bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and CD4 Cell Count Pattern of TB Co-infection Among HIV Infected Individuals In Nepal
Authors: Niraula Surya Raj , Barnawal SP , Agrahari AK , Bista N , Yadav DK , Jha N , Pokharel PK
Published: September 2013

Background: Mycobacterium tuberculosis (TB) and Human Immunodefi ciency Virus (HIV) infections are two major public health problems in many parts of the world, particularly in developing counties like Nepal. The objective of the study is to find out prevalence and clinical presentation of the TB co-infection among HIV infected individuals and pattern of CD4 cell count in relation to types of TB and response of ART. Methodology: This is a cross-sectional study carried out in three VCT clinics from Dharan and Kathmandu from April 2010 to March 2011. The appropriate samples, 313 HIV individuals were taken as study sample. Results: The study revealed that more than 36% of individuals were co-infected with TB. Among them, nearly 65% had pulmonary TB, more than one-forth had gland TB. There is signifi cant association of TB co-infection among male compared to females (P=0.021). Fever, weight loss and cough were found to have signifi cant symptoms associated with TB-HIV co-infection. The average CD4 count among TB co-infected population was signifi cantly less compared to uninfected ones just before starting ART (P=0.022) and even after six months (P=0.001). After one year of ART continuation, there was no signifi cant association on average CD4 count among the two groups. But then, the mean CD4 count became more in TB co-infected individuals compared to those who had no TB co-infection. Conclusion: TB-HIV co-infection is an emerging medical issue in Nepal. More than one third of HIV patients are co-infected with TB. Consideration of TB need to be made while caring patients with HIV infection and vice versa. ART plays very important role in increasing CD4 cell count among TB-HIV coinfected patients. SAARC Journal of Tuberculosis, Lung Diseases & HIV/AIDS; 2013; X(1); 27-36 DOI: http://dx.doi.org/10.3126/saarctb.v10i1.8674
Laryngeal Tuberculosis Presenting With Primary Symptoms Of Laryngeal Carcinoma
Authors: Junaid M , Qadeer S , Sobani ZA , Haroon S , Ghaffar S
Published: September 2013

Laryngeal tuberculosis (TB) occurs in about 1% of patients suffering from pulmonary tuberculosis; however presentation of these patients with primary laryngeal symptoms is a rarity. In such situations it forms a diagnostic dilemma between laryngeal TB and the more common laryngeal carcinoma. Highlighting this dilemma we present our patient, a 76 year old male, farmer presenting with primary complaints of progressive dysphagia for 3 weeks. This patient happens to be our second case of laryngeal TB, presenting with primary laryngeal symptoms in a span of under 2 years. We present these cases to emphasize that although laryngeal tuberculosis presenting with primary laryngeal symptoms is a rarity, it must be considered when evaluating dysphagia or dysphonia in populations where TB is endemic. SAARC Journal of Tuberculosis, Lung Diseases & HIV/AIDS; 2013; X(1); 40-42 DOI: http://dx.doi.org/10.3126/saarctb.v10i1.8676
Tuberculosis Problem In Dakahlia Governorate, Egypt
Authors: Aal Amina Mostafa Abdel , El-Mashad Noha , Magdi Dalia
Published: September 2013

Tuberculosis (TB) is a potentially fatal contagious disease that can affect almost any part of the body but is mainly an infection of the lungs. It has been present in humans since antiquity. In the past, tuberculosis has been called consumption, because it seemed to consume people from within, with a bloody cough, fever, pallor, and long relentless wasting. In Egypt, TB constitutes the second most important public health problem after schistosomiasis. Although Egypt has relatively low levels of TB according to data from the World Health of Organization, 2005:66% of TB cases occur among the socially and economically productive age groups of 15 to 54 years. According to Ministry of Health and Population (MOHP), Egypt; tuberculosis control is carried out through 111 chest centers and 39 chest disease hospitals. Treatment failure accounts for 3%–5%of the treatment outcome of new smear positive cases and 13%–17% of retreated cases and this is due to non-compliance to treatment, defi cient health education to the patient, poor patient knowledge regarding the disease and diabetes mellitus as co-morbid. The incidence and prevalence of tuberculosis in Egypt has been declining due to increased efforts of the MOHP. Prevalence dropped from 88/100,000 population in 1990 to 24 in 2008, according to data from WHO. SAARC Journal of Tuberculosis, Lung Diseases & HIV/AIDS; 2013; X(1); 43-49 DOI: http://dx.doi.org/10.3126/saarctb.v10i1.8677
Comparison of the Superpave Gyratory and Proctor Compaction Methods for the Design of Roller-Compacted Concrete Pavements
Authors: Williams Stacy G.
Published: September 2013

