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1.  Retinal ischaemia in type 1 neurofibromatosis 
PMCID: PMC1856902  PMID: 16361684
neurofibromatosis; retinal ischaemia
2.  No Time To Lose - High Throughput Screening To Assess Nanomaterial Safety 
Nanoscale  2011;3(4):1345-1360.
Nanomaterials hold great promise for medical, technological and economical benefits. Knowledge concerning the toxicological properties of these novel materials is typically lacking. At the same time, it is becoming evident that some nanomaterials could have a toxic potential in humans and the environment. Animal based systems lack the needed capacity to cope with the abundance of novel nanomaterials being produced, and thus we have to employ in vitro methods with high throughput to manage the rush logistically and use high content readouts wherever needed in order to gain more depth of information. Towards this end, high throughput screening (HTS) and high content screening (HCS) approaches can be used to speed up the safety analysis on a scale that commensurate with the rate of expansion of new materials and new properties. The insights gained from HTS/HCS should aid in our understanding of the tenets of nanomaterial hazard at biological level as well as asset the development of safe-by-design approaches. This review aims to provide a comprehensive introduction to the HTS/HCS methodology employed for safety assessment of engineered nanomaterials (ENMs), including data analysis and prediction of potentially hazardous material properties. Given the current pace of nanomaterial development, HTS/HCS is a potentially effective means of keeping up with the rapid progress in this field – we have literally no time to lose.
PMCID: PMC3980675  PMID: 21301704
4.  Niche-modulated and niche-modulating genes in bone marrow cells 
Blood Cancer Journal  2012;2(12):e97-.
Bone marrow (BM) cells depend on their niche for growth and survival. However, the genes modulated by niche stimuli have not been discriminated yet. For this purpose, we investigated BM aspirations from patients with various hematological malignancies. Each aspirate was fractionated, and the various samples were fixed at different time points and analyzed by microarray. Identification of niche-modulated genes relied on sustained change in expression following loss of niche regulation. Compared with the reference (‘authentic') samples, which were fixed immediately following aspiration, the BM samples fixed after longer stay out-of-niche acquired numerous changes in gene-expression profile (GEP). The overall genes modulated included a common subset of functionally diverse genes displaying prompt and sustained ‘switch' in expression irrespective of the tumor type. Interestingly, the ‘switch' in GEP was reversible and turned ‘off-and-on' again in culture conditions, resuming cell–cell–matrix contact versus respread into suspension, respectively. Moreover, the resuming of contact prolonged the survival of tumor cells out-of-niche, and the regression of the ‘contactless switch' was followed by induction of a new set of genes, this time mainly encoding extracellular proteins including angiogenic factors and extracellular matrix proteins. Our data set, being unique in authentic expression design, uncovered niche-modulated and niche-modulating genes capable of controlling homing, expansion and angiogenesis.
PMCID: PMC3542477  PMID: 23241658
gene-expression profile; myeloma; leukemia; contactless gene signature; niche-modulated genes; niche-modulating genes
6.  Hyperargininemia: A Family with a Novel Mutation in an Unexpected Site 
JIMD Reports  2011;5:83-88.
Hyperargininemia is a rare autosomal recessive disorder of the last step of the urea cycle characterized by a deficiency in liver arginase1. Clinically, it differs from other urea cycle defects by a progressive paraparesis of the lower limbs (spasticity and contractures) with hyperreflexia, neurodevelopmental delay and regression in early childhood. Growth is affected as well. Hyperammonemia is episodic, if present at all. The disease is caused by mutations in the ARG1 gene; there are approximately 20 different known ARG1 mutations with considerable genetic heterogeneity. We describe two Arab siblings with a late diagnosis of hyperargininemia and present the genetic findings in their family. As ARG1 sequencing was unrevealing despite suggestive clinical and laboratory findings, molecular cDNA analysis was performed. The ARG1 expression pattern identified a 125-bp out-of-frame insertion between exons 3 and 4, leading to the addition of 41 amino acids and a premature termination codon TGA at the sixth codon downstream. The insertion originated at intron 3 and was attributable to a novel c.305 + 1323 t > c intronic base change that enabled an enhancement phenomenon. This is the first reported exon-splicing-enhancer mutation in patients with hyperargininemia. The clinical course and genetic findings emphasize the possibility that hyperargininemia causes neurological deterioration in children and the importance of analyzing the expression pattern of the candidate gene when sequencing at the DNA level is unrevealing.
