Structural basis of the fanconi anemia-associated mutations within the FANCA and FANCG complex.

Monoubiquitination of the Fanconi anemia complementation group D2 (FANCD2) protein by the FA core ubiquitin ligase complex is the central event in the FA pathway. FANCA and FANCG play major roles in the nuclear localization of the FA core complex. Mutations of these two genes are the most frequently observed genetic alterations in FA patients, and most point mutations in FANCA are clustered in the C-terminal domain (CTD). To understand the basis of the FA-associated FANCA mutations, we determined the cryo-electron microscopy (EM) structures of Xenopus laevis FANCA alone at 3.35 Å and 3.46 Å resolution and two distinct FANCA-FANCG complexes at 4.59 and 4.84 Å resolution, respectively. The FANCA CTD adopts an arc-shaped solenoid structure that forms a pseudo-symmetric dimer through its outer surface. FA- and cancer-associated point mutations are widely distributed over the CTD. The two different complex structures capture independent interactions of FANCG with either FANCA C-terminal HEAT repeats, or the N-terminal region. We show that mutations that disturb either of these two interactions prevent the nuclear localization of FANCA, thereby leading to an FA pathway defect. The structure provides insights into the function of FANCA CTD, and provides a framework for understanding FA- and cancer-associated mutations.

ClpL is a functionally active tetradecameric AAA+ chaperone, distinct from hexameric/dodecameric ones.

AAA+ (ATPases associated with diverse cellular activities) chaperones are involved in a plethora of cellular activities to ensure protein homeostasis. The function of AAA+ chaperones is mostly modulated by their hexameric/dodecameric quaternary structures. Here we report the structural and biochemical characterizations of a tetradecameric AAA+ chaperone, ClpL from Streptococcus pneumoniae. ClpL exists as a tetradecamer in solution in the presence of ATP. The cryo-EM structure of ClpL at 4.5 Å resolution reveals a striking tetradecameric arrangement. Solution structures of ClpL derived from small-angle X-ray scattering data suggest that the tetradecameric ClpL could assume a spiral conformation found in active hexameric/dodecameric AAA+ chaperone structures. Vertical positioning of the middle domain accounts for the head-to-head arrangement of two heptameric rings. Biochemical activity assays with site-directed mutagenesis confirmed the critical roles of residues both in the integrity of the tetradecameric arrangement and activities of ClpL. Non-conserved Q321 and R670 are crucial in the heptameric ring assembly of ClpL. These results establish that ClpL is a functionally active tetradecamer, clearly distinct from hexameric/dodecameric AAA+ chaperones.

Integrins αvß5 and αvß6 Mediate IL-4-induced Collective Migration in Human Airway Epithelial Cells.

A positive link between persistent cellular motion and a defective tight junction barrier allows increased antigenic penetration and contact between ligand-receptor pairs, leading to exacerbated allergic airway inflammation and remodeling. Given that collective cell migration involves cell-cell and cell-extracellular matrix adhesions, and given that IL-4 induces epithelial barrier dysfunction and decreases cell-extracellular matrix adhesions, we hypothesized that IL-4 may induce collective migration in the well-differentiated primary human nasal epithelial cells (HNECs). Well-differentiated HNECs were treated with IL-4, and the effects of IL-4 on cell migration were investigated using genetic and pharmacological approaches, live-cell imaging, a vertex model, and immunostaining. IL-4 disrupted the expression and localization of the tight junction proteins zonula occludens 1 and occludin, and it induced the cleavage and asymmetric distribution of E-cadherin in the HNEC layers. It also induced collective epithelial migration and cell shape changes driven by actin cytoskeleton reorganization. In addition, the effect of IL-4 on collective HNEC migration was reversed by pharmacologic and genetic inhibition of the αv-integrin-activating enzyme furin, and function-blocking antibodies for αvß5 or αvß6. In IL-4-stimulated cells, both anti-αvß5 and anti-αvß6 inhibited the phosphorylation of focal adhesion kinase. Furthermore, both ß5- and ß6-integrins were enriched in basal cells in the injured airway epithelium with allergic rhinitis. These findings suggest that αvß5 and αvß6 serve as critical mechanoreceptors in IL-4-induced collective HNEC migration through the focal adhesion kinase signaling pathway. These results have implications for targeting treatment of exacerbation of respiratory allergic diseases.

Environmental disinfection with photocatalyst as an adjunctive measure to control transmission of methicillin-resistant Staphylococcus aureus: a prospective cohort study in a high-incidence setting.

