Formation of Graphene on Gold-Nickel Surface Alloys.

Nickel (Ni)-catalyzed growth of a single- or rotated-graphene layer is a well-established process above 800 K. In this report, a Au-catalyzed, low-temperature, and facile route at 500 K for graphene formation is described. The substantially lower temperature is enabled by the presence of a surface alloy of Au atoms embedded within Ni(111), which catalyzes the outward segregation of carbon atoms buried in the Ni bulk at temperatures as low as 400-450 K. The resulting surface-bound carbon in turn coalesces into graphene above 450-500 K. Control experiments on a Ni(111) surface show no evidence of carbon segregation or graphene formation at these temperatures. Graphene is identified by its out-of-plane optical phonon mode at 750 cm-1 and its longitudinal/transverse optical phonon modes at 1470 cm-1 while surface carbon is identified by its C-Ni stretch mode at 540 cm-1, as probed by high-resolution electron energy-loss spectroscopy. Dispersion measurements of the phonon modes confirm the presence of graphene. Graphene formation is observed to be maximum at 0.4 ML Au coverage. The results of these systematic molecular-level investigations open the door to graphene synthesis at the low temperatures required for integration with complementary metal-oxide-semiconductor processes.

Exercise as a Therapy to Maintain Telomere Function and Prevent Cellular Senescence.

Exercise transiently impacts the expression, regulation, and activity of TERT/telomerase to maintain telomeres and protect the genome from insults. By protecting the telomeres (chromosome ends) and the genome, telomerase promotes cellular survival and prevents cellular senescence. By increasing cellular resiliency, via the actions of telomerase and TERT, exercise promotes healthy aging.

Neural correlates of multidimensional motor outputs in an excitatory parafascicular-zona incerta circuit.

The parafascicular nucleus (Pf) in medial thalamus is interconnected with prefrontal cortex and basal ganglia. Though much research has determined its importance in cognitive regulation of behaviour, its projections to regions in subthalamus remain less known. Such connections include those to zona incerta (ZI), located immediately dorsal to subthalamic nuclei (STN) regulating motor output, and whose role in a motor context is only beginning to be investigated. We thus examined circuits from parafascicular (Pf) thalamus to ZI, and its activity during locomotion and spontaneous behaviours in mice. We found that a distinct group of CaMKIIα-positive excitatory parafascicular neurons, separated from VGLUT2-positive excitatory neurons, project widely into ZI, more than adjacent STN. Our results from fibre photometry and decoding with general linear model (GLM) indicate that PF-ZI pathways do not specifically correlate with amount of locomotion or movement velocity, but instead show more specified activity during relative directional changes of movements observed in turning, sniffing behaviours. These results hint at the PF-ZI pathway having a distinct role in directing action specificity and have implications for subcortical bases in dimensional control of behaviours.

PCNT is critical for the association and conversion of centrioles to centrosomes during mitosis.

A centrosome consists of a pair of centrioles and pericentriolar material (PCM). We manipulated expression of PCNT, a key PCM protein, and investigated roles of PCM in centriole behavior during mitosis. Deletion of PCNT had little effect on interphase centrosomes. However, centrioles in PCNT-deleted mitotic cells prematurely separated and frequently amplified, revealing that centrioles are limited within the spindle poles by PCNT during mitosis. It is known that specific cleavage of PCNT is necessary for centriole separation during mitotic exit. We observed delayed centriole separation in the G0 phase when a non-cleavable mutant form of PCNT was removed or when PCNT was artificially cleaved by TEV protease. Furthermore, a daughter centriole converts to a mother centriole only after experiencing both mitotic exit and specific PCNT cleavage. Based on these results, we propose that a centriole pair disengages upon entering mitosis but remains associated with the surrounding PCM proteins throughout mitosis. During mitotic exit, specific cleavage of PCNT induces PCM disintegration. As a result, a daughter centriole separates from the mother centriole and converts to a young mother centriole.

Haploinsufficiency of Cyfip2 Causes Lithium-Responsive Prefrontal Dysfunction.

