bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling the influence of predicted future climate change on the risk of wind damage within New Zealand's planted forests
Authors: Moore John R. , Watt Michael S. 
Published: February 2015

AbstractWind is the major abiotic disturbance in New Zealand's planted forests, but little is known about how the risk of wind damage may be affected by future climate change. We linked a mechanistic wind damage model (ForestGALES) to an empirical growth model for radiata pine (Pinus radiata D. Don) and a process‐based growth model (cenw) to predict the risk of wind damage under different future emissions scenarios and assumptions about the future wind climate. The cenw model was used to estimate site productivity for constant CO2 concentration at 1990 values and for assumed increases in CO2 concentration from current values to those expected during 2040 and 2090 under the B1 (low), A1B (mid‐range) and A2 (high) emission scenarios. Stand development was modelled for different levels of site productivity, contrasting silvicultural regimes and sites across New Zealand. The risk of wind damage was predicted for each regime and emission scenario combination using the ForestGALES model. The sensitivity to changes in the intensity of the future wind climate was also examined. Results showed that increased tree growth rates under the different emissions scenarios had the greatest impact on the risk of wind damage. The increase in risk was greatest for stands growing at high stand density under the A2 emissions scenario with increased CO2 concentration. The increased productivity under this scenario resulted in increased tree height, without a corresponding increase in diameter, leading to more slender trees that were predicted to be at greater risk from wind damage. The risk of wind damage was further increased by the modest increases in the extreme wind climate that are predicted to occur. These results have implications for the development of silvicultural regimes that are resilient to climate change and also indicate that future productivity gains may be offset by greater losses from disturbances.
Evaluating a hand‐held crop‐measuring device for estimating the herbage biomass, leaf area index and crude protein content in an Italian ryegrass field
Authors: Lim Jihyun , Kawamura Kensuke , Lee Hyo‐Jin , Yoshitoshi Rena , Kurokawa Yuzo , Tsumiyama Yoshimasa , Watanabe Nariyasu 
Published: February 2015

AbstractThe objective of this study is to evaluate the ability of a newly developed hand‐held crop‐measuring device and vegetation indices (VIs) to estimate the herbage biomass (BM), leaf area index (LAI) and forage crude protein mass (CPmass) in an Italian ryegrass (Lolium multiflorum Lam.) field, Japan. The device uses bi‐directional passive sensors (550, 650 and 880 nm) upward and downward to overcome the major drawback of optical remote sensing as influenced by weather conditions. The canopy reflectance and plant sample data were collected 11 times during two winter growing seasons in 2010–11 and 2011–12. Seven VIs were compared to estimate the forage parameters in the normal and logarithmic forms. The predictive ability of the VIs was assessed by the cross‐validated coefficient of determination (R2cv) and the residual prediction (RPD) values. Acceptable RPD values (>1.5) were found in most of the log‐transformed forage parameters with all of the VIs but not in most of the normal‐form. The highest R2cv and RPD were obtained in the normalized difference vegetation index (NDVI) for the ln BM (R2cv = 0.76, RPD = 2.04) and ln LAI (R2cv = 0.80, RPD = 2.25), and the highest modified soil‐adjusted vegetation index (MSAVI) was obtained for the ln CPmass (R2cv = 0.78, RPD = 2.16). By evaluating the limitation of NDVI or MSAVI sensitivity with ranges of cumulative data, the log‐transformed forage parameters showed good R2cv values in the ln BM (0.76–0.79), ln LAI (0.80–0.84) and ln CPmass (0.71–0.84) with acceptable RPD values throughout most of the range, whereas in the normal‐form, the NDVI or MSAVI was saturated at moderate‐high BM, LAI or CPmass, causing the R2cv and RPD values to decrease with increasing plant parameters. These results suggest that this device is applicable in log‐transformed BM, LAI and CPmass throughout the growing season without cloud effect.
Analysis of miRNA expression patterns in human and mouse hepatocellular carcinoma cells
Authors: Baek Sinhwa , Cho Kyung Joo , Ju Hye‐Lim , Moon Hyuk , Choi Sung Hoon , Chung Sook In , Park Jun Yong , Choi Ki Hong , Kim Do Young , Ahn Sang Hoon , Han Kwang‐Hyub , Ro Simon Weonsang 
Published: February 2015

