Successful treatment of porocarcinoma with maxacalcitol and imiquimod.

This is the first report of a case of porocarcinoma that was successfully treated with maxacalcitol and imiquimod.

Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition.

In the representative gut bacterium Lactobacillus plantarum, we identified genes encoding the enzymes involved in a saturation metabolism of polyunsaturated fatty acids and revealed in detail the metabolic pathway that generates hydroxy fatty acids, oxo fatty acids, conjugated fatty acids, and partially saturated trans-fatty acids as intermediates. Furthermore, we observed these intermediates, especially hydroxy fatty acids, in host organs. Levels of hydroxy fatty acids were much higher in specific pathogen-free mice than in germ-free mice, indicating that these fatty acids are generated through polyunsaturated fatty acids metabolism of gastrointestinal microorganisms. These findings suggested that lipid metabolism by gastrointestinal microbes affects the health of the host by modifying fatty acid composition.

A novel unsaturated fatty acid hydratase toward C16 to C22 fatty acids from Lactobacillus acidophilus.

Hydroxy FAs, one of the gut microbial metabolites of PUFAs, have attracted much attention because of their various bioactivities. The purpose of this study was to identify lactic acid bacteria with the ability to convert linoleic acid (LA) to hydroxy FAs. A screening process revealed that a gut bacterium, Lactobacillus acidophilus NTV001, converts LA mainly into 13-hydroxy-cis-9-octadecenoic acid and resulted in the identification of the hydratase responsible, fatty acid hydratase 1 (FA-HY1). Recombinant FA-HY1 was purified, and its enzymatic characteristics were investigated. FA-HY1 could convert not only C18 PUFAs but also C20 and C22 PUFAs. C18 PUFAs with a cis carbon-carbon double bond at the Δ12 position were converted into the corresponding 13-hydroxy FAs. Arachidonic acid and DHA were converted into the corresponding 15-hydroxy FA and 14-hydroxy FA, respectively. To the best of our knowledge, this is the first report of a bacterial FA hydratase that can convert C20 and C22 PUFAs into the corresponding hydroxy FAs. These novel hydroxy FAs produced by using FA-HY1 should contribute to elucidating the bioactivities of hydroxy FAs.

The Rintala flap: a versatile procedure for nasal reconstruction.

INTRODUCTION: For the nasal reconstruction, local flap using the adjacent tissue is selected from an esthetic viewpoint. The Rintala flap is a useful option, and reconstruction of the glabellar over the nasal tip with this flap is ideal, for which the procedure was modified to increase the blood flow to the Rintala flap to extend its clinical applications. METHODS: For defects of the glabellar over the middle one third of nasal dorsum, the Rintala flap is transferred employing the original design and technique dissected on supraperiosteal plane. For defects of the lower one third of nasal dorsum over the nasal tip, blood supply through the lateral nasal artery is added to the distal end of the flap, preparing a long flap with stable blood supply like Maruyama described in 1997. RESULTS: This procedure was applied for nasal reconstruction in 15 patients. The Rintala flap was applied in 12 and the modified Rintala flap with adding blood flow from the lateral nasal artery was applied in 3. Blood supply to the flap was very stable in all patients, and favorable outcomes were achieved. CONCLUSIONS: Using this procedure, the natural contour and morphology of the glabellar over the nasal tip may be reconstructed. The technique is simple and easy. Using this procedure, clinical applications of the Rintala flap can be extended, showing that it is a useful nasal reconstructive procedure.

Dynamic Reconstruction Using Bilateral Lengthening Temporalis Myoplasty for Facial Palsies in Patients with Hereditary Skin Laxity.

