Caprylic acid enhances hydroxyhexylitaconic acid production in Aspergillus niger S17-5.

AIM: Aspergillus niger S17-5 produces two alkylitaconic acids, 9-hydroxyhexylitaconic acid (9-HHIA) and 10-hydroxyhexylitaconic acid (10-HHIA), which have cytotoxic and polymer building block properties. In this study, we characterized the production of 9-HHIA and 10-HHIA by addition of their expected precursor, caprylic acid, to a culture of A. niger S17-5, and demonstrated batch fermentation of 9-HHIA and 10-HHIA in a jar fermenter with DO-stat. METHODS AND RESULTS: Production titres of 9-HHIA and 10-HHIA from 3% glucose in a flask after 25 days cultivation were 0·35 and 1·01 g l-1 respectively. Addition of 0·22 g l-1 of caprylic acid to a suspension of resting cells of A. niger S17-5 led to 32% enhancement of total 9-HHIA and 10-HHIA production compared to no addition. No enhancement of the production of 9-HHIA or 10-HHIA by the addition of oxaloacetic acid was observed. Addition of caprylic acid to the culture at mid-growth phase was more suitable for 9-HHIA and 10-HHIA production due to less cell growth inhibition by caprylic acid. DO-stat batch fermentation with 3% glucose and 14·4 g l-1 of caprylic acid in a 1·5 l jar fermenter resulted in the production titres of 9-HHIA and 10-HHIA being 0·48 and 1·54 g l-1 respectively after 10 days of cultivation. CONCLUSIONS: Addition of caprylic acid to the culture of A. niger S17-5 enhances 9-HHIA and 10-HHIA production. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that 9-HHIA and 10-HHIA are synthesized with octanoyl-CoA derived from caprylic acid, and that the supply of octanoyl-CoA is a rate-limiting step in 9-HHIA and 10-HHIA production. To the best of our knowledge, this is the first report regarding the fermentation of naturally occurring itaconic acid derivatives in a jar fermenter.

Evaluation of the effect of lanthanum carbonate hydrate on the pharmacokinetics of roxadustat in non-elderly healthy adult male subjects.

WHAT IS KNOWN AND OBJECTIVE: Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor currently being investigated for the treatment of anemia in chronic kidney disease. Lanthanum carbonate is a phosphate binder that is commonly used to treat hyperphosphatemia in patients with chronic kidney disease. This study investigated the effect of lanthanum carbonate on the pharmacokinetics, safety and tolerability of a single oral dose of roxadustat in healthy non-elderly adult male subjects. METHODS: This was an open-label, randomized, two-period, two-sequence crossover study in non-elderly healthy adult males. Subjects randomized to Group 1 received roxadustat alone during Period 1 and roxadustat concomitantly with lanthanum carbonate during Period 2; subjects randomized to Group 2 received roxadustat concomitantly with lanthanum carbonate during Period 1 and roxadustat alone during Period 2. All subjects received a single oral dose of 100 mg roxadustat on Day 1 in both periods. Subjects receiving concomitant lanthanum carbonate received 750 mg lanthanum carbonate three times daily on Days 1 and 2. Pharmacokinetic assessments were conducted on Days 1-4 in both periods. The primary study outcomes were the area under the concentration-time curve from the time of dosing extrapolated to infinity (AUCinf ), and maximum concentration (Cmax ); the geometric least squares mean ratio (GMR; roxadustat + lanthanum carbonate/roxadustat alone) and corresponding 90% confidence interval (CI) was calculated for AUCinf and Cmax . Safety was assessed by the occurrence of treatment-emergent adverse events (TEAEs), laboratory test results, vital signs and standard 12-lead electrocardiogram. RESULTS AND DISCUSSION: A total of 18 subjects were enrolled (Group 1, n = 9; Group 2, n = 9); no subjects discontinued from the study. Roxadustat was rapidly absorbed, reaching maximum plasma concentration between 1 and 4 hours. The GMRs for AUCinf and Cmax were 88.00% (90% CI: 84.01, 92.17) and 98.58% (90% CI: 92.92, 104.58), respectively. The 90% CIs for both parameters were within the no-effect boundaries of 80% and 125%, indicating a lack of effect of lanthanum carbonate on roxadustat absorption. No deaths or serious TEAEs occurred. WHAT IS NEW AND CONCLUSIONS: Concomitant administration of a single oral dose of 100 mg roxadustat and 750 mg lanthanum carbonate three times daily did not impact the AUCinf or Cmax of roxadustat and was considered safe and well tolerated in non-elderly healthy adult male Japanese subjects.

