Contribution of women to fisheries development in Kainji Lake basin

The study was carried to examine the contribution of women to fisheries development in the Kainji basin. The sample was drawn in some of the major fishing villages in the sub strata of the basin. A total of 120 respondents were used. The findings revealed that women were involved in fisheries activities most especially in the processing and marketing aspects. Many of the respondents happened to be wives of the fishermen. Few bought fishing equipment with a special arrangement for the supply of fish while some buy from fishermen. This revealed the willingness of the women to be empowered in the economic activities in the area to meet some basic household. Major constrains to the women in this area were the scarcity of fish, no support from the government or private agencies. Recommendations were made on how to enhance women participation in fisheries development

Resource studies in relation to the development of African inland fisheries

The paper discusses relevance of studies on the resources to the decisions that have taken for the development of management of African inland fisheries. Particular emphasis is given to outlining the types of advice that can be provided by the biologist, without which the decisions taken can easily be wrong. The primary information concerns the magnitude of the potential yield from the resource, and how it compares with present catches. From this the possibilities for development can be assessed, or the need for management be determined. Methods of determining the potential, and the data used in their application are briefly reviewed. Because scientific advice on the resource is desirable as early as possible in the development of a fishery, simple but rather rough methods may be equally, if not more, valuable than more precise but more difficult methods.

Behaviour of cast-iron tunnel segmental joint from the 3D FE analyses and development of a new bolt-spring model

The behaviour of cast-iron tunnel segments used in London Underground tunnels was investigated using the 3-D finite element (FE) method. A numerical model of the structural details of cast-iron segmental joints such as bolts, panel and flanges was developed and its performance was validated against a set of full-scale tests. Using the verified model, the influence of structural features such as caulking groove and bolt pretension was examined for both rotational and shear loading conditions. Since such detailed modelling of bolts increases the computational time when a full scale segmental tunnel is analysed, it is proposed to replace the bolt model to a set of spring models. The parameters for the bolt-spring models, which consider the geometry and material properties of the bolt, are proposed. The performance of the combined bolt-spring and solid segmental models are evaluated against a more conventional shell-spring model. © 2014 Elsevier Ltd.

Spectral response of winter wheat to crop development and various agronomic limitations

For maximizing the effective applications of remote sensing in crop recognition, crop performance assessment and canopy variables estimation at large areas, it is essential to fully understand the spectral response of canopy to crop development and varying growing conditions. In this paper, the spectral properties of winter wheat canopy under different growth stages and different agronomic conditions were investigated at the field level based on reflectance measurements. It was proved that crop growth and development, nitrogen fertilization rates, nutrient deficit (e.g. lacking any kind of nitrogen, phosphorus and kalium fertilizer or lacking all of them), irrigation frequency and plant density had direct influence on canopy reflectance in 400-900 nm which including the visible/near infrared bands, and resulted in great changes of spectral curves. It was suggested that spectral reflectance of crop canopy can well reflect the growth and development of crop and the impacts from various factors, and was feasible to provide vital information for crop monitoring and assessment. ©2010 IEEE.

The expression of AmphiTCTP, a TCTP orthologous gene in amphioxus related to the development of notochord and somites

The translationally controlled tumor protein (TCTP) is highly conserved and has been widely found in eukaryotic organisms. Here, we report the phylogenetic analysis and developmental expression of AmphiTCTP, a TCTP homologous gene in cephalochordate amphioxus. Phylogenetic analysis indicates that the putative protein of AmphiTCTP is close to its vertebrate orthologs. The mRNA of AmphiTCTP is found in fertilized eggs, early cleavage embryo and most of the early developmental stages by in situ hybridization and RT-PCR, but its expression is not detectable from late cleavage stage to mid-gastrula. The expression of AmphiTCTP in zygotes and early cleavage stages shows that AmphiTCTP may be a maternal gene. From the early neurula stage onward, AmphiTCTP transcript is localized in the presumptive notochord, presomitic mesoderm, and nascent somites. However, its expression is gradually down-regulated after the notochord and somites have been formed. The expression pattern of AmphiTCTP thus coincides with the differentiation of the notochord and somites, this suggests that AmphiTCTP may not be a housekeeping gene and may play an important role in mesoderm development. (c) 2007 Elsevier Inc. All rights reserved.

