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The evolution of sex determination (SD) mechanisms in teleost fishes is amazingly dynamic, as reflected by the variety of different master sex-determining genes identified, even sometimes among closely related species. Pangasiids are a group of economically important catfishes in many South-Asian countries, but little is known about their sex determination system. Here, we generated novel genomic resources for 12 Pangasiid species and provided a first characterization of their SD system. Based on an Oxford Nanopore long-read chromosome-scale high quality genome assembly of the striped catfish Pangasianodon hypophthalmus, we identified a duplication of the anti-Müllerian hormone receptor type II gene (amhr2), which was further characterized as being sex-linked in males and expressed only in testicular samples. These first results point to a male-specific duplication on the Y chromosome (amhr2by) of the autosomal amhr2a. Sequence annotation revealed that the P. hypophthalmus Amhr2by is truncated in its N-terminal domain, lacking the cysteine-rich extracellular part of the receptor that is crucial for ligand binding, suggesting a potential route for its neofunctionalization. Short-read genome sequencing and reference-guided assembly of 11 additional Pangasiid species, along with sex-linkage studies, revealed that this truncated amhr2by duplication is also conserved as a male-specific gene in many Pangasiids. Reconstructions of the amhr2 phylogeny suggested that amhr2by arose from an ancient duplication / insertion event at the root of the Siluroidei radiation that is dated around 100 million years ago. Altogether these results bring multiple lines of evidence supporting that amhr2by is an ancient and conserved master sex-determining gene in Pangasiid catfishes, a finding that highlights the recurrent usage of the transforming growth factor β pathway in teleost sex determination and brings another empirical case towards the understanding of the dynamics or stability of sex determination systems.

Caudal fin symmetry characterizes teleosts and likely contributes to their evolutionary success. However, the coordinated development and patterning of skeletal elements establishing external symmetry remains incompletely understood. We explore the spatiotemporal emergence of caudal skeletal elements in zebrafish to consider evolutionary and developmental origins of caudal fin symmetry.Transgenic reporters and skeletal staining reveal that the hypural diastema-defining gap between hypurals 2 and 3 forms early and separates progenitors of two plates of connective tissue. Two sets of central principal rays (CPRs) synchronously, sequentially, and symmetrically emerge around the diastema. The two dorsal- and ventral-most rays (peripheral principal rays, PPRs) arise independently and earlier than adjacent CPRs. Muscle and tendon markers reveal that different muscles attach to CPR and PPR sets.We propose that caudal fin symmetry originates from a central organizer that establishes the hypural diastema and bidirectionally patterns surrounding tissue into two plates of connective tissue and two mirrored sets of CPRs. Further, two peripheral organizers unidirectionally specify PPRs, forming a symmetric "composite" fin derived from three fields. Distinct CPR and PPR ontogenies may represent developmental modules conferring ray identities, muscle connections, and biomechanical properties. Our model contextualizes mechanistic studies of teleost fin morphological variation.

Cancer cachexia is a multifactorial syndrome characterized by involuntary and pathological weight loss, mainly due to skeletal muscle wasting, resulting in a decrease in patients' quality of life, response to cancer treatments, and survival. Our objective was to investigate skeletal muscle alterations in cachectic cancer patients.This is a prospective study of patients managed for pancreatic or colorectal cancer with an indication for systemic chemotherapy (METERMUCADIG - NCT02573974). One lumbar CT image was used to determine body composition. Patients were divided into three groups [8 noncachectic (NC), 18 with mild cachexia (MC), and 19 with severe cachexia (SC)] based on the severity of weight loss and muscle mass. For each patient, a pectoralis major muscle biopsy was collected at the time of implantable chamber placement. We used high-resolution oxygraphy to measure mitochondrial muscle oxygen consumption on permeabilized muscle fibres. We also performed optical and electron microscopy analyses, as well as gene and protein expression analyses.Forty-five patients were included. Patients were 67% male, aged 67 years (interquartile range, 59-77). Twenty-three (51%) and 22 (49%) patients were managed for pancreatic and colorectal cancer, respectively. Our results show a positive correlation between median myofibres area and skeletal muscle index (P = 0.0007). Cancer cachexia was associated with a decrease in MAFbx protein expression (P 0.01), a marker of proteolysis through the ubiquitin-proteasome pathway. Mitochondrial oxygen consumption related to energy wasting was significantly increased (SC vs. NC, P = 0.028) and mitochondrial area tended to increase (SC vs. MC, P = 0.056) in SC patients. On the contrary, mitochondria content and networks remain unaltered in cachectic cancer patients. Finally, our results show no dysfunction in lipid storage and endoplasmic reticulum homeostasis.This clinical protocol brings unique data that provide new insight to mechanisms underlying muscle wasting in cancer cachexia. We report for the first time an increase in mitochondrial energy wasting in the skeletal muscle of severe cachectic cancer patients. Additional clinical studies are essential to further the exploring and understanding of these alterations.

