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Environmental enrichment (EE) exerts powerful effects on brain physiology, and is widely used as an experimental and therapeutic tool. Typical EE paradigms are multifactorial, incorporating elements of physical exercise, environmental complexity, social interactions and stress, however the specific contributions of these variables have not been separable using conventional housing paradigms. Here, we evaluated the impacts of these individual variables on adult hippocampal neurogenesis by using a novel \"Alternating EE\" paradigm. For 4 weeks, adult male CD1 mice were alternated daily between two enriched environments; by comparing groups that differed in one of their two environments, the individual and combinatorial effects of EE variables could be resolved. The Alternating EE paradigm revealed that (1) voluntary running for 3 days/week was sufficient to increase both mitotic and post-mitotic stages of hippocampal neurogenesis, confirming the central importance of exercise; (2) a complex environment (comprised of both social interactions and rotated inanimate objects) had no effect on neurogenesis itself, but enhanced depolarization-induced c-Fos expression (attributable to social interactions) and buffered stress-induced plasma corticosterone levels (attributable to inanimate objects); and (3) neither social isolation, group housing, nor chronically increased levels of plasma corticosterone had a prolonged impact on neurogenesis. Mouse strain, handling and type of running apparatus were tested and excluded as potential confounding factors. These findings provide valuable insights into the relative effects of key EE variables on adult neurogenesis, and this \"Alternating EE\" paradigm represents a useful tool for exploring the contributions of individual EE variables to mechanisms of neural plasticity.

Background: Short-chain fatty acids (SCFA) are produced by colonic microbiota from dietary carbohydrates and proteins that reach the colon. It has been suggested that SCFA may promote obesity via increased colonic energy availability. Recent studies suggest obese humans have higher faecal SCFA than lean, but it is unclear whether this difference is due to increased SCFA production or reduced absorption. Objectives: To compare rectal SCFA absorption, dietary intake and faecal microbial profile in lean (LN) versus overweight and obese (OWO) individuals. Design: Eleven LN and eleven OWO individuals completed a 3-day diet record, provided a fresh faecal sample and had SCFA absorption measured using the rectal dialysis bag method. The procedures were repeated after 2 weeks. Results: Age-adjusted faecal SCFA concentration was significantly higher in OWO than LN individuals (81.3±7.4 vs 64.1±10.4 mmol kg −1 , P =0.023). SCFA absorption (24.4±0.8% vs 24.7±1.2%, respectively, P =0.787) and dietary intakes were similar between the groups, except for a higher fat intake in OWO individuals. However, fat intake did not correlate with SCFAs or bacterial abundance. OWO individuals had higher relative Firmicutes abundance (83.1±4.1 vs 69.5±5.8%, respectively, P =0.008) and a higher Firmicutes:Bacteriodetes ratio ( P =0.023) than LN individuals. There was a positive correlation between Firmicutes and faecal SCFA within the whole group ( r =0.507, P =0.044), with a stronger correlation after adjusting for available carbohydrate ( r =0.615, P =0.005). Conclusions: The higher faecal SCFA in OWO individuals is not because of differences in SCFA absorption or diet. Our results are consistent with the hypothesis that OWO individuals produce more colonic SCFA than LN individuals because of differences in colonic microbiota. However, further studies are needed to prove this.

Leishmania amazonensis is a protozoan that primarily causes cutaneous leishmaniasis in humans. The parasite relies on the amino acid arginine to survive within macrophages and establish infection, since it is a precursor for producing polyamines. On the other hand, arginine can be metabolized via nitric oxide synthase 2 (NOS2) to produce the microbicidal molecule nitric oxide (NO), although this mechanism does not apply to human macrophages since they lack NOS2 activity. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at posttranscriptional levels. Our previous work showed that mmu-miR-294 targets Nos2 favoring Leishmania survival in murine macrophages. Here, we demonstrate that human macrophages upregulate the hsa-miR-372, hsa-miR-373, and hsa-miR-520d, which present the same seed sequence as the murine mmu-miR-294. Inhibition of the miR-372 impaired Leishmania survival in THP-1 macrophages and the effect was further enhanced with combinatorial inhibition of the miR-372/373/520d family, pointing to a cooperative mechanism. However, this reduction in survival is not caused by miRNA-targeting of NOS2, since the seed-binding motif found in mice is not conserved in the human 3′UTR. Instead, we showed the miR-372/373/520d family targeting the macrophage’s main arginine transporter SLC7A2/CAT2 during infection. Arginine-related metabolism was markedly altered in response to infection and miRNA inhibition, as measured by Mass Spectrometry-based metabolomics. We found that Leishmania infection upregulates polyamines production in macrophages, as opposed to simultaneous inhibition of miR-372/373/520d, which decreased putrescine and spermine levels compared to the negative control. Overall, our study demonstrates miRNA-dependent modulation of polyamines production, establishing permissive conditions for intracellular parasite survival. Although the effector mechanisms causing host cell immunometabolic adaptations involve various parasite and host-derived signals, our findings suggest that the miR-372/373/520d family may represent a potential target for the development of new therapeutic strategies against cutaneous leishmaniasis.

Neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and Huntington’s disease manifest with the neuronal accumulation of toxic proteins. Since autophagy upregulation enhances the clearance of such proteins and ameliorates their toxicities in animal models, we and others have sought to re-position/re-profile existing compounds used in humans to identify those that may induce autophagy in the brain. A key challenge with this approach is to assess if any hits identified can induce neuronal autophagy at concentrations that would be seen in humans taking the drug for its conventional indication. Here we report that felodipine, an L-type calcium channel blocker and anti-hypertensive drug, induces autophagy and clears diverse aggregate-prone, neurodegenerative disease-associated proteins. Felodipine can clear mutant α-synuclein in mouse brains at plasma concentrations similar to those that would be seen in humans taking the drug. This is associated with neuroprotection in mice, suggesting the promise of this compound for use in neurodegeneration. A key challenge is to find/re-purpose approved drugs that could be used in humans to induce autophagy-associated clearance of neurodegenerative proteins. Here, authors demonstrate that felodipine, an anti-hypertensive drug, can induce autophagy and clear a variety of aggregated neurodegenerative disease-associated proteins in mouse brains at plasma concentrations similar to those that would be seen in humans taking the drug.

Flexible electronics can be developed with a low-cost and simple fabrication process while being environmentally friendly. Conductive silver inks have been the most applied material in flexible substrates. This study evaluated the performance of different conductive ink formulations using silver nanoparticles by studying the material properties, the inkjet printing process, and application based on electrical impedance spectroscopy using a buffer solution. Silver nanoparticles synthesis was carried out through chemical reduction of silver nitrate; then, seven conductive ink formulations were produced. Properties such as resistivity, viscosity, surface tension, adhesion, inkjet printability of the inks, and electrical impedance of the printed electrodes were investigated. Curing temperature directly influenced the electrical properties of the inks. The resistivity obtained varied from 3.3 × 10 0 to 5.6 × 10 −06 Ω.cm. Viscosity ranged from 3.7 to 7.4 mPa.s, which is suitable for inkjet printing fabrication. By using a buffer solution as an analyte, the printed electrode pairs presented electrical impedance lower than 200 Ω for all the proposed designs, demonstrating the potential of the formulated inks for utilization in flexible electronic devices for biological sensing applications.

Hydrology-oriented silviculture might adapt Mediterranean forests to climatic changes, although its implementation demands a better understanding and quantification on the water fluxes. The influence of thinning intensity (high, medium, low and a control) and its effect on the mid-term (thinned plots in 1998 and 2008) on the water cycle (transpiration, soil water and interception) and growth [basal area increment (BAI)] were investigated in 55-year-old Aleppo pine trees. Thinning enhanced a lower dependence of growth on climate fluctuations. The high-intensity treatment showed significant increases in the mean annual BAI (from 4.1 to 17.3 cm²) that was maintained in the mid-term. Thinning intensity progressively increased the sap flow velocity (v ₛ) in all cases with respect to the control. In the mid-term, an increased functionality of the inner sapwood was also observed. Mean daily tree water use ranged from 5 (control) to 18 (high intensity) l tree⁻¹. However, when expressed on an area basis, daily transpiration ranged from 0.18 (medium) to 0.30 mm (control), meaning that in spite of the higher transpiration rates in the remaining trees, stand transpiration was reduced with thinning. Deep infiltration of water was also enhanced with thinning (about 30 % of rainfall) and did not compete with transpiration, as both presented opposite seasonal patterns. The changes in the stand water relationships after 10 years were well explained by the forest cover metric. The blue to green water ratio changed from 0.15 in the control to 0.72 in the high-intensity treatment, with the remaining treatments in the 0.34–0.48 range.

PurposeFatigue, decreased functionality, and impaired quality of life are some of the most common adverse outcomes of chemo-radiotherapy (CRT). Head and neck cancers (HNC) affect more than half a million individuals globally and its treatment takes a heavy toll on the patient, often affecting their speech, swallowing, and respiratory functions, and as a result they often develop fatigue, depression, and physical inactivity. The purpose of this study was to evaluate the effectiveness of exercise-based rehabilitation on functional capacity, quality of life, fatigue, hemoglobin, and platelet counts in patients with HNC on CRT.Patients and methodsA randomized controlled trial was conducted on 148 patients with head and neck cancer undergoing CRT to evaluate the effectiveness of exercise on functional capacity measured by the 6-min walk test, quality of life measured by the Medical Outcomes Survey Short Form 36 v2 questionnaire, fatigue by the NCCN (0–10) scale, hemoglobin, and platelets. The control group received standard physical activity recommendations while the exercise group received a structured exercise program of aerobic and active resistance exercises for a period of 11 weeks.ResultsThere was a significant improvement in the functional capacity (p < 0.001), quality of life (p < 0.001), and prevention of worsening of fatigue (p < 0.001) in the exercise group. The blood parameters did not show a significant difference between the control group and the exercise group.ConclusionOur results elucidate that an 11-week structured exercise program for HNC patients receiving CRT helps in improving their functional capacity and quality of life. It also prevents deterioration of fatigue levels in the exercise group.

