Causal Nexus PATCHED

n. an established link between the most probable cause and its resulting effects. It relies on a connection (nexus) between phenomena that has been identified and observed to be one of causation. See causal analysis. Also causal chain.

Causal Nexus

A legal term that in Latin means "to bind." Legally it means to link a cause and effect. A causal nexus exists if the result is a natural and reasonable outcome or consequence of the activity. This does not equate to or require the same level of connection as does "proximate cause" (the idea that a result would not have occurred "but for" the actions of the person).

In this paper we present cellular senescence as the ultimate driver of the aging process, as a "causal nexus" that bridges microscopic subcellular damage with the phenotypic, macroscopic effect of aging. It is important to understand how the various types of subcellular damage correlated with the aging process lead to the larger, visible effects of anatomical aging. While it has always been assumed that subcellular damage (cause) results in macroscopic aging (effect), the bridging link between the two has been hard to define. Here, we propose that this bridge, which we term the "causal nexus", is in fact cellular senescence. The subcellular damage itself does not directly cause the visible signs of aging, but rather, as the damage accumulates and reaches a critical mass, cells cease to proliferate and acquire the deleterious "senescence-associated secretory phenotype" (SASP) which then leads to the macroscopic consequences of tissue breakdown to create the physiologically aged phenotype. Thus senescence is a precondition for anatomical aging, and this explains why aging is a gradual process that remains largely invisible during most of its progression. The subcellular damage includes shortening of telomeres, damage to mitochondria, aneuploidy, and DNA double-strand breaks triggered by various genetic, epigenetic, and environmental factors. Damage pathways acting in isolation or in concert converge at the causal nexus of cellular senescence. In each species some types of damage can be more causative than in others and operate at a variable pace; for example, telomere erosion appears to be a primary cause in human cells, whereas activation of tumor suppressor genes is more causative in rodents. Such species-specific mechanisms indicate that despite different initial causes, most of aging is traced to a single convergent causal nexus: senescence. The exception is in some invertebrate species that escape senescence, and in non-dividing cells such as neurons, where senescence still occurs, but results in the SASP rather than loss of proliferation plus SASP. Aging currently remains an inevitable endpoint for most biological organisms, but the field of cellular senescence is primed for a renaissance and as our understanding of aging is refined, strategies capable of decelerating the aging process will emerge.

The gut microbiota is a virtual organ which produces a myriad of molecules that the brain and other organs require. Humans and microbes are in a symbiotic relationship, we feed the microbes, and in turn, they provide us with essential molecules. Bacteroidetes and Firmicutes phyla account for around 80% of the total human gut microbiota, and approximately 1000 species of bacteria have been identified in the human gut. In adults, the main factors influencing microbiota structure are diet, exercise, stress, disease and medications. In this narrative review, we explore the involvement of the gut microbiota in Parkinson's disease, Alzheimer's disease, multiple sclerosis and autism, as these are such high-prevalence disorders. We focus on preclinical studies that increase the understanding of disease pathophysiology. We examine the potential for targeting the gut microbiota in the development of novel therapies and the limitations of the currently published clinical studies. We conclude that while the field shows enormous promise, further large-scale studies are required if a causal link between these disorders and gut microbes is to be definitively established.

A causal nexus, (TV: Logopolis) also called a spatio-temporal causal nexus point (AUDIO: The Mutant Phase), time-space nexus, temporal nexus point, causal nexus point, nexus point, or just nexus, was a place in space and time that was malleable, (PROSE: Remembrance of the Daleks) points in the space-time continuum that were very rare and hard to access. (PROSE: Invasion of the Cat-People)

Where time would normally be able to resist or absorb minor changes, the Third Doctor noted that some locations in space and time were temporal probability nexuses where multiple strands of causality were exposed and weak, and the smallest alteration could produce aberrant loops of existence or even new alternate timelines. (PROSE: The Eye of the Giant)

As related to cause and effect, i.e. causality, nexus points often served as areas for potential anomalies, since the Fourth Doctor stated that every point in time had its alternative. (TV: Pyramids of Mars)

