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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Important cytogenetic and genetic risk factors for the development of UM include chromosome 3 monosomy, mutations in the guanine nucleotide-binding proteins GNAQ/GNA11, and loss of the BRACA1-associated protein 1 (BAP 1). Most primary UMs are treated conservatively with radiotherapy, but enucleation is necessary for large tumours. Despite the effectiveness of local control, up to 50% of UM patients develop metastasis for which there are no effective therapies. Attempts to utilise the targeted therapies that have been developed for the treatment of other cancers, including a range of signal transduction pathway inhibitors, have rarely produced significant outcomes in UM. Similarly, the application of immunotherapies that are effective in cutaneous melanoma to treat UM have also been disappointing. Other approaches that have been initiated involve proteasomal inhibitors and histone deacetylase inhibitors which are approved for the treatment of other cancers. Nevertheless, there have been occasional positive outcomes from these treatments in UM. Moreover, combination approaches in UM have also yielded some positive developments. It would be valuable to identify how to apply such therapies efficiently in UM, potentially via individualised tumour profiling. It would also be important to characterise UM tumours to differentiate the potential drivers of progression from those in other types of cancers. The recent identification of novel kinases and metastatic genes in UM tumours makes the development of new UM-specific treatments feasible.

Seedling recruitment can be strongly affected by the composition of nearby plant species. At the neighborhood scale (on the order of tens of meters), adult conspecifics can modify soil chemistry and the presence of host microbes (pathogens and mutualists) across their combined canopy area or rooting zones. At local or small spatial scales (on the order of one to few meters), conspecific seed or seedling density can influence the strength of intraspecific light and resource competition and also modify the density‐dependent spread of natural enemies such as pathogens or invertebrate predators. Intrinsic correlation between proximity to adult conspecifics (i.e., recruitment neighborhood) and local seedling density, arising from dispersal, makes it difficult to separate the independent and interactive factors that contribute to recruitment success. Here, we present a field experiment in which we manipulated both the recruitment neighborhood and seedling density to explore how they interact to influence the growth and survival of Dryobalanops aromatica, a dominant ectomycorrhizal tree species in a Bornean tropical rainforest. First, we found that both local seedling density and recruitment neighborhood had effects on performance of D. aromatica seedlings, though the nature of these impacts varied between growth and survival. Second, we did not find strong evidence that the effect of density on seedling survival is dependent on the presence of conspecific adult trees. However, accumulation of mutualistic fungi beneath conspecifics adults does facilitate establishment of D. aromatica seedlings. In total, our results suggest that recruitment near adult conspecifics was not associated with a performance cost and may have weakly benefitted recruiting seedlings. Positive effects of conspecifics may be a factor facilitating the regional hyperabundance of this species. Synthesis: Our results provide support for the idea that dominant species in diverse forests may escape the localized recruitment suppression that limits abundance in rarer species., We present a rare‐field experiment in which we manipulated both the recruitment neighborhood (whether or not seedlings recruited in proximity to adult conspecifics) and seedling density to explore how they interact to influence the growth and survival of a dominant ectomycorrhizal tree species in a Bornean tropical rainforest. Our results provide support for the idea that dominant species in diverse forests may escape the localized recruitment suppression that limits abundance in rarer species and that ectomycorrhizal fungi play an important role in reducing CNDD for some tropical trees.

