bluuebunny/crossref_metadata_2025 huggingface dataset:
Dll4 activation of Notch signaling reduces tumor vascularity and inhibits tumor growth
Authors: Segarra Marta , Williams Cassin Kimmel , Sierra Maria de la Luz , Bernardo Marcelino , McCormick Peter J. , Maric Dragan , Regino Celeste , Choyke Peter , Tosato Giovanna
Published: June 2008

Gene targeting experiments have shown that Delta-like 4 (Dll4) is a vascular-specific Notch ligand critical to normal vascular development. Recent studies have demonstrated that inhibition of Dll4/Notch signaling in tumor-bearing mice resulted in excessive, yet nonproductive tumor neovascularization and unexpectedly reduced tumor growth. Because nonfunctional blood vessels have the potential to normalize, we explored the alternative approach of stimulating Notch signaling in the tumor vasculature to inhibit tumor growth. Here we show that retrovirus-induced over-expression of Dll4 in tumor cells activates Notch signaling in cocultured endothelial cells and limits vascular endothelial growth factor (VEGF)–induced endothelial cell growth. Tumors produced in mice by injection of human and murine tumor cells transduced with Dll4 were significantly smaller, less vascularized and more hypoxic than controls, and displayed evidence of Notch activation. In addition, tumor blood perfusion was reduced as documented by vascular imaging. These results demonstrate that Notch activation in the tumor microenvironment reduces tumor neovascularization and blood perfusion, and suggest that Dll4-induced Notch activation may represent an effective therapeutic approach for the treatment of solid tumors.
Histopathology of experimentally induced asthma in a murine model of sickle cell disease
Authors: Nandedkar Sandhya D. , Feroah Thomas R. , Hutchins William , Weihrauch Dorothee , Konduri Kameswari S. , Wang Jingli , Strunk Robert C. , DeBaun Michael R. , Hillery Cheryl A. , Pritchard Kirkwood A.
Published: June 2008

Asthma is a comorbid condition associated with increased rates of pain, acute chest syndrome, and premature death in human sickle cell disease (SCD). We developed an experimental asthma model in SCD and control mice expressing either normal human or murine hemoglobin to determine its effect on mortality and lung pathology. To induce lung inflammation, experimental mice were sensitized to ovalbumin (OVA) by subcutaneous OVA implantation (Sen), allowed 2 weeks to recover, and then divided into 2 groups, each receiving over a subsequent 10-day period the same dosage of aerosolized OVA but 2 different levels of exposure: 15 minutes (LoSen) and 30 minutes (HiSen). During recovery, 10% of SCD mice died compared with no deaths in control mice. An additional 30% of HiSen SCD mice died during aerosolization compared with 10% in LoSen SCD. Histologic indices of lung inflammation (eg, eosinophil recruitment, airway and vessel wall thickening, and immunoreactive TGFβ and fsp-1) and bronchial alveolar lavage fluid eosinophil peroxidase activity differentially increased in sensitized mice compared with unsensitized mice. Our findings indicate SCD mice with experimentally induced asthma are more susceptible to death and pulmonary inflammation compared with control mice, suggesting that asthma contributes significantly to morbidity and mortality in SCD.
Biochemical characterization and cellular imaging of a novel, membrane permeable fluorescent cAMP analog
Authors: Moll Daniela , Prinz Anke , Brendel Cornelia M , Berrera Marco , Guske Katrin , Zaccolo Manuela , Genieser Hans-Gottfried , Herberg Friedrich W
Published: June 2008

Background

A novel fluorescent cAMP analog (8-[Pharos-575]- adenosine-3', 5'-cyclic monophosphate) was characterized with respect to its spectral properties, its ability to bind to and activate three main isoenzymes of the cAMP-dependent protein kinase (PKA-Iα, PKA-IIα, PKA-IIβ) in vitro, its stability towards phosphodiesterase and its ability to permeate into cultured eukaryotic cells using resonance energy transfer based indicators, and conventional fluorescence imaging.

Results

The Pharos fluorophore is characterized by a Stokes shift of 42 nm with an absorption maximum at 575 nm and the emission peaking at 617 nm. The quantum yield is 30%. Incubation of the compound to RIIα and RIIβ subunits increases the amplitude of excitation and absorption maxima significantly; no major change was observed with RIα. In vitro binding of the compound to RIα subunit and activation of the PKA-Iα holoenzyme was essentially equivalent to cAMP; RII subunits bound the fluorescent analog up to ten times less efficiently, resulting in about two times reduced apparent activation constants of the holoenzymes compared to cAMP. The cellular uptake of the fluorescent analog was investigated by cAMP indicators. It was estimated that about 7 μM of the fluorescent cAMP analog is available to the indicator after one hour of incubation and that about 600 μM of the compound had to be added to intact cells to half-maximally dissociate a PKA type IIα sensor.

