A 3D approach to model the taper of irregular tree stems: making plots biomass estimates comparable in tropical forests.

In tropical forests, the high proportion of trees showing irregularities at the stem base complicates forest monitoring. For example, in the presence of buttresses, the height of the point of measurement (HPOM ) of the stem diameter (DPOM ) is raised from 1.3 m, the standard breast height, up to a regular part of the stem. While DPOM is the most important predictor for tree aboveground biomass (AGB) estimates, the lack of harmonized HPOM for irregular trees in forest inventory increases the uncertainty in plot-level AGB stock and stock change estimates. In this study, we gathered an original non-destructive three-dimensional (3D) data set collected with terrestrial laser scanning and close range terrestrial photogrammetry tools in three sites in central Africa. For the 228 irregularly shaped stems sampled, we developed a set of taper models to harmonize HPOM by predicting the equivalent diameter at breast height (DBH') from a DPOM measured at any height. We analyzed the effect of using DBH' on tree-level and plot-level AGB estimates. To do so, we used destructive AGB data for 140 trees and forest inventory data from eight 1-ha plots in the Republic of Congo. Our results showed that our best simple taper model predicts DBH' with a relative mean absolute error of 3.7% (R2 = 0.98) over a wide DPOM range of 17-249 cm. Based on destructive AGB data, we found that the AGB allometric model calibrated with harmonized HPOM data was more accurate than the conventional local and pantropical models. At the plot level, the comparison of AGB stock estimates with and without HPOM harmonization showed an increasing divergence with the increasing share of irregular stems (up to -15%). The harmonization procedure developed in this study could be implemented as a standard practice for AGB monitoring in tropical forests as no additional forest inventory measurements is required. This would probably lead to important revisions of the AGB stock estimates in regions having a large number of irregular tree stems and increase their carbon sink estimates. The growing use of three-dimensional (3D) data offers new opportunities to extend our approach and further develop general taper models in other tropical regions.

Sound production by dusky grouper Epinephelus marginatus at spawning aggregation sites.

Sound production by the dusky grouper Epinephelus marginatus was monitored both in captivity and at two Mediterranean spawning sites during the summers of 2012 and 2013. The results of long-term passive acoustic recordings provide for the first time a description of the sounds produced by E. marginatus. Two types of sounds were mainly recorded and consisted of low-frequency booms that can be produced singly or in series with dominant frequencies below 100 Hz. Recordings in captivity validated these sounds as belonging to E. marginatus and suggested that they may be associated with reproductive displays usually performed during early stages of courtship behaviour. This study also allowed the identification of a third, low-frequency growl-like type of sound typically found in other grouper species. These growls were, however, not recorded in tanks and it is cautiously proposed that they are produced by E. marginatus. Acoustic signals attributed to E. marginatus were produced throughout the spawning season, with a diel pattern showing an increase before dusk, i.e., from 1900 to 2200 hours, before decreasing until the morning. The occurrence of sounds during the spawning season of this species suggests that they are probably involved in social activity occurring close to aggregation sites. Passive acoustics offer a helpful tool to monitor aggregation sites of this emblematic species in order to improve conservation efforts.

Speciation slowing down in widespread and long-living tree taxa: insights from the tropical timber tree genus Milicia (Moraceae).

The long generation time and large effective size of widespread forest tree species can result in slow evolutionary rate and incomplete lineage sorting, complicating species delimitation. We addressed this issue with the African timber tree genus Milicia that comprises two morphologically similar and often confounded species: M. excelsa, widespread from West to East Africa, and M. regia, endemic to West Africa. We combined information from nuclear microsatellites (nSSRs), nuclear and plastid DNA sequences, and morphological systematics to identify significant evolutionary units and infer their evolutionary and biogeographical history. We detected five geographically coherent genetic clusters using nSSRs and three levels of genetic differentiation. First, one West African cluster matched perfectly with the morphospecies M. regia that formed a monophyletic clade at both DNA sequences. Second, a West African M. excelsa cluster formed a monophyletic group at plastid DNA and was more related to M. regia than to Central African M. excelsa, but shared many haplotypes with the latter at nuclear DNA. Third, three Central African clusters appeared little differentiated and shared most of their haplotypes. Although gene tree paraphyly could suggest a single species in Milicia following the phylogenetic species concept, the existence of mutual haplotypic exclusivity and nonadmixed genetic clusters in the contact area of the two taxa indicate strong reproductive isolation and, thus, two species following the biological species concept. Molecular dating of the first divergence events showed that speciation in Milicia is ancient (Tertiary), indicating that long-living tree taxa exhibiting genetic speciation may remain similar morphologically.

