The accuracy of several multiple sequence alignment programs for proteins

Background  

There have been many algorithms and software programs implemented for the inference of multiple sequence alignments of protein and DNA sequences. The "true" alignment is usually unknown due to the incomplete knowledge of the evolutionary history of the sequences, making it difficult to gauge the relative accuracy of the programs.     

Compression or tension? The stress distribution in the proximal femur

Background  

Questions regarding the distribution of stress in the proximal human femur have never been adequately resolved. Traditionally, by considering the femur in isolation, it has been believed that the effect of body weight on the projecting neck and head places the superior aspect of the neck in tension. A minority view has proposed that this region is in compression because of muscular forces pulling the femur into the pelvis. Little has been done to study stress distributions in the proximal femur. We hypothesise that under physiological loading the majority of the proximal femur is in compression and that the internal trabecular structure functions as an arch, transferring compressive stresses to the femoral shaft.     

Rapid adaptive adjustment of parental care coincident with altered migratory behaviour

The optimal duration of parental care is shaped by the trade-off between investment in current and expected future reproductive success. A change in migratory behaviour is expected to affect the optimal duration of parental care, because migration and non-migration differ in expectations of future reproductive success as a result of differential adult and/or offspring mortality. Here we studied how a recent emergence of non-migratory behaviour has affected the duration of parental care in the previously (until the 1980s) strictly migratory Russian breeding population of the barnacle geese Branta leucopsis. As a measure of parental care, we compared the vigilance behaviour of parents and non-parents in both migratory and non-migratory barnacle geese throughout the season. We estimated the duration of parental care at 233 days for migratory and 183 days for non-migratory barnacle geese. This constitutes a shortening of the duration of parental care of 21% in 25 years. Barnacle geese are thus able to rapidly adapt their parental care behaviour to ecological conditions associated with altered migratory behaviour. Our study demonstrates that a termination of migratory behaviour resulted in a drastic reduction in parental care and highlights the importance of studying the ecological and behavioural consequences of changes in migratory behaviour and the consequences of these changes for life-history evolution.     

Temporal Variation in Seed Predation by Insects in a Population of Syagrus romanzoffiana (Arecaceae) in Santa Catarina Island, SC, Brazil

Insect seed predation may vary depending on seed production. The present study considers the hypothesis that the rates of seed predation tend to be smaller in years of higher fruit production. Thus, we monitored the production of fruits and predation of seeds of the palm Syagrus romanzoffiana over 2?years in the Atlantic Forest (Parque Municipal da Lagoa do Peri, Florianópolis, SC, Brazil), between July 2006 and June 2008. Plots of 0.25?m² were fitted under 20 mother plants and fruits were monthly collected for assessment of abundance and seed predation. There was variation in fruit production between the 2?years and among reproductive plants. Predation rates were high and occurred in the predispersal phase by the Curculionidae Revena rubiginosa Boheman, Anchylorhynchus aegrotus Fahraeus, and Anchylorhynchus variabilis Gyllenhal. Seed predation by these species of Anchylorhynchus is first registered in the present study. In average, about 60% of the seeds monthly produced in the population tend to escape insect predation in year of high or low production, becoming available for recruitment. The predation rate was not related to the amount of fruits produced per reproductive plant. Also, different than expected, there was a positive relation between the rates of seed predation and the total of fruits produced monthly on the plots. Thus, no evidence for the satiation of insect seed predators was found in this study with S. romanzoffiana.     

Umbilical cord clamping in term piglets: a useful model to study perinatal asphyxia?