Conclusion

The novel analog combines good membrane permeability- comparable to 8-Br-cAMP – with superior spectral properties of a modern, red-shifted fluorophore. GFP-tagged regulatory subunits of PKA and the analog co-localized. Furthermore, it is a potent, PDE-resistant activator of PKA-I and -II, suitable for in vitro applications and spatial distribution evaluations in living cells.
Automated discovery and phylogenetic analysis of new toxin-antitoxin systems
Authors: Guglielmini Julien , Szpirer Cédric , Milinkovitch Michel C
Published: June 2008

Background

Although often viewed as elements "at the service of" bacteria, plasmids exhibit replication and maintenance mechanisms that make them purely "selfish DNA" candidates. Toxin-antitoxin (TA) systems are a spectacular example of such mechanisms: a gene coding for a cytotoxic stable protein is preceded by a gene coding for an unstable antitoxin. The toxin being more stable than the antitoxin, absence of the operon causes a reduction of the amount of the latter relative to the amount of the former. Thus, a cell exhibiting a TA system on a plasmid is 'condemned' either not to loose it or to die.

Results

Different TA systems have been described and classified in several families, according to similarity and functional parameters. However, given the small size and large divergence among TA system sequences, it is likely that many TA systems are not annotated as such in the rapidly accumulating NCBI database. To detect these putative TA systems, we developed an algorithm that searches public databases on the basis of predefined similarity and TA-specific structural constraints. This approach, using a single starting query sequence for each of the ParE, Doc, and VapC families, and two starting sequences for the MazF/CcdB family, identified over 1,500 putative TA systems. These groups of sequences were analyzed phylogenetically for a better classification and understanding of TA systems evolution.

Conclusion

The phylogenetic distributions of the newly uncovered TA systems are very different within the investigated families. The resulting phylogenetic trees are available for browsing and searching through a java program available at http://ueg.ulb.ac.be/tiq/.
Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT)
Authors: Bækken Petter M , Skorpen Frank , Stordal Eystein , Zwart John-Anker , Hagen Knut
Published: June 2008

Background

The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, which has been linked to anxiety and depression, but previous results are not conclusive. The aim of the present study was to examine the relationship between the Val158Met COMT gene polymorphism and anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS) in the general adult population.

Methods

In the Nord-Trøndelag Health Study (HUNT) the association between the Val158Met polymorphism and anxiety and depression was evaluated in a random sample of 5531 individuals. Two different cut off scores (≥ 8 and ≥ 11) were used to identify cases with anxiety (HADS-A) and depression (HADS-D), whereas controls had HADS-A <8 and HADS-D <8.

Results

The COMT genotype distribution was similar between controls and individuals in the groups with anxiety and depression using cut-off scores of ≥ 8. When utilizing the alternative cut-off score HADS-D ≥ 11, Met/Met genotype and Met allele were less common among men with depression compared to the controls (genotype: p = 0.017, allele: p = 0.006). In the multivariate analysis, adjusting for age and heart disease, depression (HADS-D ≥ 11) was less likely among men with the Met/Met genotype than among men with the Val/Val genotype (OR = 0.37, 95% CI = 0.18–0.76).

Conclusion

In this population-based study, no clear association between the Val158Met polymorphism and depression and anxiety was revealed. The Met/Met genotype was less likely among men with depression defined as HADS-D ≥ 11, but this may be an incidental finding.
Proteomic profiling of urine for the detection of colon cancer
Authors: Ward Douglas G , Nyangoma Stephen , Joy Howard , Hamilton Emma , Wei Wenbin , Tselepis Chris , Steven Neil , Wakelam Michael JO , Johnson Philip J , Ismail Tariq , Martin Ashley
Published: June 2008

Background

Colorectal cancer is the second most common cause of cancer related death in the developed world. To date, no blood or stool biomarkers with both high sensitivity and specificity for potentially curable early stage disease have been validated for clinical use. SELDI and MALDI profiling are being used increasingly to search for biomarkers in both blood and urine. Both techniques provide information predominantly on the low molecular weight proteome (<15 kDa). There have been several reports that colorectal cancer is associated with changes in the serum proteome that are detectable by SELDI and we hypothesised that proteomic changes would also be detectable in urine.

Results

We collected urine from 67 patients with colorectal cancer and 72 non-cancer control subjects, diluted to a constant protein concentration and generated MALDI and SELDI spectra. The intensities of 19 peaks differed significantly between cancer and non-cancer patients by both t-tests and after adjusting for confounders using multiple linear regressions. Logistic regression classifiers based on peak intensities identified colorectal cancer with up to 78% sensitivity at 87% specificity. We identified and independently quantified 3 of the discriminatory peaks using synthetic stable isotope peptides (an 1885 Da fragment of fibrinogen and hepcidin-20) or ELISA (β2-microglobulin).

Conclusion

Changes in the urine proteome may aid in the early detection of colorectal cancer.
Intraoperative frozen section assessment of sentinel lymph nodes in the operative management of women with symptomatic breast cancer
Authors: Ali Rohanna , Hanly Ann M , Naughton Peter , Castineira Constantino F , Landers Rob , Cahill Ronan A , Watson R Gordon
Published: June 2008

Background

Maximisation of the potential of sentinel lymph node biopsy as a minimally invasive method of axillary staging requires sensitive intraoperative pathological analysis so that rates of re-operation for lymphatic metastases are minimised. The aim of this study was to describe the test parameters of the frozen section evaluation of sentinel node biopsy for breast cancer compared to the gold standard of standard permanent pathological evaluation at our institution.

