bluuebunny/crossref_metadata_2025_split huggingface dataset:
Newly evolved introns in human retrogenes provide novel insights into their evolutionary roles
Authors: Kang Li-Fang , Zhu Zheng-Lin , Zhao Qian , Chen Li-Yong , Zhang Ze 
Published: July 2012

Abstract

Background
Retrogenes generally do not contain introns. However, in some instances, retrogenes may recruit internal exonic sequences as introns, which is known as intronization. A retrogene that undergoes intronization is a good model with which to investigate the origin of introns. Nevertheless, previously, only two cases in vertebrates have been reported.

Results
In this study, we systematically screened the human (Homo sapiens) genome for retrogenes that evolved introns and analyzed their patterns in structure, expression and origin. In total, we identified nine intron-containing retrogenes. Alignment of pairs of retrogenes and their parents indicated that, in addition to intronization (five cases), retrogenes also may have gained introns by insertion of external sequences into the genes (one case) or reversal of the orientation of transcription (three cases). Interestingly, many intronizations were promoted not by base substitutions but by cryptic splice sites, which were silent in the parental genes but active in the retrogenes. We also observed that the majority of introns generated by intronization did not involve frameshifts.

Conclusions
Intron gains in retrogenes are not as rare as previously thought. Furthermore, diverse mechanisms may lead to intron creation in retrogenes. The activation of cryptic splice sites in the intronization of retrogenes may be triggered by the change of gene structure after retroposition. A high percentage of non-frameshift introns in retrogenes may be because non-frameshift introns do not dramatically affect host proteins. Introns generated by intronization in human retrogenes are generally young, which is consistent with previous findings for Caenorhabditis elegans. Our results provide novel insights into the evolutionary role of introns.
Analysis of lead toxicity in human cells
Authors: Gillis Bruce S , Arbieva Zarema , Gavin Igor M 
Published: July 2012

AbstractBackgroundLead is a metal with many recognized adverse health side effects, and yet the molecular processes underlying lead toxicity are still poorly understood. Quantifying the injurious effects of lead is also difficult because of the diagnostic limitations that exist when analyzing human blood and urine specimens for lead toxicity.ResultsWe analyzed the deleterious impact of lead on human cells by measuring its effects on cytokine production and gene expression in peripheral blood mononuclear cells. Lead activates the secretion of the chemokine IL-8 and impacts mitogen-dependent activation by increasing the secretion of the proinflammatory cytokines IL-6 and TNF-α and of the chemokines IL-8 and MIP1-α in the presence of phytohemagglutinin. The recorded changes in gene expression affected major cellular functions, including metallothionein expression, and the expression of cellular metabolic enzymes and protein kinase activity. The expression of 31 genes remained elevated after the removal of lead from the testing medium thereby allowing for the measurement of adverse health effects of lead poisoning. These included thirteen metallothionein transcripts, three endothelial receptor B transcripts and a number of transcripts which encode cellular metabolic enzymes. Cellular responses to lead correlated with blood lead levels and were significantly altered in individuals with higher lead content resultantly affecting the nervous system, the negative regulation of transcription and the induction of apoptosis. In addition, we identified changes in gene expression in individuals with elevated zinc protoporphyrin blood levels and found that genes regulating the transmission of nerve impulses were affected in these individuals. The affected pathways were G-protein mediated signaling, gap junction signaling, synaptic long-term potentiation, neuropathic pain signaling as well as CREB signaling in neurons. Cellular responses to lead were altered in subjects with high zinc protoporphyrin blood levels.ConclusionsThe results of our study defined specific changes in gene and protein expression in response to lead challenges and determined the injurious effects of exposures to lead on a cellular level. This information can be used for documenting the health effects of exposures to lead which will facilitate identifying and monitoring efficacious treatments for lead-related maladies.
Evidence of an increased pathogenic footprint in the lingual microbiome of untreated HIV infected patients
Authors: Dang Angeline T , Cotton Sean , Sankaran-Walters Sumathi , Li Chin-Shang , Lee Chia-Yuan Michael , Dandekar Satya , Paster Bruce J , George Michael D 
Published: July 2012

