Malaria-filaria coinfection in mice makes malarial disease more severe unless filarial infection achieves patency

Coinfections are common in natural populations, and the literature suggests that helminth coinfection readily affects how the immune system manages malaria. For example, type 1–dependent control of malaria parasitemia might be impaired by the type 2 milieu of preexisting helminth infection. Alternatively, immunomodulatory effects of helminths might affect the likelihood of malarial immunopathology. Using rodent models of lymphatic filariasis (Litomosoides sigmodontis) and noncerebral malaria (clone AS Plasmodium chabaudi chabaudi), we quantified disease severity, parasitemia, and polyclonal splenic immune responses in BALB/c mice. We found that coinfected mice, particularly those that did not have microfilaremia (Mf), had more severe anemia and loss of body mass than did mice with malaria alone. Even when controlling for parasitemia, malaria was most severe in Mf coinfected mice, and this was associated with increased interferon-g responsiveness. Thus, in Mf mice, filariasis upset a delicate immunological balance in malaria infection and exacerbated malaria-induced immunopathology. Helminth infections are prevalent throughout tropical regions where malaria is transmitted [1–5]. Interactions among infections commonly alter disease severity [6, 7], and malaria-helminth coinfection can either exac

Draft genome sequences of gammaproteobacterial methanotrophs isolated from lake washington sediment.

The genomes of Methylosarcina lacus LW14(T) (=ATCC BAA-1047(T) = JCM 13284(T)), Methylobacter sp. strain 21/22, Methylobacter sp. strain 31/32, Methylomonas sp. strain LW13, Methylomonas sp. strain MK1, and Methylomonas sp. strain 11b were sequenced and are reported here. All the strains are obligately methanotrophic bacteria isolated from the sediment of Lake Washington

Provenance and Paleogeography of the 25-17 Ma Rainbow Gardens Formation: Evidence for Tectonic Activity at Ca. 19 Ma and Internal Drainage rather than Throughgoing Paleorivers on the Southwestern Colorado Plateau

The paleogeographic evolution of the Lake Mead region of southern Nevada and northwest Arizona is crucial to understanding the geologic history of the U.S. Southwest, including the evolution of the Colorado Plateau and formation of the Grand Canyon. The ca. 25–17 Ma Rainbow Gardens Formation in the Lake Mead region, the informally named, roughly coeval Jean Conglomerate, and the ca. 24–19 Ma Buck and Doe Conglomerate southeast of Lake Mead hold the only stratigraphic evidence for the Cenozoic pre-extensional geology and paleogeography of this area. Building on prior work, we present new sedimentologic and stratigraphic data, including sandstone provenance and detrital zircon data, to create a more detailed paleogeographic picture of the Lake Mead, Grand Wash Trough, and Hualapai Plateau region from 25 to 18 Ma. These data confirm that sediment was sourced primarily from Paleozoic strata exposed in surrounding Sevier and Laramide uplifts and active volcanic fields to the north. In addition, a distinctive signal of coarse sediment derived from Proterozoic crystalline basement first appeared in the southwestern corner of the basin ca. 25 Ma at the beginning of Rainbow Gardens Formation deposition and then prograded north and east ca. 19 Ma across the southern half of the basin. Regional thermochronologic data suggest that Cretaceous deposits likely blanketed the Lake Mead region by the end of Sevier thrusting. Post-Laramide northward cliff retreat off the Kingman/Mogollon uplifts left a stepped erosion surface with progressively younger strata preserved northward, on which Rainbow Gardens Formation strata were deposited. Deposition of the Rainbow Gardens Formation in general and the 19 Ma progradational pulse in particular may reflect tectonic uplift events just prior to onset of rapid extension at 17 Ma, as supported by both thermochronology and sedimentary data. Data presented here negate the California and Arizona River hypotheses for an “old” Grand Canyon and also negate models wherein the Rainbow Gardens Formation was the depocenter for a 25–18 Ma Little Colorado paleoriver flowing west through East Kaibab paleocanyons. Instead, provenance and paleocurrent data suggest local to regional sources for deposition of the Rainbow Gardens Formation atop a stripped low-relief western Colorado Plateau surface and preclude any significant input from a regional throughgoing paleoriver entering the basin from the east or northeast

