Creating a human head finite element model using a multi-block approach for predicting skull response and brain pressure

To better understand head injuries, human head finite element (FE) models have been reported in the literature. In scenarios where the head is directly impacted and measurements of head accelerations are not available, a high-quality skull model, as well as a high-quality brain model, is needed to predict the effect of impact on the brain through the skull. Furthermore, predicting cranial bone fractures requires comprehensively validated skull models. Lastly, high-quality meshes for both the skull and brain are needed for accurate strain/stress predictions across the entire head. Hence, we adopted a multi-block approach to develop hexahedral meshes for the brain, skull, and scalp simultaneously, a first approach in its kind. We then validated our model against experimental data of brain pressures (Nahum et al., 1977 Nahum AM, Smith R, Ward CC. 1977. Intracranial pressure dynamics during head impact. Proceedings of the 21st Stapp Car Crash Conference, SAE Paper No. 770922; Warrendale, PA: Society of Automotive Engineers.[Crossref] , [Google Scholar]) and comprehensive skull responses (Yoganandan et al., 1995 Yoganandan N, Pintar FA, Sances A, Jr., Walsh PR, Ewing CL, Thomas DJ, Snyder RG. 1995. Biomechanics of skull fracture. J Neurotrauma. 12(4):659–668.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar], Yoganandan et al., 2004 Yoganandan N, Zhang J, Pintar FA. 2004. Force and acceleration corridors from lateral head impact. Traffic Injury Prevention. 5(4):368–373.[Taylor &; Francis Online] , [Google Scholar], and Raymond et al., 2009 Raymond D, Van Ee C, Crawford G, Bir C. 2009. Tolerance of the skull to blunt ballistic temporo-parietal impact. J Biomech. 42(15):2479–2485.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). We concluded that a human head FE model was developed with capabilities to predict blunt- and ballistic-impact-induced skull fractures and pressure-related brain injuries.     

Computer simulations of the two-species model for the melting curve maximum

The existence of extrema, maximum and/or minimum and negative gradients of melting curves observed for several elements at high pressure is investigated by molecular dynamics simulation using the two-species model (TSM) proposed by Ogura et al. [1 OguraH, MatsudaH, OgawaT, OgitaN, UedaA. Computer simulation for the melting curve maximum phenomenon. Prog Theor Phys. 1977;58:419–433.[Crossref], [Web of Science ®] , [Google Scholar]]. TSM is a model which imitates the change in the electronic structure of an atom in terms of a species change in particles. The TSM phase diagram has two solid phases and one liquid phase with a solid–solid–liquid triple point which corresponds to the melting curve minimum. The melting curve has both a maximum and a minimum, and the gradient of the melting curve is negative between these extrema. These peculiar melting curve properties and phase diagram are common to alkali metals and some other elements.     

Evaluation of Bovine High-Density SNP Genotyping Array in Indigenous Dairy Cattle Breeds

In total 52 samples of Sahiwal (19 Excoffier L, Laval G, Schneider S. Arlequin 3.01: An integrated software package for population genetics data analysis. Evol Bioinform Online 2005; 1:47–50.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]), Tharparkar (17 Hayes BJ, Bowman PJ, Chamberlain, AJ, Goddard ME. Invited review: genomic selection in dairy cattle: progress and challenges. J Dairy Sci 2009; 92:433–443.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]), and Gir (16 Melka HD, Jeon EK, Kim SW, Han JB, Yoon D, Kim KS. Identification of genomic differences between Hanwoo and Holstein breeds using the Illumina Bovine SNP50 BeadChip. Genomics Inform 2011; 9:69–73.[Crossref] , [Google Scholar]) were genotyped by using BovineHD SNP chip to analyze minor allele frequency (MAF), genetic diversity, and linkage disequilibrium among these cattle. The common SNPs of BovineHD and 54K SNP Chips were also extracted and evaluated for their performance. Only 40%?50% SNPs of these arrays was found informative for genetic analysis in these cattle breeds. The overall mean of MAF for SNPs of BovineHD SNPChip was 0.248?±?0.006, 0.241?±?0.007, and 0.242?±?0.009 in Sahiwal, Tharparkar and Gir, respectively, while that for 54K SNPs was on lower side. The average Reynold’s genetic distance between breeds ranged from 0.042 to 0.055 based on BovineHD Beadchip, and from 0.052 to 0.084 based on 54K SNP Chip. The estimates of genetic diversity based on HD and 54K chips were almost same and, hence, low density chip seems to be good enough to decipher genetic diversity of these cattle breeds. The linkage disequilibrium started decaying (r²?相似文献   

