Dehydration-induced regulates midgut infection in mosquitoes.

Unlabelled: Climate change is predicted to increase the spread of mosquito-borne viruses, but genetic mechanisms underlying the influence of environmental variation on the ability of insect vectors to transmit human pathogens is unknown. In response to a changing climate, mosquitoes will experience longer periods of drought. An important physiological response to dry environments is the protection against dehydration, here defined as desiccation tolerance.

Low humidity enhances Zika virus infection and dissemination in mosquitoes.

As climate change alters Earth's biomes, it is expected the transmission dynamics of mosquito-borne viruses will change. While the effects of temperature changes on mosquito-virus interactions and the spread of the pathogens have been elucidated over the last decade, the impact of relative humidity changes is still relatively unknown. To overcome this knowledge gap, we exposed females to various humidity conditions.

Implementation of a pharmacogenetic panel-based test for pharmacotherapy-based supportive care in an adult oncology clinic.

The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel-based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non-hematologic cancers being treated with chemotherapy. Patients were randomized to either the intervention arm or control arm and received PGx testing immediately or at the end of the study, respectively.

Discovery of CVN293, a Brain Permeable KCNK13 (THIK-1) Inhibitor Suitable for Clinical Assessment.

The potassium (K) ion channel KCNK13 is specifically expressed in human microglia with elevated expression observed in post-mortem human brain tissue from patients with Alzheimer's disease. Modulation of KCNK13 activity by a small-molecule inhibitor is proposed as a potential treatment for neurodegenerative diseases. Herein, we describe the evolution of a series of KCNK13 inhibitors derived from a high-throughput screening campaign, resulting in , a potent, selective, and brain permeable clinical candidate molecule.

Gedunin modulates cellular growth and apoptosis in glioblastoma cell lines.

Background: Glioblastomas are characterized by aggressive behavior. Surgery, radiotherapy, and alkylating agents, including temozolomide are the most common treatment options for glioblastoma. Often, conventional therapies fail to treat these tumors since they develop drug resistance.

Low humidity enhances Zika virus infection and dissemination in mosquitoes.

As climate change alters Earth's biomes, it is expected the transmission dynamics of mosquito-borne viruses will change. While the effects of temperature changes on mosquito-virus interactions and spread of the pathogens have been elucidated over the last decade, the effects of relative humidity changes are still relatively unknown. To overcome this knowledge gap, we exposed females to various low humidity conditions and measured different components of vectorial capacity such as survival, blood-feeding rates, and changes in infection and dissemination of Zika virus.

Operationalising water safety plans for Melbourne - a large city case study.

A wholesale/retail model delivers drinking water to over 5 million residents in metropolitan Melbourne (Australia). Water Safety Plans were implemented in 1999 ahead of being regulatory mandated in 2003. With over 20 years of WSP application, this collaborative paper by the wholesaler and retailer utilities presents practical examples of drinking water quality risk management in challenging operational environments, highlighting lessons learnt, improvements made and outcomes achieved.

Graduate Medical Education Curriculum Regarding the Health and Healthcare of Older Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ+) Adults.

Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) adults experience a wide variety of unique challenges accessing healthcare. These barriers may be exacerbated among older LGBTQ+ people due to intersecting, marginalized identities. To prepare physicians to address the healthcare needs of older LGBTQ+ adults, graduate medical education (GME) must include training about the specific needs of this population.

Organisation of care for people receiving drug-resistant tuberculosis treatment in South Africa: a mixed methods study.

Objectives: Treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) is increasingly transitioning from hospital-centred to community-based care. A national policy for decentralised programmatic MDR/RR-TB care was adopted in South Africa in 2011. We explored variations in the implementation of care models in response to this change in policy, and the implications of these variations for people affected by MDR/RR-TB.

Blade Coating Poly(3-hexylthiophene): The Importance of Molecular Weight on Thin-Film Microstructures.

