Notably, the reduction at the orthogonal angle was larger than that at the preferred angle, making the absolute PSP tuning curve also appear sharper after integrating inhibition (Figure 3B, right). We summarized the inhibitory effect for all the simple cells. In our cell population, the selectivity of recorded PSP responses was similar to that of excitatory inputs (Figure 3C). Underlying

this apparent “linear” transformation are two concurrent nonlinear processes: the tuning selectivity existing in excitatory inputs would become significantly weakened or blurred when the inputs were transformed into PSP responses (Figure 3C; Vmsimu(E)); inhibitory inputs restored the level of PSP tuning back to that defined by the excitatory inputs (Figure 3C; Vmsimu(E+I)). The average tuning curves showed clearly that the PSP tuning was sharpened after integrating inhibition (Figure 3D). Screening Library in vitro Z-VAD-FMK molecular weight In addition, there was a larger reduction in PSP at the orthogonal angle than at the preferred angle (20.0 ± 4.3 versus 16.7 ± 4.1 mV, mean ± SD) (Figure 3E), indicating that inhibition had caused an additional sharpening of PSP

tuning beyond unselectively lowering responses at all orientations. Based on the derived PSP responses, we next estimated OS of spiking responses by applying a spike threshold in the integrate-and-fire neuron model (22 mV above the resting potential; see Experimental Procedures). Because PSP responses generated from excitatory inputs alone had a considerably flat tuning and most responses were above the spike threshold, OS would fail to be created in most of the cells (OSIAP < 0.3; Figure 3F; Simu(E)). In the presence of inhibition, however, derived spiking responses Carnitine dehydrogenase were as sharply tuned as those observed in loose-patch recordings (Figure 3F; Simu(E+I)). These data demonstrate that inhibition is indispensable for the generation of sharp OS in mouse simple cells. The above data have indicated that the intrinsic input-output transformation could lead to a blurring of tuning selectivity. To further illustrate this effect of membrane filtering, we carried out a more generalized simulation using the

neuron model. For simplicity, we simulated PSP responses resulting from model excitatory inputs that vary only in amplitude but not in temporal profile (see Experimental Procedures). The filtering property of the membrane is demonstrated in the plot of membrane potential depolarization versus excitatory conductance (Figure 4A, left). Within a physiological range of excitatory conductances (0.4 – 3.3 nS; see Figure 3C), the input-output function exhibited a fast saturating curve (Figure 4A, left, black). Its first-order derivative decreased rapidly to a small value (Figure 4A, left, inset), indicating that within a large input range the increase of the PSP response was much slower than the growth of the excitatory input strength.

, 2012). Together, these studies have demonstrated the power of in vivo and in vitro models in discovering a functional role for miRNAs in the Ku-0059436 research buy nervous system, providing us with a glimpse of cell contextual roles for miRNAs and a key cooperation with transcription factors. Molecular models of learning and memory have

relied heavily on the identification of activity-dependent transcription factors such as c-Fos and CREB (reviewed in Flavell and Greenberg, 2008; Miyamoto, 2006). As mentioned above, extensive studies have identified miR-132 as being regulated by CREB in activity-regulated plasticity. Initial experiments within the context of learning and memory examined miR-132 expression in response to increased activity in vivo. In these studies, miR-132 was rapidly transcribed in the hippocampus after enhanced neuronal activity and contextual fear conditioning (Nudelman et al., 2010). In addition, studies using transgenic mice overexpressing miR-132 in forebrain neurons showed a marked increase in dendritic spine density and impairments in a novel object recognition memory test (Hansen et al., 2010). This functional role for miR-132 in memory formation may at least in part be attributed to the participation of miR-132 Z-VAD-FMK order in the integration of newborn neurons into the adult dentate gyrus. Expression of miR-132 was increased during neuron differentiation and maturation and knockdown

of miR-132 resulted in decreased synapse formation as well as impaired functional integration of newborn neurons (Luikart et al., 2011). Two recent studies highlight the importance of plasticity mechanisms in the developmental refinement of neural ADP ribosylation factor circuits, demonstrating a role for miR-132 in vivo as

