Physalin B may be an excellent compound to reduce parasite

Physalin B may be an excellent compound to reduce parasite

transmission and control Chagas disease but more investigations are necessary to elucidate if the physalin inhibits parasite development due to alterations in immune responses, or in the microbiota population or in both of them together. D.P.C. is a post-doctorate researcher with CAPES and FAPERJ (Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro) scholarship. This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) to E.S.G. and P.A., Fundação Oswaldo Cruz (Papes project to P.A.). E.S.G. and P.A. are CNPq Senior Research MK-2206 chemical structure Fellows. “
“The Asian tiger mosquito Aedes albopictus is an emerging model for the study of the eco-physiology of egg diapause. It is a successful invasive species now present in all continents

excepted Antarctica ( Bonizzoni et al., 2013). It was first introduced in tropical countries around the 18th century, in water-stock of migrants’ ships, and a second wave of invasion NVP-BKM120 price is still ongoing in tropical areas ( Delatte et al., 2011). The colonization of temperate areas began in the middle of the 20th century, through used tire traffic by ships from Asian subtropical areas ( Kuno, 2012 and Urbanelli et al., 2000). As it is an effective vector for many arboviruses ( Gratz, 2004), this species represents a new public health threat for the US and Europe. Its role as the exclusive vector in epidemics in temperate areas has been proven for chikungunya and dengue fevers ( Rezza et al., 2007 and Vega-Rua et al., 2013). There is a remote risk that diapausing eggs will be infected by arboviruses

( Guo et al., 2007); this could lead to the persistence of arboviruses in mosquito Calpain populations in temperate countries. Diapause is an adaptation and a complex physiological process defined as “a form of dormancy that is hormonally programmed in advance of its onset and is not immediately terminated in response of favorable conditions” (Denlinger and Armbruster, 2014). Diapausing individuals are indeed usually more resistant to harsh environmental conditions than non-diapausing ones. Desiccation (Sota and Mogi, 1992a and Urbanski et al., 2010a) and cold resistance are generally enhanced during diapause (Hanson and Craig, 1995) and post-diapause (Thomas et al., 2012) as for A. albopictus eggs. Diapause also enhances nutritive resources ( Hahn and Denlinger, 2011), and even irradiation resistance ( Brower, 1980) in insects. Numerous examples show that the diapause status of the progeny is determined by the exposure of ovipositing females to short photoperiod ( Mousseau and Fox, 1998). The annual variation in day length is the most reliable indicator of seasonality in temperate areas.

So, understanding the changes in the reproductive biology of snai

So, understanding the changes in the reproductive biology of snails infected with A. cantonensis E7080 clinical trial is essential for developing effective methods against the spread of human eosinophilic meningoencephalitis. However, it is surprising that studies of the reproductive activity of A. cantonensis-infected snails

have not yet been conducted, since this parasite has great importance to public health and the response to infection is highly variable among snail species infected by different helminths ( Tunholi et al., 2011). To shed light on this subject, the present study analyzed for the first time, the changes in the reproductive biology of Biomphalaria glabrata caused by infection by A. cantonensis during its prepatent period (3 weeks of infection) ( Guilhon and Gaalon, 1969), using the parameters total number of eggs, number of egg masses, number of eggs/mass, number of eggs/snail, percentage of viable eggs, and galactogen content in albumen gland, as well as the histological status of the gonad (ovotestis of infected snails). The different mechanisms possibly related to this phenomenon are also discussed. The snails were kept in aquariums containing 1500 ml of dechlorinated water, to which 0.5 g of CaCO3 was added. Polystyrene plates measuring ±2 cm2 were placed inside the aquariums to serve as substrate for egg laying. The snails were fed with dehydrated lettuce leaves

(Lactuca sativa L.) ad selleck screening library libitum. Six groups were formed: three control groups (uninfected) and three treatment groups (infected). Each aquarium contained 10 snails, reared Fenbendazole in the laboratory from hatching to be certain of their age and sexual maturity. The entire experiment was conducted in duplicate, using a total of 120 snails. Third-stage larvae (L3) of A. cantonensis, obtained

