We acknowledge financial support from the Wellcome Trust Technology Transfer Award No. 090441Z09Z, and the National Institutes for Health Research, Porton for animal model development. We are grateful to Thomas Bean and the staff of the Biological Investigations Group at HPA for assistance in conducting the ferret studies and to Andrew RO4929097 clinical trial Mead (University of Warwick) for assistance with the statistical analysis. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health or the Health Protection Agency. “
“Cantagalo virus (CTGV) was isolated

during an outbreak of a pustular skin disease affecting dairy cows and milkers in the Rio de Janeiro state of Brazil. The virus was characterized as a strain of vaccinia virus (VACV; Orthopoxvirus; Poxviridae) and it shares important genotypic and phenotypic features with the smallpox vaccine used in Brazil until the late 1970s ( Damaso et al., 2000). selleck compound Most outbreaks of CTGV-like infections have been reported in Southeastern Brazil ( Damaso et al., 2007, de Souza Trindade et al., 2003, Megid et al., 2008 and Nagasse-Sugahara et al., 2004),

but the spread of the disease in cattle and humans and its establishment in northern states in the Amazon biome has been described recently ( Medaglia et al., 2009 and Quixabeira-Santos et al., 2011). Infected animals develop pustular lesions on the teats and udder, accompanied by fever and sometimes secondary mastitis. Dairy workers usually acquire the disease during milking activities, developing lesions SPTLC1 on hands and arms, with associated lymphadenopathy, fever, and prostration. Generalized infections are rarely observed. Nevertheless, infected workers are incapable of working for 3–4 weeks (Moussatche et al., 2008). The economical and occupational aspects of this emerging

zoonosis require attention because of the increasing number of affected animals and individuals (Damaso et al., 2007, Medaglia et al., 2009 and Moussatche et al., 2008). Attack rates vary from 11% to 80% of the herd depending on the farm size and herd density. Farms with high animal density combined with poor sanitation conditions usually have the highest rates (Donatele et al., 2007 and Quixabeira-Santos et al., 2011). There is no antiviral therapy commercially available to treat CTGV-infected animals or humans. The emergence of other orthopoxvirus infections worldwide poses similar concerns, such as outbreaks of monkeypox virus in Africa and cowpox virus infections in Europe (Reynolds and Damon, 2012 and Vorou et al., 2008). In addition, complications following smallpox vaccination are still a problem (Golden and Hooper, 2011). Therefore, considerable efforts have been recently invested towards the search for effective anti-orthopoxvirus drugs.

There was a significant main effect of grade (Wald χ2 = 12.9, p < 0.001), but no difference between tasks (p = 0.9) and no interaction between grade and task (Wald χ2 = 1.4, p = 0.24), suggesting the grade effects were not specific to recursion ( Fig. 7). To assure the validity of comparisons between

VRT and EIT, we balanced the order of the tasks in the procedure. However, we noticed that one of the ‘task-order’ conditions yielded lower performance than the other. Specifically, participants starting the procedure with VRT had a significantly lower response accuracy (on both tasks VRT and EIT combined; M = 0.63, SD = 0.21) than participants that check details started with EIT (M = 0.72, SD = 0.17; Mann Whitney U = 851, z = −3.2, p = 0.001). To further explore

this, we first investigated whether performance was differently affected in different tasks and in different grades ( Fig. 8). Before testing the effect of task-order, and to better interpret potential interactions between ‘task-order’ (‘VRT-EIT’ vs. ‘EIT-VRT’) and ‘task’ (VRT vs. EIT), we recoded the former variable on a trial-by-trial basis. The new variable, called ‘position’, can be understood as the position of the task in the procedure. For instance, in trials where the task is ‘VRT’ and the order of tasks is ‘VRT-EIT’, the ‘position’ variable is coded as ‘FIRST’. Likewise, in trials where the task is ‘EIT’ and the ATR inhibitor order of tasks is ‘EIT-VRT’, the ‘position’ variable is coded as ‘FIRST’, etc. We ran a GEE model with ‘task’ (VRT vs. EIT) and position (FIRST vs. SECOND) as within-subjects effects, and ‘grade’ (second vs. fourth) as a between-subjects variable. We analyzed ‘task’, ‘grade’ and ‘position’ main effects, and all possible interactions. The summary AMP deaminase of the model

