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Tsunami, storm and flash-flood event layers, which have been deposited over the last century on the shelf offshore Khao Lak (Thailand, Andaman Sea), are identified in sediment cores based on sedimentary structures, grain size compositions, Ti / Ca ratios and 210Pb activity. Individual offshore tsunami deposits are 12 to 30 cm in thickness and originate from the 2004 Indian Ocean Tsunami. They are characterized by (1) the appearance of sand layers enriched in shells and shell debris and (2) the appearance of mud and sand clasts. Storm deposits found in core depths between 5 and 82 cm could be attributed to recent storm events by using 210Pb profiles in conjunction with historical data of typhoons and tropical storms. Massive sand layers enriched in shells and shell debris characterize storm deposits. The last classified type of event layer represents reworked flash-flood deposits, which are characterized by a fining-upward sequence of muddy sediment. The most distinct difference between storm and tsunami deposits is the lack of mud and sand clasts, mud content and terrigenous material within storm deposits. Terrigenous material transported offshore during the tsunami backwash is therefore an important indicator to distinguish between storm and tsunami deposits in offshore environments.

We have investigated the benthic foraminiferal fauna from sediment event layers associated with the 2004 Indian Ocean tsunami and former storms that have been retrieved in short sediment cores from offshore environments of the Andaman Sea, off Khao Lak, western Thailand. Species composition and test preservation of the benthic foraminiferal faunas exhibit pronounced changes across the studied sections and provide information on the depositional history of the tsunami layer, particularly on the source water depth of the displaced foraminiferal tests. In order to obtain accurate bathymetric information on sediment provenance, we have mapped the distribution of modern faunas in non-tsunamigenic surface sediments and created a calibration data set for the development of a transfer function. Our quantitative reconstructions revealed that the resuspension of sediment particles by the tsunami wave was restricted to a maximum water depth of approximately 20 m. Similar values were obtained for former storm events, thus impeding an easy distinction of different high-energy events.

Understanding the tsunami cycle requires a simple method for identification of tsunami backwash deposits. This study investigates Fourier transform infrared (FTIR) spectroscopy followed by careful analysis of variance (ANOVA), Gaussian distribution, hierarchical cluster analysis (HCA) and principal component analysis (PCA) for the discrimination of typical marine sediments and tsunami backwash deposits. In order to test the suitability of FTIR spectra as innovative methods for classifications of tsunami deposits, typical marine sediments and terrestrial soils were classified into three zones, namely zone-1 (i.e. typical marine sediments), zone-2 (i.e. including tsunami backwash deposits) and zone-3 (i.e. coastal terrestrial soils). HCA was performed to group the spectra according to their spectral similarity in a dendrogram and successfully separate FTIR spectra of all three sampling zones into two main clusters with five sub-clusters. The simplicifolious (i.e. single-leafed) type of dendrogram was observed with the strong dissimilarity of terrestrial components in subcluster- 5. Graphical displays of PC1 vs PC2 highlight the prominent features of zone-1, which is explicitly different from those of zone-2 and zone-3. The acceptable discrimination of typical marine sediments and tsunami backwash deposits, even six years after the tsunami on Boxing Day 2004, dramatically demonstrates the potential of the method for the identification of paleotsunami.

In this study, we attempted to use PAHs as a chemical proxy to trace the transport of land-derived materials caused by the tsunami backwash to better understand how it may have affected the distribution of sedimentary deposition throughout the seabed of Khao Lak coastal areas. By analyzing the compositions of sedimentary PAHs in combination with application of the multivariate descriptive statistical techniques, PAHs were proven to be a promising chemical proxy to indicate the tsunami backwash in the study area. Their spatial distribution could indicate that the tsunami backwash plays an important role in transporting anthropogenic PAHs to the nearby coastal area as far as approximately 25 km from the shoreline. In addition, the results from diagnostic PAH isomer ratios suggested that road paving asphalt, originated from heavy erosion by the tsunami wave in front of Pakarang Cape, was among the identified sources of PAHs. Principle Component Analysis (PCA) results provided 2 estimated land-derived sources of PAHs, which were the road dust and oil burning sources. These estimated signature sources clearly support our hypothesis that PAHs were transported from the potential sources on land and deposited into the near-shore seabed during tsunami backwash.