from specimens of Achatina fulica collected from Olinda, Pernambuco, Brazil (8°1′0″S/34°51′0″W, altitude 16 m) in 2008, in the area surrounding the home of a human patient diagnosed with eosinophilic meningoencephalitis, were inoculated in Rattus norvegicus in the Laboratório Nacional de Referência em Malacologia Médica and Laboratório de Patologia do Instituto Oswaldo Cruz (Fiocruz, RJ, Brazil), where the cycle is maintained. The first-stage larva (L1) utilized in this study were obtained from this experimental cycle maintained in the mentioned laboratories. The feces of parasitized R. norvergicus were collected to obtain the larvae by the technique of Baermann ( Willcox and Coura, 1989). After processing the fecal samples, specimens of B. glabrata (8–12 mm) at 90 days old on average were exposed individually to approximately 1200 L1 larvae ( Yousif and Lammler, 1977). After 48 h the snails were transferred to the aquariums. The polystyrene plates were removed from the aquariums and the numbers of egg masses and eggs laid were counted under a stereoscopic microscope on alternate days until three weeks after infection.

1C) The ER-alpha was mild and showed a localization similar to t

1C). The ER-alpha was mild and showed a localization similar to that observed in group V (Fig. 1D and Table 1). However, in animals treated with oestrogen (group III), PI3K inhibitor INS-R and ER-alpha were expressed moderately (Fig. 1E and F and Table 1). In animals treated with insulin (group II), INS-R was expressed mildly and was mainly localized around the salivary ducts. In contrast, expression of oestrogen receptors was intense and these receptors were immunolocalized in epithelial cells, mainly close to the nuclei (Fig.

1G and H and Table 1). Diabetic animals of group I showed mild and intense expression of insulin and oestrogen receptors, respectively (Fig. 1I and J and Table 1). Expression of INS-R was intense in group V and was localized close to the acini and mainly in the glandular ducts (Fig. 2A). In this group, expression of ER-alpha was mild and was localized in the nucleus of ductal cells (Fig. 2B and Table 1). In group IV, INS-R was expressed intensely close to the salivary ducts (Fig. 2C). ER-alpha showed mild expression close to the nucleus of ductal cells (Fig. 2D and Table 1). In group III, expression of ER-alpha and INS-R was moderate and was localized close the nuclei of epithelial cells and glandular ducts, respectively (Fig. 2E and F and Table 1). In animals

treated with insulin (group II), there was intense expression of ER-alpha close the nuclei of epithelial cells. INS-R expression BGB324 mouse was mild and mainly

occurred close almost to the ducts (Fig. 2G and H and Table 1). In group I, expression of INS-R and ER-alpha was very mild and intense, respectively, maintaining the pattern of localization (Fig. 2I and J and Table 1). In the present study, untreated diabetic animals showed elevated glucose levels, whereas these levels returned to normal and were similar to that of the control group in animals treated with insulin alone and in combination with oestrogen. It should be pointed out that glucose levels were also significantly reduced in the group receiving only oestrogen. The non-obese diabetic (NOD) mouse represents one of the best models of insulin-dependent diabetes.46 Insulin is an anabolic hormone produced by the pancreas but is also secreted to different extents by other organs and is known to be a mediator of physiological events in the salivary glands. Insulin regulates blood glucose levels and maintains the homeostasis of different tissues.28, 32, 47 and 48 According to Hu et al.,49 under the action of insulin normal glucose levels are close to 180 mg/dl, whereas an effective diabetic state is characterized by mean levels of 300 mg/dl or higher.43 In addition to insulin, oestrogen also affects glucose metabolism and insulin resistance and might be associated with the development of diabetes mellitus.50 Other studies support these findings.

These methods were optimized as previously

described with

These methods were optimized as previously

described with some modification [27]. For both methods, each mass spectrum was obtained from the sum of 10 scans of 150 laser shots each and using 512 K data points. Typically, the target plate offset was 100 V with the deflector plate set at 180 V. The ion funnels operated at 100 V and 6.0 V, respectively, with the skimmers at 15 and 5 V. The analyzer entrance was maintained at −7 V, and side kick technology was used to further optimize peak shape and signal intensity. The two acquisition settings differentiate for the trapping potentials (LM, 0.6 and 0.55 V; Alpelisib datasheet HM, 0.95 and 0.80 V), the required excitation power (LM, 25%; HM, 28%) and pulse time (LM, 10 μs; HM, 20 μs), the time of flight to the ICR cell (LM, 1.350 ms; HM, 2.700 ms) and the quadrupole filter mass (LM, m/z 1300; HM, m/z 2500). For each spotted sample, two duplicate spots were measured using the LM and the other two using the HM. Approximately 4.5 h were needed to measure 384 MALDI spots (i.e. originating from 96 different serum samples). DataAnalysis Software 4.0 SP 5 Y 27632 (Bruker Daltonics) was used for the visualization and the calibration of the spectra. Prior to the measurement of each MALDI plate the FTICR system was externally

