G‐protein coupled receptor‐mediated nutrient sensing and developmental control in Aspergillus nidulans

Nutrient sensing and utilisation are fundamental for all life forms. As heterotrophs, fungi have evolved a diverse range of mechanisms for sensing and taking up various nutrients. Despite its importance, only a limited number of nutrient receptors and their corresponding ligands have been identified in fungi. G‐protein coupled receptors (GPCRs) are the largest family of transmembrane receptors. The Aspergillus nidulans genome encodes 16 putative GPCRs, but only a few have been functionally characterised. Our previous study showed the increased expression of an uncharacterised putative GPCR, gprH, during carbon starvation. GprH appears conserved throughout numerous filamentous fungi. Here, we reveal that GprH is a putative receptor involved in glucose and tryptophan sensing. The absence of GprH results in a reduction in cAMP levels and PKA activity upon adding glucose or tryptophan to starved cells. GprH is pre‐formed in conidia and is increasingly active during carbon starvation, where it plays a role in glucose uptake and the recovery of hyphal growth. GprH also represses sexual development under conditions favouring sexual fruiting and during carbon starvation in submerged cultures. In summary, the GprH nutrient‐sensing system functions upstream of the cAMP‐PKA pathway, influences primary metabolism and hyphal growth, while represses sexual development in A. nidulans.     

WJSC 6th Anniversary Special Issues（2）:Mesenchymal stem cells Neurotrauma and mesenchymal stem cells treatment:From experimental studies to clinical trials

Mesenchymal stem cell(MSC)therapy has attracted the attention of scientists and clinicians around the world.Basic and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spinal cord and peripheral nerve injury.These effects are believed to be due to their ability to differentiate into other cell lineages,modulate inflammatory and immunomodulatory responses,reduce cell apoptosis,secrete several neurotrophic factors and respond to tissue injury,among others.There are many pre-clinical studies on MSC treatment for spinal cord injury(SCI)and peripheral nerve injuries.However,the same is not true for clinical trials,particularly those concerned with nerve trauma,indicating the necessity of more well-constructed studies showing the benefits that cell therapy can provide for individuals suffering the consequences of nerve lesions.As for clinical trials for SCI treatment the results obtained so far are not as beneficial as those described in experimental studies.For these reasons basic and pre-clinical studies dealing with MSC therapy should emphasize the standardization of protocols that could be translated to the clinical set with consistent and positive outcomes.This review is based on pre-clinical studies and clinical trials available in the literature from 2010 until now.At the time of writing this article there were 43 and 36 pre-clinical and 19 and 1 clinical trials on injured spinal cord and peripheral nerves,respectively.     

Reduced GABAergic Inhibition in the Basolateral Amygdala and the Development of Anxiety-Like Behaviors after Mild Traumatic Brain Injury

Traumatic brain injury (TBI) is a major public health concern affecting a large number of athletes and military personnel. Individuals suffering from a TBI risk developing anxiety disorders, yet the pathophysiological alterations that result in the development of anxiety disorders have not yet been identified. One region often damaged by a TBI is the basolateral amygdala (BLA); hyperactivity within the BLA is associated with increased expression of anxiety and fear, yet the functional alterations that lead to BLA hyperexcitability after TBI have not been identified. We assessed the functional alterations in inhibitory synaptic transmission in the BLA and one mechanism that modulates excitatory synaptic transmission, the α₇ containing nicotinic acetylcholine receptor (α₇-nAChR), after mTBI, to shed light on the mechanisms that contribute to increased anxiety-like behaviors. Seven and 30 days after a mild controlled cortical impact (CCI) injury, animals displayed significantly greater anxiety-like behavior. This was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABA_A-receptor mediated inhibitory postsynaptic currents (IPSCs). Decreases in the mIPSC amplitude were associated with reduced surface expression of α1, β2, and γ2 GABA_A receptor subunits. However, significant increases in the surface expression and current mediated by α₇-nAChR, were observed, signifying increases in the excitability of principal neurons within the BLA. These results suggest that mTBI causes not only a significant reduction in inhibition in the BLA, but also an increase in neuronal excitability, which may contribute to hyperexcitability and the development of anxiety disorders.     

