Math can’t Move Matter Park, Seungbae
Metaphysica (Dettelbach, Germany),
04/2024, Volume:
25, Issue:
1
Journal Article
Causal platonism asserts that mathematical objects cause neural states in human brains. I raise the following four objections to it. (i) Quantum entanglement does not show that one object can ...causally affect another, although one is nontemporal, nonspatial, and unchanging. (ii) Causal platonism can neither be justified a posteriori nor
. (iii) To postulate mathematical media to flesh out mathematical causation is to multiply mysteries beyond necessity. (iv) To say that mathematical causation is unintelligible and inexplicable is not to complain about causation in general.
In the last decade, massive omics datasets have been generated for human brain research. It is evolving so fast that a timely update is urgently needed. In this review, we summarize the main ...multi-omics data resources for the human brains of both healthy controls and neuropsychiatric disorders, including schizophrenia, autism, bipolar disorder, Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, etc. We also review the recent development of single-cell omics in brain research, such as single-nucleus RNA-seq, single-cell ATAC-seq and spatial transcriptomics. We further investigate the integrative multi-omics analysis methods for both tissue and single-cell data. Finally, we discuss the limitations and future directions of the multi-omics study of human brain disorders.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Postmenopausal longevity distinguishes humans from our closest living evolutionary cousins, the great apes, and may have evolved in our lineage when the economic productivity of grandmothers allowed ...mothers to wean earlier and overlap dependents. Since increased longevity retards development and expands brain size across the mammals, this hypothesis links our slower developing, bigger brains to ancestral grandmothering. If foraging interdependence favoured postmenopausal longevity because grandmothers' subsidies reduced weaning ages, then ancestral infants lost full maternal engagement while their slower developing brains were notably immature. With survival dependent on social relationships, sensitivity to reputations is wired very early in neural ontogeny, beginning our lifelong preoccupation with shared intentionality. This article is part of the theme issue 'Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals'.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Insulin-like growth factor (IGF) binding protein (IGFBP)−3 and cyclic Glycine-Proline (cGP) regulate circulating IGF-1 function that is associated with cognition. The association between IGF-1 ...function and Alzheimer’s disease (AD) remains inconclusive. This study evaluated the changes of IGFBPs and cGP, and their effects on the bioavailability and function of IGF-1 in human brain of AD cases.
Using biological and mathematic analysis we measured the concentrations of total, bound and unbound forms of IGF-1, IGFBPs and cGP in the inferior-frontal gyrus and middle-frontal gyrus of human AD (n = 15) and control cases (n = 15). The association between the changes of total concentration of these peptides and total protein concentration in brain tissues were also analyzed.
The unbound bioavailable IGF-1 was lower whereas the bound cGP and IGFBP-3 were higher in AD than the control cases. Total protein that was lower in AD than control cases, was negatively associated with cGP concentration of control cases and with IGFBP-3 concentration of AD cases.
The results provide direct evidence for IGF-1 deficiency in AD brain due to lower bioavailable IGF-1. The increase of bound IGFBP-3 impaired autocrine regulation. The increase of bound cGP is an autocrine response to improve the bioavailability and function of IGF-1 in AD brain.
All data generated or analysed during this study are included in this published article. Additional datasets analysed during the current study available from the corresponding author on reasonable request.
•IGF-1 function is impaired in AD brain by showing lower bioavailable IGF-1 than the controls.•Increase of bound IGFBPs in AD brain impairs autocrine regulation of IGF-1 and reduces bioavailable IGF-1.•Increase of bound cGP in AD brain is a compensatory response to increase bioavailable IGF-1 in AD brain.•Mathematic analysis is a useful tool for analyzing autocrine regulation of IGF-1.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous ...histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project HCP 7T dataset, n=184). Although the main rostro-caudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.
Particles that are atomic and subatomic constitute up the entire cosmos. The laws of the quantum world apply to particles as well. It is essential to unravel the still-mysterious enigma of quantum ...physics in order to comprehend quantum systems. The intricacy of the human brain is almost as complicated as that of the cosmos. All of the aforementioned challenges were addressed in this study from the viewpoint of a quantum system. The comparative study and analysis of the human brain has incorporated use of quantum physics concepts including entanglement, superposition, no-cloning, and uncertainty. Also, this study investigated into how commercial quantum devices may serve hitherto unresolved areas of the brain. Investigations on quantum artificial neural networks that resemble the structure and operation of human neurons have also been undertaken. The effectiveness of the brain with various qubit sizes has then been compared. The authors next examined the efficiency of photon absorption, filtering, and transport as well as the amount of signal lost in the skin, ocular, intracranial, and intercranial spaces. Then, the intra-space and inter-space quantum entanglement error rates were compared using individual qubits, particles, and photons. These research all came to the same conclusion: the quantum mechanical principle may have been directly or indirectly developed from the human brain and other sensory organs. The human body, on the other hand, has a comparatively limited capability for comprehending quantum theory.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: Massa intermedia, a midline bar-shaped structure, connects two thalami across the third ventricle in 70–80% of healthy humans. It has become clinically important since its absence was ...comprehended as a midline malformation of the brain and brought in connection with schizophrenia indicating that some symptoms could be a consequence of disturbed neuron chains underlying the mechanisms of attention and processing of information. The aim of the investigation was to find out the incidence, position, and size of massa intermedia in the brains of the Serbian population. Materials and methods: Our investigation was performed on 41 brains of adult Serbian cadavers using a macro dissection method. Results: Massa intermedia was present in 80.49% of cases, in 1 case it was double. In most of the cases it was located in the superior quadrants of the lateral wall of the third ventricle, the larger part being in the anterosuperior one. Some other combinations were also present. The horizontal diameter of the cross-section was larger than vertical and was not in correlation with the length of the third ventricle. The average cross-sectional area was 29.58 mm2, significantly larger in females. Conclusions: Massa intermedia is present in most of the investigated brains, usually connecting the anterior-superior quadrants of the lateral walls of the third ventricle. Different in shape and size its cross-section is a horizontal ellipse, significantly larger in females. The cross-sectional area and the size of the third ventricle are not in correlation.
