Microbial ecology of the murine gut associated with the development of dextran sodium sulfate-induced colitis

Background: Dextran sodium sulfate (DSS) is used to induce murine colitis. Although the exact mechanism by which DSS administration causes disease is unknown, evidence suggests that the resident bacteria play a role in the development of murine DSS colitis, analogous to their role in human inflammatory bowel diseases. Methods: C57BL/6 mice received 5% DSS in the drinking water and were euthanized 3 days and 14 days after the initiation of DSS treatment. Culture-independent methods were used to follow changes in the community structure of the gut's microbiota following DSS treatment. Histologic evidence of disease and changes in host gene expression were assessed. Results: Histologic colitis was minimal in DSS-treated animals at 3 days, but severe after 14 days. Analysis of 16S rRNA-encoding gene clone libraries demonstrated that the microbial communities in the ceca of DSS-treated mice were distinct from those in control mice. The microbiota in the cecum of DSS-treated animals was characterized by an overall decrease in microbial richness, an increase in members of the phylum Verrucomicrobia, and decrease in Tenericutes. Changes in the host's inflammatory response and microbial communities occurred before the histologic appearance of severe disease in the colon, but were seen concurrently in the cecum. Conclusions: DSS administration is associated with reproducible changes in the gut microbial diversity of mice. Microbial and immunological changes appeared before the development of severe inflammation in the colon. This indicates that these changes in microbial community may play role in the potentiation of the abnormal inflammatory response seen in DSS-treated animals. (Inflamm Bowel Dis 2011)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83471/1/21462_ftp.pd

Pediatric Midface Fractures: Outcomes and Complications of 218 Patients

Objective To analyze management, outcomes, and complications of pediatric midface fractures. Methods Retrospective cohort study at an urban, single‐institution, multispecialty surgical teams, at two level 1 pediatric trauma centers. Query included subjects aged 0–17 diagnosed with midface fractures between 2012 and 2016. Results A total of 218 pediatric patients presented with 410 total midface fractures. The most common etiologies included motor vehicle collisions (MVC) (n = 56, 25.7%), sport‐related (n = 35, 16.1%), and assault/battery (n = 32, 14.7%). Fracture site distribution included: 125 maxillary (34 with exclusively the nasal/frontal process), 109 nasal, 47 ethmoid, 40 sphenoid, 33 zygoma, 29 frontal sinus, 21 lacrimal, and 6 palatal. Among these, there were 105 orbital, 17 naso‐orbito‐ethmoid, and 12 Le Fort fractures. One‐quarter of patients received at least one midface‐related operation during the initial encounter. Operative intervention rates for specific midface fracture subsites were not significantly different (X2 = 6.827, P = .234). One hundred thirty‐five patients (63.4%) attended follow‐up, thus known complication rate was 14.6% (n = 31). Complication rates between midface fracture subsites were not significantly different (X2 = 5.629, P = .229). Complications included facial deformity (n = 18), nasal airway obstruction (n = 8), diplopia (n = 4), hardware‐related pain (n = 3), and paresthesias (n = 3). Conclusions The most common sites of pediatric midface fractures involved the maxilla, and nasal bones. Three quarters of pediatric midface fractures were treated conservatively, with low rates of complications. Facial deformity was the most common complication; as such, proper management and follow‐up are important to ensure normal growth and development of the pediatric facial skeleton. Level of Evidence

Depression, antidepressant medications, and risk of Clostridium difficile infection

Abstract Background An ancillary finding in previous research has suggested that the use of antidepressant medications increases the risk of developing Clostridium difficile infection (CDI). Our objective was to evaluate whether depression or the use of anti-depressants altered the risk of developing CDI, using two distinct datasets and study designs. Methods In Study 1, we conducted a longitudinal investigation of a nationally representative sample of older Americans (n = 16,781), linking data from biennial interviews to physician and emergency department visits, stays in hospital and skilled nursing facilities, home health visits, and other outpatient visits. In Study 2, we completed a clinical investigation of hospitalized adults who were tested for C. difficile (n = 4047), with cases testing positive and controls testing negative. Antidepressant medication use prior to testing was ascertained. Results The population-based rate of CDI in older Americans was 282.9/100,000 person-years (95% confidence interval (CI)) 226.3 to 339.5) for individuals with depression and 197.1/100,000 person-years for those without depression (95% CI 168.0 to 226.1). The odds of CDI were 36% greater in persons with major depression (95% CI 1.06 to 1.74), 35% greater in individuals with depressive disorders (95% CI 1.05 to 1.73), 54% greater in those who were widowed (95% CI 1.21 to 1.95), and 25% lower in adults who did not live alone (95% CI 0.62 to 0.92). Self-reports of feeling sad or having emotional, nervous or psychiatric problems at baseline were also associated with the later development of CDI. Use of certain antidepressant medications during hospitalization was associated with altered risk of CDI. Conclusions Adults with depression and who take specific anti-depressants seem to be more likely to develop CDI. Older adults who are widowed or who live alone are also at greater risk of CDI.http://deepblue.lib.umich.edu/bitstream/2027.42/112859/1/12916_2012_Article_763.pd