Intravenous administration of monoclonal antibodies leads to low concentrations in the central nervous system, which is a serious concern in neuro-oncology, especially in leptomeningeal carcinomatosis of HER2-overexpressing breast cancer. Case reports of intrathecal (IT) administrations of trastuzumab have shown promising results in these patients but dosing regimens are empirical in absence of pharmacokinetic study. With a population pharmacokinetic approach, we described the fate of trastuzumab after IT administration in 21 women included in a phase I-II clinical trial. Trastuzumab was administered by IT route every week for 8 weeks and both cerebrospinal fluid (CSF) and serum were sampled to measure trough concentrations. Some patients showed noticeable CSF concentration fluctuations predicted using a target-mediated drug disposition. This target was latent and produced with a delayed feedback. Apparent volumes of distribution were close to physiological volumes (V1 = 3.25 L, V2 = 0.644 L, for serum and CSF, respectively). Estimated (constant) transfer from serum to CSF was very slow (k12 = 0.264 mg.d-1 ) while estimated half-life of transfer from CSF to serum was rapid (2.2 days). From the individual parameters of patients, a single IT administration of 150 mg of trastuzumab corresponded to median mean residence times (MRT) of 3.8 days and 15.6 days in CSF and serum, respectively. Survival without neurological relapse was not related to trastuzumab exposure. This study confirms that transfer of trastuzumab from serum to CSF is very limited and that this monoclonal antibody, when administered by IT route, is rapidly transferred to the serum.

Background The caudal fin of actinopterygians transitioned from a heterocercal dorsoventrally asymmetrical fin to a homocercal externally symmetrical fin in teleosts through poorly understood evolutionary developmental mechanisms. We studied the caudal skeleton of major living actinopterygian lineages, including polypteriformes, acipenseriformes, Holostei (gars and bowfin), and teleosts, compared with reports of extinct neopterygians and basal teleosteans. We focused on the hypural diastema complex, which includes (1) a gap between hypurals 2 and 3, that (2) separates two plates of connective tissue at (3) the branching of caudal vasculature; these features had been considered as a shared, derived trait of teleosts, a synapomorphy. Results These studies revealed that gars and teleosts share all three features of the hypural diastema complex. Absence of a complex with these features from bowfin, fossil Holostei, and stem Teleostei argues in favor of repetitive, independent emergence in several neopterygian and basal Teleostei lineages, or less likely, many independent losses. We further observed that, in gars and teleosts, the earliest developing lepidotrichia align with the horizontal adult body axis, thus participating in external symmetry. Conclusions These results suggest that the hypural diastema complex in teleosts and gars represents a homoplasy among neopterygians and that it emerged repeatedly by parallel evolution due to shared inherited underlying genetic and developmental programs (latent homology). Because the hypural diastema complex exists in gars with heterocercal tails, this complex is independent of homocercality. Developmental Dynamics 247:832-853, 2018. © 2018 Wiley Periodicals, Inc.

