bluuebunny/crossref_metadata_2025 huggingface dataset:
Access to HIV/AIDS care: a systematic review of socio-cultural determinants in low and high income countries
Authors: Gari Sara , Doig-Acuña Camilo , Smail Tino , Malungo Jacob RS , Martin-Hilber Adriane , Merten Sonja
Published: May 2013

Background

The role of socio-cultural factors in influencing access to HIV/AIDS treatment, care and support is increasingly recognized by researchers, international donors and policy makers. Although many of them have been identified through qualitative studies, the evidence gathered by quantitative studies has not been systematically analysed. To fill this knowledge gap, we did a systematic review of quantitative studies comparing surveys done in high and low income countries to assess the extent to which socio-cultural determinants of access, identified through qualitative studies, have been addressed in epidemiological survey studies.

Methods

Ten electronic databases were searched (Cinahl, EMBASE, ISI Web of Science, IBSS, JSTOR, MedLine, Psyinfo, Psyindex and Cochrane). Two independent reviewers selected eligible publications based on the inclusion/exclusion criteria. Meta-analysis was used to synthesize data comparing studies between low and high income countries.

Results

Thirty-four studies were included in the final review, 21 (62%) done in high income countries and 13 (38%) in low income countries. In low income settings, epidemiological research on access to HIV/AIDS services focused on socio-economic and health system factors while in high income countries the focus was on medical and psychosocial factors. These differences depict the perceived different barriers in the two regions. Common factors between the two regions were also found to affect HIV testing, including stigma, high risk sexual behaviours such as multiple sexual partners and not using condoms, and alcohol abuse. On the other hand, having experienced previous illness or other health conditions and good family communication was associated with adherence to ART uptake. Due to insufficient consistent data, a meta-analysis was only possible on adherence to treatment.

Conclusions

This review offers evidence of the current challenges for interdisciplinary work in epidemiology and public health. Quantitative studies did not systematically address in their surveys important factors identified in qualitative studies as playing a critical role on the access to HIV/AIDS services. The evidences suggest that the problem lies in the exclusion of the qualitative information during the questionnaire design. With the changing face of the epidemic, we need a new and improved research strategy that integrates the results of qualitative studies into quantitative surveys.
Replicating DNA by cell factories: roles of central carbon metabolism and transcription in the control of DNA replication in microbes, and implications for understanding this process in human cells
Authors: Barańska Sylwia , Glinkowska Monika , Herman-Antosiewicz Anna , Maciąg-Dorszyńska Monika , Nowicki Dariusz , Szalewska-Pałasz Agnieszka , Węgrzyn Alicja , Węgrzyn Grzegorz
Published: May 2013

Precise regulation of DNA replication is necessary to ensure the inheritance of genetic features by daughter cells after each cell division. Therefore, determining how the regulatory processes operate to control DNA replication is crucial to our understanding and application to biotechnological processes. Contrary to early concepts of DNA replication, it appears that this process is operated by large, stationary nucleoprotein complexes, called replication factories, rather than by single enzymes trafficking along template molecules. Recent discoveries indicated that in bacterial cells two processes, central carbon metabolism (CCM) and transcription, significantly and specifically influence the control of DNA replication of various replicons. The impact of these discoveries on our understanding of the regulation of DNA synthesis is discussed in this review. It appears that CCM may influence DNA replication by either action of specific metabolites or moonlighting activities of some enzymes involved in this metabolic pathway. The role of transcription in the control of DNA replication may arise from either topological changes in nucleic acids which accompany RNA synthesis or direct interactions between replication and transcription machineries. Due to intriguing similarities between some prokaryotic and eukaryotic regulatory systems, possible implications of studies on regulation of microbial DNA replication on understanding such a process occurring in human cells are discussed.
Metabolic engineering for high yielding L(-)-carnitine production in Escherichia coli
Authors: Arense Paula , Bernal Vicente , Charlier Daniël , Iborra José Luis , Foulquié-Moreno Maria Remedios , Cánovas Manuel
Published: May 2013

Background

L(-)-carnitine production has been widely studied because of its beneficial properties on various diseases and dysfunctions. Enterobacteria possess a specific biotransformation pathway which can be used for the enantioselective production of L(-)-carnitine. Although bioprocesses catalyzed by enzymes or whole cells can overcome the lack of enantioselectivity of chemical methods, current processes for L(−)-carnitine production still have severe disadvantages, such as the low yields, side reactions and the need of high catalyst concentrations and anaerobic conditions for proper expression of the biotransformation pathway. Additionally, genetically engineered strains so far constructed for L(-)-carnitine production are based on plasmids and, therefore, suffer from segregational unstability.