Design of a watercourse and riparian strip monitoring system for environmental management.

Watercourses are complex ecosystems where numerous economic, ecological and heritage issues converge. To ensure their efficient management it is essential to have a full description of these multifunctional ecosystems and to know their evolution over time. This paper describes a method for monitoring watercourses and their riparian strips developed in Wallonia (southern Belgium). It is based on an inventory constructed by stratified random sampling comprising 1,071 sampling plots distributed over a total length of 24,600 km of watercourses covered from their source. Each sampling plot is surveyed and measurements and fine observations are made on watercourse segments 50 m long. The method developed, which was applied on a regional scale, could easily be transposed to other entities, from large river basins, to an entire country. Examples of results obtained from a first inventory phase demonstrate the utility of this tool designed to supply qualitative and quantitative information to assist watercourse management.

Super-enhancers define a proliferative PGC-1α-expressing melanoma subgroup sensitive to BET inhibition.

Metabolic changes are linked to epigenetic reprogramming and play important roles in several tumor types. PGC-1α is a transcriptional coactivator controlling mitochondrial biogenesis and is linked to oxidative phosphorylation. We provide evidence that melanoma models with elevated PGC-1α levels are characteristic of the proliferative phenotype and are sensitive to bromodomain and extra-terminal domain (BET) inhibitor treatment. A super-enhancer region highly occupied by the BET family member BRD4 was identified for the PGC-1α gene. BET inhibitor treatment prevented this interaction, leading to a dramatic reduction of PGC-1α expression. Accordingly, BET inhibition diminished respiration and mitochondrial function in cells. In vivo, melanoma models with high PGC-1α expression strongly responded to BET inhibition by reduction of PGC-1α and impaired tumor growth. Altogether, our findings identify epigenetic regulatory elements that define a subset of melanomas with high sensitivity to BET inhibition, which opens up the opportunity to define melanoma patients most likely to respond to this treatment, depending on their tumor characteristics.

Inaugural tumor-like multiple sclerosis: clinical presentation and medium-term outcome in 87 patients.

BACKGROUND: Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities [multiple sclerosis (the most common), Balo's concentric sclerosis, Schilder's disease and acute disseminated encephalomyelitis] with overlapping clinical presentation. The aim of our study was to better characterize these patients. METHODS: Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded. RESULTS: Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD). CONCLUSION: This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.

Immobilization of E. coli bacteria in three-dimensional matrices for ISFET biosensor design.

In recent years, cell-based biosensors (CBBs) have been very useful in biomedicine, food industry, environmental monitoring and pharmaceutical screening. They constitute an economical substitute for enzymatic biosensors, but cell immobilization remains a limitation in this technology. To investigate into the potential applications of cell-based biosensors, we describe an electrochemical system based on a microbial biosensor using an Escherichia coli K-12 derivative as a primary transducer to detect biologically active agents. pH variations were recorded by an ion-sensitive field effect transistor (ISFET) sensor on bacteria immobilized in agarose gels. The ISFET device was directly introduced in 100 ml of this mixture or in a miniaturized system using a dialysis membrane that contains 1 ml of the same mixture. The bacterial activity could be detected for several days. The extracellular acidification rate (ECAR) was analyzed with or without the addition of a culture medium or an antibiotic solution. At first, the microorganisms acidified their micro-environment and then they alkalinized it. These two phases were attributed to an apparent substrate preference of bacteria. Cell treatment with an inhibitor or an activator of their metabolism was then monitored and streptomycin effect was tested.

Trace element concentrations in the apex predator swordfish (Xiphias gladius) from a Mediterranean fishery and risk assessment for consumers.

