Update on the possible nutritional importance of silicon

Convincing evidence that silicon is a bioactive beneficial trace element continues to accumulate. The evidence, which has come from human, animal, and in vitro studies performed by several laboratories, indicate that silicon in nutritional and supra nutritional amounts promotes bone and connective tissue health, may have a modulating effect on the immune or inflammatory response, and has been associated with mental health. A plausible mechanism of action for the beneficial effects of silicon is the binding of hydroxyl groups of polyols such that it influences the formation and/or utilization of glycosaminoglycans, mucopolysaccharides, and collagen in connective tissue and bone. In addition, silicon may affect the absorption, retention or action of other mineral elements (e.g., aluminum, copper, magnesium). Based on findings from both animal and human experiments, an intake of silicon of near 25 mg/d would be a reasonable suggestion for an adequate intake that would assure its nutritional benefits. Increased intakes of silicon through consuming unrefined grains, certain vegetables, and beverages and cereals made from grains should be recognized as a reasonable dietary recommendation.     

Role of carotenoid β-cryptoxanthin in bone homeostasis

Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Aging induces bone loss due to decreased osteoblastic bone formation and increased osteoclastic bone resorption. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public health problem. Nutritional factors may play a role in the prevention of bone loss with aging. Among various carotenoids (carotene and xanthophylls including beta (β)-cryptoxanthin, lutein, lycopene, β-carotene, astaxanthin, and rutin), β-cryptoxanthin, which is abundant in Satsuma mandarin orange (Citrus unshiu MARC.), has been found to have a stimulatory effect on bone calcification in vitro. β-cryptoxanthin has stimulatory effects on osteoblastic bone formation and inhibitory effects on osteoclastic bone resorption in vitro, thereby increasing bone mass. β-cryptoxanthin has an effect on the gene expression of various proteins that are related osteoblastic bone formation and osteoclastic bone resororption in vitro. The intake of β-cryptoxanthin may have a preventive effect on bone loss in animal models for osteoporosis and in healthy human or postmenopausal women. Epidemiological studies suggest a potential role of β-cryptoxanthin as a sustainable nutritional approach to improving bone health of human subjects. β-Cryptoxanthin may be an osteogenic factor in preventing osteoporosis in human subjects.     

Piwi/piRNAs control food intake by promoting neuropeptide F expression in locusts

Animal feeding, which directly affects growth and metabolism, is an important physiological process. However, the contribution of PIWI proteins and PIWI‐interacting RNAs (piRNAs) to the regulatory mechanism of animal feeding is unknown. Here, we report a novel function of Piwi and piRNAs in regulating food intake in locusts. Our study shows that the locust can serve as a representative species for determining PIWI function in insects. Knockdown of Piwi1 expression suppresses anabolic processes and reduces food consumption and body weight. The reduction in food intake by knockdown of Piwi1 expression results from decreased expression of neuropeptide NPF1 in a piRNA‐dependent manner. Mechanistically, intronic piRNAs might enhance RNA splicing of NPF1 by preventing hairpin formation at the branch point sites. These results suggest a novel nuclear PIWI/piRNA‐mediated mechanism that controls food intake in the locust nervous system.     

Seasonal Variation of Boron and Fluoride in Tilapia nilotica from an Egyptian Fish Farm in Relation to Human Health Hazard Assessment

This study evaluated the seasonal accumulation of boron and fluoride in different tissues of a common edible fish, Tilapia nilotica, from an Egyptian fish farm as well as their hazard to human health. Among all the determined fish tissues, brain, liver, and bone were the ones that accumulated the highest boron and fluoride contents. Interestingly, flesh tissue showed the lowest boron and fluoride concentrations (0.30 ± 0.06 and 2.50 ± 1.57 μg/g, respectively). Statistical analyses using Pearson correlation matrix and multiple regression procedures indicated that boron accumulation was highest amongst flesh, liver, brain, and bone tissues. Additionally, fluoride content in water affects its abundance in the different fish tissues: flesh, gills, bone, and skin. Human hazard assessment of fluoride and boron from water, sediment, and fish flesh tissue was studied using calculations that considered chronic daily intake from water, sediment, and fish; chronic exposure from dermal contact and ingestion of water; and fish as well as a single acute human dose. These calculations indicated that the consumption of Tilapia nilotica is still safe as regards boron intake, but for fluoride, it may pose a hazard to human health in the long term.     

