The Structure and Evolution of Beta-Rhizobial Symbiotic Genes Deduced from Their Complete Genomes

Abstract Nitrogen-fixing Rhizobia were discovered more than 100 years ago. They are classified into two clades, Alphaand Beta-rhizobia. Their symbiotic function is remarkable, but its origin and evolution has been confusing from a phylogenetic perspective.

In this study, we make use of 33 publicly available complete genome sequences downloaded from NCBI, which consist of bacteria and archaea, and focus on 10 strains, constructing symbiotic structural maps for them based on their genomes and previous gene annotations. Phylogenies of the symbiosisessential genes nodA and nifH were examined.

Although large incongruities with some hypotheses from previous studies were detected by the present study, we support the general concept that Beta-rhizobia were the original symbionts of legumes, but that their symbotic genes originated from a common ancestor to the Alpha-rhizobia.

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The Lysosome -A Central Hub for Cellular Function and Dysfunction

During the last decades our knowledge of the versatile tasks of the lysosome has increased tremendously. Several ground breaking discoveries, have positioned the lysosome as one of the central organelles for normal physiological function and in disease.

In this short overview we exemplify some of the recent achievements in our understanding of lysosomal function during nutrient sensing, cell death, exocytosis and cholesterol homeostasis as well as lysosomal malfunction during disease.

Outlined are also several of the gaps in our knowledge and challenges that need to be addressed in the future.

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Impacts of Interleukin-17 Neutralization on the Inflammatory Response in a Healing Ligament

In this study, we sought to improve ligament healing by modulating the inflammatory response after acute injury through the neutralization of Interleukin-17 (IL-17), which we hypothesized would decrease inflammatory cell infiltration and cytokine production.

Administration of an Interleukin-17 neutralizing antibody (IL-17 NA) immediately following a rat medial collateral ligament (MCL) transection resulted in alterations in inflammatory cell populations and cytokine expression within the healing ligament, but did not reduce inflammation.

Specifically, treatment resulted in a decrease in M2 (antiinflammatory) macrophages, an increase in T cells, and an increase in the levels of IL-2, IL-6, and IL-12 in the MCL 7 days post injury.

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Lymphoid Seeding in the Thymus: A New Function for Ephb2 and Ephb3

like B lymphocytes that differentiate in the bone marrow (BM), T lymphocytes need the special 3D epithelial microenvironment of the thymus to develop properly, in which they establish intimate interactions with Thymic Epithelial Cells.

Thus, whereas B lymphocytes derive from haematopoietic progenitor cells in the BM, T cells need more- or-less committed lymphoid progenitors to colonize the adult thymus through blood vessels because this organ lacks auto-renewing progenitor cells.

Mechanisms involved in the selective migration of BM progenitor cells have been largely associated with attracting chemokines and molecules involved in lymphoid cell migration through vascular endothelia, such as integrins and selectins.

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Primary Immunization among Children in Malaysia: Reasons for Incomplete Vaccination

Incomplete primary immunization against vaccine preventable diseases is a significant public health problem. This study aimed to identify population at-risk for incomplete immunization and their associated factors.

Data on immunization module from the National Health and Morbidity Survey (NHMS) 2016 was analyzed. This survey was conducted as a nation-wide community based survey using stratified random sampling design.

Immunization history of children aged 12 to 23 months from the randomly selected addresses were taken from their mothers by face-to-face interview using mobile device.

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Smad7 as a Target for Immunomodulation Strategy in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD) are chronic inflammatory pathologies of the gut, characterized by a relapsing-remitting course.

Although IBD pathogenesis is not fully understood, epidemiological and experimental data suggest that multiple environmental factors can, in genetically predisposed individuals, trigger an excessive immune response directed against the antigens of the normal intestinal microflora, which eventually leads to the tissue damage. Defects in the physiological mechanisms/factors of counter-regulation contribute to amplify and sustain such a detrimental response.