is depicted in Table 1. We found significant main effects of ‘position’ and ‘grade’ on performance (p < 0.001), in agreement with the previous analyses. Furthermore, we found a significant interaction between ‘task’ and ‘position’. Performance in EIT-FIRST position was better than performance in VRT-FIRST position (EMM difference = 0.15, p = 0.004). Conversely, VRT-SECOND position yielded better performance than EIT-SECOND position (EMM difference = 0.17, p = 0.001). Within VRT, the proportion of correct answers was higher when this task was performed in the SECOND position of the procedure than when the same task was performed in the first position (EMM difference = 0.21, p < 0.001). Within EIT, there was also a trend towards higher accuracy when this task was performed in the FIRST position than when it was performed in the second position (EMM difference = 0.11, p = 0.052). All p-values were corrected with sequential Bonferroni. Additional interaction analyses are presented in Appendix E. Overall, results suggest that the order of the task in the procedure had a strong influence on task performance.

4% of the island. From the mid 20th century, economic and emigration issues

caused the abandonment of cultivated land and traditional management practices. As a result, the terraces became unstable, especially in areas that are freely grazed by cattle, sheep, and goats, leading to an increase in wall structure damage followed by several collapses. Bevan and Conolly (2011) and Bevan et al. (2013) proposed a multidisciplinary analysis of terraces across the small island Y-27632 in vitro of Antikythera (Greece). They considered archaeology, ethnography, archival history, botany, geoarchaeology, and direct dating of buried terrace soils. Their analysis based on historical records indicated that the dated soils might come from post-abandonment erosion that occurred during the 15th and 16th centuries. Only with a multidisciplinary approach it is possible to achieve new insights into the spatial structure of terraces, the degree of correlation between terrace construction and changing human population, Caspase-independent apoptosis and the implications of terrace abandonment for vegetation and soils. According to these authors,

the terraces are more than a simple feature of the rural Mediterranean. They are part of the evolution of the social and ecological landscape. Therefore, not only environmental but also historical and social contexts can affect their cycle of construction, use and abandonment. Nyessen et al. (2009) underlined the effectiveness of integrated catchment management for the mitigation of land degradation in north Ethiopian highlands. Their analysis indicated the positive effects of stone bunds in reducing runoff coefficients and soil loss. In the Tigray region (northern Ethiopia) the stone bunds Cyclooxygenase (COX) were introduced since 1970s to enhance soil and water conservation (Munro et al., 2008), reducing the velocity of overland flow and consequently

the soil erosion (Desta et al., 2005). This practice can reduce annual soil loss due to sheet and rill erosion on average by 68% (Desta et al., 2005). Terracing is a widely used practice for the improvement of soil management in Ugandan hill landscapes (Mcdonagh et al., 2014). Bizoza and de Graaff (2012) stressed the fact that terraces, in addition to reduction of soil erosion, also provide sufficient financial gains at the farm level. They presented a financial cost–benefit analysis to examine the social and economic conditions under which bench terraces are financially viable in Northern and Southern Rwanda, which indicated that bench terraces are a financially profitable practice. The study proposed by Cots-Folch et al. (2006) merits mentioning because it differs from the others proposed previously. It is an example of how policy on landscape restructuring (in this case, supporting terrace construction) can significantly affect the surface morphology.

As reported by Caneva and Cancellieri (2007), in this area terraces appear to date back to the period of 950–1025 AC. Since the Middle Ages, these fertile but steep lands were transformed and shaped, through the terrace systems, to grow profitable crops such as chestnuts,

grapes, and especially lemons. Since the XI century, the yellow of the “sfusato” lemon has been a feature of the landscape of the Amalfi Coast. At present most of the soils are cultivated with the Amalfi Coast lemon (scientifically known as the Sfusato Amalfitano) and produce approximately 100,000 tonnes of annual harvest, with almost no use of innovative Selleckchem Androgen Receptor Antagonist technology. This special type of citrus has a Protected Geographical Indication (I.G.P.) and is preserved by the Consortium for the Promotion of the Amalfi Coast Lemon (Consorzio di Tutela del Limone Costa d’Amalfi I.G.P.). However, the spatial organization of the Amalfi Coast with terraces had not only an agronomic objective but also a hydraulic requirement. Therefore, the use of the word “system” is appropriate in this case study of terraced