Results

In this work, a stable, high yielding strain for L(-)-carnitine production from low cost substrates was constructed. A metabolic engineering strategy was implemented in a multiple mutant for use in both growing and resting cells systems. The effect of mutations on gene expression and metabolism was analyzed to characterize the productivity constraints of the wild type and the overproducer strains. Precise deletion of genes which encode proteins of central and carnitine metabolisms were performed. Specifically, flux through the TCA cycle was increased by deletion ofaceK(which encodes a bifunctional kinase/phosphatase which inhibits isocitrate dehydrogenase activity) and the synthesis of the by-product γ-butyrobetaine was prevented by deletion ofcaiA(which encodes a crotonobetainyl-CoA reductase). Both mutations led to improve the L(-)-carnitine production by 20 and 42%, respectively. Moreover, the highly regulated promoter of thecaioperon was substituted by a constitutive artificial promoter increasing the biotransformation rate, even under aerobic conditions. Resting cells of the BW ΔaceKΔcaiAp37caistrain produced 59.6 mmol l-1 · h-1of L(−)-carnitine, doubling the productivity of the wild type strain. In addition, almost total conversion was attained in less than two hours without concomitant production of the side product γ–butyrobetaine.

Conclusions

L(-)-carnitine production has been enhanced by strain engineering. Metabolic engineering strategies herein implemented allowed obtaining a robust and high yieldingE. colistrain. The new overproducer strain attained almost complete conversion of crotonobetaine into L(-)-carnitine with growing and resting cells, and even under aerobic conditions, overcoming the main environmental restriction to carnitine metabolism expression. So far, this is the best performing L(-)-carnitine productionE. colistrain described.
An improved level set method for vertebra CT image segmentation
Authors: Huang Juying , Jian Fengzeng , Wu Hao , Li Haiyun
Published: May 2013

Background

Clinical diagnosis and therapy for the lumbar disc herniation requires accurate vertebra segmentation. The complex anatomical structure and the degenerative deformations of the vertebrae makes its segmentation challenging.

Methods

An improved level set method, namely edge- and region-based level set method (ERBLS), is proposed for vertebra CT images segmentation. By considering the gradient information and local region characteristics of images, the proposed model can efficiently segment images with intensity inhomogeneity and blurry or discontinuous boundaries. To reduce the dependency on manual initialization in many active contour models and for an automatic segmentation, a simple initialization method for the level set function is built, which utilizes the Otsu threshold. In addition, the need of the costly re-initialization procedure is completely eliminated.

Results

Experimental results on both synthetic and real images demonstrated that the proposed ERBLS model is very robust and efficient. Compared with the well-known local binary fitting (LBF) model, our method is much more computationally efficient and much less sensitive to the initial contour. The proposed method has also applied to 56 patient data sets and produced very promising results.

Conclusions

An improved level set method suitable for vertebra CT images segmentation is proposed. It has the flexibility of segmenting the vertebra CT images with blurry or discontinuous edges, internal inhomogeneity and no need of re-initialization.
The financial burden of juvenile idiopathic arthritis: a Nova Scotia experience
Authors: Ens Andrea , Lang Bianca , Ramsey Suzanne , Stringer Elizabeth , Huber Adam M
Published: May 2013

Background

Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic illness. There is little published data on the financial burden of this illness. The primary objective of this study was to determine the annual costs borne by families of a child with JIA living in Nova Scotia (NS).

Methods

All families in NS with a child followed in the Pediatric Rheumatology Clinic at the Izaak Walton Killam Health Centre (IWK) in 2009 were mailed a self-report questionnaire. The questionnaire evaluated disease related costs, gross household income and perceived financial burden. Dillman's method was used to optimize return rates. Descriptive statistics were used to summarize results. Spearman’s correlation coefficient was used to assess the relationship of distance from the IWK and cost. The Mann–Whitney U test was used to compare median costs between groups.

Results

Of 172 possible respondents, we received 54 completed questionnaires and 11 blank questionnaires (overall response rate 31.4%). Approximately one third (35.9%) of parents rated the financial burden as moderate or large and 36% rated financial resources available as poor. The median annual total cost per patient was $619.50 CAD (range 0, $5535) which was a median 0.7% (range 0, 37%) of gross household incomes. The largest expense for families was visit related costs. There was not a significant relationship between total annual costs and distance from the IWK (rs = 0.18, P = 0.2). Families of a child with oligoarthritis had significantly lower costs than the families of a child with another subtype of JIA ($359.00 CAD vs. $877.00 CAD, P = 0.02).

