, 2002) These mechanisms indicate that the metabolism of BPA is

, 2002). These mechanisms indicate that the metabolism of BPA is faster and the conjugation more efficient in humans, where enterohepatic recirculation is negligible, than in rats. However, strain differences has been reported, and in female Fischer 344 (F 344) rats the excretion via urine was 42%, selleck and twice as high as in CD rats (21%) (Snyder et al., 2000). The efficient

conjugation and relatively low BPA-exposure are the main reasons why BPA is considered to be safe to humans despite a notable amount of animal studies demonstrating effects on various outcomes and in various doses. One mechanism to further evaluate is the action of the β-glucoronidase enzyme present GSI-IX in vivo within many tissues, notably e.g. the placenta of animals and humans. β-Glucoronidase deconjugates BPA to its active form which may lead to fetal exposure in the uterus (Ginsberg and Rice, 2009). There has been a focus on BPA as an endocrine disruptor because of its estrogenicity, while there also might be other mechanisms that explain the effects of BPA seen in various studies. Prenatal exposure to BPA in rodents has previously been shown to induce obesity (Miyawaki et al., 2007, Somm et al., 2009 and Wei

et al., 2011), and the effect of exposure to BPA later in life has recently been studied by e.g. Marmugi et al. (2012). But there is an inconsistency regarding BPA exposure and weight gain since other studies show no significant effects despite

exposure over generations in the environmentally relevant doses (Ema et al., 2001, Tyl et al., 2008 and Tyl et al., 2002). In order to study effects of BPA in doses in the range of tolerable daily intake (TDI) we have used three exposure levels, the medium dose being close to TDI as established by the U.S. Environmental Protection Agency (EPA) and the European Food Safety Authority (EFSA) at 50 μg/kg and day. The low dose was 10 times lower and the high dose 10 times higher than the medium dose. The primary aim of this study was to test the hypothesis that exposure to BPA in combination with carbohydrates after the sensitive prenatal and perinatal periods also could affect fat mass or liver fat content. Sorafenib cell line Since exposure to BPA only, later in life (Marmugi et al., 2012) and perinatal exposure to BPA in combination with high fat diet later in life (Wei et al., 2011) have been reported, this study will focus on exposure to BPA in combination with a diet supplemented with carbohydrates. As fructose is a widely used sweetener in processed food and has been suggested to contribute to unfavorable metabolic alterations (Bocarsly et al., 2010 and Bremer et al., 2012) juvenile rats were exposed to BPA in combination with a 5% fructose solution, which is about the same fructose concentration as in common soft drinks (9–13% sucrose).

Icy, an open source image analysis platform, also provides a plug

Icy, an open source image analysis platform, also provides a plug-in for viewing and editing tracks (de Chaumont et al., 2012). Performance evaluation, also referred as performance analysis, in image analysis compares the results obtained from an automated procedure against the manually established ‘ground truth’. Herein, a ground truth track represents

the ‘true’ positions of a cell as a sequence of bounding boxes. We used the Video Performance Evaluation Resource (ViPER) software (Doermann and Mihalcik, 2000) to manually draw bounding boxes around cells in each video frame and index the sequences of bounding boxes corresponding click here to each individual cell to designate tracks. Performance evaluation metrics were employed to quantitatively and comprehensively assess the detection and tracking performance of TIAM and the third-party tools. We used the Sequence Frame Metabolism inhibitor Detection Accuracy (SFDA) and Average Tracking Accuracy (ATA) metrics (Kasturi et al.,

2009) as these can be computed in a fully automated fashion and thus allow for reproducible quantification of the success of detection and tracking of objects. Further, they do not suffer from the risk of human error or bias. These metrics have been adopted as standardized metrics by the Video Analysis and Content Extraction (VACE) program (http://marathon.csee.usf.edu/vace-links.html) and the Classification of Events, Activities, and Relationships

(CLEAR) consortium (www.clear-evaluation.org); which are two large-scale and community-wide efforts concerned with video tracking and interaction analysis. The metrics are based on Jaccard Similarity (Fig. S5 for intuitive illustration and and Supplementary methods for mathematical description). In order to compute SFDA and ATA, a one-to-one correspondence between ground truth Liothyronine Sodium and result must be established. To establish this mapping we employed the Hungarian algorithm (Munkres, 1957) with metrics based on Jaccard Similarity used to construct the similarity matrix (see Supplementary methods for details). We have consolidated the software routines to carry out performance analysis in a separate MATLAB-based suite that we call PACT (Performance Analysis of Cell Tracking). The PACT code, its user guide and relevant ground truth datasets are available at https://github.com/willieneis/TIAM/tree/master/PACT/. The user guide also includes specific instructions on using ViPER for ground truth annotation. Performance of feature extraction was also evaluated against ground truth. Outlines drawn manually or by semi-automated procedures in ImageJ (Schneider et al., 2012) were listed as ROIs and used as ground truth (see Supplementary methods for details). A one-to-one correspondence between individual cells in ground truth and TIAM result was obtained using the Hungarian algorithm (Munkres, 1957).

