Deuterated molecules in regions of high-mass star formation

We present the results of our studies of deuterated molecules (DCN, DNC, DCO$^+$, N$_2$D$^+$ and NH$_2$D) in regions of high-mass star formation, which include a survey of such regions with the 20-m Onsala radio telescope and mapping of several objects in various lines with the 30-m IRAM and 100-m MPIfR radio telescopes. The deuteration degree reaches $\sim$10$^{-2}$ in these objects. We discuss its dependencies on the gas temperature and velocity dispersion, as well as spatial distributions of deuterated molecules. We show that the H$^{13}$CN/HN$^{13}$C intensity ratio may be a good indicator of the gas kinetic temperature and estimate densities of the investigated objects.Comment: 8 pages, 4 figures, to be published in Proceedings of Science (Proceedings of the conference "The Multifaceted Universe: Theory and Observations - 2022", 23-27 May 2022, SAO RAS, Nizhny Arkhyz, Russia

Sudomotor Testing of Diabetes Polyneuropathy

Objective: The performance of the Sudoscan technology for diagnosing diabetic polyneuropathy (DPN) was evaluated against the quantitative sudomotor axon reflex test (QSART). Furthermore, the association of Sudoscan with two clinical neuropathy scoring systems was evaluated.Methods: Forty-seven patients with type 2 diabetes (20 without DPN, 27 with DPN) and 16 matched controls were examined for neuropathic symptoms and for the extent of sensory deficits. Sweat latency and volume by QSART and the skin electrochemical conductance (ESC) by Sudoscan were measured.Results: The feet and hand ESC was significantly lower in patients with DPN as compared to controls. Patients with DPN had also lower hand ESC than patients without DPN. Sensitivity and specificity of feet and hand ESC for detecting DPN were 70/85% and 53/50% respectively. QSART could not differentiate between the three groups. ESC was inversely related to neuropathic symptoms and sensory impairment. ESC was significantly correlated with sensory impairment and pain.Conclusions: Sudoscan shows a good performance in detecting subjects with DPN and it correlates well with clinical signs and symptoms of neuropathy.Significance: This study provides evidence that Sudoscan has high potential to be used as screening tool for DPN and possibly also for small fiber neuropathy in diabetic patients.HIGHLIGHTS- The sudomotor function test Sudoscan shows a good performance to detect diabetes peripheral neuropathy.- Sudoscan measures significantly correlate with clinical signs and symptoms of neuropathy.- The Sudoscan technology may help to secure clinical diagnosis of small fiber neuropathy

CRISPR/Cas9-mediated knockout of c-REL in HeLa cells results in profound defects of the cell cycle

Slotta C, Schlüter T, Ruiz-Perera LM, et al. CRISPR/Cas9-mediated knockout of c-REL in HeLa cells results in profound defects of the cell cycle. PLOS ONE. 2017;12(8): e0182373.Cervical cancer is the fourth common cancer in women resulting worldwide in 266,000 deaths per year. Belonging to the carcinomas, new insights into cervical cancer biology may also have great implications for finding new treatment strategies for other kinds of epithelial cancers. Although the transcription factor NF-κB is known as a key player in tumor formation, the relevance of its particular subunits is still underestimated. Here, we applied CRISPR/Cas9n-mediated genome editing to successfully knockout the NF-κB subunit c-REL in HeLa Kyoto cells as a model system for cervical cancers. We successfully generated a homozygous deletion in the c-REL gene, which we validated using sequencing, qPCR, immunocytochemistry, western blot analysis, EMSA and analysis of off-target effects. On the functional level, we observed the deletion of c-REL to result in a significantly decreased cell proliferation in comparison to wildtype (wt) without affecting apoptosis. The impaired proliferative behavior of c-REL-/- cells was accompanied by a strongly decreased amount of the H2B protein as well as a significant delay in the prometaphase of mitosis compared to c-REL+/+ HeLa Kyoto cells. c-REL-/- cells further showed significantly decreased expression levels of c-REL target genes in comparison to wt. In accordance to our proliferation data, we observed the c-REL knockout to result in a significantly increased resistance against the chemotherapeutic agents 5-Fluoro-2’-deoxyuridine (5-FUDR) and cisplatin. In summary, our findings emphasize the importance of c-REL signaling in a cellular model of cervical cancer with direct clinical implications for the development of new treatment strategies

Pilot study for essentiality assessment of Standard Essential Patents

This study investigates the technical and institutional feasibility of a system that ensures better essentiality scrutiny for Standard Essential Patents (SEPs). We first studied the state of the art on essentiality assessment in literature, court cases involving larger scale essentiality assessments, essentiality assessment in patent pools, and the Japanese Hantei for Essentiality advisory opinion. A patent landscape analysis of SDO declared patents was performed to assess their use as input to essentiality assessment mechanisms. Technical feasibility was assessed in a pilot experiment, in which a variety of assessors evaluated patents for their actual essentiality. Institutional feasibility was, among other means, assessed via a stakeholder workshop. Given (1) the observed interest in transparent data on essentiality of patents for standards, from implementers, patent owners and courts alike, (2) the potential benefits of such data for these parties and for the system as a whole, and (3) our finding that a system for generating such data seems both technically and institutionally feasible, we recommend policy makers to pursue the development and implementation of a system for essentiality assessments.JRC.B.6-Digital Econom