Background The caudal fin of actinopterygians experienced substantial morphological changes during evolution. In basal actinopterygians, the caudal fin skeleton supports an asymmetrical heterocercal caudal fin, while most teleosts have a symmetrical homocercal caudal fin. The transition from the ancestral heterocercal form to the derived homocercal caudal fin remains poorly understood. Few developmental studies provide an understanding of derived and ancestral characters among basal actinopterygians. To fill this gap, we examined the development of the caudal fin of spotted gar Lepisosteus oculatus, one of only eight living species of Holostei, the sister group to the teleosts. Results Our observations of animals from fertilization to more than a year old provide the most detailed description of the development of caudal fin skeletal elements in any Holostean species. We observed two different types of distal caudal radials replacing two transient plates of connective tissue, identifying two hypaxial ensembles separated by a space between hypurals 2 and 3. These features have not been described in any gar species, but can be observed in other gar species, and thus represent anatomical structures common to lepisosteiformes. Conclusions The present work highlights the power and importance of ontogenic studies and provides bases for future evolutionary and morphological investigations on actinopterygians fins. Developmental Dynamics 247:724-740, 2018. © 2018 Wiley Periodicals, Inc.

Background: Aberrant signaling between germ cells and somatic cells can lead to reproductive disease and depends on diffusible signals, including TGFB-family proteins. The TGFB-family protein Gsdf (gonadal soma derived factor) controls sex determination in some fish and is a candidate for mediating germ cell/soma signaling. Results: Zebrafish expressed gsdf in somatic cells of bipotential gonads and expression continued in ovarian granulosa cells and testicular Sertoli cells. Homozygous gsdf knockout mutants delayed leaving the bipotential gonad state, but then became a male or a female. Mutant females ovulated a few oocytes, then became sterile, accumulating immature follicles. Female mutants stored excess lipid and down-regulated aromatase, gata4, insulin receptor, estrogen receptor, and genes for lipid metabolism, vitellogenin, and steroid biosynthesis. Mutant females contained less estrogen and more androgen than wild types. Mutant males were fertile. Genomic analysis suggests that Gsdf, Bmp15, and Gdf9, originated as paralogs in vertebrate genome duplication events. Conclusions: In zebrafish, gsdf regulates ovarian follicle maturation and expression of genes for steroid biosynthesis, obesity, diabetes, and female fertility, leading to ovarian and extra-ovarian phenotypes that mimic human polycystic ovarian syndrome (PCOS), suggesting a role for a related TGFB signaling molecule in the etiology of PCOS. This article is protected by copyright. All rights reserved.

This work aims to assess the exposure to permethrin of the adult French population from available contamination measurements of outdoor air, indoor air, and settled dust. Priority is given to the assessment of chronic exposure, given the potential of permethrin to induce cancers and/or endocrine disorders. A statistical method was devised to calculate exposure to permethrin by different pathways (inhalation, indirect dust ingestion, and dermal contact). This method considers anthropometric parameters, the population's space-time budget, and recent methods for calculating dermal exposure. Considering the media of interest, our results pointed to house dust as the main environmental source of permethrin exposure, followed by indoor and outdoor air. Dermal contact and indirect dust ingestion may be more important exposure pathways than inhalation. A sensitivity analysis indicated that exposure estimates were mainly affected by variability within contamination data. This study is the first step in aggregated exposure and risk assessment due to pyrethroid exposure. Outdoor air, indoor air, and settled dust may constitute significant exposure sources, in addition to diet, which could be important. The next step entails assessing internal doses and estimating the proportion of each exposure source and pathway relative to internal exposure.