critical for the formation of ocular dominance (Mellios et al., 2011; Tognini et al., 2011). In this model, one can study the ability to modulate ocular dominance through the reorganization of neuronal connections in response to visual experience. In both papers, visual experience was shown to regulate miR-132 levels in the visual cortex. Interestingly, light exposure increased the presence of multiple histone posttranslational modifications within the CRE locus that are important for miR-132/miR-212 cluster transcription (Tognini et al., 2011). Both upregulation of miR-132 through miRNA mimic that caused an increase in the fraction of mature dendritic spines (Tognini et al., 2011) and downregulation through miRNA sponge technologies that resulted in more immature spines disrupted optical dominance plasticity (Mellios et al., 2011). Taken together, these data indicate that a very tightly regulated balance of miR-132 expression is required in its functional role in plasticity. In addition to the established roles for miR-132 in learning and memory, novel discoveries are rapidly increasing our understanding of additional miRNAs in these processes.

As engineers know, high-pass frequency filtering of signals makes communication poorer but not hopeless. Now suppose that we introduce high-pass filters in the communication lines between neurons in the brain. This is exactly what Xu et al., (2012) have accomplished, using molecular biological tools. They find that after such manipulation neuronal transmission becomes sluggish

but is not completely abolished. For some structures and tasks, such as the hippocampus-dependent contextual fear learning task, high-pass filtering is tolerated, whereas for a prefrontal cortex-dependent remote memory recall, sluggishness of spike communication leads to a serious behavioral impairment. Let’s examine first how communication between neurons was achieved. SP600125 Neurons communicate electrochemically. The upstream neuron generates a spike, which is broadcasted to all or most of its presynaptic terminals. Here, electricity is converted to chemically mediated synaptic transmission. This conversion process can be perturbed in multiple ways. For example, tetanus toxin (TetTox) can block transmitter release and thus completely eliminate synaptic communication. PI3K Inhibitor Library Other interventions can produce

a more subtle interference. Synaptotagmin-1 (Syt1), together with other vesicle proteins, is essential for the docking and/or fusion of synaptic vesicles with the presynaptic plasma membrane following depolarization and Ca2+ influx in presynaptic bouton. Eliminating or interfering with Syt1 also impairs synaptic transmission to single, isolated spikes yet when high enough amount of Ca2+ enters the terminal in response to high-frequency spike activity chemical transmission is resumed, although it remains sluggish due to the asynchronous release of the transmitter (Maximov and Südhof, 2005). Put simply, interfering with Syt1 amounts

to the introduction of a high-pass frequency filter: no or poor transmission at many low rates of spiking but gradual restoration of the transmitter release at increasing spike frequencies. What are the physiological and, ultimately, behavioral consequences of such frequency-selective mechanisms? To explore this question, Xu and colleagues (2012) used a virus-targeted approach to knock down Syt1 in the brain of mice. After demonstrating the proof of principle in cultured cortical neurons, the authors generated recombinant adeno-associated viruses (AAV-DJ) to express only enhanced green fluorescent protein (EGFP, which served as a control), or only TetTox, or to express both EGFP and the Syt1-coding shRNA. With such convenient tools in hand, Xu and colleagues (2012) infected neurons in the dorsal hippocampus, the entorhinal cortex, and prefrontal cortex. As expected, electrical stimulation of TetTox expressing CA1 pyramidal cells failed to excite their subicular targets.

A final extension step occurred at 72 °C for 5 min. Each PCR run included a positive control (0.5 ng parasite DNA) and a no-template negative control (5 μl PCR-grade water). PCR products were resolved by electrophoresis at 6 V/cm in 2% (w/v) agarose gels stained with 0.5 μg/ml ethidium bromide, and photographed under ultraviolet light. On all blood specimens that were negative in the ITS1 TD PCR, a PCR for vertebrate cytochrome b was performed (Kocher

et al., 1989 and Fikru et al., 2012). A positive result with vertebrate cytochrome b PCR indicates that a negative ITS1 TD PCR result of the same specimen is not due to poor DNA quality selleck products or presence of inhibitors. The ITS1 TD PCR assay conditions were optimised in order to obtain maximal specificity and sensitivity using parasite-infected mouse blood, and

non-infected blood from mouse, human, bovine, goat, horse and dog. No cross-reactivity was observed with the non-infected blood specimens, while the ITS1 TD PCR allowed detection and differentiation of the trypanosome taxa by amplicon length polymorphism. Indeed, the assay generated amplicons of the expected sizes: 612 bp with T. congolense Savannah type, 165 bp with T. vivax and 391–393 bp with the Trypanozoon subgenus, including T. b. brucei, T. b. gambiense, T. b. rhodesiense, T. evansi, and CH5424802 supplier T. equiperdum. The non-pathogenic T. theileri could be discriminated by a PCR amplicon of approximately 300 bp ( Fig. 1). To assess the lower detection limit