Liver transection using indocyanine green fluorescence imaging and hepatic vein clamping.

BACKGROUND: Three-dimensional (3D) imaging has facilitated liver resection with excision of hepatic veins by estimating the liver volume of portal and hepatic venous territories. However, 3D imaging cannot be used for real-time navigation to determine the liver transection line. This study assessed the value of indocyanine green (ICG) fluorescence imaging with hepatic vein clamping for navigation during liver transection. METHODS: Consecutive patients who underwent liver resection with excision of major hepatic veins between 2012 and 2013 were evaluated using ICG fluorescence imaging after clamping veins and injecting ICG. Regional fluorescence intensity (FI) values of non-veno-occlusive regions (FINon ), veno-occlusive regions (FIVO ) and ischaemic regions (FIIS ) were calculated using luminance analysing software. RESULTS: Of the 21 patients, ten, four and seven underwent limited resection, monosegmentectomy/sectionectomy and hemihepatectomy respectively, with excision of major hepatic veins. Median veno-occlusive liver volume was 80 (range 30-458) ml. Fluorescence imaging visualized veno-occlusive regions as territories with lower FI compared with non-veno-occlusive regions, and ischaemic regions as territories with no fluorescence after intravenous ICG injection. Median FIIS /FINon was lower than median FIVO /FINon (0·22 versus 0·59; P = 0·002). There were no deaths in hospital or within 30 days, and only one major complication. CONCLUSION: ICG fluorescence imaging with hepatic vein clamping visualized non-veno-occlusive, veno-occlusive and ischaemic regions. This technique may guide liver transection by intraoperative navigation, enhancing the safety and accuracy of liver resection.

Publisher's Note: Electronic Phase Separation and Dramatic Inverse Band Renormalization in the Mixed-Valence Cuprate LiCu_{2}O_{2} [Phys. Rev. Lett. 118, 176404 (2017)].

This corrects the article DOI: 10.1103/PhysRevLett.118.176404.

Electronic Phase Separation and Dramatic Inverse Band Renormalization in the Mixed-Valence Cuprate LiCu_{2}O_{2}.

We measured, by angle-resolved photoemission spectroscopy, the electronic structure of LiCu_{2}O_{2}, a mixed-valence cuprate where planes of Cu(I) (3d^{10}) ions are sandwiched between layers containing one-dimensional edge-sharing Cu(II) (3d^{9}) chains. We find that the Cu(I)- and Cu(II)-derived electronic states form separate electronic subsystems, in spite of being coupled by bridging O ions. The valence band, of the Cu(I) character, disperses within the charge-transfer gap of the strongly correlated Cu(II) states, displaying an unprecedented 250% broadening of the bandwidth with respect to the predictions of density functional theory. Our observation is at odds with the widely accepted tenet of many-body theory that correlation effects generally yield narrower bands and larger electron masses and suggests that present-day electronic structure techniques provide an intrinsically inappropriate description of ligand-to-d hybridizations in late transition metal oxides.

Assessing the progression of chronic periodontitis using subgingival pathogen levels: a 24-month prospective multicenter cohort study.

BACKGROUND: The diagnosis of the progression of periodontitis presently depends on the use of clinical symptoms (such as attachment loss) and radiographic imaging. The aim of the multicenter study described here was to evaluate the diagnostic use of the bacterial content of subgingival plaque recovered from the deepest pockets in assessing disease progression in chronic periodontitis patients. METHODS: This study consisted of a 24-month investigation of a total of 163 patients with chronic periodontitis who received trimonthly follow-up care. Subgingival plaque from the deepest pockets was recovered and assessed for bacterial content of Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans using the modified Invader PLUS assay. The corresponding serum IgG titers were measured using ELISA. Changes in clinical parameters were evaluated over the course of 24 months. The sensitivity, specificity, and prediction values were calculated and used to determine cutoff points for prediction of the progression of chronic periodontitis. RESULTS: Of the 124 individuals who completed the 24-month monitoring phase, 62 exhibited progression of periodontitis, whereas 62 demonstrated stable disease. The P. gingivalis counts of subgingival plaque from the deepest pockets was significantly associated with the progression of periodontitis (p < 0.001, positive predictive value = 0.708). CONCLUSIONS: The P. gingivalis counts of subgingival plaque from the deepest pockets may be associated with the progression of periodontitis.

Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study.

BACKGROUND AND OBJECTIVE: A diagnosis of periodontitis progression is presently limited to clinical parameters such as attachment loss and radiographic imaging. The aim of this multicenter study was to monitor disease progression in patients with chronic periodontitis during a 24-mo follow-up program and to evaluate the amount of bacteria in saliva and corresponding IgG titers in serum for determining the diagnostic usefulness of each in indicating disease progression and stability. MATERIAL AND METHODS: A total of 163 patients with chronic periodontitis who received trimonthly follow-up care were observed for 24 mo. The clinical parameters and salivary content of Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were assessed using the modified Invader PLUS assay, and the corresponding serum IgG titers were measured using ELISA. The changes through 24 mo were analyzed using cut-off values calculated for each factor. One-way ANOVA or Fisher's exact test was used to perform between-group comparison for the data collected. Diagnostic values were calculated using Fisher's exact test. RESULTS: Of the 124 individuals who completed the 24-mo monitoring phase, 62 exhibited periodontitis progression, whereas 62 demonstrated stable disease. Seven patients withdrew because of acute periodontal abscess. The ratio of P. gingivalis to total bacteria and the combination of P. gingivalis counts and IgG titers against P. gingivalis were significantly related to the progression of periodontitis. The combination of P. gingivalis ratio and P. gingivalis IgG titers was significantly associated with the progression of periodontitis (p = 0.001, sensitivity = 0.339, specificity = 0.790). CONCLUSIONS: It is suggested that the combination of P. gingivalis ratio in saliva and serum IgG titers against P. gingivalis may be associated with the progression of periodontitis.

Comparison of Volumetric and Diametric Analysis in Endovascular Repair of Descending Thoracic Aortic Aneurysm.

OBJECTIVES: The aim was to evaluate computed tomography angiography (CTA) volumetric and diametric analysis after endovascular repair of descending thoracic aortic aneurysms (DTAAs) and its correlation with and applicability for clinical follow up. METHODS: Fifty-four consecutive endovascular repairs for DTAA were retrospectively evaluated from 2008 to 2014. All patients underwent pre-operative CTA and at least one post-operative CTA at 6 months. Fifty-four pre-operative and 137 post-operative CTAs were evaluated (using the Ziosoft 2 software) to analyze the aneurysm and thrombus volume, the maximum aneurysm diameter, and their changes at the last follow up CTA (mean 30.5 months; range 6.5-66.4 months). A statistical analysis was performed to assess the correlation between diameter and volume changes, as well as association with endoleaks. The cut off point to predict endoleaks was determined using a receiver operating characteristic (ROC) curve. The predictive accuracy of volume change versus diameter change for Type I endoleak was analyzed. RESULTS: The mean pre-operative aneurysm diameter, aneurysm volume, and thrombus volume were 56.7 ± 11.7 mm, 145.8 ± 120.0 mL, and 48.8 ± 54.8 mL, respectively. Within the observational period, a mean decrease of -27.9 ± 30.5% in the aortic volume and -15.9 ± 15.4% in diameter was observed. Correlation between aneurysm diameter and volume changes was good (r = 0.854). Volume and diameter changes were significantly different between groups with and without endoleaks (volume change 16.9 ± 38.8% vs. -35.6 ± 23.1%, p < .001; diameter change 8.0 ± 12.1% vs. -18.8 ± 14.3%, p < .001). A pre-operative thrombus volume percentage of <11.3% and increase in aneurysm volume +11.6% were predictive factors for Type II and Type I endoleak, respectively. The accuracy of a >10% volume increase in predicting a Type I endoleak was higher (accuracy 96.3%, sensitivity 75%, and specificity 98%) than a >5 mm diameter increase (accuracy 92.6%, sensitivity 25%, and specificity 98%). CONCLUSIONS: CT volumetric analysis is a more reliable modality for predicting endoleaks after endovascular repair for DTAA than diameter analysis.

Periostin of human periodontal ligament fibroblasts promotes migration of human mesenchymal stem cell through the αvß3 integrin/FAK/PI3K/Akt pathway.

