Further Evidence for Cancer as a Cell-Wall- Deficient Mycobacterial Disease

In 2014, Buehring reported that Bovine Leukemic Virus (BLV), a common oncogenic retrovirus of cattle, was present in some humans, primarily localized to the breast epithelium ― the very cell type from which most breast malignancies arise. By 2015, there appeared data (Buehring, 2015) supporting that as many as 37% of human breast cancer cases could be attributable to BLV exposure. But if recent estimates suggest over 83% of U.S. dairy operations are currently positive for BLV, they also show that approximately 68% are positive for cell-wall-deficient Mycobacterium avium subspecies paratuberculosis (MAP). Although tubercular lung infection has been said to cause 11 times the incidence of lung cancer as normal control subjects, it is its cell-wall-deficient (CWD) forms (also called L-forms) that have recently repeatedly been found through genetic analysis and appropriate stains in such cancer tissue ― suggesting that CWD tuberculosis or atypical tuberculosis " is likely to be involved in the occurrence or development of lung carcinoma ". A similar relationship between tubercular L-forms and the genesis of the very breast cancer addressed in the aforementioned BLV viral trials. This is not a coincidence. L-forms (CWD forms) predominate and are crucial to the survival of mycobacteria in vivo and they have been documented by fluorescence microscopy in all intracellular macrophage-grown M. tuberculosis observed. From its origin, the very concept of the " BLV leukemic virus" has been on shaky, unstable ground. In 1969, veterinarians Janice and Lyle Miller from the University of Wisconsin-Madison spotted C-shaped " virus-like " particles in cattle lymposarcoma insisting that these were similar to other C-type viruses " regarded as the cause of leukemia in other species. " But by 1978, scientists at Downstate reported atypical mycobacterial forms, including its preferred filterable virus-sized " L " or cell-wall-deficient (CWD) forms in not only leukemia but all other malignancies ― all having, as their common denominator the continuous presence of mycobacterial C-shaped forms. Tracing back to techniques similar to Miller and Millers original BLV study we found in the very lyophilized antigens present in commercial kits for the diagnosis of BLV (AgBLV), these very same CWD (cell-wall-deficient) mycobacteria and mycobacterial DNA in all BLV samples ― which when introduced into guinea pigs stimulated the same antibody as occurred when mycobacteria-infected internal organ homogenates themselves were injected into other guinea pigs. It is therefore assumed that the Bovine Leukemic Virus (BLV) is being mistaken for viral-like forms of cell-wall-deficient (CWD) atypical tubercular mycobacteria. Since latent tubercular infection, as well as the administration of BCG and tuberculin also results in persistent CWD forms, their possible role in carcinogenesis is also considered

CWD Tuberculosis Found in Spongiform Disease Formerly Attributed to Prions: Its Implication towards Mad Cow Disease, Scrapie and Alzheimer's

The TSE'S or transmissible spongiform enchephalopathies, include bovine spongiform encephalopathy (also called BSE or " mad cow disease "), Creutzfeldt– Jakob disease (CJD) in humans, and " scrapie " in sheep or goats (caprine spongiform encephalopathy). They remain a mystery, their cause still hotly debated. Current mad cow diagnosis lies solely in the detection of late appearing " prions " , an acronym for hypothesized, geneless, misfolded proteins, somehow claimed to cause the disease. Yet laboratory preparations of prions contain other things, which could include unidentified bacteria or viruses. And the only real evidence that prion originator Stanley Prusiner had in his original paper that the disease agent behind " Scrapie " in sheep and goats was devoid of DNA or RNA– was based upon the fact that he couldn't find any. Furthermore, the rigors of prion purification alone, might, in and of themselves, have killed any causative microorganism and Heino Dringer, who did pioneer work on their nature, candidly predicts " it will turn out that the prion concept is wrong. " Roels and Walravens as well as Hartly traced Mad Cow to Mycobacterium bovis. Moreover, epidemiologic maps of the origins and peak incidence of Mad Cow in the UK, suggestively match those of England's areas of highest bovine tuberculosis, the Southwest. The neurotaxic potential of bovine tuberculosis has for some time been well known. By 1911 Alois Alzheimer called attention to " a characteristic condition of the cortical tissue which Fischer referred to as 'spongy cortical wasting " in Alzheimer's disease (AD). But behind AD, Fischer suspected a microbe called Streptothrix which was constantly being mistaken and confused for tuberculosis. Our present investigation of the TSEs clearly shows cell-wall-deficient (CWD) tubercular mycobacteria present, verified by molecular analysis, ELISA, PCR and microscopy to cause spongiform encephalopathy

A historical overview of the classification, evolution, and dispersion of Leishmania parasites and sandflies

Background The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale. Methodology and Principal Findings Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate? Conclusions and Significance We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Assessing the functional coherence of modules found in multiple-evidence networks from Arabidopsis

<p>Abstract</p> <p>Background</p> <p>Combining multiple evidence-types from different information sources has the potential to reveal new relationships in biological systems. The integrated information can be represented as a relationship network, and clustering the network can suggest possible functional modules. The value of such modules for gaining insight into the underlying biological processes depends on their functional coherence. The challenges that we wish to address are to define and quantify the functional coherence of modules in relationship networks, so that they can be used to infer function of as yet unannotated proteins, to discover previously unknown roles of proteins in diseases as well as for better understanding of the regulation and interrelationship between different elements of complex biological systems.</p> <p>Results</p> <p>We have defined the functional coherence of modules with respect to the Gene Ontology (GO) by considering two complementary aspects: (i) the fragmentation of the GO functional categories into the different modules and (ii) the most representative functions of the modules. We have proposed a set of metrics to evaluate these two aspects and demonstrated their utility in <it>Arabidopsis thaliana</it>. We selected 2355 proteins for which experimentally established protein-protein interaction (PPI) data were available. From these we have constructed five relationship networks, four based on single types of data: PPI, co-expression, co-occurrence of protein names in scientific literature abstracts and sequence similarity and a fifth one combining these four evidence types. The ability of these networks to suggest biologically meaningful grouping of proteins was explored by applying Markov clustering and then by measuring the functional coherence of the clusters.</p> <p>Conclusions</p> <p>Relationship networks integrating multiple evidence-types are biologically informative and allow more proteins to be assigned to a putative functional module. Using additional evidence types concentrates the functional annotations in a smaller number of modules without unduly compromising their consistency. These results indicate that integration of more data sources improves the ability to uncover functional association between proteins, both by allowing more proteins to be linked and producing a network where modular structure more closely reflects the hierarchy in the gene ontology.</p