Roller-compacted concrete (RCC) is gaining popularity as a paving alternative for various roadway applications. RCC is a zero-slump concrete mixture that does not require forms, reinforcing, jointing, or finishing. This type of material combines the advantages of conventional concrete pavements with the ease of construction of an asphalt pavement and can be opened to traffic more quickly than conventional concrete pavements. The Superpave® gyratory compactor was investigated as an alternative to Proctor compaction (ASTM D1557) for the design of RCC paving mixtures. Seventeen mix designs that encompassed a range of aggregate sources, gradation types, and natural sand contents were generated. In general, the gyratory method did not produce designs equivalent to the Proctor method, in that the gyratory method resulted in higher densities and lower optimum moisture contents. Gyratory compaction tended to generate a maximum, or terminal, achievable moisture content, regardless of the amount of moisture mixed in the specimen. The corresponding densities continued to increase rather than display the parabolic relationship typical of Proctor compaction. The highest densities by both compaction methods tended to be achieved for blend gradations that most closely followed the maximum density line and included the greatest percentages of natural sand.
Le théâtre du sanctuaire de Dionysos Éleuthéreus à Athènes, au Ve s. av. J.-C.
Authors: Moretti Jean-Charles
Published: September 2013

The theaters from the classical period found in Attica (at Thorikos, Ikarion, Euonymon and Rhamnus) and in the NE Peloponnesos (at Corinth, Argos and Isthmia) appear as a pattern for the reconstruction of the theater in the sanctuary of Dionysos Eleuthéreus at Athens. The koilon was pi-shaped, with branches wich were perhaps asymmetric and divergent. It included a prohedria in stone, in form of a simple step, and about forty-five wooden benches mounted on scaffolding. A stage-building of one story was erected for performances in front of the central section of the koilon. It had no second floor, but a terasse roof which was practicable during performances. Behind it stood a crane.
La réutilisation des sanctuaires païens par les Chrétiens en Grèce continentale (IVe-VIIe s.)
Authors: Foschia Laurence
Published: September 2013

Le phénomène de réutilisation des sanctuaires grecs par les chrétiens n'est qu'un aspect de la question plus large du devenir des bâtiments sacrés et profanes au moment de la transformation de la cité grecque classique en cité chrétienne prémédiévale. Dans l'histoire de l'architecture, cette pratique est loin d'être rare mais l'étude de son application aux sanctuaires païens de Grèce propre laisse apparaître certains aspects originaux. En premier lieu, ce phénomène a fait l'objet de récits mettant en scène la conversion de temples païens en églises chrétiennes, textes qui devaient contribuer à marquer de manière triomphale le passage d'une religion à l'autre. Systématisée à l'époque byzantine, cette mythologie de la conversion réapparut dans des études modernes portant sur l'antiquité tardive. La seconde particularité est liée aux modalités d'appropriation et de conversion des temples. La prise de possession spontanée d'un sanctuaire désaffecté semble avoir été plus fréquente que l'achat légal aux autorités provinciales ou que la destruction préalable. Quant aux motifs, ils furent moins idéologiques que pragmatiques, ce dont témoigne le caractère succinct, dans bien des cas, des réaménagements effectués. Cette absence apparente de « motivation anti-païenne » contraste avec ce que l'on observe dans les autres diocèses d'Orient. On est alors conduit à réenvisager le thème plus vaste du processus de christianisation en Grèce continentale et à émettre l'hypothèse d'une non-confrontation violente entre les deux systèmes religieux.
Daubechies Complex Wavelet-Based Computer Vision Applications
Authors: Khare Manish , Srivastava Rajneesh Kumar , Khare Ashish
Published: September 2013

Many methods for computer vision applications have been developed using wavelet theory. Almost all of them are based on real-valued discrete wavelet transform. This chapter introduces two computer vision applications, namely moving object segmentation and moving shadow detection and removal, using Daubechies complex wavelet transform. Daubechies complex wavelet transform has advantages over discrete wavelet transform as it is approximately shift-invariant, has a better edge detection, and provides true phase information. Results after applying Daubechies complex wavelet transform on these two applications demonstrate that Daubechies complex wavelet transform-based methods provide better results than other real-valued wavelet transform-based methods, and it also demonstrates that Daubechies complex wavelet transform has the potential to be applied to other computer vision applications.
Activated Platelets Enhance IL-10 Secretion and Reduce TNF-α Secretion by Monocytes
Authors: Gudbrandsdottir Sif , Hasselbalch Hans C. , Nielsen Claus H.
Published: September 2013