Methods

The accuracy of intraoperative frozen section (FS) of sentinel nodes was determined in 94 consecutive women undergoing surgery for clinically node negative, invasive breast cancer (37:T1 disease; 43:T2; 14:T3). Definitive evidence of lymphatic spread on FS indicated immediate level II axillary clearance while sentinel node "negativity" on intraoperative testing led to the operation being curtailed to allow formal H&E analysis of the remaining sentinel nodal tissue.

Results

Intraoperative FS correctly predicted axillary involvement in 23/30 patients with lymphatic metastases (76% sensitivity rate) permitting definitive surgery to be completed at the index operation in 87 women (93%) overall. All SN found involved on FS were confirmed as harbouring tumour cells on subsequent formal specimen examination (100% specificity and positive predictive value) with 16 patients having additional non-sentinel nodes found also to contain tumour. Negative Predictive Values were highest in women with T1 tumours (97%) and lessened with more local advancement of disease (T2 rates: 86%; T3: 75%). Of those with falsely negative FS, three had only micrometastatic disease.

Conclusion

Intraoperative FS reliably evaluates the status of the sentinel node allowing most women complete their surgery in a single stage. Thus SN can be offered with increased confidence to those less likely to have negative axillae hence expanding the population of potential beneficiaries.
Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival
Authors: MacIver Nancie J , Jacobs Sarah R , Wieman Heather L , Wofford Jessica A , Coloff Jonathan L , Rathmell Jeffrey C
Published: June 2008

Lymphocytes require glucose uptake and metabolism for normal survival and function. The signals that regulate the expression and localization of glucose transporter 1 (Glut1) to allow glucose uptake in T cells are now beginning to be understood. Resting T cells require extracellular signals, such as cytokines, hormones, and growth factors, or low-level TCR stimulation to take up adequate glucose to maintain housekeeping functions. In the absence of extrinsic signals, resting T cells internalize and degrade Glut1 and cannot maintain viability. Activated T cells have dramatically increased metabolic requirements to support the energy and biosynthetic needs necessary for growth, proliferation, and effector function. In particular, glucose metabolism and aerobic glycolysis fuel this demand. Therefore, activation of T cells causes a large increase in Glut1 expression and surface localization. If glucose uptake is limited, glycolytic flux decreases to a level that no longer sustains viability, and proapoptotic Bcl-2 family members become activated, promoting cell death. However, excessive glucose uptake can promote hyperactive immune responses and possible immune pathology. Tight regulation of glucose uptake is required to maintain immune homeostasis, and understanding of these metabolic pathways may lead to therapeutic strategies to target some forms of cancer or autoimmunity.
Differential turnover rates of monocyte-derived cells in varied ocular tissue microenvironments
Authors: Kezic Jelena , McMenamin Paul G
Published: June 2008

Monocytes of bone marrow (BM) origin are circulating precursors that replenish dendritic cells and macrophage populations in peripheral tissues during homeostasis. The eye provides a unique range of varying tissue microenvironments in which to compare the different turnover rates of monocyte-derived cells. This was investigated in the present study using radiation chimeras, whereby BM from Cx3cr1+/gfp mice was used to rescue myeloablated wild-type (WT) BALB/c mice (conventional chimeras). The use of Cx3cr1+/gfp mice as BM donors allowed the clear visualization of newly recruited monocyte-derived cells. Following BM reconstitution, mice were killed at 2, 4, 6, and 8 weeks, and wholemount ocular tissues were processed for immunohistochemistry and confocal microscopy. “Reverse” chimeras (WT into Cx3cr1+/gfp) were also created to act as a further method of cross-referencing cell turnover rates. In conventional chimeras, Cx3cr1+/gfp cells began repopulating the uveal tract (iris, ciliary body, choroid) 2 weeks post-transplantation with close to complete replenishment by 8 weeks. By contrast, the earliest recruitment of Cx3cr1+/gfp cells into the host retina occurred at 4 weeks. In reverse chimeras, a steady accumulation of host Cx3cr1+/gfp macrophages in the subretinal space of Cx3cr1+/gfp adult mice suggests that these cells arise from long-term resident microglia and not newly recruited WT donor cells. In summary, chimeric mouse models, in which lineage-specific cells carry a fluorescent reporter, have been used in the present study to visualize the turnover of monocyte-derived cells in different tissue compartments of the eye. These data provide valuable insights into differential monocyte turnover rates within a single complex organ.
Education for All
Authors: Burnett Nicholas
Published: June 2008

