Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis

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Mutagens induced chromosomal damage in <Emphasis Type="Italic">Lablab purpureus</Emphasis> (L.) Sweet var. <Emphasis Type="Italic">typicus</Emphasis>

Cytological analysis with respect to meiotic behaviour is considered to be the one of the most dependable indices to estimate the potency of mutagens and to elucidate the response of various genotypes to a particular mutagen. Seeds of Lablab purpureus (L.) Sweet var. typicus cv. CO(Gb)14 were subjected to different doses/concentrations of gamma rays and EMS. The effects of different mutagenic treatments on meiosis were studied on treated and control plants. Various types of meiotic aberrations such as stickiness, clumping of chromosomes, laggards, ring chromosomes and precocious movements were observed in the mutagenic treatments. As increase in the concentration, the frequency of cells showing chromosomal aberrations shows a linear increase up to a certain level. However, the EMS treatments proved to be more effective in inducing meiotic aberrations as compared to gamma rays.     

Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10⁶ DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 10⁶ DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm³. In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm³. The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.     

Boron neutron capture therapy (BNCT) translational studies in the hamster cheek pouch model of oral cancer at the new “B2” configuration of the RA-6 nuclear reactor

Boron neutron capture therapy (BNCT) is based on selective accumulation of B-10 carriers in tumor followed by neutron irradiation. We demonstrated, in 2001, the therapeutic effect of BNCT mediated by BPA (boronophenylalanine) in the hamster cheek pouch model of oral cancer, at the RA-6 nuclear reactor. Between 2007 and 2011, the RA-6 was upgraded, leading to an improvement in the performance of the BNCT beam (B2 configuration). Our aim was to evaluate BPA-BNCT radiotoxicity and tumor control in the hamster cheek pouch model of oral cancer at the new “B2” configuration. We also evaluated, for the first time in the oral cancer model, the radioprotective effect of histamine against mucositis in precancerous tissue as the dose-limiting tissue. Cancerized pouches were exposed to: BPA-BNCT; BPA-BNCT + histamine; BO: Beam only; BO + histamine; CONTROL: cancerized, no-treatment. BNCT induced severe mucositis, with an incidence that was slightly higher than in “B1” experiments (86 vs 67%, respectively). BO induced low/moderate mucositis. Histamine slightly reduced the incidence of severe mucositis induced by BPA-BNCT (75 vs 86%) and prevented mucositis altogether in BO animals. Tumor overall response was significantly higher in BNCT (94–96%) than in control (16%) and BO groups (9–38%), and did not differ significantly from the “B1” results (91%). Histamine did not compromise BNCT therapeutic efficacy. BNCT radiotoxicity and therapeutic effect at the B1 and B2 configurations of RA-6 were consistent. Histamine slightly reduced mucositis in precancerous tissue even in this overly aggressive oral cancer model, without compromising tumor control.     

Early Evaluation and Monitoring of Critical Patients with Acute Respiratory Distress Syndrome (ARDS) Using Specific Genetic Polymorphisms

A high percentage of critical patients are found to develop acute respiratory distress syndrome (ARDS). Several studies have reported high mortality rates in these cases which are most frequently associated with multiple organ dysfunctions syndrome. Lately, many efforts have been made to evaluate and monitor ARDS in critical patients. In this regard, the assessment of genetic polymorphisms responsible for developing ARDS present as a challenge and are considered future biomarkers. Early detection of the specific polymorphic gene responsible for ARDS in critically ill patients can prove to be a useful tool in the future, able to help decrease the mortality rates in these cases. Moreover, identifying the genetic polymorphism in these patients can help in the implementation of a personalized intensive therapy scheme for every type of patient, based on its genotype.     

An in vitro evaluation of the effects of a Yucca schidigera extract and chestnut tannins on composition and metabolic profiles of canine and feline faecal microbiota

The in vitro effect of a Yucca schidigera extract (YSE) and tannins from chestnut wood on composition and metabolic activity of canine and feline faecal microbiota was evaluated. Four treatments were carried out: control diet, chestnut tannins (CT), YSE and CT + YSE. The YSE was added to canine and feline faecal cultures at 0.1 g/l, while CT were added at 0.3 g/l for a 24-h incubation. A total of 130 volatile compounds were detected by means of headspace-solid phase microextraction gas-chromatography/mass spectrometry analyses. Several changes in the metabolite profiles of fermentation fluids were found, including a decrease of alcohols (?19%) and esters (?42%) in feline and canine inoculum, respectively, which was due to the antibacterial properties of tannins. In canine inoculum, after 6 h, YSE + CT caused lower cadaverine concentrations (?37%), while ammonia (?4%) and quinolone (?27%) were reduced by addition of CT. After 24 h, the presence of CT resulted in a decrease of sulphur compounds, such as dimethyl sulphide (?69%) and dimethyl disulphide (?20%). In feline faecal cultures, after 6 h, CT lowered the amount of indole (?48%), whereas YSE tended to decrease trimethylamine levels (?16%). Both in canine and feline inoculum, addition of CT and, to a minor extent, YSE affected volatile fatty acids patterns. In canine faecal cultures, CT exerted a marginal inhibitory effect on Escherichia coli population (?0.45 log 10 numbers of DNA copies/ml), while enterococci were increased (+2.06 log 10 numbers of DNA copies/ml) by YSE. The results from the present study show that YSE and tannins from chestnut wood exert different effects on the composition and metabolism of canine and feline faecal microbiota. In particular, the supplementation of YSE and tannins to diets for dogs and cats may be beneficial due to the reduction of the presence of some potentially toxic volatile metabolites in the animals’ intestine.     