PMCID: PMC3509907  PMID: 23430921
7.  Antitumor Activity of VB-111, a Novel Antiangiogenic Virotherapeutic, in Thyroid Cancer Xenograft Mouse Models 
Genes & Cancer  2011;2(10):993-995.
VB-111 is an engineered antiangiogenic adenovirus that expresses Fas-c in angiogenic blood vessels and has previously been shown to have significant antitumor activity in vitro and in vivo in Lewis lung carcinoma, melanoma, and glioblastoma models. To evaluate the efficacy of VB-111 in thyroid cancer, we conducted in vivo xenograft nude mouse studies using multiple thyroid cancer-derived cell lines models. VB-111 treatment resulted in 26.6% (P = 0.0596), 34.4% (P = 0.0046), and 37.6% (P = 0.0249) inhibition of tumor growth in follicular, papillary and anaplastic thyroid cancer models, respectively. No toxicity was observed in any model. All tumor types showed a consistent and significant reduction of CD-31 staining (P < 0.05), reflecting a reduction of angiogenic activity in the tumors, consistent with the intended targeting of the virus. A phase 2 clinical trial of VB-111 in patients with advanced differentiated thyroid cancer is ongoing.
PMCID: PMC3374632  PMID: 22701765
antiangiogenic agent; angiogenesis; thyroid cancer; virotherapy
8.  Types of choroidal neovascularisation in newly diagnosed exudative age‐related macular degeneration 
The British Journal of Ophthalmology  2007;91(9):1173-1176.
To describe the types and location of choroidal neovascularisation (CNV) in exudative age‐related macular degeneration (AMD), including vascularised pigment epithelial detatchments (PED), and most recently described subtypes, such as retinal choroidal anasmostosis, also termed “retinal angiomatous proliferation” (RAP).
Prospective multicentre consecutive descriptive case series. A total of 207 consecutive cases of newly diagnosed exudative AMD undergoing fluorescein angiography (FA) were recruited by 7 French referral hospital‐based or private centres. Indocyanine green angiography (ICG) also was performed, when judged necessary by investigators. Types and location of CNV were classified by two independent experts and adjudicated by a third when discordant.
All patients had FA, while ICG was performed in 50% of subjects. A total of 17.6% had classic CNV only, 5.4% and 8.3% had predominantly and minimally classic CNV, respectively. Occult CNV could be classified in occult CNV without PED (32.7%) and occult CNV with PED, ie, vascularised PED (23.9%). RAP was observed in 15.1% of cases, and accounted for 30% of vascularised PED. In 5.8% of the cases there was haemorrhagic AMD and 4.8% had fibrovascular scars. Lesions were mainly subfoveal (80%). Agreement between the centre's ophthalmologist and the final validated expert classification was moderate (κ = 0.52 for location and 0.59 for type of lesion).
This study confirms that newly diagnosed cases of exudative AMD are mainly occult and subfoveal. RAP appeared as a common lesion in patients with newly diagnosed exudative AMD.
PMCID: PMC1954889  PMID: 17383997
9.  Prevalence of reticular pseudodrusen in age‐related macular degeneration with newly diagnosed choroidal neovascularisation 
To investigate the prevalence of reticular pseudodrusen (RPD) in eyes of patients presenting with newly diagnosed choroidal neovascularisation (CNV) in age‐related macular degeneration (AMD), and to analyse the association between RPD, age‐related maculopathy (ARM) and AMD.
Two observational consecutive prospective series. In series 1, patients with AMD with newly diagnosed CNV were sampled to determine the incidence of RPD. Eyes with and without RPD were compared by the Mann–Whitney non‐parametric test and Fisher's exact test for age, sex of patients, the eye involved and type of CNV. Series 2 comprised 100 patients referred for fundus photography, fluorescein and/or indocyanine green angiography, for whom pictures showed RPD. This second cohort was then selected from a larger group of patients.
