Monkeypox virus replication underlying circadian rhythm networks.

The mammalian brain has an endogenous central circadian clock that regulates central and peripheral cellular activities. At the molecular level, this day-night cycle induces the expression of upstream and downstream transcription factors that influence the immune system and the severity of viral infections over time. In addition, there are also circadian effects on host tolerance pathways. This stimulates adaptation to normal changes in environmental conditions and requirements (including light and food). These rhythms influence the pharmacokinetics and efficacy of therapeutic drugs and vaccines. The importance of circadian systems in regulating viral infections and the host response to viruses is currently of great importance for clinical management. With the knowledge gained from the COVID-19 pandemic, it is important to address any outbreak of viral infection that could become endemic and to quickly focus research on any knowledge gaps. For example, responses to booster vaccination COVID-19 may have different time-dependent patterns during circadian cycles. There may be a link between reactivation of latently infected viruses and regulation of circadian rhythms. In addition, mammals may show different seasonal antiviral responses in winter and summer. This article discusses the importance of the host circadian clock during monkeypox infection and immune system interactions.

No reliable gene expression biomarkers of current or impending neurocognitive impairment in peripheral blood monocytes of persons living with HIV.

Events leading to and propagating neurocognitive impairment (NCI) in HIV-1-infected (HIV+) persons are largely mediated by peripheral blood monocytes. We previously identified expression levels of individual genes and gene networks in peripheral blood monocytes that correlated with neurocognitive functioning in HIV+ adults. Here, we expand upon those findings by examining if gene expression data at baseline is predictive of change in neurocognitive functioning 2 years later. We also attempt to validate the original findings in a new sample of HIV+ patients and determine if the findings are HIV specific by including HIV-uninfected (HIV-) participants as a comparison group. At two time points, messenger RNA (mRNA) was isolated from the monocytes of 123 HIV+ and 60 HIV- adults enrolled in the Multicenter AIDS Cohort Study and analyzed with the Illumina HT-12 v4 Expression BeadChip. All participants received baseline and follow-up neurocognitive testing 2 years after mRNA analysis. Data were analyzed using standard gene expression analysis and weighted gene co-expression network analysis with correction for multiple testing. Gene sets were analyzed for GO term enrichment. Only weak reproducibility of associations of single genes with neurocognitive functioning was observed, indicating that such measures are unreliable as biomarkers for HIV-related NCI; however, gene networks were generally preserved between time points and largely reproducible, suggesting that these may be more reliable. Several gene networks associated with variables related to HIV infection were found (e.g., MHC I antigen processing, TNF signaling, interferon gamma signaling, and antiviral defense); however, no significant associations were found for neurocognitive function. Furthermore, neither individual gene probes nor gene networks predicted later neurocognitive change. This study did not validate our previous findings and does not support the use of monocyte gene expression profiles as a biomarker for current or future HIV-associated neurocognitive impairment.

Factors related to HIV-associated neurocognitive impairment differ with age.

Over 50% of HIV-infected (HIV+) persons are expected to be over age 50 by 2015. The pathogenic effects of HIV, particularly in cases of long-term infection, may intersect with those of age-related illnesses and prolonged exposure to combined antiretroviral therapy (cART). One potential outcome is an increased prevalence of neurocognitive impairment in older HIV+ individuals, as well as an altered presentation of HIV-associated neurocognitive disorders (HANDs). In this study, we employed stepwise regression to examine 24 features sometimes associated with HAND in 40 older (55-73 years of age) and 30 younger (32-50 years of age) HIV+, cART-treated participants without significant central nervous system confounds. The features most effective in generating a true assessment of the likelihood of HAND diagnosis differed between older and younger cohorts, with the younger cohort containing features associated with drug abuse that were correlated to HAND and the older cohort containing features that were associated with lipid disorders mildly associated with HAND. As the HIV-infected population grows and the demographics of the epidemic change, it is increasingly important to re-evaluate features associated with neurocognitive impairment. Here, we have identified features, routinely collected in primary care settings, that provide more accurate diagnostic value than a neurocognitive screening measure among younger and older HIV individuals.

Astrovirology and terrestrial life survival.