Hereditary skin laxity is a rare condition, some cases of which are also referred to as cutis laxa, and those involving facial skin are considered a target for treatment by plastic surgery as patients present with an aged face, which can reduce their quality of life. In some of these patients, the facial nerve and muscles may be affected, and cause weakness of mimetic muscles. We performed one-stage bilateral lengthening temporalis myoplasty reanimation, followed by lower facial contouring with partial lower lip excision and hammock-shaped fascia grafting in two patients with hereditary facial skin laxity coexisting with facial palsy. The patient was a 63-year-old woman with hereditary gelsolin amyloidosis and a 64-year-old man who was diagnosed with oculopharyngeal muscular dystrophy. Postoperatively, a symmetrical facial contour was achieved in repose, and smiling with and without biting was possible. To our knowledge, there are no reports of dynamic smile reconstruction for facial weakness in patients with hereditary facial skin laxity. Although these patients may experience progressive loss of function of the trigeminal nerve and its innervating muscles, the static suspension effect of lengthening temporalis myoplasty can be expected to continue even if the temporal muscles lose their function in the future. We believe that, with careful patient selection, dynamic reconstruction is an option for progressive facial paralysis. In this article, we present the chronological history of two patients who underwent multiple plastic surgery procedures and discuss the importance of the role of plastic surgery in improving the quality of life under these conditions.

Global trends and scenarios for terrestrial biodiversity and ecosystem services from 1900 to 2050.

Based on an extensive model intercomparison, we assessed trends in biodiversity and ecosystem services from historical reconstructions and future scenarios of land-use and climate change. During the 20th century, biodiversity declined globally by 2 to 11%, as estimated by a range of indicators. Provisioning ecosystem services increased several fold, and regulating services decreased moderately. Going forward, policies toward sustainability have the potential to slow biodiversity loss resulting from land-use change and the demand for provisioning services while reducing or reversing declines in regulating services. However, negative impacts on biodiversity due to climate change appear poised to increase, particularly in the higher-emissions scenarios. Our assessment identifies remaining modeling uncertainties but also robustly shows that renewed policy efforts are needed to meet the goals of the Convention on Biological Diversity.

VP2118 has major roles in Vibrio parahaemolyticus response to oxidative stress.

BACKGROUND: Reactive oxygen species (ROS), including superoxide anion radical, induce chronic risk of oxidative damage to many cellular macromolecules resulting in damage to cells. Superoxide dismutases (SODs) catalyze the dismutation of superoxide to oxygen and hydrogen peroxide and are a primary defense against ROS. Vibrio parahaemolyticus, a marine bacterium that causes acute gastroenteritis following consumption of raw or undercooked seafood, can survive ROS generated by intestinal inflammatory cells. However, there is little information concerning SODs in V. parahaemolyticus. This study aims to clarify the role of V. parahaemolyticus SODs against ROS. METHODS: V. parahaemolyticus SOD gene promoter activities were measured by a GFP reporter assay. Mutants of V. parahaemolyticus SOD genes were constructed and their SOD activity and resistance to oxidative stresses were measured. RESULTS: Bioinformatic analysis showed that V. parahaemolyticus SODs were distinguished by their metal cofactors, FeSOD (VP2118), MnSOD (VP2860), and CuZnSOD (VPA1514). VP2118 gene promoter activity was significantly higher than the other SOD genes. In a VP2118 gene deletion mutant, SOD activity was significantly decreased and could be recovered by VP2118 gene complementation. The absence of VP2118 resulted in significantly lowered resistance to ROS generated by hydrogen peroxide, hypoxanthine-xanthine oxidase, or Paraquat. Furthermore, both the N- and C-terminal SOD domains of VP2118 were necessary for ROS resistance. CONCLUSION: VP2118 is the primary V. parahaemolyticus SOD and is vital for anti-oxidative stress responses. GENERAL SIGNIFICANCE: The V. parahaemolyticus FeSOD VP2118 may enhance ROS resistance and could promote its survival in the intestinal tract to facilitate host tissue infection.

Bifidobacterial α-galactosidase with unique carbohydrate-binding module specifically acts on blood group B antigen.