Direct mass spectrometric characterization of disulfide linkages

Disulfide linkage is critical to protein folding and structural stability. The location of disulfide linkages for antibodies is routinely discovered by comparing the chromatograms of the reduced and non-reduced peptide mapping with location identification confirmed by collision-induced dissociation (CID) mass spectrometry (MS)/MS. However, CID product spectra of disulfide-linked peptides can be difficult to interpret, and provide limited information on the backbone region within the disulfide loop. Here, we applied an electron-transfer dissociation (ETD)/CID combined fragmentation method that identifies the disulfide linkage without intensive LC comparison, and yet maps the disulfide location accurately. The native protein samples were digested using trypsin for proteolysis. The method uses RapiGest SF Surfactant and obviates the need for reduction/alkylation and extensive sample manipulation. An aliquot of the digest was loaded onto a C₄ analytical column. Peptides were gradient-eluted and analyzed using a Thermo Scientific LTQ Orbitrap Elite mass spectrometer for the ETD-triggered CID MS³ Wypych J, Li M, Guo A, Zhang Z, Martinez T, Allen MJ, Fodor S, Kelner DN, Flynn GC, Liu YD, et al. Human IgG2 antibodies display disulfide-mediated structural isoforms. J Biol Chem. 2008;283:16194–205. doi:10.1074/jbc.M709987200. PMID:18339624[Crossref], [PubMed], [Web of Science ®] , [Google Scholar] experiment. Survey MS scans were followed by data-dependent scans consisting of ETD MS² scans on the most intense ion in the survey scan, followed by 5 MS³ CID scans on the 5 most intense ions in the ETD MS² scan. We were able to identify the disulfide-mediated structural variants A and A/B forms and their corresponding disulfide linkages in an immunoglobulin G2 monoclonal antibody with λ light chain (IgG2λ), where the location of cysteine linkages were unambiguously determined.     

Mercury risks versus nutritional benefits of tribal commercial fish harvests in the Upper Laurentian Great Lakes

The Inter-Tribal Fisheries and Assessment Program (ITFAP) of the Chippewa Ottawa Resource Authority (CORA) in Sault Ste. Marie, Michigan, has been monitoring contaminant concentrations in the fillet portions of lake trout (Salvelinus namaycush) and lake whitefish (Coregonus clupeaformis) from the waters of lakes Superior, Huron, and Michigan since 1991. The primary purpose of this article is to present a risk quantification of methylmercury (MeHg) that is adjusted for nutritional benefit, originally presented by Ginsberg and Toal (2009 Ginsberg GL and Toal BF. 2009. Quantitative approach for incorporating methylmercury risks and omega-3 fatty acid benefits in developing species-specific fish consumption advice. Environ Health Perspect 117:267–75[Crossref], [PubMed], [Web of Science ®] , [Google Scholar], 2015) on trends in contaminant concentrations in fillet portions of these commercial fish that we recently reported in Dellinger et al. (2014 Dellinger JA, Moths MD, Dellinger M, et al. 2014. Contaminant trends in freshwater fish from the Great Lakes: A 20 year analysis. Hum Ecol Risk Assess 20:461–78[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]). Both species of fish caught by tribal fishermen showed clear benefits to cardiovascular health and infant neurodevelopment if consumed at a rate of six ounces per week. However, other popularly consumed fish such as cod, tuna, and tilapia are estimated to have only marginal benefit or net negative effects on cardiovascular health and infant neurodevelopment. This dynamic assessment of benefits and risks further demonstrates the importance of traditionally caught fish in tribal health.     