Saturated steam decontamination is an application for elimination of microorganisms from the surface of different materials. This technique has been optimized for the treatment of dried spices or pharmaceuticals, which could have been contaminated with microorganisms during cultivation, processing, storage or transport. The described saturated steam decontamination is based on the Lemgo process. This method does not kill microorganisms, but removes them physically from the surface. Our investigation focused on measuring the effects of steam temperatures at 120 °C and 100 °C, respectively, for 20 s with a subsequent fl ash vacuum of 20 s. Applications of fl ash vacuum as well as saturated steam heated to 120 °C were also tested separately. The impact of these parameters on the essential oil content and on the surface of different medicinal plants such as marjoram, oregano, fennel and eucalyptus was analysed using gas chromatography and scanning electron microscopy. Especially in herbal drugs with glandular trichomes such as marjoram and oregano severe surface destruction was visible accompanied by high losses of essential oil from 93 % in marjoram tissue to 59 % in oregano tissue. For fennel and eucalyptus that possess protected essential oil storage cells only minor or no reduction of volatiles has been observed during exposure to saturated steam. The experiments show clearly a positive correlation between stability of essential oil cavities and essential oil content preservation.

In order to understand mechanisms of ontogenic resistance to apple scab, we analyzed various aspects of young and old leaves. We have introduced an apple plants cultivation system where in vitro propagated and rooting explants produce a genetically uniform population of apple (Malus domestica cv. Idared) plants. In this work, we demonstrate that apple plants produced in our cultivation system showed susceptibility to Venturia inaequalis, the cause of apple scab disease in young leaves and resistance in old leaves, which is similar to orchard situation. Our analysis shows that the cessation of epidermal cell expansion and shape formation coincided with the onset of ontogenic resistance in older leaves. Formation of specific cuticular lamellar structures did not coincide with ontogenic resistance onset. Further, chemical composition analysis of wax from young susceptible and old resistant leaves did not reveal specific compounds involved in ontogenic resistance. Differences in homogalacturonan content in cell walls in susceptible and resistant cells as well as decreased methylesterification of pectin in resistant leaves suggest that polysaccharide composition of the cell wall may play a role in mycelium growth and nutrition.

Background: Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting for cervical cancer screening. We compared both strategies within a population-based study., Methods: The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years ( n = 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, HC2). Screen-positive participants [ASC-US+ or high-risk HC2 (hrHC2)] and a random 5% sample of screen-negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias), and potential harms, including number of colposcopies needed to detect 1 precancerous lesion (NNC), were calculated., Results: In 2,627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Cotesting demonstrated higher sensitivities (HC2 cotesting: 99%; PCR cotesting: 84%), but at the cost of lower specificities (92%-95%) compared with HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Cotesting versus HPV stand-alone showed equivalent relative sensitivity [HC2: 1.06, 95% confidence interval (CI), 1.00-1.21; PCR: 1.07, 95% CI, 1.00-1.27]. Relative specificity of Pap cotesting with either HPV test was inferior to stand-alone HPV. LBC cotesting demonstrated equivalent specificity (both tests: 0.99, 95% CI, 0.99-1.00). NNC was highest for Pap cotesting., Conclusions: Cotesting offers no benefit in detection over stand-alone HPV testing, resulting in more false positive results and colposcopy referrals., Impact: HPV stand-alone screening offers a better balance of benefits and harms than cotesting. See related commentary by Wentzensen and Clarke, p. 432 ., (©2020 American Association for Cancer Research.)

