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Toxoplasmosis is a parasitic zoonotic disease caused by Toxoplasma (T.) gondii. Limited data are available on the occurrence of T. gondii in women especially pregnant women in Pakistan. The present study aimed to determine the occurrence and risk factors associated with T. gondii in pregnant and non-pregnant women in Punjab Province, Pakistan. A cross-sectional study was conducted and 593 samples were collected from pregnant (n = 293) and non-pregnant (n = 300) women of District Headquarter Hospitals of Chiniot, Faisalabad, Jhang and Okara, Pakistan. Data related to demographic parameters and risk factors were collected using a pretested questionnaire on blood sampling day. Serum samples were screened for antibodies (IgG) against T. gondii using ELISA. A univariant and binomial logistic regression was applied to estimate the association between seropositive and explanatory variables considering the 95% confidence interval. P value ⩽0.05 was considered statistically significant for all analysis. Out of 593, 44 (7.42%) women were seropositive for T. gondii IgG antibodies. Occupation, age, sampling location, socioeconomic status, contact with cat, pregnancy status and trimester of pregnancy were significantly associated with seropositivity for T. gondii antibodies. Location and trimester of pregnancy were identified as potential risk factors for T. gondii seropositivity based on binomial logistic regression. Toxoplasma gondii is prevalent in pregnant and non-pregnant women. Therefore, now a necessitated awareness is required to instruct the individuals about these infectious diseases (toxoplasmosis) and their control strategies to maintain the health of human population. Moreover, health awareness among public can help the minimization of T. gondii infection during pregnancy and subsequent risk of congenital toxoplasmosis.

Introduction: The establishment of new crops may cause climatic alterations at the local or regional level. Objective: To analyze temperature and rainfall variation by simulated replacement of current vegetation through the introduction of sugarcane (Saccharum officinarum L.), jatropha (Jatropha curcas L.) and moringa (Moringa oleifera Lam.) in the central region of the state of Veracruz, Mexico. Materials and methods: Simulations of environmental temperature and rainfall for each crop and the control (current conditions: mixed crop, perennial trees, mixed forest and irrigated agriculture) were made with the Regional Climate Model (RegCM4). The model was evaluated by comparative analysis between simulations and observed data, using the mean square error and the root-mean-square error as measures of dispersion. Results and discussion: Regions with soils devoid of natural vegetation, such as agricultural soils, would have greater climatic variability. In these soils, the displacement of current vegetation by sugarcane would generate the greatest thermal alterations with a decrease of 0.7 °C, while with jatropha and moringa, the decrease would be 0.3 °C. Regarding rainfall, the RegCM4 bias increases when there are high variations in elevation, thus other models should be explored. Conclusions: The introduction of moringa or jatropha for bioenergy purposes would be a low climatic impact alternative, while sugarcane is not considered suitable for these purposes due to the greater climatic impact that it would have in the region.

Grassland ecosystems account for more than 10% of the global CH4 sink in soils. A 4-year field experiment found that addition of P alone did not affect CH4 uptake and experimental addition of N alone significantly suppressed CH4 uptake, whereas concurrent N and P additions suppressed CH4 uptake to a lesser degree. A meta-analysis including 382 data points in global grasslands corroborated these findings. Global extrapolation with an empirical modelling approach estimated that contemporary N addition suppresses CH4 sink in global grassland by 11.4% and concurrent N and P deposition alleviates this suppression to 5.8%. The P alleviation of N-suppressed CH4 sink is primarily attributed to substrate competition, defined as the competition between ammonium and CH4 for the methane mono-oxygenase enzyme. The N and P impacts on CH4 uptake indicate that projected increases in N and P depositions might substantially affect CH4 uptake and alter the global CH4 cycle.

Fluorouracil (5-FU) is the first-line chemotherapeutic drug for cholangiocarcinoma (CCA), but its efficacy has been compromised by the development of resistance. Development of 5-FU resistance is associated with elevated expression of its cellular target, thymidylate synthase (TYMS). E2F1 transcription factor has previously been shown to modulate the expression of FOXM1 and TYMS. Immunohistochemical (IHC) analysis revealed a strong correlated upregulation of FOXM1 (78%) and TYMS (48%) expression at the protein levels in CCA tissues. In agreement, RT-qPCR and western blot analyses of four human CCA cell lines at the baseline level and in response to high doses of 5-FU revealed good correlations between FOXM1 and TYMS expression in the CCA cell lines tested, except for the highly 5-FU-resistant HuCCA cells. Consistently, siRNA-mediated knockdown of FOXM1 reduced the clonogenicity and TYMS expression in the relatively sensitive KKU-D131 but not in the highly resistant HuCCA cells. Interestingly, silencing of TYMS sensitized both KKU-D131 and HuCCA to 5-FU treatment, suggesting that resistance to very high levels of 5-FU is due to the inability of the genotoxic sensor FOXM1 to modulate TYMS expression. Consistently, ChIP analysis revealed that FOXM1 binds efficiently to the TYMS promoter and modulates TYMS expression at the promoter level upon 5-FU treatment in KKU-D131 but not in HuCCA cells. In addition, E2F1 expression did not correlate with either FOXM1 or TYMS expression and E2F1 depletion has no effects on the clonogenicity and TYMS expression in the CCA cells. In conclusion, our data show that FOXM1 regulates TYMS expression to modulate 5-FU resistance in CCA and that severe 5-FU resistance can be caused by the uncoupling of the regulation of TYMS by FOXM1. Our findings suggest that the FOXM1–TYMS axis can be a novel diagnostic, predictive and prognostic marker as well as a therapeutic target for CCA.

Objectives The aim of this study was to estimate the attributable proportion (AP) of mesothelioma resulting from living in or close to major Italian industrially contaminated areas. Methods For populations living close to 39 sites of "national priority for remediation", incident mesothelioma cases were extracted from the Italian National Mesothelioma Registry (ReNaM) in the period 2000‒2011. Each site was classified in one of seven asbestos risk groups (RG) on the basis of the type of industrial plants. RG were ranked by the a priori evidence on asbestos risk. The AP for each RG was calculated as the meta-analytic estimate of AP of sites of the same group by gender and age class (0–64, 65–74, ≥75 years). The sex ratio (men/women) was computed for each RG. Results Among men, the AP by age class had the same gradient in each RG, with the highest values in the age class 0–64 years and the lowest in the ≥75 class; in the age class 0–64 years, the AP was positive in each RG, >90% in the presence of asbestos cement factories and harbors with shipyards. Among women, the overall AP decreased by RG, with negative values in the last two ranked RG; the AP by age class was variable without a definite gradient. The sex ratio was close to one only in the RG "only asbestos-cement factories"; the highest value (9.6) was observed in the age class 0–64 years in the RG "harbors with shipyard". Conclusions The integration of a geographic- and case-based approach provides valuable insights into occupational and environmental determinants of mesothelioma risk in industrially contaminated sites.