Most proteomic quantitative analyses are thus based on isotope la

Most proteomic quantitative analyses are thus based on isotope labeling, which consists

in the introduction of a mass tag (i.e., heavy or light) to differentiate identical peptides from various samples in MS owing to a mass shift. Isotope labeling can be done at various levels (i.e., cell, protein, peptide) on different reactive groups (i.e., cysteine, lysine containing residues) and allow sample multiplexing. During the past years, Dabrafenib nmr several methods were developed including stable isotope metabolic labeling for cultured cells (SILAC), isotope-coded affinity tags (ICAT) or isobaric tagging technologies either using tandem mass tags (TMT) [216] and [217] or isobaric tags for relative and absolute quantification (iTRAQ)

[218] and [219]. In isobaric labeling, the total mass of the tag is kept constant owing to a mass normalizer group, and identical peptides from different samples sharing the same chromatographic properties co-elute in the mass spectrometer. Labeled peptides thus appear at the same mass in an MS scan, but give rise to low mass reporter signature ions upon CID fragmentation in MS/MS mode (i.e., between 126 and 131 m/z for TMT-6). This robust approach has been one of the most beneficial for the analysis of body fluids and tissues as it allows the simultaneous peptide identification and quantification of up to 10 samples in a single MS/MS experiment. The comprehensive find protocol analysis of specific PTMs known to be important for PD, such as oxidation, nitration, phosphorylation, glycosylation or ubiquitination Carbachol can also be addressed. Generally, proteomes of interest are specifically enriched before being analyzed by MS quantitative techniques. Alternatively, peptides with defined PTMS can be targeted based on their MS

fragmentation characteristics (i.e., neutral loss, multiple reaction monitoring MS modes). Selected Reaction Monitoring (SRM) allows the targeting and measurement of selected signature peptides from molecules of interest (reviewed in [220]). Given its unique potential to quantify reliably low abundant analytes in complex mixtures, SRM may represent an alternative to ELISA for clinical validation measurements which are dependent on antibody availability. Importantly, absolute quantification can be obtained through AQUA method, with the spiking of a known quantity of an isotope- labeled peptide as an internal standard, followed by SRM MS analysis [221]. To date, the clinical management of PD patients is still hampered by the lack of reliable diagnostic and therapeutic biomarkers which might pave the way for the development of better options and PD treatment and prevention. Traditional candidate-based studies have assessed the potential of specific targets typically associated to PD pathophysiology as biomarkers of PD, for example the CSF level of α-SYN.

The authors thank Prof Dr Norberto P Lopes for the HRESIMS ana

The authors thank Prof. Dr. Norberto P. Lopes for the HRESIMS analyses. This research was supported by grants from FAPESP (BIOprospecTA Proc. 04/07942-2, 06/57122-6), CNPq (472870/2004-1), and INCT-Imunologia. M.S.P., R.R.N. and C.F.T. are researchers for the Brazilian Council for Scientific and Technological Development (CNPq). “
“Envenomations by freshwater stingrays are characterized by intense pain and pathological alterations

at the injury site. These include edema, erythema and, in most cases, necrosis selleck kinase inhibitor (Haddad et al., 2004). The damage is caused by the stinger located in the back of the stingray tail, which is used by the animal to defend itself (Charvet-Almeida et al., 2002 and Garrone Neto et al., 2007). Integumentary and glandular tissues cover the stinger where the toxins are produced (Pedroso et al., 2007). The anatomical regions most afflicted in injuries caused by stingrays are the hands and feet (Haddad et al., 2004, Brisset et al., 2006, Lim and Kumarasinghe, 2007 and Garrone Neto and Haddad, 2009). Lethal injuries rarely check details occur except for cases where the stinger reaches vital organs (Isbister, 2001 and Garrone Neto and Haddad, 2009). Specific antivenom is not available for the treatment of stingray injuries, and the therapeutic approach is based on the use of analgesic and anti-inflammatory drugs, hot water to relieve the excruciating pain and antibiotics to prevent secondary

