The colica Pictonum or colic of Poitou, under these and many other names, was a frequent, widespread, and deadly disease from Roman times until the eighteenth century. Its unique pathognomonic, notably a severe colic succeeded by paralysis and other central nervous system dysfunction, makes it possible to identify the disease with certainty as chronic lead disease, usually caused by the ingestion of lead-adulterated wines. The custom of sweetening and preserving sour wines with lead-containing additives is traced to the Romans. They had made the empirical discovery that sapa, a syrup prepared by concentrating must in a lead vessel, kept wine from spoiling and that it had, moreover, an agreeable flavour.
Reports of outbreaks of the colica Pictonum appear in the medical literature from Roman times, but the correct aetiology of the disease was not discovered until the seventeenth century following a series of outbreaks in Southern Germany which were related to unfavourable climatic and political conditions. The connexion between the disease and prevailing methods for “correcting” wines was drawn in 1696 by Eberhard Gockel, then the city physician of Ulm. This achievement can be traced to his familiarity with Samuel Stockhausen's work on plumbism among miners and potters, as well as to the favourable epidemiological situation presented by Gockel's monastic patients.
From the literary evidence assembled here and from experimental determinations of the lead content of sapa and similar concentrates, it is possible to estimate the lead levels and toxicity of wines from various eras. The levels range up to 80 mg/l and make it apparent that many wines were sufficiently toxic to account for the incidence and severity of the colica Pictonum. Explanations for the disastrous persistence of the colic of Poitou are discussed, as are the similarities between Gockel's approach and the methods of modern environmental medicine.
Neoculin (NCL), a protein with sweetness approximately 500-fold that of sugar, can be utilized as a nonglycemic sweetener. It also has taste-modifying activity to convert sourness to sweetness. NCL is a heterodimer composed of an N-glycosylated acidic subunit (NAS) and a basic subunit (NBS), which are conjugated by disulfide bonds. For the production of recombinant NCL (rNCL) by Aspergillus oryzae, α-amylase with a KEX2 cleavage site, -K-R-, was fused upstream of each of NAS and NBS and the resulting fusion proteins were simultaneously expressed. For accurate and efficient cleavage of the fusion construct by KEX2-like protease, a triglycine motif was inserted after the KEX2 cleavage site. As NBS showed lower production efficiency than did NAS, a larger amount of the NBS expression plasmid than of NAS expression plasmid was introduced during cotransformation, resulting in successful production of rNCL in the culture medium. Moreover, to obtain a higher production yield of rNCL, the active form of hacA cDNA encoding a transcription factor that induces an unfolded protein response was cloned and expressed constitutively. This resulted in a 1.5-fold increase in the level of rNCL production (2.0 mg/liter). rNCL was purified by chromatography, and its NAS was found to be N-glycosylated as expected. The original sweetness and taste-modifying activity of rNCL were comparable to those of native NCL when confirmed by calcium imaging with human embryonic kidney cells expressing the human sweet taste receptor and by sensory tests.
Perception of temporal patterns is critical for speech, movement, and music. In the auditory domain, perception of a regular pulse, or beat, within a sequence of temporal intervals is associated with basal ganglia activity. Two alternative accounts of this striatal activity are possible: “searching” for temporal regularity in early stimulus processing stages or “prediction’ of the timing of future tones after the beat is found (relying on continuation of an internally generated beat). To resolve between these accounts, we used functional magnetic resonance imaging (fMRI) to investigate different stages of beat perception. Participants heard a series of beat and nonbeat (irregular) monotone sequences. For each sequence, the preceding sequence provided a temporal beat context for the following sequence. Beat sequences were preceded by nonbeat sequences, requiring the beat to be found anew (“beat finding” condition), or by beat sequences with the same beat rate (“beat continuation”), or a different rate (“beat adjustment”). Detection of regularity is highest during beat finding, whereas generation and prediction are highest during beat continuation. We found the greatest striatal activity for beat continuation, less for beat adjustment, and the least for beat finding. Thus, the basal ganglia's response profile suggests a role in beat prediction, not in beat finding.