For instance, in inflamed tissue of IBD patients there is diminished activity of the immunesuppressive cytokine transforming growth factor (TGF)-β1, due to elevated levels of Smad7, an intracellular inhibitor of TGF-β1 signaling.

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Rebound from Inhibition: Self-Correction against Neurodegeneration?

Neural networks play a critical role in establishing constraints on excitability in the central nervous system. Several recent studies have suggested that network dysfunction in the brain and spinal cord are compromised following insult by a neurodegenerative trigger and might precede eventual neuronal loss and neurological impairment.

Early intervention of network excitability and plasticity might therefore be critical in resetting hyperexcitability and preventing later neuronal damage.

Here, the behavior of neurons that generate burst firing upon recovery from inhibitory input or intrinsic membrane hyperpolarization (rebound neurons) is examined in the context of neural networks that underlie rhythmic activity observed in areas of the brain and spinal cord that are vulnerable to neurodegeneration.

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The Structure and Evolution of Beta-Rhizobial Symbiotic Genes Deduced from Their Complete Genomes

Abstract Nitrogen-fixing Rhizobia were discovered more than 100 years ago. They are classified into two clades, Alphaand Beta-rhizobia.

Their symbiotic function is remarkable, but its origin and evolution has been confusing from a phylogenetic perspective.

In this study, we make use of 33 publicly available complete genome sequences downloaded from NCBI, which consist of bacteria and archaea, and focus on 10 strains, constructing symbiotic structural maps for them based on their genomes and previous gene annotations. Phylogenies of the symbiosisessential genes nodA and nifH were examined.

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Diagnosis of Association Ankylosing Spondylitis and Rheumatoid Arthritis

The probability of one patient has ankylosing spondylitis (AS) and rheumatoid arthritis (RA) is low.

It is usually difficult to diagnose the association, indeed we require a careful diagnostic process and more tests are needed.

A 21-year-old female patient with coexisting AS and RA was reported here. 9 months later, she developed peripheral polyarthritis, erosion changes on the radiography of Metatarso-phalangeal (MTP), rheumatoid factor and cyclic citrullinated peptide antibody (anti-CCP) were positives. Here, we describe the diagnostic process that we followed.

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Regulatory T Cells Cease Fire at the Right Place

Since the characterization of CD4+CD25+ regulatory T cells (Tregs) as a specific T-cell lineage with immune regulatory function in the 1990s, approaches manipulating Treg expansion and activities have been proved potential therapeutic strategies for immune-mediated diseases. On the other hand, harnessing leukocyte migration during inflammation as a therapeutic modality for immunologic diseases has not only supported by theoretical basis but also clinically shown potential.

Whilst advances have been made in the understanding of the effector mechanisms of Treg-mediated immune suppression, the migration phenotypes as well as the anatomic sites where Tregs exert immune regulation remain obscured. In a recent study by using the footpad inflammation model and adoptive Treg-cell transfer, Huang et al. demonstrated that blockage of Treg lymph node localization abrogated the immunosuppressive function of Tregs, suggesting an indispensable role of lymph node trafficking in Treg-mediated immune regulation.

The Utilization of Needle-Free Acupuncture and Chinese Traditional Medicine Theory to Cure Two Patients Suffering from Different Types of Chronic Urticaria

A woman, aged 35 year-old, had suffered chronic idiopathic urticaria for 8 months before she started needle-free acupuncture treatment from Wendy Chen Hälsoklinik.

In August 2015, the patient suddenly started suffering from urticaria without any reasonable explanation to the origin of the cause. This occurred 11 months after giving birth.

There were no reasons for rashes, which were found all over the body and resurfaced every day. These rashes usually appeared in the night and got worse in the morning.

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Oncolytic Viruses and Immune Checkpoint Inhibitors

Oncolytic immunotherapy consists in the use of non-pathogenic replicative viruses that infect preferentially or exclusively tumor cells and induces immunogenic cell death able to induce or stimulate an antitumor immune response.