Causal nexuses existed within time fissures, which were created all the time. Though not visible, they could be sensed by time sensitives, and larger events could create fissures where time tracks diverged from the nexus point, allowing for travel to parallel universes. (AUDIO: The Wreck of the Titan)

The Doctor's TARDIS became caught in a spatio-temporal causal nexus point when it hit a bump in the time track, generated by the Daleks of an alternate timeline using a time corridor to pull the Fifth Doctor into their future. (AUDIO: The Mutant Phase)

The causal nexus divided when Nyssa changed history as part of the plan arranged by the Doctor's first TARDIS, causing the universe to exist in two quantum states and releasing blinovitch energy. When the time paradox was corrected with another paradox, the Fifth Doctor became the causal nexus as the paradox resulted from knowledge he would claim not to know in his personal future. (AUDIO: Prisoners of Fate)

In keeping with this, the "Wenley Moor Affair" was a crucial nexus-point in Earth's time stream because countless futures could diverge from that moment into alternate realities. (COMIC: Final Genesis) Similarly, the Eleventh Doctor identified the Cwmtaff incident as a temporal tipping point which would "change future events, create its own timeline, its own reality." (TV: Cold Blood)

The temporal period surrounding 1941 Earth was a crucial nexus point in the planet's development, and any alterations, such as killing Adolf Hitler, would disrupt the Web of Time. (COMIC: Me and My Shadow)

When asked why he couldn't just take the TARDIS back to the previous day, the Tenth Doctor recited, as if by rote, "I can't go back within my own timeline. I have to stay relative to the Master within the causal nexus." He earlier called the same set of events a convergence. (TV: The End of Time)

When the Kin's take-over of Earth led to humanity dying out by 2010, the Eleventh Doctor explained to Amy Pond that she still existed because she was an independent temporal nexus, "chrono-synchronistically established as an inverse...," but eventually agreed with Amy that the reason was "timey wimey." He also referred to the divergence point in 1984 for the alternate timeline as the nexus. (PROSE: Nothing O'Clock)

While discussing changing her personal past, Older Amy Pond capped a list comprised of destiny and causality with the nexus of time itself, a structure of causal nexus points that described or defined time. However, at the time she was referencing changing her own recent personal history from within a stable temporal anomaly that was generated artificially. (TV: The Girl Who Waited)

Causal nexuses seemed to exist as actual structures of the universe, based on planets. Earth was widely recognised as one of the causal nexus points of Mutter's Spiral. (PROSE: Cat's Cradle: Witch Mark)

Logopolis and its inhabitants ran the Charged Vacuum Emboitements that kept N-Space going past the point of collapse. When the Tremas Master stopped Logopolis, he caused the unravelling of the whole causal nexus. This released a wave of entropy that engulfed parts of the universe, killing them. (TV: Logopolis)

A nexus resided in the transjovian space near Jupiter, which the Hand of Omega reached using faster-than-light travel, after which traversing the nexus to reach Skaro in its own time zone by punching a hole in reality. (PROSE: Remembrance of the Daleks)

The particles of the Time Vortex could clump together at a nexus point. A TARDIS could hold onto a nexus point with mathematical anchors to resist the streaming delta flows. (PROSE: Cat's Cradle: Witch Mark)

The Seventh Doctor considered (and blamed) Earth as a "major time-space nexus" for the reason he was on Earth at certain times and the coincidences that came from that. These included him being in Mesopotamia in the time of Gilgamesh (PROSE: Timewyrm: Genesys) and being in Ife during the 10th century. In the latter travel, there may have been static electricity involved which made the Yoruba believe he was Shango, the thunder god. (PROSE: Transit)

The Edifice's interior dimensions were mapped onto its exterior, making it the same size inside as outside, cancelling its dimensional transcendence. This also caused it to become a nexus point, affecting past and future events along the causal pathways, generating temporal anomalies in the resulting temporal pulses. (PROSE: The Ancestor Cell)

A hyper reality nexus was created by Godwanna to access hyper reality and absorb all the energy she created from destroying Earth in 1994. (PROSE: Invasion of the Cat-People) There were points in the universe where parallels collided, where the Parallel Sect created a reality web threaded through the whole infinity of the universe. (AUDIO: The End of the Line) 041b061a72