Swordfish (Xiphias gladius L., 1758) is an apex predator, highly migratory meso-pelagic fish widely distributed in the Atlantic Ocean and Mediterranean. As top predators, this fish may be the end reservoir of the bioaccumulation of trace elements in a food chain because they occupy higher trophic levels and are an important food source, causing them to be potentially hazardous to consume. This study aims to investigate the concentration of 18 trace elements of Swordfish, caught in the Mediterranean Sea and to discuss human exposure risks. The mean element levels in the fish muscles were clearly below the maximum allowable concentrations established by International food safety regulations. The data suggested that the risk is minor and acceptable for human health. The findings of this study amplify the scarce database on contaminants available, especially new data on "emerging elements", for this species from the Mediterranean Sea.

Gaining deeper insight into aroma perception: An integrative study of the oral processing of breads with different structures.

The objective of this study was to investigate for the first time the influence of bread structure, volatile compounds, and oral processing on aroma perception. 3 types of French baguette were created using the same raw ingredients but different bread-making processes; they consequently varied in their crumb and crust structures. We characterized the initial volatile profiles of two bread structural subtypes-namely bread crumb and bread crumb with crust-using proton transfer reaction-mass spectrometry (PTR-MS) headspace analysis. Three types of bread were characterized by thirty-nine ion fragments from m/z 45 to 139. We then conducted a study in which 8 participants scored aroma attribute intensities for the different bread types and subtypes at 3 key stages of oral processing (10, 40, and 100% of individual swallowing time). At these 3 time points, we collected boli from the participants and characterized their volatile profiles using PTR-MS headspace analysis. The results suggest saliva addition dilutes volatile compounds, reducing volatile release during oral processing. Thus, a bread with high porosity and high hydration capacity was characterized by a low volatile release above boli. We examined the relationships between 4 aroma attributes of bread crumb with crust and 24 discriminatory fragment ions found in boli headspace. This study demonstrated for the first time that the perceived aroma of crumb with crust was influenced more by volatile profiles than by crumb texture. It thus contributes to our understanding of aroma perception dynamics and the mechanisms driving volatile release during oral processing in bread.

Continuous intraperitoneal insulin infusion does not increase the risk of organ-specific autoimmune disease in type 1 diabetic patients: results of a multicentric, comparative study.

AIM: The purpose of this national multicenter prospective study by the French EVADIAC group was to investigate the possibility that continuous intraperitoneal insulin infusion using an implanted pump (CIpii) increases the risk of autoimmune disease in type 1 diabetic patients as it increased anti-insulin immunogenicity. METHODS: Prevalence of clinical (Hashimoto's disease, hyperthyroidism, gastric atrophic disease and vitiligo) and subclinical (presence of anti-thyroperoxidase antibodies, anti-intrinsic factor antibodies, abnormal TSH levels) autoimmune diseases was estimated by comparing two groups of patients already treated by either CIpii (n=154) or external pump (CSII) (n=121) for an average of 6 years. Incidence of autoimmune disease was determined by comparing the same measurements one year after inclusion. RESULTS: No significant difference was observed for the total prevalence of clinical and subclinical auto-immune thyroid and gastric di-seases (35.6% and 3.2% respectively in the CIpii group versus 40.4% and 2.6% in the CSII group). No significant difference for the incidence of clinical and subclinical auto-immune diseases was observed: 7.2% and 0% in CIpii and 7.3% and 1.7% in CSII. CONCLUSION: As previously shown AIA (anti-insulin antibodies) levels were higher in CIpii than in CSII (32.9% vs 20.2%, P<0.0001) but no correlation was observed with either clinical or subclinical autoimmune disease. This large-scale study eliminates the possibility that CIpii increases the risk of autoimmune disease.

Breakdown pathways during oral processing of different breads: impact of crumb and crust structures.

Oral processing during bread consumption is a key process related to the dynamics of texture perceptions, sensory stimuli release and starch digestion. The aim of this study was to determine the respective contribution of bread properties (composition and structure of crumb and crust) and of the oral physiology of subjects to the breakdown pathways in the mouth. The properties of the in vivo bread bolus obtained from eight healthy subjects were studied at three key points in time during their oral processing. The progressive lubrication and breakdown of bread were observed, as well as the beginning of the enzymatic degradation of starch. The study showed that "time" was the factor responsible for the greatest variability in bolus properties. Breakdown pathways were established for crumbs with and without crust. The presence of crust modified the oral processing, increasing, for instance, the heterogeneity of particle size at the middle of the oral processing sequence. Moreover, the hydration capacity of crust contributed to high starch degradation at swallowing time, in comparison with crumb alone. The main subject characteristics impacting bolus properties were the in-mouth duration, the individual masticatory index and the mouth volume, while the main bread properties explaining the bolus properties were the initial composition and the water-absorbing capacity. We concluded that both crumb and crust structures had an impact on the oral processing, affecting the capacity of hydration, the rheology and the breakdown degree of the bolus.