In October 2015, a first oncolytic virus (OV) was approved by the FDA for the treatment of metastatic melanoma: the Talimogene Laherparepvec (T-Vec) from Amgen that is now commercialized under the name of Imlygic. T-Vec is a modified type I herpes simplex virus (HSV-I) with insertion and deletion of two genes.

The two inserted genes encode the human granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate the antitumor immune response and the HSV US11 protein to increase viral replication.

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A Multi-Disciplinary Approach to the Fibromyalgia Patients is always Needed

It is for me a great pleasure, to greet and welcome to all the readers and future contributors to this new digital Medical Journal called “Fibromyalgia”, edited online and in open access way.

Also I want to welcome to all the future readers interested in the study and understanding of the current status of this frequent, complex and very interesting multidisciplinary disease both for diagnostic and therapeutic approaches.

It has been assembled an excellent Editorial Committee composed of a selected group of experts in the different processes, from several countries, which will evaluate the works received with great scientific rigor, following the peer review system.

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Gas6/TAM System: A Promising Target in Neuroimmunology

Growth Arrest Specific 6 (Gas6) is a vitamin K-dependent protein, the biological activity of which is mediated by TAM receptors, a family of Tyrosine Kinases which includes three different members.

TAM receptors are also activated by Protein S, which shares structural similarities with Gas6, but is mainly expressed in the liver and exerts an anticoagulant effect in vivo; conversely Gas6 is more widely expressed and has much more pleiotropic effects.

Gas6/TAM seems to be particularly relevant in the regulation of immune system, raising interest in its potential involvement in autoimmune diseases.

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Natural Killers Cells can eliminate malignant tumors effectively when they get activated

Cells exert natural cytolytic activity and they are capable of eliminating the most dangerous K562 eritroleukemia cell line. However, they need to be activated to exert the optimum effctor to exert maximum pressure on them.

Natural killer cells are able to eliminate the tumors that are still in formative stage. They are however unable to eradicate the spread of well establisjed tumors.

NK cells are also abundant in numbers and the challenge lays picking up the right cell that can be activated and used for immunotherapy to fight cancer. Hence, adoptive transferred NK cell-based therapeutic protocols must choose optimal activation strategies for the in vitro activated NK cells, and, their chemokine receptor repertoire.

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Signaling Pathways that Facilitate Chronic Inflammation-Induced Carcinogenesis

Recently, growing evidences have shown that chronic inflammation is the major cause of carcinogenesis. Inflammation signaling pathways can facilitate evolution and development of cancers in a variety of aspects, such as proliferation, metastasis, and apoptosis, etc.

Nuclear factor-kappa B (NF-κB), janus-activated kinase (JAK)-signal transducers and activators 3 (STAT3), mitogen-activated protein kinase (MAPK), phosphatidylinositol-3-kinase/ protein kinase B (PKB, also known as Akt)/ mammalian target of rapamycin (PI3K/Akt/mTOR), Wnt/ β-catenin, and transforming growth factor (TGF)-β/Smad signaling pathways have been well studied, which are implicated in inflammation-induced carcinogenesis.

Although tremendous of researches have reported these signaling pathways, few has explained the mechanism by which inflammation signaling pathways sustain activation during carcinogenesis.

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Airway Hyperresponsiveness: An Unsung Clinical Manifestation

Airway Hyperresponsiveness (AHR) is one of the key features of asthma and chronic obstructive pulmonary disease (COPD), where the airway sensitivity is increased.

The research suggested that there is a relation between inflammatory state and severity of hyperresponsiveness of the airway, though the causative agents and consequences are different in asthma and COPD.

However, before estimating hyperresponsiveness, there is a need to understand the consequences of airway inflammation, which are different in asthma and COPD.

