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Objective To examine associations between local and systemic symptoms and the wear of the tin weld of Essure implants. Design study of a series of cases. Settings Two French hospitals. Participants Eighteen patients explanted by hysterectomy and salpingectomy for removal of their Essure implants between September 2019 and July 2020, have had a common anatomopathological process. Main outcome measures anatomopathological examination by optical microscopy and mineralogical analysis of the fallopian tube or uterine horn with scanning electron microscopy coupled with energy dispersive X-ray (SEM-EDX). Evaluation of local and systemic symptoms with a questionnaire. Examination of blood metal assays (nickel, chromium, and tin). Results anatomopathological examination highlights foreign body granulomas, fibrosis, adenomyosis, nonspecific inflammation, cysts and myomas in the Fallopian tubes, uterine horns, or both and mentions the presence of foreign bodies in seven cases. SEM-EDX analyses showed, systematically, the presence of tin particles integrated in the wall near the weld, generally in clusters, and with a size ranging from about one micron to several dozen microns. The questionnaire shows that the most frequent local symptoms were pelvic pain, urinary disorders, bleeding, and pains during intercourse. The most common systemic symptoms were: asthenia, visual disturbances, amnesia, giddiness, dorsal pains, headaches, and joint pains. The majority of local and systemic symptoms decreased after explantation, but sometimes incompletely. Before explantation, high levels of nickel, tin and chromium were observed in 11/17, 1/7 and 2/17 patients. After explantation, tin levels were high in 3/11 patients. Conclusions our new anatomopathological process systematically demonstrates the presence of tin particles in tissue near the weld. These particles could be responsible for granulomatous inflammations as well as local symptoms. Many of the systemic symptoms are consistent with chronic organotin poisoning but further studies are needed to find out whether tin from the solder can be converted to organotin in the patients' bodies.

The nature of the vegetative to reproductive transition in the shoot apical meristem of Camelina sativa summer annual cultivar CO46 and winter annual cultivar Joelle was confirmed by treating seedlings with or without 8 weeks of vernalization. True to their life cycle classification, Joelle required a vernalization treatment to induce bolting and flowering, whereas CO46 did not. In this study, whole genome sequence, RNAseq, and resequencing of PCR‐amplified transcripts for a key floral repressor were used to better understand factors involved in the flowering habit of summer and winter biotypes at the molecular level. Analysis of transcriptome data indicated that abundance for one of the three genes encoding the floral repressor FLOWERING LOCUS C (FLC; Csa20 g015400) was 16‐fold greater in Joelle compared to CO46 prior to vernalization. Abundance of this transcript decreased only slightly in CO46 postvernalization, compared to a substantial decrease in Joelle. The results observed in the winter annual biotype Joelle are consistent with repression of FLC by vernalization. Further characterization of FLC at both the genome and transcriptome levels identified a one base deletion in the 5th exon coding for a keratin‐binding domain in chromosome 20 of CO46 and Joelle. The one base deletion detected in chromosome 20 FLC is predicted to result in a frameshift that would produce a nonfunctional protein. Analysis of whole genome sequence indicated that the one base deletion in chromosome 20 FLC occurred at a greater ratio in the summer biotype CO46 (2:1) compared to the winter biotype Joelle (1:4); similar trends were also observed for RNAseq and cDNA transcripts mapping to chromosome 20 FLC of CO46 and Joelle.

The nature of the vegetative to reproductive transition in the shoot apical meristem of Camelina sativa summer annual cultivar CO46 and winter annual cultivar Joelle was confirmed by treating seedlings with or without 8 weeks of vernalization. True to their life cycle classification, Joelle required a vernalization treatment to induce bolting and flowering, whereas CO46 did not. In this study, whole genome sequence, RNAseq, and resequencing of PCR‐amplified transcripts for a key floral repressor were used to better understand factors involved in the flowering habit of summer and winter biotypes at the molecular level. Analysis of transcriptome data indicated that abundance for one of the three genes encoding the floral repressor FLOWERING LOCUS C (FLC; Csa20 g015400) was 16‐fold greater in Joelle compared to CO46 prior to vernalization. Abundance of this transcript decreased only slightly in CO46 postvernalization, compared to a substantial decrease in Joelle. The results observed in the winter annual biotype Joelle are consistent with repression of FLC by vernalization. Further characterization of FLC at both the genome and transcriptome levels identified a one base deletion in the 5th exon coding for a keratin‐binding domain in chromosome 20 of CO46 and Joelle. The one base deletion detected in chromosome 20 FLC is predicted to result in a frameshift that would produce a nonfunctional protein. Analysis of whole genome sequence indicated that the one base deletion in chromosome 20 FLC occurred at a greater ratio in the summer biotype CO46 (2:1) compared to the winter biotype Joelle (1:4); similar trends were also observed for RNAseq and cDNA transcripts mapping to chromosome 20 FLC of CO46 and Joelle.

