Microbial biogeochemistry of Boiling Springs Lake: a physically dynamic,oligotrophic, low‐pH geothermal ecosystem

Boiling Springs Lake (BSL) in Lassen Volcanic National Park, California, is North America's largest hot spring, but little is known about the physical, chemical, and biological features of the system. Using a remotely operated vessel, we characterized the bathymetry and near‐surface temperatures at sub‐meter resolution. The majority of the 1.2 ha, pH 2.2 lake is 10 m deep and 50–52 °C, but temperatures reach 93 °C locally. We extracted DNA from water and sediments collected from warm (52 °C) and hot (73–83 °C) sites separated by 180 m. Gene clone libraries and functional gene microarray (GeoChip 3.0) were used to investigate the BSL community, and uptake of radiolabeled carbon sources was used to assess the relative importance of heterotrophic vs. autotrophic production. Microbial assemblages are similar in both sites despite the strong temperature differential, supporting observations of a dynamic, convectively mixed system. Bacteria in the Actinobacteria and Aquificales phyla are abundant in the water column, and Archaea distantly related to known taxa are abundant in sediments. The functional potential appears similar across a 5‐year time span, indicating a stable community with little inter‐annual variation, despite the documented seasonal temperature cycle. BSL water‐derived DNA contains genes for complete C, N, and S cycles, and low hybridization to probes for N and S oxidation suggests that reductive processes dominate. Many of the detected genes for these processes were from uncultivated bacteria, suggesting novel organisms are responsible for key ecosystem services. Selection imposed by low nutrients, low pH, and high temperature appear to result in low diversity and evenness of genes for key functions involved in C, N, and S cycling. Conversely, organic degradation genes appear to be functionally redundant, and the rapid assimilation of radiolabeled organic carbon into BSL cells suggests the importance of allochthonous C fueling heterotrophic production in the BSL C cycle.     

A northward shift of range margins in British Odonata

Many species are predicted to shift their ranges to higher latitudes and altitudes in response to climate warming. This study presents evidence for 37 species of nonmigratory British dragonflies and damselflies shifting northwards at their range margins over the past 40 years, seemingly as a result of climate change. This response by an exemplar group of insects associated with fresh water, parallels polewards range changes observed in terrestrial invertebrates and other taxa.     

Ion channels and information processing in GnRH neuron dendrites

Recent findings indicate that a majority of action potentials originate from dendrites of GnRH neurons. This localization of the dendrite as the principle site of action potential initiation has sparked considerable interest in the nature of ionic channels throughout GnRH neurons. This paper will review the ionic conductances described within GnRH neurons and their implications for physiological output, such as sensitivity to steroids and diurnal state. To date, a majority of information regarding ionic conductances in GnRH neurons pertains to somata and the first 50–100 µm of dendrite length. Thus, unraveling the tapestry created by the nature and distribution of dendritic conductances in GnRH neurons lies at the forefront of understanding the control of reproductive hormone secretion.     

Eliminating onchocerciasis within the Meme River Basin of Cameroon: A social-ecological approach to understanding everyday realities and health systems

