Targeting of proteins into the peroxisomal matrix

Summary During the last few years much has been learned regarding signals that target proteins into peroxisomes. The emphasis in the near future will undoubtedly shift towards the elucidation of the mechanism of import. The use of mammalian and yeast cells deficient in peroxisome assembly and/or import (Zoeller & Raetz, 1986; Erdmann et al., 1989; Cregg et al., 1990; Morand et al., 1990; Tsukamoto, Yokota & Fujiki, 1990) should provide a handle on the genes (Erdmann et al., 1991; Tsukamoto et al., 1991) involved in these processes. This will have to be coupled with further development of in vitro systems which will permit the dissection of the steps in the translocation of proteins into peroxisomes. Though some progress has been made in the development of such assays (Imanaka et al., 1987; Small et al., 1987, 1988; Miyazawa et al., 1989), the fragility of peroxisomes and the absence of biochemical hallmarks of import (such as protein modifications or proteolytic processing) have hindered progress. Since peroxisomes exist in the form of a reticulum in mammalian cells (Gorgas, 1984), all peroxisome purification schemes (from mammalian cells at least) must undoubtedly rupture the peroxisomes, which then reseal to form vesicular structures. Additionally, the reliance on the latency of catalase alone as a major criterion for the integrity of peroxisomes ignores the fact that many other matrix proteins leak out of peroxisomes at vastly different rates during purification of the organelles (Thompson & Krisans, 1990). In view of these problems, the development of peroxisomal transport assays with semi-intact cells would also constitute an important advance. It is very likely that in the next few years we will witness some major advances in our understanding of the mechanism by which proteins enter this organelle.I would like to thank all the members of my lab and my collaborators, past and present, whose hard work provided the material for this review. This work has been supported by grants from the March of Dimes Foundation (#1081) and the NIH (DK41737).     

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Dear Editor, The rapid emergence and persistence of the pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19) pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).We have developed a traditional beta-propiolactone-inacti-vated aluminum hydroxide-adjuvanted whole-virion SARS-CoV-2 vaccine (BBIBP-CorV),which elicited protective immune responses in clinical trials (Wang et al.,2020;Xia et al.,2021).The vaccine has been granted conditional approvals or emergency use authorizations (EUAs) in China and other countries.     

MOLE: a data management application based on a protein production data model

MOLE (mining, organizing, and logging experiments) has been developed to meet the growing data management and target tracking needs of molecular biologists and protein crystallographers. The prototype reported here will become a Laboratory Information Management System (LIMS) to help protein scientists manage the large amounts of laboratory data being generated due to the acceleration in proteome research and will furthermore facilitate collaborations between groups based at different sites. To achieve this, MOLE is based on the data model for protein production devised at the European Bioinformatics Institute (Pajon A, et al., Proteins in press).     

Linkage Map of Escherichia coli K-12, Edition 10: The Traditional Map

This map is an update of the edition 9 map by Berlyn et al. (M. K. B. Berlyn, K. B. Low, and K. E. Rudd, p. 1715–1902, in F. C. Neidhardt et al., ed., Escherichia coli and Salmonella: cellular and molecular biology, 2nd ed., vol. 2, 1996). It uses coordinates established by the completed sequence, expressed as 100 minutes for the entire circular map, and adds new genes discovered and established since 1996 and eliminates those shown to correspond to other known genes. The latter are included as synonyms. An alphabetical list of genes showing map location, synonyms, the protein or RNA product of the gene, phenotypes of mutants, and reference citations is provided. In addition to genes known to correspond to gene sequences, other genes, often older, that are described by phenotype and older mapping techniques and that have not been correlated with sequences are included.     

Elephant management: why can't we throw out the babies with the artificial bathwater?

