Mutation bias reflects natural selection in Arabidopsis thaliana

Since the first half of the twentieth century, evolutionary theory has been dominated by the idea that mutations occur randomly with respect to their consequences1. Here we test this assumption with large surveys of de novo mutations in the plant Arabidopsis thaliana. In contrast to expectations, we find that mutations occur less often in functionally constrained regions of the genome—mutation frequency is reduced by half inside gene bodies and by two-thirds in essential genes. With independent genomic mutation datasets, including from the largest Arabidopsis mutation accumulation experiment conducted to date, we demonstrate that epigenomic and physical features explain over 90% of variance in the genome-wide pattern of mutation bias surrounding genes. Observed mutation frequencies around genes in turn accurately predict patterns of genetic polymorphisms in natural Arabidopsis accessions (r = 0.96). That mutation bias is the primary force behind patterns of sequence evolution around genes in natural accessions is supported by analyses of allele frequencies. Finally, we find that genes subject to stronger purifying selection have a lower mutation rate. We conclude that epigenome-associated mutation bias2 reduces the occurrence of deleterious mutations in Arabidopsis, challenging the prevailing paradigm that mutation is a directionless force in evolution.

Electromagnetic Information Transfer (EMIT) by Ultra High Diluted (UHD) solutions: the suggestive hypothesis of an epigenetic action.

The aim of this work is to confirm the theoretical possibility of an epigenetic mechanism shared between EMIT and UHD. The presentation will be divided in three sections: 1. Water aggregates with an electric dipole moment (UHD succussed solutions) as mediators of weak specific bioelectromagnetic signals on target stem cells. Recent experimental works confirm the developing concept of water mediated Electromagnetic Information Transfer (EMIT) of specific molecular signals, picked up from the source biological effector, on target stem cells with evident effect on their proliferation [1]. Similar Electromagnetic (EM) emission and consequences are also reported by the scientific literature on rotational excited aggregates with an electric dipole moment, created in polar liquids by Ultra High Diluted (UHD) or High Diluted (HD) succussed solutions. These aggregates are composed of solvent molecules only or a combination of these and solute particles [2]. 2. DNA mediated physiopathological effects of ELF EMFs In detail, according to the International Agency for Research on Cancer (IARC), the extremely low-frequency (ELF) electromagnetic fields (EMFs) are classified as "possible carcinogenic" based on their effects [3-5], although most scientists agree that they are too weak to kill cells or to cause mutations and thus initiate cancer. Besides the prevailing paradigm of the environmentally-induced acute and chronic diseases involving either cell killing (cytotoxicity) or gene/chromosome mutations (genotoxicity), many studies concerning the biological and health consequences of ELF-EM exposure report that alteration of the expression of genetic information at the transcriptional, translational, or posttranslational levels has the potential to contribute to various diseases. 3. Epigenetic mechanism shared between EMIT and UHDs The latter referred mechanism, denoted as "epigenetic" (that affects gene expression rather than gene structure), is characterized by threshold-like action, multiple biochemical pathways and it needs chronic regular exposures to be effective [6]. Epigenetic factors affect one of four potential cell states, namely alteration of cell proliferation, cell differentiation, programmed cell death (apoptosis) or adaptive responses of differentiated cells, and probably they act as co-inductors of DNA damage rather than as a genotoxic agents per se. At the present time, studies on genomic and functional genetic are identifying many genes and gene variants that potentially modulate the fundamental molecular mechanisms underpinning both physiological and pathological processes.

Epigenetics of Myotonic Dystrophies: A Minireview

Myotonic dystrophy type 1 and 2 (DM1 and DM2) are two multisystemic autosomal dominant disorders with clinical and genetic similarities. The prevailing paradigm for DMs is that they are mediated by an in trans toxic RNA mechanism, triggered by untranslated CTG and CCTG repeat expansions in the DMPK and CNBP genes for DM1 and DM2, respectively. Nevertheless, increasing evidences suggest that epigenetics can also play a role in the pathogenesis of both diseases. In this review, we discuss the available information on epigenetic mechanisms that could contribute to the DMs outcome and progression. Changes in DNA cytosine methylation, chromatin remodeling and expression of regulatory noncoding RNAs are described, with the intent of depicting an epigenetic signature of DMs. Epigenetic biomarkers have a strong potential for clinical application since they could be used as targets for therapeutic interventions avoiding changes in DNA sequences. Moreover, understanding their clinical significance may serve as a diagnostic indicator in genetic counselling in order to improve genotype–phenotype correlations in DM patients.

