A homotopy idempotent construction by means of simplicial groups

We obtain a simplicial group model for localization of (not necessarily nilpotent) spaces at sets of primes by applying a suitable functor dimensionwise, as in earlier work of Quillen and Bousfield-Kan. For a set of primesP and any groupG, letG→L _PG be a universal homomorphism fromG into a group which is uniquely divisible by primes not inP, and denote also byL _P the prolongation of this functor to simplicial groups. We prove that, ifX is any connected simplicial set andJ is any free simplicial group which is a model for the loop space ΩX, then the classifying space is homotopy equivalent to the localization ofX atP. Thus, there is a map which is universal among maps fromX into spacesY for which the semidirect products π_κ(Y)⋊ π₁(Y) are uniquely divisible by primes not inP. This approach also yields a neat construction of fibrewise localization. Both authors are supported by DGES under grant PB97-0202, and the first-named author has a DGR fellowship with reference code 1997FI 00467.     

Highly diastereoselective boron and titanium mediated aldol reactions of a mannitol derived 2,3-butanediacetal ethyl ketone

A mannitol derived 2,3-butanediacetal ethyl ketone displays high levels of diastereoselectivity in boron and titanium mediated aldol reactions with a range of aliphatic and aromatic aldehydes to afford syn aldol products in high yield. The stereochemical outcome of the reaction was determined using J-value analysis, NMR analysis of O-acetylmandelate derivatives and X-ray crystallography.     

Pyrroloquinoxaline hydrazones as fluorescent probes for amyloid fibrils

Here we describe the identification and preliminary characterization of a new class of pyrrolo(imidazo)quinoxaline hydrazones as florescent probes for Aβ(1-42) fibrils. All the newly developed compounds were able to bind amyloid fibrils formed in vitro and some of them displayed an increase of their fluorescence upon binding. When tested on brain tissue preparations presenting Aβ deposits, the described hydrazones selectively stained amyloid structures and did not display aspecific binding. The hydrazones did not show antifibrillogenic activity and electron microscopy analysis revealed that they do not interfere with fibrils structure. The described pyrrolo(imidazo)quinoxalines could be useful for studying amyloid structures in vitro. Moreover, their experimentally proven ability to cross the blood-brain barrier in mouse opens the possibility of developing these compounds as potential amyloid imaging agents for in vivo applications.     

Mixed lithium amide-lithium halide compounds: unusual halide-deficient amido metal anionic crowns

Molecular salt cellars: The addition of substoichiometric quantities of lithium halides to the lithium hexamethyldisilazide was studied. Surprisingly, a novel class of mixed amido-halide macrocyclic complexes, namely metal anionic crowns (MACs) was revealed (see picture: Li?pink, N?yellow, Cl?green, Si?orange, C?black).     

Identification of acyl protein thioesterases 1 and 2 as the cellular targets of the ras-signaling modulators palmostatin b and m

Finding the target: Activity-based proteomic profiling probes based on the depalmitoylation inhibitors palmostatin?B and M have been synthesized and were found to target acyl protein thioesterase?1 (APT1) and 2 (APT2) in cells.     

Effectiveness of Physical Therapy in Patients with Tension-type Headache: Literature Review

Background: Tension-type headache (TTH) is a disease with a great incidence on quality of life and with a significant socioeconomic impact. Objectives: The aim of this review is to determine the effectiveness of physical therapy by using manual therapy (MT) for the relief of TTH. Data sources: A review was done identifying randomized controlled trials through searches in MEDLINE, PEDro, Cochrane and CINAHL (January 2002 – April 2012). Study selection: English-language studies, with adult patients and number of subjects not under 11, diagnosed with episodic tension-type headache (ETTH) and chronic tension-type headache (CTTH) were included. Data extraction: Initial search was undertaken with the words Effectiveness, Tension-type headache, and Manual therapy (39 studies). In addition, a search which included terms related to treatments such as physiotherapy, physical therapy, spinal manipulation was performed (25 studies). Results: From the two searches 9 studies met the inclusion criteria and were analysed finding statistically significant results: 1) myofascial release, cervical traction, neck muscles trigger points in cervical thoracic muscles and stretching; 2) Superficial heat and massage, connective tissue manipulation and vertebral Cyriax mobilization; 3) cervical or thoracic spinal manipulation and cervical chin-occipital manual traction; 4) massage, progressive relaxation and gentle stretching, program of active exercises of shoulder, neck and pericranial muscles; 5) massage, passive rhythmic mobilization techniques, cervical, thoracic and lumbopelvic postural correction and cranio-cervical exercises; 6) progressive muscular relaxation combined with joint mobilization, functional, muscle energy, and strain/counterstrain techniques, and cranial osteopathic treatment; 7) massage focused on relieving myofascial trigger point activity; 8) pressure release and muscle energy in suboccipital muscles; 9) combination of mobilizations of the cervical and thoracic spine, exercises and postural correction. All studies used a combination of different techniques and none analyzed treatments separately, also all the studies have assessed aspects related to TTH beyond frequency and intensity of pain. Conclusions: The findings from these studies showed evidence that physiotherapy with articulatory MT, combined with cervical muscle stretching and massage are effective for this disease in different aspects related with TTH. No evidence was found of the effectiveness of the techniques applied separately.     

Structural investigation and biological activity of the lipooligosaccharide from the psychrophilic bacterium Pseudoalteromonas haloplanktis TAB 23

Pseudoalteromonas haloplanktis TAB 23 is a Gram-negative psychrophilic bacterium isolated from the Antarctic coastal sea. To survive in these conditions psychrophilic bacteria have evolved typical membrane lipids and "antifreeze" proteins to protect the inner side of the microorganism. As for Gram-negative bacteria, the outer membrane is mainly constituted by lipopoly- or lipooligosaccharides (LPS or LOS, respectively), which lean towards the external environment. Despite this, very little is known about the peculiarity of LPS from Gram-negative psychrophilic bacteria and what their role is in adaptation to cold temperature. Here we report the complete structure of the LOS from P. haloplanktis TAB 23. The lipid A was characterized by MALDI-TOF MS analysis and was tested in vitro showing a significant inhibitory effect on the LPS-induced pro-inflammatory cytokine production when added in culture with LPS from Escherichia coli. The product obtained after de-O-acylation of the LPS was analyzed by MALDI-TOF MS revealing the presence of several molecular species, differing in phosphorylation degree and oligosaccharide length. The oligosaccharide portion released after strong alkaline hydrolysis was purified by anion-exchange chromatography-pulsed amperometric detection (HPAEC-PAD) to give three main fractions, characterized by means of 2D NMR spectroscopy, which showed a very short highly phosphorylated saccharidic chain with the following general structure. α-Hepp3R,6R,4R'-(1→5)-α-Kdop4P-(2→6)-β-GlcpN4R-(1→6)-α-GlcpN1P (R=-H(2)PO(3) or -H; R'=α-Galp-(1→4)-β-Galp-(1→ or H-).     

Protein conformational flexibility prediction using machine learning

Using a data set of 16 proteins, a neural network has been trained to predict backbone 15N generalized order parameters from the three-dimensional structures of proteins. The final network parameterization contains six input features. The average prediction accuracy, as measured by the Pearson's correlation coefficient between experimental and predicted values of the square of the generalized order parameter is >0.70. Predicted order parameters for non-terminal amino acid residues depends most strongly on the local packing density and the probability that the residue is located in regular secondary structure.