Silicon: A neglected micronutrient essential for bone health

Bone matrix is predominantly made up of collagen, and in vitro and in animal models studies have shown that silicon is linked to glycosaminoglycans and plays an important role in the formation of cross-links between collagen and proteoglycans, determining the beneficial effects on strength, composition, and mechanical properties of bone. However, there are still no precise indications regarding a possible role of silicon on bone health in humans. Given this background, the aim of this narrative review was to consider the effectiveness of silicon dietary intake and silicon dietary supplementation (alone or with other micronutrients), in order to suggest a daily dosage of Si supplementation, on bone mineral density in humans. This review included eight eligible studies: four regarding dietary intake and four considering supplementation with silicon alone or with other nutrients. Despite the number of studies considered being low, the number of subjects studied is high (10012) and the results are interesting. Although to date the available scientific evidences are not considered valid enough to allow to establish an adequate level of Silicon intake, based on extrapolations from the data obtained with studies on animal and human models, it has been suggested that an adequate intake in order to promote beneficial effects for bone could be considered to be around 25 mg silicon/day. As for silicon dietary supplements, it has been shown that the combined treatment with orthosilicic acid (6 mg), calcium, and vitamin D has a potentially beneficial effect on femoral BMD compared to only use of calcium and vitamin D.     

A review of the functional effects of pine nut oil,pinolenic acid and its derivative eicosatrienoic acid and their potential health benefits

Pine nut oil (PNO) is rich in a variety of unusual delta-5-non-methylene-interrupted fatty acids (NMIFAs), including pinolenic acid (PLA; all cis-5,-9,-12 18:3) which typically comprises 14 to 19% of total fatty acids. PLA has been shown to be metabolised to eicosatrienoic acid (ETA; all cis-7,-11,-14 20:3) in various cells and tissues. Here we review the literature on PNO, PLA and its metabolite ETA in the context of human health applications. PNO and PLA have a range of favourable effects on body weight as well as fat deposition through increased energy expenditure (fatty acid oxidation) and decreased food energy intake (reduced appetite). PNO and PLA improve blood and hepatic lipids in animal models and insulin sensitivity in vitro and reduce inflammation and modulate immune function in vitro and in animal models. The few studies which have examined effects of ETA indicate it has anti-inflammatory properties. Another NMIFA from PNO, sciadonic acid (all cis-5,-11,-14 20:3), has generally similar properties to PLA where these have been investigated. There is potential for human health benefits from PNO, its constituent NMIFA PLA and the PLA derivative ETA. However further studies are needed to explore the effects in humans.     

Diadenosine phosphates and S-adenosylmethionine: novel boron binding biomolecules detected by capillary electrophoresis.

There is evidence that boron has a physiological role in animals and humans, but the search for boron binding biomolecules has been difficult because useful radioactive boron isotopes do not exist. To overcome this limitation we used capillary electrophoresis to identify and quantify boron binding to biomolecules by detecting the negative charge boron imparts to ligands. The effect of molecular structure and proximal electronic charges of adenosine and molecules with adenosine moieties including S-adenosylmethionine (SAM) and diadenosine polyphosphates (Ap(n)A) were compared. The boron affinity of the test species varied with the rank order SAM congruent with Ap(6)A congruent with Ap(5)A>Ap(4)A>Ap(3)A congruent with NAD(+)>Ap(2)A>NADH congruent with 5'ATP>5'ADP>5'AMP>adenosine>3'AMP congruent with 2'AMP congruent with cAMP congruent with adenine. Test species with vicinal cis-diols bound boron; species without those moieties did not. Boron binding affinity increased when proximal cationic moieties were present. Anionic moieties remote from the cis-hydroxyl binding site also positively influenced boron binding affinity. In the Ap(n)A species, cooperative complexing of boron between the terminal ribose moieties apparently occurred. In these species boron affinity greater than expected for two monocomplexes was observed and binding affinities increased as more phosphate groups (beyond three) were present separating the terminal moieties. Our results indicate that Ap(6)A, Ap(5)A, Ap(4)A, Ap(3)A, and SAM have higher affinities for boron than any other currently recognized boron ligand present in animal tissues including NAD(+).     