OBJECTIVE: Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain largely unknown. Here, we characterized Cyfip2 heterozygous (Cyfip2+/- ) mice to understand their neurobehavioral phenotypes and the underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of the Cyfip2+/- mice and specified a neuronal function mediating its efficacy. METHODS: We performed behavioral analyses of Cyfip2+/- mice. We combined molecular, ultrastructural, and in vitro and in vivo electrophysiological analyses of Cyfip2+/- prefrontal neurons. We also selectively reduced CYFIP2 in the prefrontal cortex (PFC) of mice with virus injections. RESULTS: Adult Cyfip2+/- mice exhibited lithium-responsive abnormal behaviors. We found increased filamentous actin, enlarged dendritic spines, and enhanced excitatory synaptic transmission and excitability in the adult Cyfip2+/- PFC that was restricted to layer 5 (L5) neurons. Consistently, adult Cyfip2+/- mice showed increased seizure susceptibility and auditory steady-state responses from the cortical electroencephalographic recordings. Among the identified prefrontal defects, lithium selectively normalized the hyperexcitability of Cyfip2+/- L5 neurons. RNA sequencing revealed reduced expression of potassium channel genes in the adult Cyfip2+/- PFC. Virus-mediated reduction of CYFIP2 in the PFC was sufficient to induce L5 hyperexcitability and lithium-responsive abnormal behavior. INTERPRETATION: These results suggest that L5-specific prefrontal dysfunction, especially hyperexcitability, underlies both the pathophysiology and the lithium-mediated amelioration of neurobehavioral phenotypes in adult Cyfip2+/- mice, which can be implicated in CYFIP2-associated brain disorders. ANN NEUROL 2020;88:526-543.

In Situ Observations of UV-Induced Restructuring of Self-Assembled Porphyrin Monolayer on Liquid/Au(111) Interface at Molecular Level.

Porphyrin-derived molecules have received much attention for use in solar energy conversion devices, such as artificial leaves and dye-sensitized solar cells. Because of their technological importance, a molecular-level understanding of the mechanism for supramolecular structure formation in a liquid, as well as their stability under ultraviolet (UV) irradiation, is important. Here, we observed the self-assembled structure of free-base, copper(II), and nickel(II) octaethylporphyrin formed on Au(111) in a dodecane solution using scanning tunneling microscopy (STM). As evident in the STM images, the self-assembled monolayers (SAMs) of these three porphyrins on the Au(111) surface showed hexagonal close-packed structures when in dodecane solution. Under UV irradiation (λ = 365 nm), the porphyrin molecules in the SAM or the dodecane solution move extensively and form new porphyrin clusters on the Au sites that have a high degree of freedom. Consequently, the Au(111) surface was covered with disordered porphyrin clusters. However, we found that the porphyrin molecules decomposed under UV irradiation at 254 nm. Molecular-scale observation of the morphological evolution of the porphyrin SAM under UV irradiation can provide a fundamental understanding of the degradation processes of porphyrin-based energy conversion devices.

Age-dependent gait abnormalities in mice lacking the Rnf170 gene linked to human autosomal-dominant sensory ataxia.

Really interesting new gene (RING) finger protein 170 (RNF170) is an E3 ubiquitin ligase known to mediate ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate receptors (ITPR1). It has recently been demonstrated that a point mutation of RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), which is characterized by an age-dependent increase of walking abnormalities, a rare genetic disorder reported in only two families. Although this mutant allele is known to be dominant, the functional identity thereof has not been clearly established. Here, we generated mice lacking Rnf170 (Rnf170(-/-)) to evaluate the effect of its loss of function in vivo. Remarkably, Rnf170(-/-) mice began to develop gait abnormalities in old age (12 months) in the form of asynchronous stepping between diagonal limb pairs with a fixed step sequence during locomotion, while age-matched wild-type mice showed stable gait patterns using several step sequence repertoires. As reported in ADSA patients, they also showed a reduced sensitivity for proprioception and thermal nociception. Protein blot analysis revealed that the amount of Itpr1 protein was significantly elevated in the cerebellum and spinal cord but intact in the cerebral cortex in Rnf170(-/-) mice. These results suggest that the loss of Rnf170 gene function mediates ADSA-associated phenotypes and this gives insights on the cure of patients with ADSA and other age-dependent walking abnormalities.

Thermal Evolution and Instability of CO-Induced Platinum Clusters on the Pt(557) Surface at Ambient Pressure.

