Life-history data of a key amphipod species from three NE Atlantic estuaries under different levels of anthropogenic pressure.

Knowledge on population dynamics of ecosystem's key-species is invaluable to understand how populations will respond to natural and human-induced perturbations. The amphipod Echinogammarus marinus is a key-species from European estuarine habitats with a distribution ranging from Norway to Portugal [1]. The present article contains supportive data related to a research article entitled 'Comparing production and life-history traits of a key amphipod species within and between estuaries under different levels of anthropogenic pressure' [2]. The present dataset presents the density, biomass, fecundity, and production of E. marinus in three estuaries under different anthropogenic pressure and, within each estuary, at three sampling sites, which differed in terms of the distance to the estuary mouth, vegetation cover, and organic matter content. Monthly environmental abiotic data and seasonal concentration of PAH and other contaminants are also provided. Sampling took place monthly for 13 months at low tide on intertidal mudflats. At each site, Fucus fronds containing E. marinus individuals were randomly collected. All E. marinus individuals were counted, sexed, and measured under a binocular stereo microscope to estimate the density and the biomass of E. marinus in Fucus fronds. Finally, the annual production of E. marinus at each sampling site was estimated through the size-frequency method. This dataset may be used to compare population traits of E. marinus populations across different estuaries and it may overall assist designing studies regarding population dynamics and designing management strategies in coastal systems, namely targeting at habitat conservation and restoration.

Comparing production and life-history traits of a key amphipod species within and between estuaries under different levels of anthropogenic pressure.

Inter-population variability may arise as a response to adverse natural and anthropogenic stressors. The dynamics of a key amphipod species (Echinogammarus marinus) was followed during ≈ 1-year at its southerly range (NW Portugal), in three estuaries with different levels of anthropogenic pressure (High - Ave estuary; Moderate - Mondego estuary; Low - Minho estuary). We hypothesised that E. marinus populations would present lower production and fitness, and higher intersexuality incidence with increasing anthropogenic pressure. According to a GAM model explaining ≈70% of the observed variability, E. marinus biomass depends on temperature, organic matter, Fucus area and time of the year. Significant differences were found between the gammarid biomass in Minho and Mondego estuaries and within sites from the same estuary. As expected, Ave estuary exhibited the lowest average annual production, abundance and fecundity rates. However, the highest average production was found in Mondego and not in Minho estuary, although the turnover ratio (P/B) of both estuaries was very similar. Besides the system's global ecological status, E. marinus also seems to respond to microhabitat conditions, which may explain the spatial heterogeneity observed in the amphipod production within the same estuary. Intersexuality prevalence was negligible in the three populations, which does not support the idea of a link between anthropogenic pressure and intersexuality in E. marinus. We argue that the dependence of E. marinus on Fucus sp. should be further investigated to fully understand the role of both fucoids and the gammarid in coastal foodwebs.

Decay and persistence of empty bivalve shells in a temperate riverine system.

Bivalve shells can persist over a geological time, acting as important physical resources to the associated fauna. However, few studies have investigated their relevance as persistent long-term ecological attributes to the ecosystem. As such, it is relevant to investigate the shell decays in riverine systems subjected to different environmental conditions. Towards this end, shells of four bivalve species (Anodonta anatina, Corbicula fluminea, Potomida littoralis and Unio delphinus) were made available individually and in clusters of different sizes. The effects of river flow and seasonality were assessed by recording the decay rates of shells in lentic and lotic habitats throughout the year. Our results evidenced that the decays varied among species and depend on shell size, water flow and season. Thin shelled species (A. anatina and U. delphinus) showed the highest mean percentage of decay per month, 3.17% (lotic) and 2.77% (lotic), respectively, and thick shelled species (C. fluminea and P. littoralis) the lowest, 2.02% (lotic) and 1.83% (lotic), respectively. Size was a relevant variable explaining decays, with the smallest shells presenting the highest values, 1.2-2.0 times higher compared to the other size classes. Also, robustness showed to be the most relevant feature explaining the decays in thick shelled species. River flow was also a relevant descriptor of the decays, with higher decays observed in the lotic compared to the lentic habitats. Furthermore, lower decays were observed mainly during summer (lentic site), and autumn (lotic site) associated to the burial effect of leaves. In summary, shells of the native species A. anatina and U. delphinus are expected to persist and contribute less as habitat engineering species, than shells of the native P. littoralis and invasive C. fluminea species. This is especially valid to lotic habitats where the decays were up to 2.13 times higher than in lentic habitats.