infection (Haddad et al., 2004, Clark et al., 2007, Dehghani et al., 2009 and Garrone Neto and Haddad, 2010). In Brazil, the distribution of freshwater stingrays has gradually

increased due to environmental alterations mainly represented by the construction of hydroelectric power plants (Barbaro et al., 2007, Garrone Neto et al., 2007 and Garrone Tenofovir datasheet Neto and Haddad, 2010). The ability of the extracts obtained from the tissue covering the stingers of Potamotrygon falkneri to cause toxic activities such nociception, edema, myotoxicity, necrosis and lethality has already been reported ( Barbaro et al., 2007). Many enzymes such as proteases and hyaluronidase were detected in the extract obtained from Potamotrygon freshwater stingray ( Haddad et al., 2004, Barbaro et al., 2007 and Magalhães et al., 2008). In addition, peptides effective in the microcirculatory environment were isolated from Potamotrygon gr. orbignyi venom by Conceição et al., 2006 and Conceição et al., 2009. The histopathological features after injection of toxins extracted from the stingray stingers are practically unknown. The aim of this study is to characterize the main histological alterations in mice skin induced by experimental envenomation using extracts from the tissue covering the stingers of P. falkneri. Swiss mice (18–20 g) were provided by the Butantan Institute Animal House. Animals received food and water ad libitum. Specimens of P.

No modelo 2, referente à variável CER, grande parte das variáveis

No modelo 2, referente à variável CER, grande parte das variáveis do questionário estiveram associadas significativamente: idade (quanto mais idade, menos conhecimento) (OR = 0,97; IC 0,94-0,99), nível de escolaridade mais elevada (OR = 2,90; IC 1,16-1,18), ter conhecimento da definição de CCR (OR = 3,01; IC 1,67-5,43), ter uma maior perceção do risco de CCR (OR = 1,38; IC 1,22-1,56), concordar com a existência de tratamento para o CCR (OR = 4,05; IC 1,41-11,59), recomendação de, pelo menos, um exame de rastreio (OR = 4,51; IC 2,01-10,11), todas as fontes de

informação que obtiveram do CCR (principalmente médicos/enfermeiros) (OR = 10,51; IC 3,52-31,36) e a necessidade de mais informação sobre o CCR (OR = 2,89; IC 1,60-5,22) (modelo 2, tabela 4). No modelo 3, Trichostatin A mouse das 4 variáveis independentes selecionadas, apenas 2 foram associadas significativamente à APUER: conhecimento

da definição do CCR (OR = 1,77; IC 1,03-3,02) e terem informação sobre o CCR, tanto através Apoptosis inhibitor dos médicos/enfermeiros (OR = 2,71; IC 1,19-6,19), como da comunicação social (OR = 2,42; IC 1,41-4,13) (modelo 3, tabela 4). Por último, o modelo 4, com a variável dependente APRER, apenas a recomendação de no mínimo um exame de rastreio apresentou significado estatístico (OR = 10,03; IC 3,10-32,53) (modelo 4, tabela 4). Apesar de, em Portugal, o rastreio do CCR estar dirigido à uma população com idades entre os 50 e os 74 anos, o nosso estudo abrangeu indivíduos a partir dos 40 anos, sem idade

limite máxima estabelecida, obtendo uma média de idades de 60 anos. Consideramos a inclusão destes indivíduos uma mais-valia, na medida em que acedemos aos conhecimentos e às atitudes, tanto dos que ainda não se encontravam em rastreio, valorizando a sensibilização antecipada da população, como dos que, apesar de não estarem em idade de rastreio efetivo, já foram, teoricamente, alvo do mesmo. No âmbito dos conhecimentos acerca do CCR, os nossos resultados indicaram lacunas quanto à definição, aos fatores de risco e aos exames de rastreio do CCR. A maioria dos inquiridos Anidulafungin (LY303366) (cerca de 60%) não conhecia uma definição válida de CCR. As percentagens de respostas corretas referentes ao conhecimento dos fatores de risco do CCR oscilaram entre os 29,9% para a baixa atividade física e os 52,2% para os pólipos. Menos de 1/3 dos portuenses associou a baixa atividade física ao risco de ter CCR, fração reduzida para um dos principais fatores de risco modificáveis do CCR. A PSOF e a colonoscopia foram os 2 exames de rastreio mais relatados corretamente pelos inquiridos, com percentagens muito próximas (50,6 e 49,9%, respetivamente). A análise dos resultados relativos às atitudes dos portuenses quanto à perceção do risco e da utilidade dos exames de rastreio, à prevenção e ao tratamento do CCR foram, de um modo geral, positivos.