Aims Rituximab is a monoclonal antibody directed against CD20, which is approved in rheumatoid arthritis (RA). This study aimed at assessing the influence of CD19+ cell counts as target-antigen amount, and of immunoglobulin G (IgG) serum concentrations on rituximab pharmacokinetics in RA patients. Methods In a cohort of 64 RA patients who had received repetitive courses of rituximab, the influence of CD19+ cell count, IgG serum concentration, body surface area (BSA), sex, and disease activity score in 28 joints (DAS28) on rituximab pharmacokinetic parameters was assessed using a population pharmacokinetic analysis. Results A two-compartment model, with first-order distribution and elimination best described the data. The volume of distribution of central compartment (Vc) and clearance (CL) of rituximab were estimated at 4.7 L and 0.56 L/day, respectively. Distribution (T½-α) and elimination (T½-β) half-lives were 0.9 days and 17.3 days, respectively. As expected, the central volume of distribution increased with BSA (p = 0.012) and was higher in male than in female (p = 0.004). We found that the elimination rate constant (k10) increased with CD19+ count (p = 0.00022) and IgG concentration (p = 7.4 10-8), and that k10 decreased with time (p = 0.00015), partly explained by a change in target-antigen amount. Conclusions The association between CD19+ count and k10 may be explained by target-mediated drug disposition, while the association between IgG serum concentration and k10 may be explained by a saturation of the neonatal Fc receptor (FcRn) at high IgG concentrations, resulting in decreased recycling of rituximab.

In aquatic vertebrates, dense skeletons and buoyant fat constitute important components for buoyancy regulation in addition to their roles in structural support and energy storage. Some fishes can fine-tune buoyancy using their swim bladder, whereas others rely on neutral buoyancy or constant motion to regulate vertical position. The Notothenioidei provides a model system to study the phenotypic implications of differential use of the water column over a large radiation of closely related species. It has been suggested that to expand from ancestral benthic to pelagic habitats, some notothenioids, all of which lack the swim bladder, have reduced skeletal mass and display enhanced lipid deposition. This, apparently, adaptive osteopenia has interesting medical implications in understanding the balance between osteopenic bone and structural integrity of the skeleton.While relative buoyancy in seawater (%B) and dry skeletal mass have previously been studied in some notothenioids, little is known about the specific anatomical changes resulting in osteopenia; hypotheses include reductions of bone mineralization, reductions in bone size, and/or modifications of bone architecture. Here we used a high-throughput procedure relying on quantitative X-ray computed tomography (qCT) imaging on a collection of 436 notothenioid specimens (7 families, 24 genera, 53 species) to measure overall volumetric bone mineral density (vBMD), body size-adjusted mineral content of the entire skeleton (BMCtotal), vertebrae (BMCvertebrae), and skull bones (BMCskull), and body size adjusted lipid content (LC). Dual-energy X-ray absorptiometry and magnetic resonance imaging on a subsample of 50 specimens was used for BMCtotal and LC validation.For 33 species in the collection, %B was available from the literature and we performed phylogenetic generalized least-squares analysis with seven models to explain buoyancy (%B ~ BMCtotal, %B ~ BMCskull, %B ~ BMCvertebrae, %B ~ BMCtotal + BMCskull, %B ~ BMCtotal + BMCvertebrae, %B ~ BMCtotal + BMCskull + BMCvertebrae, %B ~ LC). This phylogenetically informed multivariate data analysis showed that the model %B ~ BMCtotal + BMCvertebrae best described the data, thus evolutionary reductions in %B are best explained by reductions in both BMCtotal and BMCvertebrae.In a series of studies, Eastman et al. established the link between buoyancy, skeletal mass, and LC in notothenioids, most recently in a comprehensive report spanning 54 specimens of 20 species (Eastman et al. J Morphol. 2014, 275:841–61). The present result confirms on a much broader scale the correlation between bone mineral content and buoyancy, and shows that vertebrae are the most important bone type for overall reductions in BMC. Based on qCT, micro-CT, histology, and mechanical testing, we seek to answer to which extend the reduction in BMC compromises the mechanical integrity of the bone.

The standard four-rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti-ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study. Patients with a suboptimal response to a plasma exchange-based regimen received two infusions of rituximab 375 mg/m2 within 4 days, and a third dose at day +15 of the first infusion if peripheral B cells were still detectable. Primary endpoint was the assessment of the time required to platelet count recovery from the first plasma exchange. Three patients died after the first rituximab administration. In the remaining patients, the B cell-driven treatment hastened remission and ADAMTS13 activity recovery as a result of rapid anti-ADAMTS13 depletion in a similar manner to the standard four-rituximab infusions schedule. The 1-year relapse-free survival was also comparable between both groups. A rituximab regimen based on B cell depletion is feasible and provides comparable results than with the four-rituximab infusions schedule. This regimen could represent a new standard in TTP. This trial was registered at www.clinicaltrials.gov (NCT00907751). This article is protected by copyright. All rights reserved.