Microcystin and pyriproxyfen are toxic to early stages of development in Rhamdia quelen: An experimental and modelling study.

The recent increase of freshwater eutrophication has favored cyanobacteria blooms and consequently the increase of toxins such as microcystin-LR in aquatic environments, but few is know about the associated effect of toxin and other compounds. Pyriproxyfen is an insecticide indicated by WHO (World Health Organization) to control Aedes aegypti mosquito (vector of Dengue, Chikungunya and Zika diseases), however, the effects are not well described to non-target species, such as fish. The early life stages (ELS) of fish are more sensitive to chemical stress due to higher metabolic rate, immature immune system and high superficial area/volume ratio. In the current study, ELS of R. quelen a Neotropical fish were exposed to environmentally realistic concentrations of microcystin (1, 10 and 100 µg L-1; M1, M2 and M3 groups, respectively) from an algal extract, pyriproxyfen (1 and 10 µg L-1, P1 and P2) and their association (co-exposure). The hatching, survival and larvae deformities were analyzed, and applied a mathematical model to evaluate the effects on the population size along further generations. Both compounds were toxic to embryos/larvae of fish, but the effects were more pronounced in M2, P1M2 and P2M1 for hatching and M2, P1M2, P2M1 and P1 for survival. Deformities prevailed in groups exposed to the chemicals at 48 hpf (hours post-fertilization) were suggestions of toxicological interaction in P1M2, P2M1 and P2M2 at 48 and 72 hpf. In 96 hpf, the levels of deformities were lower than in previous times. Model predicted population density over 100 years decreased to lower than 0.5 (50%) in all groups, except for P1M1, indicating risk of extinction. P1M2 had the worse results, followed by M2, P1M3 and P2M1. Cyanobacterial blooms can lead to microcystin-LR levels higher than M2 (10 µg L-1), and the suggestion of toxicological interaction with pyriproxyfen is relevant because both compounds may potentially coexist in aquatic environments. Finally, mathematical models may provide an ecological interpretation of the risk of exposure of fish.

A new species of Diomedenema (Nematoda, Rhabditida, Spiruromorpha) from Spheniscus magellanicus (Aves, Sphenisciformes) found on the southern coast of Brazil.

A new species of the genus Diomedenema, a spiruromorph nematode, collected from the lung of Spheniscus magellanicus (Sphenisciformes) found on the southern coast of the state of Rio Grande do Sul, Brazil, is described. The new species is differentiated from the only previously described species of the genus, D. diomedeae Johston & Mawson, 1952, by males possessing a set of caudal papillae with three pairs of precloacal, two pairs of adcloacal and one pair of postcloacal papillae; precloacal papillae with the papillae of the first two pairs being closer to each other than those of the third pair; a longer and pointed tail in males; and females with the vulva at mid-body. This is the first report of a nematode infecting the lung of a sphenisciforme host.

Avaliação do fluxo de saída do ventrículo esquerdo em gatos anestesiados submetidos ao pneumoperitônio e à posição deTrendelenburg / Evaluation left ventricle Outflow in cats anesthetized submitted to pneumoperitoneum and Trendelenburg position

Objetivou-se avaliar os efeitos do pneumoperitônio e da posição de Trendelenburg sobre o fluxo de saída do ventrículo esquerdo em gatos anestesiados. Quatorze gatos foram alocados aleatoriamente em dois grupos, ambos submetidos ao pneumoperitônio com 10mmHg de dióxido de carbono (CO2). No grupo controle (GC n=7), os animais foram submetidos apenas ao pneumoperitônio e, no grupo Trendelenburg (GTREN n=7), os animais foram colocados em cefalodeclive 20° após o pneumoperitônio. A indução anestésica foi realizada com isoflurano, utilizando-se caixa de indução. Posteriormente, os animais foram mantidos sob anestesia inalatória com o mesmo fármaco. Foram avaliados a velocidade do fluxo de saída do ventrículo esquerdo (VFSVE), os gradientes máximo (GmáxSVE) e médio (GmédSVE) de pressão e a integral velocidade-tempo (IVT). Os parâmetros foram mensurados nos momentos T0 (basal), antes da insuflação; T5 (cinco), T15 (quinze) e T30 (trinta) minutos após a insuflação. Os resultados mostraram um aumento da VFSVE no GC, em T15 e T30 (P=0,024), e um aumento do GmáxSVE no GC, em T30 (P=0,045). As variáveis não se alteraram significativamente em nenhum momento no GTREN. Dessa forma, conclui-se que a posição de Trendelenburg favoreceu o sistema cardiovascular, preservando os índices de fluxo sanguíneo na saída do ventrículo esquerdo.(AU)