Patients with newly diagnosed CNV in series 1 comprised 67 women and 33 men, aged 57–96 years (mean 79.5). CNV was “classic” (32 eyes), “occult” (41) or exhibited vascularised pigment epithelial detachment (PED, 11), retinal angiomatous proliferation (RAP) with or without PED (13), or haemorrhagic or fibrovascular scarring (3). In all, 24 (24%) eyes had RPD. The prevalence of RAP was significantly higher in eyes with RPD than in those without (p = 0.0128), despite the small number of patients with RAP. In series 2, 100 patients with RPD were enrolled in 3 months, and corresponded to 8% of the overall cases referred to our centre (Centre Ophtalmologique d'Imagerie et de Laser, Paris, France). There were 77 women and 23 men, aged 54–93 years (mean 79.2). Eyes with RPD (n = 155) usually exhibited signs of ARM or AMD, including soft drusen (101 eyes) and/or retinal pigment epithelium abnormalities (70), geographical atrophy (27) and/or CNV (61). In both studies, examination of blue‐light fundus pictures was extremely helpful in diagnosing RPD.
RPD have a high prevalence among patients with AMD with newly diagnosed CNV (24% of cases). RPD were commonly associated with ARM or AMD. This study suggests that eyes with RPD could be classified as a phenotype of ARM.
PMCID: PMC1857688  PMID: 16973663
10.  Development of a tissue-engineered composite implant for treating traumatic paraplegia in rats 
European Spine Journal  2005;15(2):234-245.
This study was designed to assess a new composite implant to induce regeneration of injured spinal cord in paraplegic rats following complete cord transection. Neuronal xenogeneic cells from biopsies of adult nasal olfactory mucosa (NOM) of human origin, or spinal cords of human embryos, were cultured in two consecutive stages: stationary cultures in a viscous semi-solid gel (NVR-N-Gel) and in suspension on positively charged microcarriers (MCs). A tissue-engineered tubular scaffold, containing bundles of parallel nanofibers, was developed. Both the tube and the nanofibers were made of a biodegradable dextran sulphate–gelatin co-precipitate. The suturable scaffold anchored the implant at the site of injury and provided guidance for the regenerating axons. Implants of adult human NOM cells were implanted into eight rats, from which a 4 mm segment of the spinal cord had been completely removed. Another four rats whose spinal cords had also been transected were implanted with a composite implant of cultured human embryonic spinal cord cells. Eight other cord-transected rats served as a control group. Physiological and behavioral analysis, performed 3 months after implantation, revealed partial recovery of function in one or two limbs in three out of eight animals of the NOM implanted group and in all the four rats that were implanted with cultured human embryonic spinal cord cells. Animals of the control group remained completely paralyzed and did not show transmission of stimuli to the brain. The utilization of an innovative composite implant to bridge a gap resulting from the transection and removal of a 4 mm spinal cord segment shows promise, suggesting the feasibility of this approach for partial reconstruction of spinal cord lesions. Such an implant may serve as a vital bridging station in acute and chronic cases of paraplegia.
PMCID: PMC3489403  PMID: 16292587
Olfactory mucosa; Spinal cord; Transection; Transplantation
11.  Visual hallucinations and Charles Bonnet syndrome after photodynamic therapy for age related macular degeneration 
Aims: To report on visual hallucinations and Charles Bonnet syndrome (CBS) that may occur in patients with age related macular degeneration (AMD) treated by photodynamic therapy (PDT) with verteporfin for choroidal neovascularisation (CNV).
Methods: 100 consecutive patients were asked to respond to an orally administered questionnaire on visual hallucinations following PDT. Three groups of patients, respectively without visual hallucinations, with unstructured visual hallucinations, and with structured hallucinations—that is, CBS, were compared by ANOVA, Scheffe’s test, or the χ2 test, to establish whether age, sex, or visual acuity, as scored on ETDRS charts, are risk factors for the occurrence of visual hallucinations.
