44 research outputs found
The Intestinal Microbiota Plays a Role in Salmonella-Induced Colitis Independent of Pathogen Colonization
The intestinal microbiota is composed of hundreds of species of bacteria, fungi
and protozoa and is critical for numerous biological processes, such as nutrient
acquisition, vitamin production, and colonization resistance against bacterial
pathogens. We studied the role of the intestinal microbiota on host resistance
to Salmonella enterica serovar Typhimurium-induced colitis.
Using multiple antibiotic treatments in 129S1/SvImJ mice, we showed that
disruption of the intestinal microbiota alters host susceptibility to infection.
Although all antibiotic treatments caused similar increases in pathogen
colonization, the development of enterocolitis was seen only when streptomycin
or vancomycin was used; no significant pathology was observed with the use of
metronidazole. Interestingly, metronidazole-treated and infected C57BL/6 mice
developed severe pathology. We hypothesized that the intestinal microbiota
confers resistance to infectious colitis without affecting the ability of
S. Typhimurium to colonize the intestine. Indeed, different
antibiotic treatments caused distinct shifts in the intestinal microbiota prior
to infection. Through fluorescence in situ hybridization,
terminal restriction fragment length polymorphism, and real-time PCR, we showed
that there is a strong correlation between the intestinal microbiota composition
before infection and susceptibility to Salmonella-induced
colitis. Members of the Bacteroidetes phylum were present at significantly
higher levels in mice resistant to colitis. Further analysis revealed that
Porphyromonadaceae levels were also increased in these mice. Conversely, there
was a positive correlation between the abundance of
Lactobacillus sp. and predisposition to colitis. Our data
suggests that different members of the microbiota might be associated with
S. Typhimurium colonization and colitis. Dissecting the
mechanisms involved in resistance to infection and inflammation will be critical
for the development of therapeutic and preventative measures against enteric
pathogens
The study of atmospheric ice-nucleating particles via microfluidically generated droplets
Ice-nucleating particles (INPs) play a significant role in the climate and hydrological cycle by triggering ice formation in supercooled clouds, thereby causing precipitation and affecting cloud lifetimes and their radiative properties. However, despite their importance, INP often comprise only 1 in 10Âłâ10ⶠambient particles, making it difficult to ascertain and predict their type, source, and concentration. The typical techniques for quantifying INP concentrations tend to be highly labour-intensive, suffer from poor time resolution, or are limited in sensitivity to low concentrations. Here, we present the application of microfluidic devices to the study of atmospheric INPs via the simple and rapid production of monodisperse droplets and their subsequent freezing on a cold stage. This device offers the potential for the testing of INP concentrations in aqueous samples with high sensitivity and high counting statistics. Various INPs were tested for validation of the platform, including mineral dust and biological species, with results compared to literature values. We also describe a methodology for sampling atmospheric aerosol in a manner that minimises sampling biases and which is compatible with the microfluidic device. We present results for INP concentrations in air sampled during two field campaigns: (1) from a rural location in the UK and (2) during the UKâs annual Bonfire Night festival. These initial results will provide a route for deployment of the microfluidic platform for the study and quantification of INPs in upcoming field campaigns around the globe, while providing a benchmark for future lab-on-a-chip-based INP studies
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PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK
Background
Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment.
Methods
All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals.
Results
A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death.
Conclusion
Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions
Respiratory and Mayer wave-related discharge patterns of raphé and pontine neurons change with vagotomy
Previous models have attributed changes in respiratory modulation of pontine neurons after vagotomy to a loss of pulmonary stretch receptor âgatingâ of an efference copy of inspiratory drive. Recently, our group confirmed that pontine neurons change firing patterns and become more respiratory modulated after vagotomy, although average peak and mean firing rates of the sample did not increase (Dick et al., J Physiol 586: 4265â4282, 2008). Because raphĂ© neurons are also elements of the brain stem respiratory network, we tested the hypotheses that after vagotomy raphĂ© neurons have increased respiratory modulation and that alterations in their firing patterns are similar to those seen for pontine neurons during withheld lung inflation. RaphĂ© and pontine neurons were recorded simultaneously before and after vagotomy in decerebrated cats. Before vagotomy, 14% of 95 raphĂ© neurons had increased activity during single respiratory cycles prolonged by withholding lung inflation; 13% exhibited decreased activity. After vagotomy, the average index of respiratory modulation (η2) increased (0.05 ± 0.10 to 0.12 ± 0.18 SD; Student's paired t-test, P < 0.01). Time series and frequency domain analyses identified pontine and raphĂ© neuron firing rate modulations with a 0.1-Hz rhythm coherent with blood pressure Mayer waves. These âMayer wave-related oscillationsâ (MWROs) were coupled with central respiratory drive and became synchronized with the central respiratory rhythm after vagotomy (7 of 10 animals). Cross-correlation analysis identified functional connectivity in 52 of 360 pairs of neurons with MWROs. Collectively, the results suggest that a distributed network participates in the generation of MWROs and in the coordination of respiratory and vasomotor rhythms