Exploring Vanadium Chemical Transferrin Mimetic Compounds for Insulin Enhancement

Diabetes Mellitus (DM) is caused by a lack of insulin production (Type 1) or the body’s cells’ inability to properly receive it, also known as insulin resistance (Type 2), resulting in greatly elevated levels of blood glucose. Vanadium(IV) and vanadium(V) ions are believed to enhance insulin activity by inhibition of protein tyrosine phosphatase 1B (PTP1B). PTP1B is normally responsible for downregulating the insulin signaling, but in DM type 2, PTP1B activity is overexpressed leading to the insulin signaling blocking. The most promising V(IV) compounds are designed for oral delivery: they are absorbed into the gut and delivered into the bloodstream where they are bound by the iron transporting protein serum transferrin (sTf). STf delivers the compound into cells via endocytosis, where vanadium can bind PTP1B. A limitation of these compounds is their poor stability at the stomach acidic conditions in which they undergo a significant amount of dissociation, resulting in a very inefficient gut absorption. This study explores the use of a chemical transferrin mimetic (cTfm) ligand to create V(IV) and V(V) compounds featuring excellent acidic pH stability for improved gut absorption. The cTfm-V(IV,V) compounds are expected to be labile in the pH of the bloodstream and thus the vanadium species can be quickly ligand exchanged with sTF. The cTfm ligand N,N\u27-di(o-hydroxybenzyl)ethylenediamine-N,N\u27-diacetic acid (HBED) was used to synthesize VO(IV)HBED and VO(V)HBED which demonstrated great aqueous stability in the 1-4 pH range. The role of citrate as a vehicle for delivering vanadium to sTf to regulate the transport of vanadium is also examined

Anomalous interactions in confined charge-stabilized colloid

Charge-stabilized colloidal spheres dispersed in weak 1:1 electrolytes are supposed to repel each other. Consequently, experimental evidence for anomalous long-ranged like-charged attractions induced by geometric confinement inspired a burst of activity. This has largely subsided because of nagging doubts regarding the experiments' reliability and interpretation. We describe a new class of thermodynamically self-consistent colloidal interaction measurements that confirm the appearance of pairwise attractions among colloidal spheres confined by one or two bounding walls. In addition to supporting previous claims for this as-yet unexplained effect, these measurements also cast new light on its mechanism.Comment: 8 pages, 5 figures, RevTeX4. Conference proceedings for CODEF-04, Colloidal Dispersions in External Fields, March 29 - April 1, 200

Distribution of dwell times of a ribosome: effects of infidelity, kinetic proofreading and ribosome crowding

Ribosome is a molecular machine that polymerizes a protein where the sequence of the amino acid residues, the monomers of the protein, is dictated by the sequence of codons (triplets of nucleotides) on a messenger RNA (mRNA) that serves as the template. The ribosome is a molecular motor that utilizes the template mRNA strand also as the track. Thus, in each step the ribosome moves forward by one codon and, simultaneously, elongates the protein by one amino acid. We present a theoretical model that captures most of the main steps in the mechano-chemical cycle of a ribosome. The stochastic movement of the ribosome consists of an alternating sequence of pause and translocation; the sum of the durations of a pause and the following translocation is the time of dwell of the ribosome at the corresponding codon. We derive the analytical expression for the distribution of the dwell times of a ribosome in our model. Whereever experimental data are available, our theoretical predictions are consistent with those results. We suggest appropriate experiments to test the new predictions of our model, particularly, the effects of the quality control mechanism of the ribosome and that of their crowding on the mRNA track.Comment: This is an author-created, un-copyedited version of an article accepted for publication in Physical Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at DOI:10.1088/1478-3975/8/2/02600

Probing protein sequences as sources for encrypted antimicrobial peptides

Starting from the premise that a wealth of potentially biologically active peptides may lurk within proteins, we describe here a methodology to identify putative antimicrobial peptides encrypted in protein sequences. Candidate peptides were identified using a new screening procedure based on physicochemical criteria to reveal matching peptides within protein databases. Fifteen such peptides, along with a range of natural antimicrobial peptides, were examined using DSC and CD to characterize their interaction with phospholipid membranes. Principal component analysis of DSC data shows that the investigated peptides group according to their effects on the main phase transition of phospholipid vesicles, and that these effects correlate both to antimicrobial activity and to the changes in peptide secondary structure. Consequently, we have been able to identify novel antimicrobial peptides from larger proteins not hitherto associated with such activity, mimicking endogenous and/or exogenous microorganism enzymatic processing of parent proteins to smaller bioactive molecules. A biotechnological application for this methodology is explored. Soybean (Glycine max) plants, transformed to include a putative antimicrobial protein fragment encoded in its own genome were tested for tolerance against Phakopsora pachyrhizi, the causative agent of the Asian soybean rust. This procedure may represent an inventive alternative to the transgenic technology, since the genetic material to be used belongs to the host organism and not to exogenous sources