calibrated using a commercially available peptide mix and a protein mix (Bruker Daltonics). The spectra obtained using the LM were internally calibrated only when used for identification purposes. The m/z-values used for the internal calibration of the LM and the HM are reported in Table S1 in the Supplementary Material. Peaks were

determined using the FTMS algorithm with a signal-to-noise threshold of 3 and using the centroid for peak position with a percentage height of 80. Protein and/or peptide signals in RPC18 profiles were quantified as follows. First, based on visual inspection of the profiles, 457 and 670 peaks were selected for the LM and HM spectra, respectively, for further analysis. To this end, a so-called reference file was compiled for both types of profiles in such a way that for each selected peak the m/z-value, Temsirolimus research buy a peak number and an m/z-window were reported. In the LM profiles, this m/z-window ranged from 0.015 to 0.166 Da while in the HM it ranged from 0.05 to 0.31 Da reflecting the peak width along the spectra. Then, the in-house developed Xtractor tool was used to determine the intensity of each user-defined peak. This open source tool generates uniform data (peak) arrays regardless of spectral content ( MALDI-FTICR profiles were exported as XY (.xy) files, all containing m/z values with corresponding intensities. Although peptide and proteins were measured up to 10,000 Da using the HM method, the peak selection was limited to 9043.3 Da. The analysis of the spectra in the m/z-range from 9043.3 to 10,000 is on-going and the results will be presented in a separate study.

elsevier com/locate/withdrawalpolicy) This article has been retr This article has been retracted at the request of the first author, who accepts responsibility. Following an internal review committee at UT Southwestern Medical Center, Dallas, evidence has been found of improper duplication in Fig. 1 of this article. “
“Small-cell lung cancer (SCLC) is

the most rapidly growing lung cancer subtype and patient prognosis is extremely poor [1]. Although most SCLC patients respond to initial treatment, long-term survival is low. Unfortunately, disease progression or relapse occurs in almost all advanced-stage SCLC patients and in the majority of early-stage SCLC patients [2], [3], [4], [5] and [6]. Response to subsequent chemotherapy depends on responsiveness to previous induction chemotherapy and the interval between cessation of initial therapy and disease progression [7] and [8]. Overall response rates (ORRs) of 21–38% and median overall survival (OS) of 6.9–11.7 months were reported in chemotherapy-sensitive SCLC patients after treatment with topotecan, a topoisomerase I inhibitor [8] and [9]. A previous randomized study buy ABT-888 demonstrated similar efficacy and improved tolerability of topotecan compared with cyclophosphamide, doxorubicin, and vincristine [10]. Topotecan is also considered as a treatment option for chemotherapy-refractory

SCLC; however, low ORRs (0–11%) and OS (median, 4.7–5.4 months) have been reported [8], [9] and [11]. Thus, a standard chemotherapy for the treatment of refractory SCLC has not yet been established. However, effective treatment must be developed to improve prognosis for Tangeritin SCLC patients. Amrubicin (AMR), a fully synthetic 9-aminoanthracycline, is metabolized in the body to the active metabolite amrubicinol, which has higher antitumor activity than AMR. Both AMR and amrubicinol, which are topoisomerase II inhibitors, exhibit antitumor activities against various human tumors

in xenograft models and have shown no risk of typical anthracycline cardiotoxicity [12]. In subgroup analyses of small phase II studies, AMR showed promising activity in patients with refractory SCLC with ORR of 17–50% and median OS of 5.3–10.3 months [9] and [13]. Accordingly, the results of previous studies indicated that AMR may be useful for treating refractory SCLC. Therefore, we conducted this study to confirm the efficacy and safety of AMR, a topoisomerase II inhibitor, for treating refractory SCLC. A phase III trial was preferred to evaluate the effectiveness of AMR therapy; however, other than AMR therapy, there was no promising treatment under development for refractory SCLC at that time. As second-best evidence that was not from a randomized controlled trial, we designed a nonrandomized single-arm confirmatory study to evaluate whether AMR therapy can be considered as a standard treatment for refractory SCLC.