Medicine in Japanese Buddhism

Buddhist institutions were first established in the Japanese archipelago in the 6th century ce. In the same period, the ruling families incorporated Chinese-style medicine and Daoist ritual healing techniques into Japanese culture and society. By the 8th century, Buddhism had become a dominant cultural force in Japan. The Japanese Buddhist textual tradition was shaped by translations from Sanskrit into classical Chinese, and Chinese texts remained paramount for all branches of scholarship. In the ensuing centuries, a rich and hybrid ritual, material, and intellectual culture emerged from combining these various religious and scholarly traditions, as well as elements of the local tradition of kami神 (gods) worship. This also resulted in a distinct tradition of Buddhist medicine, which blossomed in the Kamakura period (1185–1333). The esoteric (or tantric) tradition of Mahāyāna Buddhism with its idea of mutual empowerment (kaji加持) and unification of the ritualist and a buddha, bodhisattva, or other Buddhist deity, directing their power to heal, protect, etc., was the prevailing paradigm. Other traditions developed over the course of the centuries, too, notably Pure Land, Nichiren, and Zen Buddhism, and the vinaya restoration movement (Shingon Ritsu). These also had an impact on the ideas and practices of healing and medical care. All shared the aim of providing the means for salvation and ultimate liberation from sickness and suffering. Lay patrons in early and medieval Japan funded the construction of hospitals and other care facilities as well as medicinal gardens. The Japanese monastics who studied the classical Chinese medical texts and treated their patients following the ideal of the compassionate bodhisattva were also familiar with basic ideas from Indian Āyurveda from translated sutras and commentaries. As such, etiology and diagnosis in the Japanese Buddhist context included epistemic and cosmological thought from both China and India. In the Buddhist context, rituals such as elaborate fire-offering ceremonies (goma護摩) were commonly used to take care of patients of all ages. Buddhist treatments also included empowered medicines, acupuncture, and moxibustion. Buddhist priests provided palliative care, and deathbed rituals were conducted to protect the dying from evil forces and prepare them spiritually for a good death and future birth. Buddhist medical practitioners not only included monastic doctors, usually called sōi僧医 in modern literature, but also various kinds of exorcists and healers. These groups produced talismans and amulets, and offered protective rituals within the paradigmatic framework of Japanese Buddhism. Pilgrimage to sacred sites at Buddhist temples provided a way for monastics and lay people to find healing and support. The external treatment of afflictions often went hand in hand with internal, mental, or cognitive methods such as various forms of meditation. These methods were primarily practiced by the monastically trained, but some, such as naikan内観, “internal observation,” were practiced by a wider circle of practitioners. Buddhistic methods were also used to treat animals.

Structural evidence for extracellular silica formation by diatoms

The silica cell wall of diatoms, a widespread group of unicellular microalgae, is an exquisite example for the ability of organisms to finely sculpt minerals under strict biological control. The prevailing paradigm for diatom silicification is that this is invariably an intracellular process, occurring inside specialized silica deposition vesicles that are responsible for silica precipitation and morphogenesis. Here, we study the formation of long silicified extensions that characterize many diatom species. We use cryo-electron tomography to image silica formation in situ, in 3D, and at a nanometer-scale resolution. Remarkably, our data suggest that, contradictory to the ruling paradigm, these intricate structures form outside the cytoplasm. In addition, the formation of these silica extensions is halted at low silicon concentrations that still support the formation of other cell wall elements, further alluding to a different silicification mechanism. The identification of this unconventional strategy expands the suite of mechanisms that diatoms use for silicification.

Casualties of preparedness: the Global Health Security Index and COVID-19

The 2019 Global Health Security Index (GHS Index) assessed the US and the UK as the two countries best prepared to address a catastrophic pandemic. The preparedness rankings of this index have had little correlation with the actual experiences of COVID-19 in various countries. In explaining this disrepancy, the paper argues that better indicators and more data would not have fixed the problem. Rather, the prevailing paradigm of global health security that informs instruments such as the GHS Index needs to be interrogated. This dominant paradigm narrowly conceptualises global health security in terms of the availability of a technical infrastructure to detect emerging infectious diseases and prevent their contagion, but profoundly undertheorises the broader social and political determinants of public health. The neglect of social and political features is amplified in instruments such as the GHS Index that privilege universalised templates presumed to apply across countries but that prove to be inadequate in assessing how individual societies draw on their unique histories to craft public health responses.

Tracing the Genealogy of Maqāṣid al-Sharī'ah Concept: A Historical Approach

This paper aims to explore the emergence, continuity and shifting of the meaning of maqāṣid al-sharī’ah. Initially, maqāṣid al-sharī’ah entered into the study of uṣūl al-fiqh and later became an independent scientific discipline. Historically, the journey of maqāṣid al-sharī’ah has four periods, namely, the pre-codification era, the first development era, the second development era, and the maturation era as a scientific discipline. This paper is qualitative with a descriptive-analytic method, namely exploring the concept of maqāṣid al-sharī’ah in various literature. The findings in this paper are, first, the history of the emergence and development of maqāṣid al-sharī’ah is closely related to the enforcement of Islamic law. Second, the continuity of maqāṣid al-sharī'ah is an ideological concept because it is based on the prevailing paradigm

The Beni Bousera marbles, record of a Triassic-Early Jurassic hyperextended margin in the Alpujarrides-Sebtides units (Rif belt, Morocco)?