While work in temperate forests suggests that there are consistent differences in plant-soil feedback (PSF) between plants with arbuscular and ectomycorrhizal associations, it is unclear whether these differences exist in tropical rainforests. We tested the effects of mycorrhizal type, phylogenetic relationships to overstory species, and soil fertility on the growth of tree seedlings in a tropical Bornean rainforest with a high diversity of both ectomycorrhizal and arbuscular mycorrhizal trees. We found that ectomycorrhizal tree seedlings had higher growth in soils conditioned by close relatives and that this was associated with higher mycorrhizal colonization. By contrast, arbuscular mycorrhizal tree seedlings generally grew more poorly in soils conditioned by close relatives. For ectomycorrhizal species, the phylogenetic trend was insensitive to soil fertility. For arbuscular mycorrhizal seedlings, however, the effect of growing in soils conditioned by close relatives became increasingly negative as soil fertility increased. Our results demonstrate consistent effects of mycorrhizal type on plant-soil feedbacks across forest biomes. The positive effects of ectomycorrhizal symbiosis may help explain biogeographic variation across tropical forests, such as familial dominance of the Dipterocarpaceae in southeast Asia. However, positive feedbacks also raise questions about the role of PSFs in maintaining tropical diversity.

Because interactions between plants and microbial organisms can influence species diversity and rates of nutrient cycling, how plants shape microbial communities is fundamental to understanding the structure of ecosystems. Despite this, the spatial and temporal scales over which plants influence microbial communities is poorly understood, particularly whether past abiotic or biotic legacies strongly constrain microbial community development. We examined biogeochemical cycling and microbial community structure in a coastal landscape where historical patterns of vegetation transition after a large fire in 1995 are well known, allowing us to account for past abiotic and biotic conditions. We found that alternative states in microbial community structure and ecosystem processes emerged under different plant species, regardless of past conditions. Greenhouse studies further demonstrated that these differences arise from direct plant selection of microbes, with selection stronger in roots compared with soils, especially for bacteria. Correlation of microbial community structure with seedling growth rates was also stronger for fungi compared to bacteria. Despite these effects, minimal overlap between seedling and field microbial communities indicates that the effects of initial plant selection are not stable; rather, plant selection initiated alternative successional trajectories after the fire. Using data from a guild where we have abundant natural history information, ectomycorrhizal fungi, we show that greenhouse communities are dominated by ruderal taxa that are also common in the field after the fire and that these ruderal fungi strongly alter spatial patterns in plant–soil feedback, enabling invasion and transformation of soils previously occupied by heterospecific plants, thus potentially acting as keystone mutualists.

Background: To describe the outcome of patients treated by conservative surgical excision followed by adjuvant plaque brachytherapy for early-stage primary or recurrent conjunctival melanoma. Design: Retrospective, non-comparative, interventional case series. Participants: We reviewed 19 eyes in 19 consecutive patients presenting with biopsy proven conjunctival melanoma with pathologic stage pT1c or less. Methods: Patients with primary or recurrent early-stage conjunctival melanoma were identified and treated using a conservative resection technique (tractional micro-dissection) involving avoidance of deep dissection and modest lateral clearance followed by adjuvant plaque brachytherapy. Main Outcome Measure: Local recurrence and ocular complications. Results: Mean age was 55.2 years and male : female (8:11). Mean follow up was 43.1 months (range 30.1–54.3 months). All patients were treated by conservative resection followed by adjuvant Iodine-125 plaque brachytherapy. The treatment dose was 100 Gy to a depth of 1.5–3.0 mm. Outcomes: median visual acuity and intraocular pressure were unchanged after surgery. Six patients experienced corneal ulceration in the immediate postoperative period. No patients experienced recurrence at the treatment site or metastases. Three patients experienced new lesions distant from the treatment site. Conclusions: Conservative resection and adjuvant plaque brachytherapy is an effective and well-tolerated modality for the management of patients with early-stage conjunctival melanoma.