, 2007 and Kokinou et al , 2012) Dominant lithologies include ca

, 2007 and Kokinou et al., 2012). Dominant lithologies include carbonates deposited in neritic (shallow) environments, changing into pelagic (deep-sea) carbonates and flysch, i.e., interbeded sands and shales. Carbonate rocks are vertically stacked and accreted to form a series of tectonic nappes. These nappes are separated by east–west striking structures both onshore and offshore (Alves et al., 2007 and Gallen et al., 2014). The older post-orogenic formations on Crete are continental sands and conglomerates of possible Burdigalian (Prina Group, Fassoulas, 2001) to Serravalian

age (N14 Epigenetic inhibitor cost biozone, Postma and Drinia, 1993). In Southeast Crete, limestone-rich breccia-conglomerates are observed above early Tortonian marls and sands with abundant marine fauna (Tefeli Group; van Hinsbergen and Meulenkamp, 2006). The breccia-conglomerates are followed by calcareous sediments, yellow-grey to white marls, evaporites and bioclastic limestones of the Vrysses Group (Fortuin, 1978). These strata are, in turn, overlain by Pliocene/Quaternary

sandstones and conglomerates of the Hellenikon and Finikia/Gallini Groups, which in some areas have been uplifted and rotated by active faults. Shelval sands and muds, uplifted beach rocks and coarse-grained alluvial fans with large scale boulders, are commonly observed on the Cretan shoreline (Fassoulas, 2001, Peterek and Schwarze, 2004, Pope et al., 2008 and Alves Obeticholic Acid and Lourenço, 2010). The modern seafloor offshore Crete is composed of conglomerates and coarse-grained Niclosamide sands intercalated with unconsolidated muds and debris flows within offshore tectonic troughs (Alves et al., 2007 and Strozyk et al., 2009). Dominant currents offshore South Crete are west-flowing along the shoreline, and locally influenced by sub-regional gyres and eddies (Malanotte-Rizzoli and Bergamasco, 1991 and Theocharis et al., 1993). In contrast, Northern Crete reveals a predominant current direction from northwest to southeast. Periodically,

the flow reverses its direction (Zodiatis, 1991, Zodiatis, 1992, Zodiatis, 1993a, Zodiatis, 1993b and Triantafyllou et al., 2003). In the Kythira and Karpathos Straits, currents also alternate between northerly and southerly directions (Zodiatis, 1991, Zodiatis, 1992, Zodiatis, 1993a, Zodiatis, 1993b and Theocharis et al., 1999). Current direction on the Cretan shoreline depends closely on the relative position of water gyres and eddies to the South and North of the island, and on sea-bottom topography (Theocharis et al., 1993 and Theocharis et al., 1999). Quick oil spill dispersion should be expected with strong prevailing winds and strong swells. An important observation is that moderate northerly winds are recorded in Northern Crete during the summer, exposing the shoreline to any major oil spills occurring in the Cretan Sea (Fig. 1b).

Staining with PI, having an emission wavelength of 612 nm upon ex

Staining with PI, having an emission wavelength of 612 nm upon excitation at Selleckchem ZVADFMK 488 nm, on the other hand, requires a loss of cell membrane integrity and therefore only works in the advanced apoptotic stage or in necrotic cells. For this assay, 2 × 105 SW480 cells per well were seeded into 6-well plates and allowed to recover for 24 h. Cells were then exposed to different concentrations of test compounds for 48 h. The supernatant and cells which were detached by trypsinization were transferred

into FACS tubes, centrifuged, and the supernatant was discarded. After resuspension in 0.5 mL of binding buffer, cells were incubated with 1 μL Annexin V–FITC from Bio Vision. After 5 min, propidium iodide with an end concentration of 1 μg/mL was added. Fluorescence was immediately measured by flow cytometry using a FACS Calibur instrument (Becton Dickinson),

