Clusters in social behaviour of female domestic cats (Felis silvestris catus) living in confinement

Associations between different agonistic and affiliative behavioural patterns of female domestic cats (Felis silvestris catus) were studied. In three groups of intact cats living in confinement frequencies of fourteen agonistic and affiliative behavioural patterns were recorded. The technique of factor analysis (Principal Components Analysis followed by varimax rotation on a dyads X behavioural patterns matrix) was used to detect clusters in these behavioural patterns. Five factors (or types of interindividual relationships) were extracted per group. They accounted collectively for at least 77% of the total variance present in the data. Although differences existed between groups with respect to behavioural patterns included in each factor, four clusters of behaviours could be discriminated: (I) social rubbing, lordosis and rolling in front of partner (sexual behaviour), (II) allogrooming, social sniffing, nosing, sniffing rear and treading (inspection-affiliative behaviour), (III) offensive behaviour and staring, and (IV) defensive behaviour and staring. The role of these clusters in group living is discussed.     

Expression of chemokine-like factor 1 is upregulated during T lymphocyte activation

Chemokine-like factor 1 (CKLF1) is a cytokine with chemotactic effects on leukocytes and a functional ligand of CCR4. This cytokine is widely expressed and the level of expression is reported to be upregulated in asthma and rheumatoid arthritis (RA), disease conditions in which T lymphocytes are over-activated. In order to determine the expression profile of CKLF1 in activated T lymphocytes, we first employed a PCR-based method on human blood fractions cDNA panels and found that CKLF1 was upregulated in activated CD4+ and CD8+ cells, with no obvious changes in CD19+ cells. We further performed kinetic analyses of CKLF1 expression in phytohemagglutinin (PHA)-stimulated human peripheral blood lymphocytes (PBL) at both the mRNA and protein levels. In resting PBL, the constitutive expression of CKLF1 was low at mRNA level and barely detectable at the protein level; however, both were remarkably upregulated by PHA, appearing at 8h after PHA-stimulation and persisting up to 72h. These results suggest that CKLF1 may be involved in T lymphocyte activation and further study of CKLF1 function will prove valuable.     

Supreme™ laryngeal mask airway use in general Anesthesia for category 2 and 3 Cesarean delivery: a prospective cohort study

Background

The Supreme? laryngeal mask airway (SLMA) is a single-use LMA with double lumen design that allows separation of the respiratory and the alimentary tract, hence potentially reducing the gastric volume and risk of aspiration. The purpose of this prospective cohort study is to evaluate the the role of the SLMA as an airway technique for women undergoing category 2 and 3 Cesarean delivery under general anesthesia.

Methods

We recruited 584 parturients who underwent category 2 or 3 Cesarean delivery under general anesthesia, in which 193 parturients underwent category 2 and 391 parturients underwent category 3 Cesarean delivery. The primary outcome was insertion success rate at 1st attempt in SLMA insertion. The secondary outcomes included anaesthetic, obstetric outcomes and maternal side effects associated with airway device.

Results

The 1st attempt insertion success rate was 98.3%, while the overall insertion success rate was 100%. The mean (Standard deviation) time to effective ventilation was 15.6 (4.4) seconds. Orogastric tube insertion was successful at the 1st attempt in all parturients. There was no clinical evidence of aspiration or regurgitation. No episodes of hypoxemia, laryngospasm or bronchospasm were observed intra-operatively. The incidence of complications was low and with good maternal satisfaction reported.

Conclusions

The SLMA could be an alternative effective airway in category 2 and 3 parturients emergency Cesarean Delivery under general anesthesia in a carefully-selected obstetric population.

Trial registration

Clinical Trials Registration: Clinicaltrials.gov Registration NCT02026882. Registered on December 31, 2013.

     

Association of a novel point mutation in MSH2 gene with familial multiple primary cancers

Background

Multiple primary cancers (MPC) have been identified as two or more cancers without any subordinate relationship that occur either simultaneously or metachronously in the same or different organs of an individual. Lynch syndrome is an autosomal dominant genetic disorder that increases the risk of many types of cancers. Lynch syndrome patients who suffer more than two cancers can also be considered as MPC; patients of this kind provide unique resources to learn how genetic mutation causes MPC in different tissues.

Methods

We performed a whole genome sequencing on blood cells and two tumor samples of a Lynch syndrome patient who was diagnosed with five primary cancers. The mutational landscape of the tumors, including somatic point mutations and copy number alternations, was characterized. We also compared Lynch syndrome with sporadic cancers and proposed a model to illustrate the mutational process by which Lynch syndrome progresses to MPC.

Results

We revealed a novel pathologic mutation on the MSH2 gene (G504 splicing) that associates with Lynch syndrome. Systematical comparison of the mutation landscape revealed that multiple cancers in the proband were evolutionarily independent. Integrative analysis showed that truncating mutations of DNA mismatch repair (MMR) genes were significantly enriched in the patient. A mutation progress model that included germline mutations of MMR genes, double hits of MMR system, mutations in tissue-specific driver genes, and rapid accumulation of additional passenger mutations was proposed to illustrate how MPC occurs in Lynch syndrome patients.