Results: Five patients (5%) described transient structured visual hallucinations, including known or unknown faces and geometric patterns. Fifteen patients (15%) reported photopsias and flashing lights of various colours. These symptoms usually occurred a few days after PDT. There was no significant difference between the group of patients with structured visual hallucinations and the two other groups, with regard to age (p =0.435), sex (p =0.406), or visual acuity (p =0.835).
Conclusions: Visual hallucinations and CBS appear to be a possible, although unrecognised, side effect of PDT for CNV, which occur just after treatment. These results suggest the need to include the possibility of visual hallucinations in the information given to patients before PDT.
PMCID: PMC1771786  PMID: 12881339
age related macular degeneration; Charles Bonnet syndrome; choroidal neovascularisation; photodynamic therapy; visual hallucinations
13.  Molecular identification of bacteria from a coculture by denaturing gradient gel electrophoresis of 16S ribosomal DNA fragments as a tool for isolation in pure cultures. 
Applied and Environmental Microbiology  1996;62(11):4210-4215.
Molecular information about the bacterial composition of a coculture capable of sulfate reduction after exposure to oxic and microoxic conditions was used to identify and subsequently to isolate the components of the mixture in pure culture. PCR amplification of 16S ribosomal DNA fragments from the coculture, analyzed by denaturing gradient gel electrophoresis, resulted in two distinct 16S ribosomal DNA bands, indicating two different bacterial components. Sequencing showed that the bands were derived from a Desulfovibrio strain and an Arcobacter strain. Since the phylogenetic positions of bacteria are often consistent with their physiological properties and culture requirements, molecular identification of the two components of this coculture allowed the design of specific culture conditions to separate and isolate both strains in pure culture. This approach facilitates the combined molecular and physiological analysis of mixed cultures and microbial communities.
PMCID: PMC168243  PMID: 8900013
14.  Mycobacterium avium complex infection in mice: lack of exacerbation after LP-BM5 murine leukemia virus infection. 
Infection and Immunity  1996;64(4):1203-1207.
The murine leukemia virus LP-BM5 has been used to reproduce the model of murine AIDS in order to evaluate the course of infection with the MO-1 strain of Mycobacterium avium complex (MAC). LP-BM5 was inoculated in C57BL/6 mice by intravenous (i.v.) injection either 8 weeks before an i.v. challenge with 10(3) or 10(6) CFU of MAC (coinfection 1) or 10 days after an i.v. challenge with 10(3) CFU of MAC (coinfection 2). During coinfection 2 experiments, the phenotypic alterations in blood lymphocyte subsets were analyzed. During coinfection 1, LP-BM5 infection tended to decrease the mycobacterial growth, with the difference reaching statistical significance for the lower inoculum (10(3) CFU of MAC) (P<0.001).During coinfection 2, LP-BM5 did not exacerbate MAC infection except in the spleen, at day 90 after LP-BM5 challenge (P<0.001). LP-BM5 infection and the LP-BM5-MAC coinfection increased the numbers of activated CD4+ lymphocytes (CD4+ Ly6AE+) (P<0.001), activated CD8+ lymphocytes (CD8+ Ly6AE+) (P<0.001), and activated B lymphocytes (Ly5+ Ly6AE+) (P<0.001). This activation of T lymphocytes could explain the lack of exacerbation of MAC infection and even the trend to a lower level of MAC infection. Thus, this model of retroviral infection of mice does not seem to be a reliable model of immunodepression for the study of MAC infection and its treatments.
PMCID: PMC173904  PMID: 8606079
16.  Activities of roxithromycin against Mycobacterium avium infections in human macrophages and C57BL/6 mice. 
The activity of roxithromycin against three clinical isolates of Mycobacterium avium was compared with that of clarithromycin both in a model of infection of human monocyte-derived macrophages and in a model of established infection of C57BL/6 mice. In the cell culture model, roxithromycin and clarithromycin were bactericidal for strains MO-1 and N-92159 and bacteriostatic for strain N-93043. For the three strains, the differences between the intracellular activities of roxithromycin and clarithromycin were not singificant after 7 days of treatment. Mice were infected with the MO-1 strain. Drugs were given by gavage at a dosage of 200 mg/kg of body weight 6 days per week for 16 weeks starting 5 weeks after infection. At the end of treatment, clarithromycin was more effective than roxithromycin in lungs; roxithromycin was as effective as clarithromycin in spleens. Thus, the activity of roxithromycin was comparable to that of clarithromycin both in vitro and in vivo.
