Centrosome as a micro-electronic generator in live cell.

Centrosome, composed of two centrioles arranged in an orthogonal configuration, is an indispensable cellular organelle for mitosis. 130 years after its discovery, the structural-functional relationship of centrosome is still obscure. Encouraged by the telltale signs of the "Mouse and Magnet experiment", Paul Schafer pioneered in the research on electromagnetism of centriole with electron microscopy(EM) in the late 1960s. Followed by the decades-long slow progression of the field with sporadic reports indicating the electromagnetisms of mitosis. Piecing together the evidences, we generated a mechanistic model for centrosome function during mitosis, in which centrosome functions as an electronic generator. In particular, the spinal rotations of centrioles transform the cellular chemical energy into cellular electromagnetic energy. The model is strongly supported by multiple experimental evidences. It offers an elegant explanation for the self-organized orthogonal configuration of the two centrioles in a centrosome, that is through the dynamic electromagnetic interactions of both centrioles of the centrosome.

Evidence for DNA resonance signaling via longitudinal hydrogen bonds.

The theory of the morphogenic field suggests that chemical signaling is supplemented by electromagnetic signaling governing the structure and shape of tissues, organs and the body. The theory of DNA resonance suggests that the morphogenic field is created by the genomic DNA which sends and receives electromagnetic signals in a sequence-specific manner. Previously, the authors have proposed the existence of HIDERs, genomic elements that serve as antennas in resonance signaling and demonstrated that they occur nonrandomly and are conserved in evolution. Here, it is proposed that longitudinal hydrogen bonds exist in the double helix, that chains of these bonds form delocalized proton clouds, that the shapes of these clouds are sequence-specific and form the basis of sequence-specificity of resonance between HIDERs. Based on longitudinal hydrogen bonds, a proton DNA resonance code was devised and used to identify HIDERs which are enriched 20 fold in the genome and conserved in evolution. It was suggested that these HIDERs are the key elements responsible for DNA resonance signaling and the formation of the morphogenic field.

Possible traces of resonance signaling in the genome.

Although theories regarding the role of sequence-specific DNA resonance in biology have abounded for over 40 years, the published evidence for it is lacking. Here, the authors reasoned that for sustained resonance signaling, the number of oscillating DNA sequences per genome should be exceptionally high and that, therefore, genomic repeats of various sizes are good candidates for serving as resonators. Moreover, it was suggested that for the two DNA sequences to resonate, they do not necessarily have to be identical. Therefore, the existence of sequences differing in the primary sequence but having similar resonating sub-structures was proposed. It was hypothesized that such sequences, named HIDERs, would be enriched in the genomes of multicellular species. Specifically, it was hypothesized that delocalized electron clouds of purine-pyrimidine sequences could serve as the basis of HIDERs. The consequent computational genomic analysis confirmed the enrichment of purine-pyrimidine HIDERs in a few selected genomes of mammals, an insect, and a plant, compared to randomized sequence controls. Similarly, it was suggested that hypothetical delocalized proton clouds of the hydrogen bonds of multiple stacked bases could serve as sequence-dependent hydrogen-bond-based HIDERs. Similarly, the enrichment of such HIDERs was observed. It is suggested that these enrichments are the first evidence in support of sequence-specific resonance signaling in the genome.

Optogenetic regulation of transcription.

Optogenetics has become widely recognized for its success in real-time control of brain neurons by utilizing non-mammalian photosensitive proteins to open or close membrane channels. Here we review a less well known type of optogenetic constructs that employs photosensitive proteins to transduce the signal to regulate gene transcription, and its possible use in medicine. One of the problems with existing gene therapies is that they could remain active indefinitely while not allowing regulated transgene production on demand. Optogenetic regulation of transcription (ORT) could potentially be used to regulate the production of a biological drug in situ, by repeatedly applying light to the tissue, and inducing expression of therapeutic transgenes when needed. Red and near infrared wavelengths, which are capable of penetration into tissues, have potential for therapeutic applications. Existing ORT systems are reviewed herein with these considerations in mind.

The role of Alu-derived RNAs in Alzheimer's and other neurodegenerative conditions.