BACKGROUND: Environmental disinfection with continuously antimicrobial surfaces could offer superior control of surface bioburden. We sought to decide the efficacy of photocatalyst antimicrobial coating in reducing methicillin-resistant Staphylococcus aureus (MRSA) acquisition in high incidence setting. METHODS: We performed prospective cohort study involving patients hospitalized in medical intensive care unit. A titanium dioxide-based photocatalyst was coated on high touch surfaces and walls. Five months of pre-intervention data were compared with five months of post-intervention data. The incidence rates of multidrug-resistant organism acquisition and the rates of hospital-acquired blood stream infection, pneumonia, urinary tract infection, and Clostridium difficile-associated diseases were compared using Cox proportional hazards regression analysis. RESULTS: In total, 621 patients were included. There was significant decrease in MRSA acquisition rate after photocatalyst coating (hazard ratio, 0.37; 95% confidence interval, 0.14-0.99; p = 0.04). However, clinical identification of vancomycin-resistant Enterococcus spp. and multidrug-resistant Acinetobacter baumannii did not decrease significantly. The hazard of contracting hospital-acquired pneumonia during the intervention period compared to baseline period was 0.46 (95% confidence interval, 0.23-0.94; p = 0.03). CONCLUSIONS: In conclusion, MRSA rate was significantly reduced after photocatalyst coating. We provide evidence that photocatalyst disinfection can be an adjunctive measure to control MRSA acquisition in high-incidence settings. TRIAL REGISTRATION: ISRCTN Registry ( ISRCTN31972004 ). Registered retrospectively on November 19, 2018.

Four-fold Channel-Nicked Human Ferritin Nanocages for Active Drug Loading and pH-Responsive Drug Release.

Human ferritins are emerging platforms for non-toxic protein-based drug delivery, owing to their intrinsic or acquirable targeting abilities to cancer cells and hollow cage structures for drug loading. However, reliable strategies for high-level drug encapsulation within ferritin cavities and prompt cellular drug release are still lacking. Ferritin nanocages were developed with partially opened hydrophobic channels, which provide stable routes for spontaneous and highly accumulated loading of FeII -conjugated drugs as well as pH-responsive rapid drug release at endoplasmic pH. Multiple cancer-related compounds, such as doxorubicin, curcumin, and quercetin, were actively and heavily loaded onto the prepared nicked ferritin. Drugs on these minimally modified ferritins were effectively delivered inside cancer cells with high toxicity.

VipD of Legionella pneumophila targets activated Rab5 and Rab22 to interfere with endosomal trafficking in macrophages.

Upon phagocytosis, Legionella pneumophila translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity, ultimately establishing intracellular survival and growth. VipD of L. pneumophila belongs to a family of bacterial effectors that contain the N-terminal lipase domain and the C-terminal domain with an unknown function. We report the crystal structure of VipD and show that its C-terminal domain robustly interferes with endosomal trafficking through tight and selective interactions with Rab5 and Rab22. This domain, which is not significantly similar to any known protein structure, potently interacts with the GTP-bound active form of the two Rabs by recognizing a hydrophobic triad conserved in Rabs. These interactions prevent Rab5 and Rab22 from binding to downstream effectors Rabaptin-5, Rabenosyn-5 and EEA1, consequently blocking endosomal trafficking and subsequent lysosomal degradation of endocytic materials in macrophage cells. Together, this work reveals endosomal trafficking as a target of L. pneumophila and delineates the underlying molecular mechanism.

Functionally antagonistic polyelectrolyte for electro-ionic soft actuator.

Electro-active ionic soft actuators have been intensively investigated as an artificial muscle for soft robotics due to their large bending deformations at low voltages, small electric power consumption, superior energy density, high safety and biomimetic self-sensing actuation. However, their slow responses, poor durability and low bandwidth, mainly resulting from improper distribution of ionic conducting phase in polyelectrolyte membranes, hinder practical applications to real fields. We report a procedure to synthesize efficient polyelectrolyte membranes that have continuous conducting network suitable for electro-ionic artificial muscles. This functionally antagonistic solvent procedure makes amphiphilic Nafion molecules to assemble into micelles with ionic surfaces enclosing non-conducting cores. Especially, the ionic surfaces of these micelles combine together during casting process and form a continuous ionic conducting phase needed for high ionic conductivity, which boosts the performance of electro-ionic soft actuators by 10-time faster response and 36-time higher bending displacement. Furthermore, the developed muscle shows exceptional durability over 40 days under continuous actuation and broad bandwidth below 10 Hz, and is successfully applied to demonstrate an inchworm-mimetic soft robot and a kinetic tensegrity system.

Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore.

In drug discovery, efficient screening of protein-drug interactions (PDIs) is hampered by the limitations of current biophysical approaches. Here, we develop a biological nanopore sensor for single-molecule detection of proteins and PDIs using the pore-forming toxin YaxAB. Using this YaxAB nanopore, we demonstrate label-free, single-molecule detection of interactions between the anticancer Bcl-xL protein and small-molecule drugs as well as the Bak-BH3 peptide. The long funnel-shaped structure and nanofluidic characteristics of the YaxAB nanopore enable the electro-osmotic trapping of diverse folded proteins and high-resolution monitoring of PDIs. Distinctive nanopore event distributions observed in the two-dimensional (ΔI/Io-versus-IN) plot illustrate the ability of the YaxAB nanopore to discriminate individual small-molecule drugs bound to Bcl-xL from non-binders. Taken together, our results present the YaxAB nanopore as a robust platform for label-free, ultrasensitive, single-molecule detection of PDIs, opening up a possibility for low-cost, highly efficient drug discovery against diverse drug targets.

Identification, structural, and biochemical characterization of a group of large Csn2 proteins involved in CRISPR-mediated bacterial immunity.

Many prokaryotic organisms acquire immunity against foreign genetic material by incorporating a short segment of foreign DNA called spacer into chromosomal loci, termed clustered regularly interspaced short palindromic repeats (CRISPRs). The encoded RNAs are processed into small fragments that guide the silencing of the invading genetic elements. The CRISPR-associated (Cas) proteins are the main executioners of these processes. Herein, we report the crystal structure of Stu0660 of Streptococcus thermophilus, a Cas protein involved in the acquisition of new spacers. By homotetramerization, Stu0660 forms a central channel which is decorated with basic amino acids and binds linear double-stranded DNA (dsDNA), but not circular dsDNA. Despite undetectably low sequence similarity, two N-terminal domains of Stu0660 are similar to the entire structure of an Enterococcus faecalis Csn2 protein, which also forms a homotetramer and binds dsDNA. Thus, this work identifies a previously unknown group of Stu0660-like Csn2 proteins (∼350 residues), which are larger than the known canonical Csn2 proteins (∼220 residues) by containing an extra C-terminal domain. The commonly present central channel in the two subgroups appears as a design to selectively interact with linear dsDNA.

Structural basis for assembly and disassembly of the IGF/IGFBP/ALS ternary complex.

Insulin-like growth factors (IGFs) have pleiotropic roles in embryonic and postnatal growth and differentiation. Most serum IGFs are bound in a ternary complex with IGF-binding protein 3 (IGFBP3) and acid-labile subunit (ALS), extending the serum half-life of IGFs and regulating their availability. Here, we report cryo-EM structure of the human IGF1/IGFBP3/ALS ternary complex, revealing the detailed architecture of a parachute-like ternary complex and crucial determinants for their sequential and specific assembly. In vitro biochemical studies show that proteolysis at the central linker domain of IGFBP3 induces release of its C-terminal domain rather than IGF1 release from the ternary complex, yielding an intermediate complex that enhances IGF1 bioavailability. Our results provide mechanistic insight into IGF/IGFBP3/ALS ternary complex assembly and its disassembly upon proteolysis for IGF bioavailability, suggesting a structural basis for human diseases associated with IGF1 and IGFALS gene mutations such as complete ALS deficiency (ACLSD) and IGF1 deficiency.

Designing 3D Anode Based on Pore-Size-Dependent Li Deposition Behavior for Reversible Li-Free All-Solid-State Batteries.

Li-free all-solid-state batteries can achieve high energy density and safety. However, separation of the current collector/solid electrolyte interface during Li deposition increases interfacial resistance, which deteriorates safety and reversibility. In this study, a reversible 3D porous anode is designed based on Li deposition behavior that depends on the pore size of the anode. More Li deposits are accommodated within the smaller pores of the Li hosting anode composed of Ni particles with a granular piling structure; this implies the Li movement into the anode is achieved via diffusional Coble creep. Surface modification of Ni with a carbon coating layer and Ag nanoparticles further increases the Li hosting capacity and enables Li deposition without anode/solid electrolyte interface separation. A Li-free all-solid-state full cell with a LiNi0.8 Mn0.1 Co0.1 O2 cathode shows an areal capacity of 2 mAh cm-2 for retaining a Coulombic efficiency of 99.46% for 100 cycles at 30 °C.