PMCID: PMC162646  PMID: 7785988
17.  Use of normal C57BL/6 mice with established Mycobacterium avium infections as an alternative model for evaluation of antibiotic activity. 
Several murine models have been used to evaluate the activities of antimicrobial agents against Mycobacterium avium infection. The main model used is the beige mouse model, but beige mice are expensive and not easily available. Thus, we developed a model of infection in wild C57BL/6 mice. The drugs that exhibited some activity in a previous model of early infection were evaluated in a new model of established infection. Sparfloxacin (50 mg/kg of body weight), ethambutol (50 mg/kg), minocycline (25 mg/kg), and the inhibitor of the cortisol receptors RU-40555 (100 mg/kg) were compared with clarithromycin (50 mg/kg). Treatments were started 5 weeks after the inoculation and were continued for 21 days. Sparfloxacin and RU-40555, which exhibited a moderate activity in the model of early infection, were not effective in this model of established infection. Clarithromycin and combinations with clarithromycin kept their activities against M. avium infection, both in the spleen and in lungs. The present model of established infection of normal C57BL/6 mice is more relevant than the model of early infection for a stringent evaluation of drugs.
PMCID: PMC162614  PMID: 7793882
18.  Visual function and course of basal laminar drusen combined with vitelliform macular detachment. 
Basal laminar drusen (BLD) are small round yellow drusen that are more easily visualised angiographically than biomicroscopically, with a 'stars in the sky' pattern. Patients with BLD are predisposed to macular vitelliform detachment. Little is known about the course of the disease, but the prognosis for retention of useful central vision for patients with BLD is thought to be better than for patients with typical drusen. A retrospective analysis of clinical and angiographic charts of 19 patients with BLD combined with a vitelliform macular detachment was performed to precisely describe their course. In addition, nine patients were re-examined to allow an analysis of their visual function--that is, central visual field, contrast sensitivity, and colour vision. Eyes without choroidal new vessels retained a fair visual acuity (mean final visual acuity 0.5; follow up 4 to 69 months, mean 24 months). In 11 of these eyes visual function assessment disclosed a reduction of contrast sensitivity in high and medium spatial frequencies in nine eyes (81%), a blue-yellow dyschromatopsia in nine eyes (81%), and a mild reduction of foveal threshold in seven eyes (63%). Choroidal neovascularisation (CNV) was observed in 12 eyes (31%) with a poor final outcome (mean final visual acuity 0.1). Two thirds of cases of CNV were observed at the time of presentation; thus this finding may be a bias of a referring centre. However, the high prevalence of CNV suggests the need for a close follow up of patients with BLD.
PMCID: PMC504818  PMID: 7520275
19.  Efficacy of granulocyte colony-stimulating factor and RU-40555 in combination with clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice. 
We compared the activities of two different biological-response modifiers with that of clarithromycin against Mycobacterium avium complex infection in C57BL/6 mice. Mice were pretreated daily with clarithromycin (50 mg/kg of body weight subcutaneously [s.c.]), RU-40555 (100 mg/kg s.c.), or granulocyte colony-stimulating factor (G-CSF) at low dose (15 micrograms/kg intraperitoneally [i.p.]) or high dose (300 micrograms/kg i.p.) 3 days before intravenous challenge with 2.5 x 10(7) CFU of the MO-1 strain of M. avium complex. Mice were treated daily until sacrifice at day 1, 8, 15, or 21 after challenge, and the numbers of CFU were measured per gram of tissue in lung and spleen. Compared at day 21 with control treatment, clarithromycin significantly decreased the level of infection in spleen (P < 0.0001) and lungs (P < 0.0001). Compared with control treatment, G-CSF at low dose had no activity, but G-CSF in combination with clarithromycin was more effective than clarithromycin alone in spleen (P < 0.05) and lungs (P < 0.015). The high dose of G-CSF was as effective as the low dose. RU-40555 alone had no beneficial activity. The RU-40555-clarithromycin combination was more effective than control treatment in spleen (P = 0.0001) and lungs (P < 0.0005) and more effective than clarithromycin alone in spleen (P < 0.009) but not in lungs. Thus, our experiments suggest that clarithromycin alone or in combination with G-CSF should be further evaluated for the prophylaxis of M. avium complex infection.