Purpose: To describe the outcome of patients treated by surgical excision followed by plaque brachytherapy for primary or recurrent ocular surface malignancies with evidence of deep margin (corneoscleral) invasion. Methods: Retrospective, non-comparative, interventional case series. Eleven consecutive patients presenting with biopsy-proven scleral and/or corneal stromal involvement from either conjunctival melanoma (CM) or squamous cell carcinoma (SCC) of the conjunctiva were reviewed. Results: Five patients had CM (pT3 N0 M0 [n = 3], pT4 N0 M0 [n = 2]) and six patients had SCC (T3 N0 M0 [n = 6]). Mean age was 60.8 years and male : female (3 : 8). Mean follow up was 23.4 months (range 12–36 months). All patients were treated with Iodine-125 plaque following biopsy-proven corneoscleral invasion on histopathology. The treatment dose was 100 Gy to a depth of 1.5–2.5 mm. Outcomes: Median visual acuity and intraocular pressure were unchanged after surgery. Five patients experienced corneal ulceration in the immediate postoperative period. None experienced recurrence at the treatment site. One SCC patient and two CM patients experienced new lesions distant from the treatment site. No sight-threatening complications were observed. No patients developed distant metastases. Conclusion: Plaque brachytherapy is an effective and well-tolerated modality for the management of patients with ocular surface malignancy with evidence of localized corneoscleral invasion.

The dihydrolipoamide acyltransferase (E2b) component of the branched-chain alpha-ketoacid dehydrogenase complex forms a cubic scaffold that catalyzes acyltransfer from S-acyldihydrolipoamide to CoA to produce acyl-CoA. We have determined the first crystal structures of a mammalian (bovine) E2b core domain with and without a bound CoA or acyl-CoA. These structures reveal both hydrophobic and the previously unreported ionic interactions between two-fold-related trimers that build up the cubic core. The entrance of the dihydrolipoamide-binding site in a 30-A long active-site channel is closed in the apo and acyl-CoA-bound structures. CoA binding to one entrance of the channel promotes a conformational change in the channel, resulting in the opening of the opposite dihydrolipoamide gate. Binding experiments show that the affinity of the E2b core for dihydrolipoamide is markedly increased in the presence of CoA. The result buttresses the model that CoA binding is responsible for the opening of the dihydrolipoamide gate. We suggest that this gating mechanism synchronizes the binding of the two substrates to the active-site channel, which serves as a feed-forward switch to coordinate the E2b-catalyzed acyltransfer reaction.

SUMMARY Recent molecular sequencing results involving multiple genes require evaluation in the light of preexisting morphological data, particularly as different methodologies and genes produce trees that are incongruent in some respects or have major areas with poorly supported branch resolution. The present paper summarizes the current situation, primarily from a morphologist's perspective. Most of the tabulation-based groups are coherent in small subunit (SSU) and large subunit (LSD) trees; but some, notably the prorocentroids and peridinioids, are not. In prorocen-troids this is primarily because of intrinsic inadequacies of the molecules to resolve their phylogeny. In peridinioids it seems to be because of paraphyly of the group. Other artefacts are noted, such as the drastically different positions of Oxyrrhis in phylogenetic trees based on SSU and protein genes, and of Noctiluca in SSU trees that include analyses with different numbers of nucleotides. Polyphyly in non-tabulate or poorly known groups has been confirmed, as has been the presence of cryptic thecae in members of those groups (group misattribution). Whether or not some extant groups of athecate, wholly dinokaryotic forms originated prior to polytabulate groups, like the suessioids, peridinioids and gonyaula-coids, remains unclear. Gymnodinioids with a spiral acrobase seem to have given rise to the more complex athecate forms, whereas morphological features of the genus Gymnodinium are consistent with it being a sister group to polytabulate taxa such as Woloszynskia and the suessioids. Peridinioids and gonyaulacoids appear to have originated after that split. Dinophysoid and prorocentroid dinoflagellates appear to be derived from peridinioid forms. Trees based on protein genes, such as actin or α- and β-tubulin, may help resolve some of the positions of key groups, but they do not include enough taxa to be widely useful as yet.