A Dynamic Substrate Pool Revealed by cryo-EM of a Lipid-Preserved Respiratory Supercomplex.

Aims: Mitochondrial respiratory supercomplexes mediate redox electron transfer, generating a proton gradient for ATP synthesis. To provide structural information on the function of supercomplexes in physiologically relevant conditions, we conducted cryoelectron microscopy studies with supercomplexes in a lipid-preserving state. Results: Here, we present cryoelectron microscopy structures of bovine respiratory supercomplex I1III2IV1 by using a lipid-preserving sample preparation. The preparation greatly enhances the intercomplex quinone transfer activity. The structures reveal large intercomplex motions that result in different shapes and sizes of the intercomplex space between complexes I and III, forming a dynamic substrate pool. Biochemical and structural analyses indicated that intercomplex phospholipids mediate the intercomplex motions. An analysis of the different classes of focus-refined complex I showed that structural switches due to quinone reduction led to the formation of a novel channel that could transfer reduced quinones to the intercomplex substrate pool. Innovation and Conclusion: Our results indicate potential mechanism for the facilitated electron transfer involving a dynamic substrate pool and intercomplex movement by which supercomplexes play an active role in the regulation of metabolic flux and reactive oxygen species.

Mechanical compression enhances ciliary beating through cytoskeleton remodeling in human nasal epithelial cells.

Nasal inflammatory diseases, including nasal polyps and acute/chronic sinusitis, are characterized by impaired mucociliary clearance and eventually inflammation and infection. Contact of nasal polyps with adjacent nasal mucosa or stagnated mucus within the maxillary sinus produces compressive mechanical stresses on the apical surface of epithelium which can induce cytoskeleton remodeling in epithelial cells. In this study, we hypothesized that compressive stress modulates ciliary beating by altering the mechanical properties of the cytoskeleton of ciliated cell basal bodies. For the primary human nasal epithelial cells, we found that the applied compressive stress higher than the critical value of 1.0 kPa increased the stroke speed of cilia leading to the enhancement of ciliary beating frequency and mucociliary transportability. Immunostained images of the cytoskeleton showed reorganization and compactness of the actin filaments in the presence of compressive stress. Analysis of beating trajectory with the computational modeling for ciliary beating revealed that the stroke speed of cilium increased as the relative elasticity to viscosity of the surrounding cytoskeleton increases. These results suggest that the compressive stress on epithelial cells increases the ciliary beating speed through cytoskeleton remodeling to prevent mucus stagnation at the early stage of airway obstruction. Our study provides an insight into the defensive mechanism of airway epithelium against pathological conditions. STATEMENT OF SIGNIFICANCE: Cilia dynamics of the nasal epithelium is critical for not only maintaining normal breathing but preventing inflammatory diseases. It has been shown that mechanical compressive stresses can alter the shape and phenotype of epithelial cells. However, the effect of compressive stress on cilia dynamics is unclear. In this study, we demonstrated that the oscillation speed of cilia in human nasal epithelial cells was increased by the applied compressive stress experimentally. The computational simulation revealed that the change of ciliary beating dynamics was attributed to the viscoelastic properties of the reorganized cytoskeleton in response to compressive stress. Our results will be beneficial in understanding the defensive mechanism of airway epithelium against pathological conditions.

Identification and characterization of a transcriptional regulator, SucR, that influences sucCD transcription in Corynebacterium glutamicum.

We have identified and characterized a novel transcriptional regulator that binds to the promoter region of succinyl-CoA synthetase (sucCD) in Corynebacterium glutamicum. Using biotin-labeled DNA affinity beads, we identified a DeoR-type transcriptional regulator, SucR (Cg0146), which is a protein consisting of 282 amino acids with a mass of 31 kDa and RamB (Cg0444). The results of electrophoretic mobility shift assays verified that these regulators specifically bind to the sucCD promoter region. The putative SucR binding region extends from position -155 to -146 (a 10 bp sequence, ACTCTAGGGG) relative to the transcriptional start point of the sucCD operon. The expression level of sucCD in a sucR deletion mutant was seven times higher than that in wild-type cells grown on acetate. The increase in succinyl-CoA synthetase levels caused by inactivation of sucR. These assays revealed that SucR acts as a repressor of sucCD expression during acetate metabolism.