In the year 2000, more than 160 governments adopted six goals aimed at vastly improving learning opportunities for children, youth, and adults by 2015. This article, based on an annual international report that tracks progress toward these goals and levels of aid to basic education, analyzes the significance of expanding learning opportunities for human, social, and economic development. It assesses where the world stands on meeting its commitments—developing nations and donors included. The picture is mixed, with considerable progress in some cases, especially toward universal primary education and gender parity at the primary level. Much less attention is being given to other age groups, notably through early childhood care and education programs and adult literacy—a global scourge affecting 781 million adults. Low education quality, lack of learning opportunities for the most disadvantaged groups, and insufficient aid to basic education are holding many countries back. The article outlines some of the greatest challenges for decision makers: holistic early childhood programs that target the most disadvantaged children; policies to make school free, accessible, and safe for girls and boys; and scaling up adult literacy programs. Education quality—from the recruitment and training of teachers to textbooks, sufficient instructional time, and initial instruction in the mother tongue—has a documented influence on learning outcomes. Increased domestic and international spending on education is essential. Such an agenda requires long‐term vision and strong political commitment at the highest level.
Expanding Global HIV Treatment
Authors: Furin J.J. , Behforouz H.L. , Shin S.S. , Mukherjee J.S. , Bayona J. , Farmer P.E. , Kim J.Y. , Keshavjee S.
Published: June 2008

In the last 25 years, human immunodeficiency virus (HIV) has become the leading infectious killer of adults globally, with an estimated 44 million people infected with the virus worldwide. Most of these individuals live in poor regions of the world, particularly sub‐Saharan Africa. Although a great deal of work has been done in identifying and treating individuals with the disease, there has been little action to date to address the complex socioeconomic factors that lie at the heart of this global pandemic. Understanding and responding to such factors is of paramount importance if HIV infection is to be managed in a meaningful way. This article explores the social context of people living with HIV in three different geographic and epidemiologic settings and highlights the social factors that shape and define an individual's risk of acquiring HIV. It also discusses unique programs aimed at addressing the complex realities of the world in which HIV thrives. These programs can act as models of HIV prevention and treatment.
Long‐Term Effects of Head Start on Low‐Income Children
Authors: Ludwig Jens , Phillips Deborah A.
Published: June 2008

A growing body of research suggests that the first few years of life are a particularly promising time to intervene in the lives of low‐income children, although the long‐term effects on children of the U.S. government's primary early childhood program—Head Start—remains the topic of debate. In this article we review what is known about Head Start and argue that the program is likely to generate benefits to participants and society as a whole that are large enough to justify the program's costs. Although in principle there could be more beneficial ways of deploying Head Start resources, the benefits of such changes remain uncertain and there is some downside risk.
Poverty, Gender Inequities, and Women's Risk of Human Immunodeficiency Virus/AIDS
Authors: Krishnan Suneeta , Dunbar Megan S. , Minnis Alexandra M. , Medlin Carol A. , Gerdts Caitlin E. , Padian Nancy S.
Published: June 2008

Entrenched economic and gender inequities together are driving a globally expanding, increasingly female, human immunodeficiency virus (HIV)/AIDS epidemic. To date, significant population‐level declines in HIV transmission have not been observed, at least in part because most approaches to prevention have presumed a degree of individual control in decision making that does not speak to the reality of women's and girls' circumstances in many parts of the world. Such efforts have paid insufficient attention to critical characteristics of the risk environment, most notably poverty and gender power inequities. Even fewer interventions have addressed specific mechanisms through which these inequities engender risky sexual practices that result in women's disproportionately increased vulnerabilities to HIV infection. This article focuses on identifying those mechanisms, or structural pathways, that stem from the interactions between poverty and entrenched gender inequities and recommending strategies to address and potentially modify those pathways. We highlight four such structural pathways to HIV risk, all of which could be transformed: (1) lack of access to critical information and health services for HIV/sexually transmitted infection (STI) prevention, (2) limited access to formal education and skill development, (3) intimate partner violence, and (4) the negative consequences of migration prompted by insufficient economic resources. We argue for interventions that enhance women's access to education, training, employment, and HIV/STI prevention information and tools; minimize migration; and by working with men and communities, at the same time reduce women's poverty and promote gender‐equitable norms. In conclusion, we identify challenges in developing and evaluating strategies to address these structural pathways.
Dracunculiasis, Onchocerciasis, Schistosomiasis, and Trachoma
Authors: Hopkins Donald R. , Richards, Jr Frank O. , Ruiz‐Tiben Ernesto , Emerson Paul , Craig Withers, Jr P.
Published: June 2008

The four diseases discussed in this chapter (dracunculiasis, onchocerciasis, schistosomiasis, and trachoma) are among the officially designated “Neglected Tropical Diseases,” and each is also both the result of and a contributor to the poverty of many rural populations. To various degrees, they all have adverse effects on health, agricultural productivity, and education. The Carter Center decided to work on these health problems because of their adverse effect on the lives of poor people and the opportunity to help implement effective interventions. As a result of the global campaign spearheaded by the Carter Center since 1986, the extent of dracunculiasis has been reduced from 20 to five endemic countries and the number of cases reduced by more than 99%. We have helped administer nearly 20% of the 530 million Mectizan (ivermectin) doses for onchocerciasis, which is now being controlled throughout most of Africa, and is progressing toward elimination in the Americas. Since 1999, two Nigerian states have been using village‐based health workers originally recruited to work on onchocerciasis to also deliver mass treatment and health education for schistosomiasis and lymphatic filariasis. They now also distribute vitamin A supplements and bed nets to prevent malaria and lymphatic filariasis. Ethiopia aims to eliminate blinding trachoma in the Amhara Region of that highest‐endemicity country by 2012, already constructing more than 300,000 latrines and other complementary interventions. Because of the synergy between these diseases and poverty, controlling or eliminating the disease also reduces poverty and increases self‐reliance.
Poverty, Maternal Health, and Adverse Pregnancy Outcomes
Authors: Tanya Nagahawatte N. , Goldenberg Robert L.
Published: June 2008