Valeric acid is a C5 fatty acid, naturally produced in low concentrations by specific members of the microbiota of the lower intestinal tract. Effects of valeric acid on intestinal health have been poorly investigated. Valeric acid derivatives can be produced as glyceride esters and added to broiler feed. In the current study, experiments were carried out to evaluate the effect of valeric acid glycerides (GVA) on growth performance, on the morphology of the small intestinal mucosa and on protection against necrotic enteritis. In a first feeding trial, Ross-308 chicks were randomly divided into 2 dietary treatment groups and fed either a non-supplemented diet or a diet supplemented with GVA (1.5 g/kg). In the GVA supplemented group, the feed conversion ratio was significantly decreased during the entire trial period (D1-37). In a second trial, gut wall morphology was evaluated. In broilers fed a GVA-containing diet at 5 g/kg, the villus height/crypt depth ratio in the jejunum was significantly increased (P ≤ 0.05), and the crypt depth was significantly decreased at 28 d. In a third trial, immunohistochemistry showed that the density of glucagon-like peptide-2 immunoreactive cells in jejunal and ileal villi from broilers supplemented with GVA (5 g/kg) was significantly increased (P ≤ 0.05) on d 10. In a necrotic enteritis challenge model, a significant reduction of the number of birds with necrotic lesions was found at d 21, using in-feed supplementation of low and high regimen of GVA. These data show that GVA supplementation to broiler feed can decrease the feed conversion, positively affect the morphology of the small intestinal mucosa, increase the density of glucagon-like peptide-2 producing enteroendocrine cells, and reduce the incidence of necrotic enteritis, making GVA a valuable candidate feed additive for broilers.

The total concentrations of twelve, likely carcinogenic, polycyclic aromatic hydrocarbons (PAHs) (i.e., phenanthrene (Phe), anthracene (An), fluoranthene (Fluo), pyrene (Pyr), benz[a]anthracene (B[a]A), chrysene (Chry), benzo[b]fluoranthene (B[b]F), benzo[k]fluoranthene (B[k]F), benzo[a]pyrene (B[a]P), indeno[1,2,3-cd]pyrene (Ind), dibenz[a,h]anthracene (D[a,h]A), and benzo[g,h,i]perylene (B[g,h]P) in backwash deposits of the 2004 Khao Lak tsunami were carefully investigated and compared with the concentrations of world marine sediments (WMS). In general, ∑12PAHs in this study (i.e., 69.43 ± 70.67 ng g(-1)) were considerably lower than those values observed in marine sediments from Boston (54,253 ng g(-1)), coastal sediments from Barcelona Harbour (15,069 ng g(-1)), and riverine sediment from Guangzhou Channel (12,525 ng g(-1)), but were greater than values from coastal sediments in Rosas Bay (12 ng g(-1)), Santa Ponsa Bay (26 ng g(-1)) and Le Planier (34 ng g(-1)). The total toxic benzo[a]pyrene equivalent (TEQ(Carc)) values calculated for Khao Lak coastal sediments (KCS), Khao Lak terrestrial soils (KTS), and Songkhla Lake sediments (SLS) were 10.3 ± 12.2 ng g(-1), 16.0 ± 47.7 ng g(-1), and 5.67 ± 5.39 ng g(-1), respectively. Concentrations of PAHs at all study sites resulted in risk levels that fell into the "acceptable" range of the US EPA model and were much lower than those of other WMS. The cancer risk levels of PAH content in KCS ranged from 7.44 × 10(-8) to 2.90 × 10(-7), with an average of 1.64 × 10(-7) ± 8.01 × 10(-8); this value is 119 times lower than that of WMS. In addition, soil cleanup target levels (SCTLs) for both non-carcinogens (i.e., Phe, An, Fluo and Pyr) and carcinogens (i.e., B[a]A, Chry, B[b]F, B[k]F, B[a]P, Ind, D[a,h]A and B[g,h,i]P) in the KTS samples were estimated for all target groups, with an average value of 115,902 ± 197,229 ng g(-1)., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