Teaching Bernoulli's Principle through Demonstrations

ABSTRACT

One proven strategy to help students make sense of abstract concepts is to sequence instruction so students have exploratory opportunities to investigate science before being introduced to new science explanations (Abraham and Renner 1986 Abraham, M. R. and Renner, J. W. 1986. The sequence of learning cycle activities in high school chemistry. Journal of Research in Science Teaching, 23: 121–143. [Crossref], [Web of Science ®] , [Google Scholar]; Renner, Abraham, and Birnie 1988 Renner, J. W., Abraham, M. R. and Birnie, H. H. 1988. The necessity of each phase of the learning cycle in teaching high school physics. Journal of Research in Science Teaching, 25: 39–58. [Crossref], [Web of Science ®] , [Google Scholar]). To help physical science teachers make sense of how to effectively sequence lessons, this article summarizes our experiences using an exploration–explanation sequence of instruction to teach Bernoulli's principle to prospective middle and secondary science teachers in a science methods course. We use demonstrations during our Bernoulli unit to help students go back and forth between their observations of phenomenon and what occurs on the microscopic level with what we have termed molecular talk. Students engage in guiding questions, consider their old and new understandings of science, and use evidence to construct new ideas during all stages of the lesson.     

DNA binding,photocleavage, antimicrobial and cytotoxic properties of Ru(II) polypyridyl complexes containing BOPIP ligand, (BOPIP = {2-(4-(benzyloxy) phenyl)-1H-imidazo [4,5-f] [1,2]phenanthroline})

A novel ligand BOPIP (BOPIP?=?{2-(4-(benzyloxy)phenyl)-1H-imidazo[4,5-f][1,10]phenanthroline}) and its mononuclear Ru(II) polypyridyl complexes [Ru(phen)₂ BOPIP]²⁺(1) (phen?=?1,10-Phenanthrolene), [Ru(bpy)₂ BOPIP]²⁺(2) (bpy?=?2,2′ bipyridyl), [Ru(dmb)₂ BOPIP]²⁺(3) (dmb?=?4, 4′ -dimethyl 2, 2′ -bipyridine), [Ru(Hdpa)₂ BOPIP]²⁺(4) (Hdpa?=?2,2′dipyridylamine) have been synthesized successfully and characterized by elemental analysis, UV-vis, IR, ¹H, ¹³ Gill, M. R.; Garcia-Lara, J.; Foster, S. J.; Smythe, C.; Battaglia, G.; Thomas, J. A. A Ruthenium(II) polypyridyl Complex for Direct Imaging of DNA Structure in Living Cells. Nat. Chem. 2009, 1, 662–667.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]C-NMR, and ESI-MS Spectroscopy. The interaction of these complexes with CT-DNA was studied using absorption, emission techniques, viscosity measurements and molecular docking studies. The docking study also supports the binding ability of complexes obtained through the absorption and emission techniques. These studies reveal that the Four Ru(II) polypyridyl complexes bind to DNA predominantly by intercalation. The Antimicrobial activity and cytotoxicity of these complexes are also reported.     

TopBP1-mediated DNA processing during mitosis

Maintenance of genome integrity is crucial to avoid cancer and other genetic diseases. Thus faced with DNA damage, cells mount a DNA damage response to avoid genome instability. The DNA damage response is partially inhibited during mitosis presumably to avoid erroneous processing of the segregating chromosomes. Yet our recent study shows that TopBP1-mediated DNA processing during mitosis is highly important to reduce transmission of DNA damage to daughter cells.¹ Pedersen RT, Kruse T, Nilsson J, Oestergaard VH, Lisby M. TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells. J Cell Biol 2015; 210:565-82; PMID:26283799; http://dx.doi.org/10.1083/jcb.201502107[Crossref], [PubMed], [Web of Science ®] , [Google Scholar] Here we provide an overview of the DNA damage response and DNA repair during mitosis. One role of TopBP1 during mitosis is to stimulate unscheduled DNA synthesis at underreplicated regions. We speculated that such genomic regions are likely to hold stalled replication forks or post-replicative gaps, which become the substrate for DNA synthesis upon entry into mitosis. Thus, we addressed whether the translesion pathways for fork restart or post-replicative gap filling are required for unscheduled DNA synthesis in mitosis. Using genetics in the avian DT40 cell line, we provide evidence that unscheduled DNA synthesis in mitosis does not require the translesion synthesis scaffold factor Rev1 or PCNA ubiquitylation at K164, which serve to recruit translesion polymerases to stalled forks. In line with this finding, translesion polymerase η foci do not colocalize with TopBP1 or FANCD2 in mitosis. Taken together, we conclude that TopBP1 promotes unscheduled DNA synthesis in mitosis independently of the examined translesion polymerases.     