using FL1 channel for Annexin V-FITC and FL2 channel for PI staining. Resulting dot Y27632 plots were quantified by Cell Quest Pro software (Becton Dickinson). Cytotoxicity of the compounds was assessed by means of a colorimetric microculture assay (MTT assay) in six human cancer cell lines. The calculated IC50 values are listed in Table 1, and the corresponding concentration–effect curves are depicted in Fig. 2. Generally, the ovarian cancer cell line CH1 and the colon cancer cell line SW480 are invariably more sensitive, with IC50 values ranging from 0.67 to 3.3 μM and from 0.64 to 4.1 μM, respectively, whereas the non-small cell lung cancer cell line A549 and the prostate cancer cell line LNCaP are less sensitive, with IC50 values ranging from 3.1 to 10 μM and from 2.3 to 16 μM, respectively. The IC50 values are in all investigated cell lines in the lower micromolar to submicromolar range. The following structure–activity relationships can be deduced from these data: ruthenium complexes are in general more active than the osmium analogues. oxyclozanide Ruthenium complex 1 (with L1) is in all cell lines at least

1.5 times (and up to 4.8 times) more active than its osmium analogue 2. The same applies to the complexes with L2, of which ruthenium complex 3 shows at least 1.7 times (and up to 4.4 times) higher cytotoxicity, depending on the cell line, than the analogous osmium complex 4. Ruthenium complex 1 is 1.9 to 7.3 times more cytotoxic, based on a comparison of IC50 values, than complex 3, and osmium complex 2 is 2.1 to 6.7 times more cytotoxic than 4, indicating that L1 yields more potent complexes than L2, irrespective of the chosen metal. Since paullones are known as inhibitors of cyclin-dependent kinases [9], inhibitory potencies of the ruthenium and osmium arene complexes with L1 and L2 were studied in a cell-free setting.

Nurses have a pivotal role in the early identification and manage

Nurses have a pivotal role in the early identification and management of the patient with ventriculitis. Index 407 “
“Mary Lou Warren and Melissa McLenon Jacqueline B. Broadway-Duren and Hillary Klaassen Anemias continue to present a challenge to the health care profession. Anemia is defined as a reduction in one or more of the RBC indices. Patients presenting with a mild form of anemia may be asymptomatic; however, in

more serious cases the anemia can become life threatening. In many cases the clinical presentation also reflects the underlying cause. Anemia may be attributed to various causes, whereas autoimmune RBC destruction may be attributed to intrinsic and extrinsic factors. Laboratory tests are essential in facilitating early detection and differentiation of anemia. Edythe M. (Lyn) Greenberg and Elizabeth S. (Sue) Kaled Thrombocytopenia is www.selleckchem.com/products/cx-5461.html defined as a platelet count less than 150,000/μL. It can be the result of decreased platelet production, sequestration of the

platelets, or increased destruction of the platelets. The clinical presentation may vary from an incidental finding to obvious bleeding. Causes of thrombocytopenia include infections, malignancy, liver disease, autoimmune disorders, disseminated intravascular coagulation, pregnancy, medications, and coagulation disorders. Treatment is determined by the underlying cause of the thrombocytopenia. This article discusses the evaluation and management of common causes of thrombocytopenia. Carole L. Mackavey and Robert Hanks

Coagulopathy-related bleeding events are a major concern in the management of see more acute and chronic liver disease. The liver attempts to maintain a balance between procoagulant and anticoagulant factors, and providers struggle with poor prognostic indicators to manage bleeding and critical complications. Subtle changes in patient presentation that may require extensive provider-directed interventions, such as blood transfusions, intravenous fluid management, mitigating possible sepsis, and evaluating appropriate pharmacologic treatment, are discussed. Jennifer K. Johnson and Elizabeth Sorensen Lymphoma presents itself from slow growing and asymptomatic to aggressive and destructive. Suspicion of aggressive lymphoma warrants prompt diagnostic evaluation because the tumor can be extremely fast growing and can cause significant Immune system sequelae including but not limited to tissue damage, immune suppression, organ failure, compromised circulation, and death. The standard evaluation includes laboratory assay, infectious disease panel, radiographic imaging with computed tomography, bone marrow biopsy, and tissue diagnosis. Two cases studies are presented describing the range of different acute issues that may arise with aggressive lymphomas including tumor lysis, HIV, small bowel obstruction, superior vena cava compression, aggressive disease transformation, and acute renal injury. Edythe M.