Activated platelets are known to modulate immune responses by secreting or shedding a range of immunomodulatory substances. We examined the influence of activated platelets on cytokine production by normal human mononuclear cells, induced by tetanus toxoid (TT), human thyroglobulin (TG), Escherichia coli LPS, or intact Porphyromonas gingivalis. Addition of platelets activated by thrombin-receptor–activating peptide enhanced IL-10 production induced by LPS (p < 0.001), TG (p < 0.05), and P. gingivalis (p < 0.01), and reduced the production of TNF-α induced by LPS (p < 0.001), TG (p < 0.05), and P. gingivalis (p < 0.001), and of IL-6 in LPS- and P. gingivalis–stimulated cultures (p < 0.001). Similar effects on IL-10 and TNF-α production were observed on addition of platelet supernatant to mononuclear cells, whereas addition of recombinant soluble CD40L mimicked the effects on IL-10 production. Moreover, Ab-mediated blockade of CD40L counteracted the effect of platelets and platelet supernatants on TNF-α production. Monocytes separated into two populations with respect to IL-10 production induced by TG; the high-secreting fraction increased from 0.8 to 2.1% (p < 0.001) on addition of activated platelets. Adherence of platelets increased TG- and TT-induced IL-10 secretion by monocytes (p < 0.05). In addition, activated platelets inhibited CD4+ T cell proliferation elicited by TT (p < 0.001) and P. gingivalis (p < 0.001). Our findings suggest that activated platelets have anti-inflammatory properties related to the interaction between CD40L and CD40, and exert a hitherto undescribed immunoregulatory action by enhancing IL-10 production and inhibiting TNF-α production by monocytes.
Identification of the Cellular Sentinels for Native Immunogenic Heat Shock Proteins In Vivo
Authors: Messmer Michelle Nicole , Pasmowitz Joshua , Kropp Laura Elizabeth , Watkins Simon C. , Binder Robert Julian
Published: September 2013

Select members of the heat shock proteins (HSPs) family, such as gp96, elicit immune responses specific to their chaperoned peptides. Although immunologic effects of HSPs on APCs described to date have largely been demonstrated with cell lines or primary cells in culture, their collective responses in vitro have been consistent with priming immune responses. In this study, we examine the physiologically relevant APCs in mice that are targeted after vaccination with native, murine HSPs, and we characterize those cells. Gp96 accesses the subcapsular region of the draining lymph node, and it is internalized predominantly by CD11b+ cells in this locale. Cells acquiring gp96 can transfer protective antitumor immunity to naive mice by actively cross-presenting gp96-chaperoned peptides and providing costimulation. Our studies illustrate how HSPs act to alert the immune system of cellular damage and will be of paramount importance in immunotherapy of patients with cancer and infectious disease.
The Mitochondrial Antiviral Protein MAVS Associates with NLRP3 and Regulates Its Inflammasome Activity
Authors: Park Sangjun , Juliana Christine , Hong Sujeong , Datta Pinaki , Hwang Inhwa , Fernandes-Alnemri Teresa , Yu Je-Wook , Alnemri Emad S.
Published: September 2013

NLRP3 assembles an inflammasome complex that activates caspase-1 upon sensing various danger signals derived from pathogenic infection, tissue damage, and environmental toxins. How NLRP3 senses these various stimuli is still poorly understood, but mitochondria and mitochondrial reactive oxygen species have been proposed to play a critical role in NLRP3 activation. In this article, we provide evidence that the mitochondrial antiviral signaling protein MAVS associates with NLRP3 and facilitates its oligomerization leading to caspase-1 activation. In reconstituted 293T cells, full-length MAVS promoted NLRP3-dependent caspase-1 activation, whereas a C-terminal transmembrane domain–truncated mutant of MAVS (MAVS-ΔTM) did not. MAVS, but not MAVS-ΔTM, interacted with NLRP3 and triggered the oligomerization of NLRP3, suggesting that mitochondrial localization of MAVS and intact MAVS signaling are essential for activating the NLRP3 inflammasome. Supporting this, activation of MAVS signaling by Sendai virus infection promoted NLRP3-dependent caspase-1 activation, whereas knocking down MAVS expression clearly attenuated the activation of NLRP3 inflammasome by Sendai virus in THP-1 and mouse macrophages. Taken together, our results suggest that MAVS facilitates the recruitment of NLRP3 to the mitochondria and may enhance its oligomerization and activation by bringing it in close proximity to mitochondrial reactive oxygen species.
Barriers to and facilitators of rehabilitation services for people with physical disabilities: A systematic review
Authors: Mlenzana Nondwe B. , Frantz Jose M. , Rhoda Anthea J. , Eide Arne H.
Published: September 2013

Background: As health care practitioners, it is important to have an understanding of the common barriers to and facilitators of the rehabilitation services we provide.Objectives: This article aimed to review the relevant literature regarding barriers to and facilitators of rehabilitation services for people with disabilities.Method: Articles for the period 1990–2010 using descriptors related to rehabilitation services, barriers, facilitators and the physically disabled population were retrieved for this review.Results: A total of 19 article titles were identified from references of other articles but following application of the inclusion criteria selected for this review, only six articles were chosen. Five of these articles were qualitative studies and one was a quantitative study. Barriers and facilitators regarding rehabilitation services highlighted by participants in the studies included a perception that health professionals have a lack of understanding of rehabilitation for people with disabilities and there was a lack of information sharing from health professionals about the rehabilitation process. On the other hand some participants reported that health professionals demonstrated confidence in the disability and rehabilitation process during consultation and highlighted that their needs were met by the rehabilitation professionals.Conclusion: Even though there were few studies highlighting the barriers to and facilitators of rehabilitation services, they highlighted that there are gaps in the process of rehabilitation services provided. It would be advisable for health professionals to take cognisance of the issues highlighted in this study in order to make rehabilitation services more effective.
On the Local Convexity of Intersection Bodies of Revolution
Authors: Angeles Alfonseca M. , Kim Jaegil
Published: September 2013