Background: Environmental temperature influences rates of embryonic development, but a detailed staging series for vertebrate embryos developing in the sub-zero cold of Antarctic waters is not yet available from fertilization to hatching. Given projected warming of the Southern Ocean, it is imperative to establish a baseline to evaluate potential effects of changing climate on fish developmental dynamics. Results: We studied the Bullhead notothen (Notothenia coriiceps), a notothenioid fish inhabiting waters between −1.9 and +2°C. In vitro fertilization produced embryos that progressed through cleavage, epiboly, gastrulation, segmentation, organogenesis, and hatching. We compared morphogenesis spatially and temporally to zebrafish and medaka. Experimental animals hatched after about six months to early larval stages. To help understand skeletogenesis, we analyzed late embryos for expression of sox9, and runx2, which regulate chondrogenesis, osteogenesis, and eye development. Results revealed that, despite its prolonged developmental time course, N. coriiceps embryos developed similarly to those of other teleosts with large yolk cells. Conclusions: Our studies set the stage for future molecular analyses of development in these extremophile fish. Results provide a foundation for understanding the impact of ocean warming on embryonic development and larval recruitment of notothenioid fish, which are key factors in the marine trophic system. This article is protected by copyright. All rights reserved.

Introduction: Autosomal recessive muscular dystrophies are heterogeneous genetic disorders, with 39 genes currently implicated. Genetic diagnosis using targeted single-gene analysis by Sanger sequencing yields negative results in 10−20% of samples, warranting clinical re-evaluation and time-consuming testing of additional genes. This applies to dysferlinopathies caused by mutations in the gene encoding dysferlin (DYSF), which presents mainly as limb-girdle muscular dystrophy (LGMD) or distal myopathy. Methods: We evaluated exome sequencing associated with data filtering for selected genes as a second-tier approach for genetic diagnosis in a cohort of 37 patients with an initial negative result on targeted DYSF analysis. Results: Exome sequencing allowed for establishing (16%) or suggesting (8%) the molecular diagnosis by implicating other known LGMD or distal myopathy genes or by revealing DYSF mutations previously missed using mutation-screening techniques with incomplete detection yields. Conclusions: Exome sequencing associated with data filtering constitutes an efficient second-tier analysis for genes implicated in LGMD or distal myopathies. Muscle Nerve 50: 1007–1010, 2014

Many fields of biology--including vertebrate Evo-Devo research--are facing an explosion of genomic and transcriptomic sequence information and a multitude of fish species are now swimming in this "genomic tsunami." Here, we first give an overview of recent developments in sequencing fish genomes and transcriptomes that identify properties of fish genomes requiring particular attention and propose strategies to overcome common challenges in fish genomics. We suggest that the generation of chromosome-level genome assemblies--for which we introduce the term "chromonome"--should be a key component of genomic investigations in fish because they enable large-scale conserved synteny analyses that inform orthology detection, a process critical for connectivity of genomes. Orthology calls in vertebrates, especially in teleost fish, are complicated by divergent evolution of gene repertoires and functions following two rounds of genome duplication in the ancestor of vertebrates and a third round at the base of teleost fish. Second, using examples of spotted gar, basal teleosts, zebrafish-related cyprinids, cavefish, livebearers, icefish, and lobefin fish, we illustrate how next generation sequencing technologies liberate emerging fish systems from genomic ignorance and transform them into a new model army to answer longstanding questions on the genomic and developmental basis of their biodiversity. Finally, we discuss recent progress in the genetic toolbox for the major fish models for functional analysis, zebrafish, and medaka, that can be transferred to many other fish species to study in vivo the functional effect of evolutionary genomic change as Evo-Devo research enters the postgenomic era.