Elephant management is highly controversial and any elephant-related study is quickly seen as a pro or con for one of the usual elephant management practices ( laissez-faire , culling, contraception or metapopulation management). Managing water sources has also been suggested as one option, even though no experimental data exist. In a recent issue of Diversity and Distributions , Smit et al. (2007 ) rejected this management tool as an efficient method to control elephant distribution and dynamics in Kruger National Park, South Africa. However, we believe that (1) Smit et al. 's conclusion is poorly supported by the available data, and (2) that this non-intrusive management tool has the potential for being one of the few practices able to reconcile managers, scientists, and the public opinion in the never-ending 'elephant problem'. For these reasons, we believe that the strong conclusions of Smit et al. should be moderated.     

Soil ingestion estimates for use in site evaluations based on the best tracer method

This paper develops a novel methodology, the Best Tracer method (BTM), that substantially overcomes the principal limitations (intertracer inconsistencies, and poor precision of recovery) of estimating soil ingestion by specific soil‐based tracers in massbalance studies. The BTM incorporates a biological and statistical framework that improves precision of recovery of tracer estimates, markedly reducing input‐output misalignment error resulting from a lack of correspondence between food tracer input and fecal tracer output.

This method is then used to re‐estimate the soil ingestion distribution of previously published soil ingestion estimates from two children studies (Calabrese et al. 1989; Davis et al., 1990) and one adult study (Calabrese et al., 1990). Revised estimates of soil ingestion are provided for each study. In addition, the results from the two children's studies are combined to form a single estimate of the soil ingestion distribution. These collective findings result in more reliable quantitative estimates of soil ingestion than trace element specific estimates, as well as providing improved understanding of current published soil ingestion studies, and improved methods that will enhance the design and interpretation of future soil ingestion studies.

With respect to children, the data indicate that the Calabrese et al. (1989) study provides the most reliable estimates of soil ingestion based on the estimated precision of recovery. However, estimates for the combined data of the Calabrese et al. (1989) and Davis et al. (1990) studies include all available children's data from mass balance studies, and thus provide more robust estimates. The collective data suggest that the median child in these studies ingested 30–40 mg/day of soil, while the upper 95% estimate is approximately 200 mg/day. Current data are insufficient to distinguish the children's soil ingestion distribution from that of adults. The revised and improved estimates of soil ingestion for children and adults have important implications for contaminant exposure estimates used in site evaluation risk assessment procedures.     

A quick reality check for microRNA target prediction

The regulation of protein abundance by microRNA (miRNA)-mediated repression of mRNA translation is a rapidly growing area of interest in biochemical research. In animal cells, the miRNA seed sequence does not perfectly match that of the mRNA it targets, resulting in a large number of possible miRNA targets and varied extents of repression. Several software tools are available for the prediction of miRNA targets, yet the overlap between them is limited. Jovanovic et al. have developed and applied a targeted, quantitative approach to validate predicted miRNA target proteins. Using a proteome database, they have set up and tested selected reaction monitoring assays for approximately 20% of more than 800 predicted let-7 targets, as well as control genes in Caenorhabditis elegans. Their results demonstrate that such assays can be developed quickly and with relative ease, and applied in a high-throughput setup to verify known and identify novel miRNA targets. They also show, however, that the choice of the biological system and material has a noticeable influence on the frequency, extent and direction of the observed changes. Nonetheless, selected reaction monitoring assays, such as those developed by Jovanovic et al., represent an attractive new tool in the study of miRNA function at the organism level.     

Nutritional modulation of age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro- and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/week of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available.     

Bugs beneath the surface： the functional significance of soil macroinvertebrates to landscape health in Australia＇s tropical savannas

Soil macroinvertebrates play an important role in sustaining production and biodiversity in Australia＇ s tropical savannas. For example, termites, through their foraging and nesting activities, recycle nutrients and carbon and produce soil pores that facilitate water infiltration. The challenge ahead is to quantitatively understand the relationships and processes that drive this. What roles do different species and functional groups of macroinvertebrates play in various landscape processes？ What are the effects of different land management practices （e.g., domestic cattle grazing, fire） on these relationships, and the consequences for landscape health？ This paper presents preliminary results from studies in northern Australia, that examine the effects of land condition and domestic cattle grazing on soil macroinvertebrates, and the potential for termites to be used as a tool to restore soil function in degraded areas. In northern Australia, increased degradation seems to be associated with declines in the diversity and activity of macroinvertebrates. Termites appear to be one of the most resilient groups, with some species capable of maintaining activity in degraded landscapes.     

