Xic loci and the expression of the TetR-mCherry protein in PGKT2-TetR cells
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Mutation of Ser172 in yeast β tubulin induces defects in microtubule dynamics and cell division.

Mutation of Ser172 in yeast β tubulin induces defects in microtubule dynamics and cell division.

of the b tubulin Ser172 residue in cell physiology using the yeast S. cerevisiae. Although Ser172 phosphorylation in yeast has not been detected yet, we demonstrate that mutation of the Ser172 residue (replaced either by an Alanine or a Glutamic Acid) has profound effects on microtubule properties and on cell cycle parameters. Figure 3. Nuclear movements are inhibited in SA and SE cells prior to anaphase. WT, SA and SE cells were transformed with a plasmid expressing GFP-Tub1p, and were analyzed by time-lapse microscopy. (A) Representative WT and SA pre-anaphase cells for which the bud-directed SPB was tracked at each time point of the time-lapse experiment. The track is overlaid in red on an image of the movie. Scale bar, 3 mm. Movies available in supplementary Figure S1. (B) Measurement of the travel distance covered by the bud-directed SPB in pre-anaphase cells over a period of 15–30 min (results are normalized in mm/min). Comparing to WT strain, spindle movements were reduced in both mutant strains. Number of analyzed cells: WT, n = 19; SA, n = 15; SE, n = 17. Error bars are SEM. ** p,0.01, *** p,0.001, t test comparisons of mutant cells vs. WT cells.
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Modeling Dynamics of Cell-to-Cell Variability in TRAIL-Induced Apoptosis Explains Fractional Killing and Predicts Reversible Resistance

Modeling Dynamics of Cell-to-Cell Variability in TRAIL-Induced Apoptosis Explains Fractional Killing and Predicts Reversible Resistance

important fraction of cells died fast (MOMP in ,2 hours) but 40% were still alive after 8 hours (Fig. 3C), illustrating the fractional killing property. Also, cell fate inheritance between sister cells was markedly changed: only young sister cells that underwent MOMP rapidly were importantly correlated (Fig. 4B, grey curve). We asked whether the observed cell fate variability, including fractional killing, could be reproduced in-silico. Within our modeling assumptions, absence of co-treatment with CHX makes a fundamental difference: as synthesis continues, the effect of gene expression noise during TRAIL-induced apoptosis could be investigated, and comparison with the TRAIL and CHX condition is insightful. Strikingly, we found that quantitative Figure 2. Standard stochastic protein turnover models. (A) Schematic description of the reactions constituting the stochastic protein turnover model. Gene activity switches, mRNA production and degradation (red arrows) are stochastic reactions. Protein synthesis and degradation reactions (black arrows) are deterministic. (B) For typical mRNA and protein half-lives, promoter switching rates have a limited influence on the protein level half-autocorrelation time: using an analytical derivation of the protein level autocorrelation function (see Supplementary Results, Text S1), the protein half-autocorrelation time is plotted against mean promoter switching times. (C) Behavior of a standard stochastic protein turnover model. Promoter switching rates respect typical ranges observed by Suter et al. [36] and lead to a protein level coefficient of variation (CV) of 0.25. See Fig. S3 for more details. Upper plots show three representative single-cell time courses of protein and mRNA levels. Histogram at the bottom displays the corresponding distribution of protein level obtained when simulating a large number of cells for a long duration, corresponding to a snapshot of the cell-to-cell variability expected in a population.
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Thin metal films on weakly-interacting substrates : Nanoscale growth dynamics, stress generation, and morphology manipulation

Thin metal films on weakly-interacting substrates : Nanoscale growth dynamics, stress generation, and morphology manipulation