Huntington's disease (HD) is caused by a polyglutamine expansion in the Huntingtin (Htt) protein. Proteolytic cleavage of Htt into toxic N-terminal fragments is believed to be a key aspect of pathogenesis. The best characterized putative cleavage event is at amino acid 586, hypothesized to be mediated by caspase 6. A corollary of the caspase 6 cleavage hypothesis is that the caspase 6 fragment should be a toxic fragment. To test this hypothesis, and further characterize the role of this fragment, we have generated transgenic mice expressing the N-terminal 586 aa of Htt with a polyglutamine repeat length of 82 (N586–82Q), under the control of the prion promoter. N586–82Q mice show a clear progressive rotarod deficit by 4 months of age, and are hyperactive starting at 5 months, later changing to hypoactivity before early mortality. MRI studies reveal widespread brain atrophy, and histologic studies demonstrate an abundance of Htt aggregates, mostly cytoplasmic, which are predominantly composed of the N586–82Q polypeptide. Smaller soluble N-terminal fragments appear to accumulate over time, peaking at 4 months, and are predominantly found in the nuclear fraction. This model appears to have a phenotype more severe than current full-length Htt models, but less severe than HD mouse models expressing shorter Htt fragments. These studies suggest that the caspase 6 fragment may be a transient intermediate, that fragment size is a factor contributing to the rate of disease progression, and that short soluble nuclear fragments may be most relevant to pathogenesis.

Introduction Le melanome annulaire est une forme clinique rare du melanome uveal qui se caracterise par l’envahissement circonferentiel du corps ciliaire. Un glaucome chronique unilateral et refractaire est une circonstance classique de decouverte. Observation Nous rapportons le cas d’un melanome annulaire revele par une hypertonie intraoculaire aigue secondaire a un hyphema spontane. L’iris etait le siege d’une infiltration tumorale diffuse, mais predominant sur sa racine temporale. Le fond d’œil etait inaccessible, mais l’echographie B a permis d’affirmer la presence d’une volumineuse tumeur cilio-choroidienne. Le patient a ete enuclee. L’examen anatomopathologique a confirme le diagnostic de melanome irido-ciliaire annulaire. L’angle iridocorneen etait le siege d’un envahissement tumoral circonferentiel. Le patient est decede un an plus tard de metastases. Discussion L’hypertonie intraoculaire aigue ou chronique est une circonstance rare, mais classique, de decouverte d’un melanome uveal. Plusieurs mecanismes peuvent etre en cause : rubeose angulaire, fermeture de l’angle, envahissement angulaire, obstruction trabeculaire par des cellules ou du pigment. A notre connaissance, l’hypertonie aigue secondaire a un hyphema est plus exceptionnelle. Cette observation souligne que, en dehors du tableau typique de glaucome aigu par fermeture de l’angle, toute hypertonie intraoculaire impose un examen minutieux du segment posterieur de l’œil au besoin par echographie.

Transcriptional dysregulation by mutant huntingtin (Htt) protein has been implicated in the pathogenesis of Huntington's disease (HD). We find that cultured cells expressing mutant Htt and striatal cells from HD transgenic mice have elevated nuclear factor-kappaB (NF-kappaB) activity. Furthermore, NF-kappaB is concentrated in the nucleus of neurons in the brains of HD transgenic mice. In inducible PC12 cells and in HD transgenic mice, mutant Htt activates the IkappaB kinase complex (IKK), a key regulator of NF-kappaB. Activation of IKK is likely mediated by direct interaction with mutant Htt, because the expanded polyglutamine stretch and adjacent proline-rich motifs in mutant Htt interact with IKKgamma, a regulatory subunit of IKK. Activation of IKK may also influence the toxicity of mutant Htt, because expression of IKKgamma promotes aggregation and nuclear localization of mutant Htt exon-1. Moreover, in acute striatal slice cultures, inhibition of IKK activity with an N-terminally truncated form of IKKgamma blocks mutant Htt-induced toxicity in medium-sized spiny neurons (MSNs). In addition, blocking degradation of NF-kappaB inhibitors with a dominant-negative ubiquitin ligase beta-transducin repeat-containing protein also reduces the toxicity of mutant Htt in MSNs. Therefore, aberrant NF-kappaB activation may contribute to the neurodegeneration induced by mutant Htt.