auditory perception; basal ganglia; beat perception; fMRI; music; prediction; rhythm; timing
Carbon isotopic signatures (“δ13C”) might reflect consumption of corn- and cane-based sweeteners. The authors hypothesized that the δ13C value of human serum is higher for individuals with high versus low intakes of corn- and cane-based sweeteners (measured as sweetened beverage intake). They conducted a cross-sectional study within the Atherosclerosis Risk in Communities Magnetic Resonance Imaging study (Maryland, 2005–2006). Diet was assessed by food frequency questionnaire, and blinded serum samples were assayed by natural abundance stable isotope mass spectroscopy. Studied were 186 participants (53% male; mean age, 71 years; mean body mass index, 30 kg/m2). Serum δ13C values for individuals with high sweetened beverage intakes were significantly higher than for those with low intakes (−19.15‰ vs. −19.47‰, P < 0.001). Serum δ13C value increased 0.20‰ for every serving/day of sweetened beverages (P < 0.01). The association between sweetened beverages and serum δ13C value remained significant after adjustment for confounding by corn-based product intake (P < 0.001). Serum δ13C values were also associated with waist circumference, body mass index, and waist-to-hip ratio. This study provides the first known evidence that the δ13C value of human serum differs between persons consuming low and high amounts of sweets. Within the proper framework, serum δ13C value could be developed into an objective biomarker promoting more reliable assessment of dietary sweets intake.
biological markers; body mass index; diet; isotope labeling; sweetening agents
A portable and cost-effective real-time cardiotoxicity biosensor was developed using a CMOS imaging module extracted from a commercially available webcam. The detection system consists of a CMOS imaging module, a white LED and a pinhole. Real-time image processing was conducted by comparing reference and live frame images. To evaluate the engineered system, the effects of two different drugs, isoprenaline and doxorubicin, on the beating rate and beat-to-beat variations of ESC-derived cardiomyocytes were measured. The detection system was used to conclude that the beat-to-beat variability increased under treatment with both isoprenaline and doxorubicin. However, the beating rates increased upon the addition of isoprenaline but decreased for cultures supplemented with doxorubicin. Moreover, the response time for both the beating rates and the beat-to-beat variability of ESC-derived cardiomyocytes under treatment of isoprenaline was shorter than doxorubicin, although the amount of isoprenaline used in the measurement was three orders of magnitude lower than that of doxorubicin. Given its ability to perform real-time cell monitoring in a simple and inexpensive manner, the proposed system may be useful for a range of cell-based biosensing applications.
Little is known about the underlying neurobiology of rhythm and beat perception, despite its universal cultural importance. Here we used functional magnetic resonance imaging to study rhythm perception in musicians and non-musicians. Three conditions varied in the degree to which external reinforcement versus internal generation of the beat was required. The ‘Volume’ condition strongly externally marked the beat with volume changes, the ‘Duration’ condition marked the beat with weaker accents arising from duration changes, and the ‘Unaccented’ condition required the beat to be entirely internally generated. In all conditions, beat rhythms compared to nonbeat control rhythms revealed putamen activity. The presence of a beat was also associated with greater connectivity between the putamen and the supplementary motor area (SMA), the premotor cortex (PMC) and auditory cortex. In contrast, the type of accent within the beat conditions modulated the coupling between premotor and auditory cortex, with greater modulation for musicians than non-musicians. Importantly, the putamen's response to beat conditions was not due to differences in temporal complexity between the three rhythm conditions. We propose that a cortico-subcortical network including the putamen, SMA, and PMC is engaged for the analysis of temporal sequences and prediction or generation of putative beats, especially under conditions that may require internal generation of the beat. The importance of this system for auditory-motor interaction and development of precisely timed movement is suggested here by its facilitation in musicians.
Rhythm; beat perception; basal ganglia; fMRI; timing; effective connectivity
The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli.
Methods and Findings
Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1β, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-β2, the δ-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as β-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1β, PKD2L1, phospholipase C-β2, and δ-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells.
These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals (“natural knockouts”) suggests a cell lineage for sour that is independent of the other taste modalities.