Microbial organisms have been implicated in several mass extinction events throughout Earth's planetary history. Concurrently, it can be reasoned from recent viral pandemics that viruses likely exacerbated the decline of life during these periods of mass extinction. The fields of exovirology and exobiology have evolved significantly since the 20th century, with early investigations into the varied atmospheric compositions of exoplanets revealing complex interactions between metallic and non-metallic elements. This diversity in exoplanetary and stellar environments suggests that life could manifest in forms previously unanticipated by earlier, more simplistic models of the 20th century. Non-linear theories of complexity, catastrophe, and chaos (CCC) will be important in understanding the dynamics and evolution of viruses.

Neutrinos to Astrovirology: Signatures.

In the 20th century, the concept of terrestrial life's unity was solidified, and the 21st century saw the emergence and establishment of astrovirology. To date, life originating beyond Earth has not been identified. The singular instance where NASA investigated potential microfossils in Martian ejecta found on Earth has since been refuted. This report suggests that a more comprehensive discussion and analysis of life's biosignatures and communication methods are essential. Such approaches are crucial not only to avoid overlooking the possible existence of extra-terrestrial intelligence (ETI) but also to prevent potential human infections that could arise from extra-terrestrial contact. In addition terrestrial infections by microorganism that originally derived from Earth and were returned, require investigation due to potential mutations and subsequent increased pathogenicity.

Gene network effects on brain microstructure and intellectual performance identified in 472 twins.

A major challenge in neuroscience is finding which genes affect brain integrity, connectivity, and intellectual function. Discovering influential genes holds vast promise for neuroscience, but typical genome-wide searches assess approximately one million genetic variants one-by-one, leading to intractable false positive rates, even with vast samples of subjects. Even more intractable is the question of which genes interact and how they work together to affect brain connectivity. Here, we report a novel approach that discovers which genes contribute to brain wiring and fiber integrity at all pairs of points in a brain scan. We studied genetic correlations between thousands of points in human brain images from 472 twins and their nontwin siblings (mean age: 23.7 ± 2.1 SD years; 193 male/279 female). We combined clustering with genome-wide scanning to find brain systems with common genetic determination. We then filtered the image in a new way to boost power to find causal genes. Using network analysis, we found a network of genes that affect brain wiring in healthy young adults. Our new strategy makes it computationally more tractable to discover genes that affect brain integrity. The gene network showed small-world and scale-free topologies, suggesting efficiency in genetic interactions and resilience to network disruption. Genetic variants at hubs of the network influence intellectual performance by modulating associations between performance intelligence quotient and the integrity of major white matter tracts, such as the callosal genu and splenium, cingulum, optic radiations, and the superior longitudinal fasciculus.

Neutrino and EM asterometric detection of habitable exoplanets.

Discovering habitable exoplanets and exomoons increases the possibility of detecting extraterrestrial life. A bilateral approach, using neutrino and electromagnetic (EM) radiation technologies, can be used to simultaneously characterize star types that generally have exoplanets and exomoons. This includes cool main-sequence, sub-giant, and red-giant stars. Additionally, supernovae, black holes, and neutron and dwarf stars, will be included to widen the investigation, since they sometimes have companions, including stars and planets. Currently, space exploration is advancing beyond the solar system and proliferating into deep space. For this expansion, sophisticated artificial intelligence (AI) is required and being developed for self-coordination and interactive regulation of the various exploratory vehicles and telescopes. [1,2, 3,4,5, 6].

Dangerous Risk Group-4 (RG-4) emergent viruses.

World Health Organization (WHO) Risk Group-4 (RG-4) pathogens are among the most dangerous of the emergent and re-emergent viruses. International health agencies, working in concert, bridge the gaps in health care for populations at risk for RG-4 viral pathogen exposure. RG-4 virus research incorporates Biodefense Program and Biosafety Laboratory (BSL)-4 technologies. RG-4 viruses include Arena-viridae, Filo-viridae, Flavi-viridae, Herpes-viridae, Nairo-viridae, Paramyxo-viridae, and Pox-viridae.

Emergent Risk Group-4 (RG-4) Filoviruses: A paradox in progress.