Arterial Hypertension and Skin Allergy Are Risk Factors for Progression from Dengue to Dengue Hemorrhagic Fever: A Case Control Study

Background

Currently, knowledge does not allow early prediction of which cases of dengue fever (DF) will progress to dengue hemorrhagic fever (DHF), to allow early intervention to prevent progression or to limit severity. The objective of this study is to investigate the hypothesis that some specific comorbidities increase the likelihood of a DF case progressing to DHF.

Methods

A concurrent case-control study, conducted during dengue epidemics, from 2009 to 2012. Cases were patients with dengue fever that progressed to DHF, and controls were patients of dengue fever who did not progress to DHF. Logistic regression was used to estimate the association between DHF and comorbidities.

Results

There were 490 cases of DHF and 1,316 controls. Among adults, progression to DHF was associated with self-reported hypertension (OR = 1.6; 95% CI 1.1-2.1) and skin allergy (OR = 1.8; 95% CI 1.1-3.2) with DHF after adjusting for ethnicity and socio-economic variables. There was no statistically significant association between any chronic disease and progression to DHF in those younger than 15 years.

Conclusions

Physicians attending patients with dengue fever should keep those with hypertension or skin allergies in health units to monitor progression for early intervention. This would reduce mortality by dengue.     

A mid-Holocene vegetational and anthropogenic record in the Guanabara Bay region,Rio de Janeiro State,SE Brazil,assessed by palynological and charcoal data

Palynological and charcoal fragment analyses of Guanabara Bay sediments, as well as radiocarbon dating, were carried out on one 220 cm long sedimentary core collected from the northeast sector of the bay, near the São Gonçalo coast. This study aims at recognising and explaining the environmental history of this region during the mid-Holocene, and to identify the anthropogenic influences on it. The palynological data indicate the predominance of ombrophilous forest vegetation in the Guanabara Bay Hydrographic Basin at c. 6500 calendar years bp. During this period (pollen zone 1), the concentrations of pollen grains and spores may still have been controlled by the Holocene Maximum Transgressive Event. After a phase of low concentrations of palynomorphs, there was a considerable increase in the accumulation patterns of pollen and spore grains (pollen zone 2). This increase can probably be related to the retreat of the sea level event after the Holocene Maximum Transgressive Event. The 75 cm of the core top (pollen zone 3) provide clear evidence of human influence in the area, which is inferred from the significant reduction in ombrophilous forest pollen grains, the significant increase in herbaceous pollen grains, the presence of exotic pollen types (Eucalyptus and Pinus), and high concentration of carbonaceous particles.     

Sugar levels in Charmat sparkling wines can affect the quality and resveratrol levels

Sparkling wines contain CO(2) obtained through a second fermentation by natural processes (Charmat method); they may be prepared with variable final sugar concentrations, resulting in physicochemical compositions and phenolic profiles different to those obtained with other natural methods. The purpose of this study was to verify the influence of sweetness on enological parameters, trans-resveratrol and trans-piceid levels, antioxidant capacity (power of scavenger the radical DPPH(?) (1,1-diphenyl-2-picrylhydrazyl) and mimetic enzymatic activities of superoxide dismutase (SOD-like) and catalase (CAT-like) assays, and β-glucosidase activities on Charmat sparkling wines. The interaction of polyphenol levels and sweetness was observed. Levels of trans-piceid and trans-resveratrol showed a decrease in function of glucose concentration up to 40 g/l. All samples showed antioxidant capacity and β-glucosidase activity was stable even in the presence of sugar. A positive correlation between SOD-like and DPPH(?) was observed. This work shows an approach able to clarify important aspects for the wine industry with regard to world-wide consumer demand for sweetened products.     