BackgroundOnchocerciasis affects some of the world’s most marginalized people, perpetuating poverty and inequalities. Mass Drug Administration (MDA) with Ivermectin has taken place within the Meme River basin region in Cameroon for over 15 years. Despite this, onchocerciasis is still prevalent in the region due to existing and emerging contextual challenges. Using a social-ecological approach we explore the everyday realities of communities, highlighting the challenges and potential solutions that could support Neglected Tropical Disease (NTD) programmes when transitioning from control to elimination of onchocerciasis in this highly endemic area and other similar communities.Methodology/Principal findingIn-depth interviews (71) with community members and Community Drug Distributors (CDDs) were conducted to understand current knowledge, attitudes, and behaviours in relation to transmission, prevention and treatment of onchocerciasis. Through application of the social-ecological model, four key themes were identified: 1. Contextual factors on health promotion interventions (Onchocerciasis history and understanding of the disease, prevention and mitigation strategies and MDA experience); 2. Social determinants (poverty and livelihoods, economic and social impacts on CDD volunteers and stigma); 3. Environmental determinants (exposure, housing, occupation and poverty); and 4. health seeking pathways and decision making for treatment (access, cost and preferable treatment routes).We discuss these core and cross cutting themes (gender differences and community participation/ownership) in relation to intersectoral collaboration, gender equity and health systems support, making recommendations for NTD programmes within the context of integrated and interdisciplinary approaches. These include the need for; intersectional and gender analysis at the local level, addressing environmental dimensions of onchocerciasis through integrated and regular health promotion, vector control strategies and access to safe water sources; reflection and action that embeds responses to social and economic barriers to MDA; integrated case detection and management that is responsive to onchocerciasis symptoms and related stigma and a fair and just support network for CDDs.Conclusion/SignificanceNTD programmes need to respond to diverse community circumstances and behaviours. Communities are not a homogeneous risk group and treating them in this way will delay elimination. A deeper understanding of individual needs and their capacity to seek prevention and treatment must be considered if onchocerciasis is to be eliminated and the remaining impacts managed.     

Practical considerations in clinical strategy to support the development of injectable drug-device combination products for biologics

The development of an injectable drug-device combination (DDC) product for biologics is an intricate and evolving process that requires substantial investments of time and money. Consequently, the commercial dosage form(s) or presentation(s) are often not ready when pivotal trials commence, and it is common to have drug product changes (manufacturing process or presentation) during clinical development. A scientifically sound and robust bridging strategy is required in order to introduce these changes into the clinic safely. There is currently no single developmental paradigm, but a risk-based hierarchical approach has been well accepted. The rigor required of a bridging package depends on the level of risk associated with the changes. Clinical pharmacokinetic/pharmacodynamic comparability or outcome studies are only required when important changes occur at a late stage. Moreover, an injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC. In this review, we discuss the common issues during the manufacturing process and presentation development of an injectable DDC and practical considerations in establishing a clinical strategy to address these issues, including key elements of clinical studies. We also analyze the current practice in the industry and review relevant and status of regulatory guidance in the DDC field.     

Elevational partitioning in species distribution,abundance and body size of Australian alpine grasshoppers (Kosciuscola)

Changes in the physical environment with elevation can influence species distributions and their morphological traits. In mountainous regions, steep temperature gradients can result in patterns of ecological partitioning among species that potentially increases their vulnerability to climate change. We collected data on species distributions, relative abundance and body size for three grasshopper species of the genus Kosciuscola (K. usitatus, K. tristis and K. cognatus) at three locations within the mountainous Kosciuszko National Park in Australia (Thredbo, Guthega and Jagungal). All three species showed differences in their distributions according to elevation, with K. usitatus ranging from 1400 to 2000 m asl, K. tristis from 1600 to 2000 m asl and K. cognatus from 1550 to 1900 m asl. Decreasing relative abundance with increasing elevation was found for K. usitatus, but the opposite pattern was found for K. tristis. The relative abundance of K. cognatus did not change with elevation but was negatively correlated with foliage cover. Body size decreased with elevation in both male and female K. usitatus, which was similarly observed in female K. tristis and male K. cognatus. Our results demonstrate spatial partitioning of species distributions and clines in body size in relation to elevational gradients. Species‐specific sensitivities to climatic gradients may help to predict the persistence of this grasshopper assemblage under climate change.     

The Anti-Parkinson Potential of Gingko biloba-Supplement Mitigates Cortico-Cerebellar Degeneration and Neuropathobiological Alterations via Inflammatory and Apoptotic Mediators in Mice

Neurochemical Research - Activation of nuclear factor erythroid 2 related factor 2 (Nrf2) associated with the suppression of various oxido-inflammatory pathways and the controller of several gene...