In the present work, we combine in situ film growth monitoring, ex situ characterization, and optical modeling in the framework of the finite-difference time-domain (FDTD) method to study the effect of nitrogen (N 2 ) gas surfactant on growth evolution of nanoscale silver (Ag) islands and films on silicon dioxide (SiO 2 ) substrates, with the purpose of exploring the viability of surfactant-based approaches for metal-contact synthesis. We show that N2 presence during the early film- growth stages suppresses the rate of island coalescence, which favors 2D morphology and formation of flat films. Furthermore, for later growth stages beyond coalescence, N2 causes interruption of crystal growth, which leads to grain refinement and increases the resistivity of continuous layers. FDTD calculations confirm that monitoring of the localized surface plasmon resonance (LSPR) via spectroscopic ellips- ometry can be a powerful tool to track and control in real time the early stage morphological evolution of ultrathin metal films and supported nanostructures on weakly interacting substrates. Using the insights presented above, we design and implement growth manipulation experiments in which N 2 is deployed selectively during specific growth stages. Early deployment only during the initial growth stages leads to decrease of coalescence rate and roughness development at the fi lm growth front, without compromising the film electrical resistivity. On the contrary, postcoalescence N2 deployment leads to pronounced increase in film roughness. This knowledge opens the way for growth strategies in which surfactant species will be deployed with high temporal and spatial precision to target critical film formation stages and manipulate growth morphologies, without altering the film physical properties. Moreover, targeted surfactant deployment can be used to tune the size of supported 3D nanostructures without the need to employ elevated growth temperatures and postdeposition annealing steps.
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Positioning the flagellum at the center of a dividing cell to combine bacterial division with magnetic polarity

Positioning the flagellum at the center of a dividing cell to combine bacterial division with magnetic polarity

L ⫽ 冑 D⁄k. For inactivation by phosphorylation or dephosphory- lation, this length scale can be in the submicron range (25), cor- responding to a fraction of the cell size. In the classical scheme of polar division, the localization of a flagellum at the pole opposite that of the old flagellum can thus be accomplished by the localized activation of a negative regulator or inhibitor of flagellar assembly near the old flagellum (or the localized inactivation of a positive regulator) (Fig. 4A). Evidence for such a gradient has been re- ported for C. crescentus, where, however, the developmental pro- gram is more complex due to the presence of the stalked stage (25). In turn, positioning the new flagellum in the cell center close to the septum requires a double gradient from both poles, e.g., by activation of the inhibitor both at the old flagellum and at the opposite pole. An example of such a gradient is the bipolar gradi- ent distribution of MipZ in C. crescentus (26), which organizes cell division and localization of cellular components, including the
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Typology of the flow structures in dividing open channel flows

Typology of the flow structures in dividing open channel flows

HAL Id: hal-01724972 https://hal.archives-ouvertes.fr/hal-01724972 Submitted on 1 Apr 2019 HAL is a multi-disciplinary open access archive for the deposit and dissemination of sci- entific research documents, whether they are pub- lished or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.

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Impact of physical confinement on nuclei geometry and cell division dynamics in 3D spheroids

Impact of physical confinement on nuclei geometry and cell division dynamics in 3D spheroids

3D analysis of cell division axis orientation within spheroids. As our findings indicated that nuclei between 0 and 100 µm from the surface are preferentially elongated and orientated parallel to the spheroid sur- face, we asked whether the cell division axis orientation was also parallel to the spheroid surface. The cell division axis is defined as the axis perpendicular to the metaphase plate. As the probability to detect a mitotic cell in the plane of the section is very low in spheroid cryosections, we performed this analysis using 3D images. To optimize the detection of metaphases, we monitored mitotic cells by time-lapse LSFM in spheroids made of HCT116 cells that express a histone H2B-mCherry fusion protein (Supplementary Movie 1). The achieved image resolution allowed us to distinguish metaphase plates (see Supplementary Movie 2). To determine the divi- sion axis orientation, we developed a procedure described in details in the Methods section. Briefly, the metaphase plate is segmented and represented as a 3D surface by a thin and homogeneous ellipsoid, flattened along one axis (Fig.  3a ) and the descriptive parameters (the x, y and z coordinates of the mass centre and the x, y and z coordinates of the three orthogonal axes) are extracted. Then, the orientation of the division axis is determined by calculating the angle of the shortest axis of the ellipsoid with reference to the normal to the tangent at the closest point to the spheroid convex hull (Fig.  3a ). Using this method, we observed that, in freely grown spheroids, the division axis was preferentially parallel to the surface (median angle = 74.7°) in most mitotic cells (Fig.  3b ).
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Network-selectivity and stimulus-discrimination in the primary visual cortex : cell-assembly dynamics

Network-selectivity and stimulus-discrimination in the primary visual cortex : cell-assembly dynamics