Octarya Z, Novianty R, Suraya N, Saryono. 2021. Antimicrobial activity and GC-MS analysis of bioactive constituents of Aspergillus fumigatus 269 isolated from Sungai Pinang Hot Spring, Riau, Indonesia. Biodiversitas 22: 1839-1845. A total of 16 isolates of thermophilic fungi originating from hot springs in Riau and West Sumatra have been tested for their antimicrobial ability against pathogenic microbes Candida albicans, Staphylococcus aureus, and Escherichia coli. The antimicrobial test was carried out by using the disk diffusion method. Molecular identification of the most potential isolate (LBKURCC269) was carried out by amplifying the ITS (Internal transcribed spacer) sequence on rDNA using universal primer ITS-4 and ITS-5. ITS sequence results showed that LBKURCC269 has a 99% similarity to Aspergillus fumigatus. Ethyl acetate extract of LBKURCC269 (Aspergillus fumigatus 269) showed good antimicrobial activities against three pathogenic microbes tested with the inhibition of 17 mm, 13 mm, and 13 mm against Staphylococcus aureus, Candida albicans, and Escherichia coli, respectively. There were 24 identified chemical compounds in ethyl acetate extract. The major compounds were eicosane, eicosane 2-methyl, phenol, 2,6-bis(1,1-dimethyl ethyl)-4-methyl, hexadecane 2, and 11-octadecenoic acid, methyl ester. These findings suggest that thermophilic fungi isolated from hot springs could serve as reservoirs for new bioactive compounds of industrial and medical importance.

Fear extinction requires coordinated neural activity within the amygdala and medial prefrontal cortex (mPFC). Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear extinction. Here, we investigated the effects of optogenetic manipulations of prelimbic (PrL) pyramidal neurons and amygdala gene expression to analyze the specific transcriptional pathways associated to adaptive and maladaptive fear extinction. To this aim, transgenic mice were (or not) fear-conditioned and during the extinction phase they received optogenetic (or sham) stimulations over photo-activable PrL pyramidal neurons. At the end of behavioral testing, electrophysiological (neural cellular excitability and Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the PrL pyramidal neurons. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Our results show that the optogenetic activation of PrL pyramidal neurons in fear-conditioned mice induces fear extinction deficits, reflected in an increase of cellular excitability, excitatory neurotransmission, and spinogenesis of PrL pyramidal neurons, and associated to strong modifications of the transcriptome of amygdala pyramidal neurons. Understanding the electrophysiological, morphological, and transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that represent toxic real threat for human beings and animal health. In this study we evaluated the effect of a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) on oxidative stress and on the alterations of fluid reabsorption in renal proximal tubule (PT) as possible causes of OTA nephrotoxicity. Finally, we have measured the concentration of O2- in the kidney through dihydroethidium assay (DHE) and nitric oxide (NO) concentration through nitrites and nitrates assay. Male Sprague Dawley rats weighing 120-150 g were treated for 14 days by gavage, as follows: Control group, 12 rats received a corresponding amount of saline solution (including 10% DMSO); rMnSOD group, 12 rats treated with rMnSOD (10 µg/kg bw); OTA group, 12 rats treated with OTA (0,5 mg/Kg bw) dissolved in 10% DMSO and then scaled to required volume with corn oil; rMnSOD + OTA, 12 rats treated with rMnSOD (10 µg /kg bw) plus OTA (0,5 mg/Kg bw). Our results have shown that rMnSOD restores the alteration of reabsorption in PT in rats treated with OTA plus rMnSOD, probably through the response to pressure natriuresis, where nitric oxide plays a key role. Moreover, rMnSOD prevents the nephrotoxicity induced by OTA probably restoring the balance between superoxide and NO that is most probably the cause of hypertension and renal functional alterations through the inhibition of NO synthase. In conclusion these data provide important information for understanding of mechanism of toxic action of OTA. This article is protected by copyright. All rights reserved

In the last decade, Nerve Growth Factor (NGF)-based clinical approaches have lacked specific and efficient Tyrosine Kinase A (TrkA) agonists for brain delivery. Nowadays, the characterization of novel small peptidomimetic is taking centre stage in preclinical studies, in order to overcome the main size-related limitation in brain delivery of NGF holoprotein for Central Nervous System (CNS) pathologies. Here we investigated the NGF mimetic properties of the human NGF 1&ndash, 14 sequence (hNGF1&ndash, 14) and its derivatives, by resorting to primary cholinergic and dorsal root ganglia (DRG) neurons. Briefly, we observed that: 1) hNGF1&ndash, 14 peptides engage the NGF pathway through TrkA phosphorylation at tyrosine 490 (Y490), and activation of ShcC/PI3K and Plc-&gamma, /MAPK signalling, promoting AKT-dependent survival and CREB-driven neuronal activity, as seen by levels of the immediate early gene c-Fos, of the cholinergic marker Choline Acetyltransferase (ChAT), and of Brain Derived Neurotrophic Factor (BDNF), 2) their NGF mimetic activity is lost upon selective TrkA inhibition by means of GW441756, 3) hNGF1&ndash, 14 peptides are able to sustain DRG survival and differentiation in absence of NGF. Furthermore, the acetylated derivative Ac-hNGF1&ndash, 14 demonstrated an optimal NGF mimetic activity in both neuronal paradigms and an electrophysiological profile similar to NGF in cholinergic neurons. Cumulatively, the findings here reported pinpoint the hNGF1&ndash, 14 peptide, and in particular its acetylated derivative, as novel, specific and low molecular weight TrkA specific agonists in both CNS and PNS primary neurons.

Jatropha curcas L is widely planted in people's homes. Jatropha has many bioactive compounds, including flavonoids, saponins, tannins, and alkaloids. In this research, phytochemical tests and antimicrobial activities of sap and water extraction of Jatropha curcas L leaves on Candida albicans, Aspergillus, and Pseudomonas aeruginosa were carried out. The results of the phytochemical test of sap and water extraction of leaves showed positive results in the test of flavonoids, saponins, alkaloids and tannins. While steroid testing showed negative results. The antimicrobial capabilities of sap and water extraction of leaves to Aspergillus were 10.5 mm and 11 mm and to Pseudomonas Aeruginosa were 15 mm and 11 mm. Whereas the antimicrobial ability of sap and water extraction of leaf to Candida albicans was negative. In this case, it means that Pseudomonas aeruginosa is including microbes that are sensitive to antimicrobial origin of plants.

Premise of research. Salvia is one of the most species-rich genera in the world. Its outstanding diversity and subcosmopolitan distribution have prevented the preparation of a modern comprehensive monograph and re-evaluation of its classification. As phylogenetic efforts advance to untangle the evolutionary relationships of Salvia, the need for a solid taxonomic footing is increasingly imperative. Accordingly, we present an updated checklist of the species richness and distribution of Salvia subg. Calosphace, which constitutes more than half of the diversity of the genus. Methodology. A preliminary checklist of the species of Salvia subg. Calosphace was compiled through examination of the literature and online databases; this was revised and discussed by the authors in order to retrieve a consensus list. The distribution of each species by country or territory as well as by biome was also recorded from the sources consulted; affinities in composition were visualized with the unweighted pair group method with arithmetic mean based on a dissimilarity matrix (Sørensen’s index). Pivotal results. Salvia subg. Calosphace comprises 580 species; 30 were qualified as unresolved and require further analysis. The countries with the highest species richness are Mexico (295 spp.), Peru (77 spp.), Colombia (60 spp.), Brazil (58 spp.), Guatemala (49 spp.), and Ecuador (41 spp.). The affinity in species composition between countries and between biomes is explained mainly by geographical proximity. Conclusions. The updated list of the species of Salvia subg. Calosphace will help to guide sampling for phylogenetic analyses, enabling the achievement of a more stable and solid phylogenetic hypothesis. At the same time, it is a potentially important tool for underpinning discussions toward a new sectional classification of the lineage.