The aim of this study was to evaluate the effects of pneumoperitoneum and Trendelenburg position on the left ventricular outflow in anesthetized cats. Fourteen cats were randomly divided into two groups, both submitted to pneumoperitoneum of 10 mmHg with carbon dioxide (CO2), and in the control group (GC n = 7) the animals were subjected only to pneumoperitoneum and the Trendelenburg group (n = 7 GTREN) the animals were placed in cefalodeclive 20° after pneumoperitoneum. Anesthesia of the animals was performed with isoflurane using induction box, keeping the animals under inhalation anesthesia with the same drug. We evaluated the speed of the left ventricular outflow (VFSVE), the maximum pressure gradient (GmáxSVE), mean pressure gradient (GmédSVE) and velocity-time integrals (IVT). The parameters were measured in time, T0 (baseline), before the insufflation; T5 (five); T15 (fifteen) and T30 (thirty) minutes after inflation. The results showed an increase in VFSVE in GC, T15 and T30 (p = 0,024) and an increase in GmáxSVE in GC in T30 (p = 0,045). The variables did not change significantly at any time in GTREN. Thus, it is concluded that the Trendelenburg position favored the cardiovascular system, preserving blood flow rates in the left ventricular outflow.(AU)

Estudo da ação da romã (Punica granatum L. ) na cicatrização de úlceras induzidas por queimadura em dorso de língua de ratos Wistar (Rattus norvegicus) / Pomegranate action study (Punica granatum L. ) for the healing of ulcers induced by burns to the dorso-lingual mucosa in Wistar rats (Rattus norvegicus).

RESUMO O objetivo desse estudo foi observar a ação da romã (Punica granatum L.) em estomatites induzidas por queimaduras no dorso da língua de ratos Wistar. Foram utilizados 24 ratos Wistar machos adultos, provenientes do Biotério da UNIVASF. Foram formados quatro grupos (G1: Polpa da romã por gavagem; G2: Polpa da romã por gavagem + aplicação local do chá da casca do fruto; G3: aplicação local do chá da casca do fruto e G4: Controle negativo). As queimaduras foram confeccionadas com instrumental odontológico padrão. Os tratamentos foram realizados duas vezes ao dia, durante 14 dias. Metade dos animais de cada grupo (n=3) foi eutanasiada no sétimo dia de experimentação, enquanto o restante foi eutanasiado no 14º dia. As línguas foram removidas e fixadas com formaldeído a 10% tamponado, processadas com cortes de 5 µm e coradas em HE. Clinicamente, os animais do grupo G2 tiveram melhores resultados. Na análise histológica qualitativa foi avaliada a reepitelização e os graus de inflamação numa escala de 0 a 4. Na análise estatística, utilizou-se o teste Qui-quadrado de Pearson. Houve significância estatística (p=0,026 e p=0,023) quando se comparou o tratamento com os graus de reepitelização e inflamação nos quatro grupos estudados. O grupo G2 apresentou cicatrização completa com 14 dias. Os piores escores obtidos foram atribuídos ao Grupo G4 nos dois parâmetros de avaliação qualitativa. Diante dos resultados obtidos, observa-se que a romã (Punica granatum L.) possui ação cicatrizante na mucosa lingual de ratos Wistar.

ABSTRACT The objective of this study was to observe the action of pomegranate (Punica granatum L.) on stomatitis induced burns on the dorso-lingual musosa in Wistar rats. Twenty-four male, adult Wister albino rats were used, from the bioterium of UNIVASF. There were four groups (G1: Pomegranate juice by gavage; G2: Pomegranate juice by gavage + local application of fruit peel tea; G3: Local application of fruit peel tea only and G4: a negative control). The burns were made with standard dental instruments. The treatments were performed twice a day for 14 days. Half the animals in each group (n = 3) were euthanized on the seventh day of experimentation, while the remainder were euthanized on day 14. The tongues were removed and fixed with a 10% formaldehyde buffer, processed as 5µm sections and stained with HE. Clinically the animals treated with tea showed better healing. For statistical analysis the Pearson chi-squared test was used. There was a statistical significance (p = 0.026 and p = 0.023) when compared to treatment with the degree of re-epithelialization and inflammation of the four groups studied. The G2 group showed complete healing within 14 days. The worst scores were found in the G4 group in both qualitative assessment parameters. Based on these results, it was observed that pomegranate (Punica granatum L.) has a healing action on the lingual mucosa of Wistar rats.

