Sensitivity analysis of the basic reproduction number and other quantities for infectious disease models

2012 Spring.Includes bibliographical references.Performing forward sensitivity analysis has been an integral component of mathematical modeling, yet its implementation becomes increasingly difficult with a model's complexity. For infectious disease models in particular, the sensitivity analysis of a parameter known as the basic reproduction number, or R0, has dominated the attention of ecology modelers. While the biological definition of R0 is well established, its mathematical construction is elusive. An index with a concrete mathematical definition that in many cases matches the biological interpretation of R0 is presented. A software package called Sensai that automatically computes this index and its sensitivity analysis is also presented. Other "quantities of interest" that provide similar information to R0 can also be implemented in Sensai and their sensitivities computed. Finally, some example models are presented and analyzed using Sensai

Exploring representation in Microbiology introductory courses can encourage a more inclusive and inspiring environment for students and instructors

Microbiology has a relatively brief history where significant discoveries are often linked with major events in human history - from disease outbreak to industrialization to climate change. The founders of key microbiological principles span across continents, genders, ethnicities, and socioeconomic status. However, the portrait described in many introductory textbooks center around a lone, typically white male scientist. Such narratives not only are misleading regarding the development of key principles in microbiology but can also reinforce inappropriate stereotypes as to whom belongs in microbiology. In our introductory microbiology course, we designed group work for Zoom break-out rooms to help engage students in the online environment. Here we reflect upon the benefits of this activity in enhancing not only the experience for our students but also that of the instructors

The Host-Pathogen Interactions and Epicellular Lifestyle of Neisseria meningitidis

Neisseria meningitidis is a gram-negative diplococcus and a transient commensal of the human nasopharynx. It shares and competes for this niche with a number of other Neisseria species including N. lactamica, N. cinerea and N. mucosa. Unlike these other members of the genus, N. meningitidis may become invasive, crossing the epithelium of the nasopharynx and entering the bloodstream, where it rapidly proliferates causing a syndrome known as Invasive Meningococcal Disease (IMD). IMD progresses rapidly to cause septic shock and meningitis and is often fatal despite aggressive antibiotic therapy. While many of the ways in which meningococci survive in the host environment have been well studied, recent insights into the interactions between N. meningitidis and the epithelial, serum, and endothelial environments have expanded our understanding of how IMD develops. This review seeks to incorporate recent work into the established model of pathogenesis. In particular, we focus on the competition that N. meningitidis faces in the nasopharynx from other Neisseria species, and how the genetic diversity of the meningococcus contributes to the wide range of inflammatory and pathogenic potentials observed among different lineages

Deep groundwater and potential subsurface habitats beneath an Antarctic dry valley

The occurrence of groundwater in Antarctica, particularly in the ice-free regions and along the coastal margins is poorly understood. Here we use an airborne transient electromagnetic (AEM) sensor to produce extensive imagery of resistivity beneath Taylor Valley. Regional-scale zones of low subsurface resistivity were detected that are inconsistent with the high resistivity of glacier ice or dry permafrost in this region. We interpret these results as an indication that liquid, with sufficiently high solute content, exists at temperatures well below freezing and considered within the range suitable for microbial life. These inferred brines are widespread within permafrost and extend below glaciers and lakes. One system emanates from below Taylor Glacier into Lake Bonney and a second system connects the ocean with the eastern 18 km of the valley. A connection between these two basins was not detected to the depth limitation of the AEM survey (∼350 m)

Deep Groundwater and Potential Subsurface Habitats Beneath an Antarctic Dry Valley

The occurrence of groundwater in Antarctica, particularly in the ice-free regions and along the coastal margins is poorly understood. Here we use an airborne transient electromagnetic (AEM) sensor to produce extensive imagery of resistivity beneath Taylor Valley. Regional- scale zones of low subsurface resistivity were detected that are inconsistent with the high resistivity of glacier ice or dry permafrost in this region. We interpret these results as an indication that liquid, with sufficiently high solute content, exists at temperatures well below freezing and considered within the range suitable for microbial life. These inferred brines are widespread within permafrost and extend below glaciers and lakes. One system emanates from below Taylor Glacier into Lake Bonney and a second system connects the ocean with the eastern 18 km of the valley. A connection between these two basins was not detected to the depth limitation of the AEM survey (~350 m)

Isolation of a methanogen from deep marine sediments that contain methane hydrates, and description of Methanoculleus submarinus sp. nov.

We isolated a methanogen from deep in the sediments of the Nankai Trough off the eastern coast of Japan. At the sampling site, the water was 950 m deep and the sediment core was collected at 247 m below the sediment surface. The isolated methanogen was named Nankai-1. Cells of Nankai-1 were nonmotile and highly irregular coccoids (average diameter, 0.8 to 2 μm) and grew with hydrogen or formate as a catabolic substrate. Cells required acetate as a carbon source. Yeast extract and peptones were not required but increased the growth rate. The cells were mesophilic, growing most rapidly at 45°C (no growth at ≤10°C or ≥55°C). Cells grew with a maximum specific growth rate of 2.43 day¯¹ at 45°C. Cells grew at pH values between 5.0 and 8.7 but did not grow at pH 4.7 or 9.0. Strain Nankai-1 grew in a wide range of salinities, from 0.1 to 1.5MNa+. The described phenotypic characteristics of this novel isolate were consistent with the in situ environment of the Nankai Trough. This is the first report of a methanogenic isolate from methane hydrate-bearing sediments. Phylogenetic analysis of its 16S rRNA gene sequence indicated that it is most closely related to Methanoculleus marisnigri (99.1% sequence similarity), but DNA hybridization experiments indicated a DNA sequence similarity of only 49%. Strain Nankai-1 was also found to be phenotypically similar to M. marisnigri, but two major phenotypic differences were found: strain Nankai-1 does not require peptones, and it grows fastest at a much higher temperature. We propose a new species, Methanoculleus submarinus, with strain Nankai-1 as the type strain