One of the fundamental results in convex geometry is Busemann's theorem, which states that the intersection body of a symmetric convex body is convex. Thus, it is only natural to ask if there is a quantitative version of Busemann's theorem, i.e., if the intersection body operation actually improves convexity. In this paper we concentrate on the symmetric bodies of revolution to provide several results on the (strict) improvement of convexity under the intersection body operation. It is shown that the intersection body of a symmetric convex body of revolution has the same asymptotic behavior near the equator as the Euclidean ball. We apply this result to show that in sufficiently high dimension the double intersection body of a symmetric convex body of revolution is very close to an ellipsoid in the Banach–Mazur distance. We also prove results on the local convexity at the equator of intersection bodies in the class of star bodies of revolution.
The Impact of Military Work Experience on Later Hiring Chances in the Civilian Labour Market. Evidence from a Field Experiment
Authors: Baert Stijn , Balcaen Pieter
Published: September 2013

This study directly assesses the impact of military work experience compared with civilian work experience in similar jobs on the subsequent chances of being hired in the civilian labour market. It does so through a field experiment in the Belgian labour market. A statistical examination of our experimental dataset shows that in general we cannot reject that employers are indifferent to whether job candidates gained their experience in a civilian or a military environment.
Can Failing to Check Sources Give Rise to Monsters? The Iconographical History of a Paradigmatic Case
Authors: Montemagno Ciseri Lorenzo
Published: September 2013

In the early fourteenth-century chronicle by Giovanni Villani there is a singular report of a monstrous birth. The little double monster was depicted in a sandstone panel that was exposed in the front of the Santa Maria della Scala hospital in Florence. This essay tries to prove how failing to check sources gives rise to monsters by following the extraordinary iconographical history of this particular image of conjoined twins.
Causality in Economics: A Menu of Approaches
Authors: Pol Eduardo
Published: September 2013

Causality is a notion that occurs often in economics. In using the words â€˜cause' and â€˜effect,' economists seek to distinguish causation from association, recognizing that causes are responsible for producing effects, whereas non-causal associations are not. The identification of causes is accorded a high priority because it is viewed as the basis for understanding economic phenomena and developing policy implications. In this survey we look at different approaches to causality in economics and set out the general principles of each approach, so as to assist in the communication and teaching role. Specifically, we confine attention to five approaches to causality in economics (narrative, comparative statics, theoretical, structural, and experimentalist) and elucidate their distinctive characteristics without entering into philosophical discussions. In particular, we pay close attention to the debate between the structuralist and experimentalist schools because this controversy has been extremely useful to clarify a number of fundamental points concerning causality in economics
Le libéralisme de la prudence : contribution à un minimalisme politique
Authors: Tavaglione Nicolas
Published: September 2013

Il s’agit ici de présenter une version raffinée du libéralisme de la peur de Judith Shklar : le libéralisme de la prudence. Après en avoir brièvement présenté les grandes lignes et les principales faiblesses, j’esquisse les contours du libéralisme de la prudence et montre comment il réalise, mieux que libéralisme de la peur, le programme minimaliste poursuivi par Shklar. Je montre ensuite comment le libéralisme de la prudence nous permet de sortir du dilemme libéral posé par la tradition postrawlsienne : justifier le libéralisme sur des bases morales, au risque de le priver de neutralité, ou le justifier sur des bases réalistes hobbesiennes, au risque d’en faire l’otage des rapports de force changeants. Enfin, j’examine comme le principal défaut apparent du libéralisme de la prudence – à savoir son ascétisme programmatique – est en fait son principal mérite.
Le comité d’éthique, la vie privée et l’intimité. Interpréter les droits des usagers
Authors: Clément Michèle , Gagnon Éric
Published: September 2013

Le respect de la vie privée et de l’intimité est un droit reconnu aux usagers des services de santé et des services sociaux par différents codes d’éthique, par la Charte des droits et libertés de la personne du Québec et par la Loi sur les services de santé et les services sociaux. Pour autant, la signification que prend ce droit demeure incertaine. Il n’y a pas une signification, mais bien des significations. S’appuyant sur un important travail d’observation dans deux comités d’éthique clinique situés dans des établissements de santé et de services sociaux, les auteurs présentent et analysent ici un certain nombre de situations litigieuses dans lesquelles une interprétation du droit à la vie privée et à l’intimité a été faite. Au terme de l’exercice, il ressort entre autres que, selon les situations analysées, les discussions qui se font dans les CÉC conduisent à des modalités différentes (« déplacement et hiérarchisation », « opposition et évitement », « ouverture et compromis », « élargissement et remise en question ») qui ont pour effet de changer le regard porté sur l’usager et plus spécifiquement de faire comprendre son point de vue. En outre, si le droit à la vie privée et à l’intimité contribue à modifier l’interprétation que l’on se fait d’une situation ou des usagers, il est lui-même objet d’interprétation. C’est la diversité de sens qu’il peut prendre qui lui préserve son pouvoir d’interroger.
Trapped in a Local History: Why Did Extramural Fail to Engage in the Era of Engagement?
Authors: Duke Chris
Published: September 2013

