Short-term regulation of tyrosine hydroxylase activity and expression by endothelin-1 and endothelin-3 in the rat posterior hypothalamus

Brain catecholamines are involved in several biological functions regulated by the hypothalamus. We have previously reported that endothelin-1 and -3 (ET-1 and ET-3) modulate norepinephrine release in the anterior and posterior hypothalamus. As tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, the aim of the present work was to investigate the effects of ET-1 and ET-3 on TH activity, total enzyme level and the phosphorylated forms of TH in the rat posterior hypothalamus. Results showed that ET-1 and ET-3 diminished TH activity but the response was abolished by both selective ET(A) and ET(B) antagonists (BQ-610 and BQ-788, respectively). In addition ET(A) and ET(B) selective agonists (sarafotoxin S6b and IRL-1620, respectively) failed to affect TH activity. In order to investigate the intracellular signaling coupled to endothelins (ETs) response, nitric oxide (NO), phosphoinositide, cAMP/PKA and CaMK-II pathways were studied. Results showed that N(omega)-nitro-l-arginine methyl ester and 7-nitroindazole (NO synthase and neuronal NO synthase inhibitors, respectively), 1H-[1,2,4]-oxadiazolo[4,3-alpha]quinozalin-1-one and KT-5823 (soluble guanylyl cyclase, and PKG inhibitors, respectively) inhibited ETs effect on TH activity. Further, sodium nitroprusside and 8-bromoguanosine-3',5'-cyclic monophosphate (NO donor and cGMP analog, respectively) mimicked ETs response. ETs-induced reduction of TH activity was not affected by a PKA inhibitor but it was abolished by PLC, PKC and CaMK-II inhibitors as well as by an IP(3) receptor antagonist. On the other hand, both ETs did not modify TH total level but reduced the phosphorylation of serine residues of the enzyme at positions 19, 31 and 40. Present results suggest that ET-1 and ET-3 diminished TH activity through an atypical ET or ET(C) receptor coupled to the NO/cGMP/PKG, phosphoinositide and CaMK-II pathways. Furthermore, TH diminished activity may result from the reduction of the phosphorylated sites of the enzyme without changes in its total level. Taken jointly present and previous results support that ET-1 and ET-3 may play a relevant role in the modulation of catecholaminergic neurotransmission in the posterior hypothalamus of the rat.     

Acquisition of Visuomotor Abilities and Intellectual Quotient in Children Aged 4–10 Years: Relationship with Micronutrient Nutritional Status

Lethargy, poor attention, and the high rate and severity of infections in malnourished children affect their educational achievement. We therefore studied the association between visuomotor abilities and intelligence quotient (IQ) and their relationship with iron, zinc, and copper. A cross-sectional study was carried out on a sample of 89 healthy children (age range, 4-10 years). Evaluations of visuomotor ability and IQ were performed with the Developmental Test of Visual Motor Integration (VMI) and the Scale for Measurement of Intelligence for children aged 3-18 years, respectively. Nutritional status was assessed using anthropometry and biochemical assessments, which included serum ferritin, zinc and copper levels, and Hb. The sample was classified as having low or normal VMI scores: 47 children (52.8%, mean age 7 +/- 1.5 years) had low VMI, and 42 (47.2%, mean age 7 +/- 2.06 years) had normal VMI. There were no statistically significant differences in socioeconomic and cultural condition between both groups. We found significantly higher serum copper and ferritin levels in normal as compared to low VMI, but we did not find any differences with zinc. IQ was significantly higher in normal vs low VMI children. The fact that children with abnormal VMI presented low mean serum copper and ferritin concentrations could indicate that copper and iron deficiencies in this sample could be related with visuomotor abilities.     

Palaeoecological analysis of a sclerobiont fauna on a single basibiont across the Valanginian of the Neuquén Basin,west‐central Argentina

Sclerobiont communities have proven their environmental and taphonomic value in extant and past settings; studies are beginning to quantify and evaluate their changes across time. Through the Valanginian of the Neuquén Basin, Argentina, trigonioids of the genus Steinmanella present an almost continuous record. Materials were collected from shales and shell beds across second‐order systems tracts (LST, TST and HST). Their sclerobiont communities were characterized and compared across systems tracts and facies. In addition, a link between them and coeval oyster mass occurrences (OMOs) was investigated, since studies on other local sclerobiont communities have consistently shown pronounced oyster dominance. Eleven sclerobiont taxa were found on Steinmanella (bryozoans, bivalves, foraminifers and polychaetes), of which oysters are usually strongly dominant but for the TST, in which their dominance is diminished. The sclerobiont community has a simple structure and interspecific relationships and competition for space seem to have had little importance. Few differences in richness, taxonomy and other parameters were found between facies. Across systems tracts, features of the sclerobiont communities are differentiated mostly from swings in relative abundance of taxa. The lowered oyster dominance in the TST may reflect a source–sink dynamics between OMOs (sources) and Steinmanella as sinks in shallower, soft substrate settings. Likely the sea‐level rise temporally drowned the oyster carbonate factory, resulting in decreased larvae emigration to the sinks and lowered oyster dominance during the TST.     