Pregnancy outcomes in the United States are generally worse than those in most developed countries. Contributing to these adverse outcomes are the relatively high levels of poverty in the United States, a characteristic that is associated with decreased utilization of appropriate prenatal care and delivery services as well as having an increased number of other risk factors. Poor women tend to be more obese, to have more medical conditions, such as hypertension and diabetes, to be more likely to be stressed or depressed, and to smoke cigarettes and use illicit drugs. We present some of the potential mechanisms that explain the association between these characteristics and adverse pregnancy outcomes—focusing on preterm birth.
Poverty and Health Disparities for American Indian and Alaska Native Children
Authors: Sarche Michelle , Spicer Paul
Published: June 2008

This report explores the current state of knowledge regarding inequalities and their effect on American Indian and Alaska Native children, underscoring gaps in our current knowledge and the opportunities for early intervention to begin to address persistent challenges in young American Indian and Alaska Native children's development. This overview documents demographic, social, health, and health care disparities as they affect American Indian and Alaska Native children, the persistent cultural strengths that must form the basis for any conscientious intervention effort, and the exciting possibilities for early childhood interventions.
Poverty and Elimination of Urban Health Disparities
Authors: Thomas Stephen B. , Quinn Sandra Crouse
Published: June 2008

The aim of this article is to examine the intersection of race and poverty, two critical factors fueling persistent racial and ethnic health disparities among urban populations. From the morass of social determinants that shape the health of racial and ethnic communities in our urban centers, we will offer promising practices and potential solutions to eliminating racial and ethnic health disparities.
Social and Economic Aspects of Immigration
Authors: Clark Rebecca L. , King Rosalind Berkowitz
Published: June 2008

The absolute size of the foreign‐born U.S. population is at a historical high, but neither the share of the population that is foreign born nor the share of children in immigrant families is high compared with the beginning of the 20th century. While poverty rates for immigrants and children in immigrant families are substantial, poverty is concentrated among certain groups, particularly Hispanics and blacks, non‐citizens, and recent arrivals. The general economic well‐being of immigrants improves with the move to the United States and as time in the United States increases. However, immigrants remain disadvantaged in terms of health insurance coverage. The economic situation of children in immigrant families has declined since the late 1960s, despite the high labor force participation of immigrant men and the lower prevalence of single‐parent households among immigrant families. Still, children in immigrant families are at least as healthy as children in native families and are less likely to engage in risky behaviors. With socioeconomic factors taken into account, children in immigrant families do as well as other children in school. Analyses of the socioeconomic well‐being of immigrants have been hampered by lack of information in major data sets about legal status and about the visa status of legally present immigrants, as well as by limited availability of longitudinal data.
Latent Effects of Prenatal Malnutrition on Adult Health
Authors: Susser Ezra , Clair David St. , He Lin
Published: June 2008

It is well established that malnutrition in children has adverse effects on development. Only recently, however, has it become possible to examine the full scope of adverse effects of malnutrition across the life course, which would include latent effects of fetal or childhood malnutrition on health and disease in adult life. We review here a series of studies which have linked early prenatal famine to the risk of schizophrenia in the offspring. Thus we aim to draw attention to the need to look beyond the concurrent effects of malnutrition and consider also the effects that may become apparent decades later.
The Chinese Social Benefit System in Transition
Authors: Gao Qin
Published: June 2008

Economic reforms since the late 1970s have made China one of the world's fastest growing economies but have also led to greater unmet social welfare needs and growing income inequality. This article describes social policy trends in urban and rural China and reviews recent empirical evidence on the transitions and impacts of its social benefit system. The evidence reveals that although urban social benefits experienced significant cutbacks, they are still much more generous than the minimal social benefits for rural residents and migrants. This extremely inequitable situation calls for a larger, progressive social benefit system in China.
Poverty
Authors: Delisle Hélène F.
Published: June 2008

Women are doubly vulnerable to malnutrition, because of their high nutritional requirements for pregnancy and lactation and also because of gender inequalities in poverty. Undernutrition and overnutrition coexist in developing countries undergoing rapid nutrition transition, and women are susceptible to this double burden of “dysnutrition,” often cumulating stunting or micronutrient malnutrition with obesity or other nutrition‐related chronic diseases. The purpose of the present paper is to describe the adverse impact of income and gender inequities on women's nutritional health, and the dramatic consequences, not only for women themselves, but for children, families, and societies. Improving women's resources, including health, nutrition, education, and decisional power, is critical for equity and for the health of children and adults of future generations, since poor fetal and infancy nutrition is another risk factor for chronic diseases, in particular abdominal obesity, type 2 diabetes, hypertension, and cardiovascular disease. Addressing malnutrition and nutrition‐related chronic diseases simultaneously is a challenge facing developing countries, and examples of promising initiatives are provided. Focusing on women along the lifecycle, according to the continuum of care approach, is essential to achieving the Millennium Development Goals and to breaking the intergenerational cycle of poverty, malnutrition, and ill‐health.
Chronic Diseases in Developing Countries
Authors: Nugent Rachel
Published: June 2008