Filoviruses, categorized as World Health Organization (WHO) Risk Group 4 (RG-4) pathogens, represent significant global health risks due to their extraordinary virulence. The Filoviridae family encompasses Ebola strains such as Sudan, Zaire, Bundibugyo, Tai Forest (formerly known as Ivory Coast), Reston, and Bombali, in addition to the closely related Marburg and Ravn virus strains. Filoviruses originated from a common ancestor about 10,000 years ago and displayed remarkable consistency in genetic heterogeneity until the 20th century. However, they overcame a genetic bottleneck by mid-century. Paradoxically, this resulted in the emergence of boosted virulent strains from the 1970's onward. Filovirus research is included in the NIAID Biodefense Program and utilizes the highest level specialized protective laboratories, Biosafety Laboratory (BSL)-4. The spread of Filoviruses as well as other RG-4 pathogens within Africa poses a significant health threat increasingly both in Africa and out of Africa.

Genome-wide association study of neurocognitive impairment and dementia in HIV-infected adults.

The neuropathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. Candidate gene studies have implicated genetic susceptibility loci within immune-related genes; however, these have not been reliably validated. Here, we employed genome-wide association (GWA) methods to discover novel genetic susceptibility loci associated with HAND, and validate susceptibility loci implicated in prior candidate gene studies. Data from 1,287 participants enrolled in the Multicenter AIDS Cohort Study between 1985 and 2010 were used. Genotyping was conducted with Illumina 1M, 1MDuo, or 550K platform. Linear mixed models determined subject-specific slopes for change over time in processing speed and executive functioning, considering all visits including baseline and the most recent study visit. Covariates modeled as fixed effects included: time since the first visit, depression severity, nadir CD4+ T-cell count, hepatitis C co-infection, substance use, and antiretroviral medication regimen. Prevalence of HIV-associated dementia (HAD) and neurocognitive impairment (NCI) was also examined as neurocognitive phenotypes in a case-control analysis. No genetic susceptibility loci were associated with decline in processing speed or executive functioning among almost 2.5 million single nucleotide polymorphisms (SNPs) directly genotyped or imputed. No association between the SNPs and HAD or NCI were found. Previously reported associations between specific genetic susceptibility loci, HIV-associated NCI, and HAD were not validated. In this first GWAS of HAND, no novel or previously identified genetic susceptibility loci were associated with any of the phenotypes examined. Due to the relatively small sample size, future collaborative efforts that incorporate this dataset may still yield important findings.

Bioinformation and Neutrino Communication.

Communications among civilizations may include self-descriptive bioinformation because pathogen dynamics exist in their astrobiology and astrovirology, which could become pathogenic upon actual contact. This information is of mutual benefit, if reciprocated. However, in contrast, the strategic counter-scenario of self-hidden civilizations is also discussed. Civilizations, including extra-terrestrial civilizations have been divided and stratified into three levels, using a wide non-linear logarithmic scale. The levels are based on their energy expenditures: level 1 is at 4x10^19 erg/sec; level 2 is at 4x10^33 erg/sec; and level 3 is at 4x10^44 erg/sec. Terrestrial civilization is currently below the entry level I. Particularly advanced civilizations, which are above the highest level, may engineer interstellar travel and could move their planets across interstellar distances. Communication among civilizations has always been of keen interest. In terms of ability to communicate among advanced civilizations, neutrinos may be used for galactic and inter-galactic communication, in addition to or instead of using electromagnetic radiation. Thus, at this juncture, deliberation and debate are essential to proceed with development of civilization and communication.

Neutrino communication, intergalactic transit, and Astrobiology.

This is a brief summary, snapshot, of a few issues that relate to possible communication with Extraterrestrial Intelligence (ETI) using neutrinos. Essentially, more research is required to better understand possible detection and communication with intelligent life (Astrobiology and ETI). Because of the possible scarcity of life in any single galaxy, to enhance the possibility of life detection, inter-galactic transit neutrinos necessitate consideration. Neutrino-based potential communications are inferred as the optimal mechanism or venue for detection of communications from ETI as well as sending communications to ETI. A paradox exists within this central theme. On the one hand, neutrino technology should be further developed and used to receive signals from or to send signals to ETI, because they transit inter-galactic distances. On the other hand, however, neutrinos have a very low cross-section interaction and are very difficult to detect. This concise Editorial incorporates several diverse research areas. Various issues are briefly and conjointly mentioned to inform the reader of multiple fields required towards a deeper understanding of astrobiology, astro virology, and ETI. This understanding is required for future advances, just as innovations in classical physics, quantum mechanics, particle physics, biophysics, chemistry, biochemistry, and molecular biology were required for the breakthroughs and advances in biology and virology, from the last century to the present - thus, the need for innovations and applications in neutrino particle physics research.