Salmonella Typhimurium methionine sulfoxide reductase A (MsrA) prefers TrxA in repairing methionine sulfoxide

Intraphagocytic survival of Salmonella Typhimurium (ST) depends (at least in part) upon its ability to repair oxidant-damaged macromolecules. Met residues either free or in protein bound form are highly susceptible to phagocyte-generated oxidants. Oxidation of Mets leads to Met-SO formation, consequently loss of protein functions that results in cell death. Methionine sulfoxide reductase (Msr) reductively repairs Met-SO to Met in the presence of thioredoxin (trx) and thioredoxin reductase (trxR). Earlier we reported that methionine sulfoxide reductase A (msrA) gene deletion strain of ST suffered oxidative stress.^[1 Trivedi, R.N.; Agarwal, P.; Kumawat, M.; Pesingi, P.K.; Gupta, V.K.; Goswami, T.K.; Mahawar, M. Methionine Sulfoxide Reductase A (MsrA) Contributes to Salmonella Typhimurium Survival Against Oxidative Attack of Neutrophils. Immunobiology 2015, 220(12), 1322–1327.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]^] Thioredoxin system of ST comprises of two thioredoxins (trxA and trxC) and one thioredoxin reductase (trxB). Preferred trx utilized in MsrA-mediated repair of Met-SO is not known. In current study, we cloned, expressed, and purified ST TrxA, TrxB, TrxC, and MsrA in recombinant forms. The migration of TrxA, TrxB, TrxC, and MsrA proteins was approximately 10, 36, 16, and 26?kDa on SDS-gels. The nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-linked reductase assays interpreted that MsrA utilized two times more NADPH for the reduction of S-methyl p-tolyl sulfoxide when TrxA was included in the assays as compared to TrxC.     

VEGF-A121a binding to Neuropilins – A concept revisited

All known splice isoforms of vascular endothelial growth factor A (VEGF-A) can bind to the receptor tyrosine kinases VEGFR-1 and VEGFR-2. We focus here on VEGF-A121a and VEGF-A165a, two of the most abundant VEGF-A splice isoforms in human tissue^{1 Kut C, Mac Gabhann F, Popel AS. Where is VEGF in the body? A meta-analysis of VEGF distribution in cancer. Br J Cancer. 2007;97:978-85. doi:10.1038/sj.bjc.6603923. PMID:17912242.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]}, and their ability to bind the Neuropilin co-receptors NRP1 and NRP2. The Neuropilins are key vascular, immune, and nervous system receptors on endothelial cells, neuronal axons, and regulatory T cells respectively. They serve as co-receptors for the Plexins in Semaphorin binding on neuronal and vascular endothelial cells, and for the VEGFRs in VEGF binding on vascular and lymphatic endothelial cells, and thus regulate the initiation and coordination of cell signaling by Semaphorins and VEGFs.^{2 Guo HF, Vander Kooi CW. Neuropilin Functions as an Essential Cell Surface Receptor. J Biol Chem. 2015;290:29120-6. doi:10.1074/jbc.R115.687327. PMID:26451046.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]} There is conflicting evidence in the literature as to whether only heparin-binding VEGF-A isoforms – that is, isoforms with domains encoded by exons 6 and/or 7 plus 8a – bind to Neuropilins on endothelial cells. While it is clear that VEGF-A165a binds to both NRP1 and NRP2, published studies do not all agree on the ability of VEGF-A121a to bind NRPs. Here, we review and attempt to reconcile evidence for and against VEGF-A121a binding to Neuropilins. This evidence suggests that, in vitro, VEGF-A121a can bind to both NRP1 and NRP2 via domains encoded by exons 5 and 8a; in the case of NRP1, VEGF-A121a binds with lower affinity than VEGF-A165a. In in vitro cell culture experiments, both NRP1 and NRP2 can enhance VEGF-A121a-induced phosphorylation of VEGFR2 and downstream signaling including proliferation. However, unlike VEGFA-165a, experiments have shown that VEGF-A121a does not ‘bridge’ VEGFR2 and NRP1, i.e. it does not bind both receptors simultaneously at their extracellular domain. Thus, the mechanism by which Neuropilins potentiate VEGF-A121a-mediated VEGFR2 signaling may be different from that for VEGF-A165a. We suggest such an alternate mechanism: interactions between NRP1 and VEGFR2 transmembrane (TM) and intracellular (IC) domains.     