Effects of Noise Electrical Stimulation on Proprioception, Force Control, and Corticomuscular Functional Connectivity

Sensory afferent inputs play an important role in neuromuscular functions. Subsensory level noise electrical stimulation enhances the sensitivity of peripheral sensory system and improves lower extremity motor function. The current study aimed to investigate the immediate effects of noise electrical stimulation on proprioceptive senses and grip force control, and whether there are associated neural activities in the central nervous system. Fourteen healthy adults participated in 2 experiments on 2 different days. In day 1, participants performed grip force and joint proprioceptive tasks with and without (sham) noise electrical stimulation. In day 2, participants performed grip force steady hold task before and after 30-min noise electrical stimulation. Noise stimulation was applied with surface electrodes secured along the course of the median nerve and proximal to the coronoid fossa EEG power spectrum density of bilateral sensorimotor cortex and coherence between EEG and finger flexor EMG were calculated and compared. Wilcoxon Signed-Rank Tests were used to compare the differences of proprioception, force control, EEG power spectrum density and EEG-EMG coherence between noise electrical stimulation and sham conditions. The significance level (alpha) was set at 0.05. Our study found that noise stimulation with optimal intensity could improve both force and joint proprioceptive senses. Furthermore, individuals with higher gamma coherence showed better force proprioceptive sense improvement with 30-min noise electrical stimulation. These observations indicate the potential clinical benefits of noise stimulation on individuals with impaired proprioceptive senses and the characteristics of individuals who might benefit from noise stimulation

Novel Internal Regions of Fluorescent Proteins Undergo Divergent Evolutionary Patterns

Over the past decade, fluorescent proteins (FPs) have become ubiquitous tools in biological research. Yet, little is known about the natural function or evolution of this superfamily of proteins that originate from marine organisms. Using molecular phylogenetic analyses of 102 naturally occurring cyan fluorescent proteins, green fluorescent proteins, red fluorescent proteins, as well as the nonfluorescent (purple-blue) protein sequences (including new FPs from Lizard Island, Australia) derived from organisms with known geographic origin, we show that FPs consist of two distinct and novel regions that have evolved under opposite and sharply divergent evolutionary pressures. A central region is highly conserved, and although it contains the residues that form the chromophore, its evolution does not track with fluorescent color and evolves independently from the rest of the protein. By contrast, the regions enclosing this central region are under strong positive selection pressure to vary its sequence and yet segregate well with fluorescence color emission. We did not find a significant correlation between geographic location of the organism from which the FP was isolated and molecular evolution of the protein. These results define for the first time two distinct regions based on evolution for this highly compact protein. The findings have implications for more sophisticated bioengineering of this molecule as well as studies directed toward understanding the natural function of FPs

Suppression of Leukotriene B4 Generation by Ex-vivo Neutrophils Isolated from Asthma Patients on Dietary Supplementation with Gammalinolenic Acid-containing Borage Oil: Possible Implication in Asthma

Dietary gammalinolenic acid (GLA), a potent inhibitor of 5-lipoxygenase (5-LOX) and suppressor of leukotriene B(4) (LTB(4)), can attenuate the clinical course of rheumatoid arthritics, with negligible side effects. Since Zileuton, also an inhibitor of 5-LOX, attenuates asthma but with an undesirable side effect, we investigated whether dietary GLA would suppress biosynthesis of PMN-LTB(4) isolated from asthma patients and attenuate asthma. Twenty-four mild-moderate asthma patients (16–75 years) were randomized to receive either 2.0 g daily GLA (borage oil) or corn oil (placebo) for 12 months. Blood drawn at 3 months intervals was used to prepare sera for fatty acid analysis, PMNs for determining phospholipid fatty acids and for LTB4 generation. Patients were monitored by daily asthma scores, pulmonary function, and exhaled NO. Ingestion of daily GLA (i) increased DGLA (GLA metabolite) in PMN-phospholipids; (ii) increased generation of PMN-15-HETrE (5-LOX metabolite of DGLA). Increased PMN-DGLA/15-HETrE paralleled the decreased PMN generation of proinflammatory LTB(4). However, the suppression of PMN-LTB4 did not reveal statistically significant suppression of the asthma scores evaluated. Nonetheless, the study demonstrated dietary fatty acid modulation of endogenous inflammatory mediators without side effects and thus warrant further explorations into the roles of GLA at higher doses, leukotrienes and asthma