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Natural Killer (NK) Cell Receptors and their Role in Pregnancy and Abortion

Existing data suggest that decidual Natural Killer Cells (dNK CD3-CD56brightCD16dim/-) are important in early pregnancy (local response to pathogens, control of trophoblast invasion, uterine vascular remodeling), while in ongoing pregnancy they contribute to the acceptance of the embryo through various immunoregulatory mechanisms.

In the so-called alloimmune abortions, CD3-CD56brightCD16dim/-NK cells are decreased in favor of CD3-CD56dimCD16bright NK cells, which are toxic for trophoblast.

Most of the activating and inhibitory receptors regulating dNK function belong to the highly polymorphic KIR (Killer Immunoglobulin-like) family.

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M1 and M2 Myeloid Cells in Inflammation

Inflammation is triggered in the innate immune response by tissue myeloid cells, macrophages in peripheral tissue and microglia in the nervous system, in response to microbial or endogenous danger signals.

The plasticity of these cells developing into pro-inflammatory M1 and anti-inflammatory M2 phenotypes is remarkable.

Polarization of macrophages depends on local environmental factors, especially cytokines and growth factors. Interferon-γ (IFN-γ) and bacterial lipopolysaccharide (LPS) together polarize macrophage into the M1 phenotype which produces reactive oxygen species (ROS), nitric oxide (NO), and inflammatory cytokines such as tumor necrosis factor-α

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Development of de novo Hemolytic Uremic Syndrome Post-Transplant and the Role of Donor Specific Antibodies

A 66 year old female with a past medical history of end stage renal disease presumed secondary to diabetic nephropathy (no kidney biopsy performed), who underwent hemodialysis for 3 years, presented for cadaveric renal transplant.  

Her past surgical history was remarkable for failed arteriovenous fistula, appendectomy, and tonsillectomy. Her prior known sensitizing events included a prior pregnancy, one miscarriage, remote blood transfusion, but no previous transplants.

Her relevant family history included diabetes, hypertension, with no known family history of HUS or thrombotic thrombocytopenic purpura (TTP).

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Multiple Defects Impair the HLA Class II Antigen Presentation Capacity of Burkitt Lymphoma

Burkitt lymphoma (BL) is a B-cell malignancy which occurs with varying clinical manifestations and frequencies. The most well-known presentation of BL is found in areas which are holoendemic or hyperendemic for malaria. This endemic BL occurs primarily in children and presents as tumors of the jaw.

Though a strong association exists between endemic BL and malaria, the nature of the relationship remains unclear. A sporadic form of BL also occurs elsewhere in the world and typically causes tumors in the gut and upper respiratory tract.

There are various other contributing factors which may lead to development of BL, including Epstein-Barr Virus (EBV) and Human Immunodeficiency Virus (HIV). EBV has long been associated with development of BL and is found in nearly all cases of endemic BL but, in spite of intense research, the relationship between EBV and BL remains unclear. It is generally believed that infection with EBV somehow drives transformation which then leads to development of BL

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Biomarkers of Bone Turnover: Potential, Challenges and Pitfalls from the Laboratory Point of view

The present review aim to describe the most commonly used serum bone formation and resorption biochemical markers, discuss their advantages and disadvantages and give practical information on their use and result interpretation in the laboratory and clinical settings according to current recommendations from International Scientific Societies.

Bone turnover markers (BTM) may give information on bone formation and resorption, risk of fracture and response to treatments.

BTMs have been extensively studied as markers in the diagnosis and monitoring of osteoporosis (OP), and resulted potentially useful as tools to evaluate the estimation of fracture future risk, although their significance was essentially demonstrated helpful to monitor efficacy of anti-OP treatments.

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Importance to Vaccination against Rabies in Travellers to Areas of Risk

A patient returned from Algeria showing a grade III wound (WHO standard) produced by a dog bite, was treated with rabies nerve tissue vaccines (NTVs) lacked the rabies immunoglobin, and developed a visible local reaction to the vaccine.

