LitMiner: integration of library services within a bio-informatics application

Background

This paper examines how the adoption of a subject-specific library service has changed the way in which its users interact with a digital library. The LitMiner text-analysis application was developed to enable biologists to explore gene relationships in the published literature. The application features a suite of interfaces that enable users to search PubMed as well as local databases, to view document abstracts, to filter terms, to select gene name aliases, and to visualize the co-occurrences of genes in the literature. At each of these stages, LitMiner offers the functionality of a digital library. Documents that are accessible online are identified by an icon. Users can also order documents from their institution's library collection from within the application. In so doing, LitMiner aims to integrate digital library services into the research process of its users.

Methods

Case study

Results

This integration of digital library services into the research process of biologists results in increased access to the published literature.

Conclusion

In order to make better use of their collections, digital libraries should customize their services to suit the research needs of their patrons.

     

Mitochondria-cytoskeleton associations in mammalian cytokinesis

Background

The role of the cytoskeleton in regulating mitochondrial distribution in dividing mammalian cells is poorly understood. We previously demonstrated that mitochondria are transported to the cleavage furrow during cytokinesis in a microtubule-dependent manner. However, the exact subset of spindle microtubules and molecular machinery involved remains unknown.

Methods

We employed quantitative imaging techniques and structured illumination microscopy to analyse the spatial and temporal relationship of mitochondria with microtubules and actin of the contractile ring during cytokinesis in HeLa cells.

Results

Superresolution microscopy revealed that mitochondria were associated with astral microtubules of the mitotic spindle in cytokinetic cells. Dominant-negative mutants of KIF5B, the heavy chain of kinesin-1 motor, and of Miro-1 disrupted mitochondrial transport to the furrow. Live imaging revealed that mitochondrial enrichment at the cell equator occurred simultaneously with the appearance of the contractile ring in cytokinesis. Inhibiting RhoA activity and contractile ring assembly with C3 transferase, caused mitochondrial mislocalisation during division.

Conclusions

Taken together, the data suggest a model in which mitochondria are transported by a microtubule-mediated mechanism involving equatorial astral microtubules, Miro-1, and KIF5B to the nascent actomyosin contractile ring in cytokinesis.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

Citrate usage in the leading causes of blindness: new possibilities for the old metabolite

Introduction

Citrate is an old metabolite which is best known for the role in the Krebs cycle. Citrate is widely used in many branches of medicine. In ophthalmology citrate is considered as a therapeutic agent and an useful diagnostic tool—biomarker.

Objectives

To summarize the published literature on citrate usage in the leading causes of blindness and highlight the new possibilities for this old metabolite.

Methods

We conducted a systematic search of the scientific literature about citrate usage in ophthalmology up to January 2018. The reference lists of identified articles were searched for providing in-depth information.

Results

This systematic review included 30 articles. The role of citrate in the leading causes of blindness is presented.

Conclusions

Citrate might help inhibit cataract progression, in case of questions confirm glaucoma diagnosis or improve cornea repair treatment as adjuvant agent (therapy of ulcerating cornea after alkali injury, crosslinking procedure). However, the knowledge about possible citrate usage in ophthalmology is not widely known. Promoting recent scientific knowledge about citrate usage in ophthalmology may not only benefit of medical improvement but may also limit economic costs caused by leading causes of blindness. Further studies on citrate usage in ophthalmology should continuously be the field of scientific interest.

     

Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses

Introduction

Subcellular compartmentalization enables eukaryotic cells to carry out different reactions at the same time, resulting in different metabolite pools in the subcellular compartments. Thus, mutations affecting the mitochondrial energy metabolism could cause different metabolic alterations in mitochondria compared to the cytoplasm. Given that the metabolite pool in the cytosol is larger than that of other subcellular compartments, metabolic profiling of total cells could miss these compartment-specific metabolic alterations.

Objectives

To reveal compartment-specific metabolic differences, mitochondria and the cytoplasmic fraction of baker’s yeast Saccharomyces cerevisiae were isolated and subjected to metabolic profiling.