Carbon monoxide (CO) is one of the most-studied molecules among the many modern industrial chemical reactions available. Following the Langmuir-Hinshelwood mechanism, CO conversion starts with adsorption on a catalyst surface, which is a crucially important stage in the kinetics of the catalytic reaction. Stepped surfaces show enhanced catalytic activity because they, by nature, have dense active sites. Recently, it was found that surface-sensitive adsorption of CO is strongly related to surface restructuring via roughening of a stepped surface. In this scanning tunneling microscopy study, we observed the thermal evolution of surface restructuring on a representative stepped platinum catalyst, Pt(557). CO adsorption at 1.4 mbar CO causes the formation of a broken-step morphology, as well as CO-induced triangular Pt clusters that exhibit a reversible disordered-ordered transition. Thermal instability of the CO-induced platinum clusters on the stepped surface was observed, which is associated with the reorganization of the repulsive CO-CO interactions at elevated temperature.

Assessment of altered binding specificity of bacteriophage for ciprofloxacin-induced antibiotic-resistant Salmonella Typhimurium.

This study describes a new effort toward understanding the interaction mechanisms between antibiotic-resistant Salmonella Typhimurium and phages. The antibiotic susceptibility, ß-lactamase activity, bacterial motility, gene expression, and lytic activity were evaluated in ciprofloxacin-induced antibiotic-sensitive Salmonella Typhimurium (ASST(CIP)) and ciprofloxacin-induced antibiotic-resistant S. Typhimurium (ARST(CIP)), which were compared to the wild-type strains (ASST(WT) and ARST(WT)). The MIC values of ampicillin, norfloxacin, chloramphenicol, and tetracycline were significantly increased to > 512, 16, 16, and 256 µg/ml, respectively, in the ARST(CIP). The lowest and highest extracellular lactamase activities were observed in ASST(WT) (6.85 µmol/min/ml) and ARST(CIP) (48.83 µmol/min/ml), respectively. The acrA, lpfE, and hilA genes were significantly upregulated by more than tenfold in both ASST(CIP) and ARST(CIP). The induction of multiple antibiotic resistance resulted from the increased efflux pump activity (AcrAB-TolC). The highest phage adsorption rates were more than 95 % for ASST(WT), ASST(CIP), and ARST(WT), while the lowest adsorption rate was 52 % for ARST(CIP) at 15 min of infection. The least lytic activity of phage was 20 % against the ARST(CIP), followed by ASST(CIP) (30 %). The adsorption rate of phage against ARST(CIP) was 52 % at 15 min of infection, which resulted in the decrease in lytic activity (12 %). Understanding the interaction of phage and bacteria is essential for the practical application of phage to control and detect antibiotic-resistant bacteria. The results provide useful information for understanding the binding specificity of phages for multiple antibiotic-resistant pathogens.

Assessment of antibiotic resistance in Klebsiella pneumoniae exposed to sequential in vitro antibiotic treatments.

BACKGROUND: Bacteria treated with different classes of antibiotics exhibit changes in susceptibility to successive antibiotic treatments. This study was designed to evaluate the influence of sequential antibiotic treatments on the development of antibiotic resistance in Klebsiella pneumoniae associated with ß-lactamase and efflux pump activities. METHODS: The antibiotic susceptibility, ß-lactamase activity, and efflux activity were determined in K. pneumoniae grown at 37 °C by adding initial (0 h) and second antibiotics (8 or 12 h). Treatments include control (CON; no first and second antibiotic addition), no initial antibiotic addition followed by 1 MIC ciprofloxacin addition (CON-CIP), no initial antibiotic addition followed by 1 MIC meropenem addition (CON-MER), initial 1/4 MIC ciprofloxacin addition followed by no antibiotic addition (1/4CIP-CON), initial 1/4 MIC ciprofloxacin addition followed by 1 MIC ciprofloxacin addition (1/4CIP-CIP), and initial 1/4 MIC ciprofloxacin addition followed by 1 MIC meropenem addition (1/4CIP-MER). RESULTS: Compared to the CON, the initial addition of 1/4 MIC ciprofloxacin inhibited the growth of K. pneumoniae throughout the incubation period. The ciprofloxacin treatments (CON-CIP and 1/4CIP-CIP) showed significant reduction in the number of K. pneumoniae cells compared to meropenem (CON-MER and 1/4CIP-MER). The 1/4CIP-CIP achieved a further 1 log reduction of K. pneumoniae, when compared to the 1/4CIP-CON and 1/CIP-MER. The increase in sensitivity of K. pneumoniae to cefotaxime, kanamycin, levofloxacin, nalidixic acid was observed for CON-CIP. Noticeable cross-resistance pattern was observed at the 1/4CIP-CIP, showing the increased resistance of K. pneumoniae to chloramphenicol, ciprofloxacin, kanamycin, levofloxacin, nalidixic acid norfloxacin, sulphamethoxazole/trimethoprim, and tetracycline. The levels of ß-lactamase activities were estimated to be 8.4 µmol/min/ml for CON, 7.7 µmol/min/ml for 1/4CIP-CON and as low as 2.9 µmol/min/ml for CON-CIP. Compared to the absence of phenylalanine-arginine-ß-naphthylamide (PAßN), the fluorescence intensity of EtBr was increased in K. pneumoniae cells treated at the CON, CON-CIP, and CON-MER in the presence of PAßN. However, the efflux pump activity remained in K. pneumoniae cells treated at the 1/CIP, 1/CIP-CIP, and 1/CIP-MER in the presence of PAßN. CONCLUSION: The results suggest that the pre-exposed antibiotic history, treatment order, and concentrations influenced the development of multiple antibiotic resistant associated with ß-lactamase and efflux pump activities. This study highlights the importance of antibiotic treatment conditions, which would be taken into consideration when new antibiotic strategy is designed to prevent antibiotic resistance.