landscapes. In fact, an entire terrace system was made up of not only dry-stone retaining walls (the murecine and macere, in the local dialect) and a level or nearly level soil surface (the piazzola, in the local dialect) but also important hydraulic elements supporting the agronomic practices, such as irrigation channels, Alectinib chemical structure storage tanks, and a rainwater harvesting facility (the peschiere, in the local dialect). The terrace system in the Amalfi Coast enabled water collected

at the higher positions of rivers (e.g., the Reginna Major River) or creeks to be diverted and channelled by gravity flow towards the lower parts of the landscape. The bench terraces were connected by narrow stone stairs (the scalette, in the local dialect), which were employed as both connections among the terraces and stepped conduits for rainwater flows. As noted by Maurano (2005), “… here the construction of the irrigation system seems to precede mentally the one of the terraces, the Adenosine triphosphate regimentation of water marks the site, its kinds of cultivation and the use of the pergola, and gives origin to the exceptional shape of the hills”. Therefore, terracing in the Amalfi Coast represented a complex interweaving between agriculture and hydraulics. As a result of the major socio-economic transformations of the post-war period, with the urbanization in general, but specifically with the explosion of tourism activities in this area and the related reduced interests towards agricultural practices, a gradual degradation process of the terraced landscape has begun ( Savo et al., 2013).

Subsequent to the 2009 floods, several mines in northwest Queensland were charged for environmental offences including the LACM. The mine company was eventually fined $0.5 (Australian) million Cobimetinib datasheet in March 2012 for causing serious environmental harm after its storage

ponds discharged waste water into the Saga and Inca creeks (Queensland Government, 2012a). Numerous studies are available on soil-and sediment-associated metals and metalloids (hereafter referred to as ‘metals’) within urban and industrial centres in Australia (e.g. Birch et al., 1997, Birch and Taylor, 1999, Birch and Vanderhayden, 2011, Chattopadhyay et al., 2003, Ford and Dale, 1996, Laidlaw and Taylor, 2011, Laidlaw et al., 2014, Markus and McBratney, 1996, Martley et al.,

2004 and Rouillon et al., 2013). By contrast, however, research into the environmental effects of mining on remote rangeland agricultural catchments, is notably absent. This lack of research is surprising given that the minerals sector is a major industry in Australia, contributing see more approximately 8% to the nation’s annual gross domestic product (Roarty, 2010). Although interest in northwest Queensland environments is increasing (e.g. Mackay and Taylor, 2013, Mackay et al., 2011, Taylor and Hudson-Edwards, 2008 and Taylor et al., 2009), much of the earlier work focused largely on ecology studies (e.g. Hoffman et al., 2000, Hoffman et al., 2002, Hortle and Person, 1990 and Pyatt and Pyatt, 2004). On the whole, the impact of mining on channel and floodplain environments on the region has received little attention in peer-reviewed literature. In general, an extensive research literature examines heavy metal transport and storage in temperate environments whereas a comparatively smaller body of work addresses effects in arid and semi-arid systems, even though such effects

may be equally widespread (Taylor and Hudson-Edwards, 2008). Significant limitations exist, however, in applying models across regions or hydroclimatic environments, because of the heterogeneity of responses between river systems (see Miller, 1997 for a review of these issues) or even within an individual system Dipeptidyl peptidase (Marcus et al., 2001). River networks are pivotal for the transport, dispersal and storage of contaminants, with up to 90% of the total metal load in a catchment transported (and stored) by river-related processes (e.g. Macklin et al., 2006, Marcus, 1987, Miller, 1997, Taylor, 2007 and Walling and Owens, 2003). Contaminants may be transported in solution or combined with mineral grains. They could also mobilise as grain surface coatings or adsorbe to grain surfaces (Miller and Orbock Miller, 2007). The physical and chemical availability of contaminants to the system can have measureable impacts on sediment quality, which in turn may increase potential exposure risk factors for human activity associated with channels and floodplains (cf.