Why boron?

It is now more than 80 years since boron was convincingly demonstrated to be essential for normal growth of higher plants. However, its biochemical role is not well understood at the moment. Several recent reviews propose that B is implicated in three main processes: keeping cell wall structure, maintaining membrane function, and supporting metabolic activities. However, in the absence of conclusive evidence, the primary role of boron in plants remains elusive. Besides plants, growth of specific bacteria, such as heterocystous cyanobacteria and the recently reported actinomycetes of the genus Frankia, requires B, particularly for the stability of the envelopes that control the access of the nitrogenase-poisoning oxygen when they grow under N₂-fixing conditions. Likewise, a role for B for animal embryogenesis and other developmental processes is being established. Finally, a new feature of the role of boron comes from signaling mechanisms for communication among bacteria and among legumes and rhizobia leading to N₂-fixing symbiosis, and it is possible that new roles for B, based on its special chemistry and its interaction with Ca would appear in the world of signal transduction pathways. In conclusion, the diversity of roles played by B might indicate that either the micronutrient is involved in numerous processes or that its deficiency has a pleiotropic effect. The arising question is why such an element? Since all of the roles clearly established for B are related to its capacity to form diester bridges between cis-hydroxyl-containing molecules, we propose that the main reason for B essentiality is the stabilization of molecules with cis-diol groups turning them effective, irrespectively of their function.     

Selenium nanovirus and its cytotoxicity in selenite-exposed higher living organisms

Selenium (Se) is an essential micronutrient in living organisms, having a narrow margin between essential and potentially toxic intake/exposure. Thus, the biochemistry of Se in living organisms must be studied in-depth to determine the underlying mechanism of Se cytotoxicity. In this study, we report the emergence of selenium nanovirus (SeNVs) in selenite-exposed fish (freshwater and saltwater) and plants (dryland) and its toxicity in them. SeNVs were found in both the abdomen and tail of Oryzias melastigma and saltwater Rhodeus ocellatus, which led to their death. The occurrence of the intracellular assembly of SeNVs was observed in the roots and leaves of corn Zea mays, but not in those of Limnobium laevigatum. SeNVs led to the death of Z. mays but caused chronic toxicity in L. laevigatum. SeNVs should be a system or structure that dissipates the intracellular redox gradients of the host cells, with simple information consisting Se–O, Se–N, or Se–S bond, that would ensure elemental Se ligand binding with nearly specific biomolecules in host cells, thereby maintaining their composition and stabilizing their structure. The multiple toxic effects of Se, therefore, could be the consequence of increase of entropy in the host cells caused by the intracellular assembly of SeNVs. This study may provide an insight into the underlying mechanism of Se in environmental toxicology and its applications in human health.     

Transmembrane partitioning of boron and other elements in RAW 264.7 and HL60 cell cultures

The trace element boron is essential for all higher plants and is beneficial or has been established as essential for several animal models of human nutrition. To help identify the biomolecules that require boron for function in humans, we determined whether intracellular boron is retained against a concentration gradient. Cells (Abelson leukemia virus BALB murine monocyte-macrophage RAW 264.7 [RAW] and HL60) and supplemented media (Dulbecco’s modified essential media [+10% fetal calf serum] and Iscove’s modified Dulbecco’s medium [+5% fetal calf serum], respectively) were analyzed for mineral concentrations after culture and subculture. Special corrections were made for trapped extracellular media in cell pellets and endocytosed media. For RAW cells, the partitioning coefficients (PC; intracellular/extracellular ratios) were, in rank order, as follows: Mn, 110; Fe, 67; P, 65; Zn, 32; K, 15; Cu, 7.1; Mg, 4.3; B, 1.7; Ca, 0.4; Na, 0.3. For HL60 cells, the partitioning coefficients were, in rank order, as follows: Mn, 212; Zn, 211; P, 123; K, 21; Fe, 16; Mg, 11; B, 1.7; Ca, 0.8; Na, 0.3. Trapped extracellular media was estimated to be 6.7±0.8%; trapped extracellular and endocytosed media together was 24.8±0.3% of the mass within the isolated cell pellets. The partitioning coefficients indicate a positive gradient for intracellular accumulation of boron, zinc, phosphorus, managanese, magnesium, potassium, iron, and copper in RAW264.7 and HL60 cells. Specifically, the data indicate the existence of a selective boron-binding molecular species within the cell or the existence of a boron-specific membrane transporter.     

