In M-Nha, most Asp residues (14/19) were predicted to be in the hydrophobic region, while the alignment of M-Nha with Na+/H+ antiporters of another six microorganisms indicated that three aspartates, including Asp-138, Asp-167 and Asp-224, were conserved in M-Nha (Fig. 3). The protein encoded by m-nha gene showed a high similarity of 92%, 86% and 62% to NhaH from H. dabanensis D-8T, H. aidingensis AD-6T and B.

subtilis, respectively. Interestingly, M-Nha has a long carboxyl terminal hydrophilic tail (140 amino acid residues), similar to Nhap and NhaG type Na+/H+ antiporters, whereas NhaH does not. It was reported that both the ion specificity and activity of an Na+/H+ antiporter were partially determined by the structural properties of the C-terminal hydrophilic tail (Hamada et al., 2001; Waditee et al., 2001). NhaG from B. subtilis possesses a hydrophilic segment with >100 amino acid Birinapant manufacturer residues at the carboxyl terminal region (Gouda et al., 2001), and such a long hydrophilic domain is not present in any other microbial Na+/H+ antiporter except SynNhaP (NhaS1) in Synechocystis sp. (Hamada et al., 2001) and ApnhaP in A. halophytica (Waditee et al., 2001). The activities of NhaG decreased

when 26 residues in the C-terminal of the protein were lost (Gouda et al., 2001), and 56 residues in the C-terminal region of SynNhaP were necessary for antiporter activity (Hamada et al., 2001). Hydropathy analysis RXDX-106 in vitro usually showed that the Na+/H+ antiporter had 10–12 hydrophobic and also probably membrane-spanning regions (Majernik et al., 2001; Yang et al., 2006). Our results also revealed that m-nha gene product fits well into this model. The NhaH Mirabegron and NhaG had 12 TMS, but M-Nha had only 10 TMS, although they all had high similarity of amino acid sequence. Consequently, the mechanism of ion transport by M-Nha from the Dagong Ancient Brine Well should be different from that of NhaH, NhaG and SynNhaP. With the differences of amino acid sequence and the putative secondary structure of the protein encoded

by m-nha from those Na+/H+ antiporter genes reported previously, it can be proposed that m-nha is a novel Na+/H+ antiporter gene. This study was significant in not only helping us understand the necessity of the existence of Na+/H+ antiporter in the Dagong Ancient Brine Well to maintain the intracellular environment homeostasis for halophiles, but also enriches our knowledge about the different mechanisms of Na+/H+ antiporter in halophiles in such an extreme environment. We thank Dr Terry A. Krulwich (Department of Biochemistry, Mount Sinai School of Medicine of the City University, New York) and Prof. Susheng Yang (Department of Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China) for donating the strain E. coli KNabc.

In M-Nha, most Asp residues (14/19) were predicted to be in the hydrophobic region, while the alignment of M-Nha with Na+/H+ antiporters of another six microorganisms indicated that three aspartates, including Asp-138, Asp-167 and Asp-224, were conserved in M-Nha (Fig. 3). The protein encoded by m-nha gene showed a high similarity of 92%, 86% and 62% to NhaH from H. dabanensis D-8T, H. aidingensis AD-6T and B.

subtilis, respectively. Interestingly, M-Nha has a long carboxyl terminal hydrophilic tail (140 amino acid residues), similar to Nhap and NhaG type Na+/H+ antiporters, whereas NhaH does not. It was reported that both the ion specificity and activity of an Na+/H+ antiporter were partially determined by the structural properties of the C-terminal hydrophilic tail (Hamada et al., 2001; Waditee et al., 2001). NhaG from B. subtilis possesses a hydrophilic segment with >100 amino acid PKC412 chemical structure residues at the carboxyl terminal region (Gouda et al., 2001), and such a long hydrophilic domain is not present in any other microbial Na+/H+ antiporter except SynNhaP (NhaS1) in Synechocystis sp. (Hamada et al., 2001) and ApnhaP in A. halophytica (Waditee et al., 2001). The activities of NhaG decreased