Moth pheromone-selective projection neurons with cell bodies in the antennal lobe lateral cluster exhibit diverse morphological and neurophysiological characteristics.

Olfactory projection neurons convey information from the insect antennal lobe (AL) to higher brain centers. Previous reports have demonstrated that pheromone-responsive projection neurons with cell bodies in the moth medial cell cluster (mcPNs) predominantly have dendritic arborizations in the sexually dimorphic macroglomerular complex (MGC) and send an axon from the AL to the calyces of the mushroom body (CA) as well as the lateral horn (LH) of the protocerebrum via the medial AL tract. These neurons typically exhibit a narrow odor tuning range related to the restriction of their dendritic arbors within a single glomerulus (uniglomerular). In this study, we report on the diverse physiological and morphological properties of a group of pheromone-responsive olfactory projection neurons with cell bodies in the AL lateral cell cluster (MGC lcPNs) of two closely related moth species. All pheromone-responsive lcPNs appeared to exhibit "basket-like" dendritic arborizations in two MGC compartments and made connections with various protocerebral targets including ventrolateral and superior neuropils via projections primarily through the lateral AL tract and to a lesser extent the mediolateral antennal lobe tract. Physiological characterization of MGC lcPNs also revealed a diversity of response profiles including those either enhanced by or reliant upon presentation of a pheromone blend. These responses manifested themselves as higher maximum firing rates and/or improved temporal resolution of pulsatile stimuli. MGC lcPNs therefore participate in conveying diverse olfactory information relating to qualitative and temporal facets of the pheromone stimulus to a more expansive number of protocerebral targets than their mcPN counterparts.

Serotype Distribution and Antimicrobial Resistance of Invasive and Noninvasive Streptococcus pneumoniae Isolates in Korea between 2014 and 2016.

BACKGROUND: Several factors contribute to differences in Streptococcus pneumoniae serotype distribution. We investigated the serotype distribution and antimicrobial resistance of S. pneumoniae isolated between 2014 and 2016 in Korea. METHODS: We collected a total of 1,855 S. pneumoniae isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR. We investigated the distribution of each serotype by patient age, source of the clinical specimen, and antimicrobial resistance pattern. RESULTS: The most common serotypes were 11A (10.1%), followed by 19A (8.8%), 3 (8.5%), 34 (8.1%), 23A (7.3%), and 35B (6.2%). The major invasive serotypes were 3 (12.6%), 19A (7.8%), 34 (7.8%), 10A (6.8%), and 11A (6.8%). Serotypes 10A, 15B, 19A, and 12F were more common in patients ≤5 years old, while serotype 3 was more common in patients ≥65 years old compared with the other age groups. The coverage rates of pneumococcal conjugate vaccine (PCV)7, PCV10, PCV13, and pneumococcal polysaccharide vaccine 23 were 11.8%, 12.12%, 33.3%, and 53.6%, respectively. Of the 1,855 isolates, 857 (46.2%) were multi-drug resistant (MDR), with serotypes 11A and 19A predominant among the MDR strains. The resistance rates against penicillin, cefotaxime, and levofloxacin were 22.8%, 12.5%, and 9.4%, respectively. CONCLUSIONS: There were significant changes in the major S. pneumoniae serotypes in the community. Non-PCV13 serotypes increased in patients ≤5 years old following the introduction of national immunization programs with the 10- and 13-polyvalent vaccines.

Incomplete electrical isolation of sex-pheromone responsive olfactory receptor neurons from neighboring sensilla.

In the long trichoid sensilla on male Helicoverpa zea antennae, approximately 40% of the sensilla having a large-spiking olfactory receptor neuron responding to the major pheromone component, (Z)-11-hexadecenal, also exhibit small-spiking action potentials that also seem to be responsive to this same compound. In this study, we investigated whether these small-spiking signals are a result of intrusive electrical signals generated from neighboring sensilla. Two methods were used for this study. First, the sensillum was completely covered by the saline-filled recording electrode to physically prevent the sensillum from being contacted by exposure to (Z)-11-hexadecenal. In this case, activation of the large-spiking neuron in response to the pheromone component was prevented, whereas the small-spiking activity continued to be influenced by the airborne delivery of the pheromone. In the second method the (Z)-11-hexadecenal was applied directly in solution through the cut tip of the sensillum through the recording electrode. In this case only large-spiking activity occurred in response to (Z)-11-hexadecenal, with no increase whatsoever in the firing frequency of the small spikes. We conclude that these long trichoid olfactory sensilla are not completely isolated electrically from neighboring sensilla and that small spikes in some recordings originate from large-spiking olfactory receptor neurons (ORNs) in neighboring sensilla.