The defining features of Alzheimer’s disease (AD) include alterations in protein aggregation, immunity, lipid metabolism, synapses, and learning and memory. Of these, lipid abnormalities are the least understood. Here, we investigate the role of Stearoyl-CoA desaturase (SCD), a crucial regulator of fatty acid desaturation, in AD pathogenesis. We show that inhibiting brain SCD activity for 1-month in the 3xTg mouse model of AD alters core AD-related transcriptomic pathways in the hippocampus, and that it concomitantly restores essential components of hippocampal function, including dendritic spines and structure, immediate-early gene expression, and learning and memory itself. Moreover, SCD inhibition dampens activation of microglia, key mediators of spine loss during AD and the main immune cells of the brain. These data reveal that brain fatty acid metabolism links AD genes to downstream immune, synaptic, and functional impairments, identifying SCD as a potential target for AD treatment. Alzheimer’s disease (AD) is characterized by lipid abnormalities which are not well understood. Here, the authors investigate the role of Stearoyl-CoA desaturase (SCD) in a mouse model of AD. They show that inhibiting SCD activity induces major brain and immune cell transcriptional changes and restores dendritic structure and learning and memory.

Background: Colonic fermentation of dietary fibre to short-chain fatty acids (SCFA) influences appetite hormone secretion in animals, but SCFA production is excessive in obese animals. This suggests there may be resistance to the effect of SCFA on appetite hormones in obesity. Objectives: To determine the effects of inulin (IN) and resistant starch (RS) on postprandial SCFA, and gut hormone (glucagon-like peptide (GLP-1), peptide–tyrosine–tyrosine (PYY) and ghrelin) responses in healthy overweight/obese (OWO) vs lean (LN) humans. Subjects/Methods: Overnight-fasted participants (13 OWO and 12 LN) consumed 300 ml water containing 75 g glucose (GLU) as control or 75 g GLU plus 24 g IN, or 28.2 g RS using a randomised, single-blind, cross-over design. Blood for appetite hormones and SCFA was collected at intervals over 6 h. A standard lunch was served 4 h after the test drink. Results: Relative to GLU, IN, but not RS, significantly increased SCFA areas under the curve (AUC) from 4–6 h (AUC 4–6 ). Neither IN nor RS affected GLP-1 or PYY-AUC 4–6 . Although neither IN nor RS reduced ghrelin-AUC 4–6 compared with GLU, ghrelin at 6 h after IN was significantly lower than that after GLU ( P <0.05). After IN, relative to GLU, the changes in SCFA-AUC 4–6 were negatively related to the changes in ghrelin-AUC 4–6 ( P =0.017). SCFA and hormone responses did not differ significantly between LN and OWO. Conclusions: Acute increases in colonic SCFA do not affect GLP-1 or PYY responses in LN or OWO subjects, but may reduce ghrelin. The results do not support the hypothesis that SCFA acutely stimulate PYY and GLP-1 secretion; however, a longer adaptation to increased colonic fermentation or a larger sample size may yield different results.

The inherent scalability, low production cost and mechanical flexibility of laser-induced graphene (LIG) combined with its high electrical conductivity, hierarchical porosity and large surface area are appealing characteristics for many applications. Still, other materials can be combined with LIG to provide added functionalities and enhanced performance. This work exploits the most adequate electrodeposition parameters to produce LIG/ZnO nanocomposites. Low-temperature pulsed electrodeposition allowed the conformal and controlled deposition of ZnO rods deep inside the LIG pores whilst maintaining its inherent porosity, which constitute fundamental advances regarding other methods for LIG/ZnO composite production. Compared to bare LIG, the composites more than doubled electrode capacitance up to 1.41 mF cm −2 in 1 M KCl, while maintaining long-term cycle stability, low ohmic losses and swift electron transfer. The composites also display a luminescence band peaked at the orange/red spectral region, with the main excitation maxima at ~ 3.33 eV matching the expected for the ZnO bandgap at room temperature. A pronounced sub-bandgap tail of states with an onset absorption near 3.07 eV indicates a high amount of defect states, namely surface-related defects. This work shows that these environmentally sustainable multifunctional nanocomposites are valid alternatives for supercapacitors, electrochemical/optical biosensors and photocatalytic/photoelectrochemical devices.