Screening of genes related to ovary development in Chinese shrimp Fenneropenaeus chinensis by suppression subtractive hybridization

The ovary of triploid shrimp Fenneropenaeus chinensis was apparently impaired compared to that of the diploid shrimp at the same age. Therefore triploid shrimp ovary is possible to be taken as a model to understand the mechanism of ovary development of shrimp compared to that of the ovary of diploid shrimp at the same age. In the present study, a suppression subtractive hybridization (SSH) technique was applied to identify differentially expressed genes in the ovary between diploid and triploid shrimp. For the forward library (RNA from the ovary of triploid shrimp as the tester), 54 genes were identified. For the reverse library (RNA from the ovary of diploid shrimp as the tester), 16 genes were identified. The identified genes encoded proteins with multiple functions, including extracellular matrix components, cytoskeleton, cell growth and death, metabolism, genetic information processing, signal transduction/transport or immunity related proteins. Eleven differentially expressed genes were selected to be confirmed in the ovaries of triploid and diploid shrimp by semi-quantitative RT-PCR. Genes encoding spermatogonial stem-cell renewal factor, cytochrome c oxidase subunits I and II, clottable protein, antimicrobial peptide and transposase showed up-regulated expressions in the ovary of triploid shrimp. Genes encoding tubulin, cellular apoptosis susceptibility protein, farnesoic acid O-methyltransferase, thrombospondin and heat shock protein 90 genes showed higher expressions in the ovary of diploid shrimp. The differential expressions of the above genes are suggested to be related to the ovary development of shrimp. It will provide a new clue to uncover the molecular mechanisms underlying the ovarian development in penaeid shrimp. (C) 2010 Elsevier Inc. All rights reserved.

Women's contribution to the development of the English novel: 1621-1818

Women's contribution to literature is no arbitrary or artificial distinction. However much the reformer may welcome, or the conservative lament, the growth of a harmonious sharing of ideals between men and women, that growth has been a hard-fought struggle. It has been an escape from a prison, which, when it did not entirely shut out the greater world, at least enclosed a little world of education meant for women, literature adapted to the supposed limitations of their intellect, and a course of action prescribed by the other sex. To show how the literary efforts of women developed and justified their claims to free activity is the purpose of this thesis.

Studies on factors relating to the development of defects in commercial cheese

Defects in commercial cheese result in a downgrading of the final cheese and a consequential economic loss to the cheese producer. Developments of defects in cheese are often not fully understood and therefore not controllable by the producer. This research investigated the underlying factors in the development of split and secondary fermentation defect and of pinking defects in commercial Irish cheeses. Split defect in Swiss-type cheese is a common defect associated with eye formation and manifests as slits and cracks visible in the cut cheese loaf (Reinbold, 1972; Daly et al., 2010). No consensus exists as to the definitive causes of the defect and possible factors which may contribute to the defect were reviewed. Models were derived to describe the relationship between moisture, pH, and salt levels and the distance from sample location to the closest external block surface during cheese ripening. Significant gradients within the cheese blocks were observed for all measured parameters in cheeses at 7 day post/after manufacture. No significant pH gradient was found within the blocks on exit from hot-room ripening and at three months post exit from the hot-room. Moisture content reached equilibrium within the blocks between exit from hot-room and 3 months after exit from hot-room while salt and salt-to-moisture levels had not reached equilibrium within the cheese blocks even at three months after exit from hot-room ripening. A characterisation of Swiss-type cheeses produced from a seasonal milk supply was undertaken. Cheeses were sampled on two days per month of the production year, at three different times during the manufacturing day, at internal and external regions of the cheese block and at four ripening time points (7 days post manufacture, post hot-room, 14 days post hot-room and 3 months in a cold room after exit from hot-room). Compositional, biochemical and microbial indices were determined, and the results were analysed as a splitplot with a factorial arrangement of treatments (season, time of day, area) on the main plot and ripening time on the sub-plot. Season (and interactions) had a significant effect on pH and salt-in-moisture levels (SM), mean viable counts of L. helveticus, propionic acid and non-starter lactic acid bacteria, levels of primary and secondary proteolysis and cheese firmness. Levels of proteolysis increased significantly during hot-room ripening but also during cold room storage, signifying continued development of cheese ripening during cold storage (> 8°C). Rheological parameters (e.g. springiness and cohesiveness) were significantly affected by interactions between ripening and location within cheese blocks. Time of day of manufacture significantly affected mean cheese calcium levels at 7 days post manufacture and mean levels of arginine and mean viable counts of NSLAB. Cheeses produced during the middle of the production day had the best grading scores and were more consistent compared to cheeses produced early or late during day of manufacture. Cheeses with low levels of S/M and low values of resilience were associated with poor grades at 7 days post manufacture. Chesses which had high elastic index values and low values of springiness in the external areas after exit from hot-room ripening also obtained good commercial grades. Development of a pink colour defect is an intermittent defect in ripened cheese which may or may not contain an added colourant, e.g., annatto. Factors associated with the defect were reviewed. Attempts at extraction and identification of the pink discolouration were unsuccessful. The pink colour partitioned with the water insoluble protein fraction. No significant difference was observed between ripened control and defect cheese for oxygen levels and redox potential or for the results of elemental analysis. A possible relationship between starter activity and defect development was established in cheeses with added coulourant, as lower levels of residual galactose and lactose were observed in defective cheese compared to control cheese free of the defect. Swiss-type cheese without added colourant had significantly higher levels of arginine and significantly lower lactate levels. Flow cell cytometry indicated that levels of bacterial cell viability and metabolic state differed between control and defect cheeses (without added colourant). Pyrosequencing analysis of cheese samples with and without the defect detected the previously unreported bacteria in cheese, Deinococcus thermus (a potential carotenoid producer). Defective Swiss-type cheeses had elevated levels of Deinococcus thermus compared to control cheeses, however the direct cause of pink was not linked to this bacterium alone. Overall, research was undertaken on underlying factors associated with the development of specific defects in commercial cheese, but also characterised the dynamic changes in key microbial and physicochemical parameters during cheese ripening and storage. This will enable the development of processing technologies to enable seasonal manipulation of manufacture protocols to minimise compositional and biochemical variability and to reduce and inhibit the occurrence of specific quality defects.