Conclusions

The costs associated with having a child with JIA in NS are on average modest, but may be considerable for some families. Oligoarticular JIA is associated with smaller costs. Many families perceive the burden to be at least moderate and the availability of financial resources to be poor. Supports should be targeted to those families most in need.
A phase II trial of neoadjuvant IMRT-based chemoradiotherapy followed by one cycle of capecitabine for stage II/III rectal adenocarcinoma
Authors: Zhu Ji , Gu Weilie , Lian Peng , Sheng Weiqi , Cai Gang , Shi Debing , Cai Sanjun , Zhang Zhen
Published: May 2013

Purpose

Neoadjuvant chemoradiation has become the standard treatment in locally advanced rectal cancer (LARC) and improves local control. This study explored the feasibility of an intensified chemoradiation treatment followed by one cycle of capecitabine before surgery for LARC.

Methods and materials

Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received intensity-modulated radiation therapy (IMRT) to the pelvis (total dose 44 Gy in 20 fractions), as well as concurrent oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 b.i.d. d1–5 weekly). One cycle of capecitabine (1000 mg/m2 b.i.d. d1–14) was given two weeks after the completion of concomitant chemoradiation, and radical surgery was scheduled six weeks after chemoradiation.

Results

Between October 2007 and November 2008, a total of 42 patients were enrolled in the study (median age 51 years; 31 male). Of these, 38 underwent surgical resection and 4 refused radical surgery because of almost complete primary tumor regression and complete symptom relief after neoadjuvant therapy. Fifteen patients underwent sphincter-sparing lower anterior resection. Six patients had a pathological complete response (pCR). The incidence of grade 3 hematologic, gastro-intestinal, and skin toxicities were 4.7%, 14.3%, and 26.2%, respectively. Grade 4 toxicity was not observed. Surgical complications (incisional infection within 2–3 weeks after surgery) were observed in 5 patients. Good responders (defined as TRG 3–4) had a significant difference in DFS (81.6% vs. 16.8%, respectively; p = 0.000) and OS (83.9% vs. 40.7%, respectively; p = 0.007) compared to those who were evaluated as TRG 1–2.

Conclusions

Our study indicates that neoadjuvant chemoradiation followed by one cycle of capecitabine before surgery has a good treatment efficacy, with only mild toxicities associated with chemoradiation and acceptable surgical complications. Treatment response was an early surrogate marker and correlated to oncologic prognosis.
[18F]Fluorodeoxyglucose accumulation as a biological marker of hypoxic status but not glucose transport ability in gastric cancer
Authors: Takebayashi Ryusuke , Izuishi Kunihiko , Yamamoto Yuka , Kameyama Reiko , Mori Hirohito , Masaki Tsutomu , Suzuki Yasuyuki
Published: May 2013

Background

The use of [18F] 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for detection of gastric cancer is often debated because FDG uptake varies for each patient. The purpose of this study was to clarify the molecular mechanisms involved in FDG uptake.

Material and methods

Fifty patients with gastric cancer who underwent FDG-PET and gastrectomy were studied. Snap-frozen tumor specimens were collected and examined by real-time PCR for relationships between maximum standardized uptake value (SUV) and mRNA expression of the following genes: glucose transporter 1 (GLUT1), hexokinase 2 (HK2), hypoxia-inducible factor 1α (HIF1α), and proliferating cell nuclear antigen (PCNA).

Results

Tumor size was the only clinicopathological parameter that significantly correlated with SUV. Transcripts for the genes evaluated were about three-fold higher in malignant specimens than in normal mucosa, although only HIF1α was significantly correlated with SUV. When divided into intestinal and non-intestinal tumors, there was a significant correlation between SUV and tumor size in intestinal tumors. Interestingly, the weak association between SUV and HIF1α expression in intestinal tumors was substantially stronger in non-intestinal tumors. No correlation was found between SUV and mRNA expression of other genes in intestinal or non-intestinal tumors.

Conclusion

SUV was correlated with HIF1α, but not PCNA, HK2, or GLUT1 expression. FDG accumulation could therefore represent tissue hypoxia rather than glucose transport activity for aggressive cancer growth.
WikiPathways for plants: a community pathway curation portal and a case study in rice and arabidopsis seed development networks
Authors: Hanumappa Mamatha , Preece Justin , Elser Justin , Nemeth Denise , Bono Gina , Wu Kenny , Jaiswal Pankaj
Published: May 2013

Background

Next-generation sequencing and ‘omics’ platforms are used extensively in plant biology research to unravel new genomes and study their interactions with abiotic and biotic agents in the growth environment. Despite the availability of a large and growing number of genomic data sets, there are only limited resources providing highly-curated and up-to-date metabolic and regulatory networks for plant pathways.

