119 research outputs found
Stepping Beyond the Newtonian Paradigm in Biology. Towards an Integrable Model of Life: Accelerating Discovery in the Biological Foundations of Science
The INBIOSA project brings together a group of experts across many disciplines
who believe that science requires a revolutionary transformative
step in order to address many of the vexing challenges presented by the
world. It is INBIOSA’s purpose to enable the focused collaboration of an
interdisciplinary community of original thinkers.
This paper sets out the case for support for this effort. The focus of the
transformative research program proposal is biology-centric. We admit
that biology to date has been more fact-oriented and less theoretical than
physics. However, the key leverageable idea is that careful extension of the
science of living systems can be more effectively applied to some of our
most vexing modern problems than the prevailing scheme, derived from
abstractions in physics. While these have some universal application and
demonstrate computational advantages, they are not theoretically mandated
for the living. A new set of mathematical abstractions derived from biology
can now be similarly extended. This is made possible by leveraging
new formal tools to understand abstraction and enable computability. [The
latter has a much expanded meaning in our context from the one known
and used in computer science and biology today, that is "by rote algorithmic
means", since it is not known if a living system is computable in this
sense (Mossio et al., 2009).] Two major challenges constitute the effort.
The first challenge is to design an original general system of abstractions
within the biological domain. The initial issue is descriptive leading to the
explanatory. There has not yet been a serious formal examination of the
abstractions of the biological domain. What is used today is an amalgam;
much is inherited from physics (via the bridging abstractions of chemistry)
and there are many new abstractions from advances in mathematics (incentivized
by the need for more capable computational analyses). Interspersed
are abstractions, concepts and underlying assumptions “native” to biology
and distinct from the mechanical language of physics and computation as
we know them. A pressing agenda should be to single out the most concrete
and at the same time the most fundamental process-units in biology
and to recruit them into the descriptive domain. Therefore, the first challenge
is to build a coherent formal system of abstractions and operations
that is truly native to living systems.
Nothing will be thrown away, but many common methods will be philosophically
recast, just as in physics relativity subsumed and reinterpreted
Newtonian mechanics.
This step is required because we need a comprehensible, formal system to
apply in many domains. Emphasis should be placed on the distinction between
multi-perspective analysis and synthesis and on what could be the
basic terms or tools needed.
The second challenge is relatively simple: the actual application of this set
of biology-centric ways and means to cross-disciplinary problems. In its
early stages, this will seem to be a “new science”.
This White Paper sets out the case of continuing support of Information
and Communication Technology (ICT) for transformative research in biology
and information processing centered on paradigm changes in the epistemological,
ontological, mathematical and computational bases of the science
of living systems. Today, curiously, living systems cannot be said to
be anything more than dissipative structures organized internally by genetic
information. There is not anything substantially different from abiotic
systems other than the empirical nature of their robustness. We believe that
there are other new and unique properties and patterns comprehensible at
this bio-logical level. The report lays out a fundamental set of approaches
to articulate these properties and patterns, and is composed as follows.
Sections 1 through 4 (preamble, introduction, motivation and major biomathematical
problems) are incipient. Section 5 describes the issues affecting
Integral Biomathics and Section 6 -- the aspects of the Grand Challenge
we face with this project. Section 7 contemplates the effort to
formalize a General Theory of Living Systems (GTLS) from what we have
today. The goal is to have a formal system, equivalent to that which exists
in the physics community. Here we define how to perceive the role of time
in biology. Section 8 describes the initial efforts to apply this general theory
of living systems in many domains, with special emphasis on crossdisciplinary
problems and multiple domains spanning both “hard” and
“soft” sciences. The expected result is a coherent collection of integrated
mathematical techniques. Section 9 discusses the first two test cases, project
proposals, of our approach. They are designed to demonstrate the ability
of our approach to address “wicked problems” which span across physics,
chemistry, biology, societies and societal dynamics. The solutions
require integrated measurable results at multiple levels known as “grand
challenges” to existing methods. Finally, Section 10 adheres to an appeal
for action, advocating the necessity for further long-term support of the
INBIOSA program.
The report is concluded with preliminary non-exclusive list of challenging
research themes to address, as well as required administrative actions. The
efforts described in the ten sections of this White Paper will proceed concurrently.
Collectively, they describe a program that can be managed and
measured as it progresses
Nutritional therapies for mental disorders
According to the Diagnostic and Statistical Manual of Mental Disorders, 4 out of the 10 leading causes of disability in the US and other developed countries are mental disorders. Major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD) are among the most common mental disorders that currently plague numerous countries and have varying incidence rates from 26 percent in America to 4 percent in China. Though some of this difference may be attributable to the manner in which individual healthcare providers diagnose mental disorders, this noticeable distribution can be also explained by studies which show that a lack of certain dietary nutrients contribute to the development of mental disorders. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population in America and other developed countries; and are exceptionally deficient in patients suffering from mental disorders. Studies have shown that daily supplements of vital nutrients often effectively reduce patients' symptoms. Supplements that contain amino acids also reduce symptoms, because they are converted to neurotransmitters that alleviate depression and other mental disorders. Based on emerging scientific evidence, this form of nutritional supplement treatment may be appropriate for controlling major depression, bipolar disorder, schizophrenia and anxiety disorders, eating disorders, attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD), addiction, and autism. The aim of this manuscript is to emphasize which dietary supplements can aid the treatment of the four most common mental disorders currently affecting America and other developed countries: major depression, bipolar disorder, schizophrenia, and obsessive compulsive disorder (OCD)
Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks
Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to resistance; and strengthen the case for a role in survival of systems involved in manganese and iron homeostasis
The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies
Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology
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