Microbial sulfur transformations in sediments from Subglacial Lake Whillans

Diverse microbial assemblages inhabit subglacial aquatic environments. While few of these environments have been sampled, data reveal that subglacial organisms gain energy for growth from reduced minerals containing nitrogen, iron, and sulfur. Here we investigate the role of microbially mediated sulfur transformations in sediments from Subglacial Lake Whillans (SLW), Antarctica, by examining key genes involved in dissimilatory sulfur oxidation and reduction. The presence of sulfur transformation genes throughout the top 34 cm of SLW sediments changes with depth. SLW surficial sediments were dominated by genes related to known sulfur-oxidizing chemoautotrophs. Sequences encoding the adenosine-5’-phosphosulfate (APS) reductase gene, involved in both dissimilatory sulfate reduction and sulfur oxidation, were present in all samples and clustered into 16 distinct OTUs. The majority of APS reductase sequences (74%) clustered with known sulfur oxidizers including those within the Sideroxydans and Thiobacillus genera. Reverse-acting dissimilatory sulfite reductase (rDSR) and 16S rRNA gene sequences further support dominance of Sideroxydans and Thiobacillus phylotypes in the top 2 cm of SLW sediments. The SLW microbial community has the genetic potential for sulfate reduction which is supported by experimentally measured low rates (1.4 pmol cm-3d-1) of biologically mediated sulfate reduction and the presence of APS reductase and DSR gene sequences related to Desulfobacteraceae and Desulfotomaculum. Our results also infer the presence of sulfur oxidation, which can be a significant energetic pathway for chemosynthetic biosynthesis in SLW sediments. The water in SLW ultimately flows into the Ross Sea where intermediates from subglacial sulfur transformations can influence the flux of solutes to the Southern Ocean

Brief communication: The hidden labyrinth: deep groundwater in Wright Valley, Antarctica

Since the 1960s, a deep groundwater system in Wright Valley, Antarctica, has been the hypothesized source of brines to hypersaline Don Juan Pond and Lake Vanda, both of which are rich in calcium and chloride. Modeling studies do not support other possible mechanisms, such as evaporative processes, that could have led to the current suite of ions present in both waterbodies. In 2011 and 2018, an airborne electromagnetic survey was flown over Wright Valley to map subsurface resistivity (down to 600 m) in exploration of liquid water. The surveys revealed widespread unfrozen brine in the subsurface near Lake Vanda, Don Juan Pond, and the North Fork of Wright Valley. While our geophysical survey can neither confirm nor deny deep groundwater connectivity between Lake Vanda and Don Juan Pond, it does point to the potential for deep valley-wide brine, likely within the Ferrar Dolerite formation.</p

Physiological Ecology of Microorgansisms in Subglacial Lake Whillans

Subglacial microbial habitats are widespread in glaciated regions of our planet. Some of these environments have been isolated from the atmosphere and from sunlight for many thousands of years. Consequently, ecosystem processes must rely on energy gained from the oxidation of inorganic substrates or detrital organic matter. Subglacial Lake Whillans (SLW) is one of more than 400 subglacial lakes known to exist under the Antarctic ice sheet; however, little is known about microbial physiology and energetics in these systems. When it was sampled through its 800 m thick ice cover in 2013, the SLW water column was shallow (~2 m deep), oxygenated, and possessed sufficient concentrations of C, N, and P substrates to support microbial growth. Here, we use a combination of physiological assays and models to assess the energetics of microbial life in SLW. In general, SLW microorganisms grew slowly in this energy-limited environment. Heterotrophic cellular carbon turnover times, calculated from 3H-thymidine and 3H-leucine incorporation rates, were long (60 to 500 days) while cellular doubling times averaged 196 days. Inferred growth rates (average ~0.006 d-1) obtained from the same incubations were at least an order of magnitude lower than those measured in Antarctic surface lakes and oligotrophic areas of the ocean. Low growth efficiency (8%) indicated that heterotrophic populations in SLW partition a majority of their carbon demand to cellular maintenance rather than growth. Chemoautotrophic CO2-fixation exceeded heterotrophic organic C-demand by a factor of ~1.5. Aerobic respiratory activity associated with heterotrophic and chemoautotrophic metabolism surpassed the estimated supply of oxygen to SLW, implying that microbial activity could deplete the oxygenated waters, resulting in anoxia. We used thermodynamic calculations to examine the biogeochemical and energetic consequences of environmentally imposed switching between aerobic and anaerobic metabolisms in the SLW water column. Heterotrophic metabolisms utilizing acetate and formate as electron donors yielded less energy than chemolithotrophic metabolisms when calculated in terms of energy density, which supports experimental results that showed chemoautotrophic activity in excess of heterotrophic activity. The microbial communities of subglacial lake ecosystems provide important natural laboratories to study the physiological and biogeochemical behavior of microorganisms inhabiting cold, dark environments