Respective impact of bread structure and oral processing on dynamic texture perceptions through statistical multiblock analysis.

Texture perception is a multidimensional and dynamic phenomenon resulting from both the initial structure of food and its breakdown during oral processing. The aim of this study is to identify the respective contribution of food and bolus properties to temporal changes in texture perceptions during bread consumption. For this purpose, the perception dynamics of three French baguettes with dif\ferent structures were assessed through Temporal Dominance of Sensations and Progressive Profiling. Samples of crumb with and without crust were tasted by trained panelists. The intensities of nine texture attributes were evaluated at three key stages of oral processing (10%, 40% and 100% of individual swallowing time) using the Progressive Profiling method. Six of them were related with a Multiblock Partial Least Squares (MB-PLS) regression to the initial bread properties and to some bolus properties measured at these three stages. The evolution during oral processing of some attributes such as "soft", "dry", "doughy" and "sticky" was more influenced by modifications of bolus properties than by the initial characteristics of the breads. Among bolus properties, the MB-PLS highlighted that the hydration and texture properties of the bolus had a greater impact on texture perceptions than bolus structure. The "aerated" perception was more affected by the crumb structure, while the "heterogeneousness" and the "crispiness" were more affected by the presence of crust. This study thus contributes to improving our understanding of dynamic texture perceptions through a statistical model that takes the physical properties of bread and bolus during oral processing into account.

Changes in serum level and affinity for concanavalin A of human alpha 1-proteinase inhibitor in severe burn patients: relationship to natural killer cell activity.

In serum from five patients with severe burns, alpha 1-proteinase inhibitor (alpha 1-PI) was analyzed and then isolated by immunosorption chromatography. By Con A-Sepharose chromatography alpha 1-PI was separated into two types of fractions: the first containing the Con A-non-reactive isoforms and the second containing the Con A-reactive isoforms. The increase of alpha 1-PI serum level in burn patients is associated on the fifth day after the burn with a significant shift toward species enriched in bi-antennary oligosaccharides (Con A-reactive isoforms). This latter change passed very quickly and ten days after the burn, whereas the alpha 1-PI serum level was still high, the difference in proportions of Con A-reactive and non-reactive isoforms was not statistically significant. With respect to the difference in oligosaccharide structure, it appeared that the glycan moiety was involved in the inhibitory effect on natural killer cell activity. At the same concentration, purified alpha 1-PI and retained alpha 1-PI isoforms had an equal effect, whereas the non-retained alpha 1-PI isoforms were more efficient (P less than or equal to 0.01). Purified alpha 1-PI and its isoforms inhibited the natural killer cell activity in a dose-dependent manner.

Thyroglobulin autoantibodies in iodized subjects: relationship between epitope specificities and longitudinal antibody activity.

INTRODUCTION: We previously reported a high thyroglobulin autoantibodies (TgAb) prevalence in healthy Sri Lankans after iodine supplementation. In the present study 58 TgAb-positive schoolgirls were followed up after 5 years of continued iodination. The objectives were: (1) to observe the longitudinal profile of TgAb epitope specificities and (2) to examine the relationship between these specificities and the course of thyroid autoimmunity in this population. METHODS: Paired subjects' sera (at onset and at 5-year follow-up) were tested for TgAb, thyroid peroxidase antibody (TPOAb), and TgAb epitope-specificity. Epitope reactivity was determined by employing a panel of 10 murine monoclonal antibodies (Tg-mAbs) directed against 6 Tg antigenic clusters (I-VI) in competitive enzyme-linked immunosorbent assay (ELISA) reactions with test sera. RESULTS: The overall pattern of epitope recognition in individual subject's sera remained preserved over the time period. Nine subjects showed restricted specificities while majority of the subjects were broadly heterogeneous. At follow-up, median TgAb concentration in the restricted group was higher than in the unrestricted (1650 versus 110 kIU/L; p < 0.005). Epitope specificity was a stronger determinant of TgAb persistence than the height of the initial TgAb response or the TPOAb status of subjects. CONCLUSION: Tg epitope reactivity pattern in iodised populations may identify subjects at greater risk of developing autoimmune thyroid disease (AITD).