Similarity Pattern of Cross-correlograms (Network stability) To ascertain that the revealed functional connections are indeed an outcome of specific coordinated activity between neurons rather than the result of random fluctuations, some neuron pairs recorded simultaneously were tested two times; that is, a particular test feature presentation was repeated after almost an hour. Two recordings were tested twice, i.e., four sites. Fourteen neurons were sorted from these recordings. An example of two simultaneously recorded neurons from a tip (red and blue waveforms) with their respective responses (raster and PSTH) at both attempts is shown in Fig. 12A. The black arrow pointing downwards indicates the presentation of stimulus. The CCG at each attempt in Fig. 12B points that the red neuron projects onto the blue neuron in either case with noticeable similarity. In both attempts, the significant peak appeared at the same time (+ 4 ms, green line) with P equaling 1.4%. An example of network that remains similar (same connections with similar P) in both attempts between three simultaneously recorded neurons is shown in Fig. 12C. A few connected neuron pairs (n = 26) were pooled, and no significant difference (paired t-test, P = 0.24) was found between the peak-probability at both attempts (Fig. 12D). This suggests that neurons establish specific functional connections in relation to a particular input that remain constant over time within an assembly, as suggested by Miller et al (2014).
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Actin dynamics in the cell cytoplasm and the role of actin associated proteins

Actin dynamics in the cell cytoplasm and the role of actin associated proteins

The state of the actin cycle is specified by any three of the following parameters: the average length of filaments, the rate of filament turnover, the fraction of actin polymerized, [r]

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Cell cycle dynamics and the physiology of saxitoxin biosynthesis in Alexandrium fundyense (dinophyceae)

Cell cycle dynamics and the physiology of saxitoxin biosynthesis in Alexandrium fundyense (dinophyceae)

In a previous study targeting the identification of up- and downregulated genes during toxigenesis in the toxic dinoflagellate Alexandrium fundyense, a gene for a putative [r]

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New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo

New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo

Classifying Cellular Compartments According to Metabolite Diffusion: Neurons vs. Astrocytes. The morphometric statistics resulting from the best fit of experimental ADC (averaged over cohorts) for all five metabolites in the two species are reported in Table 1. Some syn- thetic cells corresponding to the best fits are reported in Fig. 2. In this initial work, we used exactly the same model to generate the synthetic cells associated with each metabolite, because we did not want to associate metabolites with a specific cellular compartment a priori. For example, we did not introduce additional long axons that could be relevant for neuronal Glu and NAA. The rationale is that we wanted to assess the ability of our strategy to differentiate between astrocytic and neuronal metabolites based on their diffu- sion properties only, without differences imposed by different models. In this context, it is striking that the cellular compartments extracted for all five metabolites match the presumed cell-specific compartmentation: Ins and tCho, which are often thought to be mainly in astrocytes, are indeed associated with the smallest synthetic cells, whereas Glu and NAA, which are mainly in neurons, are associated with the largest synthetic cells. Within each animal species, astrocytic and neuronal metabolites are discriminated according to the L segment statistics for both species ( SI Appendix, Section IV and Tables S3 and S4 for statistical significances). Cellular compartments associated with astrocytic metabolites are also less complex (i.e., their processes exhibit a lower degree of ramification, as quantified by N branch ) than the ones associated with
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Nominal morphology and syntax

Nominal morphology and syntax

1 SG - HOD . PST 9.calabash CON 9 6.water give. HOD . PST NP 9 -big LOC 19.child ‘I gave the BIG water calabash to the child.’ Recall that the augment is a renewal of agreement morphology, that cycles of augment creation and disappearance are likely to have occurred and that eventually all agreement markers within the noun phrase must have started as demonstratives used to nominalise adnominal modifiers. v Consequently, the structure of the noun phrase in contemporary languages can be the result of cycles of appositional extraposition of modifiers followed by subsequent reintegration, giving rise to multiple layers of modifiers around a nuclear NP. This scenario should be tested in a thorough comparative study, which should pay special attention to prosodic clues for the syntactically layered nature of Bantu NPs. In loose apposition, an anchor is typically separated from the appositive by means of a prosodic boundary, as O’Connor & Patin (2015) have demonstrated for Ngazidja G44a. Differences between types of modifiers in prosodic bonding with their head in the Bantu languages could be reflexes of such boundaries. In Binza C321, for instance, there is high tone dissimilation with the last syllable of a nuclear NP ( N ( ADJ )) on a following demonstrative or possessive pronoun, but
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A maternal western diet during gestation and lactation modifies offspring's microglial cell density and morphology in the hippocampus and prefrontal cortex in Yucatan minipigs