This paper aims to enhance the credibility of applying the sulfur K-edge XANES spectroscopy as an innovative "fingerprint" for characterizing environmental samples. The sensitivities of sulfur K-edge XANES spectra of ten sulfur compound standards detected by two different detectors, namely, Lytle detector (LyD) and Germanium detector (GeD), were studied and compared. Further investigation on "self-absorption" effect revealed that the maximum sensitivities of sulfur K-edge XANES spectra were achieved when diluting sulfur compound standards with boron nitride (BN) at the mixing ratio of 0.1%. The "particle-size" effect on sulfur K-edge XANES spectrum sensitivities was examined by comparing signal-to-noise ratios of total suspended particles (TSP) and particulate matter of less than 10 millionths of a meter (PM(10)) collected at three major cities of Thailand. The analytical results have demonstrated that the signal-to-noise ratios of sulfur K-edge XANES spectra were positively correlated with sulfate content in aerosols and negatively connected with particle sizes. The combination of hierarchical cluster analysis (HCA) and principal component analysis (PCA) has proved that sulfur K-edge XANES spectrum can be used to characterize German terrestrial soils and Andaman coastal sediments. In addition, this study highlighted the capability of sulfur K-edge XANES spectra as an innovative "fingerprint" to distinguish tsunami backwash deposits (TBD) from typical marine sediments (TMS).

Almost 10 years ago, an eleventh protein of influenza A viruses was discovered in a search for CD8+ T-cell epitopes. This protein was named PB1-F2 since it is encoded in the +1 reading frame of the PB1 gene segment. Various studies have shown that PB1-F2 has a pleiotropic effect: (1) The protein can induce apoptosis in a cell type-dependent manner, (2) PB1-F2 is able to promote inflammation, and (3) finally it up-regulates viral polymerase activity by its interaction with the PB1 subunit. These properties could contribute to an enhanced pathogenicity. However, the underlying mechanism is not fully understood yet. New data suggest that some effects of PB1-F2 are strain-specific and host-specific.

As intracellular bacteria, chlamydiae block the apoptotic pathways of their host cells. However, the infection of epithelial cells causes the loss of cell membrane integrity and can result in nonapoptotic death. Normally, cells undergoing necrosis release high-mobility group box 1 protein (HMGB1) that acts as an important proinflammatory mediator. Here, we show that in Chlamydia trachomatis-infected HeLa cells HMGB1 is not translocated from the nucleus to the cytosol and not released from injured cells in increased amounts. At 48 h after infection, degradation of HMGB1 was observed. In infected cells, poly(ADP-ribose) polymerase 1 (PARP-1), a DNA repair enzyme that also regulates HMGB1 translocation, was found to be cleaved into fragments that correspond to a necrosis like pattern of PARP-1 degradation. Cell-free cleavage assays and immunoprecipitation using purified proteolytic fractions from infected cells demonstrated that the chlamydial-protease-like activity factor (CPAF) is responsible for the cleavage of both HMGB1 and PARP-1. Proteolytic cleavage of PARP-1 was accompanied by a significant decrease in the enzymatic activity in a time-dependent manner. The loss of PARP-1 function obviously affects the viability of Chlamydia-infected cells because silencing of PARP-1 in uninfected HeLa cells with specific small interfering RNA results in increased cell membrane permeability. Our findings suggest that the Chlamydia-specific protease CPAF interferes with necrotic cell death pathways. By the degradation of HMGB1 and PARP-1, the pathogen may have evolved a strategy to reduce the inflammatory response to membrane-damaged cells in vivo.

Background: Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC). We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines., Results: In contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4-Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip., Conclusions: S4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC.

Objectives: The objective of this study was to develop and pretest a questionnaire to assess the practice of withdrawal of life-sustaining treatment in the NICU on the basis of the experiences of bereaved parents., Methods: We conducted semistructured interviews with 11 parents whose infants had undergone withdrawal of life-sustaining treatment in the NICU at McMaster University Medical Centre to obtain their views on helpful practices. Interviews continued until no new items were obtained (ie, saturation point). A total of 370 items were distilled into 82 questionnaire statements on care by a multidisciplinary team and grouped for analysis into 6 domains: communication, quality of care, quality of life, shared decision-making, withdrawal of life-sustaining treatment process, and bereavement care. Respondents were asked to rank how frequently events occurred on a 7-point Likert scale anchored from 1 = never to 7 = always. A score of >5 was considered favorable. The questionnaire was distributed to a pretest sample of perinatal social workers who attended a bereavement workshop at an international conference., Results: The response rate was 48%. Respondents ranked items that pertained to the withdrawal of life-sustaining treatment process highest, indicating that items were done well. Items related to quality of care and bereavement care ranked lowest. Other domains ranked as follows: communication, shared decision-making, and quality of life. Consistency of items within domains was tested by Cronbach's alpha and split-half testing and were >0.6 for most domains., Conclusions: Parents' views on important aspects of end-of-life care in the NICU were incorporated into a quality assurance questionnaire. Pretesting assessed the performance of the instrument and the perceptions of social workers on the effectiveness of end-of-life practices. Respondents identified that parents' practical needs were met during the withdrawal process but were not consistently met in regard to the quality of in-hospital and follow-up bereavement care.