Rotifers from a humic coastal lagoon of Rio de Janeiro State,Brazil

Abstract

A four-year study of species composition of the zooplankton community was conducted at Lagoa Comprida, a Brazilian coastal lagoon. Forty-two species of rotifers were recorded and illustrated. All rotifer species, except Lecane boettgeri Koste, 1986 and Macrochaetus kostei, José de Paggi, Branco &; Kozlowsky-Suzuki, 2000 José de Paggi, S, Branco, C WC and Kozlowsky-Suzuki, B. 2000. A new species of Macrochaetus (Rotifera, Trichotriidae) in a coastal lagoon of Rio de Janeiro State (Brazil). Stud Neotrop Fauna &; Environm, 35: 157–160. [Taylor &; Francis Online], [Web of Science ®] , [Google Scholar], have already been found in other areas of Brazil. Some factors, which probably favored the dominant richness and density of rotifers in the zooplankton community, are discussed.     

Novel therapeutic interventions for p53-altered tumors through manipulation of its family members,p63 and p73

TP53 is highly mutated in human cancers, thus targeting this tumor suppressor pathway is highly desirable and will impact many cancer patients.^1,2 Iwakuma T, Lozano G, Flores ER. Li-Fraumeni syndrome: a p53 family affair. Cell Cycle 2005; 4:865-7; PMID:15917654; http://dx.doi.org/10.4161/cc.4.7.1800 Muller PA, Vousden KH. p53 mutations in cancer. Nat Cell Biol 2013; 15:2-8; PMID:23263379; http://dx.doi.org/10.1038/ncb2641  Therapeutic strategies to reactivate the p53-pathway have been challenging,^3,4 Martins CP, Brown-Swigart L, Evan GI. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006; 127:1323-34; PMID:17182091; http://dx.doi.org/10.1016/j.cell.2006.12.007 Ventura A. Restoration of p53 function leads to tumour regression in vivo. Nature 2007; 445:661-5; PMID:17251932; http://dx.doi.org/10.1038/nature05541  and no effective treatment exists.⁵ Khoo KH, Verma CS, Lane DP. Drugging the p53 pathway: understanding the route to clinical efficacy. Nat Rev Drug Discov 2014; 13:217-36; PMID:24577402; http://dx.doi.org/10.1038/nrd4288[Crossref], [PubMed], [Web of Science ®] , [Google Scholar] We utilized the p53-family members, p63 and p73, which are not frequently mutated in cancer, to treat p53-defective cancers. The N-terminal splice variants of p63 and p73 are denoted as the TA and ΔN isoforms. We recently demonstrated that deletion of either ΔNp63 or ΔNp73 in p53-deficient mouse tumors results in tumor regression mediated by metabolic programming. Using this strategy, we identified pramlintide, a synthetic analog of amylin, as an effective treatment for p53 deficient and mutant tumors. Here, we show the utility of using pramlintide, as a potential cancer preventive option for p53-deficient tumors in mouse models. Additionally, we found that in vivo inhibition of both ΔNp63 and ΔNp73 in combination accelerates tumor regression and increases survival of p53-deficient mice. We report that inhibition of both ΔNp63 and ΔNp73 in combination results in upregulation of 3 key metabolic regulators, IAPP, GLS2, and TIGAR resulting in an increase in apoptosis and tumor regression in ΔNp63/ΔNp73/p53 deficient thymic lymphomas. These data highlight the value of generating inhibitors that will simultaneously target ΔNp63 and ΔNp73 to treat cancer patients with alterations in p53.     