when 26 residues in the C-terminal of the protein were lost (Gouda et al., 2001), and 56 residues in the C-terminal region of SynNhaP were necessary for antiporter activity (Hamada et al., 2001). Hydropathy analysis ZD1839 molecular weight usually showed that the Na+/H+ antiporter had 10–12 hydrophobic and also probably membrane-spanning regions (Majernik et al., 2001; Yang et al., 2006). Our results also revealed that m-nha gene product fits well into this model. The NhaH to and NhaG had 12 TMS, but M-Nha had only 10 TMS, although they all had high similarity of amino acid sequence. Consequently, the mechanism of ion transport by M-Nha from the Dagong Ancient Brine Well should be different from that of NhaH, NhaG and SynNhaP. With the differences of amino acid sequence and the putative secondary structure of the protein encoded

by m-nha from those Na+/H+ antiporter genes reported previously, it can be proposed that m-nha is a novel Na+/H+ antiporter gene. This study was significant in not only helping us understand the necessity of the existence of Na+/H+ antiporter in the Dagong Ancient Brine Well to maintain the intracellular environment homeostasis for halophiles, but also enriches our knowledge about the different mechanisms of Na+/H+ antiporter in halophiles in such an extreme environment. We thank Dr Terry A. Krulwich (Department of Biochemistry, Mount Sinai School of Medicine of the City University, New York) and Prof. Susheng Yang (Department of Microbiology, College of Biological Sciences, China Agricultural University, Beijing, China) for donating the strain E. coli KNabc.

A total of 21 protein spots were identified to be differentially expressed. Our results indicated that the bacteriostatic mechanism of allitridi in H. pylori can be attributed to its multitarget inhibitory

effects in energy metabolism and biosynthesis including amino acid biosynthesis, protein synthesis, mRNA synthesis and fatty acid biosynthesis. Allitridi can also disturb the expression of antioxidant proteins and decrease the production of virulence factors. Western blot analysis showed that allitridi at subinhibitory concentrations can potently suppress the production of CagA and VacA. Our investigations on the antibacterial Ulixertinib mode of action of allitridi provide an insight into the potential use of allitridi as a therapeutic agent against H. pylori infection. It has been demonstrated that Helicobacter pylori infection DAPT mw is strongly associated with some gastrointestinal diseases, such as gastritis, peptic ulcers and gastric carcinoma (Marshall & Warren, 1984; Parsonnet et al., 1991). Many clinical evidences show that eradication of H. pylori results in significant remission from these diseases (Labenz & Börsch, 1994; Bayerdörffer et al., 1995). Widely used triple therapy, consisting of a proton pump inhibitor and two antibiotics such as metronidazole, amoxicillin, or clarithromycin, yields

a high eradication rate (Lind et al., 1996). However, eradication failure often occurs, which is associated with undesirable side effects of these drugs, poor patient compliance and high

cost of combination therapy. An additional reason that should be emphasized is the increasing resistance of H. pylori to antibiotics. For example, strains of H. pylori resistant to metronidazole and clarithromycin have been reported (Mégraud & Doermann, 1998). Thus, it becomes highly necessary to search for an efficacious antibacterial agent to overcome the Ribonuclease T1 above clinical problems. Moreover, according to the present view, it is better if this agent comes from natural products rather than chemical synthetics. Garlic probably has the potential to fulfill these requirements. Since ancient times, garlic has been recognized as a valuable folk medicine, and has been used extensively as an antimicrobial agent against bacteria, viruses and fungi (Bolton et al., 1982; Augusti, 1996). Garlic, a natural food in diet, has some extraordinary advantages as an antibacterial agent, including easy accessibility, low cost and negligible side effects with moderate consumption. Garlic is even active against antibiotic-resistant organisms (Fani et al., 2007). Garlic extracts in combination with antibiotics can lead to total or partial synergism (Didry et al., 1992). Garlic can also suppress toxin production by bacteria (Dewitt et al., 1979). It has been shown that garlic constituents can inhibit the growth of H. pylori in vitro (O’Gara et al., 2000; Cañizares et al., 2004a, b).