according to the trypanosome taxon, 10-fold serial dilutions of live parasites in 1 ml aliquots of naïve human blood were used. At 200 μl blood per sample, ITS1 TD PCR achieved an analytical sensitivity of 10 parasites/ml blood or 0.2 parasite equivalent/reaction with T. congolense ( Fig. 2), T. brucei and T. evansi (data not shown). The analytical sensitivity of ITS1 TD PCR for T. vivax was 100 parasites/ml blood or 2 parasite equivalent/reaction ( Fig. 3). A total of 246 blood specimens from 57 cattle were examined with ITS1 TD PCR and HCT and results were interpreted with only reference to their infection status with T. congolense Savannah or Kilifi type. Specimens that were negative in ITS1 TD PCR were verified with the vertebrate cytochrome b PCR and were all positive (data not shown). Firstly, specificity and sensitivity of ITS1 TD PCR were evaluated on a collection of 114 reference specimens (69 non-infected and 45 infected specimens) from 57 cattle of known disease status. Specificity of ITS1 TD PCR was 100%, which was in agreement with that of HCT. Sensitivity of ITS1 TD PCR at 14 days post infection was 100%, and that of HCT was 97.8%.

In contrast to its helical conformation on membranes, synuclein adopts a β sheet structure in aggregates. Indeed, Lewy bodies and neurites contain 5–10 nm filaments that appear to be composed primarily if not exclusively of α-synuclein (Spillantini et al., 1998b). In brainstem-type Lewy bodies, the pale-staining halo, which contains filaments by electron microscopy, labels more strongly for α-synuclein than the acidophilic core (Goedert et al., 2013). Dystrophic

neurites and the less discrete cortical-type Lewy bodies contain similar filaments (Marui et al., 2002). Although Lewy bodies were originally considered by some an artifact of the degenerative process, the identification of α-synuclein mutations in familial PD demonstrated a causative role for the major component of Lewy-related pathology. However, it is important to remember that this is not the same as establishing a causative role for Lewy pathology in the degenerative process. GSK1210151A solubility dmso Recombinant synuclein also forms filaments after incubation in vitro for a protracted period (Conway et al., 1998). By X-ray diffraction, click here these filaments adopt

a cross-beta structure characteristic of amyloid (Sawaya et al., 2007 and Serpell et al., 2000). Recent solid-state NMR has also begun to analyze fibrils at high resolution, identifying the repeated units that underlie this structure (Comellas et al., 2011). Since aggregation has been considered Oxalosuccinic acid the critical event in the pathogenesis of PD, the in vitro assay has received considerable attention. The point mutations originally identified in familial PD (A53T, A30P, and E46K) were originally proposed to accelerate aggregation, but the A30P mutant appears to form fibrils more slowly than the wild-type, although oligomerization may be enhanced (Conway et al., 2000, Giasson et al., 1999, Li et al., 2001 and Narhi

et al., 1999). β-synuclein does not fibrillize and both β- and γ- can inhibit the aggregation of α-synuclein in vitro and in vivo (Hashimoto et al., 2001 and Uversky et al., 2002), but as noted above, β- and γ- can still contribute to disease (see Synucleinopathies above), suggesting that tendency to aggregate may not correlate closely with potential to cause degeneration. Many other putative pathogenic factors have also been tested for their ability to influence the aggregation of synuclein, either through direct modification of the protein or indirectly through effects on its environment. α-synuclein does not contain any cysteines but can undergo nitration and methionine oxidation in response to oxidative stress (Breydo et al., 2012 and Giasson et al., 2000a). However, these modifications do not appear to promote aggregation. Similarly, the α-synuclein that deposits in Lewy bodies appears more heavily phosphorylated at Ser-129 than the soluble protein (Fujiwara et al., 2002 and Nishie et al., 2004a). Phosphorylation indeed appears to promote synuclein aggregation (Smith et al.