Integrative taxonomy of the cave-dwelling mysids of the genus Hemimysis

The genus Hemimysis (Malacostraca: Mysida: Mysidae) encompasses near-bottom, demersal and cave-dwelling mysids living in the marine, brackish and freshwater habitats around the European coast, from the Caspian Sea to the Scandinavian Peninsula. We conducted cladistic analysis of 52 morphological characters of all nine species and three subspecies of the genus Hemimysis. We also completed a molecular analysis based on three molecular markers of Hemimysis lamornae (Couch, 1856) found in the English Channel, the Mediterranean Sea, and the Black Sea. Both analyses did not support monophyly of Hemimysis lamornae. We thus consider the former subspecies H. lamornae pontica (Czerniavsky, 1882 Chevaldonné, P., &; Lejeusne, C. (2003). Regional warming‐induced species shift in north‐west Mediterranean marine caves. Ecology Letters, 6, 371–379. doi:10.1046/j.1461-0248.2003.00439.x.[Crossref], [Web of Science ®] , [Google Scholar]) and H. lamornae mediterranea Bacescu, 1936 Bacescu, M. (1936). Hemimysis lamornae sbsp. reducta, nov. sbsp. et Hemimysis anomala dans les eaux roumaines de la Mer Noire (avec une etude comparative des forms de Hem. lamornae des autres mers: H. l. typica et H.l. mediterranea, nov. sbsp.). Annales Scientifiques de L’Universite de Jassy, 23, 331–338. [Google Scholar] as valid species. Analysis of mitochondrial cytochrome oxidase subunit I (COI) sequences of H. pontica shows no significant divergence between mysids living in the marine caves of Crimea and Bulgaria. Morphological trends in Hemimysis are discussed, H. pontica Czerniavsky, 1882 Chevaldonné, P., &; Lejeusne, C. (2003). Regional warming‐induced species shift in north‐west Mediterranean marine caves. Ecology Letters, 6, 371–379. doi:10.1046/j.1461-0248.2003.00439.x.[Crossref], [Web of Science ®] , [Google Scholar] is redescribed, and a new key to all 11 species of the genus is given.     

Calibration of a Linear Free Energy Estimation Approach for Estimating Stability Constants for Metal-Bacterial Surface Complexes

In this study, we use the measured extent of metal adsorption onto bacterial cells to constrain a linear free energy relationship that allows estimation of unknown stability constants for metal-bacterial surface complexes based on the value of corresponding aqueous metal-acetate stability constants. A previous study (Fein et al., 2001 Fein, J B, Martin, A M and Wightman, P G. 2001. Metal adsorption onto bacterial surface: Development of a predictive approach. Geochim Cosmochim Acta, 65: 4267–4273. [Crossref], [Web of Science ®] , [Google Scholar]) used metal adsorption experiments to constrain a similar relationship, but the experiments were conducted using acid-washed bacteria, and subsequent evidence (Borrok et al., 2004a Borrok, D, Fein, J B, Tischler, M, O'Loughlin, E, Meyer, H, Liss, M and Kemner, K M. 2004a. The effect of acidic solutions and growth conditions on the adsorptive properties of bacterial surfaces. Chem Geol, 209: 107–119. [Crossref], [Web of Science ®] , [Google Scholar]) shows that the acid-washing step affects the extent of adsorption of a number of metals onto bacterial surfaces. We measured the adsorption of Zn, Ni, Co, Sr, and Nd onto Bacillus subtilis in 0.1 M NaClO₄ as a function of pH and metal:bacterial site ratio, using a non-electrostatic discrete four-site model of the bacterial protonation reactions as a basis for the metal adsorption modeling. The adsorption of the divalent cations (Zn, Ni, Co, and Sr) could best be modeled by considering adsorption reactions involving three sites on the bacterial surface; we used a one-site model to account for the Nd data that covered a more restricted pH range. The calculated stability constants for metal-Site 2 bacterial surface complexes are used to re-calibrate the linear free energy relationship previously defined by Fein et al. (2001) Fein, J B, Martin, A M and Wightman, P G. 2001. Metal adsorption onto bacterial surface: Development of a predictive approach. Geochim Cosmochim Acta, 65: 4267–4273. [Crossref], [Web of Science ®] , [Google Scholar]. There is a significant difference between the original and the re-calibrated lines for weakly binding cations such as Sr^{2 +}, but the difference becomes negligible for the stronger-binding cations. Because the linear free energy relationship defined in this study was calibrated from experiments that involved bacteria that were not exposed to acidic conditions, the estimated stability constant values that result from using this relationship are likely to reasonably reflect bacterial adsorption behaviors that occur in realistic geologic settings.     

The molecular mechanism of Atg13 function in autophagy induction: What is hidden behind the data?