We used the tool to screen three published

studies with sequences deposited in the first 2 months after our GenBank survey took place. Among the 1076 16S sequences published by Fujita et al. (2010), we found 403 (37%) sequences that were reverse complementary (i.e. average HMM detection ratio of 0 : 6), indicating that reverse complementary sequences can be a very significant problem. Screening the very small dataset of Jurado et al. (2010), one among the 39 sequences was reverse complementary (i.e. HMM ratio 0 : 10), indicating that reverse complementary entries can occur even in very small datasets where manual see more curation should not be an issue. No reverse complementary sequences or any other anomalies were detected among the 11 173 sequences published by Durso et al. (2010), demonstrating that v-revcomp can identify studies of high data integrity with respect to reverse complementary sequences. The fraction of reverse complementary 16S sequences in public data repositories is around 1%, which Antiinfection Compound Library price must be seen as low, given the error-prone user-controlled submission mechanism and the lack of support for third-party annotation of INSD entries (Pennisi, 2008). Nevertheless, the over 9000 reverse complementary

sequences can have serious implications for downstream analysis if the user is not aware of their status. Furthermore, the number of sequences deposited in these repositories will increase drastically with HTS technologies used in amplicon and metagenome sequencing projects, highlighting the need to detect these events in an automated manner. The clear cases of reverse complementary sequences found in this survey were reported to NCBI for reorientation. NCBI does not need prior agreement with sequence authors in order to correct sequences that were deposited in the incorrect

orientation, and such reorientations are brought about quickly. While the problem of reverse complementary sequences can be avoided with v-revcomp, the number and types of anomalous 16S sequences are of greater concern. It is worrisome that we detected 136 sequences that were taxonomically misclassified at the domain level, and more surprising that 26 cases did Ergoloid not even represent ribosomal genes. Our results stress the importance of critically examining sequences before inclusion in scientific analysis and submission to public databases (Harris, 2003). While v-revcomp is specifically designed to detect reverse complementary sequences, it has certain intrinsic capabilities of detecting some types of sequences anomalies such as reverse complementary chimeras, nontarget genes and erroneous reads. In particular, large-scale metagenome sequencing projects that require automated fragment assembly are prone to errors that could be detected by v-revcomp.

8,9 However, studies referring specifically to traveling children are scarce which may partially be explained by the fact that most of the young children of immigrant families cannot be considered as immigrants since they have been born in Western countries and therefore have a susceptibility to endemic tropical diseases which is more similar to that of a tourist than to that of their parents.10,11 Thus, the CVFR population combines a personal risk due to their age-linked vulnerability Saracatinib nmr with a situation of environmental risk related to contact with the local population and frequent accommodation in zones with poor hygienic

standards.12,13 Nearly 78% of the children were CVFR. This fact reflects Selleckchem LDE225 the high immigration density of the Barcelona North Metropolitan area (with districts such as El Fondo and Sant Roc, accounting for over 45%) thus demonstrating the emerging population of children participating in VFR trips.14,15 Overall, this population has little mother-to-child transmitted or acquired immunity to tropical pathogens since 83% had been born in the EU by long-settled immigrant women.16,17

Therefore, free access to International Health Units with prevention programs preventive activities (specifically immunization and antimalarial chemoprophylaxis) is of a great importance among families with CVFR. The significant predominance of CVFR over tourists was related to a younger age, a longer duration of the trip, a greater frequency of rural stay or private lodging as well as a high probability of consultation in the ineffective period. These findings are coherent with those of other studies and emphasize the close contact with the ecosystem and the non-European society to which these children are exposed. Multivariate analysis Amisulpride identified the main risk factors associated with being a CVFR, with staying in rural areas, visit to the Unit within the ineffective period, and age (the greater the age, the lower the probability of being CVFR).18–22 The presence of a

shorter consultation-travel time interval and a greater proportion of children seen within the ineffective period compared with tourists have been reported by other authors.23 These figures presented here, however, are globally better than those refereed by other studies undertaken in countries in which preventive international health services are entirely private.24 This may be because the Catalan Health System is easily accessible and free of charge for children and is therefore able to reach low-income immigrant families which are the majority in our reference zone. The main destinations for both CVFR and tourists were countries of the Neotropical ecosystem (Meso and South America). By contrast, most studies have reported that the main destinations were countries within the African or Asian Paleotropical biogeographic areas.