Transcriptome Deep-Sequencing and Clustering of Expressed Isoforms from Favia Corals

Background: Genomic and transcriptomic sequence data are essential tools for tackling ecological problems. Using an approach that combines next-generation sequencing, de novo transcriptome assembly, gene annotation and synthetic gene construction, we identify and cluster the protein families from Favia corals from the northern Red Sea. Results: We obtained 80 million 75 bp paired-end cDNA reads from two Favia adult samples collected at 65 m (Fav1, Fav2) on the Illumina GA platform, and generated two de novo assemblies using ABySS and CAP3. After removing redundancy and filtering out low quality reads, our transcriptome datasets contained 58,268 (Fav1) and 62,469 (Fav2) contigs longer than 100 bp, with N50 values of 1,665 bp and 1,439 bp, respectively. Using the proteome of the sea anemone Nematostella vectensis as a reference, we were able to annotate almost 20% of each dataset using reciprocal homology searches. Homologous clustering of these annotated transcripts allowed us to divide them into 7,186 (Fav1) and 6,862 (Fav2) homologous transcript clusters (E-value ≤ 2e-30). Functional annotation categories were assigned to homologous clusters using the functional annotation of Nematostella vectensis. General annotation of the assembled transcripts was improved 1-3% using the Acropora digitifera proteome. In addition, we screened these transcript isoform clusters for fluorescent proteins (FPs) homologs and identified seven potential FP homologs in Fav1, and four in Fav2. These transcripts were validated as bona fide FP transcripts via robust fluorescence heterologous expression. Annotation of the assembled contigs revealed that 1.34% and 1.61% (in Fav1 and Fav2, respectively) of the total assembled contigs likely originated from the corals’ algal symbiont, Symbiodinium spp. Conclusions: Here we present a study to identify the homologous transcript isoform clusters from the transcriptome of Favia corals using a far-related reference proteome. Furthermore, the symbiont-derived transcripts were isolated from the datasets and their contribution quantified. This is the first annotated transcriptome of the genus Favia, a major increase in genomics resources available in this important family of corals

Transcriptome Deep-Sequencing and Clustering of Expressed Isoforms from Favia Corals

Background: Genomic and transcriptomic sequence data are essential tools for tackling ecological problems. Using an approach that combines next-generation sequencing, de novo transcriptome assembly, gene annotation and synthetic gene construction, we identify and cluster the protein families from Favia corals from the northern Red Sea. Results: We obtained 80 million 75 bp paired-end cDNA reads from two Favia adult samples collected at 65 m (Fav1, Fav2) on the Illumina GA platform, and generated two de novo assemblies using ABySS and CAP3. After removing redundancy and filtering out low quality reads, our transcriptome datasets contained 58,268 (Fav1) and 62,469 (Fav2) contigs longer than 100 bp, with N50 values of 1,665 bp and 1,439 bp, respectively. Using the proteome of the sea anemone Nematostella vectensis as a reference, we were able to annotate almost 20% of each dataset using reciprocal homology searches. Homologous clustering of these annotated transcripts allowed us to divide them into 7,186 (Fav1) and 6,862 (Fav2) homologous transcript clusters (E-value ≤ 2e-30). Functional annotation categories were assigned to homologous clusters using the functional annotation of Nematostella vectensis. General annotation of the assembled transcripts was improved 1-3% using the Acropora digitifera proteome. In addition, we screened these transcript isoform clusters for fluorescent proteins (FPs) homologs and identified seven potential FP homologs in Fav1, and four in Fav2. These transcripts were validated as bona fide FP transcripts via robust fluorescence heterologous expression. Annotation of the assembled contigs revealed that 1.34% and 1.61% (in Fav1 and Fav2, respectively) of the total assembled contigs likely originated from the corals’ algal symbiont, Symbiodinium spp. Conclusions: Here we present a study to identify the homologous transcript isoform clusters from the transcriptome of Favia corals using a far-related reference proteome. Furthermore, the symbiont-derived transcripts were isolated from the datasets and their contribution quantified. This is the first annotated transcriptome of the genus Favia, a major increase in genomics resources available in this important family of corals