Perinatal asphyxia results in tissue and cellular changes during the reperfusion period and clinical signs like perinatal mortality and decreased vitality at birth in newborn piglets. This study aimed to develop and validate a model of birth asphyxia, mimicking the evolvement of birth asphyxia in natural farrowings by conducting umbilical cord clamping (UCC) in term piglets during caesarean sections under general anaesthesia. In total 23 piglets were subjected to 5-8min of UCC and 24 piglets served as controls. Acid-base balance values and heart rates measured before UCC remained fairly constant throughout the surgical procedure, indicating nearly identical starting conditions of piglets within and between litters. UCC resulted in a significant, mild, mixed respiratory-metabolic acidosis (pH 7.22, pCO(2) 9.8kPa, BE(ecf) 2mmol/L, lactate 6.5mmol/L; controls: pH 7.31, pCO(2) 8.5kPa, BE(ecf) 5mmol/L, lactate 4mmol/L) at 10min after birth (defined as simultaneous cutting of the umbilical cord and removal of a plastic bag that had been placed over the head to avoid air intake). Heart rates were significantly decreased during UCC (range: 83-107beats/min versus 128-134beats/min in controls). Rectal temperatures and changes in body weight until 72h of life were not affected by UCC. Interestingly, four control and seven clamped piglets did not survive as no independent respiration could be attained. Birth weights and duration of UCC of these piglets did not differ significantly from those in surviving control and clamped piglets. In conclusion the mixed respiratory-metabolic acidosis arising in the surviving clamped piglets is not as severe as can be expected in highly asphyxiated, vaginally delivered newborn piglets. Repeatability of the model is compromised by considerable variation in the individual response to UCC.     

Effects of morphine and naloxone on fetal heart rate and movement in the pig.

To test the hypothesis that an increasing opioid tonus is involved in decreases in fetal heart rate (FHR) and movement (FM) during late gestation, we studied the effects of intravenous bolus injections of morphine (1 mg) and naloxone (1 mg) on FHR and FM in the fetal pig. Twenty-one fetuses (1 per sow) were catheterized at 90-104 days of gestation (median 100 days). Recordings of FHR (electrocardiograph or Doppler-derived signals) and FM (ultrasonography) were made from 15 min before to 45 min after treatment. Morphine administration significantly decreased FHR, but it increased FHR variation and forelimb movements (LM). LM were clustered, and this stereotyped behavior has never before been observed in any mammalian fetus. Naloxone administration increased gross body movements and FHR without significant changes in FHR variation. It is concluded that FHR and motility are under opioidergic control in the pig fetus. Both morphine and naloxone induce hypermotility, suggesting that naloxone does not act as a pure opioid antagonist in the fetal pig.     

Changes in odor quality discrimination following recovery from olfactory nerve transection

Following recovery from olfactory nerve transection, animals regain their ability to discriminate between odors. Odor discrimination is restored after new neurons establish connections with the olfactory bulb. However, it is not known if the new connections alter odor quality perception. To address this question, 20 adult hamsters were first trained to discriminate between cinnamon and strawberry odors. After reaching criterion (> or = 90% correct response), half of the animals received a bilateral nerve transection (BTX) and half a surgical sham procedure. Animals were not tested again until day 40, a point in recovery when connections are re-established with the bulb. When BTX animals were tested without food reinforcement, they could not perform the odor discrimination task. Sham animals, however, could discriminate, demonstrating that the behavioral response had not been extinguished during the 40 day period. When reinforcement was resumed, BTX animals were able to discriminate between cinnamon and strawberry after four test sessions. In addition, their ability to discriminate between these two familiar odors was no different than that of BTX and sham animals tested with two novel odors, baby powder and coffee. These findings suggest that, after recovery from nerve transection, there are alterations in sensory perception and that restoration of odor quality discrimination requires that the animal must again learn to associate individual odor sensations with a behavioral response.      

Smad gene expression in pulmonary fibroblasts: indications for defective ECM repair in COPD

Background

Endothelial dysfunction is a major complication of pulmonary endarterectomy (PTE) that can lead to pulmonary edema and persistent pulmonary hypertension. We hypothesized that endothelial dysfunction is related to increased endothelial-cell (EC) death.

Methods

In piglets, the left pulmonary artery (PA) was ligated to induce lung ischemia then reimplanted into the main PA to reperfuse the lung. Animals sacrificed 5 weeks after ligation (n = 5), 2 days after reperfusion (n = 5), or 5 weeks after reperfusion (n = 5) were compared to a sham-operated group (n = 5). PA vasoreactivity was studied and eNOS assayed. EC apoptosis was assessed by TUNEL in the proximal and distal PA and by caspase-3 activity assay in the proximal PA. Gene expression of pro-apoptotic factors (thrombospondin-1 (Thsp-1) and plasminogen activator inhibitor 1 (PAI-1)) and anti-apoptotic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was investigated by QRT-PCR.