The justification for providing dietary guidance for the nutritional intake of boron

Because a biochemical function has not been defined for boron (B), its nutritional essentiality has not been firmly established. Nonetheless, dietary guidance should be formulated for B, because it has demonstrated beneficial, if not essential, effects in both animals and humans. Intakes of B commonly found with diets abundant in fruits, vegetables, legumes, pulses, and nuts have effects construed to be beneficial in macromineral, energy, nitrogen, and reactive oxygen metabolism, in addition to enhancing the response to estrogen therapy and improving psychomotor skills and cognitive processes of attention and memory. Perhaps the best-documented beneficial effect of B is on calcium (Ca) metabolism or utilization, and thus, bone calcification and maintenance. The paradigm emerging for the provision of dietary guidance that includes consideration of the total health effects of a nutrient, not just the prevention of a deficiency disease, has resulted in dietary guidance for chromium (Cr) and fluoride; both of these elements have beneficial effects in humans, but neither has a defined biochemical function. Knowledge of B nutritional effects in humans equals or is superior to that of Cr and fluoride; thus, establishing a dietary reference intake for B is justified. An analysis of both human and animal data suggests that an acceptable safe range of population mean intakes of B for adults could well be 1–13 mg/d. Recent findings indicate that a significant number of people do not consistently consume more than 1 mg B/d; this suggests that B could be a practical nutritional or clinical concern.     

Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity

Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX–2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA–7 and lipopolysaccharide (LPS) stimulated primary monocytes support the hypothesis that polyphenols can effect COX–2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC₅₀ values of 1.5 μM, 2.6 μM, 2.8 μM and 7.4 μM. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX–2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested.     

Types of fiber and gut microbiota composition and diversity among arab females

ObjectivesDietary fiber is recognized as an important nutrient for gut health. However, research on the relations of different types of fibers (soluble and insoluble) to the human microbiota health is limited. This study aimed to identify whether higher habitual intake of soluble and/or insoluble fiber have a different influence on the composition, diversity, and abundance of microbiota.MethodsWe examined the fecal microbial composition of 92 healthy females aged 18 and above using the novel shotgun metagenomics sequencing technique. The habitual fiber intake was determined using the Saudi food frequency questionnaire. Pearson’s correlation was used for the correlations between total, soluble, and insoluble fiber and gut microbiota. α- and β-diversities were applied to acquire the distinctions in the relative abundances of bacterial taxa.ResultsOur findings show that higher dietary fiber, particularly insoluble fiber, was significantly correlated with the abundances of Bacteroides_u_s, Bacteroides uniformis, and Lactobacillus acidophilus (r = 0.26, 0.29, 0.26, p-value < 0.05, respectively). Non-significant difference was noted in the microbial α-diversity and β-diversity in low and high soluble/insoluble dietary fiber.ConclusionsCurrent findings suggest that insoluble dietary-fiber intake is favorably correlated with the health of the human gut microbiota. However, further investigations are necessary to identify the effect of types of fiber on the specific species identified in this study.     

Betaine chemistry,roles, and potential use in liver disease

BackgroundBetaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs.Scope of reviewThe remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease.Major conclusionsA significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices.General significanceThe accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease.     