AbstractBackgroundOpportunistic oral infections can be found in over 80% of HIV + patients, often causing debilitating lesions that also contribute to deterioration in nutritional health. Although appreciation for the role that the microbiota is likely to play in the initiation and/or enhancement of oral infections has grown considerably in recent years, little is known about the impact of HIV infection on host-microbe interactions within the oral cavity. In the current study, we characterize modulations in the bacterial composition of the lingual microbiome in patients with treated and untreated HIV infection. Bacterial species profiles were elucidated by microarray assay and compared between untreated HIV infected patients, HIV infected patients receiving antiretroviral therapy, and healthy HIV negative controls. The relationship between clinical parameters (viral burden and CD4+ T cell depletion) and the loss or gain of bacterial species was evaluated in each HIV patient group.ResultsIn untreated HIV infection, elevated viremia was associated with significantly higher proportions of potentially pathogenicVeillonella,Prevotella,Megasphaera, andCampylobacterspecies in the lingual microbiome than observed in healthy controls. The upsurge in the prevalence of potential pathogens was juxtaposed by diminished representation of commensalStreptococcusandVeillonellaspecies. Colonization ofNeisseria flavescenswas lower in the lingual microbiome of HIV infected patients receiving antiretroviral therapy than in uninfected controls.ConclusionsOur findings provide novel insights into the potential impact of HIV infection and antiretroviral therapy on the community structure of the oral microbiome, and implicate potential mechanisms that may increase the capacity of non-commensal species to gain a stronger foothold.
miRNA regulation in the early development of barley seed
Authors: Curaba Julien , Spriggs Andrew , Taylor Jen , Li Zhongyi , Helliwell Chris 
Published: July 2012

Abstract

Background
During the early stages of seed development many genes are under dynamic regulation to ensure the proper differentiation and establishment of the tissue that will constitute the mature grain. To investigate how miRNA regulation contributes to this process in barley, a combination of small RNA and mRNA degradome analyses were used to identify miRNAs and their targets.

Results
Our analysis identified 84 known miRNAs and 7 new miRNAs together with 96 putative miRNA target genes regulated through a slicing mechanism in grain tissues during the first 15 days post anthesis. We also identified many potential miRNAs including several belonging to known miRNA families. Our data gave us evidence for an increase in miRNA-mediated regulation during the transition between pre-storage and storage phases. Potential miRNA targets were found in various signalling pathways including components of four phytohormone pathways (ABA, GA, auxin, ethylene) and the defence response to powdery mildew infection. Among the putative miRNA targets we identified were two essential genes controlling the GA response, a GA3oxidase1 and a homolog of the receptor GID1, and a homolog of the ACC oxidase which catalyses the last step of ethylene biosynthesis. We found that two MLA genes are potentially miRNA regulated, establishing a direct link between miRNAs and the R gene response.

Conclusion
Our dataset provides a useful source of information on miRNA regulation during the early development of cereal grains and our analysis suggests that miRNAs contribute to the control of development of the cereal grain, notably through the regulation of phytohormone response pathways.
Plasmodium vivax malaria relapses at a travel medicine centre in Rio de Janeiro, a non-endemic area in Brazil
Authors: Pedro Renata S , Guaraldo Lusiele , Campos Dayse P , Costa Anielle P , Daniel-Ribeiro Cláudio T , Brasil Patrícia 
Published: July 2012

Abstract

Background
Malaria is a potentially severe disease widely distributed in tropical and subtropical regions worldwide. Clinically, the progression of the disease can be life-threatening if it is not promptly diagnosed and properly treated. Through treatment, the radical cure of Plasmodium vivax infection can be achieved, thus preventing potential relapses and the emergence of new cases outside the Amazon region in Brazil. Surveillance for therapeutic failure in non-endemic areas is advantageous, as it is unlikely that recurrence of the disease can be attributed to a new malaria infection in these regions.

Methods
An observational study of 53 cases of P. vivax and mixed (P. vivax and Plasmodium falciparum) malaria was conducted at a travel medicine centre between 2005 and 2011 in Rio de Janeiro and a descriptive analysis of the potential factors related to recurrence of P. vivax malaria was performed. Groups with different therapeutic responses were compared using survival analysis based on the length of time to recurrence and a set of independent variables thought to be associated with recurrence.

Results
Twenty-one relapses (39.6%) of P. vivax malaria were observed. The overall median time to relapse, obtained by the Kaplan-Meier method, was 108 days, and the survival analysis demonstrated an association between non-weight-adjusted primaquine dosing and the occurrence of relapse (p < 0.03). Primaquine total dose at 3.6 mg/kg gave improved results in preventing relapses.