BACKGROUND: Climacteric fruits are harvested at the green-mature stage and ripen during their marketing cycle. However, growing conditions induce variability into the maturity stage of mangoes at harvest, with an impact on their final quality. Assuming that the physiological age can be correctly evaluated by a criterion based on the variable chlorophyll fluorescence of the skin (Fv) and that differences in physiological age depend on growing conditions, controlled stress experiments were carried out on mango fruit bymanipulating either the leaf/fruit ratio or the light environment. RESULTS: Delays from 9 to 30 days were observed, depending on stress level and harvest stage, to obtain the same Fv value. For moderate stress, fruit composition after ripening was partially compensated for, with little or no difference in sugar, dry matter, carotenoid and aroma contents. For more pronounced stress, themajor metabolites were not particularly affected, but the synthesis capacity of carotenoids and aromas was lower after maturity. CONCLUSION: The ripening ability of a fruit is acquired on the tree and defines its postharvest changes. Control of the physiological age at harvest can minimise the variability observed under natural conditions and guarantee fruit batches whose postharvest changes will be relatively homogeneous. (Resume d'auteur)

Correspondence to: Valerie Lullien-Pellerin, UMR Ingenierie des Agropolymeres et Technologies Emergentes, INRA, 2 Place Pierre Viala, F-34060 Montpellier Cedex 1, France E-mail: lullien@ensam.inra.fr; International audience; Wheat grain soaking in calcium solutions was used as a tool to enhance endogenous peroxidase activities and follow potential changes in outer layer mechanical properties and cell wall phenolic profile. Treatment with 10mmol L−1 calcium chloride was found to increase peroxidase activities in grains from two cultivars differing in kernel hardness, but at a different level. Concomitantly, mechanical properties of the outer layers from treated grains, assessed by uniaxial tension tests, showed significant stiffening depending on wheat cultivar. These changes were also observed in tissues after removal of the outer pericarp but not in each of the isolated layers, suggesting that modification of the mechanical properties occurs at the interface between the aleurone layer and the surrounding tissues. Analyses of the outer layer phenolic acid composition after mild or severe alkaline hydrolysis and of released lignin monomers after thioacidolysis appeared in accordance with the observed changes in tissue mechanical properties and suggest modification of cell wall compound interactions.

More than 600 Prunus samples were examined by using a nonradioactive digoxigenin-labelled RNA probe specific for hop stunt viroid (HSVd). Prunus salicina and Prunus armeniaca appeared to be better hosts than Prunus persica. The weak viroid concentration in flowers and young leaves of peach trees growing in the field did not permit its detection in such samples. The diagnosis was more reliable (about 85%) with bark and leaves aged 4 months and more, from regrowths of GF 305 peach seedlings inoculated and kept in the greenhouse. Detection of HSVd in leaves and bark of apricot and Japanese plum plants aged 3 months or more also proved reliable (about 80% and 90%, respectively). HSVd could be transmitted in apricot, peach and plum nucleic acid preparations to GF 305 peach seedlings by repeated stem slashing, and to cherries (Prunus avium and Prunus serrulata) by approach grafting with an infected P. salicina source. The viroid was eliminated from 18% of the clones obtained after thermotherapy. In the course of this study, 25 selected Prunus accessions suspected to be infected by unusual diseases were analysed by hybridization with a HSVd-specific probe and by indexing on GF 305 peach seedlings in the greenhouse. Fifteen of these accessions were found to be infected by HSVd, 19 induced reddish marbling, and four induced small blackish spots on the leaves aged about 4 months. Repeated assays showed that these foliar symptoms were not caused by the viroid. Peach red marbling (PRMa) has not been associated with any known virus and seems to be caused by an infectious agent not yet described. That could also be the case with the agent of peach sooty ringspot (PSRS). PRMa and PSRS symptoms were reproduced by grafting and indexing, and their causal agents eliminated by thermotherapy in a significant fraction of the treated plants. They behave like viral agents and can infect the different Prunus species studied.