Fetal bovine serum (FBS), phytohaemagglutinin, and trypsin–EDTA w

Fetal bovine serum (FBS), phytohaemagglutinin, and trypsin–EDTA were purchased from Cutilab (Campinas, SP, Brazil). RPMI 1640 medium Doramapimod solubility dmso was purchased from GIBCO (Invitrogen, Carlsbad, CA, USA). ConA, Rhodamine 123

(Rho-123), etoposide, penicillin, streptomycin, and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) were purchased from Sigma–Aldrich Co. (St. Louis, MO, USA). Normal melting point agarose (NMPA) and low melting point agarose (LMPA) were obtained from Invitrogen (Carlsbad, CA, USA). Doxorubicin (Doxolem®) was purchased from Zodiac Produtos Farmacêuticos S. A. (São Paulo, SP, Brazil). All other chemicals and reagents used were of analytical grade. ConA was obtained from SIGMA (São Paulo, Brazil) and ConBr was purified from the crude saline extract of seed flour through affinity chromatography on Sephadex G-50 fast flow (SIGMA) according to Cavada et al. (1998). The human promyelocytic leukemia

(HL-60) and acute lymphoblastic cell (MOLT-4) lines buy ICG-001 were acquired from Rio de Janeiro Cell Bank (Federal University of Rio de Janeiro, RJ, Brazil). Leukemia cells were maintained in RPMI 1640 medium supplemented with 10% FBS, 2 mM glutamine, 100 U/ml penicillin, and 100 μg/ml streptomycin at 37 °C with 5% CO2. For experiments, the concentration of FBS was reduced to 1% so that the lectins would display their effects (Faheina-Martins et al., 2011). Heparinized blood (from healthy, non-smoking Palmatine donors who had not taken any drugs for at least 15 days prior to sampling) was collected from donor blood at the blood bank of the João Pessoa, Paraíba, Brazil. From these blood samples, we isolated the peripheral blood mononuclear cells (PBMC). The study was approved by the Institutional Ethical Committee

of Lauro Wanderley Hospital/Federal University of Paraíba. PBMC were isolated by a standard method of density-gradient centrifugation over Histopaque-1077 (GE Healthcare, USA). PBMC were washed and resuspended in RPMI 1640 medium supplemented with 10% FBS, 2 mM glutamine, 100 U/ml penicillin, and 100 μg/ml streptomycin at 37 °C with 5% CO2. Phytohemagglutinin (2%) was added at the beginning of the culture. After 24 h of culture, cells were treated with the test lectins. The cytotoxicity of ConA and ConBr to leukemic cells was evaluated using the original enzymatic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to produce formazan crystals (Mosmann, 1983). Cells were seeded at 5 × 104 cells/well in 96-well tissue culture plates. Cells were exposed to different concentrations of ConA or ConBr lectins (1–200 μg/mL) dissolved in the RPMI medium (three wells per concentration) with 1% FBS. After 72 h of incubation, plates were centrifuged (500g, 5 min) and the supernatant was removed, followed by the addition of MTT solution (0.5 mg/mL in PBS) and incubation for 4 h at 37 °C. After 4 h, the MTT formazan product was dissolved in SDS/HCl 0.

, 2003) The evolution of a cheaper web-building and web maintena

, 2003). The evolution of a cheaper web-building and web maintenance in viscid orbweavers would have paved the way for increased metabolic rates, which in turn allowed higher levels of activity. If the generalist

microhabitat choice of the orbweavers of the family Uloboridae Z-VAD-FMK mouse ( Eberhard, 1971) was prevailing when these spiders traded-off a cheaper web for a costly metabolism, the increased activity pattern of the emerging clade (viscid orbweavers) could result in the exploration of a variety of niches derived from the evolution of winged insects ( Vollrath and Selden, 2007), thus explaining the radiation of Araneoidea. In this way, the cheaper web would be a step to the key feature that allowed species diversification: the expensive and enhanced mobility of ecribellate orbweavers. The association between the loss of the cribellum and the evolution of a more diversified clade could be a more general phenomenon. The cribellum has been lost multiple times along the spider phylogeny (Lehtinen, this website 1967) and many cribellate groups are sister to more diverse ecribellate clades (Kawamoto, 2007, Kawamoto and Japyassú, 2007, Spagna and Gillespie, 2008 and Blackledge et al., 2009). Behavioral evidence suggests that the loss of the cribellum is related

to an increased pattern of activity (Forster, 1970, Kawamoto, 2007 and Kawamoto and Japyassú, 2007), indicating that any model that tries to explain the high diversity of ecribellate orbweavers could possibly be an instance of a more general model of spider biodiversity. Our two species study has reinforced the idea that Araneidae has higher resting metabolism compared to the general until expectations for land arthropods.

