ISSN (Print): 1389-2029
ISSN (Online): 1875-5488
Volume 21, 8 Issues, 2020
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ISSN (Print): 1389-2029
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Special Issue Submission
""Current Genomics is establishing itself as a leader in the field of functional genomics."
Univ. of California, USA
Regenerative Medicine Advances and Pitfalls
Guest Editor(s): Wenchun Qu
I must tell you that we had a wonderful experience with Bentham Science Publication specifically with the journal "Current Genomics". We had good rapport with the team that handled our mansucript right from the review stage to the final publication.
P. Suprasanna (Plant Stress Physiology and Biotechnology Section, Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 4000085, India.)
Has contributed: Looking at Halophytic Adaptation to High Salinity Through Genomics Landscape
6 Articles Ahead of Print are available electronically
This part brings three interesting articles which are very unique and enlightening reviews on important areas of plantmicrobe
interaction. The parts I and II have been able to present extensive insights into plant-microbe interactions in various
fields which is in continuation in this part too [1, 2]. This part puts light on Clustered Regularly Interspaced Short Palindromic
Repeats (CRISPR)/Cas9 (CRISPR-associated protein 9) Era plant-microbe interaction, translational research on Fusarium Head
Blight (FHB) in Wheat and plant-virus interaction with reference to viral effector proteins.
Beginning with the article by Prabhukarthikeyan and co-authors, it presents the emerging CRISPR/Cas9 approach which
has gained immense attention in the last few years . The authors here have started with a brief introduction about the plantmicrobe
interactions and the CRISPR/Cas9 technique and continued with descriptive but precise mention of the use of this
technique for resistance against fungal, bacterial and viral disease. Apart from these, the use of CRISPR/Cas9 technique in case
of beneficial microbes and phytopathogens is also discussed. Collections of information from earlier studies have been collated
into a table to highlight the target genes. The table mentioned very important genes such as WRKY, eIF4E, etc. which are wellknown
to be the regulators of many important signaling pathways in various crops. The authors have pointed the fact that despite
this powerful technique in our hands for a time, it has only been extensively used in validating the previously identified
genes/pathways and still need to be employed in the successful development of durable resistance in crops against multiple
Teli et al. discuss a major threat to most cereal crops such as wheat and barley, commonly known as Fusarium head blight
or scab . The pathogenic strains of Fusarium are generally devastating for the host plants due to their adaptability and multifaceted
nature . History of FHB has documented evidences of most threatening epidemics during the years 1917, 1919, 1928,
1932, and 1935 in the United States . The authors have provided a comprehensive delineation on FHB along with its symptoms,
complexity and survivability. There are figures to illustrate the predominance of FHB associated pathogens worldwide,
biochemical foundation of host-pathogen interaction in FHB and cutting-edge techniques such as RNA interference (RNAi) and
CRISPR to remodel the host defence. There are two tables presenting the information regarding the RNA and CRISPR interference
mediated defense against FHB. Extensive description about various strategies such as the conventional breeding, molecular
marker, transgenic and non-transgenic genome engineering approaches has been well-documented in this article to offer
insights into host-pathogen interaction in FHB.
The third article by Marwal and Gaur describes specifically the plant-virus interactions and viral effector proteins . Plant
defense machinery is very difficult to understand as it behaves differently depending upon the type of pathogen attack. It is even
more critical in case of virus infection as all viruses infecting plants can augment their transmission leading to damaging the host
plants. The authors have provided a schematic illustration of R gene mediated resistance in plants, signaling molecule induction,
plant antiviral pathways and viral counter-defenses as well as virus effector proteins in plant resistance development. Detailed understanding
of R-Avr interactions and mode of their actions can lead to unravel the mystery of plant-virus interactions and this
article aimed for providing available information in a brief and precise way to help broaden our knowledge in this regard.
In continuation with part I, this part describes the use of genetically modified microbes, rhizospheric microbial communities,
various molecular techniques and omics approaches to shed the light on understanding plant-microbe interactions . Due
to the long ongoing controversies regarding the use of application of genetically engineered microbial inoculants in the field, it
has been a hot topic since the last two decades. The authors have been able to provide descriptive information regarding the
same with special application towards plant-microbe interactions. A bright study carried out with the help of omics technologies,
especially bioinformatics approaches to understand the microbial communities in coal samples.
Sudheer and co-authors presented a mini-review on engineered microbes and their applications in sustainable agriculture
. Authors emphasized especially on methods to shape the rhizosphere zone, which can ultimately promote the beneficial microbial
population in the soil. Microbial communities in the soil can be diverse and a deeper understanding of their nature can
help plants to provide enhanced stress tolerance, disease resistance, nutrient acquisition and also many other important factors.
