Chemical Probes and the Exploration of Bromodomains in Cancer Biology

The post-translational modification of histones and their interaction with transcription factors is essential to gene regulation. Furthermore, these targets would greatly benefit from probe molecules to fully elucidate their biological actions and to potentially lead to therapeutics. However, these protein-protein interactions have been considered difficult to inhibit and few high-quality chemical probes currently exist for the study of epigenetic biological systems in particular

Global Analysis of Nucleon Strange Form Factors at Low Q2Q^2

We perform a global analysis of all recent experimental data from elastic parity-violating electron scattering at low $Q^2$. The values of the electric and magnetic strange form factors of the nucleon are determined at $Q^2 = 0.1$ GeV/$c^2$ to be $G^s_E = -0.008 \pm 0.016$ and $G^s_M = 0.29 \pm 0.21$.Comment: 8 pages, 1 figur

Electrophilic Rh^I catalysts for arene H/D exchange in acidic media: evidence for an electrophilic aromatic substitution mechanism

A series of new rhodium (I) complexes supported by bidentate nitrogen-donor ligands with varying electronic and steric properties were synthesized in situ and evaluated for catalytic arene C−H/D activation. In trifluoroacetic acid (HTFA), these complexes are proposed to mediate H/D exchange of arene C−H/D bonds by an electrophilic aromatic substitution mechanism that involves Rh-mediated activation of HTFA (or DTFA). DFT calculations support the proposed pathway for the H/D exchange reactions

Electrophilic Rh^I catalysts for arene H/D exchange in acidic media: evidence for an electrophilic aromatic substitution mechanism

A series of new rhodium (I) complexes supported by bidentate nitrogen-donor ligands with varying electronic and steric properties were synthesized in situ and evaluated for catalytic arene C−H/D activation. In trifluoroacetic acid (HTFA), these complexes are proposed to mediate H/D exchange of arene C−H/D bonds by an electrophilic aromatic substitution mechanism that involves Rh-mediated activation of HTFA (or DTFA). DFT calculations support the proposed pathway for the H/D exchange reactions

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure.BackgroundPatients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism.MethodsOur objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (± sd) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 ± 5 and 25 ± 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 ± 1037 (887) and 1402 ± 1183 (1430)ml/24hr and 6.4 ± 5.9 (4.3) and 8.7 ± 7.2 (4.4)ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12hours with rhIGF-I, 100 μg/kg desirable body weight, or placebo for up to 14days. Injections were started within six days of the onset of ARF. The primary end-point was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate.ResultsDuring the treatment period, which averaged 10.7 ± 4.1 and 10.6 ± 4.5days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I–treated patients and 12 placebo-treated patients died during the 28days after the onset of treatment.ConclusionsrhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity

Patterns of ongoing thought in the real world

Health and well-being are impacted by our thoughts and the things we do. In the laboratory, studies suggest specific task contexts impact thought processes. More broadly, this suggests the people we are with, the places we are in, and the activities we perform may influence our thought patterns. In our study, participants completed experience sampling surveys for five days in daily life. Principal component analysis decomposed this data to identify common “patterns of thought,” and linear mixed modelling related these patterns to the participants’ activities. Our study replicated the influence of socializing on patterns of thought and established that this is part of a broader set of relationships linking activities to how thoughts are organized in daily life. Our study suggests sampling thinking in the real world may help map thoughts to activities, and these “thought-activity” mappings could be useful to researchers and health care professionals interested in health and well-being