Eu3+‐tetrakis β‐diketonate complexes for solid‐state lighting application

Eu³⁺–β‐diketonate complexes are used, for example, in solid‐state lighting (SSL) or light‐converting molecular devices. However, their low emission quantum efficiency due to water molecules coordinated to Eu³⁺ and low photostability are still problems to be addressed. To overcome such challenges, we synthesized Eu³⁺ tetrakis complexes based on [Q][Eu(tfaa)₄] and [Q][Eu(dbm)₄] (Q1 = C₂₆H₅₆N⁺, Q2 = C₁₉H₄₂N⁺, and Q3 = C₁₇H₃₈N⁺), replacing the water molecules in the tris stoichiometry. The tetrakis β‐diketonates showed desirable thermal stability for SSL and, under excitation at 390 nm, they displayed the characteristic Eu³⁺ emission in the red spectral region. The quantum efficiencies of the dbm complexes achieved values as high as 51%, while the tfaa complexes exhibited lower quantum efficiencies (28–33%), but which were superior to those reported for the tris complexes. The structures were evaluated using the Sparkle/PM7 model and comparing the theoretical and the experimental Judd–Ofelt parameters. [Q1][Eu(dbm)₄] was used to coat a near‐UV light‐emitting diode (LED), producing a red‐emitting LED prototype that featured the characteristic emission spectrum of [Q1][Eu(dbm)₄]. The emission intensity of this prototype decreased only 7% after 30 h, confirming its high photostability, which is a notable result considering Eu³⁺ complexes, making it a potential candidate for SSL.     

Simultaneous use of sodium nitrate and urea as nitrogen sources improves biomass composition of Arthrospira platensis cultivated in a tubular photobioreactor

Arthrospira platensis is widely cultivated in open ponds for industrial purposes. However, high‐protein A. platensis biomass produced in photobioreactors (PBRs) is recommended for pharmaceutical and cosmetic formulations. A. platensis was cultivated in a 3.5 L tubular airlift PBR using both sodium nitrate and urea as nitrogen sources. Sodium nitrate was added from the start of the cultivation using a batch process. Urea was supplied daily at exponentially increasing feeding rate using a fed‐batch process. The simultaneous optimization of the independent variables, namely, total quantity of sodium nitrate (m_T1) and total quantity of urea (m_T2), led to an optimal condition of m_T1 = 15.0 mmol/L and m_T2 = 7.5 mmol/L. Maximum biomass concentration (5183 ± 94 mg/L) corresponding to the highest biomass productivity (683 ± 13 mg/L/day) was obtained under such condition. The addition protocol of both nitrogen sources resulted in high productivities of protein (6.2 ± 0.4 mg/L/day) as well as chlorophyll‐a (372.2 ± 7.7 mg/L/day). Such innovative process could be applied in the large‐scale production of A. platensis using tubular PBR for novel applications.     

Extracellular α‐synuclein alters synaptic transmission in brain neurons by perforating the neuronal plasma membrane

It has been postulated that the accumulation of extracellular α‐synuclein (α‐syn) might alter the neuronal membrane by formation of ‘pore‐like structures’ that will lead to alterations in ionic homeostasis. However, this has never been demonstrated to occur in brain neuronal plasma membranes. In this study, we show that α‐syn oligomers rapidly associate with hippocampal membranes in a punctate fashion, resulting in increased membrane conductance (5 fold over control) and the influx of both calcium and a fluorescent glucose analogue. The enhancement in intracellular calcium (1.7 fold over control) caused a large increase in the frequency of synaptic transmission (2.5 fold over control), calcium transients (3 fold over control), and synaptic vesicle release. Both primary hippocampal and dissociated nigral neurons showed rapid increases in membrane conductance by α‐syn oligomers. In addition, we show here that α‐syn caused synaptotoxic failure associated with a decrease in SV2, a membrane protein of synaptic vesicles associated with neurotransmitter release. In conclusion, extracellular α‐syn oligomers facilitate the perforation of the neuronal plasma membrane, thus explaining, in part, the synaptotoxicity observed in neurodegenerative diseases characterized by its extracellular accumulation.