Sc0.43(2)Rb2Mo15S19, a partially Sc-filled variant of Rb2Mo15S19

International audienceThe structure of scandium dirubidium pentadecamolybdenum nonadecasulfide, Sc0.43 (2)Rb2Mo15S19, constitutes a partially Sc-filled variant of Rb2Mo15S19 [Picard, Saillard, Gougeon, Noel & Potel (2000), J. Solid State Chem.155, 417426]. In the two compounds, which both crystallize in the Rc space group, the structural motif is characterized by a mixture of Mo6Si8Sa6 and Mo9Si11Sa6 cluster units ('i' is inner and 'a' is apical) in a 1:1 ratio. The two components are interconnected through interunit MoS bonds. The cluster units are centred at Wyckoff positions 6b and 6a (point-group symmetries and 32, respectively). The Rb+ cations occupy large voids between the different cluster units. The Rb and the two inner S atoms lie on sites with 3. symmetry (Wyckoff site 12c), and the Mo and S atoms of the median plane of the Mo9S11S6 cluster unit lie on sites with .2 symmetry (Wyckoff site 18e). A unique feature of the structure is a partially filled octahedral Sc site with symmetry. Extended Huckel tight-binding calculations provide an understanding of the variation in the MoMo distances within the Mo clusters induced by the increase in the cationic charge transfer due to the insertion of Sc

Późny przerzut do wątroby raka rdzeniastego tarczycy z niskim stężeniem kalcytoniny skutecznie wyleczony metodą radioablacji

  A 28-year-old female consulted in 1994 for a left thyroid nodule known for two years with documented progression. Left lobe resection was performed initially followed by total thyroidectomy without lymph node dissection in September 1994. Pathological examination concluded on unilateral 10 × 40 mm medullary thyroid carcinoma (MTC). RET mutation was negative. Basal and pentagastrin-stimulated CT levels had been normal from 1994 to 2008 when her CT level was found to be elevated at 33 ng/L and increased subsequently to 111 ng/L in 2010. In accordance with guidelines, cervical ultrasound was performed repeatedly with negative results. After discussion in a multidisciplinary meeting and with patient’s consent, an F-Dopa PET scan was proposed in disagreement with guidelines. This scan showed unique uptake in liver segment VI, which was confirmed by MRI. CT levels reached to 253 ng/L when she finally accepted treatment. In February 2013 we performed radiofrequency ablation of the lesion, which allowed normalisation of CT levels. This observation highlights the possibility of late recurrence of MTC. We could propose that for MTC patients with low-calcitonin levels-recurrences F-DOPA-PET/CT is a good diagnostic tool to use in case of repeatedly negative US neck studies. (Endokrynol Pol 2016; 67 (3): 326–329)    Chora w wieku 28 lat zgłosiła się do lekarza w 1994 roku z powodu lewostronnego guzka tarczycy wykrytego 2 lata wcześniej, z potwierdzoną progresją. Wykonano resekcję lewego płata tarczycy. Totalną tyreoidektomię wykonano we wrześniu 1994 roku bez usunięcia węzłów chłonnych. W badaniu patomorfologicznych stwierdzono jednostronnego raka rdzeniastego tarczycy (MTC) o wymiarach 10 × 40 mm. Wynik badania w kierunku mutacji RET był ujemny. Stężenia kalcytoniny (CT, calcitonin), podstawowe i po stymulacji pentagastryną, były prawidłowe od 1994 roku. Do 2008 roku, kiedy stwierdzono podwyższone stężenie CT wynoszące 33 ng/l, a następnie jego dalszy wzrost do 111 ng/l w 2010 roku. Zgodnie z zaleceniami powtórnie wykonano badanie USG szyi, w którym nie stwierdzono nieprawidłowości. Po omówieniu przypadku na spotkaniu wielodyscyplinarnego zespołu i uzyskaniu zgody chorej przeprowadzono badanie F-Dopa PET (niezgodnie z zaleceniami), w którym wykazano pojedyncze ognisko wychwytu w segmencie VI wątroby, co zostało potwierdzone w badaniu MRI. Kiedy chora w końcu zaakceptowała leczenie, stężenia CT zwiększyły się do 253 ng/l. W lutym 2013 roku wykonano ablację zmiany prądem o częstotliwości radiowej, co pozwoliło uzyskać normalizację stężeń CT w 2015 r. Ta obserwacja zwraca uwagę na możliwość późnej wznowy. Autorzy sugerują, że u chorych z MTC z ponownie stwierdzonym niskim stężeniem kalcytoniny wybór F-DOPA-PET/CT jako metody diagnostycznej jest dobrym rozwiązaniem w przypadku powtórnych ujemnych wyników USG szyi. (Endokrynol Pol 2016; 67 (3): 326–329)