Atg13 is an essential subunit of the Atg1 autophagy initiation complex in yeast and its mammalian counterpart, ATG13, is indispensable for autophagy induction by the ULK1 complex. The N terminus of the protein folds into a HORMA domain, an architecture that has been revealed by crystallography.^1-4 Jao CC, Ragusa MJ, Stanley RE, Hurley JH. A HORMA domain in Atg13 mediates PI 3-kinase recruitment in autophagy. P Natl Acad Sci USA 2013; 110:5486-91; PMID:23509291; http://dx.doi.org/10.1073/pnas.1220306110 Suzuki SW, Yamamoto H, Oikawa Y, Kondo-Kakuta C, Kimura Y, Hirano H, Ohsumi Y. Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation. P Natl Acad Sci USA 2015; 112:3350-5; PMID:25737544; http://dx.doi.org/10.1073/pnas.1421092112 Suzuki H, Kaizuka T, Mizushima NNoda NN. Structure of the Atg101-Atg13 complex reveals essential roles of Atg101 in autophagy initiation. Nat Struct Mol Biol 2015; 22:572-81; PMID:26030876; http://dx.doi.org/10.1038/nsmb.3036 Qi SQ, Kim DJ, Stjepanovic G, Hurley JH. Structure of the human Atg13-Atg101 HORMA heterodimer: An interaction hub within the Ulk1 complex. Structure 2015; 23:1848-57; PMID:26299944; http://dx.doi.org/10.1016/j.str.2015.07.011  In human cells, the ATG13 HORMA domain interacts directly with ATG14, a subunit of the class III phosphatidylinositol 3-kinase complex.⁵ Park JM, Jung CH, Seo M, Otto NM, Grunwald D, Kim KH, Moriarity B, Kim YM, Starker C, Nho RS, et al. The Ulk1 complex mediates mTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating Atg14. Autophagy 2016; 12:547-64; PMID:27046250; http://dx.doi.org/10.1080/15548627.2016.1140293[Taylor & Francis Online], [Web of Science ®] [Google Scholar] In budding yeast, the HORMA domain of Atg13 recruits Atg14, but a direct interaction remains to be proven.¹ Jao CC, Ragusa MJ, Stanley RE, Hurley JH. A HORMA domain in Atg13 mediates PI 3-kinase recruitment in autophagy. P Natl Acad Sci USA 2013; 110:5486-91; PMID:23509291; http://dx.doi.org/10.1073/pnas.1220306110[Crossref], [PubMed], [Web of Science ®] [Google Scholar] The amino acid sequence that follows the HORMA domain does not adopt any 3-dimensional structure on its own; therefore, it is termed an intrinsically disordered region (IDR). Here we discuss the results of 2 recent studies in light of previous reports on Atg13 from yeast. Together, they yield an insight into the molecular mechanism for the function of this intriguing protein, and reveal why Atg13, as well as the mammalian homolog ATG13, cannot have a structurally rigid architecture.     

Behind the potential evolution towards prion resistant species

Historically, the observation of naturally occurring cases of prion disease led to the classification of different susceptibility grades and to the designation of prion resistant species. However, the development of highly efficient in vitro prion propagation systems and the generation of ad hoc transgenic models allowed determining that leporidae and equidae families have been erroneously considered resistant to prion infection. On the contrary, similar approaches revealed an unexpected high level of resistance of the canidae family. In PLoS Pathogens [1 Fernandez-Borges N, Parra B, Vidal E, et al. Unraveling the key to the resistance of canids to prion diseases. PLoS Pathog. 2017;13:e1006716. doi:10.1371/journal.ppat.1006716. eCollection 2017 Nov. PMID: 29131852[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]], we describe experiments directed toward elucidating which are the determinants of the alleged prion resistance of this family. Studies based on the sequence of the canine prion protein coupled with structural in silico analysis identified a key residue probably implicated in this resistance. Cell and brain-based PMCA highlighted that the presence of aspartic or glutamic acid at codon 163 of the canid PrP, strongly inhibits prion replication in vitro. Transgenic animals carrying this substitution in mouse PrP were resistant to prion infection after intracerebral challenge with different mouse prion strains. The confirmation of the importance of this substitution and its exclusivity in this family, suggests it could have been evolutionarily favored, due to their diet based on carrion and small ruminants.     