The above results show that in LTD, caspase-3 activation requires BAD and BAX, but activation of these proteins usually leads to cell death. This prompted us to investigate whether LTD and apoptosis differ in the mechanisms by which the BAD-BAX-caspase-3 pathway is activated, or in the level of its activation. Dephosphorylation and translocation to mitochondria are critical steps in the activation of BAD during apoptosis. To test whether BAD is activated by similar mechanisms in LTD, we analyzed the level of phosphorylated BAD and the amount Dinaciclib cell line of BAD in the mitochondrial fraction. In fact, NMDA treatment (30 μM for 5 min as used for LTD

induction) decreased phosphorylated BAD as detected by immunoblotting with an antibody against BAD phosphorylated

at Ser112 (Figures 6A and 6B and Table S2), but the total amount of BAD was not affected (Figure S5A). It is notable that the level of phosphorylated BAD was higher at 30 min than at 10 min after NMDA stimulation (Figures 6A and 6B), suggesting that dephosphorylated BAD was rapidly rephosphorylated after NMDA treatment. Concomitant with the decrease in phosphorylated BAD, there was a transient increase of BAD in the mitochondrial fraction (Figures 6G and 6H). Taken together, these data suggest that BAD undergoes transient dephosphorylation and mitochondrial selleck translocation during LTD. It is known that in apoptosis, BAD can be dephosphorylated by PP1, PP2A and PP2B/calcineurin. We therefore tested whether these phosphatases were also involved in BAD dephosphorylation during LTD. In fact, NMDA-induced

dephosphorylation of BAD was blocked by okadaic acid (50 nM, an inhibitor of PP1 and PP2A) and FK506 (50 nM, an inhibitor of PP2B/calcineurin) (Figures 6C–6F), suggesting that these phosphatases may be responsible for BAD dephosphorylation in LTD. Interestingly, PP1 and PP2B/calcineurin are well known for their roles in the induction of NMDA receptor-dependent LTD, thus the mechanism that activates BAD is in line with the canonical pathway for LTD induction. With respect to the activation Digestive enzyme of BAX in apoptosis, two processes are known to lead to an increase in active BAX in mitochondrial membranes: translocation of BAX activated in the cytosol to mitochondria, and activation of BAX associated with the mitochondrial membranes by proapoptotic BCL-2 family proteins such as BAD and BID. We measured the amount of active BAX in the whole cell lysates of NMDA-treated neurons (30 μM, 5 min) using immunoprecipitation with the antibody 6A7 that specifically recognizes BAX in the active conformation. It is known that once activated, BAX translocates to mitochondria very efficiently (George et al., 2009). Hence, immunoprecipitation of whole cell lysates with 6A7 measures active BAX predominantly in mitochondria. The amount of active BAX immunoprecipitated by 6A7 from treated cells was higher than that detected in control cells (Figures 6M and 6N; Table S2).

Will there be a mouse equivalent of primate extrastriate areas such as MT or IT, in line with the conserved aspects of visual processing seen previously? Or will the commonalities break down in extrastriate cortex? It is possible that either the mouse will lack the sophisticated invariant forms of processing supported by high acuity in primates, or that the higher visual areas might simply be specialized for different tasks that are more appropriate for the mouse’s visual experience. As we delve deeper into mouse vision, these two pioneering studies will provide valuable Galunisertib guidance and new approaches for further exploration of the territory between

primary visual

cortex and the centers for higher motor and cognitive function. “
“Dopamine (DA) neurons of the midbrain usually fire spontaneously at low rates, a firing mode that is called “tonic.” Occasionally, DA neurons fire extra spikes in brief episodes referred to as “phasic” or “burst” firing. Phasic firing is caused by events of motivational significance, such as unexpected primary rewards, and stimuli that predict reward over successive stages of a learning task (Ljungberg et al., 1992). Although DA neurons are sometimes activated by aversive stimuli, the majority of DA neurons selleck chemical are inhibited by these stimuli (Ungless et al., 2004). In theoretical work, DA neuron firing activity has been modeled as a reward prediction error signal, for example, in the temporal difference (TD) learning framework (Montague et al., 1996). In TD learning, the dopamine neuron firing activity plays the role of a teaching signal,

