Resistance to root-lesion nematode Pratylenchus neglectus identified in a new collection of two wild chickpea species (Cicer reticulatum and C. echinospermum) from Turkey

Abstract Chickpea (Cicer arietinum) is a major legume crop, with Australia being the second largest producer worldwide. Pratylenchus neglectus is a root-lesion nematode that invades, feeds and reproduces in roots of pulse and cereal crops. In Australia, chickpea and wheat (Triticum aestivum) are commonly grown in rotation and annual damage by P. neglectus accounts for large economic losses to both crops. Cultivated chickpea has narrow genetic diversity that limits the potential for improvement in resistance breeding. New collections of wild chickpea species, C. reticulatum and C. echinospermum, have substantially increased the previously limited world collection of wild Cicer germplasm and offer potential to widen the genetic diversity of cultivated chickpea through the identification of accessions with good resistance. This research assessed 243 C. reticulatum and 86 C. echinospermum accessions for response to P. neglectus in replicated experiments under controlled glasshouse conditions from 2013 and 2014 collection missions that were received, tested and analysed in two experimental sets. Multi-experiment analyses showed lower P. neglectus population densities in both sets of wild Cicer accessions tested than Australia's elite breeding cultivar PBA HatTrick at the significance level p < 0.05. Provisional resistance ratings were given to all genotypes tested in both experimental sets, with C. reticulatum accessions CudiB_008B and Kayat_066 rated as resistant in both Set 1 and Set 2. New sources of resistance to P. neglectus observed in this study can be introgressed into commercial chickpea cultivars to improve their resistance to this nematode

A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats

ABSTRACT Although respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log 10 total PFU and 2.7 log 10 PFU/g of tissue, respectively, compared to those in unvaccinated animals ( P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity. IMPORTANCE RSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by incorporating a low-fusion, subgroup B F protein in the genetic background of codon-deoptimized nonstructural protein genes and a deleted small hydrophobic protein gene. The resultant vaccine candidate, DB1, was attenuated, highly immunogenic, and protective against RSV challenge in cotton rats

A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation

Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization and there remains no pediatric vaccine. RSV live-attenuated vaccines (LAVs) have a history of safe testing in infants; however, achieving an effective balance of attenuation and immunogenicity has proven challenging. Here we seek to engineer an RSV LAV with enhanced immunogenicity. Genetic mapping identifies strain line 19 fusion (F) protein residues that correlate with pre-fusion antigen maintenance by ELISA and thermal stability of infectivity in live RSV. We generate a LAV candidate named OE4 which expresses line 19F and is attenuated by codon-deoptimization of non-structural (NS1 and NS2) genes, deletion of the small hydrophobic (SH) gene, codon-deoptimization of the attachment (G) gene and ablation of the secreted form of G. OE4 (RSV-A2-dNS1-dNS2-ΔSH-dGm-Gsnull-line19F) exhibits elevated pre-fusion antigen levels, thermal stability, immunogenicity, and efficacy despite heavy attenuation in the upper and lower airways of cotton rats

Genome-Wide Profiling of Histone H3 Lysine 4 and Lysine 27 Trimethylation Reveals an Epigenetic Signature in Prostate Carcinogenesis

BACKGROUND: Increasing evidence implicates the critical roles of epigenetic regulation in cancer. Very recent reports indicate that global gene silencing in cancer is associated with specific epigenetic modifications. However, the relationship between epigenetic switches and more dynamic patterns of gene activation and repression has remained largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide profiling of the trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) was performed using chromatin immunoprecipitation coupled with whole genome promoter microarray (ChIP-chip) techniques. Comparison of the ChIP-chip data and microarray gene expression data revealed that loss and/or gain of H3K4me3 and/or H3K27me3 were strongly associated with differential gene expression, including microRNA expression, between prostate cancer and primary cells. The most common switches were gain or loss of H3K27me3 coupled with low effect on gene expression. The least prevalent switches were between H3K4me3 and H3K27me3 coupled with much higher fractions of activated and silenced genes. Promoter patterns of H3K4me3 and H3K27me3 corresponded strongly with coordinated expression changes of regulatory gene modules, such as HOX and microRNA genes, and structural gene modules, such as desmosome and gap junction genes. A number of epigenetically switched oncogenes and tumor suppressor genes were found overexpressed and underexpressed accordingly in prostate cancer cells. CONCLUSIONS/SIGNIFICANCE: This work offers a dynamic picture of epigenetic switches in carcinogenesis and contributes to an overall understanding of coordinated regulation of gene expression in cancer. Our data indicate an H3K4me3/H3K27me3 epigenetic signature of prostate carcinogenesis

Preconception Care and Treatment with Assisted Reproductive Technologies

Couples with fertility problems seeking treatment with assisted reproductive technologies (ART) such as in vitro fertilization should receive preconception counseling on all factors that are provided when counseling patients without fertility problems. Additional counseling should address success rates and possible risks from ART therapies. Success rates from ART are improving, with the highest live birth rates averaging about 40% per cycle among women less than 35 years old. A woman’s age lowers the chance of achieving a live birth, as do smoking, obesity, and infertility diagnoses such as hydrosalpinx, uterine leiomyoma, or male factor infertility. Singletons conceived with ART may have lower birth weights. Animal studies suggest that genetic imprinting disorders may be induced by certain embryo culture conditions. The major risk from ovarian stimulation is multiple gestation. About one-third of live-birth deliveries from ART have more than one infant, and twins represent 85% of these multiple-birth children. There are more complications in multiple gestation pregnancies, infants are more likely to be born preterm and with other health problems, and families caring for multiples experience more stress. Transferring fewer embryos per cycle reduces the multiple birth rate from ART, but the patient may have to pay for additional cycles of ART because of a lower likelihood of pregnancy