Results

Endothelium-dependent relaxation was altered 5 weeks after ligation (p = 0.04). The alterations were exacerbated 2 days after reperfusion (p = 0.002) but recovered within 5 weeks after reperfusion. EC apoptosis was increased 5 weeks after PA ligation (p = 0.02), increased further within 2 days after reperfusion (p < 0.0001), and returned to normal within 5 weeks after reperfusion. Whereas VEGF and bFGF expressions remained unchanged, TSP and PAI-1 expressions peaked 5 weeks after ligation (p = 0.001) and returned to normal within 2 days after reperfusion.

Conclusion

Chronic lung ischemia induces over-expression of pro-apoptotic factors. Lung reperfusion is followed by a dramatic transient increase in EC death that may explain the development of endothelial dysfunction after PE. Anti-apoptotic agents may hold considerable potential for preventing postoperative complications.     

Therapeutic dendritic cell vaccine preparation using tumor RNA transfection: A promising approach for the treatment of prostate cancer

Background

Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo, including the skin. We have previously demonstrated efficient delivery of plasmid DNA to the skin utilizing a custom-built four-plate electrode. The experiments described here further evaluate cutaneous plasmid delivery using in vivo electroporation. Plasmid expression levels are compared to those after liposome mediated delivery.

Methods

Enhanced electrically-mediated delivery, and less extensively, liposome complexed delivery, of a plasmid encoding the reporter luciferase was tested in rodent skin. Expression kinetics and tissue damage were explored as well as testing in a second rodent model.

Results

Experiments confirm that electroporation alone is more effective in enhancing reporter gene expression than plasmid injection alone, plasmid conjugation with liposomes followed by injection, or than the combination of liposomes and electroporation. However, with two time courses of multiple electrically-mediated plasmid deliveries, neither the levels nor duration of transgene expression are significantly increased. Tissue damage may increase following a second treatment, no further damage is observed after a third treatment. When electroporation conditions utilized in a mouse model are tested in thicker rat skin, only higher field strengths or longer pulses were as effective in plasmid delivery.

Conclusion

Electroporation enhances reporter plasmid delivery to the skin to a greater extent than the liposome conjugation method tested. Multiple deliveries do not necessarily result in higher or longer term expression. In addition, some impact on tissue integrity with respect to surface damage is observed. Pulsing conditions should be optimized for the model and for the expression profile desired.     

Nasal gene expression differentiates COPD from controls and overlaps bronchial gene expression

Background

Nasal gene expression profiling is a promising method to characterize COPD non-invasively. We aimed to identify a nasal gene expression profile to distinguish COPD patients from healthy controls. We investigated whether this COPD-associated gene expression profile in nasal epithelium is comparable with the profile observed in bronchial epithelium.

Methods

Genome wide gene expression analysis was performed on nasal epithelial brushes of 31 severe COPD patients and 22 controls, all current smokers, using Affymetrix Human Gene 1.0 ST Arrays. We repeated the gene expression analysis on bronchial epithelial brushes in 2 independent cohorts of mild-to-moderate COPD patients and controls.

Results

In nasal epithelium, 135 genes were significantly differentially expressed between severe COPD patients and controls, 21 being up- and 114 downregulated in COPD (false discovery rate?<?0.01). Gene Set Enrichment Analysis (GSEA) showed significant concordant enrichment of COPD-associated nasal and bronchial gene expression in both independent cohorts (FDR_GSEA <?0.001).

Conclusion

We identified a nasal gene expression profile that differentiates severe COPD patients from controls. Of interest, part of the nasal gene expression changes in COPD mimics differentially expressed genes in the bronchus. These findings indicate that nasal gene expression profiling is potentially useful as a non-invasive biomarker in COPD.

Trial registration

ClinicalTrials.gov registration number NCT01351792 (registration date May 10, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 19, 2009), ClinicalTrials.gov registration number NCT00807469 (registration date December 11, 2008).