This high metabolism is associated to an important evolutionary web type transition which is frequently cited as the cause of orbweb radiation. We put forward a model that could explain, from a physiological standpoint, the possible correlation between energetic budget and species diversity in spiders. Variation in such basic physiological parameters certainly has strong fitness consequences, and we expect that our findings motivate the exploration of the possible evolutionary outcomes of changes in the metabolic rate of spiders. We thank Dr. Carlos A. Navas Iannini for the respirometric equipment, materials, and enlightening discussions, Dr. Ingi Agnarsson for insightful discussions about spider behavior, Antônio D. Brescovit for the suggestions of species used and identification of the spiders, Thiago Zahn for providing language help and the two anonymous reviewers for valuable comments that greatly improved the quality of the manuscript. This work was supported by a CAPES grant to T.H.K. and partially supported by a FAPESP grant to F.A.M. (proc. no. 07/52144-5).

Primary dRTA may be a dominant (SLC4A1 gene) or

a recessi

Primary dRTA may be a dominant (SLC4A1 gene) or

a recessive condition (ATP6V1B1 or ATP6V0A4 genes). The inability to secrete H+ ions from the α-intercalated cells of the distal tubule is caused by either a defective vacuolar H+-ATPase (ATP6V1B1 or ATP6V0A4 genes) or a defective Cl−/HCO3− anion exchanger-1 (SLC4A1 gene). Sensorineural hearing loss may be found in patients with ATP6V1B1 mutations. HHRH is a rare, autosomal recessive disorder caused by mutations in the SLC34A3 gene, resulting in loss-of-function of the type IIc sodium phosphate see more cotransporters of the proximal tubule. The decreased renal phosphate reabsorption can result in profound hypophosphatemia, normocalcemia, rickets, and bone pain. Hypercalciuria and nephrolithiasis are also commonly observed

and may be the result of a hypophosphatemia-induced stimulation of 1,25-dihydroxyvitamin D synthesis. The increased synthesis purportedly causes increased gastrointestinal absorption of calcium and excessive urinary calcium losses in the face of normal serum calcium levels. 21 Oxalate is an Vorinostat purchase end product of the metabolic pathways for glyoxylate and ascorbic acid and is primarily excreted by the kidneys. The vast majority (80%–85%) of daily urinary oxalate excretion is derived from normal metabolic homeostasis, and the remainder (10%–15%) is from dietary intake. Daily urine oxalate excretion is generally less than 50 mg/d/1.73 m2 of body surface area. The impracticality of performing 24-hour urine collections in very young patients requires the use of a random urine oxalate to creatinine ratio, which can be used to estimate oxalate excretion (see Table 1). Increased urinary oxalate excretion may be caused by an inherited metabolic disorder (primary hyperoxaluria [PH]) or, more commonly, as a secondary phenomenon caused by increased oxalate absorption or excessive intake of oxalate precursors. PH type I and II are relatively rare, autosomal recessive disorders of endogenous oxalate production. Overproduction Calpain of oxalate by the liver causes excessive urinary oxalate excretion with resultant nephrocalcinosis and nephrolithiasis. The calcium oxalate

deposition results in progressive renal damage; however, the clinical presentation can vary from end-stage renal failure in the neonate to occasional stone passage into adulthood. Because of the clinical variability, the diagnosis is often overlooked and only realized after the loss of a transplanted kidney.22 PH type I is caused by mutations in the AGXT gene, which result in a functional defect of the hepatic peroxisomal enzyme alanine–glyoxylate aminotransferase (AGT). The deficit leads to accumulation of glyoxylate, glycolate, and oxalate in the urine.Pyridoxine is an essential cofactor for proper AGT activity and, rarely, profound vitamin B6 deficiency can mimic PH type I. PH type II is caused by mutations in the GRHPR gene with resultant deficient glyoxylate reductase–hydroxypyruvate reductase enzyme activity.