Embryonic development of Anodontites trapesialis (Lamarck, 1819) (Bivalvia: Mycetopodidae).

The phases of embryonic development of Anodontites trapesialis lasidia are described for the first time. Adult specimens were obtained from two fish farms located in Londrina, Paraná, Brazil. The internal demibranchs of 120 individuals were studied using a routine histological technique; 70 of these carried eggs and/or larvae in the marsupium and were utilized for the description of the phases of embryonic development. The demibranchs of five specimens were evaluated by scanning electron microscopy to detail the morphology of the larvae. Five phases of development were established: phase I, corresponding to the initial stage of cleavage with the formation of apical cells; phase II, including the stages of the morula and blastula; phase III, where the gastrula forms; phase IV, where the larva formed is still inside the egg envelope; and phase V, where the lasidium can still be identified immediately after eclosion.

Expanded description of Dolops bidentata (Bouvier, 1899) (Branchiura: Argulidae) based on specimens collected on Pygocentrus nattereri Kner, 1858 (Characiformes) from Poconé Wetland, MT, Brazil.

The current information on the branchiuran Dolops bidentata, a species described more one hundred years ago, is valid but incomplete; hence, an expanded description is given herein. Additional morphological information was obtained by light and scanning electron microscopy from specimens collected on Pygocentrus nattereri from the Poconé Wetland, MT, Brazil. Description of the appendages and other structures such as respiratory area, mouth, details and ornamentation of antennules and maxillae are provided for the first time.

Habitat use and behavioural ecology of the juveniles of two sympatric damselfishes (Actinopterygii: Pomacentridae) in the south-western Atlantic Ocean.

Spatial distribution, microhabitat use and territorial and feeding behaviours were compared between the juveniles of two sympatric territorial damselfishes Stegastes variabilis and Stegastes fuscus on a small tropical reef in the south-western Atlantic Ocean. Juvenile S. variabilis were most abundant at sites subject to stronger hydrodynamics and with mixed benthic cover, whereas juvenile S. fuscus were most abundant at sheltered sites with dense turf algae cover. No differences regarding feeding habits were detected, with both species preferentially feeding on turf algae. Also, despite similarities in territory area and agonistic encounter rates, the identity and proportion of intruders involved in agonistic interactions differed significantly between species. These interdependent traits suggest strong asymmetric competition, with juvenile S. fuscus dominating high-quality sites and evicting juvenile S. variabilis to low quality, marginal areas of the reef.

Parasitism of Cichlasoma paranaense Kullander, 1983 and Gymnotus carapo Linnaeus, 1814 by Clinostomum complanatum (Rudolphi, 1814) metacercariae in the Taquari river.

The infection, known as yellow spot disease, produced by metacercariae of Clinostomum spp. was studied in fishes of the Taquari river, located in Jataizinho, Paraná State, Brazil. A total of 1,582 specimens, belonging to 36 species, were collected between March 1999 and April 2001. Yellow spot disease was observed only in Gymnotus carapo Linnaeus, 1814 (Gymnotiformes, Gymnotidae) and Cichlasoma paranaense Kullander, 1983 (Perciformes, Cichlidae). This parasitism was generated by metacercariae of Clinostomum complanatum (Rudolphi, 1814) (Digenea, Clinostomidae). Among the 88 specimens of G. carapo examined, 7 (prevalence = 8%) had cysts of the parasite. Four of them were captured in July 1999 and three in October 1999. In the other months, no specimen found was infected. Using relative condition factor (Kn) analysis, it was determined that both infected and non-infected specimens had a total weight equal to the theoretically expected value for each total length (Kn = 1.0). Among 56 individuals of Cichlasoma paranaense, 6 (prevalence = 10.7%) had between 1 and 27 metacercariae of C. complanatum (mean intensity of infection = 9.3 +/- 9.6). In March 1999 and April of both 2000 and 2001, the specimens examined were not infected. The infected fish had a total weight higher than the expected value (Kn > 1.0), while the non-infected fish had a weight equal to the expected value (Kn = 1.0).