Changes in rainfall pattern affect crab herbivory rates in a SW Atlantic salt marsh

Climatic fluctuations usually change the intensity of existing interactions. Thus, in the context of the global climate change, it is important to consider new potential interactions or changes that may appear. Heavy rainy periods (one of the consequences of global climate change in eastern-central Argentina) can promote flooding in some estuaries (mainly on coastal lagoons), and thus, affect interactions between species. In this work we investigate if climatic fluctuations can affect Spartina densiflora Brong. (dominant marsh plant) survival through a chain of biotic and abiotic interactions in a SW Atlantic costal lagoon (37° 40′S, 57° 23′W; Mar Chiquita, Argentina). To achieve this, the long-term rainfall behavior of this region, and the effect of rainy periods on submergence of estuarine marsh areas (using satellite images) were analyzed. Then, the effect of flooding on the activity of the dominant herbivore of this system, the burrowing crab Neohelice granulata (= Chasmagnathus granulatus), was studied using pitfall traps. Finally, the effect of flooding on crab herbivory rates and plant survival were analyzed using transplants, stem-marking and flooding experiments. Long-term rainfall behavior showed that mean annual rainfall has increased during the last century, with the occurrence of more rainy years, and increases in cumulative monthly rainfall increased the submerged area of the S. densiflora marsh. Also, crab activity in the marsh largely increased during periods of flooding, associated with more than 100% increments in herbivory rates and stem mortality. These results reveal that increments in rainfall regime can trigger a cascade of abiotic and biotic interactions leading to increased marsh mortality, and stresses the importance of considering both, biotic and abiotic factors, together to predict changes in community organization.     

Water kefir: Factors affecting grain growth and health-promoting properties of the fermented beverage

Nowadays, the interest in the consumption of healthy foods has increased as well as the homemade preparation of artisanal fermented product. Water kefir is an ancient drink of uncertain origin, which has been passed down from generation to generation and is currently consumed practically all over the world. Considering the recent and extensive updates published on sugary kefir, this work aims to shed light on the scientific works that have been published so far in relation to this complex ecosystem. We focused our review evaluating the factors that affect the beverage microbial and chemical composition that are responsible for the health attribute of water kefir as well as the grain growth. The microbial ecosystem that constitutes the grains and the fermented consumed beverage can vary according to the fermentation conditions (time and temperature) and especially with the use of different substrates (source of sugars, additives as fruits and molasses). In this sense, the populations of microorganisms in the beverage as well as the metabolites that they produce varies and in consequence their health properties. Otherwise, the knowledge of the variables affecting grain growth are also discussed for its relevance in maintenance of the starter biomass as well as the use of dextran for technological application.     

Halting ErbB-2 isoforms retrograde transport to the nucleus as a new theragnostic approach for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is clinically defined by the absence of estrogen and progesterone receptors and the lack of membrane overexpression or gene amplification of receptor tyrosine kinase ErbB-2/HER2. Due to TNBC heterogeneity, clinical biomarkers and targeted therapies for this disease remain elusive. We demonstrated that ErbB-2 is localized in the nucleus (NErbB-2) of TNBC cells and primary tumors, from where it drives growth. We also discovered that TNBC expresses both wild-type ErbB-2 (WTErbB-2) and alternative ErbB-2 isoform c (ErbB-2c). Here, we revealed that the inhibitors of the retrograde transport Retro-2 and its cyclic derivative Retro-2.1 evict both WTErbB-2 and ErbB-2c from the nucleus of BC cells and tumors. Using BC cells from several molecular subtypes, as well as normal breast cells, we demonstrated that Retro-2 specifically blocks proliferation of BC cells expressing NErbB-2. Importantly, Retro-2 eviction of both ErbB-2 isoforms from the nucleus resulted in a striking growth abrogation in multiple TNBC preclinical models, including tumor explants and xenografts. Our mechanistic studies in TNBC cells revealed that Retro-2 induces a differential accumulation of WTErbB-2 at the early endosomes and the plasma membrane, and of ErbB-2c at the Golgi, shedding new light both on Retro-2 action on endogenous protein cargoes undergoing retrograde transport, and on the biology of ErbB-2 splicing variants. In addition, we revealed that the presence of a functional signal peptide and a nuclear export signal (NES), both located at the N-terminus of WTErbB-2, and absent in ErbB-2c, accounts for the differential subcellular distribution of ErbB-2 isoforms upon Retro-2 treatment. Our present discoveries provide evidence for the rational repurposing of Retro-2 as a novel therapeutic agent for TNBC.Subject terms: Breast cancer, Protein translocation, Oncogenes, Nuclear transport, Targeted therapies     

<Emphasis Type="Italic">In vitro</Emphasis> shoot culture and antimicrobial activity of <Emphasis Type="Italic">Berberis buxifolia</Emphasis> Lam

Berberis buxifolia Lam., known as “Calafate”, is a plant native to Argentina that exhibits antimicrobial activity. This biological activity is attributed to the isoquinoline alkaloid berberine. The aim of this research was to test the antimicrobial properties of different extracts of this species, taking berberine as the reference molecule, and to examine if the expression of bacterial multidrug resistance (MDR) efflux pumps could be responsible for possible resistance mechanisms. To this end, a wild-type and a mutant strain of Staphylococcus aureus with a defective MDR efflux pump were used and the minimum inhibitory concentrations of the extracts were determined. The studies were carried out with infusions of in vivo shoots and “Calafate” commercial tea, as well as with the media derived from shoot cultures incubated with different plant growth regulators (thidiazuron, picloram, and jasmonic acid). As far as antimicrobial activity is concerned, all the extracts tested were significantly more effective than berberine standard. “Calafate” commercial tea and shoot tea had inhibitory concentrations similar to the one observed for ampicillin standard. The media from the shoot cultures, however, were significantly more effective than all the others, particularly the one derived from jasmonic acid, suggesting the presence of compounds that could be acting synergistically with berberine. There were no differences in antimicrobial activity against the wild-type and the mutant S. aureus; no definite conclusions could be drawn concerning the relationship between MDR pumps and possible pathogen resistance to extracts of B. buxifolia.