Seasonal shelf-sea front mapping using satellite ocean colour and temperature to support development of a marine protected area network

Front detection and aggregation techniques were applied to 300m resolution MERIS satellite ocean colour data for the first time, to describe frequently occurring shelf-sea fronts near to the Scottish coast. Medium resolution (1km) thermal and colour data have previously been used to analyse the distribution of surface fronts, though these cannot capture smaller frontal zones or those in close proximity to the coast, particularly where the coastline is convoluted. Seasonal frequent front maps, derived from both chlorophyll and SST data, revealed a number of key frontal zones, a subset of which were based on new insights into the sediment and plankton dynamics provided exclusively by the higher-resolution chlorophyll fronts. The methodology is described for applying colour and thermal front data to the task of identifying zones of ecological importance that could assist the process of defining marine protected areas. Each key frontal zone is analysed to describe its spatial and temporal extent and variability, and possible mechanisms. It is hoped that these tools can provide guidance on the dynamic habitats of marine fauna towards aspects of marine spatial planning and conservation.

Seasonal shelf-sea front mapping using satellite ocean colour and temperature to support development of a marine protected area network

Front detection and aggregation techniques were applied to 300m resolution MERIS satellite ocean colour data for the first time, to describe frequently occurring shelf-sea fronts near to the Scottish coast. Medium resolution (1km) thermal and colour data have previously been used to analyse the distribution of surface fronts, though these cannot capture smaller frontal zones or those in close proximity to the coast, particularly where the coastline is convoluted. Seasonal frequent front maps, derived from both chlorophyll and SST data, revealed a number of key frontal zones, a subset of which were based on new insights into the sediment and plankton dynamics provided exclusively by the higher-resolution chlorophyll fronts. The methodology is described for applying colour and thermal front data to the task of identifying zones of ecological importance that could assist the process of defining marine protected areas. Each key frontal zone is analysed to describe its spatial and temporal extent and variability, and possible mechanisms. It is hoped that these tools can provide guidance on the dynamic habitats of marine fauna towards aspects of marine spatial planning and conservation.