improving subsequent predictions by strengthening the appropriate synapses. However, although such work offers attractive explanations for observed DA cell activity, which correlates with the predictions of the models, it is important to go beyond correlation and experimentally investigate the causal role of phasic bursts of Resminostat DA neurons in animal learning. Previous studies have shown that excitatory drive required for burst firing of DA neurons is mediated by NMDA receptors (Tepper and Lee, 2007). In order to investigate the role of NMDAR-mediated phasic DA activity in behavioral learning, Wang et al. (2011) generated dopamine-neuron-specific NMDAR1 knockout (DAT-NR1-KO) mice. Wang et al. (2011) show that compared with control DA neurons, phasic firing activity was, as expected, greatly reduced in DA neurons of DAT-NR1-KO mice. On the other hand, no difference between controls and DAT-NR1-KO mice was observed in the tonic firing rate. Thus, by using these mice it should be possible to assess which behavioral functions require the phasic firing of dopamine neurons.

We further verified the binding of the Crb extracellular domains to Notch1a using a cell-surface binding assay. We constructed the plasmids encoding the extracellular domains of the Crb family proteins fused to the Fc portion of human IgG to generate soluble forms (Crb-Fc) and prepared conditioned media from cultures of 293T cells that were transfected with these vectors. We then added the conditioned media that contained the Crb-Fc fusion proteins to nonpermeabilized 293T cells that were transfected with a Notch1a PI3K cancer construct in which the intracellular ankyrin repeats and the transactivation domain were replaced with EYFP (hereafter referred to as EcRAM-EYFP since

it consists of the extracellular domain and the intracellular RBP-J association module) ( Eiraku et al., 2005) ( Figure 5Ba). Crb-Fc specifically bound to the surfaces of the EcRAM-EYFP-expressing cells but not to the surfaces of EcRAM-EYFP-nonexpressing cells (dotted lines in Figures 5Bb–5Bp). Vitamin D binding protein (VDBP) fused with the Fc portion of human IgG did not bind to either EcRAM-EYFP-expressing or EcRAM-EYFP-nonexpressing cells ( Figures 5Bf, 5Bk, and 5Bp). These results indicate that the extracellular domains of the Crb family proteins specifically and directly interact with the Notch1a extracellular domain. Next, we examined the effects of the Crb family proteins on Notch activity using luciferase reporter assays and the C2C12

myoblast cell line (Shawber et al., 1996). We transfected C2C12 cells with the Notch-responsive reporter construct (pGa981-6) (Kurooka et al., 1998). When the C2C12 cells were cocultured selleck kinase inhibitor with mock-transfected 293T cells, the promoter activity was increased approximately 6.5-fold compared with that of monocultured C2C12 cells, presumably because of the presence of endogenous Notch ligands in the 293T cells (Figure 5C, columns 1 and 2). This activation was further enhanced more than 12-fold by the overexpression Sclareol of murine Delta-like 1 (Dll1, formerly known as Delta1) in the 293T cells (Figure 5C, column 3). However, the incubation of Crb-Fc with the C2C12 cells

prior to coculturing with Dll1-overexpressing 293T cells reduced Notch activity to the basal level (Figure 5C, columns 4–6). In addition, overexpression of Crb family proteins in C2C12 cells reduced the Notch activity (Figure 5C, columns 7–9). In contrast, the Crb family proteins did not affect the activation of Notch when coexpressed with Dll1 in 293T cells (p = 0.34) (Figures 5Da and 5Db), which suggests that the Crb inhibition of Notch signaling in the present study occurs mainly in cis. We further examined the effect of Moe on the inhibition of Notch activity by Crb using CaCo-2 cells, which are human epithelial colorectal adenocarcinoma cells with apicobasal polarity. In CaCo-2 cells, Notch was also activated by coculturing with Dll1-expressing 293T cells, and this activation was inhibited by the expression of Crb2 in the CaCo-2 cells (Figures 5Ea and 5Eb).

From the day after dosing (31 dpi), twice weekly auscultatory respiratory assessments were performed with the quality (normal/deepened normal sound/stertor/stridor/rhonchus/wheeze/crackle), and intensity of inspiratory and expiratory sounds graded on a scale from