Results

Using PathVisio, a pathway editor tool associated with WikiPathways, we created a gene interaction network of 430 rice (Oryza sativa) genes involved in the seed development process by curating interactions reported in the published literature. We then applied an InParanoid-based homology search to these genes and used the resulting gene clusters to identify 351 Arabidopsis thaliana genes. Using this list of homologous genes, we constructed a seed development network in Arabidopsis by processing the gene list and the rice network through a Perl utility software called Pathway GeneSWAPPER developed by us. In order to demonstrate the utility of these networks in generating testable hypotheses and preliminary analysis prior to more in-depth downstream analysis, we used the expression viewer and statistical analysis features of PathVisio to analyze publicly-available and published microarray gene expression data sets on diurnal photoperiod response and the seed development time course to discover patterns of coexpressed genes found in the rice and Arabidopsis seed development networks. These seed development networks described herein, along with other plant pathways and networks, are freely available on the plant pathways portal at WikiPathways (http://plants.wikipathways.org).

Conclusion

In collaboration with the WikiPathways project we present a community curation and analysis platform for plant biologists where registered users can freely create, edit, share and monitor pathways supported by published literature. We describe the curation and annotation of a seed development network in rice, and the projection of a similar, gene homology-based network in Arabidopsis. We also demonstrate the utility of the Pathway GeneSWAPPER (PGS) application in saving valuable time and labor when a reference network in one species compiled in GPML format is used to project a similar network in another species based on gene homology.
Comparative amino acid decomposition analysis of potent type I p38α inhibitors
Authors: Ebadi Ahmad , Razzaghi-Asl Nima , Khoshneviszadeh Mehdi , Miri Ramin
Published: May 2013

Background and purpose of the study

p38α is a member of mitogen-activated protein kinases (MAPK) considered as a prominent target in development of anti-inflammatory agents. Any abnormality in the phosphorylation process leads to the different human diseases such as cancer, diabetes and inflammatory diseases. Several small molecule p38α inhibitors have been developed up to now. In this regard, structural elucidation of p38 inhibitors needs to be done enabling us in rational lead development strategies.

Methods

Various interactions of three potent inhibitors with p38α active site have been evaluated in terms of binding energies and bond lengths via density function theory and MD simulations.

Results

Our comparative study showed that bothab initioand MD simulation led to the relatively similar results in pharmacophore discrimination of p38α inhibitors.

Conclusion

The results of the present study may find their usefulness in pharmacophore based modification of p38α inhibitors.
Understanding brain dysfunction in sepsis
Authors: Sonneville Romain , Verdonk Franck , Rauturier Camille , Klein Isabelle F , Wolff Michel , Annane Djillali , Chretien Fabrice , Sharshar Tarek
Published: May 2013

Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors.
CD4 T cell-intrinsic IL-2 signaling differentially affects Th1 and Th17 development
Authors: Fujimura Kenjiro , Oyamada Akiko , Iwamoto Yukihide , Yoshikai Yasunobu , Yamada Hisakata
Published: May 2013

IL-2 signaling is involved in clonal expansion of antigen-specific CD4 T cells. IL-2 is also reported to promote Th1 but inhibit Th17 differentiation, although in vivo relevance remains unclear. In addition, IL-2-dependent Foxp3+ CD4 Tregs suppress T cell proliferation, complicating the in vivo role of IL-2 in the development of Th cell responses. To elucidate the roles of cell-intrinsic IL-2 signaling in CD4 T cells, we cotransferred TCR-Tg CD4 T cells from IL-2Rα (CD25)-deficient and WT mice and analyzed development of antigen-specific Th1 and Th17 responses. It was revealed that Th17 development of antigen-specific CD4 T cells was largely unaffected, whereas Th1 development was impaired by the lack of IL-2 signaling. Similar data were obtained from mixed BM chimera experiments using BM cells from CD25-deficient and WT mice. In addition, although in vitro blockade of IL-2 during Th17 development greatly increased the percentages of Th17 cells, it did not affect their numbers, indicating that in vitro Th17 development is also IL-2-independent. Th1 development was dependent on IL-2 in vitro as well. Thus, our data suggest that cell-intrinsic IL-2 signaling is critical for Th1 development but plays a limited role in Th17 development in vitro as well as in vivo.
Significant Improvement in Survival After Allogeneic Hematopoietic Cell Transplantation During a Period of Significantly Increased Use, Older Recipient Age, and Use of Unrelated Donors
Authors: Hahn Theresa , McCarthy Philip L. , Hassebroek Anna , Bredeson Christopher , Gajewski James L. , Hale Gregory A. , Isola Luis M. , Lazarus Hillard M. , Lee Stephanie J. , LeMaistre Charles F. , Loberiza Fausto , Maziarz Richard T. , Rizzo J. Douglas , Joffe Steven , Parsons Susan , Majhail Navneet S.
Published: May 2013

Purpose

Over the past four decades, allogeneic hematopoietic cell transplantation (alloHCT) has evolved as a curative modality for patients with hematologic diseases. This study describes changes in use, technique, and survival in a population-based cohort.