Pacific salmon (Oncorhynchus spp.) are ecological and cultural keystone species along the Northwest Coast of North America and are ubiquitous in archaeological sites of the region. The inability to morphologically identify salmonid post-cranial remains to species, however, can limit our understanding of the ecological and cultural role different taxa played in the seasonal subsistence practices of Indigenous groups in the past. Here, we present a rapid, cost-effective ZooMS method to distinguish salmonid species based on collagen peptide mass-fingerprinting. Using modern reference material and an assemblage of 28 DNA-identified salmonid bones from the pre-contact Yup'ik site of Nunalleq, Western Alaska, we apply high-resolution mass spectrometry (LC-MS/MS) to identify a series of potential collagen peptide markers to distinguish Pacific salmon. We then confirm these peptide markers with a blind ZooMS analysis (MALDI-TOF-MS) of the archaeological remains. We successfully distinguish five species of anadromous salmon with this ZooMS approach, including one specimen that could not be identified through ancient DNA analysis. Our biomolecular identification of chum (43%), sockeye (21%), chinook (18%), coho (11%) and pink (7%), confirm the exploitation of all five available species of salmonid at Nunalleq.

Coccothrinax argentata (Arecaceae) occurs in southern Florida, both on the mainland and in the islands of the Florida Keys. However, the palms from the mainland and Keys display morphological differences that led taxonomists to recognize them as distinct species in the past. They are now treated as a single, polymorphic species, but the question remains: Are the morphological differences best explained by genetics or environment? In 1999, seedlings grown from seeds collected from different populations were planted in a common garden in a randomized plot design. In 2007, the first research was published comparing genetics based on ISSRs to morphological measurements. The research from 2007 showed evidence for a genetic explanation, but with poor resolution. Here, we present new genetic data using microsatellite regions (SSRs), in combination with morphological data from more mature palms. The results support the recognition of two taxa, which we propose at the rank of subspecies.

Although Salvia roemeriana has long been known to produce both chasmogamous and cleistogamous flowers, the mericarps resulting from those flowers have received little attention. We germinated seeds from chasmogamous and cleistogamous flowers, recorded germination times, and fit time‐to‐germination, three‐parameter log‐logistic regressions to analyze differences in germination progress. Additionally, we compared the mass and size of mericarps from both kinds of flowers. Our results show that the mericarps produced from chasmogamous flowers are larger and heavier than those from cleistogamous flowers. In addition, seeds from chasmogamous flowers had a longer dormancy than those from cleistogamous flowers. This is the first report of heterocarpy in Salvia and in the family Lamiaceae. Together, cleistogamy and heterocarpy are a multiple strategy that may be advantageous in heterogeneous environments.

Zinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to investigate the physiological mechanisms by which zinc is important to placental morphogenesis and the maternal blood pressure changes during pregnancy. A 26% reduction in circulating zinc (P = 0.005) was exhibited in mice fed a moderately zinc-deficient diet. Zinc deficiency in pregnancy resulted in an 8% reduction in both near term fetal and placental weights (both P in utero programming of offspring growth and development largely through effects to the placenta and maternal cardiovascular system.

Previous research has implicated the positive modulation of anandamide, an endocannabinoid neurotransmitter, on feeding behavior. Anandamide is particularly noteworthy as it acts as an endogenous ligand of the CB1 receptor, the same receptor that is activated by tetrahydrocannabinol, the primary psychoactive component in Cannabis sativa. Cannabis legalization in North America has presented with a need to study endocannabinoid agonists and their effects on behavior. Much has yet to be determined in terms of the role of the endocannabinoid system in decision-making scenarios. The research presented here tested the hypothesis that anandamide would augment motivation and reward processing via appetitive and consummatory measures during an operant, foraging task. A three-box design was used in order to provide the animals with a free choice, exploratory foraging environment. Discrimination, preference, and incentive contrast were analyzed as discrete measures of decision-making in the three-box paradigm. Anandamide administration (1mg/kg) was found to significantly increase motivation for the optimal foraging outcome and alter basic processing of reward information involved in discrimination and relative valuation. The positive effects of anandamide on eating behavior and motivation have implications toward possible treatment modalities for patient populations presenting with disorders of motivation. These findings suggest the need for continued investigation of the endocannabinoid system as a central component of motivated behavior.

Introduced species can have diverse effects on recipient ecosystems. Here we share observations suggesting the formation of a reciprocally positive interaction, seed dispersal, between an introduced lizard and a native palm. We present evidence that the large arboreal lizard ( Anolis equestris ), native to the West Indies but well-established in south Florida USA, has a diet dominated by the fruit of several native trees including the endangered royal palm ( Roystonea regia ). We also show that seeds passed through the gut of A. equestris are viable, suggesting their role as seed dispersers in their introduced range. These findings are the first to document the passage of viable seeds by Anolis lizards, a speciose and ecologically-diverse Neotropical group that exhibits widespread frugivory. We believe these observations highlight potentially important, but understudied interactions between these Neotropical lizards and plants.

The seed dispersal mechanisms of Salvia species are reviewed, with particular attention to quantitative or experimental evidence of dispersal. Despite having rather uniform fruit morphology, Salvia has several dispersal mechanisms: dispersal of mericarps by water (hydrochory), wind (anemochory), animals (zoochory) or gravity (barochory). Cases of myrmecochory are highlighted, along with dispersal by the plant itself via springy or hygroscopic pedicels. Despite having no visible means of dispersal, many Salvia species disperse for short to medium distances. Many gaps in our knowledge of dispersal exist, despite the fact that knowledge of dispersal mechanisms is critical in evaluating invasive potential, conservation status, usefulness in habitat restoration, and geographic distribution.

A recent survey of the liverworts of Mahogany Hammock, Everglades National Park, Florida, USA, complements the surveys in the 1950s, 1970s, and 1980s. Despite disturbances by hurricanes, changes in local ecology, and millions of park visitors, Mahogany Hammock still supports a rich hepatic flora with mostly tropical affinities. We collected 29 of ca. 47 taxa that have been recorded from the hammock, including six new records. Most taxa were found growing on the bark of trees and shrubs, but some were epiphyllous on the leaves of trees, ferns, and epiphytic Tillandsia (Bromeliaceae). The boardwalk in the hammock also served as a substrate for liverworts.