AimHepatocellular carcinoma (HCC), one of the most common malignancies in adults displays aberrant miRNA expression during its pathogenesis. We assessed expression of miRNA in surgically resected human HCC of an early stage and murine HCC with a high malignancy in order to find miRNA overexpressed in HCC regardless of tumor stage and underlying etiology. Further, the role of the deregulated miRNA in HCC pathogenesis was investigated.MethodsmiRNA were isolated from HCC tissues and surrounding non‐tumorous tissues from HCC patients and a murine transgenic model of HCC. A quantitative reverse transcription polymerase chain reaction was performed to determine expression levels of miRNA. Human HCC cell lines stably expressing individual miRNA were generated to investigate the biological function of overexpressed miRNA.ResultsWe found that levels of miR‐221, ‐181b‐1, ‐155‐5p, ‐25 and ‐17‐5p were significantly upregulated in both human and murine HCC regardless of tumor stage, underlying etiology or the presence of fibrosis. Using HCC cell lines stably expressing respective miRNA, we found that miR‐221 increased the proliferation of hepatoma cells, while miR‐17‐5p induced cell migration.ConclusionWe identified miRNA that are consistently upregulated in HCC. The overexpressed miRNA could potentially be used as a bona fide biomarker for HCC.
Cytokine and lipid mediator networks in tuberculosis
Authors: Mayer‐Barber Katrin D. , Sher Alan 
Published: February 2015

SummaryA major approach for immunologic intervention in tuberculosis involves redirecting the outcome of the host immune response from the induction of disease to pathogen control. Cytokines and lipid mediators known as eicosanoids play key roles in regulating this balance and as such represent important targets for immunologic intervention. While the evidence for cytokine/eicosanoid function derives largely from the investigation of murine and zebrafish experimental infection models, clinical studies have confirmed the existence of many of the same pathways in tuberculosis patients. Here, we summarize new data that reveal important intersections between the cytokine and eicosanoid networks in the host response to mycobacteria and discuss how targeting this crosstalk can promote resistance to lethal Mycobacterium tuberculosis infection. This approach could lead to new host‐directed therapies to be used either as an adjunct for improving the efficacy of standard antibiotic treatment or for the management of drug‐resistant infections.
Release of mycobacterial antigens
Authors: Majlessi Laleh , Prados‐Rosales Rafael , Casadevall Arturo , Brosch Roland 
Published: February 2015

SummaryMycobacterium tuberculosis has evolved from a Mycobacterium canettii‐like progenitor pool into one of the most successful and widespread human pathogens. The pathogenicity of M. tuberculosis is linked to its ability to secrete/export/release selected mycobacterial proteins, and it is also established that active release of mycobacterial antigens is a prerequisite for strong immune recognition. Recent research has enabled mycobacterial secretion systems and vesicle‐based release of mycobacterial antigens to be elucidated, which together with host‐related specificities constitute key variables that determine the outcome of infection. Here, we discuss recently discovered, novel aspects on the nature and the regulation of antigen release of the tuberculosis agent with particular emphasis on the biological characterization of mycobacteria‐specific ESX/type VII secretion systems and their secreted proteins, belonging to the Esx, PE, and PPE categories. The importance of specific mycobacterial antigen release is probably best exemplified by the striking differences observed between the cellular events during infection with the ESX‐1‐deficient, attenuated Mycobacterium bovis BCG compared to the virulent M. tuberculosis, which are clearly important for design of more specific diagnostics and more efficient vaccines.
Heterogeneity in tuberculosis pathology, microenvironments and therapeutic responses
Authors: Lenaerts Anne , Barry Clifton E. , Dartois Véronique 
Published: February 2015

SummaryTuberculosis (TB) lesions are extremely complex and dynamic. Here, we review the multiple types and fates of pulmonary lesions that form following infection by Mycobacterium tuberculosis and the impact of this spatial and temporal heterogeneity on the bacteria they harbor. The diverse immunopathology of granulomas and cavities generates a plethora of microenvironments to which M. tuberculosis bacilli must adapt. This in turn affects the replication, metabolism, and relative density of bacterial subpopulations, and consequently their respective susceptibility to chemotherapy. We outline recent developments that support a paradigm shift in our understanding of lesion progression. The simple model according to which lesions within a single individual react similarly to the systemic immune response no longer prevails. Host‐pathogen interactions within lesions are a dynamic process, driven by subtle and local differences in signaling pathways, resulting in diverging trajectories of lesions within a single host. The spectrum of TB lesions is a continuum with a large overlap in the lesion types found in latently infected and active TB patients. We hope this overview will guide TB researchers in the design, choice of read‐outs, and interpretation of future studies in the search for predictive biomarkers and novel therapies.
CD1 and mycobacterial lipids activate human T cells
Authors: Van Rhijn Ildiko , Moody D. Branch 
Published: February 2015