Making modelling count - increasing the contribution of shelf-seas community and ecosystem models to policy development and management

Marine legislation is becoming more complex and marine ecosystem-based management is specified in national and regional legislative frameworks. Shelf-seas community and ecosystem models (hereafter termed ecosystem models) are central to the delivery of ecosystem-based management, but there is limited uptake and use of model products by decision makers in Europe and the UK in comparison with other countries. In this study, the challenges to the uptake and use of ecosystem models in support of marine environmental management are assessed using the UK capability as an example. The UK has a broad capability in marine ecosystem modelling, with at least 14 different models that support management, but few examples exist of ecosystem modelling that underpin policy or management decisions. To improve understanding of policy and management issues that can be addressed using ecosystem models, a workshop was convened that brought together advisors, assessors, biologists, social scientists, economists, modellers, statisticians, policy makers, and funders. Some policy requirements were identified that can be addressed without further model development including: attribution of environmental change to underlying drivers, integration of models and observations to develop more efficient monitoring programmes, assessment of indicator performance for different management goals, and the costs and benefit of legislation. Multi-model ensembles are being developed in cases where many models exist, but model structures are very diverse making a standardised approach of combining outputs a significant challenge, and there is a need for new methodologies for describing, analysing, and visualising uncertainties. A stronger link to social and economic systems is needed to increase the range of policy-related questions that can be addressed. It is also important to improve communication between policy and modelling communities so that there is a shared understanding of the strengths and limitations of ecosystem models.

An archaeological approach to the development of the late medieval peasant house

Archaeological excavation has provided an alternative source of evidence for the development of the late medieval peasant house. It is argued that whilst there was a significant change in building techniques in the decades around 1200 with the adoption of ground-set timbers, the most important factor which led to the survival of houses was a fall in real wages during the thirteenth century. This encouraged peasants to repair existing buildings, rather than replace them with new ones. Alternative traditions of building are also investigated. Stone construction was adopted in a number of areas of England, but in spite of the durability of the material, few medieval peasant buildings of this type have survived in use because of the failure to use lime mortar. Decisions about whether to invest in a building’s renovation will depend on the capital initially expended upon it. This interpretation is considered against the data from the fifteenth century and found to conform satisfactorily. Its implications are considered for the period between 1200 and 1350. Data collected from archaeological excavations combined with the results of dendrochronology on a growing number of closely dated standing buildings suggest that there was a significant ‘cull’ of houses in the period after 1350 as new dwellings were constructed.

Does childhood bullying lead to the development of psychotic symptoms? A meta-analysis and review of prospective studies

Purpose: Researchers have demonstrated associations between trauma and psychosis. Childhood trauma, in particular, appears to be an important determinant. Recently, bullying has become considered a traumatic experience in its own right. This review aims to analyse research with prospective designs, which will enable conclusions about whether or not bullying causes psychosis.

Methods: A systematic review of the literature was carried out independently by two reviewers. Eligibility and quality assessment criteria were applied. A meta-analysis and narrative synthesis were then completed.

Results: Ten studies met inclusion criteria. Four used data from the same large database, and were combined as one. The majority provided confirmation that bullying appears to cause later development of psychosis. A meta-analysis yielded an unadjusted odds ratio (OR) of 2.148 [95% confidence interval (CI) 1.140–4.044].

Conclusions: The studies reviewed here suggest that bullying does predict the later development of psychotic symptoms. What is lacking from the literature is adequate investigation into other potential mediating factors. The current review highlights the significant role of bullying within this complex interaction. Potential mediating variables are explored, including a dose–response effect for the severity and frequency of victimization. Suggestions for targeting intervention are also suggested alongside clinical implications and recommendations for future research.

Identification of the cellular and molecular mechanism by which CD2AP, a regulator of neuronal intracellular transport contributes to the development of Alzheimer’s disease

Tese de mestrado. Biologia (Biologia Molecular e Genética). Universidade de Lisboa, Faculdade de Ciências,2014

Primary cilia and the regulation of hedgehog signaling: link to cardiac development