Conclusions
A known challenge to individual cure and environmental control of malaria is the possibility of an inappropriate, non-weight-based primaquine dosing, which should be considered a potential cause of P. vivax malaria relapse. Indeed, the total dose of primaquine associated with non-occurrence of relapses was higher than recommended by Brazilian guidelines.
Parental stress when caring for a child with cancer in Jordan: a cross-sectional survey
Authors: Masa’Deh Rami , Collier Jacqueline , Hall Carol 
Published: July 2012

Abstract

Background
Most studies report that being parents of a child with cancer is a stressful experience, but these have tended to focus on mothers and few have included both parents. Moreover, studies have focussed on families in Western countries and none have been published examining the psychological outcomes for parents living in an Arabic country.
This research explores the stress levels of Jordanian parents caring for a child with cancer in order to identify the psychological needs of parents in this environment and to explore how mothers and fathers stress levels might differ.

Methods
The study was carried out in Jordan using the Perceived Stress Scale 10-items (PSS10). The questionnaire was completed by 300 couples with a child who has cancer and a comparison group of 528 couples where the children do not have any serious illness. Multivariate backward regression analysis was carried out.

Results
Analysis adjusting for spousal stress and sociodemographic predictors revealed that stress levels of mothers with a child who had cancer remained significantly higher than mothers whose children did not have any serious illness (p < 0.001). However, having a child with cancer did not show a significant association with the fathers’ reported stress scores (p = 0.476) when spousal stress was in the model, but was highly significant once that was removed (p < 0.001).
Parental stress was analysed for those with a child who has cancer and in models which included spouse’s stress scores, sociodemographic and cancer-related predictors 64 % of the variance was explained for mothers (adjusted R2 = 0.64, p < 0.001) and fathers (adjusted R2 = 0.64, p < 0.001). Models excluding spousal stress scores explained just 26 % of the variance for fathers and 22 % for mothers.

Conclusions
This is the first study into the psychological outcomes for parents living in an Arabic country who care for a child with cancer. Both mothers and fathers with a child diagnosed with cancer reported higher stress levels than those from the normal Jordanian parent population. Mothers and fathers of children with cancer reported significantly different levels of stress to each other but models reveal significant contributions of the stress score of fathers upon mothers, and vice versa. The findings provide evidence of the need for psychological support to be developed for families caring for a child with cancer in Jordan.
Sport and exercise medicine and the Olympic health legacy
Authors: Tew Garry A , Copeland Robert J , Till Simon H 
Published: July 2012

Abstract
London 2012 is the first Olympic and Paralympic Games to explicitly try and develop socioeconomic legacies for which success indicators are specified - the highest profile of which was to deliver a health legacy by getting two million more people more active by 2012. This editorial highlights how specialists in Sport and Exercise Medicine can contribute towards increasing physical activity participation in the UK, as well as how the National Centre for Sport and Exercise Medicine might be a useful vehicle for delivering an Olympic health legacy. Key challenges are also discussed such as acquisition of funding to support new physical activity initiatives, appropriate allocation of resources, and how to assess the impact of legacy initiatives.
Phosphatase PPM1A negatively regulates P-TEFb function in resting CD4+ T cells and inhibits HIV-1 gene expression
Authors: Budhiraja Sona , Ramakrishnan Rajesh , Rice Andrew P 
Published: July 2012

