OR15-5 Human Sex Determination at the Edge of Ambiguity: Impaired SRY Phosphorylation Attenuates Expression of the Male Program

A paradox is posed by metazoan gene-regulatory networks (GRNs) that are robust yet evolvable. Insight may be obtained through studies of bistable genetic circuits mediating developmental decisions. A model in organogenesis is provided by the sex-specific differentiation of the embryonic gonadal ridge to form a testis or ovary. Here, we investigated a Swyer mutation in human testis-determining factor SRY that impairs its phosphorylation in association with variable developmental outcomes: fertile male, intersex, or infertile female (46, XY pure gonadal dysgenesis). The mutation (R30I) abrogates serine phosphorylation within a putative target site for protein kinase A (PKA) N-terminal to the HMG box. Diverse processes can be regulated by protein phosphorylation, including DNA recognition by transcription factors (TFs). Phosphorylation of this site in human SRY (LRRSSSFLCT; italics) in vitro was previously shown to enhance specific DNA affinity. Biological consequences of the mutation were evaluated in SRY-responsive mammalian cell lines following transient transfection. The mutation attenuated in concert occupancy of a target enhancer (TESCO) and SOX9 transcriptional activation. These perturbations were mitigated by acidic substitution (LRIDDDFL) whereas Ala substitutions (RRAAAFL or RIAAAFL) attenuated activity to an extent similar to R30I alone. No differences were observed in nuclear localization. Mutagenesis suggested that the central Ser is most efficiently phosphorylated in accord with PKA targeting rules. Replacement of the native site by an optimized “Kemptide” PKA site (LRRASLGCT) enhanced both SRY phosphorylation and SOX9 transcriptional activation whereas a “swapped” protein-kinase C determinant (LRRSSFRRCT) blocked phosphorylation. Among SRY variants, extent of cellular phosphorylation mirrored relative in vitro efficiencies of synthetic SRY-derived peptides as PKA-specific substrates. Although several kinases are predicted in silico to target this tri-serine motif, cell-based studies implicate PKA as the relevant kinase in vivo. Our results provide evidence that primate Sry requires its phosphorylation for full gene-regulatory activity. A PKA site N-terminal to the SRY HMG box, unique to primates, exemplifies network “tinkering” through recruitment of a new regulatory linkage. Molecular characterization of the R30I inherited Swyer mutation in SRY thus demonstrates that impaired TF phosphorylation can attenuate a human developmental switch at the edge of ambiguity

Some models of crack growth in brittle materials

This work is devoted to the study of models of fractures growth in brittle elastic materials; it collects the results obtained during my Ph.D., that are contained in [77, 76, 78]. We consider quasi-static rate-independent models, as well as rate-dependent ones and the case in which the first ones are limits of the second ones when certain physical parameters vanish. The term quasistatic means that, at each instant, the system is assumed to be in equilibrium with respect to its time-dependent data; this setting is typical of systems whose internal time scale is much smaller than that of the loadings. By rate-independent system we mean that, if the time-dependent data are rescaled by a strictly monotone increasing function, then the system reacts by rescaling the solutions in the same manner

21st Century Trends in Conversation Concerning Women’s Roles in the Stone-Campbell Movement: 2000–2017

This study examined the trends in conversation concerning women’s roles within two streams of the Stone-Campbell Movement, the Churches of Christ and the Christian Churches/Churches of Christ, within the twenty-first century. In addition, it explored possible answers to the emerging questions from the study through thoughtful analysis, comparison, and observation of the present trends in conversation. The data were accumulated, organized, charted, and analyzed by researching every article and issue of the primary publication of each stream, The Christian Chronicle and The Christian Standard, to gauge the intensity and attention given to the issue. While there were no significant answers provided to the raised questions generated from the trends, the analysis of the trends yields powerful results and helps guide the direction of future studies on this topic

Discrimination of human and dog faces and inversion responses in domestic dogs (Canis familiaris)

Although domestic dogs can respond to many facial cues displayed by other dogs and humans, it remains unclear whether they can differentiate individual dogs or humans based on facial cues alone and, if so, whether they would demonstrate the face inversion effect, a behavioural hallmark commonly used in primates to differentiate face processing from object processing. In this study we first established the applicability of the Visual Paired Comparison (VPC or preferential looking) procedure for dogs using a simple object discrimination task with 2D pictures. The animals demonstrated a clear looking preference for novel objects when simultaneously presented with prior-exposed familiar objects. We then adopted this VPC procedure to assess their face discrimination and inversion responses. Dogs showed a deviation from random behaviour, indicating discrimination capability when inspecting upright dog faces, human faces and object images; but the pattern of viewing preference was dependent upon image category. They directed longer viewing time at novel (vs. familiar) human faces and objects, but not at dog faces, instead, a longer viewing time at familiar (vs. novel) dog faces was observed. No significant looking preference was detected for inverted images regardless of image category. Our results indicate that domestic dogs can use facial cues alone to differentiate individual dogs and humans, and that they exhibit a non-specific inversion response. In addition, the discrimination response by dogs of human and dog faces appears to differ with the type of face involved

