Trichothiodystrophy (TTD) is an autosomal recessive disorder with symptoms affecting several tissues and organs. The most relevant features are hair abnormalities, physical and mental retardation, ...ichthyosis, signs of premature aging and cutaneous photosensitivity. The clinical spectrum of TTD varies widely from patients with only brittle, fragile hair to patients with the most severe neuroectodermal symptoms. To date, four genes have been identified as responsible for TTD:
XPD,
XPB,
p8/
TTDA, and
TTDN1. Whereas the function of
TTDN1 is still unknown, the former three genes encode subunits of TFIIH, the multiprotein complex involved in basal and activated transcription and in nucleotide excision repair (NER). Ongoing investigations on TTD are elucidating not only the pathogenesis of the disease, which appears to be mainly related to transcriptional impairment, but also the modalities of NER and transcription in human cells and how TFIIH operates in these two fundamental cellular processes.
The FINUDA experiment at DAΦNE, Frascati, has found evidence for the neutron-rich hypernucleus HΛ6_ \wedge ^6{\rm{H}}$ studying (π+, π−) pairs in coincidence from the ...Kstop−+L6i→HΛ6+π+$K_{{\rm{stop}}}^ - + {}^{\rm{6}}{\rm{Li}} \to {}_ \wedge ^6{\rm{H}} + {\pi ^ + }$ production reaction followed by HΛ6→H6e +π−_ \wedge ^6{\rm{H}} \to {}^6{\rm{He + }}{\pi ^ - }$ weak decay. The production rate of HΛ6_ \wedge ^6{\rm{H}}$ undergoing this two-body π− decay has been found to be (2.9±2.0)⋅10−6/Kstop−$(2.9 \pm 2.0) \cdot {10^{ - 6}}/K_{{\rm{stop}}}^ - $. Its binding energy has been evaluated to be BΛ(HΛ6)=(4.0±1.1)${B_ \wedge }({}_ \wedge ^6H) = (4.0 \pm 1.1)$ MeV with respect to (H5+Λ)$({}^5{\rm{H}} + \Lambda )$, jointly from production and decay. A systematic difference of (0.98 ± 0.74) MeV between BΛ values derived separately from decay and from production has been tentatively assigned to the HΛ6 0g.s.+→1+_\Lambda ^6{\rm{H 0}}_{{\rm{g}}{\rm{.s}}{\rm{.}}}^ + \to {1^ + }$ excitation. A similar investigation has been carried out for the neutron-rich hypernucleus HΛ9e_\Lambda ^9{\rm{He}}$ studying the Kstop−+B9e→HΛ9e+π+$K_{{\rm{stop}}}^ - + {}_{}^{\rm{9}}{\rm{Be}} \to {}_\Lambda ^9{\rm{He}} + {\pi ^ + }$ reaction in coincidence with the H Λ 9e→ L 9i + π −_\Lambda ^9{\rm{He}} \to {}_{}^{\rm{9}}{\rm{Li + }}{\pi ^ - }$ weak decay; an upper limit for the production rate of HΛ9e_\Lambda ^9{\rm{He}}$ undergoing the two-body π− decay has been found to be 4.2⋅10 −6 /K stop− $4.2 \cdot {10^{ - 6}}/{\rm{K}}_{stop}^ - $ (90% C.L.).
The recent determination of the partial decay widths for the one-proton and the two-nucleon induced Non-Mesonic Weak Decay of Λ-Hypernuclei in the A=5–16 range permitted to reconstruct the full ...pattern of decay widths for 5ΛHe and 11ΛB. A consistency check on 12ΛC decay widths confirms the validity of the adopted method.
Introduction:
Pulmonary arterial hypertension is a progressive haemodynamic disease with high morbidity and mortality. Of the different treatments available, the prostacyclin analogues are the drugs ...of choice for high-risk patients, with treprostinil being the most commonly used drug in Argentina.
Methodology:
The objective of this study is to perform a retrospective evaluation of the efficacy and safety of subcutaneous treprostinil in regular clinical practice in Argentina in 51 patients with pulmonary arterial hypertension after 12 months of follow-up.
Results:
The results showed that treatment with subcutaneous treprostinil is associated with a significant improvement in different clinical efficacy parameters: 65% reduction in advanced functional class (p < 0.0001), 130-m increase in the 6-min walk test (p < 0.0001), 65% reduction in the pro B-type natriuretic peptide value (–531 pg/dL; p < 0.0001), significant reduction of 15.7% in pulmonary vascular resistance –1.3 wood units (WU); p < 0.0001, improved cardiac index with an increase of 16.7% (+0.4 L/min/m2; p = 0.002), as well as a high survival rate (92%) and a 44% incidence of combined events (mortality, heart failure, syncope and/or lung transplantation), without a significant increase in previously reported adverse events. The risk stratification evaluation according to ESC/ERS guidelines showed a significant decrease in the proportion of patients at high risk after the treatment period (p = 0.004).
Conclusions:
These real-world results corroborate the efficacy and safety of subcutaneous treprostinil, even at high doses, and open up the possibility of improving its current use in clinical practice as a first-line therapy, especially in high-risk patient profiles.