Bifidobacterium bifidum is one of the most frequently found bifidobacteria in the intestines of newborn infants. We previously reported that B. bifidum possesses unique metabolic pathways for O-linked glycans on gastrointestinal mucin (Yoshida E, Sakurama H, Kiyohara M, Nakajima M, Kitaoka M, Ashida H, Hirose J, Katayama T, Yamamoto K, Kumagai H. 2012. Bifidobacterium longum subsp. infantis uses two different ß-galactosidases for selectively degrading type-1 and type-2 human milk oligosaccharides. Glycobiology. 22:361-368). The nonreducing termini of O-linked glycans on mucin are frequently covered with histo-blood group antigens. Here, we identified a gene agabb from B. bifidum JCM 1254, which encodes glycoside hydrolase (GH) family 110 α-galactosidase. AgaBb is a 1289-amino acid polypeptide containing an N-terminal signal sequence, a GH110 domain, a carbohydrate-binding module (CBM) 51 domain, a bacterial Ig-like (Big) 2 domain and a C-terminal transmembrane region, in this order. The recombinant enzyme expressed in Escherichia coli hydrolyzed α1,3-linked Gal in branched blood group B antigen [Galα1-3(Fucα1-2)Galß1-R], but not in a linear xenotransplantation antigen (Galα1-3Galß1-R). The enzyme also acted on group B human salivary mucin and erythrocytes. We also revealed that CBM51 specifically bound blood group B antigen using both isothermal titration calorimetry and a solid-phase binding assay, and it enhanced the affinity of the enzyme toward substrates with multivalent B antigens. We suggest that this enzyme plays an important role in degrading B antigens to acquire nutrients from mucin oligosaccharides in the gastrointestinal tracts.

Effect of different substituents on the water-solubility and stability properties of 1 : 2 [60]fullerene derivative·gamma-cyclodextrin complexes.

We have demonstrated that C60 derivatives bearing a pyrrolidine moiety as well as a variety of other substituents can form 1 : 2 complexes with γ-cyclodextrin (γ-CDx) using a mechanochemical high-speed vibration milling apparatus. When the influence of the steric hindrance of the substituents on the formation of the complexes was negligible, the water-solubilities of the complexes were shown experimentally to be completely dependent on the hydrophobic properties of the substituent. Furthermore, the stabilities of the γ-CDx-complexes of several different C60 derivatives were found to be similar to or slightly higher than that of the C60·Î³-CDx complex, with the solubilities of the complexes showing no correlation to the stabilities. Based on the results of a series of theoretical investigations, we have shown that the stabilities of the γ-CDx-complexes can be affected not only by steric effects but also by the polarities of the substituent groups, which exist in the vicinity of the upper rim of γ-CDx, because the water bound to the polar group can assist in the stabilisation of the complexes.

Extensive epidural pneumatosis and pneumomediastinum combined with diabetic ketoacidosis.

Key Clinical Message: Epidural pneumatosis and pneumomediastinum are rare, benign complications of diabetic ketoacidosis. As they can mimic serious conditions including esophageal rupture, diagnostic evaluation, and attentive monitoring are crucial. Abstract: Diabetic ketoacidosis can rarely present with epidural pneumatosis and pneumomediastinum, possibly due to forceful vomiting and Kussmaul breathing. Recognizing these pneumocomplications is crucial, as they can mimic severe conditions, including esophageal rupture. Consequently, diagnostic workup and vigilant monitoring are critical, even though these pneumocomplications are typically benign and self-resolving.

Glycoside hydrolase family 89 alpha-N-acetylglucosaminidase from Clostridium perfringens specifically acts on GlcNAc alpha1,4Gal beta1R at the non-reducing terminus of O-glycans in gastric mucin.