Background: Today, there is a growing need in bioinformatics to combine available software tools into chains, thus building complex applications from existing single-task tools. To create such workflows, the tools involved have to be able to work with each other's data--therefore, a common set of well-defined data formats is needed. Unfortunately, current bioinformatic tools use a great variety of heterogeneous formats., Results: Acknowledging the need for common formats, the Helmholtz Open BioInformatics Technology network (HOBIT) identified several basic data types used in bioinformatics and developed appropriate format descriptions, formally defined by XML schemas, and incorporated them in a Java library (BioDOM). These schemas currently cover sequence, sequence alignment, RNA secondary structure and RNA secondary structure alignment formats in a form that is independent of any specific program, thus enabling seamless interoperation of different tools. All XML formats are available at http://bioschemas.sourceforge.net, the BioDOM library can be obtained at http://biodom.sourceforge.net., Conclusion: The HOBIT XML schemas and the BioDOM library simplify adding XML support to newly created and existing bioinformatic tools, enabling these tools to interoperate seamlessly in workflow scenarios.

TRANSPATH is a database about signal transduction events. It provides information about signaling molecules, their reactions and the pathways these reactions constitute. The representation of signaling molecules is organized in a number of orthogonal hierarchies reflecting the classification of the molecules, their species-specific or generic features, and their post-translational modifications. Reactions are similarly hierarchically organized in a three-layer architecture, differentiating between reactions that are evidenced by individual publications, generalizations of these reactions to construct species-independent 'reference pathways' and the 'semantic projections' of these pathways. A number of search and browse options allow easy access to the database contents, which can be visualized with the tool PathwayBuildertrade mark. The module PathoSign adds data about pathologically relevant mutations in signaling components, including their genotypes and phenotypes. TRANSPATH and PathoSign can be used as encyclopaedia, in the educational process, for vizualization and modeling of signal transduction networks and for the analysis of gene expression data. TRANSPATH Public 6.0 is freely accessible for users from non-profit organizations under http://www.gene-regulation.com/pub/databases.html.

EndoNet is a new database that provides information about the components of endocrine networks and their relations. It focuses on the endocrine cell-to-cell communication and enables the analysis of intercellular regulatory pathways in humans. In the EndoNet data model, two classes of components span a bipartite directed graph. One class represents the hormones (in the broadest sense) secreted by defined donor cells. The other class consists of the acceptor or target cells expressing the corresponding hormone receptors. The identity and anatomical environment of cell types, tissues and organs is defined through references to the CYTOMER ontology. With the EndoNet user interface, it is possible to query the database for hormones, receptors or tissues and to combine several items from different search rounds in one complex result set, from which a network can be reconstructed and visualized. For each entity, a detailed characteristics page is available. Some well-established endocrine pathways are offered as showcases in the form of predefined result sets. These sets can be used as a starting point for a more complex query or for obtaining a quick overview. The EndoNet database is accessible at http://endonet.bioinf.med.uni-goettingen.de/.

The thioamide derivatives 3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-[(2-methyl-1-thioxo- propyl)amino]thymidine 1 and 3'-deoxy-5'-O-(4,4'-dimethoxytrityl)-3'-((6-([(9H-(fluo-ren-9- ylmethoxy)carbonyl]-amino)-1-thioxohexyl)amino) thymidine 2 were synthesized by regioselective thionation of their corresponding amides 7 and 8 with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson's reagent). The thioamides were converted into the corresponding 5'-triphosphates 3 and 4. Compound 3 was chosen for DNA sequencing experiments and 4 was further labelled with fluorescein.