We have searched for a deeply bound kaonic state by using the FINUDA spectrometer installed at the e(+)e(-) collider DAPhiNE. Almost monochromatic K(-)'s produced through the decay of phi(1020) ...mesons are used to observe K(-) absorption reactions stopped on very thin nuclear targets. Taking this unique advantage, we have succeeded to detect a kaon-bound state K(-)pp through its two-body decay into a Lambda hyperon and a proton. The binding energy and the decay width are determined from the invariant-mass distribution as 115(+6)(-5)(stat)(+3)(-4)(syst) MeV and 67(+14)(-11)(stat)(+2)(-3)(syst) MeV, respectively.
The MerR family is a group of bacterial transcriptional regulators that respond to different environmental stimuli, such as heavy metals, oxidative stress or antibiotics. Here we characterize a new ...member of this family that is highly selective for Au ions. We show that this Salmonella regulator, named GolS, directly controls the expression of at least two transcriptional units specifically required for Au resistance. By chromosomal mutagenesis, we demonstrated that Au-selectivity is accomplished by a metal-binding motif in GolS. Among the monovalent metal-ion sensing MerR regulators GolS clusters in a branch distant from enterobacterial CueR orthologues. We propose that GolS and its homologues evolved to cope with toxic concentration of Au ion, allowing microorganisms to withstand contaminated environments.
Background: Children living at high altitude in San Antonio de los Cobres (SAC), Argentina, were shown to have lower high-density lipoprotein cholesterol (HDL-C) levels than Buenos Aires (BA) ...children. HDL antioxidant capacity is mainly attributed to paraoxonase1 (PON1).
Objective: To compare PON1 activity in indigenous SAC vs. BA children.
Methods: A cross-sectional study compared 158 SAC vs. 97 BA children (6-16 years). Anthropometric data and lipoprotein profile were measured. PON1 was evaluated employing paraoxon (PON) and phenylacetate (ARE) activity.
Results: The prevalence of overweight/obesity was lower in SAC than in BA children (18.3 vs. 30.9%). Triglycerides (1.34 vs. 0.90 mmol/l), apo B (0.84 vs.0.72 g/l), apo A-I (1.33 vs. 1.27 g/l), and ARE activity (100 vs. 90 µmol/ml/min) were higher, while HDL-C (1.16 vs. 1.32 mmol/l) and PON activity (170 vs. 203 nmol/ml/min) were lower in SAC than in BA. Separate multiple linear regression analyses showed that SAC children had significantly higher triglyceride (Beta −0.38), apo B (Beta −0.34), and ARE (Beta −0.36) plus lower HDL-C (Beta 0.33) and PON (Beta 0.25) compared with BA; adjusted for age, gender, and BMI.
Conclusion: SAC showed an unfavorable lipoprotein profile, lower PON and higher ARE activities compared with BA children, suggesting the presence of altered HDL metabolism and antioxidant capacity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In recent years, several experiments using magnetic spectrometers provided high precision results in the field of Hypernuclear Physics. In particular, the accurate determination of the Λ-binding ...energy, BΛ, contributed to stimulate considerably the discussion about the Charge Symmetry Breaking effect in Λ-hypernuclei isomultiplets.
We have reorganized the results from the FINUDA experiment and we have obtained a series of BΛ values for Λ-hypernuclei with A≤ 16 by taking into account data only from magnetic spectrometers implementing an absolute calibration of the energy scale (FINUDA at DAΦNE and electroproduction experiments at JLab and at MaMi). We have then critically revisited the results obtained at KEK by the SKS Collaboration in order to make possible a direct comparison between data from experiments with and without such an absolute energy scale. A synopsis of recent spectrometric measurements of BΛ is presented, including also emulsion experiment results.
Several interesting conclusions are drawn, among which the equality within the errors of BΛ for the A=7,12,16 isomultiplets, based only on recent spectrometric data. This observation is in nice agreement with a recent theoretical prediction.
Ideas for possible new measurements which should improve the present experimental knowledge are finally put forward.
Mutations in the XPD subunit of the transcription/DNA repair factor (TFIIH) give rise to trichothiodystrophy (TTD), a rare hereditary multisystem disorder with skin abnormalities. Here, we show that ...TTD primary dermal fibroblasts contain low amounts of collagen type VI alpha1 subunit (COL6A1), a fundamental component of soft connective tissues. We demonstrate that COL6A1 expression is downregulated by the sterol regulatory element-binding protein-1 (SREBP-1) whose removal from the promoter is a key step in COL6A1 transcription upregulation in response to cell confluence. We provide evidence for TFIIH being involved in transcription derepression, thus highlighting a new function of TFIIH in gene expression regulation. The lack of COL6A1 upregulation in TTD is caused by the inability of the mutated TFIIH complexes to remove SREBP-1 from COL6A1 promoter and to sustain the subsequent high rate of COL6A1 transcription. This defect might account for the pathologic features that TTD shares with hereditary disorders because of mutations in COL6A genes.
PDF