Atrial natriuretic peptides in canine hypoxic pulmonary vasoconstriction.

STUDY OBJECTIVE: The aim of the study was to investigate whether atrial natriuretic peptides have a physiological role in regulation of the pulmonary circulation. DESIGN: Plasma concentrations of immunoreactive atrial natriuretic peptide and guanosine-3',5'-cyclic monophosphate (cGMP) were measured during evaluation of pulmonary vascular tone by multipoint pulmonary arterial pressure-cardiac index (Ppa/Q) relationships. SUBJECTS: Experimental animals were 17 mongrel dogs of either sex, 21-35 kg weight, anaesthetised with pentobarbitone. MEASUREMENTS AND MAIN RESULTS: Measurements of Ppa/Q relationships and atrial natriuretic peptide/cGMP were made during hyperoxia (Fio2 0.4) and hypoxia (Fio2 0.1). Hypoxic pulmonary vasoconstriction, defined as hypoxia induced increase in pulmonary artery pressure over the entire range of Q studied from 2-5 litre.min-1.m-2, was elicited in nine dogs ("responders"). In the other eight dogs, hypoxia did not change pulmonary artery pressure over the entire range of Q studied ("non-responders"). At neither the highest nor the lowest Q in hyperoxia did atrial natriuretic peptide and cGMP concentrations differ between these two groups, nor did acute reduction in Q affect the concentrations in either group. At the highest Q, plasma atrial natriuretic peptide increased in hypoxia from 11(SEM 2) to 15(3) pmol.litre-1 in the responders (p less than 0.05), and from 15(2) to 20(2) pmol.litre-1 in the non-responders (p less than 0.05). However at the lowest Q, atrial natriuretic peptide was increased in non-responders only, from 17(3) to 23(4) pmol.litre-1 (p less than 0.05). CGMP did not vary significantly in any experimental condition. CONCLUSIONS: Hypoxia slightly increased plasma atrial natriuretic peptides without any relationship with associated pulmonary haemodynamic changes. These data do not support the hypothesis that atrial natriuretic peptides play a physiological role in the regulation of the pulmonary circulation in dogs.

Sympathetic modulation of hypoxic pulmonary vasoconstriction in intact dogs.

BACKGROUND: The effects of the sympathetic nervous system on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We studied the effects of adrenergic receptor blockade and epidural blockade on HPV in 32 pentobarbital-anaesthetised intact dogs. METHODS: Pulmonary arterial flow-pressure relationships were determined in hyperoxia and hypoxia, at baseline and after alpha-blockade (phentolamine 2 mg/kg + 50 micrograms.kg-1.-1), beta-blockade (propranolol 2 mg/kg), alpha beta-blockade, epidural blockade (lignocaine 20 mg/kg), and alpha beta-plus epidural blockade. RESULTS: At reference flow of 3.5 1.min-1.m-2, the mean hypoxic response (hypoxia-induced increase in transpulmonary pressure gradient, each n = 8) changed from 6.0 +/- 0.9 to 3.5 +/- 1.0 mmHg after alpha-blockade, from 5.8 +/- 0.9 to 0.7 mmHg after beta-blockade, from 4.1 +/- 0.8 to 0.9 +/- 1.4 mmHg after alpha beta-blockade from 3.4 +/- 1.0 to 4.3 +/- 0.9 mmHg after epidural blockade (all P < 0.05), and was not affected by epidural blockade after alpha beta-blockade. CONCLUSIONS: In pentobarbital-anaesthetised dogs, (1) HPV is attenuated by alpha- and enhanced by beta-, alpha beta- and epidural blockade, and (2) epidural blockade has no significant adrenergic-unrelated effect on the pulmonary vasculature.

Effects of low flow on pulmonary vascular flow-pressure curves and pulmonary vascular impedance.