Humans hunted seals and sea lions since at least the Terminal Pleistocene, but early records of pinniped hunting are scarce, with dramatic increases at some locations beginning around 1500 years ago ( Braje et al., 2011a, Braje et al., 2011b and Erlandson et al., 2013). One of the more interesting trends in

pinniped demographics during the Holocene compared to today is the changing abundance of Guadalupe fur seals and elephant seals ( Fig. 2c; Rick et al., 2009a and Rick et al., 2011). For much of the Holocene, Guadalupe fur seals are the most abundant taxa found in archeological sites, suggesting they were frequently encountered when hunting and scavenging. In contrast, elephant seals are rarely found in archeological sites, with just a handful of bones found in island (or mainland) sites. Both of these species were hunted to near Venetoclax cost extinction during the 18th–19th century global fur and oil trade. Following federal protection in the 1970s, populations have grown exponentially and

there are now more than 50,000 elephant seals in Alta California waters. Guadalupe fur seals, however, are very rare north of BGB324 mw Mexico, with only a few observations during the last decade ( Rick et al., 2009a). These dramatic differences in abundance between Holocene seal and sea lion populations and those of today suggest that recovered pinniped populations are not ‘natural’ and are largely an artifact of management and conservation (see Braje et al., 2011a, Braje et al., 2011b and Erlandson et al., 2013). Seal and sea lion conservation can lead to debate between conservationists focused on the management of marine mammal populations and commercial fisheries concerned about shellfish and fish stocks that are common prey of pinnipeds and sea otters. Such conflicts have also begun in Hawaii with debate over monk seal conservation and the effects on Hawaiian fisheries and recreation. Finally, the extensive growth of some pinniped

populations in California demonstrates the conflicts between natural and cultural resource management, with pinnipeds hauling Endonuclease out on, disturbing, and destroying non-renewable archeological sites located on the shoreline of the Channel Islands and elsewhere (see Braje et al., 2011a and Braje et al., 2011b). The records of finfish and seabirds are just beginning to be explored in detail, but Braje et al. (2012) recently documented size changes in rockfish (Sebastes spp.), including estimates that many prehistoric specimens were larger than modern fishes. Chendytes lawi, an extinct flightless duck, appears to have been slowly pushed to extinction on the Channel Islands and mainland by human predation and other variables over several millennia ( Jones et al., 2008 and Rick et al., 2012a). Along with human hunting, the extinction of C.

Crucially, the authors provide compelling evidence that repression of N-cadherin is the key event that mediates the two activities of Foxp proteins in the spinal cord, i.e., their ability to promote both delamination and neuronal differentiation. First, high-level expression of a dominant-negative version of N-cadherin results in a Antidiabetic Compound Library disorganization of the neuroepithelium as well as in the premature differentiation of the delaminated cells, defects that are similar to those resulting from the misexpression of Foxp proteins. Second, expression of wild-type N-cadherin together with Foxp4 restores both the neuroepithelial architecture and the size of the progenitor pool, both of which are disrupted

when Foxp4 is overexpressed alone. Together, these findings suggest that N-cadherin repression is the central buy MK-2206 signal by which Foxp proteins couple apical process detachment with the onset of neuronal differentiation in nascent spinal cord neurons. The study by Rousso et al. (2012) together with earlier work from Matsumata and colleagues

(Matsumata et al., 2005) suggest that the regulation of N-cadherin expression during neurogenesis might strongly influence the rate at which progenitors differentiate. Sox2 directly activates N-cadherin transcription (Matsumata et al., 2005) and therefore acts in opposition to Foxp4 to sustain N-cadherin expression levels and maintain the progenitor pool. Rousso et al. (2012) propose that the fine tuning of N-cadherin transcription by the combined input of Foxp4 and Sox2, and possibly other transcription factors, might determine the rate at which NPCs enter neurogenesis. Thus, the reduced level of N-cadherin in motor neuron progenitors compared to adjacent domains in the spinal cord may explain why motor neurons differentiate earlier than other populations of spinal cord neurons. However, the authors also provide evidence that Foxp proteins regulate neurogenesis PJ34 HCl by repressing target genes other than N-cadherin and in particular the Sox2 gene itself. Because Sox2 has been shown to inhibit neurogenesis by promoting N-cadherin expression (Matsumata et al., 2005) and antagonizing the activity of proneural transcription factors

(Bylund et al., 2003), its repression might also contribute significantly to the neurogenic activity of Foxp proteins. The Foxp genes are expressed throughout the developing central nervous system, and Rousso et al. (2012) propose that their function in the cerebral cortex is broadly similar to that in the spinal cord. The cortex of Foxp4 mutant mice exhibits an increase in N-cadherin expression and a reduction in the number of differentiated neurons and, like in the spinal cord, some neurons remain in the progenitor zone. Conversely, Foxp4 overexpression in the mouse embryonic cortex by electroporation results in a downregulation of N-cadherin expression, a reduction in expression of Sox2, and a concomitant increase in expression of the intermediate progenitor marker Tbr2 (Rousso et al., 2012).