An important avenue for future work is exploring the relative roles of these candidate musical features on ISS. Our results demonstrate that auditory structures of the temporal lobe, including HG, PT, PP and pSTG bilaterally, were highly synchronized across subjects during music listening. Interestingly, no differences were evident in auditory cortical synchronization for the Natural Music > Spectrally-Rotated comparison, although differences were evident for the Natural Music > Phase-Scrambled comparison (Fig. 4). Amplitude modulation in the Natural Music and Spectrally-Rotated conditions is one possible explanation Pritelivir nmr for ISS across both tasks in the auditory cortex. This interpretation

is supported by previous studies which have shown auditory cortical sensitivity to low-frequency amplitude modulation in speech (Ahissar et al., 2001; Abrams et al., 2008, 2009; Aiken & Picton, 2008) and other auditory stimuli (Boemio et al., 2005), and is further supported by single and multi-unit activity measured in auditory cortex of animal models during the processing of spectro-temporally complex auditory stimuli (Wang et al.,

1995; Nagarajan et al., 2002). In this context it is noteworthy that a significant ISS difference was evident in auditory cortex for the Natural Music > Phase-Scrambled comparison (Fig. 4, right). These results indicate that despite the well-documented sensitivity of auditory cortex to spectral and harmonic information (Zatorre et al., 2002), which are selleck kinase inhibitor present in the Phase-Scrambled condition, these features alone, in the absence of Quizartinib mw temporal patterns, are insufficient to drive ISS. Our results extend these previous findings by showing that the disruption of temporal patterns in music significantly reduces the consistency of auditory cortical activity measured across individuals. Moreover, our results point to the involvement of both primary and secondary auditory cortical structures, including HG, PP, PT and pSTG, in tracking the temporal structure of music across time periods lasting minutes. Additionally, a recent ISS study showed that activity in bilateral STG and HG are recruited during timbral

processing of a naturalistic musical stimulus, and bilateral STG and right-hemisphere HG are also active during rhythm processing (Alluri et al., 2012). ISS results in the current study also support a role for STG and HG in rhythm processing given that (1) ISS in these auditory cortical regions was only evident when temporal features were present in the stimuli (see Fig. 4), and (2) temporal features, such as amplitude modulation, are fundamental to the perception of rhythm (Sethares, 2007). An intriguing aspect of the results was the finding of differences in ISS for the Natural Music > Spectrally-Rotated condition in sub-cortical structures but not in auditory cortex. While both sub-cortical (Chandrasekaran et al., 2009) and cortical structures (Fecteau et al., 2004; Chait et al.

The diagnostic accuracy of TIMP-1 alone to predict F≥2 was high, and the diagnosis of F≥2 was slightly increased when a regression model that included TIMP-1 and hyaluronic acid was applied [15]. These results disagree with those reported here. Different degrees of liver inflammation might account for this disagreement, as TIMP-1 levels correlate with liver inflammation [27]. High necro-inflammatory

activity may reduce the specificity of TIMP-1. Indeed, in previous studies in HCV monoinfection, TIMP-1 levels alone had high sensitivity, but relatively low specificity [27–29]. However, previous studies on MMP-2 in HCV monoinfection also yielded conflicting results, with some studies finding MMP-2 useful in predicting fibrosis [28,30] and other studies showing low diagnostic utility [27,29]. The reason for these contradictory results is not clear. In the present study, a regression Y-27632 model combining AST, platelet count and MMP-2 predicted with high certainty the Decitabine in vivo absence and presence of F≥2. One-third of the study population could be spared liver biopsy by applying this model. This figure

is in agreement with that reported in a recent systematic review, in which cut-off values of biomarkers could rule out or rule in fibrosis in 35% of patients [13]. Importantly, there were a few diagnostic errors both for excluding and for detecting F≥2 in the present study. In addition, we found that using a simple index that includes in the calculation AST and platelets, as the APRI, in the first step in a diagnostic algorithm and, in the second step, a high cut-off value of MMP-2 levels increased the yield of correct F≥2 diagnoses. With this approach, it was possible to save 46% of the study group from liver biopsy. Moreover, all the classification errors were a result of patients showing F1 in the liver biopsy. The goal of the present study was to achieve maximal diagnostic accuracy with the lowest possible rate of classification errors. Thus, the Rebamipide lower cut-off for the diagnosis of F≥2 yielded an NPV of 88%, and the higher cut-off yielded a PPV of 87%. The rate of misclassifications using both cut-offs was 13%. This strategy reduced the proportion of the study population who could

be classified to one-third of the patients. In a study by Larrousse et al. [15], the cut-off point with the lowest diagnostic errors derived from their model to detect F≥2 yielded a PPV of 80% and an NPV of 77% and involved 78% of the population. However, 22% of the patients were erroneously classified [15]. This high rate of misclassification precludes the application of the Larrousse and colleagues model in clinical practice. However, the selection of two cut-off values from that model with the highest predictive values would probably decrease its rate of classification errors. In the present study, cirrhosis could be detected with a higher cut-off value using the MAPI with a relatively low rate of diagnostic errors. However, only 60% of patients with cirrhosis were detected.