Basic research has revealed that the chemical sensory world of children is different from that of adults, as evidenced by their heightened preferences for sweet and salty tastes. However, little is known about the ontogeny of sour taste preferences, despite the growing market of extreme sour candies. The present study investigated whether the level of sourness most preferred in a food matrix and the ability to discriminate differences in sour intensity differed between 5- to 9-year-old children and their mothers, by using a rank-by-elimination procedure embedded in the context of a game. Mothers also completed a variety of questionnaires and children were asked several questions to assess whether children’s temperament and food preferences and habits related to sour preferences. The results indicated that, although every mother and all but two of the children (92%) were able to rank the gelatins from most to least sour, more than one-third (35%) of the children, but virtually none of the adults, preferred the high levels of sour taste (0.25 M citric acid) in gelatin. Those children who preferred the extreme sour tastes were significantly less food neophobic (P < 0.05) and tended to experience a greater variety of fruits when compared with the remaining children (P = 0.11). Moreover, the children’s preference for sour tastes generalized to other foods, such as candies and lemons, as reported by both children and mothers. These findings are the first experimental evidence to demonstrate that sour taste preferences are heightened during childhood and that such preferences are related to children’s food habits and preferences. Further research is needed to unfold the relationship between the level of sour taste preferred and the actual consumption of sour-tasting foods and flavors in children.
children; taste preferences; sour taste; food neophobia; picky eating; nutrition
A patient is described with a right-sided tortuous siphon-like extracranial internal carotid artery leading to highly distressing ipsilateral heart beat synchronous pulsatile tinnitus, scoring 9/10 measuring loudness. Dilating the balloon during the occlusion test in or distal to the siphon-like anomaly reduces the arterial pulsations. Subsequently, surgery is performed using Teflon as an external construct to straighten the siphon-like anomaly. Postoperatively, the pulsations improve to 5/10 in a standing position and disappear during a reclined position. By adding a hearing aid, the pulsations are almost completely gone during a standing position (1/10) and remain absent in a reclined position.
It has been postulated for decades that ion channels serve as receptors for most sour tasting stimuli. Though many candidates exist, definitive evidence linking any particular channel to sour taste perception has been elusive. Several studies have suggested that two members of the polycystic kidney disease-like family may function as components of an ionotropic taste receptor mediating the transduction of acids. However, the precise role of these proteins in sour taste is controversial. In this issue of Chemical Senses, Nelson et al. use behavioral and electrophysiological approaches in gene-targeted mice to show that one of these putative sour taste receptor subunits, Pkd1l3, is unnecessary for normal taste responses to acids. Their results suggest that other mechanisms and/or other candidate receptors must be contributing to the transduction of acids and the subsequent perception of sour taste.
gustatory nerves; preference; Pkd1l3; receptor; transduction; threshold
Tetraploid sour cherry (Prunus cerasus L.) exhibits gametophytic self-incompatibility (GSI) whereby the specificity of self-pollen rejection is controlled by alleles of the stylar and pollen specificity genes, S-RNase and SFB (S haplotype-specific F-box protein gene), respectively. As sour cherry selections can be either self-compatible (SC) or self-incompatible (SI), polyploidy per se does not result in SC. Instead the genotype-dependent loss of SI in sour cherry is due to the accumulation of non-functional S-haplotypes. The presence of two or more non-functional S-haplotypes within sour cherry 2x pollen renders that pollen SC. Two new S-haplotypes from sour cherry, S33 and S34, that are presumed to be contributed by the P. fruticosa species parent, the complete S-RNase and SFB sequences of a third S-haplotype, S35, plus the presence of two previously identified sweet cherry S-haplotypes, S14 and S16 are described here. Genetic segregation data demonstrated that the S16-, S33-, S34-, and S35-haplotypes present in sour cherry are fully functional. This result is consistent with our previous finding that ‘hetero-allelic’ pollen is incompatible in sour cherry. Phylogenetic analyses of the SFB and S-RNase sequences from available Prunus species reveal that the relationships among S-haplotypes show no correspondence to known organismal relationships at any taxonomic level within Prunus, indicating that polymorphisms at the S-locus have been maintained throughout the evolution of the genus. Furthermore, the phylogenetic relationships among SFB sequences are generally incongruent with those among S-RNase sequences for the same S-haplotypes. Hypotheses compatible with these results are discussed.
Prunus cerasus; self-incompatibility; SFB; S-RNase
Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS) and a neoculin basic subunit (NBS). Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s) responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor–taste substance in particular.