RESUMO: As células eucarióticas evoluíram um sistema de sinalização complexo que lhes permite responder aos sinais extracelulares e intracelulares. Desta forma, as vias de sinalização são essenciais para a sobrevivência da célula e do organismo, uma vez que regulam processos fundamentais, tais como o desenvolvimento, o crescimento, a imunidade, e a homeostase dos tecidos. A via de transdução de sinal Hedgehog (Hh) envolve o receptor Patched1 (Ptch1), que tem um efeito inibidor sobre a proteína Smoothened (Smo) na ausência dos seus ligandos, as proteínas Sonic hedgehog (Shh). Estas proteínas são reguladores fundamentais do desenvolvimento embrionário, como ilustrado pelas malformações drásticas observadas em embriões humanos e de murganho com perturbações da transdução de sinal da via Hh e que incluem polidactilia, defeitos craniofaciais e malformações ósseas. Igualmente importantes são as consequências da ativação inapropriada da via de sinalização Hh na formação de tumores. Curiosamente, os componentes desta via localizam-se nos cílios primários. Além disso, demonstrou-se que esta localização é crucial para a sinalização através da via Hh. Na presença dos ligandos, Ptch1 é internalizado e destinado a degradação ou sequestrado num compartimento da célula de onde não pode desempenhar o seu papel inibitório. A proteína Arl13b é uma pequena GTPase pertencente à família Arf/Arl da superfamília Ras de pequenas GTPases e foi implicada no síndrome de Joubert, uma ciliopatia caracterizada por ataxia congénita cerebelar, hipotonia, atrso mental e cardiopatia congénita. Murganhos deficientes para Arl13b, chamado hennin (hnn) morrem morrem prematuramente ao dia 13,5 de gestação (E13,5) e exibem anomalias morfológicas nos cílios que levam à interrupção da sinalização Hh. Além disso, a Arl13b está diretamente envolvida na regulação da via Hh, controlando a localização de vários componentes desta via nos cílios primários. Neste trabalho, mostramos que a Arl13b se localiza em circular dorsal ruffles (CDRs), que são estruturas de actina envolvidas em macropinocitose e internalização de recetores, e que regula a sua formação. Além disso, aprofundámos o conhecimento do processo de ativação da via de sinalização Hh, mostrando que as CDRs sequestram seletivamente e internalizam o recetor Ptch1. As CDRs formam-se minutos após ativação da via por ligandos Shh ou pelo agonista de Smo SAG e continuam a ser formadas a partir daí, sugerindo uma indução contínua da reorganização do citoesqueleto de actina quando a via está ativada. Observámos ainda que a inibição da formação de CDRs através do silenciamento de WAVE1, uma proteína necessária para a formação destas estruturas, resulta na diminuição da ativação da via de sinalização Hh. Além disso, o bloqueio da macropinocitose, que se segue ao fecho das CDRs, através do silenciamento de uma proteína necessária para a cisão de macropinossomas, nomeadamente a proteína BARS, tem um efeito semelhante. Estes resultados sugerem que as CDRs e a macropinocitose são necessárias para a ativação da via de sinalização Hh e indicam que esta via de internalização controla os níveis de sinal Hh. Durante o desenvolvimento, as células proliferativas dependem do cílio primário para a transdução de várias vias de sinalização. A via Hh induz a diferenciação do músculo cardíaco. Por conseguinte, os murganhos deficientes na via de sinalização Hh exibem uma variedade de defeitos de lateralidade, incluindo alteração do looping do coração, como pode ser visto em murganhos deficientes para Arl13b. Por conseguinte, investigámos o papel da Arl13b no desenvolvimento do coração. Mostramos que a Arl13b é altamente expressa no coração de embriões de murganho e de murganhos adultos ao nível do mRNA e da proteína. Além disso, o perfil de distribuição da Arl13b no coração segue o dos cílios primários, que são essenciais para o desenvolvimento cardíaco. Corações de murganhos hnn no estadio E12,5 mostram um canal átrio-ventricular aberto, espessamento da camada compacta ventricular e aumento do índice mitótico no ventrículo esquerdo. Além disso, um atraso de 1 a 2 dias no desenvolvimento é observado em corações de murganhos hnn, quando comparados com controlos selvagens no estadio E13,5. Assim, estes resultados sugerem que a Arl13b é necessária para o desenvolvimento embrionário do coração e que defeitos cardíacos podem contribuir para a letalidade embrionária de murganhos hnn. Em suma, foi estabelecido um novo mecanismo para a regulação dos níveis de superfície do recetor Ptch1, que envolve a remodelação do citoesqueleto de actina e a formação de CDRs após a ativação da via de sinalização Hh. Este mecanismo permite um feedback negativo que evita a repressão excessiva da via através da remoção de Ptch1 da superfície da célula. Além disso, determinou-se que uma mutação de perda de função na Arl13b causa defeitos cardíacos durante o desenvolvimento, possivelmente relacionados com a associação dos defeitos em cílios primários e na sinalização Hh, existentes em murganhos deficientes para Arl13b. A via de sinalização Hh tem tido um papel central entre as vias de sinalização, uma vez que a sua regulação é crucial para o funcionamento apropriada da célula. Assim, a