We investigate an organism that closely resembles the nonphotosynthetic dinoflagellate "Gymnodinium elongatum" Hope 1954 using EM and molecular methods. Cells are 20-35 μm long, 10 μm wide, biconical, transparent, and have a faint broad girdle. Thecal plates are thin but present (plate formula Po Pi CP 3' 1-2A 5" 3C 6S 4"' 3""). With the exception of one feature, the presence of three antapical plates, the amphiesmal arrangement of this species is consistent with that of the order Peridiniales, family Podolampaceae; it is not at all consistent with the characteristics of the genus Gymnodinium. On the basis of these ultrastructural findings, we establish a new genus, Lessardia, and a new species, Lessardia elongata Saldarriaga et Taylor. Molecular phylogenetic analyses were performed using the small subunit rRNA genes of L. elongata as well as Roscoffia capitata, a member of a genus of uncertain systematic position that has been postulated to be related to the Podolampaceae. These analyses place Lessardia and Roscoffia as sister lineages within the so-called GPP complex. Thecal plate arrangements led us to expand the family Podolampaceae to include the genus Lessardia and, in combination with new molecular results, to propose a close relationship between the Podolampaceae and Roscoffia. Within this lineage, Lessardia and Roscoffia appear to have retained a number of ancestral characters: Roscoffia still has a well-developed cingulum, a feature absent in all members of the Podolampaceae, and Lessardia has more than one antapical plate, a character reminiscent of some members of the family Protoperidiniaceae.

Primary cutaneous lymphoma represents a distinct clinical entity within the spectrum of haematological malignancy. A case of primary cutaneous B cell lymphoma is reported, presenting in an 87-year-old female with a 2-year history of intermittent swelling and discolouration of the right upper and lower eyelids, in the absence of systemic symptoms. Histopathological examination of an incision biopsy revealed a lymphoid infiltrate in the dermis with immunophenotypic features of B cell lymphoma. Staging investigations confirmed the absence of systemic disease. Treatment with oral chemotherapy was undertaken with a good response. Ophthalmologists should include primary cutaneous lymphoma in the differential diagnosis of recurrent eyelid swelling.

Previous studies of the Photosystem I reaction center complex, the chlorophyll protein 1 complex (CPI), have shown it is a heterodimer of two high-molecular-mass subunits of 83000 and 82000, the psa A and psa B gene products. The present work has identified another intrinsic low-molecular-mass subunit of 5 500 (as determined by SDS-PAGE) that is tightly associated with the CPI complex. This subunit can be separated from CPI after treatment with thiol agents. CPI complexes prepared either in the presence or absence of thiols show no differences in photochemical activity under steady-state actinic illumination. A comparison of the N-terminal amino acid sequence of the 5.5 kDa subunit with the sequence of a Chlamydomonas PSI subunit, P37, identifies this low-molecular-mass subunit as the PSI psa K gene product.

Purpose: Inflammatory bowel disease (IBD) and Spondyarthropathies (SpA) are said to be associated with distinct types of Uveitis. We compared Uveitis subtypes in patients with IBD and SpA, as well as in different SpA subtypes. Methods: We identified 162 patients with SpA (AMOR classification): 93 Ankylosing Spondylitis (AS), 43 with undifferenciated (u)Spa, 10 reactive Arthritis, 12 Psoriasis Arthropathy (PsA), and 5 enteropathy associated (eSpA) and their Uveitis (SUN classification). Results: Patients with AS were male (67%) and HLA-B27+ (84%) showing typical unilateral or alternating anterior Uveitis with sudden onset in 77%. Still, 23% (21) showed bilateral anterior Uveitis. In this subgroup females predominated with 55% . They were HLA-B27+ in 80%. Patients with uSpA were male (60 %) and HLA-B27+ (82%), but only showed typical Uveitis in 58%. A higher number of other Uveitis subtypes was found: 27% showed bilateral anterior and 15% other Uveitis subtypes. Again there was a female predominance, without change in HLA-B27 positivity (79%). A different pattern was found in the PsA cohort, which was female (58%) and HLA-B27 was infrequent. Here 25% of the patients had typical Uveitis, whereas 17% showed bilateral anterior and 58% other subtypes of Uveitis. Patients with eSpA were female in 80%, and HLA B27 was less frequent (40%). None of the eSpA group had typical Uveitis, 80% a bilateral anterior and 20% other Uveitis subtypes. Conclusions: The frequency of a “typical” Uveitis associated with SpA in our cohort varied from 77% to 0 %, decreasing from AS to eSpA. We saw a high number of other Uveitis subtypes, with a female predominance. Maybe women with SpA have a higher risk for atypical Uveitis.