Extramural liberal adult education (LAE), as conceived in the particular UK tradition, was doomed by its high-minded origins and its privileged status, and contributed little to the new concepts of éducation permanente, lifelong learning, the knowledge society, the learning society and region, or to the new understandings of university engagement and regional development becoming prominent with the new millennium. The recent introduction of equivalent or lower qualifications (ELQs) is likely to bring about the complete demise of the tradition. Meanwhile ‘the university’ grows and changes in diverse and important ways and directions little informed by the commendable and abiding purposes for which extramural LAE was founded, although this might benefit from the socially informed liberal perspectives of and the facilitation skills honed in extra-mural departments (EMDs). University engagement in regional development has become unbalanced towards the (neo) liberal economic and the technical/skills agenda. Universities as well as regions are the poorer as a result. As the world experiences new forms and intensities of economic, environmental, geopolitical and cultural crisis, rebalancing in favour of a wider civic mission becomes the more urgent.
Mitochondrial Genome Sequences and Their Phylogeographic Interpretation
Authors: Macaulay Vincent , Richards Martin B
Published: September 2013

The strong phylogenetic signal provided bymitochondrial deoxyribonucleic acid (mtDNA)sequences within species is being exploited to reconstruct the maternal genealogy and anchor it in space and time. This is the starting point for interpretations of the processes in population history that led to those patterns, as illustrated here for humans. Mitochondrial phylogeography began by revolutionising our view of modern human origins, with the demonstration that modern humans dispersed from Africa approximately 60 000 years ago. Now benefitting from the high genealogical and chronological resolution afforded by whole‐mtDNA sequences, and despite the advent of genome‐wide analyses, mtDNA continues to illuminate prehistoric settlement and dispersal history. It has often led to challenges to received wisdom, such as the stress on pre‐Neolithic dispersals at the end of the Ice Age in many parts of the world, and the database of contemporary variation is currently being augmented by rapidly increasing information from ancient DNA.

Key Concepts:

Mitochondrial DNA is now routinely analysed at the level of whole‐mtDNA genome sequences.

The human mtDNA gene tree is an estimate of the maternal genealogy and preserves a record of the dispersal history of our species, in the distribution of its branching points in space and time, or ‘phylogeography’.

A time scale is provided by an independently calibrated mutation rate, the ‘molecular clock’, which is now available for whole‐mtDNA sequences and allows for the effects of purifying selection.

Although phylogeographic inference can be criticised for lacking a formal hypothesis testing framework, proposed alternatives based on simulation are currently insufficient to tackle the nuances of real human dispersal histories.

Variation in mtDNA has led to a number of revolutionary models in human evolutionary history, beginning with the African origin of modern humans.

More recent suggestions have included a single southern‐coastal dispersal route out of Africa and the importance to the shaping of extant human diversity of hunter–gatherer dispersals and expansions at the end of the last Ice Age.

An increasing volume of data from ancient DNA holds great promise not only for testing interpretations of contemporary variation but also for identifying both ancient processes that left no trace in the modern gene pool and more recent dispersals that studying extant cannot resolve.

Genome‐wide analyses now allow both testing of hypotheses arising from mtDNA studies and access to many previously unanswerable questions, but mtDNA nevertheless retains a vital role due to its relative genealogical and chronological precision.
Transplantation of Haematopoietic Stem Cells
Authors: Alam Naheed , Kim Dennis
Published: September 2013

Haematopoietic cell transplantation encompasses infusion of progenitor cells (stem cells) into patients with haematological and other diseases. These cells can be obtained from the patients themselves (autologous) or from somebody else (allogeneic). The source of the cells can be bone marrow or peripheral or cord blood. Autologous transplantation can be used as consolidation for diseases like lymphoma and myeloma. Allogeneic transplantation can be potentially curable in certain diseases like bone marrow failure syndromes, leukaemias and myelodysplastic syndrome. There are several types of donors available including sibling, unrelated (adult or cord blood) and haploidentical. Chemotherapy ± radiation is given before infusion of these cells. In addition, there are risks of acute and chronic graft‐versus‐host disease as well as infections. Ongoing studies seek to improve the outcomes of these transplantations.

Key Concepts:

Haematopoietic cell transplantation is a process which includes treatment of a patient with chemotherapy ± radiation after which the patient receives infusion of stem cells.

Autologous transplantation implies receiving patients' own stem cells.

Allogeneic transplantation implies receiving stem cells from another person (donor).

Donor options include sibling, related or unrelated adult and umbilical cord blood.

Haematopoietic cell transplantation can be performed for malignant and nonmalignant haematological disease.

Stem cells can be obtained from peripheral blood after mobilisation or from bone marrow.

Acute and chronic graft‐versus‐host disease are common complications, which are the process of graft recognising patient (recipient) as foreign and hence initiating an immune response against them.

Acute and chronic graft‐versus‐host disease are treated with immune‐suppressive agents, which can cause problems with infections.