There are various efficient genetic engineering/molecular techniques which are available and being used to attain better plant
health and yield. The authors provided a simpler version of understanding plant-microbe interaction and how the networks
work in the soil. Also mentioned briefly about the microbial inoculants and their function as biofertilizers, biocontrol agents,
and in biotic and abiotic stress tolerance. Though the application of genetically engineered microbial inoculants in the field is
still not approved fully, the potential of these cannot be denied. Upon more research and better as well as safe practices, these
can be used as huge assets to achieve sustainable agriculture.
In addition, a review is presented on genomics approaches to provide insights into the role of rhizospheric microbial communities
in plant-microbe synergy for enhanced phytoremediation . This review aims at drawing an understanding of genetic
approach integrated with bioremediation of contaminated sites. Authors have described extensively on phytoremediation and
the role of predominant rhizospheric microbial communities in it. In the later part, the application of genetically modified plants
and microbes for phytoremediation has been described. The cutting-edge genomic approaches such as CRISPR (clustered regularly
interspaced short palindromic repeats) technology was illustrated in plant-microbe synergy. Authors also presented a table
containing various plants, microbes, target pollutants and their enhanced effect on phytoremediation.
Another review by Sharma and co-authors provided insights into overall omics technologies for plant-microbe interaction
. The review tries to bring together important aspects such as plant growth promotion, nitrogen fixation, stress suppressions
and metabolic interactions along with the recent studies on various advanced omics approaches. The basics of various types of
plant-microbe interactions have been stated briefly with a vivid description of various molecular techniques. It continues with
an extensive discussion of applications of next generation sequencing techniques and meta-omics approaches in unravelling
plant-microbe interaction understandings. The authors also discussed the research gaps and future prospects of omics approaches
with respect to plant-microbe interaction studies.
Jha and team carried out bioinformatics analyses of the metagenomic data obtained from the West Jharia coal seam, Moonidih,
Jharkhand . Pyrosequencing was performed on DNA extracted from the coal samples following by bioinformatics analyses
which are taxonomic assignment and functional analysis. The upshot of the study helped in revealing important information
regarding biodiversity such as the dominance of hyperthermophilic archaea Pyrococcus furiosus along with Thermococcus
kodakarensis present in the underground coal mines of Jharia. The results also revealed the presence of dissimilatory sulfite
reductase and formylmethanofuran dehydrogenase enzymes involved in sulfite reduction and methanogenesis processes respectively.
Much information about real efficiency of coal degrading microbes is still hidden. The study has been able to provide
preliminary as well as extensive insight into meta-genomic information such as taxonomic and functional diversity of the microbial
communities in coal mines.
In the present scenario, increasing pollution and green house effect on climate are serious concerns that lead to extreme environment
conditions. Therefore, the major aim of scientist is to resolve environmental issues in an economic and sustainable
way. To deal with extreme conditions, extremophiles are safer option for scientist or industries. In industries, most of possesses
are completed in extreme environment like temperature, pH, pressure etc. However, the majority of enzymes used in industrial
process are derived from mesophilic microbes, few are from extremophiles. The mesophilic enzymes are unable to perform at
extreme conditions in industrial processes . Thus, the need of extrmophilic enzymes is increasing globally to meet out the
industrial requirements. In addition, industrial processes are also performed with chemical compounds or enzymes, which are
very cost effective and harmful. In this context, extremophilic microbes can be used directly as a cell or enzymes (extremozymes)
to carry out chemical reaction in an eco-friendly manner .
Extremophiles are used in food, pharmaceutical, textile, beverages and agricultural industries. Extremophilic microbes possess
different types of enzymes and metabolites, which can work on harsh condition and make them perfect for the industrial
purposes. These microbes are used at different physical conditions i.e. elevated level of extreme temperature, pH, heavy metal
contamination, organic solvents etc . We can improve the efficiency of extremophiles by using modern technologies such as
genetic engineering and protein engineering. The demand of extremophilic products is very large in global market. The fulfilling
of this demand requires recombinant technology for large scale production and also purification . However, there is
still need to explore multiple extremophilic microbes that can be used for society.
In continuation to first part of this special issue, this part describes different extremophilic microbes and their role in biofuel
production, industrial dye degradation and abiotic stress tolerance. Topic is also included on metagenomic analysis of plastic
degrading bacteria. In this sense, a review article by Fongaro et al.  described the importance of muiti-omics tools including
(genomics, transcriptomics, proteiomics and metabolomics) in exploitation of extremophile microorganism and their novel metabolites
for bioenergitic application. Authors discussed about different types of extremozymes including, thermophilic, psychrophilic,
piezophilic, acidophilic and halophilic in details. In another review, Purohit et al.  documented about metagenomic
approach for exploration of microbial population involved in plastic biodegradation. Metagenomic approach helps in
harnessing predominant uncultured microbial species and also opens up the scope for mining genes or enzymes (hydrolases,
laccase, etc.) engaged in polymer or plastic degradation. The comparative metagenomic study allows us to engineer microbial
community to speed up the degradation process. Authors have targeted different metagenomic approach based on 16S V2-V6
regions for identifying plastic degrading microbes from different habitat.
