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

Prediction of muscle fiber composition using multiple repetition testing

Direct determination of muscle fiber composition is invasive and expensive, with indirect methods also requiring specialist resources and expertise. Performing resistance exercises at 80% 1RM is suggested as a means of indirectly estimating muscle fiber composition, though this hypothesis has never been validated against a direct method. The aim of the study was to investigate the relationship between the number of completed repetitions at 80% 1RM of back squat exercise and muscle fiber composition. Thirty recreationally active participants’ (10 females, 20 males) 1RM back squat load was determined, before the number of consecutive repetitions at 80% 1RM was recorded. The relationship between the number of repetitions and the percentage of fast-twitch fibers from vastus lateralis was investigated. The number of completed repetitions ranged from 5 to 15 and was independent of sex, age, 1RM, training frequency, training type, training experience, BMI or muscle fiber cross-sectional area. The percentage of fast-twitch muscle fibers was inversely correlated with the number of repetitions completed (r = –0.38, P = 0.039). Participants achieving 5 to 8 repetitions (n = 10) had significantly more fast-twitch muscle fibers (57.5 ± 9.5 vs 44.4 ± 11.9%, P = 0.013) than those achieving 11–15 repetitions (n = 11). The remaining participants achieved 9 or 10 repetitions (n = 9) and on average had equal proportion of fast- and slow-twitch muscle fibers. In conclusion, the number of completed repetitions at 80% of 1RM is moderately correlated with muscle fiber composition

Three DNA Polymorphisms Previously Identified as Markers for Handgrip Strength Are Associated With Strength in Weightlifters and Muscle Fiber Hypertrophy.

Three DNA polymorphisms previously identified as markers for handgrip strength are associated with strength in weightlifters and muscle fiber hypertrophy. J Strength Cond Res XX(X): 000-000, 2019-Muscle strength is a highly heritable trait. So far, 196 single nucleotide polymorphisms (SNPs) associated with handgrip strength have been identified in 3 genome-wide association studies. The aim of our study was to validate the association of 35 SNPs with strength of elite Russian weightlifters and replicate the study in Polish weightlifters. Genotyping was performed using micro-array analysis or real-time polymerase chain reaction. We found that the rs12055409 G-allele near the MLN gene (p = 0.004), the rs4626333 G-allele near the ZNF608 gene (p = 0.0338), and the rs2273555 A-allele in the GBF1 gene (p = 0.0099) were associated with greater competition results (total lifts in snatch and clean and jerk adjusted for sex and weight) in 53 elite Russian weightlifters. In the replication study of 76 sub-elite Polish weightlifters, rs4626333 GG homozygotes demonstrated greater competition results (p = 0.0155) and relative muscle mass (p = 0.046), adjusted for sex, weight, and age, compared with carriers of the A-allele. In the following studies, we tested the hypotheses that these SNPs would be associated with skeletal muscle hypertrophy and handgrip strength. We found that the number of strength-associated alleles was positively associated with fast-twitch muscle fiber cross-sectional area in the independent cohort of 20 male power athletes (p = 0.021) and with handgrip strength in 87 physically active individuals (p = 0.015). In conclusion, by replicating previous findings in 4 independent studies, we demonstrate that the rs12055409 G-, rs4626333 G-, and rs2273555 A-alleles are associated with higher levels of strength, muscle mass, and muscle fiber size

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

Assembling a global database of malaria parasite prevalence for the Malaria Atlas Project

BACKGROUND: Open access to databases of information generated by the research community can synergize individual efforts and are epitomized by the genome mapping projects. Open source models for outputs of scientific research funded by tax-payers and charities are becoming the norm. This has yet to be extended to malaria epidemiology and control. METHODS: The exhaustive searches and assembly process for a global database of malaria parasite prevalence as part of the Malaria Atlas Project (MAP) are described. The different data sources visited and how productive these were in terms of availability of parasite rate (PR) data are presented, followed by a description of the methods used to assemble a relational database and an associated geographic information system. The challenges facing spatial data assembly from varied sources are described in an effort to help inform similar future applications. RESULTS: At the time of writing, the MAP database held 3,351 spatially independent PR estimates from community surveys conducted since 1985. These include 3,036 Plasmodium falciparum and 1,347 Plasmodium vivax estimates in 74 countries derived from 671 primary sources. More than half of these data represent malaria prevalence after the year 2000. CONCLUSION: This database will help refine maps of the global spatial limits of malaria and be the foundation for the development of global malaria endemicity models as part of MAP. A widespread application of these maps is envisaged. The data compiled and the products generated by MAP are planned to be released in June 2009 to facilitate a more informed approach to global malaria control

Sap Transporter Mediated Import and Subsequent Degradation of Antimicrobial Peptides in Haemophilus

Antimicrobial peptides (AMPs) contribute to host innate immune defense and are a critical component to control bacterial infection. Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharyngeal mucosa, yet is commonly associated with opportunistic infections of the upper and lower respiratory tracts. An important aspect of NTHI virulence is the ability to avert bactericidal effects of host-derived antimicrobial peptides (AMPs). The Sap (sensitivity to antimicrobial peptides) ABC transporter equips NTHI to resist AMPs, although the mechanism of this resistance has remained undefined. We previously determined that the periplasmic binding protein SapA bound AMPs and was required for NTHI virulence in vivo. We now demonstrate, by antibody-mediated neutralization of AMP in vivo, that SapA functions to directly counter AMP lethality during NTHI infection. We hypothesized that SapA would deliver AMPs to the Sap inner membrane complex for transport into the bacterial cytoplasm. We observed that AMPs localize to the bacterial cytoplasm of the parental NTHI strain and were susceptible to cytoplasmic peptidase activity. In striking contrast, AMPs accumulated in the periplasm of bacteria lacking a functional Sap permease complex. These data support a mechanism of Sap mediated import of AMPs, a novel strategy to reduce periplasmic and inner membrane accumulation of these host defense peptides

The apicomplexan plastid and its evolution

Protistan species belonging to the phylum Apicomplexa have a non-photosynthetic secondary plastid—the apicoplast. Although its tiny genome and even the entire nuclear genome has been sequenced for several organisms bearing the organelle, the reason for its existence remains largely obscure. Some of the functions of the apicoplast, including housekeeping ones, are significantly different from those of other plastids, possibly due to the organelle’s unique symbiotic origin

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