Long‐term survivors should be monitored closely for long‐term complications.
Tumour Immunology
Authors: Copier John , Dalgleish Angus
Published: September 2013

Tumour immunology is central to our understanding of the mechanisms of both tumour rejection and tumour progression. Virtually every known cell type of the immune system is represented in the tumour microenvironment, but as yet the functional significance of intratumoral effector cells is not fully understood. Moreover, the complex interactions between these immune cells within the tumour have yet to be fully elucidated. Although many individual effector cells have the capacity to kill tumour cells
in vitro
, they are frequently suppressed within the tumour microenvironment through a range of mechanisms. In this article, the known functions of immune effector cells within the tumour and the suppressive processes limiting the function of those cells are described. The purpose of tumour immunology should be to give us a better understanding of how to manipulate the immune system to fight cancer. Some relevant applications of tumour immunotherapy are therefore described.

Key Concepts:

Tumours are infiltrated by a broad range of immune cell types, all of which have demonstrable functions within the tumour microenvironment.

The immune system can play a role in tumorigenesis and metastasis.

The concept of immunesurveillance means that the innate and adaptive immune response is able to seek out and kill tumours, particularly at early stages in development.

Cells of the innate immune system play a crucial role in both antitumorigenic and protumorigenic processes. NK, NKT and γδ T cells all have tumoricidal functions.

The discovery of TAAs that make tumours immunologically different from other healthy tissues explains the ability of the adaptive immune system to recognise tumours as ‘nonself’.

The current paradigm suggests that a TH1 effector response is required for effective antitumour T‐cell responses. CD8+ T cells recognise tumour cells bearing peptides derived from TAAs in the context of self‐MHC.

Antibodies may play a role in the adaptive response to tumours. A number of mechanisms have been defined (such as ADCC and CDC), which are dependent on antibody responses. Monoclonal antibody therapy for cancer has shown the potential power of humoral responses.

The tumour microenvironment is infiltrated by immune suppressive cells, including T‐regs, MDSCs and TAMs. These cells play a key role in both suppression of adaptive and innate responses against tumours, and also contribute towards tumour progression.

Tumour cells are known to have the capacity to escape the immune response by modulating the expression of key target molecules.

Over the last 30 years advances in our understanding of tumour immunology have led to an array of new cancer therapies based on manipulation of the immune system.
Dinosaur Physiology: Were Dinosaurs Warm‐Blooded?
Authors: Quick Devon E , Hillenius Willem J
Published: September 2013

To evaluate the possible physiology of dinosaurs, comparisons must be made with their closest living relatives: birds and crocodilians. Although crocodilians maintain ectothermic metabolic rates and have anatomy reflective of this, modern birds achieve high, endothermic metabolic rates through specialised soft tissues supported by unique skeletal attributes. Finding similar shared characters in dinosaurs that are functionally linked to metabolic rates in birds or crocodilians allows plausible reconstruction of dinosaur physiology. Examinations of dinosaur remains reveal no structures with clear functional association with bird‐like respiratory or metabolic physiology, and in some cases indicate crocodilian‐like anatomy. Consequently, dinosaurs were most likely ectothermic, with resting and maximal metabolic rates that were lower than those of modern mammals or birds. However, given the favourable Mesozoic climatic conditions, most dinosaurs were probably able to maintain high, constant body temperatures through behavioural or inertial thermoregulation.

Key Concepts:

Reconstructing the biology of extinct forms relies on comparison with living taxa that share the same specialised features linked to specific function.

Stable body temperature can be achieved through behavioural mechanisms or through virtue of large mass, and need not rely on a particular metabolic strategy.

The closest living relatives of dinosaurs are birds and crocodilians, which have widely different metabolic rates supported by different respiratory and skeletal anatomy.

Some dinosaur remains preserve evidence, such as postcranial pneumaticity, that may be superficially suggestive of modern bird‐like respiratory anatomy, but they lack other features critical for the ability to ventilate bird‐like lungs or achieve bird‐like aerobic capacity.

No dinosaur remains show evidence of respiratory turbinates, a skeletal character functionally associated with modern endothermy.

Endothermy was not likely achieved in dinosaurs, but was first present in mid‐Cretaceous birds.

Some dinosaurs may have increased aerobic capacity using a crocodilian‐like ventilatory mechanism.
Gymnosperms
Authors: MacKinnon Andy
Published: September 2013

Gymnosperms are a diverse group of plants with the common characteristic of having a ‘naked’, or unprotected, seed. (This contrasts with the other major seed‐bearing plant group, the angiosperms, whose seeds are enclosed in layers of tissue during development.) Historically common, today only approximately 1000 species exist worldwide. Four broad divisions (cycads, ginkgos, conifers and gnetophytes) are generally recognised. Gymnosperms are found in a wide variety of habitats, throughout most of the world. Many are trees: conifers are mostly evergreen trees with needle‐ or scale‐like leaves; cycads are palm‐like trees; ginkgos are deciduous, broad‐leaved trees and gnetophytes are mostly woody climbers (vines) or shrubs. The conifers are the most significant group of timber‐producing trees, and provide the majority of solid wood products worldwide. The economies of many countries depend on ‘softwood’ lumber derived from conifers.