Moxibustion Therapy in Traditional Mongolian Medicine.

From the medical history of traditional Eastern Asian and Tibetan medicine, the origin and development of moxibustion seems to be closely related to Mongolia. To explore the current clinical practice of moxibustion in Mongolia, we visited a teaching hospital, the Traditional Medical Science, Technology and Production Corporation of Mongolia, in February 2014. Many types of moxibustion are found to be used, and various modalities and methods are practiced based on the principles of traditional Mongolian medicine. In particular, Mongolian drug moxibustion, which uses small butter-warmed bags packed with powdered aromatic herbs instead of moxa cones, is a unique moxibustion technique not found in other countries. In this paper, we introduce the clinical practice of moxibustion, specifically Mongolian drug moxibustion in Mongolia.

Clinical features of HBsAg seroclearance in hepatitis B virus carriers in South Korea: A retrospective longitudinal study.

AIM: To investigate the characteristic features of hepatitis B surface antigen (HBsAg) seroclearance among Korean hepatitis B virus (HBV) carriers. METHODS: Carriers with HBsAg seroclearance were selected by analyzing longitudinal data collected from 2003 to 2015. The period of time from enrollment to the negative conversion of HBsAg (HBsAg-NC) was compared by stratifying various factors, including age, sex, hepatitis B e antigen (HBeAg), HBV DNA, sequential changes in the signal-to-cutoff ratio of HBsAg (HBsAg-SCR), as measured by qualitative HBsAg assay, and chronic liver disease on ultrasonography (US-CLD). Quantification of HBV DNA and HBsAg (HBsAg-QNT) in the serum was performed by commercial assay. RESULTS: Among the 1919 carriers, 90 (4.7%) exhibited HBsAg-NC at 6.2 ± 3.6 years after registration, with no differences observed among the different age groups. Among these carriers, the percentages of those with asymptomatic liver cirrhosis (LC) and hepatocellular carcinoma (HCC) at registration were 31% and 7.8%, respectively. The frequency of HBsAg-NC significantly differed according to the HBV DNA titer and US-CLD. HBeAg influenced HBsAg-NC in the 40-50 and 50-60 year age groups. HBsAg-SCR < 1000 was correlated with an HBsAg-QNT < 200 IU/mL. A gradual decrease in the HBsAg-SCR to < 1000 predicted HBsAg-NC. Six patients developed HCC after registration, including two before and four after HBsAg-NC. The rate at which the patients developed new HCC after HBsAg seroclearance was 4.8%. LC with excessive drinking and vertical infection were found to be risk factors for HCC in the HBsAg-NC group. CONCLUSION: HCC surveillance should be continued after HBsAg seroclearance. An HBsAg-SCR < 1000 and its decrease in sequential testing are worth noting as predictive markers of HBsAg loss.

Transplant Antennae and Host Brain Interact to Shape Odor Perceptual Space in Male Moths.

Behavioral responses to odors rely first upon their accurate detection by peripheral sensory organs followed by subsequent processing within the brain's olfactory system and higher centers. These processes allow the animal to form a unified impression of the odor environment and recognize combinations of odorants as single entities. To investigate how interactions between peripheral and central olfactory pathways shape odor perception, we transplanted antennal imaginal discs between larval males of two species of moth Heliothis virescens and Heliothis subflexa that utilize distinct pheromone blends. During metamorphic development olfactory receptor neurons originating from transplanted discs formed connections with host brain neurons within olfactory glomeruli of the adult antennal lobe. The normal antennal receptor repertoire exhibited by males of each species reflects the differences in the pheromone blends that these species employ. Behavioral assays of adult transplant males revealed high response levels to two odor blends that were dissimilar from those that attract normal males of either species. Neurophysiological analyses of peripheral receptor neurons and central olfactory neurons revealed that these behavioral responses were a result of: 1. the specificity of H. virescens donor olfactory receptor neurons for odorants unique to the donor pheromone blend and, 2. central odor recognition by the H. subflexa host brain, which typically requires peripheral receptor input across 3 distinct odor channels in order to elicit behavioral responses.