The use and impact of 3M™ Emphaze™ AEX Hybrid Purifier, a single‐use, fully synthetic chromatographic product, was explored to reduce host cell DNA (HC‐DNA) concentration during the primary clarification of a monoclonal antibody (mAb). An approximately 5‐log reduction in HC‐DNA was achieved at an Emphaze AEX Hybrid Purifier throughput of 200 L/m2. The appreciable reduction in HC‐DNA achieved during primary clarification enhanced Protein A chromatography performance, resulting in a sharper and narrower elution profile. In addition, a 24× improvement in host cell protein (HCP) removal and fewer impurities nonspecifically bound to the Protein A column were observed compared to those resulting from the use of depth filtration for clarification. The use of a rapid, qualitative acidification assay to facilitate HC‐DNA monitoring was also investigated. This assay involves the acidification‐induced precipitation of HC‐DNA, enabling the easy and rapid detection of DNA breakthrough across purification media such as Emphaze AEX Hybrid Purifier by means of turbidimetric and particle size measurements.

The lack of in-depth knowledge about the molecular determinants of glioblastoma (GBM) occurrence and progression, combined with few effective and BBB crossing-targeted compounds represents a major challenge for the discovery of novel and efficacious drugs for GBM. Among relevant molecular factors controlling the aggressive behavior of GBM, chloride intracellular channel 1 (CLIC1) represents an emerging prognostic and predictive biomarker, as well as a promising therapeutic target. CLIC1 is a metamorphic protein, co-existing as both soluble cytoplasmic and membrane-associated conformers, with the latter acting as chloride selective ion channel. CLIC1 is involved in several physiological cell functions and its abnormal expression triggers tumor development, favoring tumor cell proliferation, invasion, and metastasis. CLIC1 overexpression is associated with aggressive features of various human solid tumors, including GBM, in which its expression level is correlated with poor prognosis. Moreover, increasing evidence shows that modification of microglia ion channel activity, and CLIC1 in particular, contributes to the development of different neuropathological states and brain tumors. Intriguingly, CLIC1 is constitutively active within cancer stem cells (CSCs), while it seems less relevant for the survival of non-CSC GBM subpopulations and for normal cells. CSCs represent GBM development and progression driving force, being endowed with stem cell-like properties (self-renewal and differentiation), ability to survive therapies, to expand and differentiate, causing tumor recurrence. Downregulation of CLIC1 results in drastic inhibition of GBM CSC proliferation in vitro and in vivo, making the control of the activity this of channel a possible innovative pharmacological target. Recently, drugs belonging to the biguanide class (including metformin) were reported to selectively inhibit CLIC1 activity in CSCs, impairing their viability and invasiveness, but sparing normal stem cells, thus representing potential novel antitumor drugs with a safe toxicological profile. On these premises, we review the most recent insights into the biological role of CLIC1 as a potential selective pharmacological target in GBM. Moreover, we examine old and new drugs able to functionally target CLIC1 activity, discussing the challenges and potential development of CLIC1-targeted therapies.

Basal forebrain cholinergic neurons (BFCNs) depend on nerve growth factor (NGF) for their survival/differentiation and innervate cortical and hippocampal regions involved in memory/learning processes. Cholinergic hypofunction and/or degeneration early occurs at prodromal stages of Alzheimer's disease (AD) neuropathology in correlation with synaptic damages, cognitive decline and behavioral disability. Alteration(s) in ubiquitin-proteasome system (UPS) is also a pivotal AD hallmark but whether it plays a causative, or only a secondary role, in early synaptic failure associated with disease onset remains unclear. We previously reported that impairment of NGF/TrkA signaling pathway in cholinergic-enriched septo-hippocampal primary neurons triggers "dyingback" degenerative processes which occur prior to cell death in concomitance with loss of specific vesicle trafficking proteins, including synapsin I, SNAP-25 and alpha-synuclein, and with deficit in presynaptic excitatory neurotransmission. Here, we show that in this in vitro neuronal model: (i) UPS stimulation early occurs following neurotrophin starvation (-1 h up to -6 h); (ii) NGF controls the steady-state levels of these three presynaptic proteins by acting on coordinate mechanism(s) of dynamic ubiquitin-C-terminal hydrolase 1 (UCHL-1)-dependent (mono) ubiquitin turnover and UPS-mediated protein degradation. Importantly, changes in miniature excitatory post-synaptic currents (mEPSCs) frequency detected in -6 h NGF-deprived primary neurons are strongly reverted by acute inhibition of UPS and UCHL-1, indicating that NGF tightly controls in vitro the presynaptic efficacy via ubiquitination-mediated pathway(s). Finally, changes in synaptic ubiquitin and selective reduction of presynaptic markers are also found in vivo in cholinergic nerve terminals from hippocampi of transgenic Tg2576 AD mice, even from presymptomatic stages of neuropathology (1-month-old). By demonstrating a crucial role of UPS in the dysregulation of NGF/TrkA signaling on properties of cholinergic synapses, these findings from two well-established cellular and animal AD models provide novel therapeutic targets to contrast early cognitive and synaptic dysfunction associated to selective degeneration of BFCNs occurring in incipient early/middle-stage of disease.

The curious habit of shingle-leaf climbers – root-climbing plants whose leaves are closely adpressed to the phorophyte and often overlap like shingles – has attracted the attention of both botanists and horticulturists for more than a century. The habit has arisen in ten families, 22 genera, and at least 158 species and is especially common in several genera of Araceae and Marcgravia (Marcgraviaceae). Herein, the species are tabulated, and various hypotheses for the evolution of the habit are reviewed. Two hypotheses that emerge as having explanatory power for understory shingle-leaf climbers are 1) Trapping & Recycling CO2 and 2) Stemflow Nutrient Capture, but other hypotheses may also have support in some cases. Three hypotheses (Balancing Carbon Allocation, Avoiding Damage from Falling Objects, and Avoiding Herbivory) have some support for some species. One hypothesis (Protecting against Desiccation of Roots and Leaves) has some support for shingle-leaf climbers in exposed, sunny habitats (viz., Hoya, Dischidia, Cattleya cernua and other orchids). Different selective pressures may have led to convergence on the shingle-leaf habit in different habitats. Moreover, these hypotheses are not necessarily mutually exclusive. Few hypotheses have been explicitly tested, and so the adaptive significance of the shingle-leaf climber habit remains uncertain.

Statins are a class of drugs that inhibit the rate-limiting steps in the cholesterol biosynthesis pathway. They act by inhibiting 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate. Blocking of mevalonate synthesis leads to inhibition of the farnesylation and geranylgeranylation of several functional proteins, such as RhoA and other small guanosine triphosphate-binding proteins, that are important in maintaining the undifferentiated status of the cells. In the present study, we hypothesized that simvastatin, likely through the inhibition of farnesylation and geranylgeranylation of Rac1, Cd42 and RhoA, induces a destruction/restructuration of the cytoskeleton that decreases mechanical strain transfer to the nuclei, inducing the loss of transmission of regulatory signals from the cytoskeleton to the nucleoskeleton. Although this remains at present a hypothesis and is not easy to define if the de-structuration of the cytoskeleton is a secondary effect of simvastatin treatment or the inhibition of post-translational protein modification have a precise role in the structuration of actin cytoskeleton, we speculate that these signal variations could inhibit the expression of certain stemness genes, which could therefore be considered nucleoskeleton-associated and mechanically regulated genes. On the other hand, the restructuration of the cytoskeleton inhibits the formation of lamellipodia and filopodia, which likely decreases the capability of cancer cells to invade the extracellular matrix, thereby modulating the equilibrium between proliferation, differentiation and metastatic invasion in human cancer cells. On the basis of our results we think that simvastatin, alone or in combination with conventional drugs, may have a possible role in cancer therapy.