In mammals, α-linked GlcNAc is primarily found in heparan sulfate/heparin and gastric gland mucous cell type mucin. α-N-acetylglucosaminidases (αGNases) belonging to glycoside hydrolase family 89 are widely distributed from bacteria to higher eukaryotes. Human lysosomal αGNase is well known to degrade heparin and heparan sulfate. Here, we reveal the substrate specificity of αGNase (AgnC) from Clostridium perfringens strain 13, a bacterial homolog of human αGNase, by chemically synthesizing a series of disaccharide substrates containing α-linked GlcNAc. AgnC was found to release GlcNAc from GlcNAcα1,4Galß1pMP and GlcNAcα1pNP substrates (where pMP and pNP represent p-methoxyphenyl and p-nitrophenyl, respectively). AgnC also released GlcNAc from porcine gastric mucin and cell surface mucin. Because AgnC showed no activity against any of the GlcNAcα1,2Galß1pMP, GlcNAcα1,3Galß1pMP, GlcNAcα1,6Galß1pMP, and GlcNAcα1,4GlcAß1pMP substrates, this enzyme may represent a specific glycosidase required for degrading α-GlcNAc-capped O-glycans of the class III mucin secreted from the stomach and duodenum. Deletion of the C-terminal region containing several carbohydrate-binding module 32 (CBM32) domains significantly reduced the activity for porcine gastric mucin; however, activity against GlcNAcα1,4Galß1pMP was markedly enhanced. Dot blot and ELISA analyses revealed that the deletion construct containing the C-terminal CBM-C2 to CBM-C6 domains binds strongly to porcine gastric mucin. Consequently, tandem CBM32 domains located near the C terminus of AgnC should function by increasing the affinity for branched or clustered α-GlcNAc-containing glycans. The agnC gene-disrupted strain showed significantly reduced growth on the class III mucin-containing medium compared with the wild type strain, suggesting that AgnC might have an important role in dominant growth in intestines.

VopB1 and VopD1 are essential for translocation of type III secretion system 1 effectors of Vibrio parahaemolyticus.

Vibrio parahaemolyticus is a pathogenic Vibrio species that causes food-borne acute gastroenteritis, often related to the consumption of raw or undercooked seafood. Vibrio parahaemolyticus has 2 type III secretion systems (T3SS1 and T3SS2). Here, we demonstrate that VP1657 (VopB1) and VP1656 (VopD1), which share sequence similarity with Pseudomonas genes popB (38%) and popD (36%), respectively, are essential for translocation of T3SS1 effectors into host cells. A VP1680CyaA fusion reporter system was constructed to observe effector translocation. Using this reporter assay we showed that the VopB1 and VopD1 deletion strains were unable to translocate VP1680 to host cell but that the secretion of VP1680 into the culture medium was not affected. VopB1 or VopD1 deletion strains did not enhance cytotoxicity and failed to activate mitogen-activated protein kinases and secretion of interleukin-8, which depend on VP1680. Thus, we conclude that VopB1 and VopD1 are essential components of the translocon. To target VopB1 and VopD1 may have therapeutic potential for the treatment or prevention in V. parahaemolyticus infection.

Global estimates of stress-reflecting indices reveal key climatic drivers of climate-induced forest range shifts.

Climate change has the potential to cause forest range shifts at a broad scale and consequently can alter crucial forest functions, including carbon sequestration. However, global-scale projections of future forest range shifts remain challenging because our knowledge of the physiological responses of plants to climatic stress is limited to particular species and is insufficient for wide-range projections, in addition to the uncertainties in the impacts of non-climatic factors, such as wildfire, wind, and insect outbreaks. To evaluate the vulnerability and resilience of forests to climate change, we developed a new empirical approach using climatic indices reflecting physiological stressors on plants. We calculated the global distributions of seven indices based on primary climatic stressors (drought, solar radiation, and temperature) at high resolution. We then modeled the relationship between the seven indices and global forest extent. We found two key stressors driving climate-induced forest range shifts on a global scale: low temperature under high radiation and drought. At high latitudes of the Northern Hemisphere, forest establishment became difficult when the mean temperature was less than approximately 7.2 °C in the highest radiation quarter. Forest sensitivity to drought was more pronounced at mid-latitudes. In areas where the humidity index (ratio of precipitation to potential evapotranspiration) was below 0.45, shrubland and grassland became more dominant than forests. Our results also suggested that the impacts of climate change on global forest range shifts will be geographically biased depending on the areas affected by the key climatic stressors. Potential forest gain was remarkable in boreal regions due to increasing temperature. Potential forest loss was remarkable in current tropical grassland and temperate forest/grassland ecoregions due to increasing drought. Our approach using stress-reflecting indices could improve our ability to detect the roles of climatic stressors on climate-induced forest range shifts.