PMCID: PMC187736  PMID: 7684213
20.  Sparfloxacin, ethambutol, and cortisol receptor inhibitor RU-40 555 treatment for disseminated Mycobacterium avium complex infection of normal C57BL/6 mice. 
Antimicrobial Agents and Chemotherapy  1992;36(11):2408-2412.
Sparfloxacin (50 mg/kg of body weight given subcutaneously each day), alone or in combination with ethambutol (50 mg/kg given subcutaneously each day), was examined for its therapeutic efficacy against experimental infection induced with the Mycobacterium avium complex in normal C57BL/6 mice. In addition, the potential anti-infective role of RU-40 555 (100 mg/kg given intraperitoneally each day), a drug that inhibits the cortisol receptors, was examined in the same model. Treatments were started 24 h after intravenous bacterial challenge and were continued for 21 days. Compared with controls, sparfloxacin or ethambutol decreased the CFU counts in spleens and lungs (P < 0.001). The sparfloxacin plus ethambutol combination was more effective than sparfloxacin alone in spleens (P < 0.001) but not in lungs. The sparfloxacin plus ethambutol plus RU-40 555 combination was more effective than the sparfloxacin plus ethambutol combination in spleens and lungs (P < 0.001). Thus, in this model, RU-40 555 enhanced the antibacterial activities of the antibiotics tested. Results of the study showed that normal C57BL/6 mice infected with the M. avium complex can be used for the evaluation of antimicrobial agents.
PMCID: PMC284344  PMID: 1336944
21.  Activities of WIN-57273, minocycline, clarithromycin, and 14-hydroxy-clarithromycin against Mycobacterium avium complex in human macrophages. 
Antimicrobial Agents and Chemotherapy  1992;36(10):2104-2107.
The activities of the fluoroquinolone WIN-57273, 14-OH clarithromycin (a human metabolite of clarithromycin), and minocycline against two virulent strains of Mycobacterium avium complex were evaluated in a model of intracellular infection and compared with that of clarithromycin. Human monocyte-derived macrophages were infected at day 6 of culture. Intracellular CFU at 60 min and intracellular and supernatant CFU on days 4 and 7 were counted after inoculation. The concentrations used, which were equal to peak levels in serum, were 3 micrograms of WIN-57273 per ml (MICs for the two strains, 1 microgram/ml), 4 microgram of 14-OH clarithromycin per ml (MICs, 8 and 2 micrograms/ml, respectively, at pH 7.4), 4 micrograms of minocycline per ml (MICs, 64 and 32 micrograms/ml, respectively), and 4 micrograms of clarithromycin per ml (MICs, 2 and 0.5 micrograms/ml, respectively, at pH 7.4). On day 7, compared with controls, WIN-57273, minocycline (P less than 0.02), clarithromycin, or different combinations of clarithromycin and the other drugs (P less than 0.001) slowed the intracellular replication of strain MO-1. 14-OH clarithromycin (P less than 0.02), clarithromycin (P less than 0.02), 14-OH clarithromycin plus clarithromycin (P less than 0.01), clarithromycin plus minocycline, or clarithromycin plus minocycline plus 14-OH clarithromycin (P less than 0.001) slowed the intracellular replication of strain LV-2. WIN-57273 was less effective than clarithromycin against strain MO-1 (P less than 0.05). Clarithromycin plus 14-OH clarithromycin plus minocycline (P less than 0.02) was more effective than clarithromycin alone against strain LV-2. Thus, clarithromycin plus minocycline, which corresponds in humans to three active molecules, may exhibit a better efficacy than clarithromycin in this model.
PMCID: PMC245463  PMID: 1332586
22.  Yield of the admission complete blood count in medical inpatients. 
Postgraduate Medical Journal  1989;65(766):525-527.
