Parallel Computation of the Matrix of the Chemical Distances on the Connection Machine

Abstract

We report here the parallel implementation of an original algorithm allowing a fast calculation of the distance matrix D of a graph representing a given chemical structure (molecule, polymer, crystal, etc.). Our algorithm fits perfectly in the SIMD parallel architecture of the Connection Machines CM-200 as we shall show. After discussing the performances of the parallel evaluation of D, we will end with a relevant application concerning C₆₀ and C₇₀ fullerenes. The present study applies to a generic globally connected graph without any restriction on the local connectivity of each graph's vertex.     

Elimination of foot-and-mouth disease in South America: lessons and challenges

Foot-and-mouth disease (FMD) is a highly transmissible and economically devastating disease of cloven-hoofed livestock. Although vaccines are available and have been instrumental in eliminating the disease from most of the South American animal population, viral circulation still persists in some countries and areas, posing a threat to the advances of the last 60 years by the official veterinary services with considerable support of the livestock sectors. The importance of the disease for the social and economic development of the American continent led to the establishment in 1951 of the Pan American Centre for Foot-and-Mouth Disease (PANAFTOSA), which has been providing technical cooperation to countries for the elimination of the disease. The first FMD national elimination programmes were established in South America around the 1960s and 1970s. To advance the regional elimination efforts in the 1980s, countries agreed on a Plan of Action 1988–2009 of the Hemispheric Program for the Eradication of Foot-and-Mouth Disease. The Plan of Action 1988–2009 did not reach the goal of elimination from the continent; and a new Plan of Action 2011–2020 was developed in 2010 based on the experience acquired by the countries and PANAFTOSA during the past 60 years. This plan is now being implemented; several challenges are still to be overcome to ensure the elimination of FMD from the Americas by 2020, however, the goal is achievable.     

Correlation between the age of the conceptus and various ultrasonographic measurements during the first 30 days of pregnancy in domestic cats (Felis catus)

We ultrasonographically evaluated the prenatal development in cats, from the early phases to Day 30 of pregnancy, subjecting a group of pregnant cats (n = 12) to a daily ultrasonographic exam. The ultrasonographic images allowed us to measure the minor diameter of the gestational sac and the crown-rump length of the embryo/fetus. Ten subjects underwent ovariohysterectomy at specific intervals during the pregnancy, with the aim of comparing the ultrasonographic data with real data; only two subjects brought their pregnancy to term. The earliest ultrasonographic observation of the gestational sac was on Day 10 after mating, while the embryo could be measured only beginning with Day 18. This study allowed to gather useful new data in order to clinically monitor the normal course of pregnancy in cats and to date the gestational age.     

Differential protein–protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways

Genetic studies show that LRRK2, and not its closest paralogue LRRK1, is linked to Parkinson's disease. To gain insight into the molecular and cellular basis of this discrepancy, we searched for LRRK1‐ and LRRK2‐specific cellular processes by identifying their distinct interacting proteins. A protein microarray‐based interaction screen was performed with recombinant 3xFlag‐LRRK1 and 3xFlag‐LRRK2 and, in parallel, co‐immunoprecipitation followed by mass spectrometry was performed from SH‐SY5Y neuroblastoma cell lines stably expressing 3xFlag‐LRRK1 or 3xFlag‐LRRK2. We identified a set of LRRK1‐ and LRRK2‐specific as well as common interactors. One of our most prominent findings was that both screens pointed to epidermal growth factor receptor (EGF‐R) as a LRRK1‐specific interactor, while 14‐3‐3 proteins were LRRK2‐specific. This is consistent with phosphosite mapping of LRRK1, revealing phosphosites outside of 14‐3‐3 consensus binding motifs. To assess the functional relevance of these interactions, SH‐SY5Y‐LRRK1 and ‐LRRK2 cell lines were treated with LRRK2 kinase inhibitors that disrupt 14‐3‐3 binding, or with EGF, an EGF‐R agonist. Redistribution of LRRK2, not LRRK1, from diffuse cytoplasmic to filamentous aggregates was observed after inhibitor treatment. Similarly, EGF induced translocation of LRRK1, but not of LRRK2, to endosomes. Our study confirms that LRRK1 and LRRK2 can carry out distinct functions by interacting with different cellular proteins.

     

Looking over toxin-K(+) channel interactions. Clues from the structural and functional characterization of α-KTx toxin Tc32, a Kv1.3 channel blocker

α-KTx toxin Tc32, from the Amazonian scorpion Tityus cambridgei, lacks the dyad motif, including Lys27, characteristic of the family and generally associated with channel blockage. The toxin has been cloned and expressed for the first time. Electrophysiological experiments, by showing that the recombinant form blocks Kv1.3 channels of olfactory bulb periglomerular cells like the natural Tc32 toxin, when tested on the Kv1.3 channel of human T lymphocytes, confirmed it is in an active fold. The nuclear magnetic resonance-derived structure revealed it exhibits an α/β scaffold typical of the members of the α-KTx family. TdK2 and TdK3, all belonging to the same α-KTx 18 subfamily, share significant sequence identity with Tc32 but diverse selectivity and affinity for Kv1.3 and Kv1.1 channels. To gain insight into the structural features that may justify those differences, we used the recombinant Tc32 nuclear magnetic resonance-derived structure to model the other two toxins, for which no experimental structure is available. Their interaction with Kv1.3 and Kv1.1 has been investigated by means of docking simulations. The results suggest that differences in the electrostatic features of the toxins and channels, in their contact surfaces, and in their total dipole moment orientations govern the affinity and selectivity of toxins. In addition, we found that, regardless of whether the dyad motif is present, it is always a Lys side chain that physically blocks the channels, irrespective of its position in the toxin sequence.     