Neutrino intergalactic communication, metal life, and viruses: Part 1 quo vadis ex machina.

At one spectrum extreme, Astrobiology conjectures that for exoplanets with Goldilocks conditions, terrestrial-like life is inevitable. Moreover, it is envisaged that via panspermia, terrestrial-like life and its precursors are transferred among galaxies, stars, and within solar systems via transiting comets, asteroids, and planetoids. In addition, expelled stars, which have solar systems, it is inferred, transfer life as well. However, at the other extreme, we propose a paradigm shift that on some planets, subject to non- Goldilocks conditions, metal machine life could arise, ab initio, and evolve viruses, intelligence, and civilizations, conjointly. Accordingly, intelligent mechanized civilizations could readily and efficiently commence space exploration. Furthermore, as a counter paradigm shift, such civilizations could experiment and produce non-metallic life, based on carbon and other non-metal elements, under suitable conditions, related to Goldilocks life. Even a single example of validated interstellar or intergalactic communication received on the Earth would support the existence of life elsewhere. However, the communication platform should not be restricted to electromagnetic radiation. Other platforms should be included as well - one such example, which would require sophisticated technology, is neutrino communication. This is the case for any advanced civilization, be it metal-machine based, biological-based, and carbon-based. In sum, civilizations based on machine life, would be highly productive due to the longevity and hardiness of machine life. However, significant caveats are raised in this brief report, because possibly dissimilar psychologies and intelligence may lead to conflicts between metal machine life and biological life, inter-paradigm conflict.

The role of host genetics in the susceptibility for HIV-associated neurocognitive disorders.

Despite progress in the treatment of the Human Immunodeficiency virus (HIV), there continues to be a high prevalence of infected individuals who develop neurocognitive deficits and disorders. Our understanding of the potential cause of HIV-associated neurocognitive disorders (HAND) continues to develop on many fronts. Among them is the study of host genetics. Here, we review the most current information regarding the association between host genetics and risk for HIV infection, AIDS, and HAND. We focus on the role of dopamine dysfunction in the etiology of HAND, and propose a number of genetic polymorphisms within genes related to dopaminergic functioning and other neurobiological factors that may confer vulnerability or protection against HAND.

Artificial Intelligence and brain.

From the start, Kurt Godel observed that computer and brain paradigms were considered on a par by researchers and that researchers had misunderstood his theorems. He hailed with displeasure that the brain transcends computers. In this brief article, we point out that Artificial Intelligence (AI) comprises multitudes of human-made methodologies, systems, and languages, and implemented with computer technology. These advances enhance development in the electron and quantum realms. In the biological realm, animal neurons function, also utilizing electron flow, and are products of evolution. Mirror neurons are an important paradigm in neuroscience research. Moreover, the paradigm shift proposed here - 'hall of mirror neurons' - is a potentially further productive research tactic. These concepts further expand AI and brain research.

Astrobiology - an opposing view.

The use of quantum computers and Artificial Intelligence (AI) is imperative for use in space exploration and astrobiology investigations. Considerable progress has been made since the commencement of origin of life laboratory and theoretical studies in the mid 20th century. However, the sheer amount of data amassed to date in all these studies including exoplanetary and astrobiological studies is enormous and increasing steadily. Thus, there is the need for AI and quantum computers. As AI develops, it will become crucial in the development of the statistical and database programs that are indispensable to analyze the huge quantity of cumulative data. Diverse biotic and geochemical processes have been shown to produce methane on the Earth. Elsewhere in the solar system, on other planets (e.g. Mars) and moons (e.g. Titan), as well as on exoplanets, abiotic processes are considered the primary sources of methane. Astronomers and astro-biologists infer that the presence of methane supports the possibility of the presence of at least microbial life. In addition, on the Earth, there are also degradative reactions that include smog-related compounds and hazes that are produced as artefacts of intrinsic methane geochemistry as well as due to human footprint. Astronomers and astro-biologists envision life, away from the Earth, elsewhere in the solar system and on exoplanets, to occur under conditions similar or related to terrestrial life (goldilocks zone) conditions. These properties that are compatible with life as we know it on the Earth, include planetary orbits, gravitation, star radiant energy, presence of liquid water, and compatible temperatures and pressures, found on Earth. Generally, extraterrestrial life is also considered to resemble the biochemistry, molecular biology, and physiology of life on Earth - thus the focus on detection of supposed biosignatures of microbial life that resemble the Earth's. Nevertheless a crucial factor is absent in these deliberations - viruses. On the Earth, viruses that infect Archaea and bacteria form local and widespread global ecosystems. These viruses play a crucial role and facilitate the molecular transfer of host genes among various hosts. This essential function is underestimated in evolutionary as well as astrobiological speculations. Thus, it is of substantial importance to consider the roles that viruses may have played during the origin of life as well as in any exobiology.