Protocol for in vivo dual-color fiber photometry in the mouse thalamus.

In vivo calcium imaging of neural activity is an indispensable approach for understanding the mechanisms and functions of neural system. Development of advanced imaging tools and various genetically encoded calcium indicators allows us to simultaneously record the activity of different neural populations. Here, we present a protocol for acquiring neural activity of two discrete neural populations in mice using dual-color fiber photometry. We describe steps for injecting viral constructs and implanting the fiber optic through stereotaxic surgery, calcium signal acquisition, and data analysis. We also describe the incorporation of electroencephalogram and electromyography recordings with dual-color fiber photometry analysis. For complete details on the use and execution of this protocol, please refer to Shin et al.1.

The Surface Chemistry of Methanol on Pd(111) and H-Pd(111) Surfaces: C-O Bond Cleavage and the Effects of Metal Hydride Formation.

Palladium catalysts are frequently employed in processes where methanol is an energy vector or carrier, being useful for the synthesis of methanol from mixtures of carbon dioxide and hydrogen (CO2/H2) or its steam reforming on demand. Results of synchrotron-based ambient pressure X-ray photoelectron spectroscopy for the adsorption of methanol on a Pd(111) model catalyst show a rich surface chemistry and complex phenomena that strongly depend on pressure and temperature. At low pressures (<10-6 Torr) and temperatures (<300 K), CO is the dominant decomposition product. As the pressure increases, cleavage of C-H, O-H, and C-O bonds is observed, and at elevated temperatures (400-600 K) the formation of CO and CHx/C fragments compete on the surface. Thus, existing reaction networks for methanol decomposition must be modified. Furthermore, surface and subsurface hydrogen (coming from PdHx) play a significant role in the stability and removal of CHx and C species.

Study of CO2 Adsorption Properties on the SrTiO3(001) Surface with Ambient Pressure XPS.

The adsorption properties of CO2 on the SrTiO3(001) surface were investigated using ambient pressure X-ray photoelectron spectroscopy under elevated pressure and temperature conditions. On the Nb-doped TiO2-enriched (1 × 1) SrTiO3 surface, CO2 adsorption, i.e., the formation of CO3 surface species, occurs first at the oxygen lattice site under 10-6 mbar CO2 at room temperature. The interaction of CO2 molecules with oxygen vacancies begins when the CO2 pressure increases to 0.25 mbar. The adsorbed CO3 species on the Nb-doped SrTiO3 surface increases continuously as the pressure increases but starts to leave the surface as the surface temperature increases, which occurs at approximately 373 K on the defect-free surface. On the undoped TiO2-enriched (1 × 1) SrTiO3 surface, CO2 adsorption also occurs first at the lattice oxygen sites. Both the doped and undoped SrTiO3 surfaces exhibit an enhancement of the CO3 species with the presence of oxygen vacancies, thus indicating the important role of oxygen vacancies in CO2 dissociation. When OH species are removed from the undoped SrTiO3 surface, the CO3 species begin to form under 10-6 mbar at 573 K, thus indicating the critical role of OH in preventing CO2 adsorption. The observed CO2 adsorption properties of the various SrTiO3 surfaces provide valuable information for designing SrTiO3-based CO2 catalysts.