Immune plexins and semaphorins: old proteins,new immune functions

Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapoval, 2011; McCormick and Leipzig, 2012; Yaron and Sprinzak, 2012), epithelial (Miao et al., 1999; Fujii et al., 2002), and immune systems (Takamatsu and Kumanogoh, 2012) as well as diverse cell processes including angiogenesis (Serini et al., 2009; Sakurai et al., 2012), embryogenesis (Perala et al., 2012), and cancer (Potiron et al., 2009; Micucci et al., 2010). Plexins and semaphorins are transmembrane proteins that share a conserved extracellular semaphorin domain (Hota and Buck, 2012). The plexins and semaphorins are divided into four and eight subfamilies respectively based on their structural homology. Semaphorins are relatively small proteins containing the extracellular semaphorin domain and short intracellular tails. Plexins contain the semaphorin domain and long intracellular tails (Hota and Buck, 2012). The majority of plexin and semaphorin research has focused on the nervous system, particularly the developing nervous system, where these proteins are found to mediate many common neuronal cell processes including cell movement, cytoskeletal rearrangement, and signal transduction (Choi et al., 2008; Takamatsu et al., 2010). Their roles in the immune system are the focus of this review.     

Kernel-based data fusion for gene prioritization

MOTIVATION: Hunting disease genes is a problem of primary importance in biomedical research. Biologists usually approach this problem in two steps: first a set of candidate genes is identified using traditional positional cloning or high-throughput genomics techniques; second, these genes are further investigated and validated in the wet lab, one by one. To speed up discovery and limit the number of costly wet lab experiments, biologists must test the candidate genes starting with the most probable candidates. So far, biologists have relied on literature studies, extensive queries to multiple databases and hunches about expected properties of the disease gene to determine such an ordering. Recently, we have introduced the data mining tool ENDEAVOUR (Aerts et al., 2006), which performs this task automatically by relying on different genome-wide data sources, such as Gene Ontology, literature, microarray, sequence and more. RESULTS: In this article, we present a novel kernel method that operates in the same setting: based on a number of different views on a set of training genes, a prioritization of test genes is obtained. We furthermore provide a thorough learning theoretical analysis of the method's guaranteed performance. Finally, we apply the method to the disease data sets on which ENDEAVOUR (Aerts et al., 2006) has been benchmarked, and report a considerable improvement in empirical performance. AVAILABILITY: The MATLAB code used in the empirical results will be made publicly available.     

Nest Site Preference and Fidelity of Chinese Alligator(Alligator sinensis)

Oviparous female reptiles select nesting sites with optimal ecological factors that contribute to egg development. Chinese alligator(Alligator sinensis), an oviparous reptile, is a critically endangered crocodilian with temperature-dependent sex determination. Research on its nesting behavior may facilitate the protection of this species. In this study, we monitored nesting behavior over eight years. We compared selected frequency of nest sites, distance from nest site to water, height from nest site top to the water surface, distance from nest site to human activity region, and canopy density between nest sites on the island and bank. The results showed that 45 nest sites were used by female alligators over eight years and each site was selected from one to 10 times. The selected frequency of nest site occurrence on the island was higher than that on the bank(P 0.001). We observed that 88% of the individual alligators(15/17) showed different degrees of nest site fidelity. However, Chinese alligators might not always be loyal to only one nest site because of environmental changes or interspecific competition at nest sites. Our findings suggest that female alligators prefer to nest at island, which might be because of the nests on the island had a higher canopy density(P = 0.010) and were further from the human activity region(P 0.001) than those on the bank did. It would be beneficial to reduce human activities during the breeding season and protect the vegetation of Chinese alligator habitats in the future. of the beach(Ali et al., 2005; Kamel and Mrosovsky, 2005; Turkozan et al., 2012). Other species such as snakes and lizards select nest sites with more moist substrates, which significantly increases their body size at hatching(Brown and Shine, 2004; Reedy et al., 2013). Nest site preference may be maintained for one or more breeding seasons(Janzen and Morjan, 2001; Kamel et al., 2006). When female chose the same site or area during different years, it is called nest site fidelity(Switzer, 1993). This nest choice behavior may influence offspring survival(Lindeman, 1992) and nest site fidelity has been documented in numerous species such as birds(Lindberg and Sedinger, 1997), turtles(Mitrus, 2006; Walde et al., 2007), tuatara(Refsnider et al., 2010), and crocodilians(Elsey et al., 2008).Chinese alligator(Alligator sinensis) is a critically endangered freshwater crocodilian endemic to China(Thorbjarnarson and Wang, 1999). Recent investigations show that there are no more than 130 Chinese alligators     