Non-coding RNAs have emerged as essential contributors to neuroinflammation. The Alu element is the most abundant potential source of non-coding RNA in the human genome represented by over 1.1 million copies totaling ∼10% of the genome's mass. Accumulation of "Alu RNA" was observed in the brains of individuals with dementia and Creutzfeldt-Jakob disease - a degenerative brain disorder. "Alu RNAs" activate inflammatory pathways and apoptosis in the non-neural cells. In particular, the "Alu RNA" cytotoxicity is suggested as a mechanism in retinal pigment epithelium (RPE), a compartment damaged in the process of age-related macular degeneration. In RPE cells, the deficiency of Dicer is reported to lead to an accumulation of P3Alu transcripts, subsequent activation of the ERK1/2 signaling pathway, and the formation of NLRP3 inflammasome. In turn, these events result in RPE cell death by apoptosis. Importantly, RPE cells are of neuroectodermal origin, these cells display more similarity to neurons than to other epithelial cells. Thus, it is plausible that the mechanisms of "Alu RNA" cytotoxicity in brain neurons are similar to that in RPE. We hypothesize that accumulation of polymerase III-transcribed noncoding RNA of Alu (P3Alu) may contribute to both neuroinflammation and neurodegeneration associated with Alzheimer's disease (AD) and other degenerative brain disorders. This hypothesis points toward a novel molecular pathway not previously considered for the treatment of AD.

Red Light Modulates Ultraviolet-Induced Gene Expression in the Epidermis of Hairless Mice.

OBJECTIVE: The purpose of this study was to investigate whether low-level light therapy (LLLT) was capable of modulating expression of ultraviolet (UV) light-responsive genes in vivo. MATERIALS AND METHODS: The effects of 670 nm light-emitting diode (LED) array irradiation were investigated in a hairless SHK-1 mouse epidermis model. Mice were given a single dose of UVA/UVB light, or three doses of red light (670 nm @ 8 mW/cm(2) x 312 sec, 2.5 J/cm(2) per session) spread over 24 h along with combinations of pre- and post-UV treatment with red light. Levels of 14 UV-responsive mRNAs were quantified 24 h after UV irradiation by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: The transcription of mRNAs encoding for cluster of differentiation molecule 11b (CD11b) (p < 0.05) and interferon (IFN)-γ (p < 0.012) increased after irradiation with red light alone, whereas expression level of cyclooxygenase (COX)-2 (p < 0.02) was downregulated. Genes unresponsive to UV did not change their expression levels after exposure to red light either. Pretreatment with red light significantly modified response of Fos to UV exposure (p < 0.01). A synergy of UV and post-treatment with red light in reducing the transcription levels of CD11b (p < 0.05) and inducible nitric oxide synthase (iNOS) (p < 0.05) was observed. CONCLUSIONS: This is an initial observation that in mouse red light LLLT more often than not causes opposite gene expression changes or reduces those caused by moderate UVA-UVB irradiation.

High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat.

The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer. Here we identify a mechanism responsible for the naked mole rat's cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

A preliminary study of the safety of red light phototherapy of tissues harboring cancer.

OBJECTIVE: Red light phototherapy is known to stimulate cell proliferation in wound healing. This study investigated whether low-level light therapy (LLLT) would promote tumor growth when pre-existing malignancy is present. BACKGROUND DATA: LLLT has been increasingly used for numerous conditions, but its use in cancer patients, including the treatment of lymphedema or various unrelated comorbidities, has been withheld by practitioners because of the fear that LLLT might result in initiation or promotion of metastatic lesions or new primary tumors. There has been little scientific study of oncologic outcomes after use of LLLT in cancer patients. METHODS: A standard SKH mouse nonmelanoma UV-induced skin cancer model was used after visible squamous cell carcinomas were present, to study the effects of LLLT on tumor growth. The red light group (n=8) received automated full body 670 nm LLLT delivered twice a day at 5 J/cm(2) using an LED source. The control group (n=8) was handled similarly, but did not receive LLLT. Measurements on 330 tumors were conducted for 37 consecutive days, while the animals received daily LLLT. RESULTS: Daily tumor measurements demonstrated no measurable effect of LLLT on tumor growth. CONCLUSIONS: This experiment suggests that LLLT at these parameters may be safe even when malignant lesions are present. Further studies on the effects of photoirradiation on neoplasms are warranted.