Atypical Angioma Serpiginosum

Angioma serpiginosum is an uncommon, acquired vascular nevoid disorder with capillary dilation and proliferation in the papillary dermis. The eruptions are asymptomatic and characterized by grouped, erythematous to violaceous, serpiginous and punctate macules. The condition usually appears in females during adolescence on unilateral lower extremities and the buttocks. We report a rare case with a late onset and atypical distribution of lesions in a 48-year-old female patient who had groups of punctate lesions on her left foot for four to five years. Histopathological examination showed hyperkeratosis and multiple dilated and proliferated capillaries in the papillary dermis. Inflammation and extravasation of red blood cells were not found. According to the clinical and pathological findings, we established a diagnosis of angioma serpiginosum. She was treated with a pulsed dye laser, and the angiomatous lesions subsequently improved

GEPAS, a web-based tool for microarray data analysis and interpretation

Gene Expression Profile Analysis Suite (GEPAS) is one of the most complete and extensively used web-based packages for microarray data analysis. During its more than 5 years of activity it has continuously been updated to keep pace with the state-of-the-art in the changing microarray data analysis arena. GEPAS offers diverse analysis options that include well established as well as novel algorithms for normalization, gene selection, class prediction, clustering and functional profiling of the experiment. New options for time-course (or dose-response) experiments, microarray-based class prediction, new clustering methods and new tests for differential expression have been included. The new pipeliner module allows automating the execution of sequential analysis steps by means of a simple but powerful graphic interface. An extensive re-engineering of GEPAS has been carried out which includes the use of web services and Web 2.0 technology features, a new user interface with persistent sessions and a new extended database of gene identifiers. GEPAS is nowadays the most quoted web tool in its field and it is extensively used by researchers of many countries and its records indicate an average usage rate of 500 experiments per day. GEPAS, is available at http://www.gepas.org

Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals.

The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function

Correction to: The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease.

Following publication of the original article [1], the author identified an error in Fig. 4E. The data and statistics were correct, but the synaptophysin blot was incorrect. The incorrect (Fig. 1) and correct figure (Fig. 2) are shown in this correction article. (Figure presented.)

The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease

Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions. In vitro, PBT434 was far less potent than deferiprone or deferoxamine at lowering cellular iron levels, yet was found to inhibit iron-mediated redox activity and iron-mediated aggregation of α-synuclein, a protein that aggregates in the neuropathology. In vivo, PBT434 did not deplete tissue iron stores in normal rodents, yet prevented loss of substantia nigra pars compacta neurons (SNpc), lowered nigral α-synuclein accumulation, and rescued motor performance in mice exposed to the Parkinsonian toxins 6-OHDA and MPTP, and in a transgenic animal model (hA53T α-synuclein) of PD. These improvements were associated with reduced markers of oxidative damage, and increased levels of ferroportin (an iron exporter) and DJ-1. We conclude that compounds designed to target a pool of pathological iron that is not held in high-affinity complexes in the tissue can maintain the survival of SNpc neurons and could be disease-modifying in PD