SummaryFor decades, proteins were thought to be the sole or at least the dominant source of antigens for T cells. Studies in the 1990s demonstrated that CD1 proteins and mycobacterial lipids form specific targets of human αβ T cells. The molecular basis by which T‐cell receptors (TCRs) recognize CD1‐lipid complexes is now well understood. Many types of mycobacterial lipids function as antigens in the CD1 system, and new studies done with CD1 tetramers identify T‐cell populations in the blood of tuberculosis patients. In human populations, a fundamental difference between the CD1 and major histocompatibility complex systems is that all humans express nearly identical CD1 proteins. Correspondingly, human CD1 responsive T cells show evidence of conserved TCRs. In addition to natural killer T cells and mucosal‐associated invariant T (MAIT cells), conserved TCRs define other subsets of human T cells, including germline‐encoded mycolyl‐reactive (GEM) T cells. The simple immunogenetics of the CD1 system and new investigative tools to measure T‐cell responses in humans now creates a situation in which known lipid antigens can be developed as immunodiagnostic and immunotherapeutic reagents for tuberculosis disease.
New tricks for old dogs: countering antibiotic resistance in tuberculosis with host‐directed therapeutics
Authors: Hawn Thomas R. , Shah Javeed A. , Kalman Daniel 
Published: February 2015

SummaryDespite the availability of Mycobacterium tuberculosis (Mtb) drugs for over 50 years, tuberculosis (TB) remains at pandemic levels. New drugs are urgently needed for resistant strains, shortening duration of treatment, and targeting different stages of the disease, especially for treatment during human immunodeficiency virus co‐infection. One solution to the conundrum that antibiotics kill the bacillus yet select for resistance is to target the host rather than the pathogen. Here, we discuss recent progress in so‐called ‘host‐directed therapeutics’ (HDTs), focusing on two general mechanistic strategies: (i) HDTs that disrupt Mtb pathogenesis in macrophages and (ii) immunomodulatory HDTs that facilitate protective immune responses that kill Mtb or reduce deleterious responses that exacerbate disease. HDTs hold significant promise as adjunctive therapies in that they are less likely to engender resistance, will likely have efficacy against antibiotic‐resistant strains, and may have activity against non‐replicating Mtb. However, TB is a complex and variegated disease, and human populations exhibit significant diversity in their immune responses to it, which presents a complicated landscape for HDTs to navigate. Nevertheless, we suggest that a detailed mechanistic understanding of drug action, together with careful selection of disease stage targets and dosing strategies may overcome such limitations and allow the development of HDTs as effective adjunctive treatment options for TB.
Mycobacterial genes essential for the pathogen's survival in the host
Authors: Ehrt Sabine , Rhee Kyu , Schnappinger Dirk 
Published: February 2015

SummaryMycobacterium tuberculosis (Mtb) has evolved within the human immune system as both host and reservoir. The study of genes required for its growth and persistence in vivo thus offers linked insights into its pathogenicity and host immunity. Studies of Mtb mutants have implicated metabolic adaptation (consisting of carbon, nitrogen, vitamin, and cofactor metabolism), intrabacterial pH homeostasis, and defense against reactive oxygen and reactive nitrogen species, as key determinants of its pathogenicity. However, the mechanisms of host immunity are complex and often combinatorial. Growing evidence has thus begun to reveal that the determinants of Mtb's pathogenicity may serve a broader and more complex array of functions than the isolated experimental settings in which they were initially found. Here, we review select examples, which exemplify this complexity, highlighting the distinct phases of Mtb's life cycle and the diverse microenvironments encountered therein.
Co‐evolution of Mycobacterium tuberculosis and Homo sapiens
Authors: Brites Daniela , Gagneux Sebastien 
Published: February 2015

SummaryThe causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co‐evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter‐response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future ‘genome‐to‐genome’ studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines.
Macrophage defense mechanisms against intracellular bacteria
Authors: Weiss Günter , Schaible Ulrich E. 
Published: February 2015

SummaryMacrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti‐microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti‐microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well‐adapted facultative intracellular bacterium, has learned during evolution to counter‐balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host‐pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi‐resistance of M. tuberculosis against conventional antibiotics.
Immunoevasion and immunosuppression of the macrophage by Mycobacterium tuberculosis
Authors: Hmama Zakaria , Peña‐Díaz Sandra , Joseph Sunil , Av‐Gay Yossef 
Published: February 2015