Although males and females differ in eating behavior and prevalence rates for eating disorders and obesity, little is known about gender differences in cortical activation to pleasant and unpleasant pure tastes during the physiological states of hunger and satiety. Twenty-one healthy young adults (12 females and 9 males) underwent two functional magnetic resonance imaging scans. Using four pure tastants of differing qualities (i.e., salty, sour, bitter, sweet), the present study examined gender differences in fMRI activation during two motivational states (hunger and satiety). There was greater change in fMRI activation from hunger to satiety in males than females in response to all tastes within the middle frontal gyrus (BA 10), insula, and cerebellum. Males also had greater change in activation from hunger to satiety, relative to females, in limbic regions including dorsal striatum, amygdala, parahippocampal gyrus, and posterior and anterior cingulate; however, activation was stimulus dependent, despite equivalent ratings in perceived pleasantness and intensity. Interestingly, males and females showed significant change from hunger to satiety in response to citric acid, suggesting that in addition to gender and physiological condition, stimulus quality is an important factor in taste fMRI activation. These gender differences may have implications for the pathophysiology of eating disorders and obesity.
Gender; Taste; Hunger; Satiety; Reward; fMRI
The taste system is one of our fundamental senses, responsible for detecting and responding to sweet, bitter, umami, salty and sour stimuli. In the tongue, the five basic tastes are mediated by separate classes of taste receptor cells each finely tuned to a single taste quality. Here, we explored the logic of taste coding in the brain by examining how sweet, bitter, umami and saltiness are represented in the primary taste cortex. Using in vivo two-photon calcium-imaging we demonstrated striking topographic segregation in the functional architecture of the gustatory cortex. Each taste quality is represented in its own separate cortical field, revealing the existence of a gustotopic map in the brain. These results expose the basic logic for the central representation of taste.
A medium was developed which permitted isolation, apparently for the first time, of the bacteria responsible for the acid production in the 100-year-old San Francisco sour dough French bread process. Some of the essential ingredients of this medium included a specific requirement for maltose at a high level, Tween 80, freshly prepared yeast extractives, and an initial pH of not over 6.0. The bacteria were gram-positive, nonmotile, catalase-negative, short to medium slender rods, indifferent to oxygen, and producers of lactic and acetic acids with the latter varying from 3 to 26% of the total. Carbon dioxide was also produced. Their requirement for maltose for rapid and heavy growth and a proclivity for forming involuted, filamentous, and pleomorphic forms raises a question as to whether they should be properly grouped with the heterofermentative lactobacilli.
The fermentation of the batter of idli, a fermented food of India, was studied. The microorganisms responsible for the characteristic changes in the batter were isolated and identified. Although there is a sequential change in the bacterial flora, the predominant microorganism responsible for souring, as well as for gas production, was found to be Leuconostoc mesenteroides. In the later stages of fermentation, growth of Streptococcus faecalis and, still later, of Pediococcus cerevisiae becomes significant. The fermentation of idli demonstrates a leavening action caused by the activity of the heterofermentative lactic acid bacterium, L. mesenteroides. As far as is known, this is the first record of a leavening action produced exclusively by the activity of a lactic acid bacterium.
Industrial uses of tellurium are limited, and reported cases of tellurium absorption of occupational origin are rare. Two such cases are reported here. Both showed typical signs and symptoms of intoxication; in particular, the stench of sour garlic was noted on breath and from excreta. An unusual feature was the bluish-black discoloration of the webs of the fingers and streaks on the face and neck. Full hospital investigation was negative. No permanent damage resulted and each patient made a spontaneous recovery without treatment.
Analysis of ciliary function for assessment of patients suspected of primary ciliary dyskinesia (PCD) and for research studies of respiratory and ependymal cilia requires assessment of both ciliary beat pattern and beat frequency. While direct measurement of beat frequency from high-speed video recordings is the most accurate and reproducible technique it is extremely time consuming. The aim of this study was to develop a freely available automated method of ciliary beat frequency analysis from digital video (AVI) files that runs on open-source software (ImageJ) coupled to Microsoft Excel, and to validate this by comparison to the direct measuring high-speed video recordings of respiratory and ependymal cilia. These models allowed comparison to cilia beating between 3 and 52 Hz.
Digital video files of motile ciliated ependymal (frequency range 34 to 52 Hz) and respiratory epithelial cells (frequency 3 to 18 Hz) were captured using a high-speed digital video recorder. To cover the range above between 18 and 37 Hz the frequency of ependymal cilia were slowed by the addition of the pneumococcal toxin pneumolysin. Measurements made directly by timing a given number of individual ciliary beat cycles were compared with those obtained using the automated ciliaFA system.
The overall mean difference (± SD) between the ciliaFA and direct measurement high-speed digital imaging methods was −0.05 ± 1.25 Hz, the correlation coefficient was shown to be 0.991 and the Bland-Altman limits of agreement were from −1.99 to 1.49 Hz for respiratory and from −2.55 to 3.25 Hz for ependymal cilia.