AbstractBackgroundProcessive elongation of the integrated HIV-1 provirus is dependent on recruitment of P-TEFb by the viral Tat protein to the viral TAR RNA element. P-TEFb kinase activity requires phosphorylation of Thr186 in the T-loop of the CDK9 subunit. In resting CD4+T cells, low levels of T-loop phosphorylated CDK9 are found, which increase significantly upon activation. This suggests that the phosphorylation status of the T-loop is actively regulated through the concerted actions of cellular proteins such as Ser/Thr phosphatases. We investigated the role of phosphatase PPM1A in regulating CDK9 T-loop phosphorylation and its effect on HIV-1 proviral transcription.ResultsWe found that overexpression of PPM1A inhibits HIV-1 gene expression during viral infection and this required PPM1A catalytic function. Using an artificial CDK tethering system, we further found that PPM1A inhibits CDK9, but not CDK8 mediated activation of the HIV-1 LTR. SiRNA depletion of PPM1A in resting CD4+T cells increased the level of CDK9 T-loop phosphorylation and enhanced HIV-1 gene expression. We also observed that PPM1A protein levels are relatively high in resting CD4+T cells and are not up-regulated upon T cell activation.ConclusionsOur results establish a functional link between HIV-1 replication and modulation of CDK9 T-loop phosphorylation by PPM1A. PPM1A represses HIV-1 gene expression by inhibiting CDK9 T-loop phosphorylation, thus reducing the amount of active P-TEFb available for recruitment to the viral LTR. We also infer that PPM1A enzymatic activity in resting and activated CD4+T cells are likely regulated by as yet undefined factors.
Predicted HIV-1 coreceptor usage among Kenya patients shows a high tendency for subtype d to be cxcr4 tropic
Authors: Wambui Veronica , Kiptoo Michael , Kinyua Joyceline , Odera Irene , Muge Edward , Muiruri Peter , Lihana Raphael , Kinyanjui Peter , Songok Elijah M 
Published: July 2012

AbstractBackgroundCCR5 antagonists have clinically been approved for prevention or treatment of HIV/AIDS. Countries in Sub-Saharan Africa with the highest burden of HIV/AIDS are due to adopt these regimens. However, HIV-1 can also use CXCR4 as a co-receptor. There is hence an urgent need to map out cellular tropism of a country’s circulating HIV strains to guide the impending use of CCR5 antagonists.ObjectivesTo determine HIV-1 coreceptor usage among patients attending a comprehensive care centre in Nairobi, Kenya.MethodsBlood samples were obtained from HIV infected patients attending the comprehensive care centre, Kenyatta National Hospital in years 2008 and 2009. The samples were separated into plasma and peripheral blood mononuclear cells (PBMCs). Proviral DNA was extracted from PBMCs and Polymerase Chain reaction (PCR) done to amplify the HIVenvfragment spanning the C2-V3 region. The resultant fragment was directly sequenced on an automated sequencer (ABI, 3100). Co-receptor prediction of theenvsequences was done using Geno2pheno[co-receptor], and phylogenetic relationships determined using CLUSTALW and Neighbor Joining method.ResultsA total of 67 samples (46 treatment experienced and 21 treatment naive) were successfully amplified and sequenced. Forty nine (73%) sequences showed a prediction for R5 tropism while 18(27%) were X4 tropic. Phylogenetic analysis showed that 46(69%) were subtype A, 11(16%) subtype C, and 10(15%) subtype D. No statistical significant associations were observed between cell tropism and CD4+ status, patient gender, age, or treatment option. There was a tendency for more X4 tropic strains being in the treatment experienced group than the naive group: Of 46 treatment experiencing participants, 14(30%) harboured X4, compared with 4(19%) of 21 of the treatment-naïve participants, the association is however not statistically significant (p = 0.31). However, a strong association was observed between subtype D and CXCR4 co- receptor usage (p = 0.015) with 6(60%) of the 10 subtype D being X4 tropic and 4(40%) R5 tropic.ConclusionHIV-1 R5 tropic strains were the most prevalent in the study population and HIV infected patients in Kenya may benefit from CCR5 antagonists. However, there is need for caution where subtype D infection is suspected or where antiretroviral salvage therapy is indicated.
Acute Cold Hypersensitivity Characteristically Induced by Oxaliplatin is Caused by the Enhanced Responsiveness of TRPA1 in Mice
Authors: Zhao Meng , Isami Kouichi , Nakamura Saki , Shirakawa Hisashi , Nakagawa Takayuki , Kaneko Shuji 
Published: July 2012