Does Faceted Ice Growth Follow a Characteristic Pattern

Under certain heat conditions, ice crystals can form differently from the snowflakes that generally grow. Instead of attaching on the boundaries of a plane of ice, under these conditions, new water molecules will permeate a quasi-liquid layer above the ice that causes them to attach closer to the center of the plane and build up from there. These ice formations are close to cylindrical with patterns of roughness on the sides and top at the micrometer scale. The growth can be modeled with a system of partial differential equations that is similar to a reaction diffusion system. This project tries to fit the roughness on the ice to a Turing Pattern, a common phenomenon in reaction diffusion systems. This was done first by finding existing Turing Pattern models and altering them to fit the ice model. Then the pattern was assumed and parameters were tested for how they influence the frequency of roughness

Darboux Approach to Mα-integration

It is known that one can develop Riemann integration theory via Darboux approach. Themain idea in the Darboux approach is to define an integral using upper and lower Riemannsums. In this study we look at how -integration can be develop via Darboux approach.Here is a brief discussion of the methodology. We define an equivalence relation on the set of-divisions of , - such that for - divisions *(, - )+ and *(, - )+ wesay that if and only if the intervals in are exactly the intervals in . Given agauge on , - and a -fine division *(, - )+ of , -, we set, - * + Given a function on , -, and a -fine - division , we define the upper and lowersums (respectively) in the following manner( ) , -( ) ( )( ) and ( ) , -( ) ( )( )provided these values exists. We were able to show that a function on , - is -ntegrable if and only if the following exists and are equal:() ∫̅̅̅̅̅ ( ) and () ∫ ( ) In this approach we were able to prove the basic properties of the -integral. It is our nextgoal to extend -integration to other spaces via Darboux approach

SIMCOL – A Decision Support System for integrated control of anthracnose on blue lupin

Für das Pathosystem Anthraknose an Lupine wurde das wetterbasierte Entscheidungshilfesystem (EHS) SIMCOL entwickelt. SIMCOL prognostiziert temperaturbasiert die Entwicklung des Lupinenbestandes als BBCH-Stadien und empfiehlt auf der Basis von Temperatur, relativer Luftfeuchte, Niederschlag und schlagspezifischen Informa­tionen eine Bekämpfungsstrategie für die Anthraknose (Colletotrichum lupini) an Blauer Lupine (Lupinus angusti­folius). Das EHS besteht aus den 3 folgenden Modellen: –SIMONTO-Lupine: Berechnung des BBCH-Verlaufs von L. angustifolius, –SIMCOL1: Berechnung des Befallsbeginns, –SIMCOL3: Berechnung gefährlicher Infektionsperioden und Planung der Fungizidstrategie mit einem Fungizidmodul (Faktoren für den Einfluss des Saatgutbefalls und der Beizung wurden zusätzlich integriert). Für die Analyse des Pathosystems und die Modellerstellung wurden folgende Daten verwendet: –Daten von Klimaschrankversuchen zur Untersuchung der Zusammenhänge zwischen Temperatur, Blattnässe­dauer, Pflanzenentwicklung und Krankheitsentwicklung als Basis zur Modellierung der Krankheitseffizienz, –Literaturdaten zur Entwicklung des Modells SIMONTO-Lupine, –Historische Monitoringdaten zur Krankheitsentwicklung im Feld für die Modellvalidierung, –Spezielle Laboruntersuchungen zur Untersuchung der Fungizidwirkung auf die Krankheitsentwicklung zur Modellierung eines Faktors, der die Fungizidwirkung abbildet. Die Validierung von SIMCOL1 und SIMONTO-Lupine wurde mit unabhängigen Daten der Pflanzenschutzdienste der Länder Brandenburg, Mecklenburg-Vorpommern und Sachsen-Anhalt, sowie der Saatzucht Steinach, dem Julius Kühn-Institut und der ZEPP durchgeführt und hat gute Ergebnisse geliefert. Das EHS steht ab der Saison 2011 der landwirtschaftlichen Praxis über die Beratung als auch im Bereich der Saatguterzeugung zur Verfügung.    The weather-based decision support system (DSS) SIMCOL for the anthracnose – lupin pathosystem was developed. SIMCOL forecasts the lupin growth development on the basis of temperature (in form of BBCH growth stages) and recommends based on temperature, relative humidity, precipitation and field specific information a control strategy for anthracnose (Colletotrichum lupini) of blue lupin (Lupinus angustifolius). The DSS consists of the following 3 models: –SIMONTO-Lupin: simulation of the BBCH development of L. angustifolius, –SIMCOL1: calculation of the first disease occurrence and the beginning of the treatment in the field, –SIMCOL3: calculation of dangerous infectious periods and scheduling of treatments with the help of a fungicide module (factors for the influence of seed contami­nation and seed treatment were also integrated). For the analysis of the pathosystem and the modelling the following data-sets were used: –Data from climate chambers to study the relationship between temperature, leaf wetness duration, plant growth stage and disease development. These data were used as a basis for the modelling of the disease efficiency, –Literature data for the development of the SIMONTO-Lupin model, –Historical data of field disease development from moni­toring activities for the models validation, –Specific laboratory experiments to analyse the effect of fungicides on the disease development to obtain a fungicide efficacy factor. The validation of SIMCOL1 and SIMONTO-Lupin was carried out with independent data from the Govern­mental Crop protection services of the federal states Brandenburg, Mecklenburg-Western Pomerania and Saxony-Anhalt, the seed breeder Saatzucht Steinach, the Julius Kühn-Institut (Federal Research Centre for Cultivated Plants) and the ZEPP and delivered good results. The DSS is available since the season 2011 for advisory activities of the Governmental Crop protection services and for the seed producers.   &nbsp