Parasitism of Cichlasoma paranaense Kullander, 1983 and Gymnotus carapo Linnaeus, 1814 by Clinostomum complanatum (Rudolphi, 1814) Metacercariae in the Taquari river

Estudou-se a infecção por metacercárias de Clinostomum spp., conhecida como doença das manchas amarelas, em peixes do rio Taquari, localizado no município de Jataizinho, Paraná, Brasil. Um total de 1.582 espécimes pertencentes a 36 espécies foram capturados entre março de 1999 e abril de 2001. As manchas amarelas foram observadas apenas em Gymnotus carapo Linnaeus, 1814 (Gymnotiformes, Gymnotidae) e Cichlasoma paranaense Kullander, 1983 (Perciformes, Cichlidae). Esse parasitismo foi produzido por larvas de Clinostomum complanatum (Rudolphi, 1814) (Digenea, Clinostomidae), na fase de metacercária. Dentre os 88 espécimes de G. carapo examinados, 7 (prevalência = 8%) tinham cistos do parasita. Destes, 4 foram capturados em julho de 1999, quando foi observada a mais alta intensidade de infecção, e 3 em outubro de 1999. Nos outros meses, nenhum espécime encontrava-se infectado. Analisando o fator de condição relativo (Kn) foi possível determinar que tanto os exemplares parasitados como os não parasitados estavam com o peso igual ao teoricamente esperado para cada comprimento (Kn = 1,0). Entre os 56 indivíduos de Cichlasoma paranaense, 6 (prevalência = 10,7%) apresentavam entre 1 e 27 metacercárias de C. complanatum (intensidade média de infecção = 9,3 ± 9,6). A mais alta intensidade de infecção foi registrada em janeiro de 2000. Em março de 1999 e em abril de 2000 e de 2001, nenhum dos espécimes examinados estava infectado. Os peixes parasitados encontravam-se com o peso total acima do esperado (Kn > 1,0), enquanto os não parasitados apresentaram peso total igual ao esperado (Kn = 1,0).

Co-infestation of gills by different parasite groups in the mullet, Mugil platanus Günther, 1880 (Osteichthyes, Mugilidae): effects on relative condition factor.

This study involved 334 specimens of mullet, Mugil platanus, captured monthly in the estuarine region of Cananéia, São Paulo State, Brazil, from July 1988 to June 1989, and examined for the presence of gill parasites. Parasitological inspections revealed the occurrence of the following groups: Trichodina sp., Monogenoidea, Copepoda, and Hirudinea. Only four mullets were not parasitized. Total weight and total length of all 334 mullet specimens examined were used for adjusting the weight-length relationship curve and calculating the relative condition factor (Kn). The 118 specimens infested with monogenoideans on average had lower weights than expected (Kn < 1.0), and the 81 fish co-infested with Copepoda, Monogenoidea, and Trichodina sp. showed a Kn < 1.0. The other infested and non-infested mullets had a Kn > 1.0. It was possible to infer that gill infestation with monogenoideans alters mullet weight, especially in the presence of co-infestation with Trichodina sp. and copepods.

Co-infestation of gills by different parasite groups in the mullet, Mugil platanus Günther, 1880 (Osteichthyes, Mugilidae): effects on relative condition factor

Foram examinados exemplares de tainha, Mugil platanus, capturados mensalmente na região estuarino-lagunar de Cananéia, SP, entre julho de 1988 e junho de 1989, a fim de verificar a ocorrência de parasitos branquiais. Das 334 tainhas examinadas, apenas quatro não apresentaram nenhum parasito. Nas demais, foram encontrados os seguintes grupos: Trichodina sp., Monogenoidea, Copepoda e Hirudinea. Utilizando os valores de peso total (Wt) e de comprimento total (Lt) de todos os espécimes estudados calculou-se o fator de condição relativo (Kn). Constatou-se que os 118 espécimes infestados por monogenóideos encontravam-se, em média, com peso inferior ao esperado. Os 81 espécimes que tinham, concomitantemente nas brânquias, Trichodina sp., copépodos e monogenóideos apresentaram, em média, peso inferior ao esperado. Os demais espécimes parasitados, assim como os não parasitados, estavam com o peso igual ou acima do esperado. Foi possível constatar que o parasitismo das brânquias por monogenóideos afeta o peso das tainhas, Mugil platanus, da região estuarino-lagunar de Cananéia, SP, especialmente quando co-infestado com Trichodina sp. e copépodos.