Model for the formation of single-thread rivers in barren landscapes and implications for pre-Silurian and martian fluvial deposits

Flume experiments and field observations show that bank vegetation promotes the formation of narrow and deep single‐thread channels by strengthening riverbanks. Consistent with this idea, the pre‐Silurian fluvial record generally consists of wide monotonous sand bodies often interpreted as deposits of shallow braided rivers, whereas single‐thread rivers with muddy floodplains become more recognizable in Silurian and younger rocks. This shift in the architecture of fluvial deposits has been interpreted as reflecting the rise of single‐thread rivers enabled by plant life. The deposits of some single‐thread rivers, however, have been recognized in pre‐Silurian rocks, and recent field studies have identified meandering rivers in modern unvegetated environments. Furthermore, single‐thread‐river deposits have been identified on Mars, where macroscopic plants most likely never evolved. Here, we seek to understand the formation of those rarely recognized and poorly characterized single‐thread rivers in unvegetated landscapes. Specifically, we quantitatively explore the hypothesis that cohesive muddy banks alone may enable the formation of single‐thread rivers in the absence of plants. We combine open‐channel hydraulics and a physics‐based erosion model applicable to a variety of bank sediments to predict the formation of unvegetated single‐thread rivers. Consistent with recent flume experiments and field observations, results indicate that single‐thread rivers may form readily within muddy banks. Our model has direct implications for the quantification of riverbank strengthening by vegetation, understanding the hydraulic geometry of modern and ancient unvegetated rivers, interpreting pre‐Silurian fluvial deposits, and unraveling the hydrologic and climate history of Mars

Mobility and strength training with and without protein supplements for pre-frail or frail older adults with low protein intake: the Maximising Mobility and Strength Training (MMoST) feasibility randomised controlled trial protocol

Background Frailty is a common syndrome affecting older people and puts them at risk of hospitalisation, needing care or death. First signs of frailty include reduced muscle strength and mobility decline. A key cause of mobility decline as we age is sarcopenia (age related reduction in muscle strength and mass). Poor nutrition contributes to sarcopenia. A shortfall in protein is associated with reduced muscle mass and strength. This may be due to inadequate intake but also because older people have higher protein needs, especially those with multimorbidity. We need to develop effective treatment to reduce or slow the onset of frailty and mobility decline. Exercise is a recommended treatment. Protein supplements to address the shortfall in protein have the potential to enhance the benefit of regular exercise in frail or pre-frail older adults. This has yet to be definitively demonstrated. Aim To establish the feasibility of conducting an RCT evaluating mobility and strength training with or without protein supplements for people over 60 years old who are frail or pre-frail with a low protein intake. Methods A multicentre, parallel, 2-group, feasibility RCT. Participants (recruitment target = 50) with problems walking, low protein intake and classified as frail or pre-frail will be recruited from four NHS Physiotherapy community services. Participants will be randomised (secure computer-generated: 1:1) to receive 24 weeks of mobility and strength training (delivered in 16 group sessions plus home exercises) or 24 weeks of mobility and strength training with daily protein supplements. Primary feasibility objectives are to estimate 1) ability to screen and recruit eligible participants, 2) intervention fidelity, adherence, and tolerance and 3) retention of participants at follow up. Secondary objectives are to 1) test data collection procedures, 2) assess data completeness and 3) confirm sample size calculation for a definitive RCT. Registration ISRCTN Registry (ISRCTN30405954; 18/10/2022)

Modeling and Measuring the Nocturnal Drainage Flow in a High-Elevation, Subalpine Forest with Complex Terrain