Carnitine and acetyl-carnitine,natural substances endowed with interesting pharmacological properties.

The inotropic and anti-fatigue effects of d, l-carnitine, l-carnitine and d, l-acetyl-carnitine in laboratory animals were studied. In the isolated rabbit heart these substances at the concentration level of 10^?5 g/l increase significantly the contractile force depressed by anoxia, without changes in ECG, heart rate and coronary flow. The following rank order of activity was observed: d, l-acetyl-carnitine > l-carnitine > d, l-carnitine. Sodium acetate + d, l-carnitine mixture exerts the same inotropic effect as d, l-carnitine alone, showing the important role of the acetyl-bond. In rats submitted to a fatigue test (rotarod) only d, l-acetyl-carnitine induces a significant anti-fatigue effect. Since endogenous carnitine depletion is linked with many pathological states, particularly of the heart, exogenous carnitine and especially its acetyl-derivative might represent an important drug treatment with high tolerance advantages.     

Fertility in the mare after repeated transvaginal ultrasound-guided aspirations

Ovum pick-up (OPU) by transvaginal ultrasound guided aspiration (TUGA) is a procedure applied in equine-assisted reproduction programs such as oocyte transfer and in vitro embryo production. Despite a large number of studies reporting that it is a repeatable and safe technique, little information is available about the effect of repeated punctures on fertility of mares. Moreover, even if flushing follicles improves the oocyte recovery rate, to our knowledge the efficiency of flushing estrous and diestrous follicles has not been evaluated. The aims of the present study were (1) evaluate if repeated TUGAs negatively effects fertility and (2) investigate the influence of flushing the follicular cavity (as compared to aspiration only-unflushed) on the recovery rate from follicles of different sizes and in different stages of the estrous cycle. Seventy-six TUGAs were carried out on 20 mares during the breeding season; 153 follicles were aspirated and 31 oocytes were recovered (20.3% per follicle; 40.8% per TUGA attempt). Of the 76 aspirations, 52 were carried out during estrus and 24 in diestrus. Flushing the follicular cavity significantly increased (P < 0.01) the oocyte recovery rate from estrous follicles (13/28, 46.4% flushed versus 3/24, 12.5% aspirated only) but not (P > 0.05) from diestrous follicles of different diameters (3/30, 10% flushed versus 2/36, 5.6% aspirated only for follicles <2 cm in diameter; 6/20, 30% flushed versus 4/15, 26.7% aspirated only for follicles > or =2 cm in diameter). Mares underwent ultrasonic examinations after every aspiration and no alteration was found with the exception of two mares in which the corpus luteum (CL) did not form following aspiration of estrous follicle. Of the 20 mares involved in this study, 10 were artificially inseminated with fresh semen from a single fertile stallion at the first spontaneous heat following the previous aspiration. Of the 10 inseminated mares, 7 were found to be pregnant 16, 30 and 50 days after artificial insemination (AI), indicating that repeated TUGAs did not adversely affect fertility.     

Computer-Aided Topological Analysis of the Faujasite Lattice I: Exact Solution for Zeolite-X

Abstract

In order to study the possible configurations of Aluminum and Silicon atoms on a Faujasite lattice, two different methods of analysis are presented. The first method is based on the study of the physical properties of different lattice structures: the energy and the dipolar moment. The second one examines the topological properties of the configurations in order to count the inequivalent lattice structures. An original algorithm selects the configurations to be generated and compared in order to keep the computer time required at an acceptable level. The results from the two methods are compared and found to be in agreement.

In this paper we specialize our study to zeolite-X but the methods are general and can be applied to other types of lattices.     

Potent analgesic activity of the enkephalin-like tetrapeptide H-Tyr-D-Ala-Gly-Phe-NH2.

The N-terminal tetrapeptide amide analog of enkephalin (H-Tyr-D-Ala-Gly-Phe-NH₂) is approximately equipotent with highly active pentapeptide analogs of enkephalin (and with morphine) in producing analgesia after either intracerebroventricular or intravenous administration. Smaller fragments exhibited diminished potency, but even the dipeptide (H-Tyr-D-Ala-NH₂) retained naloxone-reversible analgesic activity at high intraventricular doses. These findings suggest that while the dipeptide has full intrinsic activity, the tetrapeptide sequence may be a minimum structural requirement for potent analgesia.