Synchrony and diachrony in Menominee derivational morphology

This paper identifies two difficulties with treatments of derivation in Algonquian languages. In traditional approaches to grammar, in which the morpheme is seen as a unitary entity, morphemes are understood as minimal units of meaning and/or function. Definitions share an appeal to the morpheme’s indivisibility. In the Algonquianist literature, in contrast, some morphemes (‘components’) can themselves contain other morphemes (which we call ‘formatives’) and they can also be synchronically derived from other components or stems. Drawing data from Menominee, we propose that these difficulties disappear if the formatives are seen as historical rather than synchronic units, while the components are the synchronic morphemes. Formatives bear the hallmarks of historical products of morphologization (phonetic/phonological reduction, semantic bleaching, and increase in grammatical function), and we conclude that they are not part of synchronic grammatical computation. This resolves problems present in traditional and modern theoretical approaches to Algonquian derivation, and has broader ramifications for linguistic theory: in both the structuralist and generativist traditions, synchronic grammar has often been seen as expansive, responsible for generating surface patterns that may instead be products of history. This has been the case in phonology and syntax. The present paper provides a study of the phenomenon in derivational morphology, and suggests that a more modest role for synchronic rules is called for.     

TRPA1 ion channel stimulation enhances cardiomyocyte contractile function via a CaMKII-dependent pathway

Rationale: Transient receptor potential channels of the ankyrin subtype-1 (TRPA1) are non-selective cation channels that show high permeability to calcium. Previous studies from our laboratory have demonstrated that TRPA1 ion channels are expressed in adult mouse ventricular cardiomyocytes (CMs) and are localized at the z-disk, costamere and intercalated disk. The functional significance of TRPA1 ion channels in the modulation of CM contractile function have not been explored.

Objective: To identify the extent to which TRPA1 ion channels are involved in modulating CM contractile function and elucidate the cellular mechanism of action.

Methods and Results: Freshly isolated CMs were obtained from murine heart and loaded with Fura-2 AM. Simultaneous measurement of intracellular free Ca²⁺ concentration ([Ca²⁺]_i) and contractility was performed in individual CMs paced at 0.3 Hz. Our findings demonstrate that TRPA1 stimulation with AITC results in a dose-dependent increase in peak [Ca²⁺]_i and a concomitant increase in CM fractional shortening. Further analysis revealed a dose-dependent acceleration in time to peak [Ca²⁺]_i and velocity of shortening as well as an acceleration in [Ca²⁺]_i decay and velocity of relengthening. These effects of TRPA1 stimulation were not observed in CMs pre-treated with the TRPA1 antagonist, HC-030031 (10 µmol/L) nor in CMs obtained from TRPA1^?/? mice. Moreover, we observed no significant increase in cAMP levels or PKA activity in response to TRPA1 stimulation and the PKA inhibitor peptide (PKI 14–22; 100 nmol/L) failed to have any effect on the TRPA1-mediated increase in CM contractile function. However, TRPA1 stimulation resulted in a rapid phosphorylation of Ca²⁺/calmodulin-dependent kinase II (CaMKII) (1–5 min) that correlated with increases in CM [Ca²⁺]_i and contractile function. Finally, all aspects of TRPA1-dependent increases in CM [Ca²⁺]_i, contractile function and CaMKII phosphorylation were virtually abolished by the CaMKII inhibitors, KN-93 (10 µmol/L) and autocamtide-2-related peptide (AIP; 20 µmol/L).

Conclusions: These novel findings demonstrate that stimulation of TRPA1 ion channels in CMs results in activation of a CaMKII-dependent signaling pathway resulting in modulation of intracellular Ca²⁺ availability and handling leading to increases in CM contractile function. Cardiac TRPA1 ion channels may represent a novel therapeutic target for increasing the inotropic and lusitropic state of the heart.     

Phylogeny and evolutionary history of the blister beetles (Coleoptera, Meloidae)

Meloid beetles are well characterised by both morphological and biological features. Previous phylogenetic hypotheses based on morphological characters assumed the repeated parallel evolution of complex biological novelties. In this work relationships among several taxa of the four subfamilies and almost all tribes representing meloid diversity are examined by using mitochondrial (16S) and nuclear (ITS2) DNA sequences, in 25 genera (using Anthicidae as outgroup). Secondary structure of 16S and ITS2 rRNAs were modelled. ITS2 structure represents a synapomorphic condition for the family and informative characters at the tribal level. Phylogenetic hypotheses based on separate and combined analysis of the 16S and ITS2 rDNA sequences, and morpho-biological characters were tested, and compared with previous morphological classifications. Molecular dating allowed an outline of the main steps of the evolutionary history of Meloidae, which evolved during Early Cretaceous and then radiated considerably with the adoption of hypermetaboly and parasitic behaviour, and with repeated, parallel evolution of larval phoresy on its hosts.