A Dermocystidium infection in Trichomycterus sp. (Osteichthyes, Trichomycteridae).

Two whitish elongate cysts in the left pectoral fin of Trichomycterus sp. (Osteichthyes, Trichomycteridae) were packed with Dermocystidium sp. spores. The spores were spherical and had a large PAS positive central refractile body, the cytoplasm being restricted to a narrow peripheral layer containing the nucleus. The cysts were surrounded by a thin homogeneous wall of parasite origin, and there was no encapsulation of the cysts by host tissue.

Altered ligand binding by insulin-like growth factor II/mannose 6-phosphate receptors bearing missense mutations in human cancers.

The M6P/IGF2R gene, encoding the insulin-like growth factor II (IGF-II)/mannose 6-phosphate receptor (IGF2R), is frequently inactivated during carcinogenesis. M6P/IGF2R is postulated to be a tumor suppressor gene due to its ability to bind and degrade the mitogen IGF-II, promote activation of the growth inhibitor transforming growth factor beta, and regulate the targeting of lysosomal enzymes. In this study, we determined the effects of four M6P/IGF2R missense mutations associated with loss of heterozygosity in hepatocellular and breast cancers on the ligand binding properties of full-length membrane-bound receptors. Site-directed mutagenesis was used to prepare COOH-terminal, c-myc epitope-tagged human IGF2R cDNA expression constructs bearing point mutations that lead to the substitutions I1572T, G1464E, G1449V, and Q1445H, all of which are located in the receptor's extracytoplasmic domain. Ligand binding was measured in plasma membranes from 293T cells expressing full-length receptors. No binding of 125I-IGF-II to I1572T mutant receptors was observed. Binding to G1449V mutant receptors was decreased by 50% relative to wild-type (WT). However, IGF-II binding to the G1464E and Q1445H mutant receptors was equivalent to WT when plasma membranes were assayed immediately after preparation. The phosphomannosylated pseudoglycoprotein pentamannose 6-phosphate-BSA (PMP-BSA) was synthesized as a ligand for the M6P binding site. Binding of 125I-PMP-BSA was equivalent to WT for the I1572T, G1464E, and Q1445H mutations, but there was a 60% reduction in PMP-BSA binding to the G1449V mutant receptor. Thus, several missense mutations in M6P/IGF2R disrupt the ligand binding functions of the intact IGF2R, lending further support to the hypothesis that the M6P/IGF2R is a tumor suppressor gene.

Disruption of ligand binding to the insulin-like growth factor II/mannose 6-phosphate receptor by cancer-associated missense mutations.

The insulin-like growth factor II/mannose 6-phosphate receptor (IGF2R) carries out multiple regulatory and transport functions, and disruption of IGF2R function has been implicated as a mechanism to increase cell proliferation. Several missense IGF2R mutations have been identified in human cancers, including the following amino acid substitutions occurring in the extracytoplasmic domain of the receptor: Cys-1262 --> Ser, Gln-1445 --> His, Gly-1449 --> Val, Gly-1464 --> Glu, and Ile-1572 --> Thr. To determine what effects these mutations have on IGF2R function, mutant and wild-type FLAG epitope-tagged IGF2R constructs lacking the transmembrane and cytoplasmic domains were characterized for binding of insulin-like growth factor (IGF)-II and a mannose 6-phosphate-bearing pseudoglycoprotein termed PMP-BSA (where PMP is pentamannose phosphate and BSA is bovine serum albumin). The Ile-1572 --> Thr mutation eliminated IGF-II binding while not affecting PMP-BSA binding. Gly-1449 --> Val and Cys-1262 --> Ser each showed 30-60% decreases in the number of sites available to bind both (125)I-IGF-II and (125)I-PMP-BSA. In addition, the Gln-1445 --> His mutant underwent a time-dependent loss of IGF-II binding, but not PMP-BSA binding, that was not observed for wild type. In all, four of the five cancer-associated mutants analyzed demonstrated altered ligand binding, providing further evidence that loss of IGF2R function is characteristic of certain cancers.