SummaryBy virtue of their position at the crossroads between the innate and adaptive immune response, macrophages play an essential role in the control of bacterial infections. Paradoxically, macrophages serve as the natural habitat to Mycobacterium tuberculosis (Mtb). Mtb subverts the macrophage's mechanisms of intracellular killing and antigen presentation, leading ultimately to the development of tuberculosis (TB) disease. Here, we describe mechanisms of Mtb uptake by the macrophage and address key macrophage functions that are targeted by Mtb‐specific effector molecules enabling this pathogen to circumvent host immune response. The macrophage functions described in this review include fusion between phagosomes and lysosomes, production of reactive oxygen and nitrogen species, antigen presentation and major histocompatibility complex class II expression and trafficking, as well as autophagy and apoptosis. All these are Mtb‐targeted key cellular pathways, normally working in concert in the macrophage to recognize, respond, and activate ‘proper’ immune responses. We further analyze and discuss major molecular interactions between Mtb virulence factors and key macrophage proteins and provide implications for vaccine and drug development.
The human immune response to tuberculosis and its treatment: a view from the blood
Authors: Cliff Jacqueline M. , Kaufmann Stefan H. E. , McShane Helen , van Helden Paul , O'Garra Anne 
Published: February 2015

SummaryThe immune response upon infection with the pathogen Mycobacterium tuberculosis is poorly understood, hampering the discovery of new treatments and the improvements in diagnosis. In the last years, a blood transcriptional signature in tuberculosis has provided knowledge on the immune response occurring during active tuberculosis disease. This signature was absent in the majority of asymptomatic individuals who are latently infected with M. tuberculosis (referred to as latent). Using modular and pathway analyses of the complex data has shown, now in multiple studies, that the signature of active tuberculosis is dominated by overexpression of interferon‐inducible genes (consisting of both type I and type II interferon signaling), myeloid genes, and inflammatory genes. There is also downregulation of genes encoding B and T‐cell function. The blood signature of tuberculosis correlates with the extent of radiographic disease and is diminished upon effective treatment suggesting the possibility of new improved strategies to support diagnostic assays and methods for drug treatment monitoring. The signature suggested a previously under‐appreciated role for type I interferons in development of active tuberculosis disease, and numerous mechanisms have now been uncovered to explain how type I interferon impedes the protective response to M. tuberculosis infection.
MR1‐restricted mucosal associated invariant T (MAIT) cells in the immune response to Mycobacterium tuberculosis
Authors: Gold Marielle C. , Napier Ruth J. , Lewinsohn David M. 
Published: February 2015

SummaryThe intracellular pathogen Mycobacterium tuberculosis (Mtb) and its human host have long co‐evolved. Although the host cellular immune response is critical to the control of the bacterium information on the specific contribution of different immune cell subsets in humans is incomplete. Mucosal associated invariant T (MAIT) cells are a prevalent and unique T‐cell population in humans with the capacity to detect intracellular infection with bacteria including Mtb. MAIT cells detect bacterially derived metabolites presented by the evolutionarily conserved major histocompatibility complex‐like molecule MR1. Here, we review recent advances in our understanding of this T‐cell subset and address the potential roles for MR1‐restricted T cells in the control, diagnosis, and therapy of tuberculosis.
Inherited and acquired immunodeficiencies underlying tuberculosis in childhood
Authors: Boisson‐Dupuis Stéphanie , Bustamante Jacinta , El‐Baghdadi Jamila , Camcioglu Yildiz , Parvaneh Nima , El Azbaoui Safaa , Agader Aomar , Hassani Amal , El Hafidi Naima , Mrani Nidal Alaoui , Jouhadi Zineb , Ailal Fatima , Najib Jilali , Reisli Ismail , Zamani Adil , Yosunkaya Sebnem , Gulle‐Girit Saniye , Yildiran Alisan , Cipe Funda Erol , Torun Selda Hancerli , Metin Ayse , Atikan Basak Yildiz , Hatipoglu Nevin , Aydogmus Cigdem , Kilic Sara Sebnem , Dogu Figen , Karaca Neslihan , Aksu Guzide , Kutukculer Necil , Keser‐Emiroglu Melike , Somer Ayper , Tanir Gonul , Aytekin Caner , Adimi Parisa , Mahdaviani Seyed Alireza , Mamishi Setareh , Bousfiha Aziz , Sanal Ozden , Mansouri Davood , Casanova Jean‐Laurent , Abel Laurent 
Published: February 2015

SummaryTuberculosis (TB), caused byMycobacterium tuberculosis(M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life‐threatening primaryTBof childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not onlyM.tbbut also weakly virulent mycobacteria, such asBCGvaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer thanTB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhoodTB, as illustrated by the discovery of single‐gene inborn errors ofIFN‐γ immunity underlying severe cases ofTB. Novel findings are expected from ongoing and future human genetic studies of childhoodTBin countries that combine a high proportion of consanguineous marriages, a high incidence ofTB, and an excellent clinical care, such as Iran, Morocco, and Turkey.