Current role of surgery in small cell lung carcinoma

Small cell lung carcinoma represents 15–20% of lung cancer. Is is characterized by rapid growth and early disseminated disease with poor outcome. For many years surgery was considered a contraindication in Small Cell Lung Cancer (SCLC) since radiotherapy and chemoradiotherapy were found to be more efficient in the management of these patients. Never the less some surgeons continue to be in favor of surgery as part of a combined modality treatment in patients with SCLC. The revaluation of the role of surgery in this group of patients is based on clinical data indicating a much better prognosis in selected patients with limited disease (T1-2, N0, M0), the high rate of local recurrence after chemoradiotherapy with surgery considered eventually more efficient in the local control of the disease and the fact that surgery is the most accurate tool to access the response to chemotherapy, identify carcinoids misdiagnosed as SCLC and treat the Non Small Cell Lung Cancer component of mixed tumors. Performing surgery for local disease SCLC requires a complete preoperative assessment to exclude the presence of nodal involvement. In stage I surgery must always be followed by adjuvant chemotherapy, while in stage II and III surgery must be planned only in the context of clinical trials and after a pathologic response to induction chemoradiotherapy has been confirmed. Prophylactic cranial irradiation should be used to reduce the incidence of brain metastasi

Socioeconomic inequalities in cause specific mortality among older people in France

<p>Abstract</p> <p>Background</p> <p>European comparative studies documented a clear North-South divide in socioeconomic inequalities with cancer being the most important contributor to inequalities in total mortality among middle aged men in Latin Europe (France, Spain, Portugal, Italy). The aim of this paper is to investigate educational inequalities in mortality by gender, age and causes of death in France, with a special emphasis on people aged 75 years and more.</p> <p>Methods</p> <p>We used data from a longitudinal population sample that includes 1% of the French population. Risk of death (total and cause specific) in the period 1990-1999 according to education was analysed using Cox regression models by age group (45-59, 60-74, and 75+). Inequalities were quantified using both relative (ratio) and absolute (difference) measures.</p> <p>Results</p> <p>Relative inequalities decreased with age but were still observed in the oldest age group. Absolute inequalities increased with age. This increase was particularly pronounced for cardiovascular diseases. The contribution of different causes of death to absolute inequalities in total mortality differed between age groups. In particular, the contribution of cancer deaths decreased substantially between the age groups 60-74 years and 75 years and more, both in men and in women.</p> <p>Conclusions</p> <p>This study suggests that the large contribution of cancer deaths to the excess mortality among low educated people that was observed among middle aged men in Latin Europe is not observed among French people aged 75 years and more. This should be confirmed among other Latin Europe countries.</p

Factors associated with tocolytic hospitalizations in Taiwan: evidence from a population-based and longitudinal study from 1997 to 2004

<p>Abstract</p> <p>Background</p> <p>The use of tocolytic hospitalization in antenatal care is controversial and worthy of more research. We investigated individual, institutional, and area factors that affect the use of tocolytic hospitalizations in Taiwan where fertility has rapidly declined.</p> <p>Methods</p> <p>Longitudinal data from the 1996 to 2004 National Health Insurance Research Database in Taiwan were used to identify tocolytic hospitalizations. The probit model was used to estimate factors associated with tocolytic hospitalizations.</p> <p>Results</p> <p>The decline in fertility was significantly associated with the probability of tocolytic hospitalizations. Several physician and institutional factors-including physician's age, hospital ownership, accreditation status, bed size, and teaching status-were also significantly correlated to the dependent variables.</p> <p>Conclusions</p> <p>The provision of inpatient tocolysis is influenced not only by clinical considerations but also by physician, institutional, and area factors unrelated to clinical need. Fertility declines in Taiwan may have led obstetricians/gynecologists to provide more tocolysis to make up for their lost income. If the explanation is further validated, reimbursement policies may need to be reviewed to correct for overuse of inpatient tocolysis. The correlation could also be explained by the increasing use of artificial reproductive technologies and higher social value of newborns. In addition, the physician and institutional variations observed in the study indicate potential misuse of inpatient tocolysis that warrant further investigation.</p

Demographic routes to variability and regulation in bird populations

There is large interspecific variation in the magnitude of population fluctuations, even among closely related species. The factors generating this variation are not well understood, primarily because of the challenges of separating the relative impact of variation in population size from fluctuations in the environment. Here, we show using demographic data from 13 bird populations that magnitudes of fluctuations in population size are mainly driven by stochastic fluctuations in the environment. Regulation towards an equilibrium population size occurs through density-dependent mortality. At small population sizes, population dynamics are primarily driven by environment-driven variation in recruitment, whereas close to the carrying capacity K, variation in population growth is more strongly influenced by density-dependent mortality of both juveniles and adults. Our results provide evidence for the hypothesis proposed by Lack that population fluctuations in birds arise from temporal variation in the difference between density-independent recruitment and density-dependent mortality during the non-breeding season