Laccases isolated from the lacquer tree Rhus vernicifera and the fungus Polyporus versicolor show fluorescence emission near 420 nm and phosphorescence emission in the 440–465 nm region. The fluorescence and phosphorescence excitation spectra for both laccases show maxima in the 315–330 nm range, a spectral region corresponding to the absorbance maxima for the type 3 binuclear Cu centers of the two enzymes. Additional evidence is presented for the association of the newly discovered emissions with the type 3 Cu centers of the two laccases.

We investigated the effects of a number of experimental perturbations on choline acetyltransferase (ChAT) in a cholinergic mouse neuroblastoma cell line (S-20Y). ChAT specific activity increased by 4.5-fold during growth, suggesting that enzyme activity is dependent on increased cell density. This was confirmed by assessing enzyme activity at differential initial seeding densities. ChAT activity was also markedly enhanced by 1 mM di-butyryl cyclic-3′,5′-AMP (dBcAMP), an effect that was blocked by cycloheximide. Confirmation of the dBcAMP effect was achieved with forskolin, a compound known to enhance intracellular cyclic AMP; forskolin (100 μM) caused a significant increase in ChAT activity. After a 20-h latent interval ChAT activity was also enhanced significantly by cytosine arabinoside. The common element in these diverse effects on ChAT activity may be cessation of cell division, although cell-cell interactions at the level of the cell membrane may also be important in the control of ChAT in S-20Y.

The rate of increase of glucose 6-phosphate dehydrogenase activity in denervated rat extensor digitorum longus muscle shows sexual dimorphism. This phenomenon is further investigated in this report by assessing the effects of ovariectomy, hypophysectomy, hormone replacement therapy, and treatment with an estrogen antagonist, MER-25. The data demonstrate that physiologic doses of estrogens enhance the rate and extent of the increase in glucose 6-phosphate dehydrogenase activity after denervation. The data further indicate that aromatization of androgens may be a significant source of estrogen involved in hormonal modulation of the neural control of glucose 6-phosphate dehydrogenase and other processes in muscle. Furthermore, choline acetyltransferase activity, a marker for the neuromuscular synapse, decreased in rat extensor digitorum longus muscles after denervation, but was unaffected by ovariectomy.

An iron-sulfur protein of approx. 9 kDa has been isolated from spinach chloroplast membranes. Based on iron and sulfide content (∼900 nmol Fe and S2− per mg protein), optical absorbance and low-temperature EPR spectra, it appears that this protein contains 8Fe and 8S2− in two [4Fe4S] clusters. The protein cross-reacts with an antibody raised against a 9 kDa PS I subunit previously identified as the psaC (frxA) gene product. This identity was confirmed by the N-terminal amino acid sequence of the isolated FeS protein. It is concluded that the isolated FeS protein binds PS I centers FeSA and FeSB and that each of these centers contains 4Fe and 4S2−.

The effects of denervation and disuse on cytosolic androgen receptor binding by rat striated muscle are investigated. Denervation of the extensor digitorum longus and tibialis anterior muscles caused by a 40-50-percent increase in cytosolic androgen receptor concentration with no change in apparent binding affinity. This effect was evident at 6 h postdenervation, maximal at 24 h, and declined to 120 percent of the control level 72 h after denervation. A 40-percent increase in cytosolic androgen receptor concentration was also noted 24 hr after denervation of the hormone-sensitive levator ani muscle. The effect of denervation on androgen receptors was blocked by in vivo injection of cycloheximide; therefore, de novo receptor synthesis probably is not involved in the observed increase. Disuse, produced by subperineurial injection of tetrodotoxin into the tibial and common peroneal branches of the sciatic nerve, mimicked the effect of denervation on androgen receptor binding, suggesting that neuromuscular activity is important in regulation of receptor concentration. Possible mechanisms subserving this effect are discussed.