Patients and Methods

The study included 38,060 patients with hematologic malignancies or disorders who underwent first alloHCT in a US or Canadian center from 1994 to 2005 and were reported to the Center for International Blood and Marrow Transplant Research.

Results

AlloHCT as treatment for acute lymphoblastic (ALL) and myeloid leukemias (AML), myelodysplastic syndrome (MDS), and Hodgkin and non-Hodgkin lymphomas increased by 45%, from 2,520 to 3,668 patients annually. From 1994 to 2005, use of both peripheral (7% to 63%) and cord blood increased (2% to 10%), whereas use of marrow decreased (90% to 27%). Despite a median age increase from 33 to 40 years and 165% increase in unrelated donors for alloHCT, overall survival (OS) at day 100 significantly improved for patients with AML in first complete remission after myeloablative sibling alloHCT (85% to 94%; P < .001) and unrelated alloHCT (63% to 86%; P < .001); 1-year OS improved among those undergoing unrelated alloHCT (48% to 63%; P = .003) but not among those undergoing sibling alloHCT. Similar results were seen for ALL and MDS. Day-100 OS after cord blood alloHCT improved significantly from 60% to 78% (P < .001) for AML, ALL, MDS, and chronic myeloid leukemia. Use of reduced-intensity regimens increased, yielding OS rates similar to those of myeloablative regimens.

Conclusion

Survival for those undergoing alloHCT has significantly improved over time. However, new approaches are needed to further improve 1-year OS.
Fertility Preservation for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update
Authors: Loren Alison W. , Mangu Pamela B. , Beck Lindsay Nohr , Brennan Lawrence , Magdalinski Anthony J. , Partridge Ann H. , Quinn Gwendolyn , Wallace W. Hamish , Oktay Kutluk
Published: May 2013

Purpose

To update guidance for health care providers about fertility preservation for adults and children with cancer.

Methods

A systematic review of the literature published from March 2006 through January 2013 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Panel reviewed the evidence and updated the recommendation language.

Results

There were 222 new publications that met inclusion criteria. A majority were observational studies, cohort studies, and case series or reports, with few randomized clinical trials. After review of the new evidence, the Update Panel concluded that no major, substantive revisions to the 2006 American Society of Clinical Oncology recommendations were warranted, but clarifications were added.

Recommendations

As part of education and informed consent before cancer therapy, health care providers (including medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, and surgeons) should address the possibility of infertility with patients treated during their reproductive years (or with parents or guardians of children) and be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, the Update Panel encourages providers to advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm and embryo cryopreservation as well as oocyte cryopreservation are considered standard practice and are widely available. Other fertility preservation methods should be considered investigational and should be performed by providers with the necessary expertise.
Tumor suppressors: enhancers or suppressors of regeneration?
Authors: Pomerantz Jason H. , Blau Helen M.
Published: May 2013

Tumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine.
Neurotransmitter-mediated control of neurogenesis in the adult vertebrate brain
Authors: Berg Daniel A. , Belnoue Laure , Song Hongjun , Simon András
Published: May 2013

It was long thought that no new neurons are added to the adult brain. Similarly, neurotransmitter signaling was primarily associated with communication between differentiated neurons. Both of these ideas have been challenged, and a crosstalk between neurogenesis and neurotransmitter signaling is beginning to emerge. In this Review, we discuss neurotransmitter signaling as it functions at the intersection of stem cell research and regenerative medicine, exploring how it may regulate the formation of new functional neurons and outlining interactions with other signaling pathways. We consider evolutionary and cross-species comparative aspects, and integrate available results in the context of normal physiological versus pathological conditions. We also discuss the potential role of neurotransmitters in brain size regulation and implications for cell replacement therapies.
Nuclear reprogramming
Authors: Halley-Stott Richard P. , Pasque Vincent , Gurdon J. B.
Published: May 2013

There is currently particular interest in the field of nuclear reprogramming, a process by which the identity of specialised cells may be changed, typically to an embryonic-like state. Reprogramming procedures provide insight into many mechanisms of fundamental cell biology and have several promising applications, most notably in healthcare through the development of human disease models and patient-specific tissue-replacement therapies. Here, we introduce the field of nuclear reprogramming and briefly discuss six of the procedures by which reprogramming may be experimentally performed: nuclear transfer to eggs or oocytes, cell fusion, extract treatment, direct reprogramming to pluripotency and transdifferentiation.
Stem cells in retinal regeneration: past, present and future
Authors: Ramsden Conor M. , Powner Michael B. , Carr Amanda-Jayne F. , Smart Matthew J. K. , da Cruz Lyndon , Coffey Peter J.
Published: May 2013