华南特马豆克期笔石地层分带及全球对比

特马豆克阶是奥陶系底部第一个阶,笔石是特马豆克阶高分辨率地层划分与对比的重要化石类群。江南斜坡带是我国早奥陶世特马豆克期漂浮笔石分异度和丰度最高的相区之一,位于该区的湖南益阳南坝剖面,发育有完整的上特马豆克阶笔石地层,特马豆克阶-弗洛阶界线附近地层连续,上特马豆克阶笔石地层研究已取得较大进展,但下特马豆克阶地层缺乏系统研究。近年来,通过对该剖面笔石标本的不间断采集,新识别出下特马豆克阶笔石带Rhabdinopora flabelliformis parabola带。到目前为止,湖南益阳南坝剖面特马豆克阶可以识别出5个笔石带,自下而上依次为:Rhabdinopora flabelliformis parabola带、Adelograptus tenellus带、Aorograptus victoriae带、Araneograptus murrayi带以及Hunnegraptus copiosus带。基于目前已识别出的笔石带,参考国内外同期笔石地层资料,本文详细讨论华南特马豆克期笔石带序列,并与国内外同期地层进行精确对比。     

A comparative review of statistical methods for discovering differentially expressed genes in replicated microarray experiments

MOTIVATION: A common task in analyzing microarray data is to determine which genes are differentially expressed across two kinds of tissue samples or samples obtained under two experimental conditions. Recently several statistical methods have been proposed to accomplish this goal when there are replicated samples under each condition. However, it may not be clear how these methods compare with each other. Our main goal here is to compare three methods, the t-test, a regression modeling approach (Thomas et al., Genome Res., 11, 1227-1236, 2001) and a mixture model approach (Pan et al., http://www.biostat.umn.edu/cgi-bin/rrs?print+2001,2001a,b) with particular attention to their different modeling assumptions. RESULTS: It is pointed out that all the three methods are based on using the two-sample t-statistic or its minor variation, but they differ in how to associate a statistical significance level to the corresponding statistic, leading to possibly large difference in the resulting significance levels and the numbers of genes detected. In particular, we give an explicit formula for the test statistic used in the regression approach. Using the leukemia data of Golub et al. (Science, 285, 531-537, 1999), we illustrate these points. We also briefly compare the results with those of several other methods, including the empirical Bayesian method of Efron et al. (J. Am. Stat. Assoc., to appear, 2001) and the Significance Analysis of Microarray (SAM) method of Tusher et al. (PROC: Natl Acad. Sci. USA, 98, 5116-5121, 2001).     