Background: Oxaliplatin, a platinum-based chemotherapeutic agent, causes an unusual acute peripheral neuropathy. Oxaliplatin-induced acute peripheral neuropathy appears in almost all patients rapidly after infusion, and is triggered or exacerbated by cold, while its mechanisms are poorly understood. In this study, the involvement of thermosensitive transient receptor potential channels (TRPA1, TRPM8 and TRPV1) in oxaliplatin-induced acute hypersensitivity was investigated in mice. Results: A single intraperitoneal administration of oxaliplatin (1–10 mg/kg) induced cold but not mechanical hypersensitivity within 2 h in a dose-dependent manner. Infusion of the oxaliplatin metabolite, oxalate (1.7 mg/kg), also induced acute cold hypersensitivity, while another platinum-based chemotherapeutic agent, cisplatin (5 mg/kg), or the non-platinum-containing chemotherapeutic agent, paclitaxel (6 mg/kg) failed to induce mechanical or cold hypersensitivity. The oxaliplatin-induced acute cold hypersensitivity was abolished by the TRPA1 antagonist HC-030031 (100 mg/kg) and by TRPA1 deficiency. The nocifensive behaviors evoked by intraplantar injections of allyl-isothiocyanate (AITC; TRPA1 agonist) were significantly enhanced in mice treated for 2 h with oxaliplatin (1–10 mg/kg) in a dose-dependent manner, while capsaicin (TRPV1 agonist)-evoked nocifensive behaviors were not affected. Menthol (TRPM8/TRPA1 agonist)-evoked nocifensive-like behaviors were also enhanced by oxaliplatin pretreatment, which were inhibited by TRPA1 deficiency. Similarly, oxalate enhanced, but neither cisplatin nor paclitaxel affected AITC-evoked nocifensive behaviors. Pretreatment of cultured mouse dorsal root ganglia (DRG) neurons with oxaliplatin (30–300 μM) for 1, 2, or 4 h significantly increased the number of AITC-sensitive neurons in a concentration-dependent manner whereas there was no change in the number of menthol- or capsaicin-sensitive neurons. Conclusions: Taken together, these results suggest that a brief treatment with oxaliplatin or its metabolite oxalate is sufficient to enhance the responsiveness of TRPA1 but not that of TRPM8 and TRPV1 expressed by DRG neurons, which may contribute to the characteristic acute peripheral neuropathy induced by oxaliplatin.
Seed storage proteins of the globulin family are cleaved post-translationally in wheat embryos
Authors: Koziol Adam G , Loit Evelin , McNulty Melissa , MacFarlane Amanda J , Scott Fraser W , Altosaar Illimar 
Published: July 2012

AbstractBackgroundThe 7S globulins are plant seed storage proteins that have been associated with the development of a number of human diseases, including peanut allergy. Immune reactivity to the wheat seed storage protein globulin-3 (Glo-3) has been associated with the development of the autoimmune disease type 1 diabetes in diabetes-prone rats and mice, as well as in a subset of human patients.FindingsThe present study characterized native wheat Glo-3 in salt-soluble wheat seed protein extracts. Glo-3-like peptides were observed primarily in the wheat embryo. Glo-3-like proteins varied significantly in their molecular masses and isoelectric points, as determined by two dimensional electrophoresis and immunoblotting with anti-Glo-3A antibodies. Five major polypeptide spots were identified by mass spectrometry and N-terminal sequencing as belonging to the Glo-3 family.ConclusionsThese results in combination with our previous findings have allowed for the development of a hypothetical model of the post-translational events contributing to the wheat 7S globulin profile in mature wheat kernels.
Does Beta-lactam Pharmacokinetic Variability in Critically Ill Patients Justify Therapeutic Drug Monitoring? A Systematic Review
Authors: Sime Fekade Bruck , Roberts Michael S , Peake Sandra L , Lipman Jeffrey , Roberts Jason A 
Published: July 2012

Abstract
The pharmacokinetics of beta-lactam antibiotics in intensive care patients may be profoundly altered due to the dynamic, unpredictable pathophysiological changes that occur in critical illness. For many drugs, significant increases in the volume of distribution and/or variability in drug clearance are common. When “standard” beta-lactam doses are used, such pharmacokinetic changes can result in subtherapeutic plasma concentrations, treatment failure, and the development of antibiotic resistance. Emerging data support the use of beta-lactam therapeutic drug monitoring (TDM) and individualized dosing to ensure the achievement of pharmacodynamic targets associated with rapid bacterial killing and optimal clinical outcomes. The purpose of this work was to describe the pharmacokinetic variability of beta-lactams in the critically ill and to discuss the potential utility of TDM to optimize antibiotic therapy through a structured literature review of all relevant publications between 1946 and October 2011. Only a few studies have reported the utility of TDM as a tool to improve beta-lactam dosing in critically ill patients. Moreover, there is little agreement between studies on the pharmacodynamic targets required to optimize antibiotic therapy. The impact of TDM on important clinical outcomes also remains to be established. Whereas TDM may be theoretically rational, clinical studies to assess utility in the clinical setting are urgently required.