C1q/TNF-related Protein 4 (CTRP4) Is a Unique Secreted Protein with Two Tandem C1q Domains That Functions in the Hypothalamus to Modulate Food Intake and Body Weight

CTRP4 is a unique member of the C1q family, possessing two tandem globular C1q domains. Its physiological function is poorly defined. Here, we show that CTRP4 is an evolutionarily conserved, ∼34-kDa secretory protein expressed in the brain. In human, mouse, and zebrafish brain, CTRP4 expression begins early in development and is widespread in the central nervous system. Neurons, but not astrocytes, express and secrete CTRP4, and secreted proteins form higher-order oligomeric complexes. CTRP4 is also produced by peripheral tissues and circulates in blood. Its serum levels are increased in leptin-deficient obese (ob/ob) mice. Functional studies suggest that CTRP4 acts centrally to modulate energy metabolism. Refeeding following an overnight fast induced the expression of CTRP4 in the hypothalamus. Central administration of recombinant protein suppressed food intake and altered the whole-body energy balance in both chow-fed and high-fat diet-fed mice. Suppression of food intake by CTRP4 is correlated with a decreased expression of orexigenic neuropeptide (Npy and Agrp) genes in the hypothalamus. These results establish CTRP4 as a novel nutrient-responsive central regulator of food intake and energy balance.     

Mutations in LRRC50 Predispose Zebrafish and Humans to Seminomas

Seminoma is a subclass of human testicular germ cell tumors (TGCT), the most frequently observed cancer in young men with a rising incidence. Here we describe the identification of a novel gene predisposing specifically to seminoma formation in a vertebrate model organism. Zebrafish carrying a heterozygous nonsense mutation in Leucine-Rich Repeat Containing protein 50 (lrrc50 also called dnaaf1), associated previously with ciliary function, are found to be highly susceptible to the formation of seminomas. Genotyping of these zebrafish tumors shows loss of heterozygosity (LOH) of the wild-type lrrc50 allele in 44.4% of tumor samples, correlating with tumor progression. In humans we identified heterozygous germline LRRC50 mutations in two different pedigrees with a family history of seminomas, resulting in a nonsense Arg488* change and a missense Thr590Met change, which show reduced expression of the wild-type allele in seminomas. Zebrafish in vivo complementation studies indicate the Thr590Met to be a loss-of-function mutation. Moreover, we show that a pathogenic Gln307Glu change is significantly enriched in individuals with seminoma tumors (13% of our cohort). Together, our study introduces an animal model for seminoma and suggests LRRC50 to be a novel tumor suppressor implicated in human seminoma pathogenesis.     

Influence of dietary strategy on progression of health and behaviour in mule ducks reared for fatty liver production

Overfeeding in ducks is questioned because forced introduction of food into the animal and metabolic overload may induce damage to health and discomfort. In this context, the objective of our experiment was to measure the impact of dietary strategy on the progression of animal status evaluated through 28 health and behavioural indicators in ducks reared for fatty liver production. To do this, 320 ducks were forced-fed twice a day from 70 to 90 days of age including 10 days of overfeeding (87 to 96 days). They were divided into two groups differing in the feeding strategy during overfeeding period: a moderate feed intake (MI, an average of 376 g of maize flour per meal, n = 160 ducks) or at high feed intake (HI, 414 g/meal, n = 160 ducks). We evaluated 28 indicators related to Good feeding (n = 3), Good housing (n = 4), Good health (n = 10) and Appropriate behaviour (n = 11) principles, taken from the European Welfare Quality Consortium® at four stages: before overfeeding (BEF; 80 days), at the beginning (88 days), the middle (MID; 92 days) or the end of overfeeding (END; 96 days). Animals were slaughtered at 93 and 97 days to measure fatty liver weight at MID and END stages (n = 80 per group). The results showed that dietary strategy influenced the fatty liver weight at MID (+23% in HI v. MI group; P < 0;05) and END stage (+23%; P < 0.05). Assessment stage influenced 13 of the 28 indicators measured. Among these 13 indicators, (i) BEF differed from END stage for 7 indicators and (ii) the dietary strategy degraded all the indicators chosen to evaluate the Good feeding (2/2) principle, but had no effect on the indicators related to the Good health (0/4) principle while (iii) most of the indicators that evaluated Good housing (2/3) and Appropriate behaviour (2/4) principles were affected by an interaction between both factors. Our results suggest that (i) duck fattening status, including the fatty liver weight, and several welfare indicators progressed during the fatty liver production process; and (ii) feeding strategy influenced or even interacted with this progression.     