Functional genomic analysis unravels a metabolic-inflammatory interplay in adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) and (iii) a childhood variant, cALD, characterized by severe cerebral demyelination. Loss of function of the ABCD1 peroxisomal fatty acid transporter and subsequent accumulation of very-long-chain fatty acids (VLCFAs) are the common culprits to all forms of X-ALD, an aberrant microglial activation accounts for the cerebral forms, whereas inflammation allegedly plays no role in AMN. How VLCFA accumulation leads to neurodegeneration and what factors account for the dissimilar clinical outcomes and prognosis of X-ALD variants remain elusive. To gain insights into these questions, we undertook a transcriptomic approach followed by a functional-enrichment analysis in spinal cords of the animal model of AMN, the Abcd1− null mice, and in normal-appearing white matter of cAMN and cALD patients. We report that the mouse model shares with cAMN and cALD a common signature comprising dysregulation of oxidative phosphorylation, adipocytokine and insulin signaling pathways, and protein synthesis. Functional validation by quantitative polymerase chain reaction, western blots and assays in spinal cord organotypic cultures confirmed the interplay of these pathways through IkB kinase, being VLCFA in excess a causal, upstream trigger promoting the altered signature. We conclude that X-ALD is, in all its variants, a metabolic/inflammatory syndrome, which may offer new targets in X-ALD therapeutics

CCS and NH3 emission associated with low-mass young stellar objects

In this work we present a sensitive and systematic single-dish survey of CCS emission (complemented with ammonia observations) at 1 cm, toward a sample of low- and intermediate-mass young star forming regions known to harbor water maser emission, made with NASA's 70 m antenna at Robledo de Chavela, Spain. Out of the 40 star forming regions surveyed in the CCS(2_{1}-1_{0}) line, only 6 low-mass sources show CCS emission: one transitional object between pre-stellar and protostellar Class 0 phase (GF9-2), three Class 0 protostars (L1448-IRS3, L1448C, and B1-IRS), a Class I source (L1251A), and a young T Tauri star (NGC2071-North). Since CCS is considered an ``early-time'' (<10E+5 yr) molecule, we explain these results by either proposing a revision of the classification of the age of NGC2071-North and L1251A, or suggesting the possibility that the particular physical conditions and processes of each source affect the destruction/production of the CCS. No statistically significant relationship was found between the presence of CCS and parameters of the molecular outflows and their driving sources. Nevertheless, we found a significant relationship between the detectability of CCS and the ammonia peak intensity (higher in regions with CCS), but not with its integrated intensity. This tendency found may suggest that the narrower ammonia line widths in the less turbulent medium associated with younger cores may compensate for the differences in ammonia peak intensity, rendering differences in integrated intensity negligible. From the CCS detection rate we derive a lifetime of this molecule of ~(0.7-3) x 10E+4 yr in low-mass star forming regions.Comment: 28 pages, 1 figure, 3 tables, to appear in the 2006 May 1 issue of the Astrophysical Journa

Comparative proteomic analysis of spermatozoa isolated by swim-up or density gradient centrifugation

Abstract BACKGROUND: Reports about the morphologic and functional characteristics of spermatozoa prepared by density gradient centrifugation (DC) or swim-up (SU) have produced discordant results. We have performed a proteomic comparison of cells prepared by DC and SU providing a molecular insight into the differences between these two methods of sperm cell isolation. METHODS: Protein maps were obtained by 2-dimensional (2-D) separations consisting of isoelectrofocusing (IEF) from pI 3 to 11 followed by SDS-polyacrylamide gel electrophoresis. 2-D gels were stained with Sypro Ruby. Map images of DC and SU spermatozoa were compared using dedicated software. Intensities of a given spot were considered different between DC and SU when their group mean differed by >1.5-fold (p<0.05, Anova). RESULTS: No differences were observed for 853 spots, indicating a 98.7% similarity between DC and SU. Five spots were DC>SU and 1 was SU>DC. Proteins present in 3 of the differential spots could be identified. One DC>SU spot contained lactate dehydrogenase C and gamma-glutamylhydrolase, a second DC>SU spot contained fumarate hydratase and glyceraldehyde-3-phosphate dehydrogenase-2, and a SU>DC spot contained pyruvate kinase M1/M2. CONCLUSIONS: The differences in protein levels found on comparison of DC with SU spermatozoa indicate possible dissimilarities in their glycolytic metabolism and DNA methylation and suggest that DC cells may have a better capacitation potential