The clinical efficacy of routine admission complete blood count was evaluated in 302 patients admitted to internal medicine wards of a university teaching hospital. Patient medical problems, physical findings and medication history were evaluated by preset criteria to determine the proportion of tests performed for screening and the proportion of test results directly influencing patient management. Of the 282 complete blood counts performed, 80% were ordered routinely with no medical indications (screening tests). An haemoglobin abnormality was found in 16.7% of the patients, leucocyte abnormality in 16.1% and platelet abnormality in 4.6%. However, these results directly influenced patient management in only one case (0.14%). It is concluded that the utility of screening admission complete blood counts in medical inpatients is negligible.
PMCID: PMC2429491  PMID: 2602251
23.  Sulfur metabolism in Beggiatoa alba. 
Journal of Bacteriology  1987;169(12):5466-5472.
The metabolism of sulfide, sulfur, and acetate by Beggiatoa alba was investigated under oxic and anoxic conditions. B. alba oxidized acetate to carbon dioxide with the stoichiometric reduction of oxygen to water. In vivo acetate oxidation was suppressed by sulfide and by several classic respiratory inhibitors, including dibromothymoquinone, an inhibitor specific for ubiquinones. B. alba also carried out an oxygen-dependent conversion of sulfide to sulfur, a reaction that was inhibited by several electron transport inhibitors but not by dibromothymoquinone, indicating that the electrons released from sulfide oxidation were shuttled to oxygen without the involvement of ubiquinones. Intracellular sulfur stored by B. alba was not oxidized to sulfate or converted to an external soluble form under aerobic conditions. On the other hand, sulfur stored by filaments of Thiothrix nivea was oxidized to extracellular soluble oxidation products, including sulfate. Sulfur stored by filaments of B. alba, however, was reduced to sulfide under short-term anoxic conditions. This anaerobic reduction of sulfur was linked to the endogenous oxidation of stored carbon and to hydrogen oxidation.
PMCID: PMC213973  PMID: 3316186
24.  Photosynthetic action spectra and adaptation to spectral light distribution in a benthic cyanobacterial mat. 
We studied adaptation to spectral light distribution in undisturbed benthic communities of cyanobacterial mats growing in hypersaline ponds at Guerrero Negro, Baja California, Mexico. Microscale measurements of oxygen photosynthesis and action spectra were performed with microelectrodes; spectral radiance was measured with fiber-optic microprobes. The spatial resolution of all measurements was 0.1 mm, and the spectral resolution was 10 to 15 nm. Light attenuation spectra showed absorption predominantly by chlorophyll a (Chl a) (430 and 670 nm), phycocyanin (620 nm), and carotenoids (440 to 500 nm). Blue light (450 nm) was attenuated 10-fold more strongly than red light (600 nm). The action spectra of the surface film of diatoms accordingly showed activity over the whole spectrum, with maxima for Chl a and carotenoids. The underlying dense Microcoleus population showed almost exclusively activity dependent upon light harvesting by phycobilins at 550 to 660 nm. Maximum activity was at 580 and 650 nm, indicating absorption by phycoerythrin and phycocyanin as well as by allophycocyanin. Very little Chl a-dependent activity could be detected in the cyanobacterial action spectrum, even with additional 600-nm light to excite photosystem II. The depth distribution of photosynthesis showed detectable activity down to a depth of 0.8 to 2.5 mm, where the downwelling radiant flux at 600 nm was reduced to 0.2 to 0.6% of the surface flux.
PMCID: PMC203772  PMID: 11536572
25.  Ultrastructure of square bacteria from a brine pool in Southern Sinai. 
Journal of Bacteriology  1982;150(2):851-860.
The square bacterium discovered by Walsby (Nature [London] 283:69-71, 1980) has been shown to possess the ultrastructural features of a typical halophile. The cell wall is comprised of regularly arranged subunits demonstrated by thin sectioning, shadowed replicas, and negative staining. Optical diffraction confirms the existence of both hexagonal and tetragonal arrangements of the cell wall subunits and also of different lattice constants and suggests a mixed population of bacteria.
PMCID: PMC216438  PMID: 7068535

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