The need for renewable energy sources will lead to a considerable expansion in the planting of dedicated fast‐growing biomass crops across Europe. These are commonly cultivated as short‐rotation coppice (SRC), and currently poplar (Populus spp.) is the most widely planted. In this study, we report the greenhouse gas (GHG) fluxes of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) measured using eddy covariance technique in an SRC plantation for bioenergy production. Measurements were made during the period 2010–2013, that is, during the first two rotations of the SRC. The overall GHG balance of the 4 years of the study was an emission of 1.90 (±1.37) Mg CO2eq ha−1; this indicated that soil trace gas emissions offset the CO2 uptake by the plantation. CH4 and N2O contributed almost equally to offset the CO2 uptake of −5.28 (±0.67) Mg CO2eq ha−1 with an overall emission of 3.56 (±0.35) Mg CO2eq ha−1 of N2O and of 3.53 (±0.85) Mg CO2eq ha−1 of CH4. N2O emissions mostly occurred during one single peak a few months after the site was converted to SRC; this peak comprised 44% of the total N2O loss during the two rotations. Accurately capturing emission events proved to be critical for deriving correct estimates of the GHG balance. The nitrogen (N) content of the soil and the water table depth were the two drivers that best explained the variability in N2O and CH4, respectively. This study underlines the importance of the ‘non‐CO2 GHGs’ on the overall balance. Further long‐term investigations of soil trace gas emissions should monitor the N content and the mineralization rate of the soil, as well as the microbial community, as drivers of the trace gas emissions.

FOXO3a and FOXM1 are two forkhead transcription factors with antagonistic roles in cancer and DNA damage response. FOXO3a functions like a typical tumour suppressor, whereas FOXM1 is a potent oncogene aberrantly overexpressed in genotoxic resistant cancers. FOXO3a not only represses FOXM1 expression but also its transcriptional output. Recent research has provided novel insights into a central role for FOXO3a and FOXM1 in DNA damage response. The FOXO3a-FOXM1 axis plays a pivotal role in DNA damage repair and the accompanied cellular response through regulating the expression of genes essential for DNA damage sensing, mediating, signalling and repair as well as for senescence, cell cycle and cell death control. In this manner, the FOXO3a-FOXM1 axis also holds the key to cell fate decision in response to genotoxic therapeutic agents and controls the equilibrium between DNA repair and cell termination by cell death or senescence. As a consequence, inhibition of FOXM1 or reactivation of FOXO3a in cancer cells could enhance the efficacy of DNA damaging cancer therapies by decreasing the rate of DNA repair and cell survival while increasing senescence and cell death. Conceptually, targeting FOXO3a and FOXM1 may represent a promising molecular therapeutic option for improving the efficacy and selectivity of DNA damage agents, particularly in genotoxic agent resistant cancer. In addition, FOXO3a, FOXM1 and their downstream transcriptional targets may also be reliable diagnostic biomarkers for predicting outcome, for selecting therapeutic options, and for monitoring treatments in DNA-damaging agent therapy.

The phenology, floral biology and pollination ecology of Salvia arborescens Urb. & Ekman (Lamiaceae) are reported, based on field and garden observations. The flowers of S. arborescens are white, fragrant and rich in nectar. Anthesis begins in the late afternoon, and flowers wilt by late morning of the following day. Floral features fit the moth pollination syndrome. S. arborescens flowers are visited by a variety of nocturnal moths in the wild, including Celiptera levinum (Lepidoptera: Noctuoidea: Erebidae), which was observed carrying pollen of this Salvia. This is the first report of a night-blooming, moth-pollinated Salvia. Hummingbirds, butterflies and beetles may play a role as secondary pollinators.

Accurate estimates of annual budgets of methane (CH4) efflux in arctic regions are severely constrained by the paucity of non-summer measurements. Moreover, the incomplete understanding of the ecosystem-level sensitivity of CH4 emissions to changes in tundra moisture makes prediction of future CH4 release from the Arctic extremely difficult. This study addresses some of these research gaps by presenting an analysis of eddy covariance and chamber measurements of CH4 efflux and supporting environmental variables during the autumn season and associated beginning of soil freeze-up at our large-scale water manipulation site near Barrow, Alaska (the Biocomplexity Experiment). We found that the autumn season CH4 emission is significant (accounting for 21–25% of the average growing season emission), and that this emission is mostly controlled by the fraction of inundated landscape, atmospheric turbulence, and the decline in unfrozen water during the period of soil freezing. Drainage decreased autumn CH4 emission by a factor of 2.4 compared to our flooded treatment. Flooding slowed the soil freezing process which has implications for extending elevated CH4 emissions longer into the winter season.

Myotonic Dystrophy type 1 (DM1) is a multisystemic disease, autosomal dominant, caused by a CTG repeat expansion in DMPK gene. We assessed the appropriateness of patient-specific induced pluripotent stem cell-derived cardiomyocytes (CMs) as a model to recapitulate some aspects of the pathogenetic mechanism involving cardiac manifestations in DM1 patients. Once obtained in vitro, CMs have been characterized for their morphology and their functionality. CMs DM1 show intranuclear foci and transcript markers abnormally spliced respect to WT ones, as well as several irregularities in nuclear morphology, probably caused by an unbalanced lamin A/C ratio. Electrophysiological characterization evidences an abnormal profile only in CMs DM1 such that the administration of antiarrythmic drugs to these cells highlights even more the functional defect linked to the disease. Finally, Atomic Force Measurements reveal differences in the biomechanical behaviour of CMs DM1, in terms of frequencies and synchronicity of the beats. Altogether the complex phenotype described in this work, strongly reproduces some aspects of the human DM1 cardiac phenotype. Therefore, the present study provides an in vitro model suggesting novel insights into the mechanisms leading to the development of arrhythmogenesis and dilatative cardiomyopathy to consider when approaching to DM1 patients, especially for the risk assessment of sudden cardiac death (SCD). These data could be also useful in identifying novel biomarkers effective in clinical settings and patient-tailored therapies.