Identification of an Antagonist Targeting G Protein and ß-Arrestin Signaling Pathways of 5-HT7R.

In consideration of the limited number of FDA-approved drugs for autism spectrum disorder (ASD), significant efforts have been devoted to identifying novel drug candidates. Among these, 5-HT7R modulators have garnered considerable attention due to their potential in alleviating autism-like behaviors in ASD animal models. In this study, we designed and synthesized biphenyl-3-ylmethylpyrrolidines 3 and biphenyl-3-yl-dihydroimidazoles 4 as 5-HT7R modulators. Through extensive biological tests of 3 and 4 in G protein and ß-arrestin signaling pathways of 5-HT7R, it was determined that 2-(2'-methoxy-[1,1'-biphenyl]-3-yl)-4,5-dihydro-1H-imidazole 4h acted as a 5-HT7R antagonist in both signaling pathways. In in vivo study with Shank3-/- transgenic (TG) mice, the self-grooming behavior test was performed with 4h, resulting in a significant reduction in the duration of self-grooming. In addition, an immunohistochemical experiment with 4h restored reduced neurogenesis in Shank3-/- TG mice, which is confirmed by the quantification of doublecortin (DCX) positive neurons, suggesting the promising therapeutic potential of 4h.

A brainstem-to-mediodorsal thalamic pathway mediates sound-induced arousal from slow-wave sleep.

Auditory-induced arousal is a defense mechanism of animals against potential dangers. Although the thalamus is the neural substrate that relays sensory information to the cortex, its function is reduced during slow-wave sleep (SWS), also known as deep sleep. Despite this, animals are capable of waking up in response to external sensory stimuli, suggesting the existence of neural circuits that are involved in this response. Here, we report that kainate-class-type ionotropic glutamate receptor subunit 4 (GRIK4)-positive mediodorsal (MD) thalamic neurons act as a neural substrate for arousals from SWS. These neurons become active during arousal from SWS and their photoactivation can induce arousal from SWS. Moreover, we show that these neurons are influenced by glutamatergic neurons in the brainstem, the activity of which increases during auditory-induced arousals. These results suggest that this brainstem-MD pathway can mediate wakefulness from SWS.

Dynamics of TERT regulation via alternative splicing in stem cells and cancer cells.

Part of the regulation of telomerase activity includes the alternative splicing (AS) of the catalytic subunit telomerase reverse transcriptase (TERT). Although a therapeutic window for telomerase/TERT inhibition exists between cancer cells and somatic cells, stem cells express TERT and rely on telomerase activity for physiological replacement of cells. Therefore, identifying differences in TERT regulation between stem cells and cancer cells is essential for developing telomerase inhibition-based cancer therapies that reduce damage to stem cells. In this study, we measured TERT splice variant expression and telomerase activity in induced pluripotent stem cells (iPSCs), neural progenitor cells (NPCs), and non-small cell lung cancer cells (NSCLC, Calu-6 cells). We observed that a NOVA1-PTBP1-PTBP2 axis regulates TERT alternative splicing (AS) in iPSCs and their differentiation into NPCs. We also found that splice-switching of TERT, which regulates telomerase activity, is induced by different cell densities in stem cells but not cancer cells. Lastly, we identified cell type-specific splicing factors that regulate TERT AS. Overall, our findings represent an important step forward in understanding the regulation of TERT AS in stem cells and cancer cells.

Revealing CO2 dissociation pathways at vicinal copper (997) interfaces.

Size- and shape-tailored copper (Cu) nanocrystals can offer vicinal planes for facile carbon dioxide (CO2) activation. Despite extensive reactivity benchmarks, a correlation between CO2 conversion and morphology structure has not yet been established at vicinal Cu interfaces. Herein, ambient pressure scanning tunneling microscopy reveals step-broken Cu nanocluster evolutions on the Cu(997) surface under 1 mbar CO2(g). The CO2 dissociation reaction produces carbon monoxide (CO) adsorbate and atomic oxygen (O) at Cu step-edges, inducing complicated restructuring of the Cu atoms to compensate for increased surface chemical potential energy at ambient pressure. The CO molecules bound at under-coordinated Cu atoms contribute to the reversible Cu clustering with the pressure gap effect, whereas the dissociated oxygen leads to irreversible Cu faceting geometries. Synchrotron-based ambient pressure X-ray photoelectron spectroscopy identifies the chemical binding energy changes in CO-Cu complexes, which proves the characterized real-space evidence for the step-broken Cu nanoclusters under CO(g) environments. Our in situ surface observations provide a more realistic insight into Cu nanocatalyst designs for efficient CO2 conversion to renewable energy sources during C1 chemical reactions.