Magnetic prospecting is used mainly for horizontal mapping, whereas the determination of the depth of features receives only limited attention. The inverse problem has an infinity of solutions and it is not possible to define precisely either the exact shape or the exact depth of a given feature. On the one hand, the depth of the source of an anomaly is limited and minimal information about contrast, horizontal location and depth of the centre can be extracted from the data. On the other hand, comparison between results obtained from different methods or by the simultaneous interpretation of their results necessitates in the first place an evaluation of the correspondence between the depth of the sources indicated by the different methods. Details of a series of four techniques that deliver information about the depth or the range of depths of magnetic anomaly sources are presented here. The search for the equivalent dipole (i.e. a spherical body) is of very limited interest owing to the difference that exists between the actual archaeological features and a sphere. In contrast, Euler deconvolution provides interesting results when using a structural index approaching 2. The depth of the centre of magnetization and the total magnetic moment also can be determined. The latter allows an estimation of the product of the volume and the susceptibility contrast (the possible presence of non-induced magnetizations being considered). The downward continuation of the equivalent stratum susceptibility needs more empirical tests to define divergence criteria, but it delivers another estimation of the susceptibility changes and information about its depth variation. Copyright © 1999 John Wiley & Sons, Ltd.

For 25 years the fluxgate gradiometer has been in common use in magnetic archaeological prospecting. It constitutes a cheap and light solution well adapted for the detection of earth-filled and burned features and of elements built with brick or magnetic stones. Among the different processing techniques that can be applied to the magnetic data, we chose to use linear transforms, which aim at locating and delineating precisely the buried features and at correcting for field inclination using no a priori information about causative bodies. We applied these transforms to fluxgate ΔZ gradiometer data, by calculation in the spectral domain for both synthetic and measured data. The advantages of this application depend on the characteristics of the features searched for and of their environment, and several transformed maps can be calculated by the interpreter in order to choose the most convenient for a given survey. © 1997 John Wiley & Sons, Ltd.

Contact sensitivity (CS) is a form of delayed-type hypersensitivity to haptens applied epicutaneously and is thought to be mediated, like classical delayed-type hypersensitivity responses, by CD4+ T helper-1 cells. The aim of this study was to identify the effector T cells involved in CS. We studied CS to the strongly sensitizing hapten dinitrofluorobenzene (DNFB) in mice rendered deficient by homologous recombination in either major histocompatibility complex (MHC) class I, MHC class II, or both, and which exhibited deficiencies in, respectively, CD8+, CD4+, or both, T cells. MHC class I single-deficient and MHC class I/class II double-deficient mice, both of which have a drastic reduction in the number of CD8+ T cells, were unable to mount a CS response to DNFB. In contrast, both MHC class II-deficient mice and normal mice treated with an anti-CD4 monoclonal antibody (mAb) developed exaggerated and persistent responses relative to heterozygous control littermates. Furthermore, anti-CD8 mAb depletion of class II-deficient mice totally abolished their ability to mount an inflammatory response to DNFB. Removal of residual CD4+ T cells in class II-deficient mice by anti-CD4 mAb treatment did not diminish the intensity of CS. These data clearly demonstrate that class I-restricted CD8+ T cells are sufficient for the induction of CS to DNFB, and further support the idea that MHC class II-restricted CD4+ T cells down-regulate this inflammatory response.

Magnetic susceptibility measured by electromagnetic prospecting does not deliver equivalent information to that measured by magnetic prospecting. This originates from the natural remanent magnetization in magnetic anomalies and from differences in geometrical factors governing the responses of the features. This is illustrated by both theoretical and experimental results. Advantage can be taken by applying both methods simultaneously on magnetically favourable archaeological sites.

A bench-top procedure was developed and tested for estimating the acid requirement for modifying the pH of low acid foods. Acid amounts needed to achieve desired equilibrium pH in finished products depended on total solids, protein and ash contents of foods, and on buffering capacities of acidulants and foods. Acid requirements to modify pH were calculated from titration curves. Specified equilibrium pH values were achieved within 0.08 pH unit. Effective gluconic acid diffusion (Deff) into a buffered model food was 8.3 × 10−10±1.5 × 10−10 m2sec-1.