A maternal western diet during gestation and lactation modifies offspring's microglial cell density and morphology in the hippocampus and prefrontal cortex in Yucatan minipigs

In a previous paper in the minipig model, we showed that maternal Western diet during gestation and lactation decreased hippocampus neurogenesis and food-rewarded cognitive abilities in the progeny. Whether these alterations are concomitant with a central inflammatory process in brain structures involved in learning and memory (hippocampus, HPC), cognitive (prefrontal cortex, PFC), or hedonic (orbitofrontal cortex, OFC) control of food intake is still unknown. In the present study, Yucatan minipigs (Sus scrofa) sows were exposed to two different diets during gestation and lactation (standard, SD N=7 vs. Western diet, WD N=9). Iba1 is a calcium-binding protein specifically expressed in microglia in the brain, which plays an important role in the regulation of the microglia function. Iba1 expression was examined by immunohistochemical analyses in the PFC, OFC and HPC of piglets. The density of microglial cells, as well as their morphology, were assessed in order to have an indirect insight of microglial cell activation state possibly in relationship with neuroinflammation. The density of Iba1-positive cells was higher in the PFC but not in the HPC of WD compared to SD piglets (p<0.001). In the HPC, anterior and dorsolateral PFC, WD piglets had more unipolar cells, contrary to SD that had more multipolar cells (P<0.0001). Opposite effects were observed in the OFC, with SD presenting more unipolar (P<0.001) microglial cells compared to WD. We showed here that maternal diet during pregnancy and lactation had significant effects on morphological changes of microglial cells in the offspring, and that these effects differed between the HPC and PFC, suggesting different response mechanisms to the early nutritional environment.
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Anterior dental loading and root morphology in Neanderthals

Anterior dental loading and root morphology in Neanderthals

Moskowitsch and Smith, 1993). On the one hand, interactions with the environment and manipulation of food would exert selective constraints acting on the anterior part of the mandible. On the other hand, comminution of the food particles would represent the major selective factor on the posterior part of the lower jaw. Following the theory by Moss and Rankow (1968), the teeth represent the functional matrix, which the growth of the alveolar process depends on. This is in agreement with Daegling’s (1996) ¿ndings on mandibular growth in gorillas and chimpanzees. In other words, and as stated by Dean and Beynon (1991), the space available in the jaws for the developing teeth is determined by the jaw growth pattern. Emphasizing how narrow the anterior portion of the U-shaped mandible in great apes is, these authors explain how an increased antero- posterior cross-sectional area of the symphysis allows for the accommodation of the tooth germs in the alveolar bone. This has been investigated using Finite Element Analysis on Macaca fascicularis by Cobb and Panagiotopoulou (2011), who demonstrated that the spatial requirement for the developing incisors can constrain the future adult morphology and the functional adaptation of the symphysis. In light of our results in root size and cross-sectional symphyseal size, one could speculate that the evenly thick symphysis of the Neanderthals is adapted to accommodate the development and the migration of the anterior tooth germs that will eventually give rise to permanent large-rooted teeth. This hypothesis is in agreement with Tillier (1996), suggesting that the morphological variability observed in the posterior surface of the symphysis in the Roc de Marsal and Pech de l’Azé Neanderthal children may be related to the position of the developing permanent incisors in the bone. Bastir et al. (2007) also propose that the observed differences in shape trajectories of the alveolar region of the Neanderthal mandible could be related to ontogenetic differences in the maturation of the teeth. Fig. 7 illustrates this hypothesis, showing juvenile and adult modern humans with a tear-drop shaped symphyseal section, while the juvenile and adult Neanderthals show a pillar shaped symphysis. Note the wider permanent tooth germ in the Neanderthal child compared with the modern human, where the slender germ is located LQDZHOOGH¿QHG crypt, and underneath a noticeable amount of cancelous bone.
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