Chronic diseases are increasing in global prevalence and seriously threaten developing nations' ability to improve the health of their populations. Although often associated with developed nations, the presence of chronic disease has become the dominant health burden in many developing countries. Chronic diseases were responsible for 50% of the disease burden in 23 high‐burden developing countries in 2005 and will cost those countries $84 billion by 2015 if nothing is done to slow their growth. The rise of lifestyle‐related chronic disease in poor countries is the result of a complex constellation of social, economic, and behavioral factors. Variability in the prevalence of chronic disease is found both at the country level and within countries as differences in risk factors are observed. This upward trend is forecast to continue as epidemiologic profiles and age structures of developing countries further shift. More research is needed to identify a full range of prevention‐focused, cost‐effective interventions against chronic diseases in the developing world.
Building an Alliance for a Green Revolution in Africa
Authors: Toenniessen Gary , Adesina Akinwumi , DeVries Joseph
Published: June 2008

Most of Africa's people live in rural areas and depend on agriculture for their livelihoods. These predominantly small‐scale farmers face many challenges, including food insecurity, rising poverty, and natural resource degradation. To increase the productivity, profitability, and sustainability of their farms, they need greater access to affordable yield‐enhancing inputs, including well‐adapted seeds and new methods for integrated soil fertility management, as well as to output markets where they can convert surplus production into cash. To address these needs, the Rockefeller Foundation and the Bill and Melinda Gates Foundation established the Alliance for a Green Revolution in Africa (AGRA). AGRA is now African led and is working within the context of the comprehensive agricultural development program established by Africa's leaders. From offices in Nairobi, Kenya, and Accra, Ghana, AGRA will support work across all key aspects of the African agricultural value chain to help millions of small‐scale farmers and their families lift themselves out of poverty and hunger.
Trends in Private Insurance, Medicaid/State Children's Health Insurance Program, and the Healthcare Safety Net
Authors: Shields Alexandra E. , McGinn‐Shapiro Mary , Fronstin Paul
Published: June 2008

This chapter examines trends in private and public health coverage, as well as implications for vulnerable populations and health disparities. We find that there has been erosion in employment‐based health benefits. Both the percentage of employers offering coverage and the percentage of workers with coverage declined in recent years. Those with coverage face eroding benefits and increased cost sharing. Within the public sector, Medicaid enrollment has decreased, with benefits increasingly restricted. Although State Children's Health Insurance Program (SCHIP) enrollment has increased among low‐income children, the future of SCHIP remains uncertain. Meeting the healthcare needs of Americans and reducing health disparities requires both the provision of health coverage to all and sufficient comprehensiveness of benefits within private and public programs to meet enrollees' healthcare needs. Our findings suggest that we have a long way to go in reaching these goals.
Role of Income and Family Influence on Child Outcomes
Authors: Heckman James J.
Published: June 2008

This chapter examines the role of income and family background in models of capability formation that explains a variety of findings established in the child development and child intervention literatures.
Intersectoral Approaches to Neglected Diseases
Authors: Ault Steven K.
Published: June 2008

The neglected diseases are a diverse group of communicable diseases that affect principally the world's poorest people. They are linked to poverty, as both a cause and a consequence of same, and affect community security and family productivity. The neglected diseases cause acute and chronic illness, disability, and sometimes death, and they may carry stigma for those infected. Current interventions for neglected diseases emphasize the health sector, but to achieve sustainability and simultaneously combat poverty, an intersectoral approach to their prevention and control is needed. This chapter outlines some concepts for an intersectoral approach, including interventions from the nutrition and food security, education, and environmental sectors.
Agriculture in Africa: Strategies to Improve and Sustain Smallholder Production Systems
Authors: Jama Bashir , Pizarro Gonzalo
Published: June 2008

Agricultural development lies at the heart of poverty reduction and increased food security of most developing nations. Sub‐Saharan Africa (hereafter referred to as Africa) is, however, the only region in the world where per capita agricultural productivity has remained stagnant over the past 40 years. In Asia and Latin America, the use of tailored techniques and technologies has transformed agricultural practice and its productivity, leading to what has been called the “green revolution.” The dissemination of uniquely African green revolution technologies has not occurred on the continent. This chapter will argue that the same results in increased productivity and food security can be achieved in Africa if the appropriate investments are made in key interventions: soil fertility improvement, improved seeds, water management, market access, extension services, access to credit, and improvements in weather forecasting. Where these have happened, even partially, the outcome has been remarkable. However, bringing them to scale in ways that sustainably increase agricultural productivity and alleviate poverty requires increased investments and innovative institutional arrangements. Fortunately, several research and development projects on the continent, including the Millennium Villages Project, are providing valuable insights. Finally, this chapter outlines the key remaining challenges.
Diseases of Poverty with High Mortality in Infants and Children
Authors: Kaler Stephen G.
Published: June 2008