Methods

Mitochondria were isolated through differential centrifugation and were analyzed together with the remaining cytoplasm by gas chromatography–mass spectrometry (GC–MS) based metabolic profiling.

Results

Seventy-two metabolites were identified, of which eight were found exclusively in mitochondria and sixteen exclusively in the cytoplasm. Based on the metabolic signature of mitochondria and of the cytoplasm, mutants of the succinate dehydrogenase (respiratory chain complex II) and of the F_OF₁-ATP-synthase (complex V) can be discriminated in both compartments by principal component analysis from wild-type and each other. These mitochondrial oxidative phosphorylation machinery mutants altered not only citric acid cycle related metabolites but also amino acids, fatty acids, purine and pyrimidine intermediates and others.

Conclusion

By applying metabolomics to isolated mitochondria and the corresponding cytoplasm, compartment-specific metabolic signatures can be identified. This subcellular metabolomics analysis is a powerful tool to study the molecular mechanism of compartment-specific metabolic homeostasis in response to mutations affecting the mitochondrial metabolism.

     

Production,purification, characterization,immobilization, and application of Serrapeptase: a review

Background

Serrapeptase is a proteolytic enzyme with many favorable biological properties like anti-inflammatory, analgesic, anti-bacterial, fibrinolytic properties and hence, is widely used in clinical practice for the treatment of many diseases. Although Serrapeptase is widely used, there are very few published papers and the information available about the enzyme is very meagre. Hence this review article compiles all the information about this important enzyme Serrapeptase.

Methods

A literature search against various databases and search engines like PubMed, SpringerLink, Scopus etc. was performed.

Results

We gathered and highlight all the published information regarding the molecular aspects, properties, sources, production, purification, detection, optimizing yield, immobilization, clinical studies, pharmacology, interaction studies, formulation, dosage and safety of the enzyme Serrapeptase.

Conclusion

Serrapeptase is used in many clinical studies against various diseases for its anti-inflammatory, fibrinolytic and analgesic effects. There is insufficient data regarding the safety of the enzyme as a health supplement. Data about the antiatherosclerotic activity, safety, tolerability, efficacy and mechanism of action of the Serrapeptase are still required.

     

Impaired mitochondrial calcium uptake caused by tacrolimus underlies beta-cell failure

Background

One of the most common side effects of the immunosuppressive drug tacrolimus (FK506) is the increased risk of new-onset diabetes mellitus. However, the molecular mechanisms underlying this association have not been fully clarified.

Methods

We studied the effects of the therapeutic dose of tacrolimus on mitochondrial fitness in beta-cells.

Results

We demonstrate that tacrolimus impairs glucose-stimulated insulin secretion (GSIS) in beta-cells through a previously unidentified mechanism. Indeed, tacrolimus causes a decrease in mitochondrial Ca²⁺ uptake, accompanied by altered mitochondrial respiration and reduced ATP production, eventually leading to impaired GSIS.

Conclusion

Our observations individuate a new fundamental mechanism responsible for the augmented incidence of diabetes following tacrolimus treatment. Indeed, this drug alters Ca²⁺ fluxes in mitochondria, thereby compromising metabolism-secretion coupling in beta-cells.

     

Type 2 diabetes increases oocyte mtDNA mutations which are eliminated in the offspring by bottleneck effect

Background

Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown.

Methods

We generated a T2D mouse model by using high-fat-diet (HFD) and Streptozotocin (STZ) injection. We examined mtDNA mutations in oocytes of diabetic mice by high-throughput sequencing techniques.

Results

T2D mice showed glucose intolerance, insulin resistance, low fecundity compared to the control group. T2D oocytes showed increased mtDNA mutation sites and mutation numbers compared to the control counterparts. mtDNA mutation examination in F1 mice showed that the mitochondrial bottleneck could eliminate mtDNA mutations.

Conclusions

T2D mice have increased mtDNA mutation sites and mtDNA mutation numbers in oocytes compared to the counterparts, while these adverse effects can be eliminated by the bottleneck effect in their offspring. This is the first study using a small number of oocytes to examine mtDNA mutations in diabetic mothers and offspring.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Association between HMGB1 and asthma: a literature review

Background

Recently, some studies demonstrated that HMGB1, as proinflammatory mediator belonging to the alarmin family, has a key role in different acute and chronic immune disorders. Asthma is a complex disease characterised by recurrent and reversible airflow obstruction associated to airway hyper-responsiveness and airway inflammation.