Amyotrophic Lateral Sclerosis (ALS) is a chronic neurodegenerative disease affecting upper and lower motor neurons, with unknown aetiology. Lipid rafts, cholesterol enriched microdomains of the plasma membrane, have been linked to neurodegenerative disorders like ALS. The NMDA-receptor subcellular localization in lipid rafts is known to play many roles, from modulating memory strength to neurotoxicity. In this study, performed on the widely used G93A mouse model of ALS, we have shown an equal content of total membrane cholesterol in Control and G93A cortical cultures. Moreover, by electrophysiological studies, we have recorded NMDA- and AMPA-evoked currents which were not significantly different between the two neuronal populations. To study the role of membrane cholesterol on glutamate receptor functionality, we have analysed NMDA and AMPA receptors following cholesterol membrane depletion by methyl-β-cyclodextrin (MβCD). Interestingly, MβCD chronic treatment has provoked a significant reduction of NMDA-evoked currents in both cellular populations which was dose- and time-dependent but significantly higher in ALS neurons compared to Control. The different MβCD effect on NMDA-evoked currents was not due to a different membrane receptor subunit composition but seemed to cause in both neuronal populations a NMDA receptor membrane redistribution. MβCD treatment effect was receptor-specific since no alterations in the two neuronal populations were detected on AMPA receptors. These results lead us to speculate for an altered proteomic composition of lipid rafts in cortical mutated neurons and suggest the need for further studies on the lipid rafts composition and on their interaction with membrane receptors in ALS cortices.

Litter-trapping plants have specialized growth habits and morphologies that enable them to capture falling leaf litter and other debris, which the plants use for nutrition after the litter has decayed. Litter is trapped via rosettes of leaves, specially modified leaves and/or upward-growing roots (so-called ‘root baskets’). Litter-trappers, both epiphytic and terrestrial, are found throughout the tropics, with only a few extra-tropical species, and they have evolved in many plant families. The trapped litter mass is a source of nutrients for litter-trapping plants, as well as food and housing for commensal organisms. Despite their unique mode of life, litter-trapping plants are not well documented, and many questions remain about their distribution, physiology and evolution.–© 2015 The Linnean Society of London, Botanical Journal of the Linnean Society, 2015, 179, 554–586.

We used the eddy-covariance technique to measure the temporal dynamics and the relationships between leaf area index (LAI) and exchanges of carbon dioxide (CO2), latent heat (LE) and sensible heat (H) in a multi-genotype short-rotation poplar coppice (SRC) located in East-Flanders (Belgium). The study was carried out over four years (20102013) corresponding to the first two rotations of the plantation. The net carbon (C) balance during the first two-year rotation was 75.2 (±4.4) g C m−2 in the establishment year 2010 and −95.6 (±5.9) g C m−2 in 2011. After the harvest (second two-year rotation) the coppice was a net source of carbon, 151.0 (±10.5) g C m−2 in 2012, but a sink of −274.6 (±18.8) g C m−2 in 2013. Overall, at the end of the second rotation this SRC, was a net CO2 sink with a cumulative uptake of −144.0 (±22.8) g C m−2. The temporal dynamics and the magnitude of the ratio between gross primary production (GPP) and ecosystem respiration (Reco) were similar to a deciduous forest. The evolution of LAI showed values ranging from 0.96 (±0.4) to 2.0 (±1.2) and from 5.1 (±1.5) to 4.5 (±0.84) during the first and the second rotation, respectively. The GPP (measured close to light saturation) was significantly related to LAI (r2 of 0.76, p < 0.001). The cumulative evapotranspiration (ET) measured during the first rotation was 241.7 mm and 349.9 mm for 2010 and 2011, respectively, and 464.6 mm and 372.1 mm for 2012 and 2013. The average value of surface conductance (Gs) was 0.35 mol m−2 s−1 and 0.24 mol m−2 s−1 for the foliated and unfoliated periods, respectively. The mean decoupling factors (Ω) were 0.35 and 0.23 for the foliated and unfoliated periods, respectively, indicating that ET was primarily controlled by vapor pressure deficit (VPD) and Gs (a well-coupled system). The mean PriestleyTaylor coefficient (α) was 0.77 and 0.53 for the foliated and the unfoliated periods, respectively. Such low values indicate that ET was significantly lower than the equilibrium evaporation and thus also lower than the ET of a hypothetical reference crop. During the whole experiment only two short episodes of drought were identified when in MayJune 2011 and June 2013 the evaporative fraction dropped below 0.4. The analysis of Gs showed a rather low stomatal control (anisohydric stomatal response) that put the poplar SRC at greater risk during severe drought conditions. All the three mentioned parameters related to ET and GPP (Gs, Ω and α) were significantly and positively correlated to LAI (r2 from 0.14 to 0.2, p < 0.0001), suggesting that LAI was the main biophysical driver controlling the carbon and water balances in this bioenergy production system.

The forkhead transcription factor FOXM1 has a key role in DNA damage response, and its deregulated overexpression is associated with genotoxic drug resistance in breast cancer. However, little is known about the posttranslational mechanisms by which FOXM1 expression is regulated by genotoxic agents and how they are deregulated in resistant cells. Initial co-immunoprecipitation studies verified previous proteomic analysis finding that the OTUB1 is a novel FOXM1-interacting protein. Western blot analysis showed that both OTUB1 and FOXM1 expression reduced upon genotoxic agent treatment in MCF-7 cells, but remained relatively constant in resistant cells. FOXM1 expression reduced upon OTUB1 depletion by siRNA and increased with OTUB1 overexpression in MCF-7 cells, arguing that OTUB1 positively regulates FOXM1 expression. In agreement, co-immunoprecipitation experiments demonstrated that FOXM1 expression is associated with OTUB1 binding but inversely correlates with conjugation to the protein degradation-associated Lys-48-linked ubiquitin-chains. Overexpression of wild-type (WT) OTUB1, but not the OTUB1(C91S) mutant, disrupted the formation of Lys48-linked ubiquitin-conjugates on FOXM1. Importantly, knockdown of OTUB1 by siRNA resulted in an increase in turnover of FOXM1 in MCF-7 cells treated with the protein synthesis inhibitor cycloheximide, whereas overexpression of WT OTUB1, but not the OTUB1(C91S) mutant, significantly enhances the half-life of FOXM1. In addition, proliferative and clonogenic assays also show that OTUB1 can enhance the proliferative rate and epirubicin resistance through targeting FOXM1, as OTUB1 has little effect on FOXM1-deficient cells. The physiological relevance of the regulation of FOXM1 by OTUB1 is further underscored by the significant correlations between FOXM1 and OTUB1 expression in breast cancer patient samples. Cox-regression survival analysis indicates that OTUB1 overexpression is linked to poorer outcome in particular in patients treated with chemotherapy. Collectively, these data suggest that OTUB1 limits the ubiquitination and degradation of FOXM1 in breast cancer and has a key role in genotoxic agent resistance.

A new survey of liverworts in three tropical hardwood hammocks in South Florida 100 years after they were first surveyed by John Kunkel Small found that the liverwort flora is mostly intact. The new survey collected 24 species, recollecting eight of the 13 species first collected by Small in these hammocks. Some taxa not noted by Small are xerophytic species that may have colonized the hammocks since Small's time. Epiphyllous species are a characteristic and noteworthy component of the hammock liverwort flora; eight taxa were found in this survey.

Forkhead Box M1 (FOXM1) is a bona fide oncofoetal transcription factor, which orchestrates complex temporal and spatial gene expression throughout embryonic and foetal development as well as during adult tissue homeostasis and repair. Controlled FOXM1 expression and activity provides a balanced transcriptional programme to ensure proper growth and maturation during embryogenesis and foetal development as well as to manage appropriate homeostasis and repair of adult tissues. Conversely, deregulated FOXM1 upregulation likely affects cell migration, invasion, angiogenesis, stem cell renewal, DNA damage repair and cellular senescence, which impact tumour initiation, progression, metastasis, angiogenesis and drug resistance. A thorough understanding of the regulation and role of FOXM1 in health and in cancer should contribute to the development of better diagnostics and treatments for cancer as well as congenital disorders and other developmental diseases.