TRACE ELEMENTS IN SHEEP AND GOATS REPRODUCTION: A REVIEW

The reproduction of small ruminants like goats and sheep managed under extensive range grazing conditions can be affected by nutrients availability and especially by the mineral content of the forages resources on the rangeland. It has been particularly demonstrated that trace elements can have equally, beneficial or detrimental effects, depending on its balance, on reproductive functions in small ruminants. Trace elements as copper, molybdenum, selenium and zinc play key role on the metabolism of carbohydrates, proteins and lipids; however, the mode of action by which these elements affect reproduction in sheep and goats are not completely understood, due to the complexity in the mode of action of the metallobiomolecules and the neuro-hormonal relationship. In this way, their absence or presence of these minerals in several organs, fluids, or tissues of the reproductive tract have allowed obtaining information on the metabolism and the role of these elements on reproduction in sheep and goats. On this regard, the objective of this document is to review the relationships and effects of some trace elements, on reproductive events in sheep and goats

Zero Temperature Properties of RNA Secondary Structures

We analyze different microscopic RNA models at zero temperature. We discuss both the most simple model, that suffers a large degeneracy of the ground state, and models in which the degeneracy has been remove, in a more or less severe manner. We calculate low-energy density of states using a coupling perturbing method, where the ground state of a modified Hamiltonian, that repels the original ground state, is determined. We evaluate scaling exponents starting from measurements of overlaps and energy differences. In the case of models without accidental degeneracy of the ground state we are able to clearly establish the existence of a glassy phase with $\theta \simeq 1/3$.Comment: 20 pages including 9 eps figure

Structure of Polyelectrolytes in Poor Solvent

We present simulations on charged polymers in poor solvent. First we investigate in detail the dilute concentration range with and without imposed extension constraints. The resulting necklace polymer conformations are analyzed in detail. We find strong fluctuations in the number of pearls and their sizes leading only to small signatures in the form factor and the force-extension relation. The scaling of the peak in the structure factor with the monomer density shows a pertinent different behavior from good solvent chains.Comment: 7 pages, 5 figures. submitted to EP

EFFECT OF SEASON ON SERUM COPPER AND ZINC CONCENTRATIONS IN CROSSBRED GOATS HAVING DIFFERENT REPRODUCTIVE STATUS UNDER SEMIARID RANGELAND CONDITIONS IN SOUTHERN MEXICO STATE

The effect of season (rainy: RS, and dry: DS) and reproductive status on copper (Cu) and zinc (Zn) concentrations in blood serum of crossbred goats (BW= 36.01 ± 1.59 kg) were studied under semiarid rangeland conditions in Southern Mexico State. Blood samples from 80 crossbred goats were taken each season (RS and DS). The goats were clustered into 10 different groups considering their reproductive status. Concentrations of Cu and Zn in serum were assayed using atomic absorption. Data were analyzed using a general linear model procedure for a completely randomized design and differences among means were examined using a Tukey test. Blood serum concentrations of Cu and Zn were affected by reproductive status and season (P<0.001). In relation to the season, Cu and Zn serum levels were lower in RS than DS (P<0.05). Overall, kidded goats had the highest values (P<0.01) for Cu than other animals in both seasons (RS or DS). Anestrous goats had the lowest concentrations (P<0.01) for Zn during RS, while all goats at their second or more kidding, rearing single or twins, showed the highest concentrations of Zn (P<0.001) in this season. Adult goats in Southern Mexico State showed a deficiency of Cu and Zn, especially during RS. As such, mineral supplements should be provided with respect to these elements in feeding systems for goats under semiarid rangeland conditions in order to evaluate their impact on health and reproduction

Comparative analysis of performance by cows confined in different typologies of compost barns

The compost barn system was designed to be a sustainable alternative housing system for dairy cows. In order to help producers in the region to choose the best type of facility from the point of view of the milk production of the animals, this study compared the productivity of cows confined in an open composting barn with natural ventilation and in a closed composting barn with negative pressure ventilation and evaporative cooling panels. The temperature and relative humidity of the air were monitored, as well as the milk production of the animals housed in the facilities, and THI (Temperature and Humidity Index) were calculated. During the trials, the maximum daily temperatures of the air reached values around 27 °C and the THI remained within the normal range of up to 70. The average productivity remained in the general pattern described in the literature from 23 to 44 kg of milk cow1 day-1 , with lower rates obtained in the closed house. As the variation of the index used to describe the internal environment was not significant, it can be inferred that climatic elements as temperature and air humidity, under the conditions analyzed were not the main factors influencing the productivity rates of dairy cattle. In conclusion, under the analysed conditions the use of a closed barn with negative pressure ventilation is hardly justified as a plant that favoured the productivity of the confined cows

Like-charge attraction through hydrodynamic interaction

We demonstrate that the attractive interaction measured between like-charged colloidal spheres near a wall can be accounted for by a nonequilibrium hydrodynamic effect. We present both analytical results and Brownian dynamics simulations which quantitatively capture the one-wall experiments of Larsen and Grier (Nature 385, p. 230, 1997).Comment: 10 pages, 4 figure