To determine the degree to which the leptin receptor mutation (fa) influences the responsiveness to leptin during the first postnatal week, we injected recombinant leptin (600 pmol. g-1. day-1 sc from day 1 to day 7) into wild-type (+/+), heterozygous (+/fa), and fatty (fa/fa) rat pups. Growth and final body fat content of these leptin-treated pups were compared with those of saline-treated littermates of the same genotype. The body mass of the leptin-treated +/+ pups, but not that of the +/fa and fa/fa pups, increased more slowly than that of their respective controls, and fat content at day 7 was reduced by 37% in +/+ pups, by 22% in +/fa pups, but not at all in fa/fa pups. Plasma leptin remained excessively high throughout the day under this treatment, but a 30-fold lower leptin dose, causing only moderate changes of plasma leptin, still reduced the body fat of +/+ pups significantly. We conclude that leptin participates in the control of even the earliest stages of fat deposition and that the response to supraphysiological doses of leptin is markedly reduced in 1-wk-old pups with one fa allele and absent in pups with two fa alleles.

Objective: To find out whether leptin can attenuate hypometabolic torpor-like states of metabolic rate (MR) in adult lean animals, as it attenuates the morning suppression of thermoregulatory thermogenesis in suckling-age rat pups., Design: Leptin effects on MR and food intake were studied in mice aged 4-7 months, in which a high incidence of exaggerated circadian reductions of MR had been induced by chronic food-restriction and, for comparison, in free-feeding mice., Protocol: Continuous recordings of MR, for a group of seven mice maintained at an ambient temperature of 24 degrees C, while they were repeatedly-with pauses of at least six days-treated for three consecutive days with either recombinant murine leptin (20, 200 or 600 pmol x g(-1) x d[-1]) or saline., Results: Leptin treatment caused dose-dependent 5-15% increases in energy expenditure by moderating the decreases in MR during the circadian minima, without affecting either the MR during the circadian maxima or food intake. Similar treatment of free-feeding mice caused dose-dependent decreases of food intake without changing MR., Conclusion: Leptin controls thermoregulatory energy expenditure when food supplies are scarce and changes food intake, rather than energy expenditure, when food is abundant.

The possibility that the leptin receptor (LEPR) mediates autocrine regulation of leptin expression in adipose tissue was examined in 10-day-old Zucker rat pups with different copy numbers of the leptin receptor mutation (Lepr(fa)). Plasma leptin concentrations and adipose tissue mRNA levels for leptin were related to copy number of the mutation (fa/fa > fa/+ > +/+). These relationships were independent of plasma insulin concentration. Reduced copy number for the functional leptin receptor apparently results in a diminished negative feedback signal to the leptin gene in adipose tissue. Thus, leptin appears to close a short regulatory loop controlling its own synthesis in adipose tissue.

To find out whether the most characteristic physiological traits distinguishing suckling-age fa/fa pups from lean littermates also differ between +/+ and +/fa littermates, we analyzed the body composition and cold defense of 7- and 16-day-old pups and the plasma concentrations of insulin, glucose, triglycerides, and free fatty acids in 16-day-old pups. Zucker rat x Brown Norway hybrid pups were genotyped by using a molecular marker within 0.5 cM of the fa gene. At both ages the +/fa pups had significantly more body fat than their +/+ littermates. At 7 days this difference was as large as that between +/fa and fa/fa pups, but at 16 days it was only one-seventh of the fa/fa vs. +/fa difference. In contrast, there were no heterozygote differences for three parameters that show crucial abnormalities in the fa/fa pups: thermoregulatory thermogenesis and plasma concentrations of insulin and triglycerides. The physiological mechanisms underlying the increased fat content of +/fa pups thus differ from those known to fuel most of the excessive fat deposition of their fa/fa littermates.