Bishydrazone-Based Antifungal Agents

Hydrazone compounds and pharmaceutical compositions including same are disclosed as having antifungal activity. Such compounds are useful for treating or preventing fungal conditions in a subject in need thereof by administering same

Amyloid-β Probes: Review of Structure-Activity and Brain-Kinetics Relationships

The number of people suffering from Alzheimer\u27s disease (AD) is expected to increase dramatically in the coming years, placing a huge burden on society. Current treatments for AD leave much to be desired, and numerous research efforts around the globe are focused on developing improved therapeutics. In addition, current diagnostic tools for AD rely largely on subjective cognitive assessment rather than on identification of pathophysiological changes associated with disease onset and progression. These facts have led to numerous efforts to develop chemical probes to detect pathophysiological hallmarks of AD, such as amyloid-β plaques, for diagnosis and monitoring of therapeutic efficacy. This review provides a survey of chemical probes developed to date for AD with emphasis on synthetic methodologies and structure-activity relationships with regards to affinity for target and brain kinetics. Several probes discussed herein show particularly promising results and will be of immense value moving forward in the fight against AD

Patterns of Oral Microbiota Diversity in Adults and Children: A Crowdsourced Population Study.

Oral microbiome dysbiosis has been associated with various local and systemic human diseases such as dental caries, periodontal disease, obesity, and cardiovascular disease. Bacterial composition may be affected by age, oral health, diet, and geography, although information about the natural variation found in the general public is still lacking. In this study, citizen-scientists used a crowdsourcing model to obtain oral bacterial composition data from guests at the Denver Museum of Nature & Science to determine if previously suspected oral microbiome associations with an individual's demographics, lifestyle, and/or genetics are robust and generalizable enough to be detected within a general population. Consistent with past research, we found bacterial composition to be more diverse in youth microbiomes when compared to adults. Adult oral microbiomes were predominantly impacted by oral health habits, while youth microbiomes were impacted by biological sex and weight status. The oral pathogen Treponema was detected more commonly in adults without recent dentist visits and in obese youth. Additionally, oral microbiomes from participants of the same family were more similar to each other than to oral microbiomes from non-related individuals. These results suggest that previously reported oral microbiome associations are observable in a human population containing the natural variation commonly found in the general public. Furthermore, these results support the use of crowdsourced data as a valid methodology to obtain community-based microbiome data

Analogy Training Multilingual Encoders

Language encoders encode words and phrases in ways that capture their local semantic relatedness, but are known to be globally inconsistent. Global inconsistency can seemingly be corrected for, in part, by leveraging signals from knowledge bases, but previous results are partial and limited to monolingual English encoders. We extract a large-scale multilingual, multi-word analogy dataset from Wikidata for diagnosing and correcting for global inconsistencies and implement a four-way Siamese BERT architecture for grounding multilingual BERT (mBERT) in Wikidata through analogy training. We show that analogy training not only improves the global consistency of mBERT, as well as the isomorphism of language-specific subspaces, but also leads to significant gains on downstream tasks such as bilingual dictionary induction and sentence retrieval

Designing multiplayer games to facilitate emergent social behaviours online

This paper discusses an exploratory case study of the design of games that facilitate spontaneous social interaction and group behaviours among distributed individuals, based largely on symbolic presence 'state' changes. We present the principles guiding the design of our game environment: presence as a symbolic phenomenon, the importance of good visualization and the potential for spontaneous self-organization among groups of people. Our game environment, comprising a family of multiplayer 'bumper-car' style games, is described, followed by a discussion of lessons learned from observing users of the environment. Finally, we reconsider and extend our design principles in light of our observations

The Response of the Honey Bee Gut Microbiota to Nosema ceranae Is Modulated by the Probiotic Pediococcus acidilactici and the Neonicotinoid Thiamethoxam.

The honey bee Apis mellifera is exposed to a variety of biotic and abiotic stressors, such as the highly prevalent microsporidian parasite Nosema (Vairimorpha) ceranae and neonicotinoid insecticides. Both can affect honey bee physiology and microbial gut communities, eventually reducing its lifespan. They can also have a combined effect on the insect's survival. The use of bacterial probiotics has been proposed to improve honey bee health, but their beneficial effect remains an open question. In the present study, western honey bees were experimentally infected with N. ceranae spores, chronically exposed to the neonicotinoid thiamethoxam, and/or supplied daily with the homofermentative bacterium Pediococcus acidilactici MA18/5M thought to improve the honey bees' tolerance to the parasite. Deep shotgun metagenomic sequencing allowed the response of the gut microbiota to be investigated with a taxonomic resolution at the species level. All treatments induced significant changes in honey bee gut bacterial communities. Nosema ceranae infection increased the abundance of Proteus mirabilis, Frischella perrara, and Gilliamella apicola and reduced the abundance of Bifidobacterium asteroides, Fructobacillus fructosus, and Lactobacillus spp. Supplementation with P. acidilactici overturned some of these alterations, bringing back the abundance of some altered species close to the relative abundance found in the controls. Surprisingly, the exposure to thiamethoxam also restored the relative abundance of some species modulated by N. ceranae. This study shows that stressors and probiotics may have an antagonistic impact on honey bee gut bacterial communities and that P. acidilactici may have a protective effect against the dysbiosis induced by an infection with N. ceranae

Bis(\u3cem\u3eN\u3c/em\u3e-amidinohydrazones) and \u3cem\u3eN\u3c/em\u3e-(amidino)-\u3cem\u3eN\u3c/em\u3e\u27-aryl-bishydrazones: New Classes of Antibacterial/Antifungal Agents

The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicr obial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N\u27-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step, resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity. In summary, we found that these compounds exhibited broad-spectrum antibacterial and antifungal activities against most of the tested strains with minimum inhibitory concentration (MIC) values ranging from \u3c 0.5- \u3e 500 μM against bacteria and 1.0- \u3e 31.3 μg/mL against fungi; and in most cases, they exhibited either superior or similar antimicrobial activity compared to those of the standard drugs used in the clinic. We also observed minimal emergence of drug resistance to these newly synthesized compounds by bacteria and fungi even after 15 passages, and we found weak to moderate inhibition of the human Ether-à-go-go-related gene (hERG) channel with acceptable IC50 values ranging from 1.12-3.29 μM. Overall, these studies sh ow that bis(N-amidinohydrazones) and N-(amidino)-N\u27-aryl-bishydrazones are potentially promising scaffolds for the discovery of novel antibacterial and antifungal agents

Modelling trace metal transfer in large rivers under dynamic hydrology: a coupled hydrodynamic and chemical equilibrium model

Trace metals (TMs) in rivers experience a complex chemistry that affects their partitioning between the dissolved and particulate fractions. Predictive modelling of this partitioning is challenging, particularly under variable hydrodynamic conditions in rivers. This paper presents a coupled hydrodynamic–geochemical model for trace metal dynamics in rivers, to highlight key parameters and set a basis for developing simplified models. A coupled model based on the hydrodynamic model MOHID and the chemical speciation model WHAM was applied to the middle part of the Garonne River (SW-France). The predictions of the coupled model are compared to those of a fixed Kd partitioning model. The model accurately simulates trace metal behaviour under varying hydrological conditions. The importance of the riverbed geomorphology and the diurnal variations in pH on TM concentrations in the water column are underlined. The sensitivity analysis ranked all physico-chemical parameters according to their influence on TM behaviour