Tongue thickness measured by ultrasonography is associated with tongue pressure in the Japanese elderly.

The term "oral frailty" reflects the fact that oral health is associated with physical frailty and mortality. The gold standard methods for evaluating the swallowing function have several problems, including the need for specialized equipment, the risk of radiation exposure and aspiration, and general physicians not possessing the requisite training to perform the examination. Hence, several simple and non-invasive techniques have been developed for evaluating swallowing function, such as those for measuring tongue pressure and tongue thickness. The aim of this study was to investigate the relationship between tongue thickness ultrasonography and tongue pressure in the Japanese elderly. We evaluated 254 elderly patients, who underwent tongue ultrasonography and tongue pressure measurement. To determine tongue thickness, we measured the vertical distance from the surface of the mylohyoid muscle to the tongue dorsum using ultrasonography. The results of the analyses revealed that tongue thickness was linearly associated with tongue pressure in both sexes. In male participants, dyslipidemia, lower leg circumference, and tongue pressure were independently and significantly associated with tongue thickness. In female participants, body mass index and tongue pressure were independently and significantly associated with tongue thickness. The optimal cutoff for tongue thickness to predict the tongue pressure of < 20 kPa was 41.3 mm in males, and 39.3 mm in females. In the Japanese elderly, tongue thickness using ultrasonography is associated with tongue pressure. Tongue thickness and tongue pressure, which are sensitive markers for oral frailty, decrease with age. We conclude that tongue ultrasonography provides a less invasive technique for determining tongue thickness and predicts oral frailty for elderly patients.

Biodiversity can benefit from climate stabilization despite adverse side effects of land-based mitigation.

Limiting the magnitude of climate change via stringent greenhouse gas (GHG) mitigation is necessary to prevent further biodiversity loss. However, some strategies to mitigate GHG emission involve greater land-based mitigation efforts, which may cause biodiversity loss from land-use changes. Here we estimate how climate and land-based mitigation efforts interact with global biodiversity by using an integrated assessment model framework to project potential habitat for five major taxonomic groups. We find that stringent GHG mitigation can generally bring a net benefit to global biodiversity even if land-based mitigation is adopted. This trend is strengthened in the latter half of this century. In contrast, some regions projected to experience much growth in land-based mitigation efforts (i.e., Europe and Oceania) are expected to suffer biodiversity loss. Our results support the enactment of stringent GHG mitigation policies in terms of biodiversity. To conserve local biodiversity, however, these policies must be carefully designed in conjunction with land-use regulations and societal transformation in order to minimize the conversion of natural habitats.

Potential distribution of pine wilt disease under future climate change scenarios.

Pine wilt disease (PWD) constitutes a serious threat to pine forests. Since development depends on temperature and drought, there is a concern that future climate change could lead to the spread of PWD infections. We evaluated the risk of PWD in 21 susceptible Pinus species on a global scale. The MB index, which represents the sum of the difference between the mean monthly temperature and 15 when the mean monthly temperatures exceeds 15°C, was used to determine current and future regions vulnerable to PWD (MB ≥ 22). For future climate conditions, we compared the difference in PWD risks among four different representative concentration pathways (RCPs 2.6, 4.5, 6.0, and 8.5) and two time periods (2050s and 2070s). We also evaluated the impact of climate change on habitat suitability for each Pinus species using species distribution models. The findings were then integrated and the potential risk of PWD spread under climate change was discussed. Within the natural Pinus distribution area, southern parts of North America, Europe, and Asia were categorized as vulnerable regions (MB ≥ 22; 16% of the total Pinus distribution area). Representative provinces in which PWD has been reported at least once overlapped with the vulnerable regions. All RCP scenarios showed expansion of vulnerable regions in northern parts of Europe, Asia, and North America under future climate conditions. By the 2070s, under RCP 8.5, an estimated increase in the area of vulnerable regions to approximately 50% of the total Pinus distribution area was revealed. In addition, the habitat conditions of a large portion of the Pinus distribution areas in Europe and Asia were deemed unsuitable by the 2070s under RCP 8.5. Approximately 40% of these regions overlapped with regions deemed vulnerable to PWD, suggesting that Pinus forests in these areas are at risk of serious damage due to habitat shifts and spread of PWD.