Progenitor expansion in apc mutants is mediated by Jak/Stat signaling

Background

We recently identified a novel oncogene, Cancer-upregulated gene 2 (CUG2), which is essential for kinetochore formation and promotes tumorigenesis in mammalian cells. However, the in vivo function of CUG2 has not been studied in animal models.

Results

To study the function of CUG2 in vivo, we isolated a zebrafish homologue that is expressed specifically in the proliferating cells of the central nervous system (CNS). Morpholino-mediated knockdown of cug2 resulted in apoptosis throughout the CNS and the development of neurodegenerative phenotypes. In addition, cug2-deficient embryos contained mitotically arrested cells displaying abnormal spindle formation and chromosome misalignment in the neural plate.

Conclusions

Therefore, our findings suggest that Cug2 is required for normal mitosis during early neurogenesis and has functions in neuronal cell maintenance, thus demonstrating that the cug2 deficient embryos may provide a model system for human neurodegenerative disorders.     

RNA Protein Granules Modulate tau Isoform Expression and Induce Neuronal Sprouting

The neuronal microtubule-associated protein Tau is expressed in different variants, and changes in Tau isoform composition occur during development and disease. Here, we investigate a potential role of the multivalent tau mRNA-binding proteins G3BP1 and IMP1 in regulating neuronal tau expression. We demonstrate that G3BP1 and IMP1 expression induces the formation of structures, which qualify as neuronal ribonucleoprotein (RNP) granules and concentrate multivalent proteins and mRNA. We show that RNP granule formation leads to a >30-fold increase in the ratio of high molecular weight to low molecular weight tau mRNA and an ∼12-fold increase in high molecular weight to low molecular weight Tau protein. We report that RNP granule formation is associated with increased neurite formation and enhanced process growth. G3BP1 deletion constructs that do not induce granule formation are also deficient in inducing neuronal sprouting or changing the expression pattern of tau. The data indicate that granule formation driven by multivalent proteins modulates tau isoform expression and suggest a morphoregulatory function of RNP granules during health and disease.     

Human Salmonella Clinical Isolates Distinct from Those of Animal Origin

The global trend toward intensive livestock production has led to significant public health risks and industry-associated losses due to an increased incidence of disease and contamination of livestock-derived food products. A potential factor contributing to these health concerns is the prospect that selective pressure within a particular host may give rise to bacterial strain variants that exhibit enhanced fitness in the present host relative to that in the parental host from which the strain was derived. Here, we assessed 184 Salmonella enterica human and animal clinical isolates for their virulence capacities in mice and for the presence of the Salmonella virulence plasmid encoding the SpvB actin cytotoxin required for systemic survival and Pef fimbriae, implicated in adherence to the murine intestinal epithelium. All (21 of 21) serovar Typhimurium clinical isolates derived from animals were virulent in mice, whereas many (16 of 41) serovar Typhimurium isolates derived from human salmonellosis patients lacked this capacity. Additionally, many (10 of 29) serovar Typhimurium isolates derived from gastroenteritis patients did not possess the Salmonella virulence plasmid, in contrast to all animal and human bacteremia isolates tested. Lastly, among serovar Typhimurium isolates that harbored the Salmonella virulence plasmid, 6 of 31 derived from human salmonellosis patients were avirulent in mice, which is in contrast to the virulent phenotype exhibited by all the animal isolates examined. These studies suggest that Salmonella isolates derived from human salmonellosis patients are distinct from those of animal origin. The characterization of these bacterial strain variants may provide insight into their relative pathogenicities as well as into the development of treatment and prophylactic strategies for salmonellosis.