The nocturnal drainage flow of air causes significant uncertainty in ecosystem CO2, H2O, and energy budgets determined with the eddy covariance measurement approach. In this study, we examined the magnitude, nature, and dynamics of the nocturnal drainage flow in a subalpine forest ecosystem with complex terrain. We used an experimental approach involving four towers, each with vertical profiling of wind speed to measure the magnitude of drainage flows and dynamics in their occurrence. We developed an analytical drainage flow model, constrained with measurements of canopy structure and SF6 diffusion, to help us interpret the tower profile results. Model predictions were in good agreement with observed profiles of wind speed, leaf area density, and wind drag coefficient. Using theory, we showed that this one‐dimensional model is reduced to the widely used exponential wind profile model under conditions where vertical leaf area density and drag coefficient are uniformly distributed. We used the model for stability analysis, which predicted the presence of a very stable layer near the height of maximum leaf area density. This stable layer acts as a flow impediment, minimizing vertical dispersion between the subcanopy air space and the atmosphere above the canopy. The prediction is consistent with the results of SF6 diffusion observations that showed minimal vertical dispersion of nighttime, subcanopy drainage flows. The stable within‐canopy air layer coincided with the height of maximum wake‐to‐shear production ratio. We concluded that nighttime drainage flows are restricted to a relatively shallow layer of air beneath the canopy, with little vertical mixing across a relatively long horizontal fetch. Insight into the horizontal and vertical structure of the drainage flow is crucial for understanding the magnitude and dynamics of the mean advective CO2 flux that becomes significant during stable nighttime conditions and are typically missed during measurement of the turbulent CO2 flux. The model and interpretation provided in this study should lead to research strategies for the measurement of these advective fluxes and their inclusion in the overall mass balance for CO2 at this site with complex terrain

Azole Antifungal Agents To Treat the Human Pathogens Acanthamoeba castellanii and Acanthamoeba polyphaga through Inhibition of Sterol 14α-Demethylase (CYP51)

Herein, we have investigated the amebicidal activities of the pharmaceutical triazole CYP51 inhibitors fluconazole, itraconazole, and voriconazole against Acanthamoeba castellanii and Acanthamoeba polyphaga and assess their potential as therapeutic agents against Acanthamoeba infections in humans. Amebicidal activities of the triazoles were assessed by in vitro minimum inhibition concentration (MIC) determinations using trophozoites of A. castellanii and A. polyphaga. In addition, triazole effectiveness was assessed by ligand binding studies and inhibition of CYP51 activity of purified A. castellanii CYP51 (AcCYP51) that was heterologously expressed in Escherichia coli. Itraconazole and voriconazole bound tightly to AcCYP51 (dissociation constant [Kd] of 10 and 13 nM), whereas fluconazole bound weakly (Kd of 2,137 nM). Both itraconazole and voriconazole were confirmed to be strong inhibitors of AcCYP51 activity (50% inhibitory concentrations [IC50] of 0.23 and 0.39 μM), whereas inhibition by fluconazole was weak (IC50, 30 μM). However, itraconazole was 8- to 16-fold less effective (MIC, 16 mg/liter) at inhibiting A. polyphaga and A. castellanii cell proliferation than voriconazole (MIC, 1 to 2 mg/liter), while fluconazole did not inhibit Acanthamoeba cell division (MIC, >64 mg/liter) in vitro. Voriconazole was an effective inhibitor of trophozoite proliferation for A. castellanii and A. polyphaga; therefore, it should be evaluated in trials versus itraconazole for controlling Acanthamoeba infections

Expanding the results of a high throughput screen against an isochorismate-pyruvate lyase to enzymes of a similar scaffold or mechanism

Antibiotic resistance is a growing health concern, and new avenues of antimicrobial drug design are being actively sought. One suggested pathway to be targeted for inhibitor design is that of iron scavenging through siderophores. Here we present a high throughput screen to the isochorismatepyruvate lyase of Pseudomonas aeruginosa, an enzyme required for the production of the siderophore pyochelin. Compounds identified in the screen are high nanomolar to low micromolar inhibitors of the enzyme and produce growth inhibition in PAO1 P. aeruginosa in the millimolar range under iron-limiting conditions. The identified compounds were also tested for enzymatic inhibition of E. coli chorismate mutase, a protein of similar fold and similar chemistry, and of Y. enterocolitica salicylate synthase, a protein of differing fold but catalyzing the same lyase reaction. In both cases, subsets of the inhibitors from the screen were found to be inhibitory to enzymatic activity (mutase or synthase) in the micromolar range and capable of growth inhibition in their respective organisms (E. coli or Y. enterocolitica)