Stem cell therapy for retinal disease is under way, and several clinical trials are currently recruiting. These trials use human embryonic, foetal and umbilical cord tissue-derived stem cells and bone marrow-derived stem cells to treat visual disorders such as age-related macular degeneration, Stargardt's disease and retinitis pigmentosa. Over a decade of analysing the developmental cues involved in retinal generation and stem cell biology, coupled with extensive surgical research, have yielded differing cellular approaches to tackle these retinopathies. Here, we review these various stem cell-based approaches for treating retinal diseases and discuss future directions and challenges for the field.
How to make a functional β-cell
Authors: Pagliuca Felicia W. , Melton Douglas A.
Published: May 2013

Insulin-secreting pancreatic β-cells are essential regulators of mammalian metabolism. The absence of functional β-cells leads to hyperglycemia and diabetes, making patients dependent on exogenously supplied insulin. Recent insights into β-cell development, combined with the discovery of pluripotent stem cells, have led to an unprecedented opportunity to generate new β-cells for transplantation therapy and drug screening. Progress has also been made in converting terminally differentiated cell types into β-cells using transcriptional regulators identified as key players in normal development, and in identifying conditions that induce β-cell replication in vivo and in vitro. Here, we summarize what is currently known about how these strategies could be utilized to generate new β-cells and highlight how further study into the mechanisms governing later stages of differentiation and the acquisition of functional capabilities could inform this effort.
The cloning of a frog
Authors: Gurdon J. B.
Published: May 2013

It is relatively unusual for the Nobel Prize in Physiology or Medicine to be made, to a large extent, on the basis of a single author paper, published over 50 years ago, for work carried out by a graduate student. This was largely true of a paper published in 1962 in the journal Development (called at that time the Journal of Embryology and Experimental Morphology). The main subject of that paper was the production of normal tadpoles from the nuclei of intestinal epithelium cells of Xenopus laevis. In view of this unusual situation, I have been invited to comment on the 1962 paper.
Limits to sustained energy intake. XIV. Heritability of reproductive performance in mice
Authors: Vaanholt Lobke M. , Sinclair Rachel E. , Speakman John R.
Published: May 2013

Limits to sustained energy intake (SusEI) are important because they constrain many aspects of animal performance. Individual variability in SusEI may be imposed by genetic factors that are inherited from parents to offspring. Here, we investigated heritability of reproductive performance in MF1 mice. Food intake, milk energy output (MEO) and litter mass were measured in mothers (F0) and daughters (F1) that were raising litters of 10 pups. Cross-fostering was designed so that half of each litter consisted of biological offspring and the rest came from one unrelated female (i.e. fostered pups). Food intake increased linearly during early lactation and reached a plateau during late lactation (day 9–13, called the asymptotic food intake, FIAS, equivalent to SusEI). Parent–offspring regression showed that FIAS, MEO and litter mass were all positively and significantly related between mothers and their biological daughters, but no significant relationships were found between the same traits for mothers and fostered daughters. FIAS at peak lactation was significantly correlated to adult food intake and body mass when the mice were 6 months old and not lactating. In conclusion, a large part of the variation in FIAS could be explained by genetic variation or maternal effects in pregnancy whereas non-genetic maternal effects in lactation were negligible. As a consequence, biological daughters of mothers with high reproductive performance (i.e. high milk production and hence higher litter mass at weaning) had a better reproductive performance themselves, independent of the mother that raised them during lactation.
Sperm-attractant peptide influences the spermatozoa swimming behavior in internal fertilization in Octopus vulgaris
Authors: De Lisa Emilia , Salzano Anna Maria , Moccia Francesco , Scaloni Andrea , Di Cosmo Anna
Published: May 2013

Marine invertebrates exhibit both chemokinesis and chemotaxis phenomena, induced in most cases by the release of water-borne peptides or pheromones. In mollusks, several peptides released during egg-laying improve both male attraction and mating. Unlike other cephalopods, Octopus vulgaris adopts an indirect internal fertilization strategy. We here report on the identification and characterization of a chemoattractant peptide isolated from mature eggs of octopus females. Using two-chamber and time-lapse microscopy assays, we demonstrate that this bioactive peptide is able to increase sperm motility and induce chemotaxis by changing the octopus spermatozoa swimming behavior in a dose-dependent manner. We also provide evidence that chemotaxis in the octopus requires the presence of extracellular calcium and membrane protein phophorylation at tyrosine. This study is the first report on a sperm-activating factor in a non-free-spawning marine animal.
Synthesis and Characterization of Novel Liquid Crystalline Polystyrene
Authors: Wang Bai , Ma Hong Wei , Wang Yan Shai , Li Yang
Published: May 2013