Comparing the firmness of the

Control bread and of the br

Comparing the firmness of the

Control bread and of the breads of the experimental design during the storage period, it was observed that the firmness that the Control bread presented on Day 1 after processing, was presented by Assay 6 only on Day 10 of storage or that the firmness that the Control bread presented on Day 6 after processing was presented by Assay 5 only on Day 10 of storage. From this analysis, the effectiveness of SSL and/or MALTO in reducing bread firmness, extending softness for a longer storage period, was clearly observed. The four formulations, apart from the Control (without emulsifier or enzyme), selected for the sensory evaluation on Day 6 of storage were: Assay 2 (0.43 g SSL/100 g flour + 0.01 g MALTO/100 g flour), Assay 4 (0.43 g Mitomycin C research buy SSL/100 g flour + 0.03 g MALTO/100 g flour), Assay 6 (0.50 g SSL/100 g

flour + 0.02 g MALTO/100 g flour) and Assay 8 (0.25 g SSL/100 g flour + 0.04 g MALTO/100 g flour), which were those with best results for specific volume and texture. It can be seen that they are the assays with the highest amounts of SSL. The results obtained in the evaluation of bread quality of these 5 formulations Belnacasan nmr through the scoring system described by El-Dash (1978), carried out by a team of 5 specialists in bakery products, are presented in Table 3. It can be observed that all breads from the assays of the experimental design were better evaluated than the Control. The parameters that most contributed to this were the lower scores for volume and crumb texture of the Control. The best total scores, 81.7 and 82 (good, according to Camargo & Camargo, 1987), were obtained for the breads of Assays 4 and 6, with 0.43 g SSL/100 g flour + 0.03 g MALTO/100 g flour and 0.50 g SSL/100 g flour + 0.02 g MALTO/100 g flour, respectively, corroborating the results of specific volume and instrumental

texture. It can be observed that the individual characteristics in which these two assays received higher scores than the other assays and the Control were: volume (specific volume × 3), crust color, crumb structure and crumb texture. The results for specific volume are in accordance with those presented in Fig. 1. Assays 4 and Interleukin-3 receptor 6 presented slightly higher volumes than the others two assays evaluated sensorially. Gómez et al. (2004) report that products elaborated with SSL exhibit marked improvement in crumb structure. The resulting loaves are characterized by a soft, fine crumb structure (Sluimer, 2005). This can be observed in Fig. 1. Relating the sensory results for crumb texture with the instrumental firmness on Day 6 (day of the sensory analysis), it can observed that Assay 6 presented the lowest firmness amongst the assays evaluated sensorially.

addressed this question by exposing live mice to the soiled beddi

addressed this question by exposing live mice to the soiled bedding from many different species of animal, then quantifying the number of VSNs that were stimulated [9]. They found ∼30% of

male VSNs were activated by a mix of difference species, compared to the ∼7% that responded to bedding from NVP-LDE225 female mice. Moreover, by combining the detection of neuronal activity with in situ hybridisation of receptor transcript-specific probes, it was possible to infer which VRs were detecting heterospecific or conspecific cues. They found 63 single VRs that were activated by hetero-specific cues and 25 that responded to mouse-specific cues. Consistent with the different behaviours provoked by pheromones and kairomones, only 11 VRs were activated by both [9]. Taken together these studies revealed that mediating social behaviour may be a minor function of the mouse VNO. In fact the majority of the VRs could be tuned to detect a diversity of chemical signals generated by other species that share an environment with mice. Parallel to Cyclopamine order this, however, is a growing body of literature reporting

pheromone-like signals that are mediated by specific sensory neurons in other olfactory subsystems 10, 11 and 12]. The subfamilies of receptors implicated in detecting many of these tend to be relatively small and are therefore unlikely to balance out the proportion of VRs tuned to kairomones. With fewer receptors tuned to detect pheromones that Selleckchem CHIR-99021 previously thought, a linear relationship between signals, VRs and behaviours remains possibility. However, a number of studies have provided evidence that there is both redundancy and synergy in the receptor/ligand repertoire. Haga-Yamanaka and colleagues [13••] used a genetically encoded calcium indicator to identify VSNs that responded to sulphated

estrogens (SEs). These sensory neurons were also specifically activated by urine from female mice in oestrus, suggesting SEs may act as female-to-male sex pheromones. Two VRs were repeatedly identified in the activated VSNs: Vmn1r89 and Vmn1r85. By fluorescently tagging, it was possible to determine that two different SEs activate both classes of VSN ( Figure 1). Moreover Vmn1r89-expressing VSNs were activated by two further SEs and at least one sulphated androgen [13••]. While it remains a possibility that these VSNs buck the ‘one receptor per neuron’ paradigm and express additional chemosensory receptors [14], it appears more likely that they each express single VRs that are tuned to detect multiple and overlapping chemical signals. What advantages does this coding strategy provide for detecting pheromones that mediate behaviour? From the perspective of an investigating male, receptor redundancy would insure against the reproductively catastrophic consequences of losing the ability to assess when a female is receptive.