The RNA integrity number (RIN) is often considered to be a critical measure of the quality of postmortem human brains. However, it has been suggested that RINs do not necessarily reflect the ...availability of intact mRNA. Using the Agilent bioanalyzer and qRT‐PCR, we explored whether RINs provide a meaningful way of assessing mRNA degradation and integrity in human brain samples by evaluating the expression of 3′–5′ mRNA sequences of the cytochrome C‐1 (CYC1) gene. Analysis of electropherograms showed that RINs were not consistently correlated with RNA or cDNA profiles and appeared to be poor predictors of overall cDNA quality. Cycle thresholds from qRT‐PCR analysis to quantify the amount of CYC1 mRNA revealed positive correlations of RINs with amplification of full‐length transcripts, despite the variable degree of linear degradation along the 3′–5′ sequence. These data demonstrate that in postmortem human brain tissue the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality.
Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs.
Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Core spliceosome and related RNA-binding proteins aggregate in Alzheimer's disease (AD) brain even in early asymptomatic stages (AsymAD) of disease. To assess the specificity of RNA-binding protein ...aggregation in AD, we developed a targeted mass spectrometry approach to quantify broad classes of RNA-binding proteins with other pathological proteins including tau and amyloid beta (Aβ) in detergent insoluble fractions from control, AsymAD, AD and Parkinson's disease (PD) brain. Relative levels of specific insoluble RNA-binding proteins across different disease groups correlated with accumulation of Aβ and tau aggregates. RNA-binding proteins, including splicing factors with homology to the basic-acidic dipeptide repeats of U1-70K, preferentially aggregated in AsymAD and AD. In contrast, PD brain aggregates were relatively depleted of many RNA-binding proteins compared to AsymAD and AD groups. Correlation network analyses resolved 29 distinct modules of co-aggregating proteins including modules linked to spliceosome assembly, nuclear speckles and RNA splicing. Modules related to spliceosome assembly and nuclear speckles showed stage-specific enrichment of insoluble RBPs from AsymAD and AD brains, whereas the RNA splicing module was reduced specifically in PD. Collectively, this work identifies classes of RNA-binding proteins that distinctly co-aggregate in detergent-insoluble fractions across the specific neurodegenerative diseases we examined.
Machado-Joseph disease (MJD) is a dominant neurodegenerative disease caused by an expanded CAG repeat in the
gene encoding the ataxin-3 protein. Several cellular processes, including transcription ...and apoptosis, are disrupted in MJD. To gain further insights into the extent of dysregulation of mitochondrial apoptosis in MJD and to evaluate if expression alterations of specific apoptosis genes/proteins can be used as transcriptional biomarkers of disease, the expression levels of
,
and
and the
/
ratio (an indicator of susceptibility to apoptosis) were assessed in blood and post-mortem brain samples from MJD subjects and MJD transgenic mice and controls. While patients show reduced levels of blood
transcripts, this measurement displays low accuracy to discriminate patients from matched controls. However, increased levels of blood
transcripts and decreased
/
ratio are associated with earlier onset of disease, indicating a possible association with MJD pathogenesis. Post-mortem MJD brains show increased
/
transcript ratio in the dentate cerebellar nucleus (DCN) and increased BCL2/BAX insoluble protein ratio in the DCN and pons, suggesting that in these regions, severely affected by degeneration in MJD, cells show signs of apoptosis resistance. Interestingly, a follow-up study of 18 patients further shows that blood
and
transcript levels increase over time in MJD patients. Furthermore, while the similar levels of blood
,
, and
transcripts observed in preclinical subjects and controls is mimicked by pre-symptomatic MJD mice, the expression profile of these genes in patient brains is partially replicated by symptomatic MJD mice. Globally, our findings indicate that there is tissue-specific vulnerability to apoptosis in MJD subjects and that this tissue-dependent behavior is partially replicated in a MJD mouse model.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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