Conclusion

Our findings demonstrate that both germline and somatic alterations are driving forces of carcinogenesis, which may resolve the carcinogenic theory of Lynch syndrome.

     

Rad9 plays an important role in DNA mismatch repair through physical interaction with MLH1

Rad9 is conserved from yeast to humans and plays roles in DNA repair (homologous recombination repair, and base-pair excision repair) and cell cycle checkpoint controls. It has not previously been reported whether Rad9 is involved in DNA mismatch repair (MMR). In this study, we have demonstrated that both human and mouse Rad9 interacts physically with the MMR protein MLH1. Disruption of the interaction by a single-point mutation in Rad9 leads to significantly reduced MMR activity. This disruption does not affect S/M checkpoint control and the first round of G₂/M checkpoint control, nor does it alter cell sensitivity to UV light, gamma rays or hydroxyurea. Our data indicate that Rad9 is an important factor in MMR and carries out its MMR function specifically through interaction with MLH1.     

Elucidation of 2-hydroxybiphenyl effect on dibenzothiophene desulfurization by Microbacterium sp. strain ZD-M2

The effect of 2-hydroxybiphenyl (2-HBP), the end product of dibenzothiophene (DBT) desulfurization via 4S pathway, on cell growth and desulfurization activity was investigated by Microbacterium sp. The experimental results indicate that 2-HBP would inhibit the desulfurization activity. Providing 2-HBP was added in the reaction media, the DBT degradation rate decreased along with the increase of 2-HBP addition. By contrast, cell growth would be promoted in the addition of 2-HBP at a low concentration (<0.1mM). At high concentration of 2-HBP, the inhibition on the cell growth occurred. Meanwhile, the inhibitory effect of 2-HBP on DBT desulfurization activity was tested both in the oil/aqueous two-phase system and the aqueous system. A mathematical model was developed to explain the product formation kinetics with DBT as the sole sulfur source. The predicted results were close to the experimental data, it elucidated that along with the 2-HBP accumulation, the inhibitory effect of 2-HBP on DBT desulfurization and cell growth was enhanced.     

Antidiabetic potential of oleanolic acid from Ligustrum lucidum Ait

Ligustrum lucidum Ait. has been used in traditional Chinese medicine for over 1000 years because of its anti-tumor, antimutagenic, antidiabetic, and hepatoprotective properties. The aim of this study was to determine whether oleanolic acid (OA) is the principal active compound of L. lucidum responsible for its antidiabetic properties, and to examine its effect on the expression of thyroid hormones and insulin secretion, thus revealing the mechanism by which L. lucidum modulates insulin levels in diabetes. When rats with streptozotocin-induced diabetes were treated with OA (100 and 200 mg/kg body mass per day, for 40 days), the changes in blood glucose levels and in oral glucose tolerance tests showed that hypoglycemia was more pronounced in OA-treated groups than in the diabetic control rats, and that the levels of triglyceride, total cholesterol, and low-density lipoportein cholesterol in OA-treated rats were lower than those in the diabetic control rats, whose high-density lipoprotein cholesterol increased. OA-treated rats also gained weight, and exhibited increased serum insulin levels. In contrast, OA treatment did not effect the levels of thyroid hormone or TSH in rats with streptozotocin-induced diabetes. These results indicate that OA has hypoglycemic and hypolipidemic effects. OA treatment might stimulate insulin release, and consequently, results in the modulation of glucose levels and regulation of lipid metabolism.     

Genome sequence of Thermotoga sp. strain RQ2, a hyperthermophilic bacterium isolated from a geothermally heated region of the seafloor near Ribeira Quente, the Azores

Thermotoga sp. strain RQ2 is probably a strain of Thermotoga maritima. Its complete genome sequence allows for an examination of the extent and consequences of gene flow within Thermotoga species and strains. Thermotoga sp. RQ2 differs from T. maritima in its genes involved in myo-inositol metabolism. Its genome also encodes an apparent fructose phosphotransferase system (PTS) sugar transporter. This operon is also found in Thermotoga naphthophila strain RKU-10 but no other Thermotogales. These are the first reported PTS transporters in the Thermotogales.     

Discovery of new thienopyrimidine derivatives as potent and orally efficacious phosphoinositide 3-kinase inhibitors

A series of new thienopyrimidine derivatives has been discovered as potent PI3K inhibitors. The systematic SAR studies for these analogues are described. Among them, 8a and 9a exhibit nanomolar enzymatic potencies and sub-micromolar cellular anti-proliferative activities. 8a displays favorable pharmacokinetic profiles, while 9a easily undergoes deacetylation to yield a major metabolite 8a. Furthermore, 8a and 9a potently inhibit tumor growth in a dose-dependent manner in the NCI-H460 xenograft model with an acceptable safety profile.