OBJECTIVE: Flow-pressure curves and vascular impedance are commonly used to investigate pulmonary circulation, but they may be affected at low flow by reflex neurohumoral activation. We therefore investigated the mechanical effects and the reflex effects of decreased flow on pulmonary vascular resistance and impedance. METHODS: In ten anaesthetized dogs, we compared flow-pressure curves generated in less than 10 s to prevent sympathetic activation (fast curves), or generated over 20-30 min to allow neurohumoral equilibration (slow curves), in hyperoxia (inspired oxygen, 40%) and in hypoxia (inspired oxygen, 10%), before and after adrenergic blockade by phentolamine and propranolol. Resistance was assessed from the flow-pressure relationship. Impedance was computed from instantaneous flow and pressure obtained with an ultrasonic flowmeter and a micromanometer-tipped catheter. RESULTS: At baseline, fast flow-pressure curves were steeper and had a lower pressure intercept. Transient low flow did not affect heart rate or pulmonary arterial elastance. Sustained low flow increased heart rate, resistance and elastance, suggesting baroreceptor-induced sympathetic stimulation. After adrenergic blockade, no difference persisted between effects of transient and sustained low flow. In hypoxia, slow and fast flow-pressure curves were similar. Hypoxia increased heart rate and resistance but did not decrease elastance, suggesting chemoreceptor-induced sympathetic stimulation. In hypoxia, differences between transient and sustained low flow were no longer significant, and were completely suppressed by adrenergic blockade. In two additional dogs, epinephrine infusion increased pulmonary vascular resistance and elastance. CONCLUSIONS: We conclude that (1) compared to transient low flow, sustained low flow is associated with increases in distal resistance and proximal elastance due to sympathetic stimulation and (2) these differences between the effects of transient and sustained low flow do not persist in hypoxia, because of an already present chemoreceptor-induced sympathetic stimulation.

Hormone synthesis in human thyroglobulin: possible cleavage of the polypeptide chain at the tyrosine donor site.

At moderate iodination levels (20 iodine atoms/mol) human thyroglobulin (hTg) produces after reduction a hormone-rich peptide of 26 kDa which contains the preferential hormonogenic 'acceptor' tyrosine (Tyr 5) of the protein. The site of cleavage of the hTg chain was demonstrated by analysis of the 26 kDa tryptic hydrolysis products. It consistently yielded the peptide Gln-82-Val-129 which consequently made it possible to localize the hTg chain cleavage at tyrosine residue 130. Evidence for tyrosine involvement in hTg cleavage during thyroid hormone formation supports the hypothesis that peptide bond cleavage would occur at the 'donor' tyrosine residue and suggests that tyrosine 130 would be the donor site reacting with the major hormone-forming acceptor site (Tyr 5) of hTg.

In vitro and in vivo iodination of human thyroglobulin in relation to hormone release.

Reduced and S-alkylated thyroglobulin (Tgb) from different species were shown by SDS-PAGE to contain small peptides (from 45-9 kDa) rich in thyroxine. Several hypotheses were proposed to explain their origin. The polypeptide composition of iodine-poor (Tgb A) and normally iodinated (Tgb B) human Tgb prepared by two different procedures (one minimizing and the other favoring post-mortem proteolysis) was compared in the native state and after in vitro iodination. Results show that one of the hormonogenic sites of human Tgb is part of a domain of the molecule most susceptible to proteolysis, especially when it is very iodinated.

Precursor-product relationship between the 26-kDa and 18-kDa fragments formed by iodination of human thyroglobulin.

At moderate iodination levels (20 iodine at atoms/molecule), human thyroglobulin (hTgb) produces after reduction a thyroxinyl-peptide of 26 kDa which represents the N-terminal part of the protein. At higher iodination levels, the 26-kDa peptide is accompanied by another T4-containing peptide of 18 kDa. A precursor-product relationship between the 26- and 18-kDa fragments was demonstrated by the study of the tryptic fragments of both hormonopeptides. In addition, comparison with the protein sequence deduced from the nucleotide sequence of the 5'-end of hTgb mRNA demonstrated that the N-terminal region of Htgb from which are issued the 26-kDa peptide and its 18-kDa derivative is especially sensitive to proteolysis. This character is possibly related with a facilitated release of thyroid hormones in vivo.