Key Concepts:

Gymnosperms are plants with a ‘naked’, or unprotected, seed.

Gymnosperms live in a variety of habitats worldwide.

There are approximately 1000 species of gymnosperms alive today, in four broad divisions: cycads, ginkgos, conifers and gnetophytes.

Many gymnosperms are trees, and some are economically important as a source of timber and pulp.

Most gymnosperms are evergreen, woody perennials.
Single‐Step Method of Total
RNA
Isolation by Guanidine–Phenol Extraction
Authors: Chomczynski Piotr , Wilfinger William , Mackey Karol
Published: September 2013

The original single‐step method is the first procedure to isolate purified total
ribonucleic acid (RNA)
from a variety of sources including tissues and cells from human, animal, plant, yeast, bacterial and viral origins, without the requirement of high‐speed ultracentrifugation. The method is based on liquid‐phase separation resulting in sequestration of pure RNA into the aqueous phase. RNA is precipitated from the aqueous phase, dissolved, reprecipitated and washed with alcohol before the final solubilisation step. The entire procedure can be completed in less than 4 h and it provides RNA that is suitable for many sensitive downstream applications such as RNase protection assays, northern blotting, sequencing studies and reverse transcription‐polymerase chain reaction. This pioneering methodology has served as the impetus for the development of newer and improved RNA extraction methodology that now enable investigators to extract and purify RNA in less than 60 min.

Key Concepts:

Enzymes within living cells rapidly degrade RNA after a tissue sample is removed from the donor. To prevent RNA degradation, tissue samples that cannot be immediately processed must be rapidly frozen with dry ice or liquid nitrogen and stored frozen at −80 °C until the RNA can be extracted.

At the time of RNA extraction, frozen cells or tissues must be immersed in the denaturing solution and rapidly homogenised before the tissue thaws in order to inactivate RNAse and avoid RNA degradation.

The quality of the recovered RNA is dependent on a delicate balance of salt concentration and optimal pH. Overloading the extraction solution with too much tissue or diluting the denaturing solution beyond what is specified in the protocol will impact the quality of the resulting RNA.

The extraction of RNA from samples that have a high buffering capacity, such as blood, plasma or tissue culture medium, requires greater care in order to maintain optimal salt balance and pH control.

Overdrying of the RNA pellets will impede RNA solubilisation.

RNA should be solubilised at a concentration that will be appropriate for meaningful spectrophotometric quantitation as well as subsequent downstream molecular biology applications.

Enzymes that are involved in RNA degradation are ubiquitous and special care must be taken to avoid RNAse contamination during RNA solubilisation and storage.
Mammalian Sex Chromosome Evolution
Authors: Wyckoff Gerald J , Malcom Christine M
Published: September 2013

Although they are highly dissimilar in sequence content in extant organisms, the mammalian sex chromosomes (i.e. the X and Y) evolved from a pair of autosomes. Differentiation of the sex chromosomes during evolution was initiated by the suppression of X–Y recombination, likely through changes in genomic structure. This was followed by the degeneration of genes on the Y chromosome, with specific instances of gene specialisation on the nonrecombining portion of the Y. Findings of evolutionary ‘strata’ on the sex chromosomes of mammals suggest that multiple events have given rise to the current arrangement of genes on the X and Y chromosomes of mammals. However, new studies utilising more divergent genomic data are challenging conclusions regarding the number and frequency of events that led to the current arrangement of mammalian sex chromosomes, and future studies with complete genomic sequences of marsupials will continue to further our understanding of the evolution of these critical chromosomes.

Key Concepts:

Mammalian sex chromosomes arose from a pair of autosomes.

Genomic rearrangements repressed recombination in a stepwise fashion on these chromosomes.

Genes on these chromosomes diverged due to a combination of forces, including sexual antagonism and removal of deleterious mutations.

Chromosomal studies outside placental mammals continue to contribute to our understanding of mammalian sex chromosome evolution.

Groups of genes on sex chromosomes with similar evolutionary origins are called gene ‘strata’ and exist on both the X and Y chromosomes in the nonrecombining regions.
Evolutionarily Conserved Noncoding
DNA
Authors: Jegga Anil G , Aronow Bruce J
Published: September 2013

Noncoding
deoxyribonucleic acid (DNA)
, which includes all sequences within the genome except exon sequences that encode the protein‐reading frames, harbours a wide variety of regulatory genomic features and elements. The availability of increasingly complete and accurate genomic sequence data from evolutionarily separated species – as well as diverse strain and ethnic variants within species – is providing an unprecedented opportunity to identify potentially functional regions within the genomic noncoding DNA. A variety of computational approaches enable genome‐wide detection, characterisation and visualisation of highly conserved sequences and the occurrence of potentially functional elements within both the conserved and evolved elements. As a result of the continued discovery of these functional elements, the nongenic genetic neighbourhoods are now considered as keys to identifying regulatory elements that are essential for gene and chromosomal function. In this article is given an overview of the various known components of the noncoding DNA landscape and present some of the bioinformatic‐based approaches and resources to identify and analyse the potential regulatory regions in genomic sequences.