BACKGROUND AND OBJECTIVE: The periodontal ligament (PDL) is characterized by rapid turnover, high remodeling capacity and high inherent regenerative potential compared with other connective tissues. Periostin, which is highly expressed in the fibroblasts in the PDL, has been widely discussed in relation to collagen fibrillogenesis in the PDL. Recently, several reports have indicated periostin in cell migration. The aim of this study was to examine whether human PDL fibroblasts (hPDLFs) with high levels of periostin expression promote the migration of human bone marrow mesenchymal stem cells (hMSCs). MATERIAL AND METHODS: The migration of hMSCs was examined by transwell chamber migration assay under different conditions: medium alone, hPDLFs, human dermal fibroblasts, recombinant periostin, integrin αvß3 blocking antibody (anti-CD51/61 antibody) and inhibitors of FAK (PF431396) and PI3K (LY294002). Phosphorylation of FAK and Akt in hMSCs under stimulation of periostin was examined by western blotting. RESULTS: The migration assay revealed that the number of migrated hMSCs by hPDLFs was significantly larger than those by dermal fibroblasts, periostin small interfering RNA hPDLFs and medium alone. Furthermore, recombinant periostin also strongly induced hMSC migration. The addition of anti-CD51/61 antibody, PF431396 and LY294002 caused a significant reduction in the number of migrated hMSCs respectively. The anti-CD51/61 antibody inhibited both FAK and Akt phosphorylations under periostin stimulation. PF431396 inhibited both FAK and Akt phosphorylations. LY294002 inhibited only Akt phosphorylation, and FAK phosphorylation was not influenced under periostin stimulation. CONCLUSION: Periostin expression in hPDLFs promotes the migration of hMSCs through the αvß3 integrin/FAK/PI3K/Akt pathway in vitro.

Evaluation of hamstring muscle strength and morphology after anterior cruciate ligament reconstruction.

This study aimed to clarify the relationship between knee flexor strength and hamstring muscle morphology after anterior cruciate ligament (ACL) reconstruction using the semitendinosus (ST) tendon and to determine the causative factors of decreased knee flexor muscle strength. Fourteen male and ten female patients who resumed sports activities after surgery participated in the experiment. Isometric knee flexion torque was measured at 30°, 45°, 60°, 90°, and 105° of knee flexion. Magnetic resonance imaging (MRI) was used to calculate ST muscle length and hamstring muscle volume, and to confirm the status of ST tendon regeneration. The correlation between the MRI findings and flexor strength was analyzed. Regenerated ST tendon was confirmed in 21 of the 24 patients, but muscle volume (87.6%) and muscle length (74.5%) of the ST in the operated limb were significantly smaller than those in the normal limb. The percentage of the knee flexion torque of the operated limb compared with that of the normal was apparently lower at 105° (69.1%) and 90° (68.6%) than at 60° (84.4%). Tendon regeneration, ST muscle shortening, and ST muscle atrophy correlated with decreased knee flexion torque. These results indicated that preserving the morphology of the ST muscle-tendon complex is important.

Loss-of-function mutations in the gene encoding filaggrin underlie a Japanese family with food-dependent exercise-induced anaphylaxis.

BACKGROUND: Food-dependent exercise-induced anaphylaxis (FDEIA) is a serious food allergy in which anaphylaxis develops when exercise is performed within several hours after food intake. The precise mechanism underlying allergic sensitization in FDEIA has been an important issue but remains poorly understood. OBJECTIVES: We aimed to elucidate the pathomechanism including the route of allergen sensitization involved in FDEIA. METHODS: A Japanese family with wheat-dependent exercise-induced anaphylaxis (WDEIA), a specific form of FDEIA, were clinically examined. Mutation analysis of the gene encoding filaggrin (FLG) was also performed. RESULTS: Two of the family members were confirmed as WDEIA on the basis of their medical history and positive provocation test results. Notably, the two affected individuals in the family had concomitant ichthyosis vulgaris. Mutation analysis of FLG revealed that they carry one or more loss-of-function mutations that have not been described in the Japanese population. CONCLUSION: These results indicate that FLG mutations might be involved in the pathogenesis of WDEIA in the present case.

Oral administration of bovine lactoferrin attenuates ultraviolet B-induced skin photodamage in hairless mice.