Behavioral responses to chemical cues have been demonstrated for a range of aquatic animals. Injury-released chemical alarm cues from conspecifics are released when a prey's predator is actively foraging. Detection of these cues elicits antipredator behaviors that reduce the probability of predation. Amphipod crustaceans in the genus Gammarusare widespread denizens of ponds and streams. Antipredator responses by Gammarusto conspecific alarm cues, and subsequent reduction of predation risk, are known from experiments in the laboratory. Here, we verify laboratory findings by demonstrating an avoidance response to alarm cues using a field population of G. lacustris.We used small traps baited with sponge blocks containing either water (control) or injury-released cues from Gammarus.We repeated the experiment twice. In both experiments, significantly fewer Gammaruswere captured in traps with alarm cue sponges than in traps with water sponges. Predatory leeches Dina parvawere attracted to Gammarustraps in the first experiment but not the second experiment. In the second experiment, we measured the individual weight of captured amphipods. Two size classes were present; small (1–5 mg) and large (35–108 mg). Both sizes contributed to the avoidance response. Within the large size class, small individuals were significantly less responsive to the alarm cue than large individuals, implying that small adult Gammarusmay have different cost/benefit decision criteria for risk assessment than large Gammarus.

Ring melanoma is a rare form of uveal melanoma characterized by the circumferential involvement of the ciliary body. Unilateral chronic and refractory glaucoma is a classic circumstance of diagnosis.We report a case of ring melanoma revealed by acute intraocular hypertonia secondary to spontaneous hyphema. Iris and iridocorneal angle were diffusely invaded by the tumor. The fundus was masked but B-scan ultrasonography revealed a voluminous ciliochoroidal tumor. The patient had been enucleated. Pathological examination confirmed the diagnosis of ring melanoma. The tumor involved angle structures. The patient died 1 year later because of metastasis.Acute or chronic ocular hypertonia is a classic but rare circumstance of uveal melanoma diagnosis. Many mechanisms exist: neovascular glaucoma, secondary angle closure, involvement of angle structures, and trabecular obstruction by tumor cells or pigment. Acute intraocular hypertonia secondary to hyphema is more exceptional. Our observation highlights that apart from the classic situation of acute angle closure glaucoma, intraocular hypertonia requires meticulous fundus examination, if necessary using B-scan ultrasonography.

Phosphorylation has been shown to have a significant impact on expanded huntingtin-mediated cellular toxicity. Several phosphorylation sites have been identified on the huntingtin (Htt) protein. To find new potential therapeutic targets for Huntington's Disease (HD), we used mass spectrometry to identify novel phosphorylation sites on N-terminal Htt, expressed in HEK293 cells. Using site-directed mutagenesis we introduced alterations of phosphorylation sites in a N586 Htt construct containing 82 polyglutamine repeats. The effects of these alterations on expanded Htt toxicity were evaluated in primary neurons using a nuclear condensation assay and a direct time-lapse imaging of neuronal death. As a result of these studies, we identified several novel phosphorylation sites, validated several known sites, and discovered one phospho-null alteration, S116A, that had a protective effect against expanded polyglutamine-mediated cellular toxicity. The results suggest that S116 is a potential therapeutic target, and indicate that our screening method is useful for identifying candidate phosphorylation sites.