Bioaccumulation of Lead, Cadmium, and Arsenic in a Mining Area and Its Associated Health Effects.

Soil contamination is associated with a high potential for health issues. This study aimed to investigate the bioaccumulation of heavy metals and its associated health impact among residents near a mining area. We performed environmental monitoring by analyzing lead (Pb), cadmium (Cd), and arsenic (As) levels in soil and rice samples, as well as biomonitoring by analyzing blood and urine samples from 58 residents living near the mine. Additionally, concentration trends were investigated among 26 participants in a 2013 study. The Cd and As levels in the soil samples and Cd levels in the rice samples exceeded the criteria for concern. The geometric mean blood Cd level (2.12 µg/L) was two times higher than that in the general population aged > 40 years. The blood Cd level showed decreasing trends from the previous measurements of 4.56-2.25 µg/L, but was still higher than that in the general population. The blood and urine Cd levels were higher in those with a low estimated glomerular filtration rate (eGFR) than in those with normal eGFR. In conclusion, heavy metals from mining areas can accumulate in soil and rice, adversely impacting human health. Continuous environmental monitoring and biomonitoring are required to ensure the safety of residents.

Thalamic T-type Ca²+ channels mediate frontal lobe dysfunctions caused by a hypoxia-like damage in the prefrontal cortex.

Hypoxic damage to the prefrontal cortex (PFC) has been implicated in the frontal lobe dysfunction found in various neuropsychiatric disorders. The underlying subcortical mechanisms, however, have not been well explored. In this study, we induced a PFC-specific hypoxia-like damage by cobalt-wire implantation to demonstrate that the role of the mediodorsal thalamus (MD) is critical for the development of frontal lobe dysfunction, including frontal lobe-specific seizures and abnormal hyperactivity. Before the onset of these abnormalities, the cross talk between the MD and PFC nuclei at theta frequencies was enhanced. During the theta frequency interactions, burst spikes, known to depend on T-type Ca(2+) channels, were increased in MD neurons. In vivo knockout or knockdown of the T-type Ca(2+) channel gene (Ca(V)3.1) in the MD substantially reduced the theta frequency MD-PFC cross talk, frontal lobe-specific seizures, and locomotor hyperactivity in this model. These results suggest a two-step model of prefrontal dysfunction in which the response to a hypoxic lesion in the PFC results in abnormal thalamocortical feedback driven by thalamic T-type Ca(2+) channels, which, in turn, leads to the onset of neurological and behavioral abnormalities. This study provides valuable insights into preventing the development of neuropsychiatric disorders arising from irreversible PFC damage.

Improvement of atopic dermatitis-like skin lesions by Platycodon grandiflorum fermented by Lactobacillus plantarum in NC/Nga mice.

Atopic dermatitis (AD) is characterized as a multi-factorial inflammatory skin disease that has been increasing worldwide. Previously, we demonstrated that FPG, which is Platycodon grandiflorum (PG) fermented by Lactobacillus plantarum (LP), increases the level of interferon (IFN)-gamma in mouse splenocytes in vitro. In this study, we investigated the effects of FPG in an animal model of AD, with a particular emphasis on its effects on T helper (Th)1 and Th2 immune responses. To assess the potential use of FPG for the inhibition of AD, we established a model of AD-like skin lesions in NC/Nga mice. Immunoglobulin isotypes (Igs) and Th1/Th2 cytokines in the sera and spleens of AD-like mice were examined. In addition, histological examination was also performed. AD symptoms in skin lesions improved following oral administration of FPG. IgE secretion was significantly down-regulated, and this was accompanied by decreased levels of interleukin (IL)-4 and IgG1 and increased serum levels of IL-12p40 and IgG2a in FPG-treated animals. In splenocytes, the production of the Th1 cytokines IL-12p40 and IFN-gamma was up-regulated, while the levels of the Th2 cytokines IL-4 and 5 were down-regulated by FPG treatment. These results suggest that FPG inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the Th2 cell response and increasing the Th1 cell responses. Our results indicate that FPG is safe and effective for the prevention of AD-like skin lesions.