0 (no abnormal sound) to 3 (severe sound). In addition, faecal sampling was performed from 40 dpi until a dog was confirmed to be shedding larvae using the methods described above (Baermann, 1917). Dogs were euthanized and necropsied on Days 26–28 post-treatment (56–58 dpi). Post-necropsy examinations were carried out following Schnyder et al. (2009). For each dog, the heart and lungs were examined in detail to determine the presence or absence of adult A. vasorum. All worms were counted and identified to gender

and stage of development, whenever possible. If worm fragments were present, they selleck compound were only included in the count if the head was present. Efficacy calculations were based on the total number of adult worms recovered from each dog at necropsy in the treated and control groups to determine whether or not treatment had prevented development of infections with adult A. vasorum. To show adequate infection, a minimum of five A. vasorum must have been present in at least 6 control dogs. For each treatment group, the total number of adult A. vasorum along with the group geometric mean (GM) was calculated. The mean worm counts were determined and compared post-treatment between treated (spinosad/MO combination) and control (placebo) groups. Efficacy was calculated based on GM using the formula: %Efficiency=meancontrol−meantreatedmeancontrol×100 learn more To demonstrate prevention, both of the following criteria must have been satisfied: 1. Efficacy ≥90% against A. vasorum with the combination tablet, based on GM. A logarithmic transformation (ln[count + 1]) was applied to the post-treatment counts for each dog to address skewness of the data, as well as zero counts. Back transformed geometric means were calculated by ex − 1, where x¯ equals log transformed treatment mean. Transformed GM worm counts were analyzed with a general linear mixed ADP ribosylation factor model with

fixed effect treatment. A contrast between spinosad/MO and the placebo groups was conducted to confirm effectiveness. A covariance structure allowing for heterogeneous error variance between treatment groups was considered via a test for heterogeneity but was not deemed necessary in the final analysis. There were no adverse events within the 8 h post treatment period, and no abnormal respiratory signs were detected in any of the dogs treated with spinosad/MO. Auscultation revealed minor intensity respiratory sounds in two dogs in the placebo group, one on Days 7 and 12, and one on Day 12. No other physical abnormalities were observed in any dog during the study period, and a pre-necropsy physical examination of each dog did not detect any clinical abnormalities.

, 1982). Despite the complex

host finding mechanism ( Haas et al., 1990), the free swimming cercaria can locate appropriate species of fish in reservoirs. For C. sinensis, the shedding of cercariae from snails is governed by water temperature. HTS assay Flukes may over winter as rediae in the snail host and erupt in spring, or new infections may re-establish each year from faecal contamination. In either case, peak transmission would occur in summer months ( Rim, 1986). Prevalence of liver fluke in reservoir hosts such as pigs, cats, and dogs, varies considerably by area (Scholz et al., 2003, Sithithaworn and Haswell-Elkins, 2003, Lin et al., 2005 and Nguyen et al., 2009). A relatively high prevalence of liver fluke infection has been reported in cats (36.4%) and to a lesser extent in dogs (3.8%) in the Chi River basin of Northeast Thailand (Enes et al., 2010) where the prevalence of O. viverrini infection is high ( Sripa, 2008). Similarly, high prevalence of C. sinensis in cats (70%), dogs (50%) and pigs (27%) correlates with human prevalence (31.6%) in southern China ( Yu et al., 2003 and Lin et al., 2005). Faecal contamination from infected animals undoubtedly contributes to transmission to snails

in liver fluke endemic Adriamycin mw areas, particularly during flooding. Therefore, control of reservoir host transmission by anthelmintic treatment, concurrent with human treatment, is recommended to prevent re-emergence after liver fluke elimination in humans. Despite control campaigns over the past three decades in Thailand and Laos, food-borne zoonotic trematodes remain major health problems in the see more region. Recent evidence suggests that climate change may affect geographical distribution of certain parasitic diseases (Poulin, 2006 and Yang et al., 2010).

Reinfection or re-emergence is common due to the persistence of environmental risk factors including infected snails and fish intermediate hosts, reservoir hosts (cats and dogs) and humans. Transmission occurs in both natural habitats and in aquaculture ponds, and is most variable both geographically and temporally, with the variability related to climatic conditions. In SE Asia, climate change is a real phenomenon, causing more frequent intense events such as storms and flooding (ADB, 2009). Climate change is expected to have a significant effect on the food-borne zoonoses (Mas-Coma et al., 2009). More frequent extreme weather conditions, mainly heavy rainfall, can readily change the transmission pattern through different mechanisms. For example, flooding can quickly change habitats affecting the density of intermediate snail host species, and transport infected snails to new areas. Moreover, runoff from human settlements and animal keeping areas can carry liver fluke eggs into snail habitats and thereby increase infection pressure on the first intermediate hosts.