Evolution of metal hyperaccumulation and phytoremediation hype

Cadmium accumulation and tolerance are discussed in a New Phytologist article by Krämer (2000), which comments on a paper by Lombi et al . (2000). In this context, a number of additional points should be made, putting the role of humans in the evolution of metal resistance into context and emphasizing what is the 'hype' of phytoremediation.
It is important that sites created by humans should not be overemphasized in considering the evolution of metal resistance. Plants resistant to heavy metals have their primary sites not on these, but on soils where ores are outcropping, the so-called metalliferous or orogenic soils (Ernst, 1974). Over thousands of years, natural exposure to a surplus of various metals, depending on the mineralization process, has driven the evolution of metal resistance in many plant species under the local environmental conditions. Many publications have shown that Thlaspi caerulescens can hyperaccumulate Zn (e.g. Vázquez et al ., 1992), and accumulate other heavy metals such as Cu and Pb depending on soil chemistry (e.g. Baker et al ., 1994). It has been known for more than 30 years that T. caerulescens gives a good response to experimentally supplied high Zn levels (Ernst, 1968). One of the ecological effects of hyperaccumulation of heavy metals is a defence against herbivorous insects (Boyd & Martens, 1994). This effect is enhanced by a preferential accumulation of heavy metals in the epidermal leaf layer (Heath et al ., 1997).     

New basic discoveries and frontiers in diagnosis, prognosis and prediction of response to therapy in human thyroid, urinary bladder, and prostate tumors

The fourth edition of this workshop mainly focused on three different human oncotypes, which included thyroid, urinary bladder, and prostate tumors as clinical models to gain new basic knowledge on tumor diagnosis, prognosis, and treatment. At the previous editions (Giordano et al., 2000, J Cell Physiol 183:284-287; Giordano et al., 2001, J Cell Physiol 188:274-280; Giordano et al., 2002, J Cell Physiol 191:362-365), leaders in the fields of pathology, clinical oncology, and basic research presented and discussed the most recent and prevalent findings in such neoplasms from a basic and clinical perspective. A concept that has been widely proposed is that the analysis of intrinsic biological factors displayed by primary tumors may be a valid method for diagnosing different neoplasias and for measuring both their aggressiveness and response to therapy. To date, however, no single prognostic factor, such as oncogenes, suppressor genes, or genes involved in the control of the cell cycle and/or apoptosis has yet proven to be potent enough to be used in clinical practice as a prognostic and predictive factor. The new possibility to simultaneously analyze the expression of the complete repertoire of human genes and a large number of proteins could offer a new scenario in tumor classification, allowing for the formulation of a list of genes able to define a "signature" of tumor outcome. Moreover, starting from data obtained from biomolecular tumor analyses, it has been demonstrated that with this approach, it is also possible to design future therapeutic strategies.     

Distribution of DDT residues (DDT,DDD, and DDE) in California soils

DDT residues (DDT, DDD, and DDE, or DDT_R) occur in detectable concentrations in soils from southern California over 20 years after a ban (1973) on the widespread use of the pesticide in the U.S. A comparison of DDT residues found in soils from western Riverside/San Bernardino Counties to a much larger statewide database of Mischke et al. (1985) suggests that a systematic regional variation in relative abundances of DDT_R exists in California soils. It is suggested that factors such as physical/chemical properties of DDT residues, local/regional soil‐forming processes, soil management practices, and climatological regimes may help to explain the observed relative abundances of DDT‐related species in California soils. Knowledge of regional trends in the concentrations and composition of soil DDT_R may be useful in formulating more rational risk‐based soil management strategies where soil DDT_R concentrations are at or above regulatory levels.     

Liver function parameters in HIV/HCV co-infected patients treated with amprenavir and ritonavir and correlation with plasma levels

Acute liver toxicity is a frequent adverse event that occurs during antiretroviral therapy and was observed in 6-30% of the patients on treatment, especially in presence of HCV coinfection (Cooper et al., 2002, Maida et al., 2006, Sulkowski et al., 2000). A correlation between HCV-associated liver-fibrosis severity and the risk of HAART associated hepatoxicity has been demonstrated (Aranzabal et al., 2005, Sulkowski et al., 2004). This high liver toxicity rate might be due to increased drug exposure in patients with liver disease (Veronese et al., 2000). It has been reported that patients with chronic hepatitis C show significantly reduced CPY3A4 and CYP2D6 activity in comparison with healthy volunteers (Becquemont et al., 2002). The aim of this study was to evaluate the liver function tests in HCV-co-infected patients treated with fos-amprenavir and ritonavir.