Lactoferrin (LF) is recognized as a host defensive glycoprotein, especially for newborn infants. The aim of this study was to investigate whether orally administered LF had protective activity against UV-induced skin damage in hairless mice. Transepidermal water loss and skin hydration were evaluated in nonirradiated mice, UVB-irradiated mice, and UVB-irradiated and LF-administered mice. Supplementation with LF (1,600 mg/kg per day) effectively suppressed the increase in transepidermal water loss, reduction in skin hydration, aberrant epidermal hyperplasia, and cell apoptosis induced by UV irradiation. Although no significant changes in superoxide dismutase-like activity or malondialdehyde levels were observed in the skin with both UV irradiation and LF administration, UV-stimulated IL-1ß levels in the skin were significantly suppressed by the administration of LF. Oral supplementation with LF has the potential to reduce IL-1ß levels and prevent UV-induced skin damage. Further studies are needed to elucidate the relationships between the antiinflammatory effects and skin protective function of LF.

Adipose cells induce phospho-Thr-172 AMPK production by epinephrine or CL316243 in mouse 3T3-L1 adipocytes or MAPK activation and G protein-associated PI3K responses induced by CL316243 or aluminum fluoride in rat white adipocytes.

Responses of adipose cells to adrenoceptor regulation, including that of ß-adrenoceptor (AR), and the signalling machinery involved in these responses are not sufficiently understood; information that is helpful for elucidating the adrenoceptor (adrenergic and ß-AR)-responsive machinery is insufficient. We examined phospho-Thr-172 AMPK production in mouse-derived 3T3-L1 adipocytes treated with epinephrine or CL316243 (a ß3-AR agonist) for 15 min. We also examined MAPK activation or G protein-associated PI3K activation or -associated PI3K p85 complex formation in rat epididymal (white) adipocytes treated with CL316243 for 15 min or aluminum fluoride (a G-protein signalling activator) for 20 min. Furthermore, we examined the effect of PTX (a trimeric G-protein inactivator) on p85 complex formation induced by aluminum fluoride treatment. Western blot analysis revealed that epinephrine or CL316243 treatment increased the phospho- Thr-172 AMPK (an active form of AMPK) level in 3T3-L1 adipocytes. Activated kinase analysis with a specific substrate showed that CL316243 or aluminum fluoride treatment activated MAPK in rat adipocytes. Immunoprecipitation experiments with a G-protein ß subunit (Gß) antibody showed that treatment of rat adipocytes with CL316243 activated PI3K and increased the PI3K p85 level in the Gß antibody immunoprecipitates. Such an increase in the p85 level was similarly elicited by aluminum fluoride treatment in a PTX-sensitive manner. Our results provide possible clues for clarifying the signalling machinery involved in adrenoceptor responses, including those of ß3-AR, in mouse-derived adipocytes and rat white adipocytes. Our findings advance the understanding of responses to adrenoceptor regulation in adipose cells and of the cellular signalling machinery present in the cells.

Strong plastic responses in aerenchyma formation in F1 hybrids of Imperata cylindrica under different soil moisture conditions.

Hybrids can express traits plastically, enabling them to occupy environments that differ from parental environments. However, there is insufficient evidence demonstrating how phenotypic plasticity in specific traits mediates hybrid performance. Two parental ecotypes of Imperata cylindrica produce F1 hybrids. The E-type in wet habitats has larger internal aerenchyma than the C-type in dry habitats. This study evaluated relationships between habitat utilisation, aerenchyma plasticity, and growth of I. cylindrica accessions. We hypothesize that plasticity in expressing parental traits explains hybrid establishment in habitats with various soil moisture conditions. Aerenchyma formation was examined in the leaf midribs, rhizomes and roots of two parental ecotypes and their F1 hybrids in their natural habitats. In common garden experiments, we examined plastic aerenchyma formation in leaf midribs, rhizomes and roots of natural and artificial F1 hybrids and parental ecotypes and quantified vegetative growth performance. In the natural habitats where soil moisture content varied widely, the F1 hybrids showed larger variation in aerenchyma formation in rhizomes than their parental ecotypes. In the common garden experiments, F1 hybrids showed high plasticity of aerenchyma formation in rhizomes, and their growth was similar to that of C-type and E-type under drained and flooded conditions, respectively. The results demonstrate that F1 hybrids of I. cylindrica exhibit plasticity in aerenchyma development in response to varying local soil moisture content. This characteristic allows the hybrids to thrive in diverse soil moisture conditions.