The diagnostic accuracy of TIMP-1 alone to predict F≥2 was high, and the diagnosis of F≥2 was slightly increased when a regression model that included TIMP-1 and hyaluronic acid was applied [15]. These results disagree with those reported here. Different degrees of liver inflammation might account for this disagreement, as TIMP-1 levels correlate with liver inflammation [27]. High necro-inflammatory

activity may reduce the specificity of TIMP-1. Indeed, in previous studies in HCV monoinfection, TIMP-1 levels alone had high sensitivity, but relatively low specificity [27–29]. However, previous studies on MMP-2 in HCV monoinfection also yielded conflicting results, with some studies finding MMP-2 useful in predicting fibrosis [28,30] and other studies showing low diagnostic utility [27,29]. The reason for these contradictory results is not clear. In the present study, a regression www.selleckchem.com/products/r428.html model combining AST, platelet count and MMP-2 predicted with high certainty the Dasatinib chemical structure absence and presence of F≥2. One-third of the study population could be spared liver biopsy by applying this model. This figure

is in agreement with that reported in a recent systematic review, in which cut-off values of biomarkers could rule out or rule in fibrosis in 35% of patients [13]. Importantly, there were a few diagnostic errors both for excluding and for detecting F≥2 in the present study. In addition, we found that using a simple index that includes in the calculation AST and platelets, as the APRI, in the first step in a diagnostic algorithm and, in the second step, a high cut-off value of MMP-2 levels increased the yield of correct F≥2 diagnoses. With this approach, it was possible to save 46% of the study group from liver biopsy. Moreover, all the classification errors were a result of patients showing F1 in the liver biopsy. The goal of the present study was to achieve maximal diagnostic accuracy with the lowest possible rate of classification errors. Thus, the BCKDHA lower cut-off for the diagnosis of F≥2 yielded an NPV of 88%, and the higher cut-off yielded a PPV of 87%. The rate of misclassifications using both cut-offs was 13%. This strategy reduced the proportion of the study population who could

be classified to one-third of the patients. In a study by Larrousse et al. [15], the cut-off point with the lowest diagnostic errors derived from their model to detect F≥2 yielded a PPV of 80% and an NPV of 77% and involved 78% of the population. However, 22% of the patients were erroneously classified [15]. This high rate of misclassification precludes the application of the Larrousse and colleagues model in clinical practice. However, the selection of two cut-off values from that model with the highest predictive values would probably decrease its rate of classification errors. In the present study, cirrhosis could be detected with a higher cut-off value using the MAPI with a relatively low rate of diagnostic errors. However, only 60% of patients with cirrhosis were detected.

The bacterial indicator strains used in this study are listed in Table 1. Bacterial growth was performed in Luria–Bertani (LB) broth at 37 °C. The producer strain B. subtilis B38 was grown in tryptic soy broth (TSB) at 30 °C. The antibacterial activity was assayed using the agar disk diffusion method as described previously (Tabbene et al., 2009a). The titer of antibacterial activity was expressed as activity units (AU) mL−1 and corresponded to the reciprocal of the highest dilution showing growth inhibition of the Pseudomonas aeruginosa ATCC 27853 indicator strain. To purify the S07-2 compound,

B. subtilis B38 was cultured in 1 L TSB as described previously (Tabbene et al., 2009a). The cell-free supernatant was subjected to methanol extraction. After centrifugation, the supernatant TSA HDAC in vitro was evaporated and the resulting precipitate was dissolved in MilliQ water and fractionated onto a Sep-Pak plus C18 cartridge (Waters, Division of Millipore Corp., Bedford, MA) using a discontinuous gradient of acetonitrile (0%, 20%, 40%, 60%, 80%

and 100%). The active fraction was applied onto a DEAE-Sepharose column (Amersham Pharmacia Biotech). Elution was performed using 10 mM ammonium acetate buffers at different pH (7.5, 6, 5, 4 and 3). The active fraction was applied onto a C18 RP-HPLC column (250 × 4.6 mm). Elution was performed using a linear gradient of acetonitrile from 0% to 100% at a flow rate of 1 mL min−1 for 70 min. All collected fractions were dried under vacuum, dissolved in methanol and tested for their antibacterial activity against P. aeruginosa. The active fraction was chromatographed once more, onto an HS PEG HPLC check details column (250 ×