descoberta de um novo mecanismo de tráfego através de macropinocitose e CDRs que controla a ativação e repressão da via de sinalização Hh traz novas perspetivas de como esta via pode ser regulada e pode ainda conduzir à identificação de novos alvos e estratégias terapêuticas. --------------------ABSTRACT: Eukaryotic cells have evolved a complex signaling system that allows them to respond to extracellular and intracellular cues. Signaling pathways are essential for cell and organism survival, since they regulate fundamental processes such as development, growth, immunity, and tissue homeostasis. The Hedgehog (Hh) pathway of signal transduction involves the receptor Patched1 (Ptch1), which has an inhibitory effect on Smoothened (Smo) in the absence of its ligands, the Sonic hedgehog (Shh) proteins. These proteins are fundamental regulators of embryonic development, as illustrated by the dramatic malformations seen in human and mouse embryos with perturbed Hh signal transduction that include polydactyly, craniofacial defects and skeletal malformations. Equally important are the consequences of inappropriate activation of the Hh signaling response in tumor formation. Interestingly, the components of this pathway localize to primary cilia. Moreover, it has been shown that this localization is crucial for Hh signaling. However, in the presence of the ligands, Ptch1 is internalized and destined for degradation or sequestered in a cell compartment where it no longer can play its inhibitory role. ADP-ribosylation factor-like (Arl) 13b, a small GTPase belonging to Arf/Arl family of the Ras superfamily of small GTPases has been implicated in Joubert syndrome, a ciliopathy characterized by congenital cerebellar ataxia, hypotonia, intellectual disability and congenital heart disease. Arl13b-deficient mice, called hennin (hnn) die at embryonic day 13.5 (E13.5) and display morphological abnormalities in primary cilia that lead to the disruption of Hh signaling. Furthermore, Arl13b is directly involved in the regulation of Hh signaling by controlling the localization of several components of this pathway to primary cilia. Here, we show that Arl13b localizes to and regulates the formation of circular dorsal rufles (CDRs), which are actin-basedstructures known to be involved in macropinocytosis and receptor internalization. Additionally, we extended the knowledge of the Hh signaling activation process by showing that CDRs selectively sequester and internalize Ptch1 receptors. CDRs are formed minutes after Hh activation by Shh ligands or the Smo agonist SAG and keep being formed thereafter, suggesting a continuous induction of actin reorganization when the pathway is switched on. Importantly, we observed that disruption of CDRs by silencing WAVE1, a protein required for CDR formation, results in down-regulation of Hh signaling activation. Moreover, the blockade of macropinocytosis, which follows CDR closure, through silencing of a protein necessary for the fission of macropinosomes, namely BARS has a similar effect. These results suggest that CDRs and macropinocytosis are necessary for activation of Hh signaling and indicate that this pathway of internalization controls Hh signal levels. During development, proliferating cells rely on the primary cilium for the transduction of several signaling pathways. Hh induces the differentiation of cardiac muscle. Accordingly, Hh-deficient mice display a variety of laterality defects, including alteration of heart looping, as seen in Arl13b-deficient mice. Therefore, we investigated the role of Arl13b in heart development. We show that Arl13b is highly expressed in the heart of both embryonic and adult mice at mRNA and protein levels. Also, Arl13b localization profile mimics that of primary cilia, which have been shown to be essential to early heart development. E12.5 hnn hearts show an open atrioventricular channel, increased thickening of the ventricular compact layer and increased mitotic index in the left ventricle. Moreover, a delay of 1 to 2 days in development is observed in hnn hearts, when compared to wild-type controls at E13.5. Hence, these results suggest that Arl13b is necessary for embryonic heart development and that cardiac defects might contribute to the embryonic lethality of hnn mice. Altogether, we established a novel mechanism for the regulation of Ptch1 surface levels, involving cytoskeleton remodeling and CDR formation upon Hh signaling activation. This mechanism allows a negative feedback loop that prevents excessive repression of the pathway by removing Ptch1 from the cell surface. Additionally, we determined that the Arl13b loss-offunction mutation causes cardiac defects during development, possibly related to the associated ciliary and Hh signaling defects found in Arl13b-deficient mice. Hh signaling has taken a center stage among the signaling pathways since its regulation is crucial for the appropriate output and function of the cell. Hence, the finding of a novel trafficking mechanism through CDRs and macropinocytosis that controls Hh signaling activation and repression brings new insights to how this pathway can be regulated and can lead to the discovery of novel therapeutic targets and strategies.