Objective

This literature review aims to analyse advances on HMGB1 role, employment and potential diagnostic application in asthma.

Methods

We reviewed experimental studies that investigated the pathogenetic role of HMGB in bronchial airway hyper-responsiveness, inflammation and the correlation between HMGB1 level and asthma.

Results

A total of 19 studies assessing the association between HMGB1 and asthma were identified.

Conclusions

What emerged from this literature review was the confirmation of HMGB-1 involvement in diseases characterised by chronic inflammation, especially in pulmonary pathologies. Findings reported suggest a potential role of the alarmin in being a stadiation method and a marker of therapeutic efficacy; finally, inhibiting HMGB1 in humans in order to contrast inflammation should be the aim for future further studies.

     

Choroidal eye metastases from (recurrent) primary peritoneal carcinoma: case report and review of the literature

Background

Choroidal metastases from gynaecological primary are extremely rare. There is no documented case in the literature of choroid metastasis in a patient with primary peritoneal carcinoma (PPC).

Methods & Results

We describe the first case of a 54-year-old woman with a history of borderline mucinous tumour who presented 17 months later with PPC and 21 months after with recurrent disease metastatic to the eye, and review pertinent literature.

Conclusion

High index of suspicion is warranted when patients with history of primary peritoneal carcinoma present with visual complaints in order to treat and/or relieve symptomatology from metastatic eye disease.

     

Applications of metabolomics in the study and management of preeclampsia: a review of the literature

Introduction

Preeclampsia represents a major public health burden worldwide, but predictive and diagnostic biomarkers are lacking. Metabolomics is emerging as a valuable approach to generating novel biomarkers whilst increasing the mechanistic understanding of this complex condition.

Objectives

To summarize the published literature on the use of metabolomics as a tool to study preeclampsia.

Methods

PubMed and Web of Science were searched for articles that performed metabolomic profiling of human biosamples using either Mass-spectrometry or Nuclear Magnetic Resonance based approaches and which included preeclampsia as a primary endpoint.

Results

Twenty-eight studies investigating the metabolome of preeclampsia in a variety of biospecimens were identified. Individual metabolite and metabolite profiles were reported to have discriminatory ability to distinguish preeclamptic from normal pregnancies, both prior to and post diagnosis. Lipids and carnitines were among the most commonly reported metabolites. Further work and validation studies are required to demonstrate the utility of such metabolites as preeclampsia biomarkers.

Conclusion

Metabolomic-based biomarkers of preeclampsia have yet to be integrated into routine clinical practice. However, metabolomic profiling is becoming increasingly popular in the study of preeclampsia and is likely to be a valuable tool to better understand the pathophysiology of this disorder and to better classify its subtypes, particularly when integrated with other omic data.

     

An oncoplastic technique to reduce the formation of lateral 'dog-ears' after mastectomy

Background

Lateral skin folds or 'dog-ears' are frequent following mastectomy, particularly in patients with large body habitus.

Methods

We describe a method of modifying the mastectomy incision and suturing to eliminate these lateral 'dog-ears'.

Conclusion

This surgical technique, as compared to others described in the literature, is simple, does not require additional incisions and is cosmetically acceptable to the patient.

     

Cytogenetic changes of mesenchymal stem cells in the neoplastic bone marrow niche in leukemia

Background

Bone marrow mesenchymal stromal cells (BM-MSCs) are an essential cell type in the hematopoietic microenvironment. The question of whether MSCs from patients with different leukemias have cytogenetic abnormalities is controversial. In this study, we attempted to review the cytogenetic profiles of MSCs in patients with leukemia, and verify whether these profiles were related to different ex vivo culture conditions or to chronic or acute disease states. This information could be useful in clarifying the origin of MSCs and developing clinical applications for this cell type.