Poly(3-hexylthiophene) is one of the most prevalent and promising conjugated polymers for use in organic electronics. However, the deposition of this material in thin films is highly dependent on the process, such as blade coating versus spin coating and material properties such as molecular weight. Typically, large polymer dispersity makes it difficult to isolate the effect of molecular weight without considering a distribution.

Dehydration induced regulates midgut infection in .

In the face of climate change, mosquitoes will experience evolving climates including longer periods of drought. An important physiological response to dry environments is the protection against water loss or dehydration, here defined as desiccation tolerance. Various environmental factors including temperature are known to alter interactions between the mosquito, , and the arboviruses it transmits, but little is known about how low humidity impacts arboviral infection.

Variable microbiomes between mosquito lines are maintained across different environments.

The composition of the microbiome is shaped by both environment and host in most organisms, but in the mosquito Aedes aegypti the role of the host in shaping the microbiome is poorly understood. Previously, we had shown that four lines of Ae. aegypti harbored different microbiomes when reared in the same insectary under identical conditions.

Discovery and Characterization of Novel CNS-Penetrant GPR55 Agonists.

From our NETSseq-derived human brain transcriptomics data, we identified GPR55 as a potential molecular target for the treatment of motor symptoms in patients with Parkinson's disease. From a high-throughput screen, we identified and optimized agonists with nanomolar potency against both human and rat GPR55. We discovered compounds with either strong or limited β-arrestin signaling and receptor desensitization, indicating biased signaling.

Discovery of , a Novel Brain-Penetrant α6-Containing Nicotinic Receptor Antagonist for the Modulation of Motor Dysfunction.

Nicotinic acetylcholine receptor (nAChR) α6 subunit RNA expression is relatively restricted to midbrain regions and is located presynaptically on dopaminergic neurons projecting to the striatum. This subunit modulates dopamine neurotransmission and may have therapeutic potential in movement disorders. We aimed to develop potent and selective α6-containing nAChR antagonists to explore modulation of dopamine release and regulation of motor function in vivo.

Complete Genome Sequences of Subcluster C1 Mycobacteriophages Blackbrain, Cactojaque, Kboogie, Trinitium, and YoungMoneyMata.

Five subcluster C1 mycobacteriophages, Blackbrain, Cactojaque, Kboogie, Trinitium, and YoungMoneyMata, were isolated from soil using the host Mycobacterium smegmatis mc155. The genome sizes range from 154,512 to 156,223 bp. The largest genome encodes 237 predicted proteins, 34 tRNAs, and 1 transfer-messenger RNA (tmRNA).

Discovery of : A Highly Potent, Selective, and CNS Penetrant mGluR Allosteric Agonist.

The low affinity metabotropic glutamate receptor mGluR has been implicated in numerous CNS disorders; however, a paucity of potent and selective activators has hampered full delineation of the functional role and therapeutic potential of this receptor. In this work, we present the identification, optimization, and characterization of highly potent, novel mGluR agonists. Of particular interest is the chromane , a potent (EC 7 nM) allosteric agonist which demonstrates exquisite selectivity for mGluR compared to not only other mGluRs, but also a broad range of targets.

An Investigation into Compound Likelihood Ratios for Forensic DNA Mixtures.

Simple propositions are defined as those with one POI and the remaining contributors unknown under and all unknown contributors under . Conditional propositions are defined as those with one POI, one or more assumed contributors, and the remaining contributors (if any) unknown under , and the assumed contributor(s) and N unknown contributors under . In this study, compound propositions are those with multiple POI and the remaining contributors unknown under and all unknown contributors under Ha.

The role of emergent champions in policy implementation for decentralised drug-resistant tuberculosis care in South Africa.

Objective: Champions are recognised as important to driving organisational change in healthcare quality improvement initiatives in high-income settings. In low-income and middle-income countries with a high disease burden and constrained human resources, their role is highly relevant yet understudied. Within a broader study on policy implementation for decentralised drug-resistant tuberculosis care in South Africa, we characterised the role, strategies and organisational context of emergent policy champions.