Behavioral responses to chemical cues have been demonstrated for a range of aquatic animals. Injury-released chemical alarm cues from conspecifics are released when a prey's predator is actively foraging. Detection of these cues elicits antipredator behaviors that reduce the probability of predation. Amphipod crustaceans in the genus Gammarus are widespread denizens of ponds and streams. Antipredator responses by Gammarus to conspecific alarm cues, and subsequent reduction of predation risk, are known from experiments in the laboratory. Here, we verify laboratory findings by demonstrating an avoidance response to alarm cues using a field population of G. lacustris. We used small traps baited with sponge blocks containing either water (control) or injury-released cues from Gammarus. We repeated the experiment twice. In both experiments, significantly fewer Gammarus were captured in traps with alarm cue sponges than in traps with water sponges. Predatory leeches Dina parva were attracted to Gammarus traps in the first experiment but not the second experiment. In the second experiment, we measured the individual weight of captured amphipods. Two size classes were present; small (1-5 mg) and large (35-108 mg). Both sizes contributed to the avoidance response. Within the large size class, small individuals were significantly less responsive to the alarm cue than large individuals, implying that small adult Gammarus may have different cost/benefit decision criteria for risk assessment than large Gammarus.

Background The expression of mutant HTT leads to many cellular alterations, including abnormal vesicle recycling, loss of signalling by brain-derived neurotrophic factor, excitotoxicity, perturbation of Ca 2+ signalling, decreases in intracellular ATP, alterations of gene transcription, inhibition of protein clearance pathways, mitochondrial and metabolic disturbances, and ultimately cell death. While robust mammalian systems have been developed to model disease and extensive mechanistic insights have emerged, significant differences between rodent and human cells and between non-neuronal cells and neurons limit the utility of these models for accurately representing human disease. Human pluripotent stem cells can generate highly specified cell populations, including DARPP32-positive MSNs of the striatum, and provide a method for modelling HD in human neurons carrying the mutation. As it is caused by one single gene, HD is an ideal disorder for exploring the utility of modelling disease in induced pluripotent stem cells (iPSCs) through reprogramming adult cells from HD patients with known patterns of disease onset and duration. Aims Generate iPSC lines from HD patients and controls and identify CAG-repeat expansion associated phenotypes. Methods/techniques Through the efforts of an international consortium effort, 14 lines were generated, differentiated into neuronal populations and assessed for CAG-repeat dependent outcome measures. Results/outcomes HD iPSC lines have reproducible CAG expansion–associated phenotypes upon differentiation, including CAG expansion-associated changes in gene expression patterns and alterations in electrophysiology, metabolism, cell adhesion, and ultimately an increased risk of cell death. While the lines with the longest repeats (HD180) showed a phenotype across all assays, those with shorter repeats (HD60) showed phenotypes in a specific sub set of assays. The most sensitive assay for establishing repeat dependent effects was found to be calcium responses to stress. Conclusions This HD iPSC collection represents a unique and well-characterised resource to elucidate disease mechanisms in HD and provides a novel human stem cell platform for screening new candidate therapeutics. Funding NIH, CHDI, CIRM.

Butyrivibrio sp. C3 degrades rutin anaerobically to yield phloroglucinol, carbon dioxide, 3,4-dihydroxy-benzaldehyde, and 3,4-dihydroxyphenylacetic acid. The sugars are first released by intracellular glycosidases and then the heterocyclic ring of the aglycone undergoes hydrolytic cleavage. The glycosides of quercetin added to the medium are readily metabolized, but the aglycone is not.

The effect on the conversion of carbon14 to quercetin by a buckwheat plant caused by variation in the dose rate of a carbon 14-labelled precursor in μmoles over a 100-fold range has been studied. The results expressed as dilution of carbon14 varied over a 200-fold range for the same precursor with most of the variation being found at low dose rates. When expressed as the percentage of administered carbon14 converted to quercetin the results for acetate, D-glucose, and L-phenyllactic acid were mostly constant over this range but L-phenylalanine had a maximum percentage conversion or an optimal dose rate. An explanation of the results in metabolic terms has been attempted.It is recommended that the "percentage of C14 converted" be used to express results in plant biosynthetic work.

An account has been given of observations made for over two years on the composition of the milk of the breeds of goat distributed throughout Great Britain. The average percentages of fat and solids-not-fat in the milk of the breeds, together with their standard errors, are recorded. The frequency with which evening and morning samples fell within specified limits of these constituents is indicated for each breed, and diagrammatically for all goats. Detailed analyses of the milk of each breed are given, with the maximum and minimum values encountered and the standard errors of the average figures. Comparison is made of the composition of the milk of the goat with that of the cow. The effect of stage of lactation on yield of milk and on percentages of fat and solids-not-fat are shown by means of curves. the effect of age on the yield and composition of milk is indicated. The average yields per lactation for each breed, based upon the records of animals officially recorded during the last ten years are noted.