The paper introduces a simple method to synthesize novel liquid crystalline polystyrene (LC-PS) containing a mesogenic unit at a side chain by hydrosilylation through poly[(4-vinylphenyl)dimethylsilanol] (PVPDMS) and liquid crystal monomer cholesteryl 4-[4-(undec-10-enoyloxy)benzoyloxy]phenyladipate (M). The LC-PS had high purity, high molecular weight, narrow distribution, good thermal stability, and typical thermotropic liquid crystallinity (SA phase), as shown by 1H NMR analyses, size exclusion chromatography (SEC), thermogravimetry analysis (TGA), differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and X-ray diffraction (XRD). The glass-transition temperature (Tg) of LC-PS was much lower than that of PVPDMS, while the clearing point (Ti) of LC-PS significantly increased compared with M.
Loop–loop interaction in an adenine-sensing riboswitch: A molecular dynamics study
Authors: Allnér Olof , Nilsson Lennart , Villa Alessandra
Published: May 2013

Riboswitches are mRNA-based molecules capable of controlling the expression of genes. They undergo conformational changes upon ligand binding, and as a result, they inhibit or promote the expression of the associated gene. The close connection between structural rearrangement and function makes a detailed knowledge of the molecular interactions an important step to understand the riboswitch mechanism and efficiency. We have performed all-atom molecular dynamics simulations of the adenine-sensing add A-riboswitch to study the breaking of the kissing loop, one key tertiary element in the aptamer structure. We investigated the aptamer domain of the add A-riboswitch in complex with its cognate ligand and in the absence of the ligand. The opening of the hairpins was simulated using umbrella sampling using the distance between two loops as the reaction coordinate. A two-step process was observed in all the simulated systems. First, a general loss of stacking and hydrogen bond interactions is seen. The last interactions that break are the two base pairs G37-C61 and G38-C60, but the break does not affect the energy profile, indicating their pivotal role in the tertiary structure formation but not in the structure stabilization. The junction area is partially organized before the kissing loop formation and residue A24 anchors together the loop helices. Moreover, when the distance between the loops is increased, one of the hairpins showed more flexibility by changing its orientation in the structure, while the other conserved its coaxial arrangement with the rest of the structure.
Diversion at the ER: How Plasmodium falciparum exports proteins into host erythrocytes
Authors: Römisch Karin
Published: May 2013

Malaria is caused by parasites which live in host erythrocytes and remodel these cells to provide optimally for the parasites’ needs by exporting effector proteins into the host cells. Eight years ago the discovery of a host cell targeting sequence present in both soluble and transmembrane P. falciparum exported proteins generated a starting point for investigating the mechanism of parasite protein transport into infected erythrocytes. Since then many confusing facts about this targeting signal have emerged. In this paper, I try to make sense of them.
Considerations for clinical read alignment and mutational profiling using next-generation sequencing
Authors: Oliver Gavin R
Published: May 2013

Next-generation sequencing technologies are increasingly being applied in clinical settings, however the data are characterized by a range of platform-specific artifacts making downstream analysis problematic and error- prone. One major application of NGS is in the profiling of clinically relevant mutations whereby sequences are aligned to a reference genome and potential mutations assessed and scored. Accurate sequence alignment is pivotal in reliable assessment of potential mutations however selection of appropriate alignment tools is a non-trivial task complicated by the availability of multiple solutions each with its own performance characteristics. Using targeted analysis of BRCA1 as an example, we have simulated and mutated a test dataset based on Illumina sequencing technology. Our findings reveal key differences in the abilities of a range of common commercial and open source alignment tools to facilitate accurate downstream detection of a range of mutations. These observations will be of importance to anyone using NGS to profile mutations in clinical or basic research.
A rare variation of hydranencephaly: case report
Authors: Wijerathne Buddhika TB , Rathnayake Geetha K , Ranaraja Sisira K
Published: May 2013

Hydranencephaly is a rare congenital abnormality characterized by the absence and replacement of the cerebral hemispheres with cerebrospinal fluid. Here, we present an ultrasonographic diagnosis of a case of a rare variant of fetal hydranencephaly at 38 weeks of gestation. Obstetric sonography revealed the absence of the cerebral cortex, thalami and basal ganglia with a disrupted falx and preserved posterior fossa structures. This is the first reported case of hydranencephaly with the absence of the thalami and basal ganglia, which was diagnosed prenatally. The diagnosis was confirmed with postnatal computed tomography. The early prenatal diagnosis allowed for prompt obstetric attention at a tertiary care hospital which had specialized pediatric facilities including prenatal counseling and support.
Female circumcision: Limiting the harm
Authors: Kandil Mohamed
Published: May 2013

Objective: To review the strength of evidence that links many health hazards to female genital cutting.

Material and methods: Literature search in Medline/Pubmed and Google scholar.

Results: Female genital cutting is still practiced secretly in both underdeveloped and developed countries due to prevailing strong traditional beliefs. There is insufficient evidence to support the claims that genital cutting is a harmful procedure if performed by experienced personnel in a suitable theatre with facilities for pain control and anesthesia. Cutting, however, is advised not to go beyond type I.