4.6 mm). Elution was performed using a linear gradient of acetonitrile from 0% to 100% in 10 mM ammonium acetate buffer, pH 6.8, at a flow rate of 0.8 mL min−1 for 40 min. The HPLC-purified fraction was subjected to TLC using n-butanol–methanol–water (39 : 10 : 20, v/v/v) as the mobile phase. The bioassay was performed as described previously (Tabbene et al., 2009a) using P. aeruginosa as the indicator strain. S07-2 compound was detected by UV light at 254 nm or by exposure to iodine and subjected to ninhydrin and 4,4′-bis(dimethylamino)diphenylmethane (TDM) staining methods according to Yu et al., 2002. The iron-binding capacity of the S07-2 compound was determined Anidulafungin (LY303366) using chrome azurol sulfonate (CAS) agar blue solution according to Schwyn & Neilands (1987). The CAS agar solution was poured onto the developed TLC plate. A positive reaction was revealed by a change in the color of the CAS–iron complex from blue to orange. A preliminary detection of the radical-scavenging activity was conducted as described previously (Sreenivasan et al., 2007). The developed TLC plate was sprayed with 0.1% w/v 1-diphenyl-2-picrylhydrazyl (DPPH) methanolic solution. The compound with antiradical activity appeared as a yellow spot against the purple–blue background.

In this review article, we describe some of the latest advances in our knowledge on the role of the endocannabinoid system, in its most recent and wider conception, in pain pathways, by focusing on: (1) neuron–glia interactions; and (2) emerging data on endocannabinoid cross-talk with neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor. “
“Chronic N-methyl-d-aspartate

receptor (NMDAR) hypofunction has been proposed as a contributing factor to symptoms of schizophrenia. NVP-BKM120 solubility dmso However, it is unclear how sustained NMDAR hypofunction throughout development affects other neurotransmitter systems that have been implicated in the disease. Dopamine neuron biochemistry and activity were examined to determine whether sustained NMDAR hypofunction causes

a state of hyperdopaminergia. We report that a global, genetic reduction in NMDARs led to a remodeling of dopamine neurons, substantially affecting two key regulators of dopamine homeostasis, i.e. MLN8237 manufacturer tyrosine hydroxylase and the dopamine transporter. In NR1 knockdown mice, dopamine synthesis and release were attenuated, and dopamine clearance was increased. Although these changes would have the effect of reducing dopamine transmission, we demonstrated that a state of hyperdopaminergia existed in these mice because dopamine D2 autoreceptors were desensitized. In support of this conclusion, NR1 knockdown dopamine neurons have higher tonic firing rates. Although the tonic firing rates are higher, phasic signaling is impaired, and dopamine overflow cannot be achieved with exogenous high-frequency stimulation that models phasic firing. Through the examination of several parameters of dopamine neurotransmission, we provide evidence that chronic NMDAR hypofunction leads to a state of elevated synaptic dopamine. Compensatory mechanisms to attenuate hyperdopaminergia also impact the ability to generate dopamine surges through phasic firing. “
“Elimination of granule cells (GCs) in the olfactory bulb (OB) is not a continual event but is promoted during a short time window in the postprandial period, typically

with postprandial sleep. However, the neuronal mechanisms for the enhanced GC elimination during the postprandial period are not understood. Here, we addressed the question of whether top-down inputs of Methamphetamine centrifugal axons from the olfactory cortex (OC) during the postprandial period are involved in the enhanced GC elimination in the OB. Electrical stimulation of centrifugal axons from the OC of anesthetized mice increased GC apoptosis. Furthermore, pharmacological suppression of top-down inputs from the OC to the OB during the postprandial period of freely behaving mice by γ-aminobutyric acid (GABA)A receptor agonist injection in the OC significantly decreased GC apoptosis. Remarkable apoptotic GC elimination in the sensory-deprived OB was also suppressed by pharmacological blockade of top-down inputs.