Malaria, measles, lower respiratory infections, and diarrheal illnesses are common pediatric medical problems that are often fatal in the context of extreme poverty. In nonpoor environments, however, these infections are controlled and managed in ways that minimize mortality. From a scientific perspective, genetic variation among microbes is a frequent and important component of their epidemiology, pathophysiology, treatment, and prevention. From a public health perspective, relatively simple measures can reduce the mortal effects of these diseases until successful vaccines become available and immunizations programs are established. Infants and children are especially vulnerable to poor outcomes from infections when undernutrition and other circumstances of poverty are present.
Death in the First Person
Authors: Brooks Peter
Published: June 2008

In France, debate on the death penalty runs from the French Revolution until abolition in 1981. One of the more remarkable contributions to the debate is the novel by Victor Hugo, Le dernier jour d'un condamné [The Last Day of a Man Sentenced to Death], first published in 1829, then reprinted with a long, discursive preface in 1832. Hugo makes the strange decision to tell this story of the last day of a man sentenced to die on the guillotine—at four o'clock in the afternoon—in the first person. The implausibility of the narrative technique is a problem, as are Hugo's decisions never to name his condemned man or to give any specifics about his crime. Yet, the first-person perspective develops an undeniable power: getting inside the consciousness of someone about to have his head cut off by the state makes the obscenity of execution powerfully evident. Hugo's novel serves as a starting point for a reflection on the impossible discourses of capital punishment, from the vindictive to the reassuring, including instances from legal opinions.
Ethical Exception: Capital Punishment in the Figure of Sovereignty
Authors: Thurschwell Adam
Published: June 2008

Capital punishment has been analyzed in recent Anglo-American jurisprudence as a problem of moral rather than political philosophy—as a question of when, if ever, the heinousness of a crime justifies the imposition of death as a matter of retributive justice; when, if ever, the deterrent consequences of a sentence of death will outweigh the punishment's deleterious consequences from a utilitarian perspective; and so on. Yet, even the most cursory examination of the cultural, legal, and political roles of capital punishment as it is actually institutionalized (or not institutionalized) and practiced (or not practiced) around the world today demonstrates that this theoretical orientation gets it precisely backward—the most fundamental issues are neither individual nor moral but the profoundly political ones of the constitution and exercise of state sovereignty.

Beginning with Michel Foucault's discussion of capital punishment (which forms one part of his analysis of the nature of political sovereignty) and some recent work by U.S. legal academics that echoes Foucault's discussion (not always consciously), this essay attempts to show how such a shift from the moral perspective to a political-philosophical perspective might be effected and to demonstrate both the theoretical-explanatory and prescriptive-practical benefits of such a change in viewpoint.
eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions
Authors: Lin Yu-Min , Chen Yi-Ru , Lin Jia-Ren , Wang Won-Jing , Inoko Akihito , Inagaki Masaki , Wu Yi-Chun , Chen Ruey-Hwa
Published: June 2008

Keratins 8 and 18 (collectively referred to as K8/K18) are the major components of intermediate filaments of simple epithelial cells. Recent studies have revealed the function of K8/K18 in apoptosis modulation. Here, we show that eIF3k, originally identified as the smallest subunit of eukaryotic translation initiation factor 3 (eIF3) complexes, also localizes to keratin intermediate filaments and physically associates with K18 in epithelial cells. Upon induction of apoptosis, eIF3k colocalizes with K8/K18 in the insoluble cytoplasmic inclusions. Depletion of endogenous eIF3k de-sensitizes simple epithelial cells to various types of apoptosis through a K8/K18-dependent mechanism and promotes the retention of active caspase 3 in cytoplasmic inclusions by increasing its binding to keratins. Consequently, the cleavage of caspase cytosolic and nuclear substrates, such as ICAD and PARP, respectively, is reduced in eIF3k-depleted cells. This study not only reveals the existence of eIF3k in a subcellular compartment other than the eIF3 complex, but also identifies an apoptosis-promoting function of eIF3k in simple epithelial cells by relieving the caspase-sequestration effect of K8/K18, thereby increasing the availability of caspases to their non-keratin-residing substrates.
PKCζ-mediated phosphorylation controls budding of the pre-chylomicron transport vesicle
Authors: Siddiqi Shadab A. , Mansbach Charles M.
Published: June 2008