A plugin for ImageJ was developed that extracts pixel intensities and performs fast Fourier transformation (FFT) using Microsoft Excel. The ciliaFA software allowed automated, high throughput measurement of respiratory and ependymal ciliary beat frequency (range 3 to 52 Hz) and avoids operator error due to selection bias. We have included free access to the ciliaFA plugin and installation instructions in Additional file 1 accompanying this manuscript that other researchers may use.
The polycystic kidney disease-like ion channel PKD2L1 and its associated
partner PKD1L3 are potential candidates for sour taste receptors. PKD2L1 is
expressed in type III taste cells that respond to sour stimuli and genetic
elimination of cells expressing PKD2L1 substantially reduces chorda tympani
nerve responses to sour taste stimuli. However, the contribution of PKD2L1
and PKD1L3 to sour taste responses remains unclear.
We made mice lacking PKD2L1 and/or PKD1L3 gene and investigated whole nerve
responses to taste stimuli in the chorda tympani or the glossopharyngeal
nerve and taste responses in type III taste cells. In mice lacking PKD2L1
gene, chorda tympani nerve responses to sour, but not sweet, salty, bitter,
and umami tastants were reduced by 25–45% compared with those
in wild type mice. In contrast, chorda tympani nerve responses in PKD1L3
knock-out mice and glossopharyngeal nerve responses in single- and
double-knock-out mice were similar to those in wild type mice. Sour taste
responses of type III fungiform taste cells (GAD67-expressing taste cells)
were also reduced by 25–45% by elimination of PKD2L1.
These findings suggest that PKD2L1 partly contributes to sour taste responses
in mice and that receptors other than PKDs would be involved in sour
Psychophysical judgments often depend on stimulus context. For example, sugar solutions are judged sweeter when a tasteless fruity aroma has been added. Response context also matters; adding a fruity aroma to sugar increases the rated sweetness when only sweetness is considered but not when fruitiness is judged as well. The interaction between stimulus context and response context has been explored more extensively in taste–odor mixtures than in taste–taste mixtures. To address this issue, subjects in the current study rated the sourness of citric acid mixed with quinine (bitter), sodium chloride (salty), and cyclamate (sweet) (stimulus context). In one condition, subjects rated sourness alone. In another, subjects rated both sourness and the other salient quality (bitterness, saltiness, or sweetness) (response context). Sourness ratings were most sensitive to response context for sour–salty mixtures (i.e., ratings of sourness alone exceeded ratings of sourness made simultaneously with saltiness) and least sensitive to context for the sour–sweet mixtures (sourness ratings made under the 2 conditions were essentially identical). Response-context effects for the sour–bitter mixture were nominally intermediate. The magnitudes of these context effects were related to judgments of qualitative similarity between citric acid and the other stimuli, consistent with prior findings. These types of context effects are relevant to the study of taste–taste mixture interactions and should provide insight into the perceptual similarities among the taste qualities.
gustatory; psychophysics; similarity
Tristeza, caused by Citrus tristeza virus (CTV), has long been present in Florida but outbreaks of decline on sour orange rootstock were occasional events until the late 1970s. Sour orange rootstock was valued for the high quality of fruit produced and was widely used because of its tolerance of citrus blight, a disease of unknown etiology. Research was directed towards the selection and screening of mild strains of CTV which could protect against sour orange decline strains. Following the introduction of Toxoptera citricida (also known as the brown citrus aphid) in 1995 there was a greater concern for maintaining production of existing blocks of citrus on sour orange rootstock. Availability of the CTV genome sequence around the same time as well as molecular characterization of in planta CTV populations led to the selection of mild CTV isolates which when inoculated into existing field trees, extended the productive life of the groves and enabled a more graduate replanting of trees on CTV-tolerant rootstocks. The history of CTV in Florida and the methods developed to select mild isolates for use for mild strain cross protection will be reviewed.
biological indexing; strain differentiation; serology; stem pitting; mild isolate selection
Epidemiological data have demonstrated an association between artificial sweetener use and weight gain. Evidence of a causal relationship linking artificial sweetener use to weight gain and other metabolic health effects is limited. However, recent animal studies provide intriguing information that supports an active metabolic role of artificial sweeteners. This systematic review examines the current literature on artificial sweetener consumption in children and its health effects. Eighteen studies were identified. Data from large, epidemiologic studies support the existence of an association between artificially-sweetened beverage consumption and weight gain in children. Randomized controlled trials in children are very limited, and do not clearly demonstrate either beneficial or adverse metabolic effects of artificial sweeteners. Presently, there is no strong clinical evidence for causality regarding artificial sweetener use and metabolic health effects, but it is important to examine possible contributions of these common food additives to the global rise in pediatric obesity and diabetes.