HIV-1 RNA concentration and cognitive performance in a cohort of HIV-positive people.

OBJECTIVE: To determine whether higher viral concentrations in the cerebrospinal fluid (CSF) and/or peripheral blood were associated with greater severity of cognitive impairment in HIV-1-seropositive subjects with cognitive-motor impairment. METHODS: Cognitive performance measurements and viral load were obtained from HIV-1-seropositive individuals with cognitive-motor impairment entering a clinical trial before the introduction of highly active antiretroviral therapy (HAART). CSF viral load (UltraSensitive Roche HIV-1 Monitor test with detection limit of 50 copies/ml) was available from 179 patients, and peripheral (plasma or serum) viral load from 111 patients. Of these patients, 62% met the 1993 Centers for Disease Control (CDC) criteria for AIDS, and 19% had clinically significant cognitive impairment (i.e., global deficit score > or = 0.5). Possible associations between viral load and cognitive scores were examined with general linear regression models with and without adjustment for age, education, study site, antiretroviral use, CD4 cell count, and CDC stage. RESULTS: The mean CSF viral load was 2.83 log(10)/ml +/- 0.94 (SD) (undetectable in 19.5%). Mean peripheral viral load was 4.11 log(10)/ml +/- 0.90 (SD). No statistically significant associations emerged between either CSF or peripheral viral load and the global deficit score, or any of the seven cognitive domain deficit scores. CONCLUSIONS: Among these HIV-1-sero-positive individuals with mainly minor HIV-1-associated cognitive deficits and not receiving HAART, no association between CSF or blood concentration of HIV-1 RNA and cognitive performance could be found. These results suggest that the severity of HIV-1-associated cognitive impairment is not directly related to concurrent viral concentration in the CSF or the peripheral blood.

Crack cocaine: effect modifier of RNA viral load and CD4 count in HIV infected African American women.

This study reports on the role of cocaine as effect modifier of the association of CD4+ cell counts and RNA viral load. HIV-1 seropositive (n = 80) and seronegative (n = 42) African American women (AAW) crack cocaine smokers were recruited. Increasing cocaine use, based on self-reports and laboratory values, significantly exacerbates the immunopathology of HIV-1 in a dose-response manner, confirmed by a non-linear drop in CD4+ cell number for a given viral load in HIV+ AAW. This report supports a view of deleterious effects due to cocaine use in humans.

Psychiatric implications of hepatitis-C infection.

Hepatitis-C virus (HCV) has infected an estimated 130 million people worldwide, most of whom are chronically infected. Infection is marked by both treatment- and non-treatment-related psychiatric symptoms. Symptoms associated with antiretroviral therapy, interferon-alpha (IFN-alpha), include acute confusional states, delirium, depression, irritability, and even mania. These psychiatric symptoms are further complicated by the high rate of substance abuse and comorbid HIV infection inherent to this population. Even in the absence of IFN-alpha therapy, comorbid depression, cognitive decline, and especially fatigue are common in patients suffering HCV. These comorbidities have significant effects on both treatments and outcomes, and thus are reviewed herein.

Artificial Intelligence and Virology - quo vadis.

Artificial Intelligence (AI), robotics, co-robotics (cobots), quantum computers (QC), include surges of scientific endeavor to produce machines (mechanical and software) among numerous types and constructions that are accelerating progress to defeat infectious diseases. There is a plethora of additional applications and uses of these methodologies and technologies for the understanding of biomedicine through bioinformation discovery. Therefore, we briefly outline the use of such techniques in virology.