The last WHO position paper (2010) recommends replacing nerve-tissue vaccines with CCVs. The nerve tissue vaccines induce more-severe adverse reaction sand are less immunogenic than CCVs.

It should be assessed in travellers to areas of risk, pre-exposure vaccination, and eliminated the need to the use of rabies globulin post exposition, and avoid as much as possible the use of of nerve-tissue vaccines.

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Gas6/TAM System: A Promising Target in Neuroimmunology

Growth Arrest Specific 6 (Gas6) is a vitamin K-dependent protein, the biological activity of which is mediated by TAM receptors, a family of Tyrosine Kinases which includes three different members Tyro3, Axl and Mer.

TAM receptors are also activated by Protein S, which shares structural similarities with Gas6, but is mainly expressed in the liver and exerts an anticoagulant effect in vivo.

Conversely, Gas6 is more widely expressed (lung, heart, kidney, intestine, endothelial cells, bone marrow, vascular smooth muscle cells, monocytes and liver) and has much more pleiotropic effects.

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The Development of Prophylactic EBV Vaccines

Epstein-Barr virus (EBV) is an important global human pathogen found in over 90% of the world’s population. EBV infection usually occurs in young children and causes no or only nonspecific symptoms. However, EBV is the major cause of infectious mononucleosis.

Epstein-Barr virus (EBV) is an important global human pathogen found in over 90% of the world’s population. EBV infection usually occurs in young children and causes no or only nonspecific symptoms.

However, EBV is the major cause of infectious mononucleosis (IM). EBV is an oncogenic virus associated with various human malignancies of both epithelial and lymphoid origin such as nasopharyngeal carcinoma (NPC), a subset of gastric carcinoma (GC), Burkitt’s lymphoma (BL), Hodgkin lymphoma (HL) and post-transplant lymphoproliferative disorder.

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Influence of Culture Medium on Production of Nitric Oxide and Expression of Inducible Nitric Oxide Synthase by Activated Macrophages In Vitro

Activated macrophage phenotypes were influenced by the culture medium; a murine macrophage-like cell line, J774.1/JA-4, expresses different activated-macrophage phenotypes induced by lipopolysaccharide (LPS) and/or interferon-γ (IFN-γ) when the cells are incubated in either Ham’s F-12 medium (F-12) or Dulbecco’s modified Eagle medium (DMEM).

Among these phenotypes, NO production and iNOS expression are the most remarkably influenced by the medium; the induction of iNOS mRNA and iNOS protein is higher in DMEM than in F-12, but NO production by activated macrophages is less in DMEM than in F-12.

These results suggest that the interpretation of the experimental results requires consideration of the possibility that the differences obtained by different laboratories were caused by the culture medium used.

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Antarctic Fish IgT, a Weird Option of Immunoglobulin Genes

Antarctic fish, most of which belonging to the Perciform Suborder Notothenioidei, have acquired, during their evolution, specific features that allow them to thrive, at present, at cold and stable temperature (-1.86°C).

The morphological evolution and diversification of AntarCtic Notothenioid teleosts into over 120 species is one of the best examples of adaptive radiation in the marine environment triggered by new ecological chances, for instance the extinction of antagonists.

The colonization of vacant niches, or the emergence of key innovative features such as the gain of antifreeze glycoproteins that allow them to live in cold habitats where other species would die.

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Single Nucleotide Polymorphism (SNP) and Its Preview

The announcement of human genome in June of 2000 pleasantly sent shock waves throughout the scholarly community and the general world population.

It announced the completion of a draft of human genome, along with the arrival of post-genomic era. In fact, in the post-genomic era, we are focusing on DNA sequences, as these sequences in the human body determine the sphcific trait of an individual.

To fully understand the significanch of these sequences in the human body, we must first truly understand the "single nucleotide polymorphisms" (Single Nucleotide Polymorphism, SNP).

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