Methods

A systematic literature search was performed using the PubMed search engine. Studies published over the past 15 years, i.e., between 1995 and January 2015, were considered for review. The following keywords were used: “cytogenetic,” “leukemia,” “bone marrow,” and “mesenchymal stromal cells.”

Results

Some studies demonstrated that BM-MSCs are cytogenetically normal, whereas others provided evidence of aberrations in these cells

Conclusions

Studying cytogenetic changes of MSCs in a variety of leukemias will help researchers understand the nature of these tumors and ensure the safety of human stem cells in clinical applications.

     

High salt and fat intake,inflammation, and risk of cancer

Background

Inflammatory conditions are involved in the pathophysiology of cancer. Recent findings have revealed that excessive salt and fat intake is involved in the development of severe inflammatory reactions.

Methods

literature search was performed on various online databases (PubMed, Scopus, and Google Scholar) regarding the roles of high salt and fat intake in the induction of inflammatory reactions and their roles in the etiopathogenesis of cancer.

Results

The results indicate that high salt and fat intake can induce severe inflammatory conditions. However, various inflammatory conditions have been strongly linked to the development of cancer. Hence, high salt and fat intake might be involved in the pathogenesis of cancer progression via putative mechanisms related to inflammatory reactions.

Conclusion

Reducing salt and fat intake may decrease the risk of cancer.

     

Xanthurenic acid translocates proapoptotic Bcl-2 family proteins into mitochondria and impairs mitochondrial function

Background

Xanthurenic acid is an endogenous molecule produced by tryptophan degradation, produced in the cytoplasm and mitochondria. Its accumulation can be observed in aging-related diseases, e.g. senile cataract and infectious disease. We previously reported that xanthurenic acid provokes apoptosis, and now present a study of the response of mitochondria to xanthurenic acid.

Results

Xanthurenic acid at 10 or 20 μM in culture media of human aortic smooth muscle cells induces translocation of the proteins Bax, Bak, Bclx_s, and Bad into mitochondria. In 20 μM xanthurenic acid, Bax is also translocated to the nucleus. In isolated mitochondria xanthurenic acid leads to Bax and Bclx_s oligomerization, accumulation of Ca²⁺, and increased oxygen consumption.

Conclusion

Xanthurenic acid interacts directly with Bcl-2 family proteins, inducing mitochondrial pathways of apoptosis and impairing mitochondrial functions.

     

The metabolome 18 years on: a concept comes of age

Background

The term ‘metabolome’ was introduced to the scientific literature in September 1998.

Aim and key scientific concepts of the review

To mark its 18-year-old ‘coming of age’, two of the co-authors of that paper review the genesis of metabolomics, whence it has come and where it may be going.

     

Biobanking and omics

Background

The “Era of Big Data” and “Precision Medicine” is now upon us. That is, interrogation of large data sets obtained from groups of similar patients or from the patient themselves over time will now hypothetically permit therapies to be designed to provide maximal efficacy with minimal side effects. However, such discoveries depend upon recruitment of very large numbers of subjects (tens of thousands) along with their associated biospecimens and medical records. When considering the establishment of a biobank or the refocusing of an existing repository for the purpose of “omics” research (i.e., genomics, metabolomics, proteomics, microbiomics, etc.) and/or precision medicine, there are a number of considerations to ponder. Each of these facets is discussed.

Objective

The objective of this review is to describe best practices for the establishment and operations of a biobank that will be used for omics (genomics, proteomics, metabolomics, microbiomics) analyses based on published literature and our own practical experiences.

Methods

We describe the most commonly described approaches to a variety of biobanking issues, including our own practical experiences over the past 5 years.

Results

Based on the particular biobanking situation and downstream application, we have described best practices based on the literature and own experience, taking into consideration ease of application and costs.

Conclusions

The banking of various types of clinical biospecimens has many valuable uses but often depends on overall costs versus sample utility. In addition, specimen flexibility is important but is influenced by the ease or difficulty of the application. It is always preferable to collect and stored a biospecimen in a format that allows for multiple types of downstream analyses, but that often requires additional expertise, equipment and reagents that can increase overall costs. We have described the methodologies most successfully applied to many situations.