The renal phenotype in Bardet-Biedl syndrome (BBS) is highly variable. The present study describes renal findings in 41 BBS patients and analyzes the pathogenesis of hyposthenuria, the most common renal dysfunction. Five of 41 patients (12%) showed an estimated glomerular filtration rate 60 ml·min-1·1.73 m-2. Urine protein and urine albumin-to-creatinine ratio were over 200 and 30 mg/g in 9/24 and 7/23 patients, respectively. Four of 41 patients showed no renal anomalies on ultrasound. Twenty of 34 patients had hyposthenuria in the absence of renal insufficiency. In all 8 of the hyposthenuric patients studied, dDAVP failed to elevate urine osmolality (Uosm), suggesting a nephrogenic origin. Interestingly, water loading (WL) did not result in a significant reduction of Uosm, indicating combined concentrating and diluting defects. dDAVP infusion induced a significant increase of plasma Factor VIII and von Willebrand Factor levels, supporting normal function of the type 2 vasopressin receptor at least in endothelial cells. While urinary aquaporin 2 (u-AQP2) abundance was not different between patients and controls at baseline, the dDAVP-induced increased u-AQP2 and the WL-induced reduction of u-AQP2 were blunted in patients with a combined concentrating and diluting defect, suggesting a potential role of AQP2 in the defective regulation of water absorption. Urine Uromodulin excretion was reduced in all hyposthenuric patients, suggesting a thick ascending limb defect. Interestingly, renal Na, Cl, Ca, but not K handling was impaired after acute WL but not at basal. In summary, BBS patients show combined urinary concentration and dilution defects; a thick ascending limb and collecting duct tubulopathy may underlie impaired water handling. The renal phenotype in BardetBiedl syndrome (BBS) is highly variable. The present study describes renal findings in 41 BBS patients and analyzes the pathogenesis of hyposthenuria, the most common renal dysfunction. Five of 41 patients (12%) showed an estimated glomerular filtration rate < 60 ml.min(-1).1.73 m(-2). Urine protein and urine albumin-to-creatinine ratio were over 200 and 30 mg/g in 9/24 and 7/23 patients, respectively. Four of 41 patients showed no renal anomalies on ultrasound. Twenty of 34 patients had hyposthenuria in the absence of renal insufficiency. In all 8 of the hyposthenuric patients studied, dDAVP failed to elevate urine osmolality (Uosm), suggesting a nephrogenic origin. Interestingly, water loading (WL) did not result in a significant reduction of Uosm, indicating combined concentrating and diluting defects. dDAVP infusion induced a significant increase of plasma Factor VIII and von Willebrand Factor levels, supporting normal function of the type 2 vasopressin receptor at least in endothelial cells. While urinary aquaporin 2 (u-AQP2) abundance was not different between patients and controls at baseline, the dDAVP-induced increased u-AQP2 and the WL-induced reduction of u-AQP2 were blunted in patients with a combined concentrating and diluting defect, suggesting a potential role of AQP2 in the defective regulation of water absorption. Urine Uromodulin excretion was reduced in all hyposthenuric patients, suggesting a thick ascending limb defect. Interestingly, renal Na, Cl, Ca, but not K handling was impaired after acute WL but not at basal. In summary, BBS patients show combined urinary concentration and dilution defects; a thick ascending limb and collecting duct tubulopathy may underlie impaired water handling.

Leaves of fast-growing, woody bioenergy crops often emit volatile organic compounds (VOC). Some reactive VOC (especially isoprene) play a key role in climate forcing and may negatively affect local air quality. We monitored the seasonal exchange of VOC using the eddy covariance technique in a coppiced' poplar plantation. The complex interactions of VOC fluxes with climatic and physiological variables were also explored by using an artificial neural network (Self Organizing Map). Isoprene and methanol were the most abundant VOC emitted by the plantation. Rapid development of the canopy (and thus of the leaf area index, LAI) was associated with high methanol emissions and high rates of gross primary production (GPP) since the beginning of the growing season, while the onset of isoprene emission was delayed. The highest emissions of isoprene, and of isoprene photo-oxidation products (Methyl Vinyl Ketone and Methacrolein, i(ox)), occurred on the hottest and sunniest days, when GPP and evapotranspiration were highest, and formaldehyde was significantly deposited. Canopy senescence enhanced the exchange of oxygenated VOC. The accuracy of methanol and isoprene emission simulations with the Model of Emissions of Gases and Aerosols from Nature increased by applying a function to modify their basal emission factors, accounting for seasonality of GPP or LAI. center dot Some reactive volatile organic compounds (VOC) (especially isoprene) emitted in the atmosphere from leaves of widespread fast-growing woody bioenergy crops play a key role in climate forcing and local air quality. center dot Eddy covariance VOC emission and deposition fluxes were monitored in a coppiced' poplar plantation during an entire growing season, and their complex interactions with climatic and physiological variables also including canopy structural traits were explored by using the Self-organizing Map. center dot Rapid development of a canopy (and thus of leaf area index, LAI) was associated with high methanol emissions and high rates of gross primary production (GPP) since the beginning of the growing season, while the onset of isoprene emission was delayed. center dot The highest emissions of isoprene, and of isoprene photooxidation products (methyl vinyl ketone and methacrolein, iox) occurred on the hottest and sunniest days, when also GPP and evapotranspiration were highest and formaldehyde was significantly deposited. center dot The accuracy of methanol and isoprene emission simulations with the MEGAN model increased by applying a function to modify their basal emission factors, accounting for seasonality of GPP or LAI.

Garnett and Christidis (2017) slammed taxonomy for hampering conservation. They painted a picture of capricious taxonomists arbitrarily creating or dismissing species and claimed “the scientific community's failure to govern taxonomy threatens the effectiveness of global efforts to halt biodiversity loss, damages the credibility of science, and is expensive to society”. We reject their premise that taxonomy is but a service in need of governance, rather than an independent—and foundational—scientific discipline.

The endoplasmic reticulum (ER) is a cellular organelle with central roles in maintaining proteostasis due to its involvement in protein synthesis, folding, quality control, distribution and degradation. The accumulation of misfolded proteins in the ER lumen causes ‘ER stress’ and threatens overall cellular proteostasis. To restore ER homeostasis, cells evoke an evolutionarily conserved adaptive signalling and gene expression network collectively called the ‘unfolded protein response (UPR)’, a complex biological process which aims to restore proteostasis. When ER stress is overwhelming and beyond rectification, the normally pro-survival UPR can shift to induce cell termination. Emerging evidence from mammalian, fly and nematode worm systems reveals that the FOXO Forkhead proteins integrate upstream ER stress and UPR signals with the transcriptional machinery to decrease translation, promote cell survival/termination and increase the levels of ER-resident chaperones and of ER-associated degradation (ERAD) components to restore ER homeostasis. The high rates of protein synthesis/translation associated with cancer cell proliferation and metabolism, as well as mutations resulting in aberrant proteins, also induce ER stress and the UPR. While the pro-survival side of the UPR underlies its ability to sustain and promote cancers, its apoptotic functions can be exploited for cancer therapies by offering the chance to ‘flick the proteostatic switch’. To this end, further studies are required to fully reevaluate the roles and regulation of these UPR signalling molecules, including FOXO proteins and their targets, in cancer initiation and progression as well as the effects on inhibiting their functions in cancer cells. This information will help to establish these UPR signalling molecules as possible therapeutic targets and putative biomarkers in cancers.