Conclusion: Law makers around the globe are invited to review the legal situation in relation to female genital cutting. Proper counseling of parents about possible risks is a must in order to make informed decision about circumcising their daughters. The procedure should be offered to parents who insist on it; otherwise, they will do it illegally, exposing their daughters to possible complications.
Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma
Authors: Fathy Hanan , Amin Maha M , El-Gilany Abdel-Hady
Published: May 2013

Background:Kaposi’s sarcoma (KS) is a rare neoplasm of lymphatic endothelial cells. Human herpes virus 8 (HHV-8) is considered to be a necessary, but not sufficient causal agent of KS and additional cofactors remain unknown. In this study we evaluated the expression of human β defensin (HBD)-3 and LL-37 in cutaneous lesions of KS in comparison to the healthy skin of normal subjects.

Methods:We performed a quantitative immunohistochemical study of HBD-3 and LL-37 on skin lesions from 18 patients having KS, and on healthy skin from 12 normal controls.

Results:HBD-3 and LL-37 were significantly upregulated in epidermal and dermal specimens of all KS patients in comparison to normal skin of healthy controls. The immunostaining score of dermal HBD-3 was significantly higher in nodular lesions (9.6 ± 2.4) versus plaque lesions (4.1 ± 2.2), P = 0.001. Also the immunostaining score of dermal LL-37 was significantly higher in nodular lesions versus plaque lesions (P = 0.001).

Conclusions:We have demonstrated for the first time that HBD-3 and LL-37 are significantly upregulated in lesional skin of KS in comparison to the skin of healthy controls. The obtained data suggest a possible involvement of these antimicrobial peptides in the pathogenesis of KS. However, the biological significance of HBD-3 and LL-37 in KS lesions needs further research.
Local indigenous knowledge about some medicinal plants in and around Kakamega forest in western Kenya
Authors: Otieno Nickson Erick , Analo Caleb
Published: May 2013

Kakamega forest is Kenya’s only rainforest and is distinguishably rich in biodiversity but threatened by agricultural encroachment and other forms of human activity. It is also one of Kenya’s Important Bird Areas and a significant source of natural products to neighboring rural communities, such as medicinal plants, food, wood and other fibers. By using structured questionnaires for direct interviews, local indigenous knowledge was tapped through involvement of a focal group of elderly key informants in three blocks of the forest. Forty key species of medicinal plants used by local people were identified and recorded. Fifty-five percent of these were shrubs, thirty-two percent trees, seven-and-a-half percent lower plants such as herbs or forbs while five percent were climbers. About seventy percent of the medicinal plants occurred inside the forest itself and thirty percent around the edge and the immediate surroundings outside the forest. Thirty-eight (95%) of the plants were indigenous to Kenya and two (5%) exotic. Such extensive indigenous knowledge of the medicinal uses of the plants, including their distribution trends in the forest, may be tapped for decision support in rural health service planning, policy formulation for conserving the forest, tracking and mitigation of climate change impacts.
A mutation in negative regulator of basal resistance WRKY17 of Arabidopsis increases susceptibility to Agrobacterium-mediated transient genetic transformation
Authors: Lacroix Benoît , Citovsky Vitaly
Published: May 2013

Agrobacterium is a phytopathogenic bacterium that induces crown gall disease in many plant species by transferring and integrating a segment of its own DNA (T-DNA) into its host genome. Whereas Agrobacterium usually does not trigger an extensive defense response in its host plants, it induces the expression of several defense-related genes and activates plant stress reactions. In the complex interplay between Agrobacterium and its host plant, Agrobacterium has evolved to take advantage of these plant defense pathways for its own purpose of advancement of the infection process. For example, Agrobacterium utilizes the host stress response transcriptional regulator VIP1 to facilitate nuclear import and proteasomal uncoating of its T-DNA during genetic transformation of the host cell. In Arabidopsis, the VIP1 gene expression is repressed by WRKY17, a negative regulator of basal resistance to Pseudomonas. Thus, we examined whether WRKY17 is also involved in plant susceptibility to genetic transformation by Agrobacterium. Using reverse genetics, we showed that a wrky17 mutant displays higher expression of the VIP1 gene in roots, but not in shoots. In a root infection assay, the wrky17 mutant plants were hyper-susceptible to Agrobacterium compared to wild type plants. WRKY17, therefore, may act as a positive regulator of Arabidopsis resistance to Agrobacterium. This notion is important for understanding the complex regulation of Agrobacterium-mediated transient genetic transformation; thus, although this paper reports a relatively small set of data that we do not plan to pursue further in our lab, we believe it might be useful for the broad community of plant pathologists and plant biotechnologists.