The timing and process of exhumation of the subcontinental peridotites of the Gibraltar Arc (Ronda, Beni Bousera) have been repeatedly discussed in the last decades. Here we report on high-grade marbles that crop out around the central and southeastern parts of the Beni Bousera antiform of northern Rif. Instead of being mere intercalations in the granulitic envelope (kinzigites) of the peridotites, as currently admitted, they are localized between the kinzigites and the gneisses of the overlying Filali Unit. The marbles occur in the form of minor, dismembered units in a ~30 to 300 m-thick Filali-Beni Bousera ductile shear zone (FBBSZ). They display silicate-rich dolomitic marbles, sandy-conglomeratic calcareous marbles and thinly bedded marble with interleaved phyllites, which demonstrates their sedimentary origin. A stratigraphic or tectonic unconformable contact onto the kinzigites can be locally observed. Pebbles or detrital grains include K-feldspar, quartz, and zircon. Prograde metamorphic minerals are forsterite, Mg-Al-spinel, geikielite, phlogopite, scapolite, diopside, and titanite, which characterize a peak HT-LP metamorphism close to 700-750°C, 4-7 kbar, comparable to that of the overlying Filali gneisses and of the late migmatitic stage of the kinzigites. Second-order structures within the FBBSZ are northwestward ductile thrusts, which determine kinzigite horses thrust over the marbles. Within the latter, NNE-trending folds are conspicuous. The mylonitic structures are crosscut by late, northward dipping normal faults. Varied correlations with comparable settings in the other West Mediterranean Alpine belts are discussed. We propose to correlate the Beni Bousera marbles with the Triassic carbonates deposited over the crustal units of the Alpujarrides-Sebtides. The Triassic protoliths may have been deposited onto the kinzigites or carried as allochthons over a detachment during the Early Jurassic in the frame of the hyper-extension of the Alboran Domain continental crust, as observed in the Adria and Europe inverted margins of the Western Alps. In either of these hypotheses, the currently prevailing paradigm of “hot” exhumation of the Rif–Betic peridotites during the Alpine orogeny would be reconsidered.

Defining the composition of the deep mantle and the primordial He inventory of the Afar plume

<p>Basaltic rocks generated by upwelling mantle plumes display a range of trace element and isotope compositions indicative of strong heterogeneity in deep material brought to Earth surface.  Helium isotopes are an unrivalled tracer of the deep mantle in plume-derived basalts.  It is frequently difficult to identify the composition of the deep mantle component as He isotopes rarely correlate with incompatible trace element and radiogenic isotope tracers. It is supposed that this is due to the high He concentration of the deep mantle compared to degassed/enriched mantle reservoirs dominating the He in mixtures, although this is far from widely accepted.  The modern Afar plume is natural laboratory for testing the prevailing paradigm.</p><p>The <sup>3</sup>He/<sup>4</sup>He of basalt glasses from 26°N to 11°N along the Red Sea spreading axis increases systematically from 7.9 to 15 R<sub>a</sub>. Strong along-rift relationships between <sup>3</sup>He/<sup>4</sup>He and incompatible trace element ratios are consistent with a binary mixture between moderately enriched shallow asthenospheric mantle in the north and plume mantle evident in basalts from the Gulf of Tadjoura, Djibouti (the Ramad enriched component of Barrat et al. 1990).  The high-<sup>3</sup>He/<sup>4</sup>He basalts have trace element-isotopic compositions that are similar, but not identical, to the high <sup>3</sup>He/<sup>4</sup>He (22 R<sub>a</sub>) high Ti (HT2) flood basalts erupted during the initial phase of the Afar plume volcanism (Rogers et al. in press). This suggests that the deep mantle component in the modern Afar plume has a HIMU-like composition. From the hyperbolic <sup>3</sup>He/<sup>4</sup>He-K/Th-Rb/La mixing relationships we determine that the upwelling deep mantle has 3-5 times higher He concentration than the asthenosphere mantle beneath the northern Red Sea.</p><p>Barrat et al. 1990.  Earth and Planetary Science Letters 101, 233-247.</p>

Chapter 5.1a Northern Victoria Land: volcanology

Neogene volcanism is widespread in northern Victoria Land, and is part of the McMurdo Volcanic Group. It is characterized by multiple coalesced shield volcanoes but includes a few relatively small stratovolcanoes. Two volcanic provinces are defined (Hallett and Melbourne), with nine constituent volcanic fields. Multitudes of tiny monogenetic volcanic centres (mainly scoria cones) are also scattered across the region and are called the Northern Local Suite. The volcanism extends in age between middle Miocene (c. 15 Ma) and present but most is <10 Ma. Two centres may still be active (Mount Melbourne and Mount Rittmann). It is alkaline, varying between basalt (basanite) and trachyte/rhyolite. There are also associated, geographically restricted, alkaline gabbro to granite plutons and dykes (Meander Intrusive Group) with mainly Eocene–Oligocene ages (52–18 Ma). The isotopic compositions of the plutons have been used to infer overall cooling of climate during the Eocene–Oligocene. The volcanic sequences are overwhelmingly glaciovolcanic and are dominated by ‘a‘ā lava-fed deltas, the first to be described anywhere. They have been a major source of information on Mio-Pliocene glacial conditions and were used to establish that the thermal regime during glacial periods was polythermal, thus necessitating a change in the prevailing paradigm for ice-sheet evolution.