Single-shot detection of mid-infrared spectra by chirped-pulse upconversion with four-wave difference frequency generation in gases.

Single-shot detection of ultrabroadband mid-infrared spectra was demonstrated by using chirped-pulse upconversion technique with four-wave difference frequency generation in gases. Thanks to the low dispersion of the gas media, the bandwidth of the phase matching condition of the upconversion process becomes very broad and the entire mid-infrared spectrum spanning from 200 to 5500 cm(-1) was upconverted by using a 10 ps chirped pulse to visible wavelength radiation, which was detected with a conventional visible dispersive spectrometer. This method was demonstrated by the successful measurement of infrared absorption spectra of organic polymer films.

Beaming of high-order harmonics generated from laser-plasma interactions.

Beam divergences of high-order extreme ultraviolet harmonics from intense laser interactions with steep plasma density gradients are studied through experiment and Fourier analysis of the harmonic spatial phase. We show that while emission due to the relativistically oscillating mirror mechanism can be explained by ponderomotive surface denting, in agreement with previous results, the divergence of the emission due to the coherent wake emission mechanism requires a combination of the dent phase and an intrinsic emission phase. The temporal dependence of the divergences for both mechanisms is highlighted while it is also shown that the coherent wake emission divergence can be small in circumstances where the phase terms compensate each other.

A novel splice site mutation in NCSTN underlies a Japanese family with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic follicular occlusive disease with characteristic recurrent draining sinuses, skin abscesses and disfiguring scars, mainly involving the axilla, groin, perianal and perineal regions. While most HS cases are nonfamilial, familial cases showing autosomal dominant inheritance have been reported. Recently, loss-of-function mutations in the genes encoding γ-secretase have been identified as a cause of familial HS in the Chinese and British populations. OBJECTIVES: To identify mutations in the genes encoding γ-secretase in Japanese patients with familial and nonfamilial HS. METHODS: Two affected and three unaffected individuals from a Japanese family with familial HS and nine patients with nonfamilial HS were recruited. We conducted mutation analysis of the γ-secretase genes in Japanese patients with familial and nonfamilial HS. RESULTS: A novel splice site mutation in the nicastrin gene NCSTN, one of the six key component genes encoding γ-secretase, was identified in the patients with familial HS. Neither unaffected individuals in the family nor 100 ethnically matched control alleles carry this mutation. None of the nine patients with nonfamilial HS carry nonsense, frameshift or splice site mutations in this gene. CONCLUSIONS: A novel splice site mutation, c.582+1delG, in NCSTN was identified in the familial patients with HS. We also reveal for the first time that a γ-secretase gene mutation is not linked to the development of nonfamilial HS. These results would further pave the way to a better understanding of the contribution of γ-secretase and other genes to the pathogenesis of HS and to the development of a new therapeutic strategy for HS.

Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene.

Hereditary progressive dystonia with marked diurnal fluctuation (HPD) (also known as dopa responsive dystonia) is a dystonia with onset in childhood that shows a marked response without any side effects to levodopa. Recently the gene for dopa responsive dystonia (DRD) was mapped to chromosome 14q. Here we report that GTP cyclohydrolase I is mapped to 14q22.1-q22.2. The identification of four independent mutations of the gene for GTP cyclohydrolase I in patients with HPD, as well as a marked decrease in the enzyme's activity in mononuclear blood cells, confirms that the GTP cyclohydrolase I gene is a causative gene for HPD/DRD. This is the first report of a causative gene for the inherited dystonias.

Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31-33.

Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. Twenty-one FCMD families, 13 of them with consanguineous marriages, were analysed by genetic linkage analyses with polymorphic microsatellite markers to map the FCMD gene. Significant lod scores were obtained with the markers D9S58 (Zmax = 5.81 at theta = 0.06), D9S59 (Zmax = 4.33 at theta = 0.02), and HXB (Zmax = 3.28 at theta = 0.09) on chromosome 9q31-33. Multipoint analysis placed FCMD between D9S58 and D9S59, with a maximum lod score of 16.93. These markers will be useful for presymptomatic, prenatal and carrier diagnosis of family members carrying FCMD, and they represent important resources for the identification of a gene responsible for FCMD.