Various C14-labelled compounds were administered to Fagopyrum tataricum. After allowing 24 hours for metabolism the quercetin was isolated and degraded, by a modified alkaline fusion, into phloroglucinol (ring A) and protocatechuic acid (ring B plus carbon 2). Uniformly labelled sucrose or C14O2 (assimilated photosynthetically) formed quercetin equally labelled in the A and B rings, but sodium acetate-1-C14 (or acetate-2-C14) gave quercetin labelled almost entirely in ring A. Isotope competition experiments indicated meso-inositol and phloroglucinol were not precursors of ring A. The biosynthesis of quercetin from C14O2 or acetate required the combined action of stem and leaves. Light was not required for synthesis of quercetin from acetate.

The results discussed in this paper are based on the weights and composition of the excrements of eight pullets, fed for the periods stated on three rations, which differed only in the amounts of calcium and phosphorus supplied in various combinations. The total amounts of calcium and phosphorus supplied daily were approximately the same in all cases.The birds were 5 months old White Wyandottes, and increased considerably in weight during the experimental period. No eggs were laid, but Pullet No. 2 died of prolapsus of the oviduct, and was found to have seven nearly full-sized yolks and one unshelled egg in the oviduct.

An account has been given of the lipin, phytin and inorganic phosphorus, and of the protein and non-protein nitrogen present in the wheat plant, from seven weeks before ear emergence until the crop was harvestedThe percentages and amounts of phosphorus and nitrogen so combined, together with their distribution between straw and ear, have been discussed.Relationships between phytin phosphorus and protein nitrogen, and between lipin phosphorus and non-protein nitrogen, have been indicated.

Cuttings of Fagopyrum tataricum were allowed to metabolize various labelled compounds for 24 hours in the light. Quercetin was then isolated and degraded by alkaline hydrolysis of its pentamethyl ether into veratric acid (ring B plus carbon 2) and 2′-hydroxy-2,4′,6′-trimethoxyacetophenone (ring A plus carbons 3 and 4). Eleven amino acids, including tyrosine, were poor precursors of quercetin as were also protocatechuic acid and p-hydroxybenzoic acid. Shikimic acid, phenylalanine, p-hydroxycinnamic acid, and cinnamic acid were very good precursors followed by (in decreasing order of effectiveness) caffeic acid (fair), sinapic acid, m-methoxycinnamic acid, and ferulic acid (very poor). Quercetin formed from β- or ring-labelled cinnamic acid gave labelled veratric acid on degradation, and that from α- or carboxyl-labelled cinnamic acid gave labelled 2′-hydroxy-2,4′,6′-trimethoxyacetophenone. Two-ninths of the activity of quercetin formed from uniformly labelled phenylalanine was found in the acetophenone derivative and seven-ninths in the veratric acid. These results show that C6.C3 compounds are used with the carbon skeleton unchanged for the synthesis of ring B and carbons 2, 3, and 4 of quercetin and that the ring hydroxylation pattern of the compound used determines its effectiveness. None of the compounds were good precursors of ring A.

The use of lime and phosphates in reclaiming heather moorland was investigated in two experiments. Large initial dressings of hme resulted in a rapid rise in pH. An initial dressing of 9 tons CaCO3/ac resulted in a more rapid rise to pH 6 than did 6 tons/ac and the soil was maintained above pH 6 for a longer period. Three annual dressings of 3 tons/ac gave a slower rise in pH and a longer period above pH 6. Split treatments, half before and half after the first ploughing, gave no long–term advantage where a programme of pioneer cropping was being followed. Basic slag and North African phosphate were as effective as superphosphate for root crops at low pH values. Basic slag was as effective as superphosphate for grassland establishment and gave a greater rise in soil phosphate. North African phosphate was virtually worthless as a source of phosphate for establishing grasses and clovers, and gave a negligible rise in soil phosphate. Given adequate supphes of lime and phosphate, frequent small apphcations of N over the first 2 or 3 years are vital to the success of a reclamation programme under the conditions described.