This opposing regulation has been demonstrated in epithelial cells, where mTORC1 signaling was increased and mTORC2 signaling was decreased due to

the knockout of Syndecan 4 (Partovian et al., 2008). Interestingly, it was noted that epithelial cell size was decreased, suggesting that decreased mTORC2 signaling, even in the presence of increased mTORC1 signaling, is capable of decreasing cell size. Recent evidence, in cultured cells, suggests that the interplay between these two mTOR complexes may be mediated in part by the ability of the mTORC1 substrate p70S6K to phosphorylate Rictor at residue Thr-1135 (Dibble et al., 2009, Julien et al., 2010 and Treins et al., 2010). Such phosphorylation of Rictor may decrease mTORC2 activity, as two groups have found that mutation of Thr-1135 to Ala increases phosphorylation of AKT Talazoparib solubility dmso at Thr-473, an mTORC2 specific site (Dibble et al., 2009 and Julien Androgen Receptor animal study et al., 2010), although other groups do not observe such an alteration in mTORC2 activity (Boulbes et al., 2010 and Treins et al.,

2010). The potential interplay between mTORC1 and mTORC2 signals highlights the complexity of dissecting their roles in the opiate-mediated effects in VTA in vivo. We propose the model depicted in Figure 7. Chronic opiates, through a reduction in BDNF signaling, reduce AKT activity via reduced phosphorylation at its two main sites. This occurs through two mechanisms: a decrease in total levels of IRS2 and a decrease in mTORC2 activity.

Epothilone B (EPO906, Patupilone) These mechanisms may not be functionally distinct, as downregulation of IRS2 may also lead to decreased mTORC2 activity, consistent with the idea that phosphorylation of the two AKT sites occurs sequentially (Pearce et al., 2010 and Oh and Jacinto, 2011). Reduced AKT-mTORC2 activity then increases VTA neuronal excitability via reduced phosphorylation of GABAA β-subunits (Krishnan et al., 2008 and Wang et al., 2003) and decreased expression of K+ channels. Whether mTORC2 decreases VTA DA activity only via AKT modulation of GABAA and K+ channel activity or via additional mechanisms has yet to be determined. Such increased VTA DA neuron excitability directly triggers shrinkage in the soma size of these neurons, which we propose is a key cellular adaptation that impairs DA output to target regions and mediates reward tolerance. Given that mTORC2′s first noted function was in regulating actin cytoskeleton organization (Sarbassov et al., 2004), decreased mTORC2 activity may alter VTA DA morphology independent of AKT and cell excitability, but this will require identification of additional mTORC2 substrates, a major gap of knowledge in the field. This scheme leaves unanswered two key questions. By what mechanism does chronic morphine repress IRS2 expression, and by what mechanism does chronic morphine induce mTORC1 activity despite a reduction in AKT signaling and lack of alteration in several other upstream proteins.

, 2012). Nevertheless, time and the methods of conditioning may be important variables. Although appetitive and aversive memory retrieval requires output from the αβ ensemble at 3 hr and 24 hr after conditioning (McGuire et al., 2001, Isabel et al., 2004, selleck chemicals Krashes et al., 2007, Krashes et al., 2009 and Trannoy et al., 2011), αβ neurons were shown to be dispensable for 2 hr appetitive memory retrieval (Trannoy et al., 2011). Instead, appetitive retrieval required γ neuron

output at this earlier point (Trannoy et al., 2011). Our experiments were generally supportive of the γ-then-αβ neuron model but revealed a slightly different temporal relationship. The αβ neurons were dispensable for memory retrieved 30 min after training but were essential for 2 hr and 3 hr memory after training (Figures 2 and S7). An early role for γ neurons is further supported by the importance of reinforcing DA input to the γ neurons for aversive memory formation (Qin et al., 2012). It will be interesting to determine whether there is a stratified representation of valence within the γ neuron population. Finding an