MicroRNAs are a class of non-coding RNAs with a growing relevance in the regulation of gene expression related to brain function and plasticity. They have the potential to orchestrate complex phenomena, such as the neuronal response to homeostatic challenges. We previously demonstrated the involvement of miR-135a in the regulation of early stress response. In the present study, we examine the role of miR-135a in stress-related behavior. We show that the knockdown (KD) of miR-135a in the mouse amygdala induces an increase in anxiety-like behavior. Consistently with behavioral studies, electrophysiological experiments in acute brain slices indicate an increase of amygdala spontaneous excitatory postsynaptic currents, as a result of miR-135a KD. Furthermore, we presented direct evidences, by in vitro assays and in vivo miRNA overexpression in the amygdala, that two key regulators of synaptic vesicle fusion, complexin-1 and complexin-2, are direct targets of miR-135a. In vitro analysis of miniature excitatory postsynaptic currents on miR-135a KD primary neurons indicates unpaired quantal excitatory neurotransmission. Finally, increased levels of complexin-1 and complexin-2 proteins were detected in the mouse amygdala after acute stress, accordingly to the previously observed stress-induced miR-135a downregulation. Overall, our results unravel a previously unknown miRNA-dependent mechanism in the amygdala for regulating anxiety-like behavior, providing evidences of a physiological role of miR-135a in the modulation of presynaptic mechanisms of glutamatergic neurotransmission.

Brother Marie-Victorin (1885–1944) was a member of the Roman Catholic congregation of the La Salle Brothers and one of the most important figures in the botanical history of Canada. In 1929, he undertook a 7-month trip across Europe, Africa and the Middle East. During this journey he visited the islands of Gran Canaria (26–27 June) and Tenerife (28 June to 3 July), where he took 118 photographs. The travelogue for this trip (447 pages) is an unpublished document, 26 pages of which are devoted to the Canaries. We provide English and Spanish translations for the portion of this travelogue devoted to the Canary Islands and a catalogue of the photos taken there. Botanical highlights of this visit include accounts for: (1) the Botanic Garden of La Orotava and its Head Gardener, Juan Bolinaga; (2) landmark specimens of Dracaena draco in Tenerife; (3) hybrids between the endemic Phoenix canariensis and the introduced Phoenix dactylifera; (4) an historical individual of Pinus canariensis found in Buen Paso (Icod municipality); and (5) endemic and invasive plants. This travelogue shows that Marie-Victorin had an interest in social, ethnobotanical and historical aspects of the Canaries.

The accumulation of β-amyloid (Aβ) is one of the hallmarks of Alzheimer disease (AD). Beyond the inflammatory reactions promoted by Aβ, it has been demonstrated that the prokineticin (PK) system, composed of the chemokine prokineticin 2 (PK2) and its receptors, is involved in Aβ toxicity. In this study we have analyzed how the Aβ chronic treatment affects the glutamatergic transmission on neurons from primary cortical cultures, clearly demonstrating the PK system involvement on its action mechanism. In fact, we have observed a significant increase of the ionic current through the AMPA receptors in primary cortical neurons and an up-regulation of the PK system in cultures chronically treated with Aβ. All effects were nullified by the prokineticin antagonist PC-1. Moreover, we have herein firstly demonstrated that the incubation of primary cortical culture with Bv8, the amphibian homologue of PK2, was able to increase in neurons the AMPA currents at specific doses and exposure times, measured both as evoked and as spontaneous currents. This effect was not due to a modification of the AMPA receptor subunit expression. In contrast, the up-modulation of AMPA currents were blocked by PC-1 and were mediated by the activation of the intracellular protein kinase C (PKC) transduction pathways because Gö6983, the PKC inhibitor added in the medium, nullified the effect. Finally, cellular death induced by kainate was also reduced following treatment with PC1. In conclusion, our results show that the prokineticin system may be a key mediator in the Aβ-induced neuronal damage, suggesting PK antagonists as new therapeutic compounds to ameliorate the AD progression.

Small molecules altering protein functions as inhibitors, agonists or antagonists, find application in systems biology enabling an analysis of the in vivo consequences of these alterations. In this context carbohydrates are ideal tools, not only because they are involved in a variety of recognition phenomena of biological relevance, but also because they are ideal scaffolds to generate libraries of bioactive compounds. Examples of design, synthesis and biological assays of different carbohydrate based inhibitors or protein ligands are reported. Exploiting NMR methods, the binding between a small molecules (inhibitor or ligand) and a protein can be detected, the affinity measured, and the interaction topology defined. This set of information is useful not only to clarify the mechanism of protein-ligand interaction, but also to improve the design of new inhibitors/ligands. The multifunctionality and the conformational rigidity of carbohydrates make this class of compounds the ideal scaffolds to generate libraries exploiting the combinatorial approach. An example of solid phase combinatorial synthesis of a library of 37 compounds is reported.

The importance and consequences of extreme events on the global carbon budget are inadequately understood. This includes the differential impact of extreme events on various ecosystem components, lag effects, recovery times, and compensatory processes. In the summer of 2007 in Barrow, Arctic Alaska, there were unusually high air temperatures (the fifth warmest summer over a 65-year period) and record low precipitation (the lowest over a 65-year period). These abnormal conditions were associated with substantial desiccation of the Sphagnum layer and a reduced net Sphagnum CO2 sink but did not affect net ecosystem exchange (NEE) from this wet-sedge arctic tundra ecosystem. Microbial biomass, NH4+ availability, gross primary production (GPP), and ecosystem respiration (Reco) were generally greater during this extreme summer. The cumulative ecosystem CO2 sink in 2007 was similar to the previous summers, suggesting that vascular plants were able to compensate for Sphagnum CO2 uptake, despite the impact on other functions and structure such as desiccation of the Sphagnum layer. Surprisingly, the lowest ecosystem CO2 sink over a five summer record (2005–2009) was observed during the 2008 summer (~70% lower), directly following the unusually warm and dry summer, rather than during the extreme summer. This sink reduction cannot solely be attributed to the potential damage to mosses, which typically contribute ~40% of the entire ecosystem CO2 sink. Importantly, the return to a substantial cumulative CO2 sink occurred two summers after the extreme event, which suggests a substantial resilience of this tundra ecosystem to at least an isolated extreme event. Overall, these results show a complex response of the CO2 sink and its sub-components to atypically warm and dry conditions. The impact of multiple extreme events requires further investigation.