We studied the effects of denervation and reinnervation of the rat extensor digitorum longus muscle (EDL) on the oxidation of [6-14C]glucose to 14CO2. The rate of 14CO2 production decreased dramatically following denervation, and the decrease became significant 20 days after nerve section. Prior to day 20, changes apparently reflected the decline of muscle mass. Decreased 14CO2 production was due to reduced capacity of the enzymatic system (apparent Vmax); there was no change in apparent affinity for glucose (apparent Km). Mixing experiments revealed that the loss of oxidative capacity following denervation is not caused by production of soluble inhibitors by degenerating muscle. Oxidative metabolism, as measured by 14CO2 evolution, recovered during reinnervation. Surprisingly, the specific activity in reinnervated muscles displayed an "overshoot" of approximately 50%, which returned to control by day 60, possibly reflecting increased energy demand by the growing muscle. The time-course of the denervation-mediated change indicates that altered oxidative capacity is secondary to events that initiate denervation changes in muscle. Nevertheless, diminished oxidative capacity may be of considerable metabolic significance in denervated muscle.

A deletion of the long arm of chromosome 15 (usually involving bands 15q11-q12) has been seen in approximately 50% of Prader-Willi syndrome (PWS) patients [Ledbetter et al, 1982]. However, 14 patients with non-PWS (or atypical PWS) phenotype with 15q deletion indicate great clinical variability. A deletion was found in a propositus with a de novo translocation [45,XY, -15, -22, +rec(15;22) (22pter----22q13.2::15q14----15qter)], who had anomalies not normally observed in PWS patients. Activities of several enzymes mapped to the involved chromosomes were studied in the patient and control individuals. A 50% decrease in the level of arylsulfatase-A confirmed a small deletion in 22q(22q13.2----qter), and additional studies localized more precisely the loci for alpha-mannosidase (cytoplasmic) and beta-galactosidase.

A 13-year-old boy developed cramps and myoglobinuria following exertion. Mitochondrial preparations from a skeletal muscle biopsy were deficient in carnitine palmitoyltransferase (CPT) activity when assayed by the hydroxamate and kinetic assays. The patient's fibroblasts were also deficient when assayed by the hydroxamate and kinetic assays, but not when tested by the DTNB (5′,5′-dithiobis-[2-nitrobenzoic acid]) method. This disparity probably indicates a specific deficiency in fibroblasts of one of the two carnitine palmitoyltransferases, presumably CPT II.

Exogenously administered estrogens can enhance the rate of increase of glucose 6-phosphate dehydrogenase activity in rat extensor digitorum longus muscles following denervation. In this communication, we report that the effect of denervation on glucose 6-phosphate dehydrogenase activity is modified by variations in endogenous estradiol during the estrous cycle.

—The activities of choline acetyltransferase and cholinesterase have been measured in homogenates of rat anterior tibial muscles following intramuscular injection of the myotoxic agent Marcaine (plus hyaluronidase). Marcaine causes rapid degeneration of skeletal muscle followed by complete regeneration. By the first day after administration of Marcaine the activities of both enzymes decreased markedly. The activities then increased concomitantly with regeneration of drug-treated muscles. Choline acetyltransferase attained the control level by the 19th day following Marcaine treatment. Cholinesterase activity became greater than the control value by the seventh day and decreased to control activity by the 19th day following injection of Marcaine. The results are discussed in terms of the relationship between nerve and muscle during Marcaine induced degeneration and regeneration.