Dietary triacylglycerols are absorbed by enterocytes and packaged in the endoplasmic reticulum (ER) in the intestinal specific lipoprotein, the chylomicron, for export into mesenteric lymph. Chylomicrons exit the ER in an ER-to-Golgi transport vesicle, the pre-chylomicron transport vesicle (PCTV), which is the rate-limiting step in the transit of chylomicrons across the cell. Here, we focus on potential mechanisms of control of the PCTV-budding step from the intestinal ER. We incubated intestinal ER with intestinal cytosol and ATP to cause PCTV budding. The budding reaction was inhibited by 60 nM of the PKC inhibitor Gö 6983, suggesting the importance of PKCζ in the generation of PCTV. Immunodepletion of PKCζ from the cytosol and the use of washed ER greatly inhibited the generation of PCTVs, but was restored following the addition of recombinant PKCζ. Intestinal ER incubated with intestinal cytosol and [γ-32P]ATP under conditions supporting the generation of PCTVs showed the phosphorylation of a 9-kDa band following autoradiography. The phosphorylation of this protein correlated with the generation of PCTVs but not the formation of protein vesicles and was inhibited by depletion of PKCζ. Phosphorylation of the 9-kDa protein was restored following the addition of recombinant PKCζ. The association of the 9-kDa protein with proteins that are important for PCTV budding was phosphorylation dependent. We conclude that PKCζ activity is required for PCTV budding from intestinal ER, and is associated with phosphorylation of a 9-kDa protein that might regulate PCTV budding.
Lipid droplets are arrested in the ER membrane by tight binding of lipidated apolipoprotein B-100
Authors: Ohsaki Yuki , Cheng Jinglei , Suzuki Michitaka , Fujita Akikazu , Fujimoto Toyoshi
Published: June 2008

Apolipoprotein B-100 (ApoB) is a major component of very-low-density lipoproteins, and is deposited in a region around lipid droplets (LDs) called the `ApoB-crescent'. The ApoB-crescent is thought to be related to ApoB degradation because it drastically increases when proteasome or autophagy is inhibited. In the present study, we found that ApoB-crescents were significantly reduced when ApoB lipidation was suppressed by either the inhibition or knockdown of the microsomal triglyceride-transfer protein. By contrast, ApoB-crescents increased under conditions that are presumed to cause lipidated ApoB abnormalities in secretory compartments. By electron microscopic analyses, we identified the ApoB-crescent as a thin cholesterol-rich ER cistern fused to an LD, and – topologically – this structure is equivalent to a lipid-ester globule between the two leaflets of the ER membrane. ApoB localized in the thin cisternal lumen, and its binding to LDs was resistant to alkaline treatment. Overexpression of ADRP or TIP47 suppressed the increase in the number of ApoB-crescents, whereas knockdown of these proteins had the opposite effect. From these results, we inferred that the ApoB-crescent is formed by an LD that is arrested in the ER membrane by tight binding of lipidated ApoB to its luminal surface. We suggest that ApoB processing and LD formation are closely linked.
Crystal Structure of Boryllithium with Two THF Molecules and DFT Analysis of Its Property as a Boryl Anion
Authors: Yamashita Makoto , Suzuki Yuta , Segawa Yasutomo , Nozaki Kyoko
Published: June 2008

The second crystal structure of boryllithium 2 with two coordinating THF solvent molecules was obtained. The 11B NMR chemical shift of a THF solution, made by dissolving single crystals of 2·(THF)2 in THF-d8, significantly and reversibly changed depending on temperature (from 20 to −100 °C). The calculated 11B chemical shift by GIAO method was close to two experimental values. The character of the sp2 lone pair on the boron center in opt-2·(THF)2 was shown to be similar to those in the calculated free phenyl anion and boryl anion. AIM analyses for opt-2·(THF)2 suggested that the B–Li bond of boryllithium is polarized, similar to the C–Li bond of alkyllithium.
Does HbA1C predict isolated impaired fasting glycaemia in the oral glucose tolerance test in subjects with impaired fasting glycaemia?
Authors: Likhari Taruna , Aulakh T S , Singh Baldev M , Gama R
Published: June 2008

Background

To assess the usefulness of erythrocyte glycated haemoglobin (HbA1C) as a screening tool to identify those subjects with impaired fasting glycaemia (IFG) who do not have impaired glucose tolerance (IGT) or diabetes mellitus (DM) on a 75 g oral glucose tolerance test (OGTT).

Design and methods

All subjects undergoing an OGTT had HbA1C measured at baseline. Receiver operator characteristics analysis was used to identify optimal HbA1C cut-off values for diagnosing and excluding IGT and DM.

Results

We studied 140 subjects (69 women) with IFG (fasting capillary plasma glucose between 6.1–6.9 mmol/L). Using World Health Organisation criteria, 27 had isolated IFG, 56 had IGT and 57 had DM. HbA1C was higher ( P < 0.001) in patients with DM (6.8 ± 0.93%) when compared with those with IGT (6.3 ± 0.68%) and isolated IFG (6.2 ± 0.30%), but HbA1C was similar in those with IGT and isolated IFG. There was no HbA1C cut-off value differentiating isolated IFG from IGT or DM. None of the subjects with isolated IFG had HbA1C concentration of >6.8%, but 76% and 54% subjects with IGT and DM, respectively, had HbA1C of ≤6.8%.

Conclusions

HbA1C measurement is of limited value in differentiating isolated IFG, IGT and DM in subjects with IFG. It cannot be used to identify which subjects with IFG do not require an OGTT.