Key Concepts:

An indeterminate fraction of the noncoding proportion of the human genome has a decisive role in regulating gene expression.

Comparisons among genome sequences are keys to identifying the functional regions of noncoding DNA.

Identifying and analysing ‘phylogenetic footprints’ is a standard approach to examine for potential regulatory regions.

Two common features of long‐range regulatory elements are that they are frequently conserved in other mammals and are unique within the human genome.

It is not only the conservation of the noncoding DNA but also the loss of the same that holds some of the clues to understand our phenotypic complexity and diversity.

Post‐ENCODE, the genome is viewed as a network of collaborating RNA transcripts with many of the regulatory regions of proteins transcribed into RNA and serve as regulators (e.g., microRNAs and siRNAs).
Human Lineage‐Specific Gene Inactivation
Authors: Grus Wendy E , Zhang Jianzhi
Published: September 2013

Pseudogenes are nonfunctional vestiges of genes. Investigating genes that were inactivated specifically on the human lineage or within humans can reveal the genetic basis of interspecies differences between humans and chimpanzees and interindividual differences within humans. It can also help understand the selective pressures that altered during human evolution or vary among human populations. Recent genome‐wide surveys showed that human‐specific pseudogenisation events occurred much more frequently to chemosensory and immune response genes than to other genes. Although nondeleterious pseudogenisation events were traditionally considered to be neutral, emerging evidence suggests that some of them are beneficial. One well‐characterised case is the human
CASP12
locus, where the null allele decreases the incidence of sepsis and has apparently been selected for in human evolution. Exploration of roles of pseudogenisation in genome evolution and phenotype evolution has started.

Key Concepts:

Pseudogenes in our genome can be (1) shared with other species, (2) functional only in non‐human species or (3) functional in some but not all humans.

According to the ‘less‐is‐more’ hypothesis, human‐specific pseudogenes that are functional in related primates reveal insight into how gene loss helped shape human evolution.

Large‐scale human genetic variation databases reveal hundreds of segregating pseudogenes, suggesting individual and population differences in functional gene content.

Although most gene‐disrupting variants are under negative selective pressure, some population genetic studies of segregating pseudogene loci reveal signatures of positive selection for the disrupted allele, suggesting that gene loss can be beneficial.

Among fixed and segregating human‐specific pseudogenes, chemoreception and immune response are over‐represented functional categories.
Tricks and Tracks in the Identification and Quantification of Endocannabinoids
Authors: Lerner Raissa , Lutz Beat , Bindila Laura
Published: September 2013

The endocannabinoid system serves pivotal roles in a diverse range of physiological and pathophysiological states, including behavior, pain, schizophrenia, obesity, Alzheimer disease, multiple sclerosis and cardiovascular disease. A number of endocannabinoids (eCBs) and their receptors have been characterised and identified in a plethora of biological matrices. The eCBs include
N
‐arachidonoyl ethanolamine (anandamide), 2‐arachidonoyl glycerol, 2‐arachidonoyl glyceryl ether (noladin ether),
O
‐arachidonoyl ethanolamine (virodhamine) and
N
‐arachidonoyl dopamine. Advanced targeted mass spectrometry methods, particularly the selected reaction monitoring, has facilitated sensitive quantification of eCBs owing particularly to minimisation of the complex and abundant lipid matrix, invariably accompanying the eCBs in biological extracts. In this article, state‐of‐the‐art analytical workflows for eCBs extraction and mass‐spectrometry identification and quantification are concisely reviewed. Challenges and considerations on the isolation and analytical conditions to prevent artificial interferences in the measurement of eCBs concentration will be highlighted.

Key Concepts:

Endocannabinoids are lipid signalling molecules with pivotal role in a plethora of physiological and pathophysiological states, including anxiety, fear, learning and memory, pain
etc
.

Imbalances in the ECS activity underlie various psychiatric, neurological, metabolic and immunological diseases, and thus ECS is emerging as an appealing therapeutic target.

Quantitative profiling of endocannabinoids in various biological tissues is imperative to discover their site of action and determine the reference and altered concentration values.

Chemical isomerisation of eCBs, as well as
ex‐vivo
degradation and synthesis can occur during biological matrix sampling and processing, leading to artificial changes in the endogenous levels of eCBs.

Conditions for biological matrix sampling, storage, transportation and eCBs extraction methods have to be tailored and standardised with respect to biological matrix to achieve a reliable determination of reference and disease or pathological state‐related altered concentrations of eCBs in tissues and bodily fluids.

LC–ESI/SRM is the method of choice for eCBs quantification owing to the increased selectivity, specificity, robustness, precision and accuracy of quantification.

Validation and standardisation of LC/MS assays, biological matrix sampling and processing from tissues and bodily fluids are pivotal to allow comparison of eCB levels across studies and for prospective clinical research.