Organisms can change their physiological/behavioural traits to adapt and survive in changed environments. However, whether these acquired traits can be inherited across generations through non-genetic alterations has been a topic of debate for over a century. Emerging evidence indicates that both ancestral and parental experiences, including nutrition, environmental toxins, nurturing behaviour, and social stress, can have powerful effects on the physiological, metabolic and cellular functions in an organism. In certain circumstances, these effects can be transmitted across several generations through epigenetic (i.e. non-DNA sequence-based rather than mutational) modifications. In this review, we summarize recent evidence on epigenetic inheritance from parental environment-induced developmental and physiological alterations in nematodes, fruit flies, zebrafish, rodents, and humans. The epigenetic modifications demonstrated to be both susceptible to modulation by environmental cues and heritable, including DNA methylation, histone modification, and small non-coding RNAs, are also summarized. We particularly focus on evidence that parental environment-induced epigenetic alterations are transmitted through both the maternal and paternal germlines and exert sex-specific effects. The thought-provoking data presented here raise fundamental questions about the mechanisms responsible for these phenomena. In particular, the means that define the specificity of the response to parental experience in the gamete epigenome and that direct the establishment of the specific epigenetic change in the developing embryos, as well as in specific tissues in the descendants, remain obscure and require elucidation. More precise epigenetic assessment at both the genome-wide level and single-cell resolution as well as strategies for breeding at relatively sensitive periods of development and manipulation aimed at specific epigenetic modification are imperative for identifying parental environment-induced epigenetic marks across generations. Considering their diverse epigenetic architectures, the conservation and prevalence of the mechanisms underlying epigenetic inheritance in non-mammals require further investigation in mammals. Interpretation of the consequences arising from epigenetic inheritance on organisms and a better understanding of the underlying mechanisms will provide insight into how gene-environment interactions shape developmental processes and physiological functions, which in turn may have wide-ranging implications for human health, and understanding biological adaptation and evolution.
Synaptic cytoskeleton dysfunction represents a common pathogenesis in neurodevelopmental disorders, such as autism spectrum disorder (ASD). The serine/threonine kinase PAK2 is a critical regulator of cytoskeleton dynamics. However, its function within the central nervous system and its role in ASD pathogenesis remain undefined. Here, we found that Pak2 haploinsufficiency resulted in markedly decreased synapse densities, defective long-term potentiation, and autism-related behaviors in mice. Phosphorylation levels of key actin regulators LIMK1 and cofilin, together with their mediated actin polymerization, were reduced in Pak2mice. We identified one de novo PAK2 nonsense mutation that impaired PAK2 function in vitro and in vivo and four de novo copy-number deletions containing PAK2 in large cohorts of patients with ASD. PAK2 deficiency extensively perturbed functional networks associated with ASD by regulating actin cytoskeleton dynamics. Our genetic and functional results demonstrate a critical role of PAK2 in brain development and autism pathogenesis.
The iCT navigation system provides desirable accuracy of posterior spinal instrumentation for patients during surgical correction of spinal deformity without radiation exposure to the medical staff, especially in thoracic spine instrumentation. Meanwhile, the iCT in itself is an effective means of assessing complex instrumentation of the spinal deformity.
Extremely severe Pott's kyphotic deformity cannot be completely corrected by conventional techniques, including vertebral body resection, Smith-Peterson, pedicle subtraction osteotomy or even vertebral column resection (VCR). The authors developed a new technique combining transpedicular eggshell osteotomies and VCR as multilevel modified vertebral column resection (MVCR) through a single posterior approach for surgical treatment of Pott's kyphosis with Konstam's angle beyond 90°. A total of 9 patients (6 males, 3 females) in our institution with severe Pott's kyphosis who underwent single-stage posterior-only multilevel MVCR were retrospectively reviewed. The candidates for multilevel MVCR were those with a sharp, angular kyphosis in the lower thoracic or upper lumbar spine with a Konstam's angle beyond 90°.
Rapid cell division and expansion in early fruit development are important phases for cucumber fruit yield and quality. Kinesin proteins are microtubule-based motors responsible for modulating cell division and enlargement. In this work, the candidate kinesin genes involved in rapid cell division and expansion during cucumber fruit development were investigated. The morphological and cellular changes during early fruit development were compared in four cucumber genotypes with varied fruit size. The correlation between the expression profiles of cucumber kinesin genes and cellular changes in fruit was investigated. Finally, the biochemical characteristics and subcellular localizations of three candidate kinesins were studied. The results clarified the morphological and cellular changes during early cucumber fruit development. This study found that CsKF2–CsKF6 were positively correlated with rapid cell production; CsKF1 and CsKF7 showed a strongly positive correlation with rapid cell expansion. The results also indicated that CsKF1 localized to the plasma membrane of fast-expanding fruit cells, that CsKF2 might play a role in fruit chloroplast division, and that CsKF3 is involved in the function or formation of phragmoplasts in fruit telophase cells. The results strongly suggest that specific fruit-enriched kinesins are specialized in their functions in rapid cell division and expansion during cucumber fruit development.
The management goal of sharp angular spinal deformity is to realign the spinal deformity and safely decompress the neurological elements. However, some shortcomings related to current osteotomy treatment for these deformities are still evident. We have developed a new spinal osteotomy technique—vertebral column decancellation (VCD), including multilevel vertebral decancellation, removal of residual disc, osteoclasis of the concave cortex, compression of the convex cortex accompanied by posterior instrumentation with pedicle screws, with the expectation to decrease surgical-related complications. From January 2004 to March 2007, 45 patients (27 males/18 females) with severe sharp angular spinal deformities at our institution underwent VCD. The diagnoses included 29 congenital kyphoscoliosis and 16 Pott’s deformity. Preoperative and postoperative radiographic evaluation was performed. Intraoperative, postoperative and general complications were noted. For a kyphosis deformity, an average of 2.2 vertebrae was decancellated (range, 2–4 vertebrae). The mean preoperative kyphosis was +98.6° (range, 82°–138°), and the mean kyphosis in the immediate postoperative period was +16.4° (range, 4°–30°) with an average postoperative correction of +82.2° (range, 61°–124°). For a kyphoscoliosis deformity, the correction rate was 64% in the coronal plane (from 83.4°–30.0°) postoperatively and 32.5° (61% correction) at 2 years’ follow-up. In the sagittal plane, the average preoperative curve of 88.5° was corrected to 28.6° immediately after surgery and to 31.0° at 2 years’ follow-up. All patients had solid fusion at latest follow-up. Complications were encountered in eight patients (17.8%), including CSF leak (n = 1), deep wound infection (n = 1), epidural hematoma (n = 1), transient neurological deficit (n = 4), and complete paralysis (n = 1). The results of this study show that single-stage posterior VCD is an effective option to manage severe sharp angular spinal deformities.
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