Acesulfame-K; artificial sweetener; aspartame; neotame; obesity; saccharine; sucralose; weight gain
We have reported that compared with glucose-sweetened beverages, consuming fructose-sweetened beverages with meals results in lower 24-h circulating glucose, insulin and leptin concentrations, and elevated triacylglycerol (TG). However, pure fructose and glucose are not commonly used as sweeteners. High fructose corn syrup (HFCS) has replaced sucrose as the predominant sweetener in beverages in the U.S.
We compared the metabolic/endocrine effects of HFCS with sucrose, and in a subset of subjects with pure fructose and glucose.
34 men and women consumed 3 isocaloric meals with either sucrose- or HFCS-sweetened beverages, and blood samples were collected over 24 hours. Eight of the male subjects were also studied when fructose- or glucose-sweetened beverages were consumed.
In 34 subjects, 24-h glucose, insulin, leptin, ghrelin and TG profiles were similar between days that sucrose or HFCS were consumed. Postprandial TG excursions after HFCS or sucrose were larger in men than women. In the men in whom the effects of 4 sweeteners were compared, the 24-h glucose and insulin responses induced by HFCS and sucrose were intermediate between the lower responses during consumption of fructose and the higher responses during glucose. Unexpectedly, postprandial TG profiles after HFCS or sucrose were not intermediate, but comparably high as after pure fructose.
Sucrose and HFCS do not have substantially different short-term endocrine/metabolic effects. In male subjects, short-term consumption of sucrose and HFCS resulted in postprandial TG responses comparable to those induced by fructose.
glucose; fructose; high fructose corn syrup; sucrose; insulin; leptin; ghrelin; triacylglycerol; free fatty acids; postprandial hypertriacylglycerolemia; humans
The three isoforms of transforming growth factor-beta (TGF-beta) have previously been implicated in embryonic development of the heart as well as in repair of myocardial damage after ischemia/reperfusion injury. TGF-beta 1 has also been localized intracellularly to both mitochondria and contractile filaments of cardiac myocytes, although its role in these structures has not been defined. We now report that exogenous TGF-beta stabilizes the beating rate of neonatal rat cardiac myocytes cultured on fibroblast matrix, and sustains their spontaneous rhythmic beating in serum-free medium. Moreover, using blocking antibodies to TGF-beta, we show that endogenous TGF-beta secreted by these myocytes acts in an autocrine fashion to maintain their beating rate. In contrast, IL-1 beta, an inflammatory mediator secreted by immune cells during myocardial injury, inhibits the beating of cardiac myocytes, and TGF-beta can overcome this inhibition. The antagonistic effects of TGF-beta and IL-1 were not observed when the myocytes were cultured on gelatin, as compared to native fibroblast matrix. The data indicate that TGF-beta is an important regulator of contractile function of the heart and have significant implications for understanding cardiac physiology in health and disease.
Cilia and eukaryotic flagella are slender cellular appendages whose regular beating propels cells and microorganisms through aqueous media. The beat is an oscillating pattern of propagating bends generated by dynein motor proteins. A key open question is how the activity of the motors is coordinated in space and time. To elucidate the nature of this coordination we inferred the mechanical properties of the motors by analyzing the shape of beating sperm: Steadily beating bull sperm were imaged and their shapes were measured with high precision using a Fourier averaging technique. Comparing our experimental data with wave forms calculated for different scenarios of motor coordination we found that only the scenario of interdoublet sliding regulating motor activity gives rise to satisfactory fits. We propose that the microscopic origin of such “sliding control” is the load dependent detachment rate of motors. Agreement between observed and calculated wave forms was obtained only if significant sliding between microtubules occurred at the base. This suggests a novel mechanism by which changes in basal compliance could reverse the direction of beat propagation. We conclude that the flagellar beat patterns are determined by an interplay of the basal properties of the axoneme and the mechanical feedback of dynein motors.