appetitive memory-specific role for αβc neurons suggests that the simplest model in which each odor-activated KC has plastic output synapses driving either approach or avoidance (Schwaerzel et al., 2003) appears incorrect. Such a KC output synapse-specific organization dictates that it would not be possible to functionally segregate aversive and appetitive memory by blocking KC-wide output. We however found

a specific role for the αβc neurons in conditioned approach that supports the alternative model of partially nonoverlapping KC representations tuclazepam ISRIB cell line of aversive and appetitive memories (Schwaerzel et al., 2003). The anatomy of the presynaptic terminals of reinforcing DA neurons in the MB lobes suggests that the functional asymmetry in αβ could be established during training in which αβc only receive appetitive reinforcement. Rewarding DA neurons that innervate the β lobe tip ramify throughout the βs and βc, whereas aversive reinforcing DA neurons appear restricted to the αβs. Consistent with this organization of memory formation, aversive MB-V2α output neurons (Séjourné et al., 2011) have dendrites biased toward αs, whereas the dendrites of aversive (Pai et al., 2013) or appetitive (P.Y. Plaçais and T. Preat personal communication) MB-V3 output neurons are broadly distributed throughout the α lobe tip. We therefore propose a model that learned odor aversion is driven by αβs neurons, whereas learned approach comes from pooling inputs from the αβs and αβc neurons (Figure 7). Another property that distinguishes appetitive from aversive memory retrieval is state dependence; flies only efficiently express appetitive memory if they are hungry (Krashes and Waddell, 2008). Prior work has shown that the dopaminergic MB-MP1 neurons are also critical for this level of control (Krashes et al.

, 2000; see also Li et al., 2008), Vardi and colleagues subsequently attributed this result to cross-reactivity of the “T4” antibody and showed that NKCC1 found in the outer plexiform layer of the retina is expressed in horizontal cells (Zhang et al., 2007). The lack of NKCC1 in rod DBCs is also consistent with the demonstration that the chloride reversal potentials are the same at the dendritic and axonal ends of rod DBCs in retinal slices (Satoh et al., 2001), which argues against chloride transport in opposite

directions at these locations. Based on this evidence, we predicted that inactivation of KCC2 in WT mice should shift the chloride equilibrium potential to a more positive value and reduce the amplitude of DBC light response and the ERG b-wave. Indeed, intraocular injections of a KCC2 blocker reduced dark sensitivity, operational range, learn more and Rmax,dark of WT rod-driven b-waves (Figure 3 and Figure 4E), closely resembling reductions seen in GABACR−/− mice. Furthermore, the effects of the KCC2 blockade were see more not restored

by exogenous GABA, which is consistent with a disrupted chloride gradient. Another prerequisite for our hypothesis is the existence of a tonic hyperpolarizing GABA-mediated current. GABACRs are particularly well suited for this function due to lack of GABA-dependent desensitization (Amin and Weiss, 1994). Tonic GABACR-mediated currents have been observed in goldfish bipolar cell terminals (Hull et al., 2006 and Jones and Palmer, 2009) but have not been observed previously in mammalian rod DBCs. To directly document this current, we conducted patch-clamp recordings from rod DBCs in retinal slices. We supplemented our slices with a low concentration of exogenous GABA (5 μM) in the bath to replace GABA lost by perfusion, following the experimental paradigm reviewed in Glykys and Mody (2007). These experiments revealed the presence of a tonic GABAergic current of ∼7 pA in WT rod DBCs that was antagonized by TPMPA (Figures 5A and 5B). This current was absent in GABACR−/− rod DBCs. We next tested whether this GABACR-mediated sustained current could change the rod DBC Purple acid phosphatases resting membrane potential. When we measured the resting membrane potential in

current clamp with zero holding current, TPMPA depolarized the resting potential of WT rod DBCs but had no effect on GABACR−/− rod DBCs ( Figure 5C). This tonic GABACR-mediated conductance is expected to change the input resistance of WT rod DBCs and reduce the degree of depolarization caused by light-dependent synaptic inputs. To test this idea, we determined the input resistance in WT rod DBCs by measuring voltage changes in response to current injection in the presence or absence of TPMPA. As predicted, blocking GABACRs in WT rod DBCs increased the slope of the current-voltage (I-V) plot and, consequently, the rod DBC input resistance (Figures 5D and 5E). In contrast, TPMPA did not significantly alter the input resistance of GABACR−/− rod DBCs.