[Sucessful treatment by micafungin of pulmonary aspergillosis occurring in an old lung abscess].

A 55-year-old man, who had diabetes from age 46 years old had been treated for a lung abscess in the right upper lobe at age 51. He underwent an operation for stomach cancer at age 52. When he was 55 years old, a cavity lesion appeared in his right upper lobe at the site of the treated lung abscess. Pulmonary aspergillosis was diagnosed by bronchial biopsy. In this case, we controlled his diabetes and used micafungin which has a mechanism unlike other conventional antifungal agents. The shadow decreased and examination of the resected specimen showed that the fungus had disappeard. Pulmonary aspergillosis is an important mycosis profunda and micafungin seems to be an effective antifungal agent against it.

Characterization of the linoleic acid Δ9 hydratase catalyzing the first step of polyunsaturated fatty acid saturation metabolism in Lactobacillus plantarum AKU 1009a.

Linoleic acid Δ9 hydratase, which is involved in linoleic acid saturation metabolism of Lactobacillus plantarum AKU 1009a, was cloned, expressed as a his-tagged recombinant enzyme, purified with an affinity column, and characterized. The enzyme required FAD as a cofactor and its activity was enhanced by NADH. The maximal activities for the hydration of linoleic acid and for the dehydration of 10-hydroxy-cis-12-octadecenoic acid (HYA) were observed at 37 °C in buffer at pH 5.5 containing 0.5 M NaCl. Free C16 and C18 fatty acids with cis-9 double bonds and 10-hydroxy fatty acids served as substrates for the hydration and dehydration reactions, respectively. The apparent Km value for linoleic acid was estimated to be 92 µM, with a kcat of 2.6∙10(-2) s(-1) and a Hill factor of 3.3. The apparent Km value for HYA was estimated to be 98 µM, with a kcat of 1.2∙10(-3) s(-1).

Gut Microbial Fatty Acid Metabolites Reduce Triacylglycerol Levels in Hepatocytes.

Hydroxy and oxo fatty acids were recently found to be produced as intermediates during gut microbial fatty acid metabolism. Lactobacillus plantarum produces these fatty acids from unsaturated fatty acids such as linoleic acid. In this study, we investigated the effects of these gut microbial fatty acid metabolites on the lipogenesis in liver cells. We screened their effect on sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells treated with a synthetic liver X receptor α (LXRα) agonist (T0901317). The results showed that 10-hydroxy-12(Z)-octadecenoic acid (18:1) (HYA), 10-hydroxy-6(Z),12(Z)-octadecadienoic acid (18:2) (γHYA), 10-oxo-12(Z)-18:1 (KetoA), and 10-oxo-6(Z),12(Z)-18:2 (γKetoA) significantly decreased SREBP-1c mRNA expression induced by T0901317. These fatty acids also downregulated the mRNA expression of lipogenic genes by suppressing LXRα activity and inhibiting SREBP-1 maturation. Oral administration of KetoA, which effectively reduced triacylglycerol accumulation and acetyl-CoA carboxylase 2 (ACC2) expression in HepG2 cells, for 2 weeks significantly decreased Srebp-1c, Scd-1, and Acc2 expression in the liver of mice fed a high-sucrose diet. Our findings suggest that the hypolipidemic effect of the fatty acid metabolites produced by L. plantarum can be exploited in the treatment of cardiovascular diseases or dyslipidemia.