1. An account has been given of the percentages of nutrients in the dry matter and weights of nutrients in tops, tubers and roots of potato plants throughout growth under six fertilizer treatments.2. Manurial treatment affected dry-matter content of tops but not of tubers.3. Balanced manuring, as represented by N2PK treatment, resulted in tubers in which nitrogen content of dry matter declined with age. The effect of the K was to lower the nitrogen, phosphorus and calcium contents, to increase chlorine content of all parts of the plant, and to maintain a much higher and more constant concentration of potassium in tops and roots. With unbalanced manuring the nitrogen content of the tubers was more constant.4. Manuring with nitrogen only raised the content of potassium in the dry matter of all parts of the plant.5. Nitrogenous manuring, whether alone or in combination, raised the nitrogen content of the dry matter of all parts of the plant, a smaller proportion of which was present as protein. Calcium and chlorine contents were lowered.6. Phosphate manuring in conjunction with nitrogen depressed the concentration of potash in the dry matter of all parts of the plant.7. N2P plants were the first to attain their maximum uptake of all nutrients, namely, about 7 weeks from appearance above ground, at which time N2PK plants had absorbed only 40% of the quantities finally noted.8. No losses of elements were observed in the plants which received balanced manuring (N2PK), but losses of calcium and chlorine occurred in all other plants, amounting on the average to 25 and 37% respectively, but being highest in N2P plants. A significant loss of potassium occurred in N2 plants and a highly suggestive loss of phosphorus occurred in N2P plants.

1. An account has been given of the composition and weights of nutrients in 3200 wheat plants from seven weeks before ear emergence until the crop was harvested. The distribution of the plant nutrients, and the rate of assimilation and translocation of these nutrients, have been discussed. 2. In the case of the whole plant, the percentage of nutrients in the dry matter decreased from the time of the first sampling, with the exception of silica, which had a tendency to remain constant throughout. In the case of the ear, diminution in the percentage of nutrients in the dry matter was observed from a fortnight after ear emergence until harvest. 3. Marked increases in the weights of all nutrients in the whole plant were noted until ear emergence, from then onwards assimilation was much slower. The plant attained its maximum quantities of the nutrients in the following order: potash seven weeks, lime and chlorine five weeks, nitrogen three weeks, carbon, phosphoric acid and silica two weeks, before harvest. Assimilation of these had, therefore, ceased at the above stated times, although transference to the ear proceeded until within about a week before harvest.

Field instrumentation is investigated on an in-service highway bridge over a 2-year period. Extrinsic Fabry-Perot interferometric (EFPI) strain sensors provide a permanent health-monitoring capability. The bridge is a reinforced-concrete (RC) structure that was repaired and strengthened using fiber-reinforced-polymer (FRP) wraps. A sensor network monitors the load-induced strain in the FRP reinforcement and the steel rebar. Colocated electrical resistance strain gauges and a finite element analysis are used for comparison. Both dynamic and static load characteristics are analyzed for a near-capacity truck. The fiber optic measurements are generally consistent with the comparison measurements and the analytical results; and they show no failure or degradation as opposed to the electrical resistance gauges. We demonstrate the implementation and the performance of in situ EFPI sensors in a long-term field environment. Embedded fiber optic sensors can provide the required information for the intelligent management of a transportation infrastructure.

An all-composite, smart bridge design for shortspan applications is described. The bridge dimensions are 9.14-m (30-ft.) long and 2.74-m (9-ft.) wide. A modular construction based on assemblies of pultruded fiber-reinforced-polymer (FRP) composite tubes is used to meet American Association of State Highway and Transportation Officials (AASHTO) H20 highway load ratings. The hollow tubes are 76 mm (3 in.) square and are made of carbon/vinyl-ester and glass/vinyl-ester. An extensive experimental study was carried out to obtain and compare properties (stiffness, strength, and failure modes) for a quarter portion of the full-sized bridge. The bridge response was measured for design loading, two-million-cycle fatigue loading, and ultimate load capacity. In addition to meeting H20 load criteria, the test article showed almost no reduction in stiffness or strength under fatigue loading and excellent linear elastic behavior up to failure. Fiber optic strain sensors were evaluated on the test article during testing. Sensor characteristics are determined as preparation for permanent field installation.