Translational control of gurken mRNA in Drosophila development

Localized mRNA translation is a widespread mechanism for targeting protein synthesis, important for cell fate, motility and pathogenesis. In Drosophila, the spatiotemporal control of gurken/TGF-α mRNA translation is required for establishing the embryonic body axes. A number of recent studies have highlighted key aspects of the mechanism of gurken mRNA translational control at the dorsoanterior corner of the mid-stage oocyte. Orb/CPEB and Wispy/GLD-2 are required for polyadenylation of gurken mRNA, but unlocalized gurken mRNA in the oocyte is not fully polyadenylated.¹ Norvell A, Wong J, Randolph K, Thompson L. Wispy and Orb cooperate in the cytoplasmic polyadenylation of localized gurken mRNA. Dev Dyn Off Publ Am Assoc Anat 2015; 244:1276-1285. [Google Scholar] At the dorsoanterior corner, Orb and gurken mRNA have been shown to be enriched at the edge of Processing bodies, where translation occurs.² Weil TT, Parton RM, Herpers B, Soetaert J, Veenendaal T, Xanthakis D, Dobbie IM, Halstead JM, Hayashi R, Rabouille C, et al. Drosophila patterning is established by differential association of mRNAs with P bodies. Nat Cell Biol 2012; 14:1305-1313; PMID:23178881; http://dx.doi.org/10.1038/ncb2627[Crossref], [PubMed], [Web of Science ®] [Google Scholar] Over-expression of Orb in the adjacent nurse cells, where gurken mRNA is transcribed, is sufficient to cause mis-expression of Gurken protein.³ Davidson A, Parton RM, Rabouille C, Weil TT, Davis I. Localized translation of gurken/TGF-α mRNA during axis specification is controlled by access to Orb/CPEB on processing bodies. Cell Rep 2016; 14:2451-2462; PMID:26947065; http://dx.doi.org/10.1016/j.celrep.2016.02.038[Crossref], [PubMed], [Web of Science ®] [Google Scholar] In orb mutant egg chambers, reducing the activity of CK2, a Serine/Threonine protein kinase, enhances the ventralized phenotype, consistent with perturbation of gurken translation.⁴ Wong LC, Costa A, McLeod I, Sarkeshik A, Yates J 3rd, Kyin S, Perlman D, Schedl P, et al. The functioning of the drosophila CPEB protein Orb is regulated by phosphorylation and requires casein kinase 2 activity. PLoS One 2011; 6:e24355; PMID:21949709; http://dx.doi.org/10.1371/journal.pone.0024355[Crossref], [PubMed], [Web of Science ®] [Google Scholar] Here we show that sites phosphorylated by CK2 overlap with active Orb and with Gurken protein expression. Together with our new findings we consolidate the literature into a working model for gurken mRNA translational control and review the role of kinases, cell cycle factors and polyadenylation machinery highlighting a multitude of conserved factors and mechanisms in the Drosophila egg chamber.     

Tyr(less) kinase signaling during mitosis

Tyrosine phosphorylation is rare, representing only about 0.5% of phosphorylations in the cell under basal conditions. While mitogenic tyrosine kinase signaling has been extensively explored, the role of phosphotyrosine signaling across the cell cycle and in particular during mitosis is poorly understood.

Two recent, independent studies tackled this question from different angles to reveal exciting new insights into the role of this modification during cell division. Caron et al.¹ Caron D, Byrne DP, Thebault P, Soulet D, Landry CR, Eyers PA, Elowe S. Mitotic phosphotyrosine network analysis reveals that tyrosine phosphorylation regulates Polo-like kinase 1 (PLK1). Sci Signal 2016; 9:rs14; PMID:27965426; http://dx.doi.org/10.1126/scisignal.aah3525[Crossref], [PubMed], [Web of Science ®] [Google Scholar] exploited mitotic phosphoproteomics data sets to determine the extent of mitotic tyrosine phosphorylation, and St-Denis et al.² St-Denis N, Gupta GD, Lin ZY, Gonzalez-Badillo B, Veri AO, Knight JD, Rajendran D, Couzens AL, Currie KW, Tkach JM, et al. Phenotypic and interaction profiling of the human phosphatases identifies diverse mitotic regulators. Cell Rep 2016; 17:2488-501; PMID:27880917; http://dx.doi.org/10.1016/j.celrep.2016.10.078[Crossref], [PubMed], [Web of Science ®] [Google Scholar] identified protein tyrosine phosphatases from all subfamilies as regulators of mitotic progression or spindle formation. These studied collectively revealed that tyrosine phosphorylation may play a more prominent and active role in mitotic progression than previously appreciated.