Commonly cited society guidelines supporting the use of preoperat

Commonly cited society guidelines supporting the use of preoperative IN were created using the results of other meta-analyses that did not account for this heterogeneity as in the current meta-analysis.1 and 2 Preoperative supplementation with standard ONS has not been studied extensively. Although our results suggest the similarity of standard and immune-modulating supplements, we cannot absolutely conclude that preoperative standard ONS will result in improved outcomes. One study evaluating preoperative supplementation with standard ONS vs nonsupplemented control diet demonstrated less postoperative weight loss and fewer

minor complications with preoperative supplementation.40 buy Alectinib Several past studies have failed NVP-BKM120 price to identify a major benefit from the use of standard preoperative ONS.41, 42 and 43 This might be due to the lack of a clear definition of “malnutrition” and inclusion of well-nourished patients. Adherence to the new definitions of malnutrition, as is being popularized by several societies,44 may serve to identify which patients will benefit the most from preoperative supplements. Future studies of preoperative nutrition should incorporate these new definitions. Additionally,

the varied composition and individual nutrients of the standard ONS, particularly the amount and biologic value of protein contained, might explain these conflicting results. Dietary protein

is critical to help promote muscle protein synthesis and decrease inflammation-associated loss of lean body mass and function. A meta-analysis by Cawood and colleagues of 36 RCTs (3,790 patients) showed that the use of high-protein Celecoxib supplements (>20% of calories from protein) was associated with reduced complications and readmission to hospital, improved grip strength, increased intake of protein and energy, and improvements in weight.45 Given the lack of a significant difference between IN and standard ONS in the preoperative setting, and the fact that standard ONS are less expensive and widely available, we recommend use of standard ONS for nutritional optimization of the surgical patient. Cost and accessibility are key factors to patient compliance. As with smoking cessation or exercise, achieving patient buy-in is crucial to any successful preoperative optimization regimen. Study conception and design: Hegazi, Evans Acquisition of data: Hegazi, Hustead, Evans Analysis and interpretation of data: Hegazi, Hustead, Evans Drafting of manuscript: Hegazi, Hustead, Evans Critical revision: Hegazi, Hustead, Evans The authors wish to thank Lianbo Yu, PhD, Center for Biostatistics, The Ohio State University for his help reviewing the analysis.

The sharp boundaries of gap and pair-rule domains, together with

The sharp boundaries of gap and pair-rule domains, together with evidence for auto-regulation and mutual repression has led to proposals that

these genes operate as bistable switches [56, 57 and 58]. In the simplest model [57], the posterior hb boundary forms owing to bistability arising from hb auto-activation. As Bcd concentration decreases from anterior to posterior, a bifurcation creates a ‘Hb off’ state, repressing hb in the posterior of the embryo. However, a boundary formed by this mechanism is extremely sensitive HIF-1 activation to fluctuations in Bcd concentration. More generally, creating a series of boundaries along the A–P axis in this manner will not be structurally stable since it would require bifurcations to occur every few nuclei. While the models described above remain largely conceptual, the non-linear dynamics of morphogen target interactions can also be studied using regulatory networks inferred from quantitative gene expression data [48, 50••, 59 and 60]. The key advantage of such an approach is that it does not prescribe any particular mechanism, such as bistability, but instead

derives systems dynamics directly from data. This has led to important new insights into gap gene regulation: for instance, the establishment of seven gap gene boundaries, involving 24 regulatory interactions, can be understood in terms of just three dynamical mechanisms: (1) movement of attractor position, (2) selection of attractors by initial conditions, and (3) selection of states Gefitinib on a transient attracting trajectory. In contrast to the model described above [57], posterior hb boundary formation does not rely on the creation of a Galunisertib solubility dmso ‘Hb

off’ state by a bifurcation – such a state coexists with ‘Hb on’ in both anterior and posterior nuclei – but on the selection of one of these two states by maternal Hb concentration (Figure 2d). Since the attractors and their basins of attraction are determined by Bcd and Cad concentrations and their selection is determined by maternal Hb concentration, these dynamics imply that hb integrates both anterior and posterior maternal information to form its border. The integration of regulatory input from both anterior and posterior maternal systems is supported by experimental evidence [ 21• and 61]. It underlies the insensitivity of hb boundary position to Bcd variation [ 49 and 60]. There is only one bifurcation in the middle of the embryo, posterior to the hb boundary, and therefore, the dynamics in the two halves of the embryo are structurally stable. Regulatory networks among morphogen targets are complex, and remain difficult to model. No models exist that accurately and systematically reproduce interactions involving pair-rule genes, or D–V target genes. Furthermore, little progress has been made in the past few years, beyond the models described above and in [15••], with regard to modeling gap or segment-polarity gene expression.