In a research article, Ghosh et al. , studied the diversity of the psychrotolerant actinomycetes sp. nov., in the Bay of Bengal
and recovered cold active industrial and pharmaceutical biomolecules. In this study, authors have isolated cold-adapted actinomycetes
from 1200 mts below the surface in Bay-of-Bengal. A total number of 37 novel actinomycetes from 17 distinct
groups were characterized on the basis of phenotypic and genotypic level. The major dominant group was Streptomyces. The
optimum growth of isolated strains was observed at 15°C to 20°C and also able to survive at 4°C. All the recovered isolates
were able to produce extracellular enzymes including amylase, cellulase, lipase, pectinase, and L-asparaginase and also showed
In another study, Mawad et al.  have applied microbial consortium including Pseudomoans aeruginosa and Aspergillus
flavus for the degradation of Disperse Blue 64 (DB 64) and Acid Yellow 17 (AY 17) dyes. The consortium was able to possess
higher ability to degrade dye even at 300mg/L as compared to individual one. This microbial consortium and their derived metabolites
were also able to promote Vicia faba and Triticum vulgaris germination and health of seedlings in in-vitro assay.
Chatterjee et al.  studied the abiotic stress tolerance mechanism of Cyanobacteria through Alr0765 protein study of Anabaena
PCC7120. Alr0765 is a novel CBS-CP12 domain protein that has function to provide protection against stress through
involving cellular energy mechanism and iron homeostasis. The gene expression of Alr0765 was found to increase in Anabaena
PCC7120 treated under heat, arsenic, cadmium, butachlor, salt, mannitol (drought), UV-B, and methyl viologen stresses. Further
study with FTIR confirmed the binding of Alr0765 with ATP, ADP, AMP and NADH. The same protein was also able to
accumulate iron in E. coli cells upon heterologous expression. The ROS content and total cellular H2O2 content was reduced
when Alr0765 was expressed.
For the last few decades, the constant striving to understand the mechanism of plant-microbe interaction has increased manifold,
even though a lot of inaccessible information is yet to unfold. Ingress into such covered information can be a notable aid
for mankind, particularly by helping plants fight against pathogens and other stresses. Crops are continuously exposed to many
stresses, which may be abiotic or/and biotic. At times the interactivity of microbes with plants assists plants to stand against
various environmental stresses; on the contrary, sometimes they act as stresses for plants. Plants are always at higher risks as
most of the microbes interact with the plants to feed or to survive [1, 2]. There is an extensive range of beneficial microorganisms
which play vital role in plant growth, development and survival . These are most often known as agriculturally important
microbes which not only help plants to get proper nutrients but also regulate the plant and other microbe interactions.
Knowing the nature of microbe and its connection with particular plants be useful to control diseases in plants. There are several
mechanisms for plant-microbe interactions which vary from plant to plant and microbe to microbe as well . The interaction
can materialize in any part of the plants, may it be underground or above the soil. It can also be both endophytic and epiphytic,
depending on the microbes. In addition to these two major participants, it also relies on the environment neighboring the
area where the interaction occurs.
Zooming into the high definition resolution of the genomic arrangements with the help of emerging and advanced techniques
in the post-genomics era has been of primary focus. Comparative genomics studies have successfully revealed the genetic
make-up of both plants and microbes in the past using powerful molecular approaches. In the last few decades, the advancement
in the sequencing, as well as data analysis techniques have provided the most efficient way of studying the genetic variation,
differential expression, gene regulatory networks, and many more . Microarray technologies created a new world for
the scientists which has been almost replaced by the Next generation sequencing (NGS) and before the NGS has been used to
even its full capabilities, we have single cell genomics in the picture which promises to provide the genomic resolution up to
the single cell level. Technologies such as CRISPR-Cas-9 (Clustered regularly interspaced short palindromic repeats- CRISPRassociated
protein 9) have been a boon to the world of research, especially in the field of plant pathology. Keeping in mind all
these points, the current issue is aiming at shining light into the current scenario as well as past researches that brought so much
useful information to improve crop protection.
The review article by Agrahari et al.  describes the importance of studying plant-microbe interaction and its use to crop
improvement. The article discusses the post-genomic era omics approaches such as next-generation sequencing (NGS) in association
with marker assisted selection, cloning and recombination techniques, Genome-wide association studies (GWAS) and
also CRISPR-Cas-9 technology. A brief overview of various models such as zig-zag model, invasion model, spatial immunity
model, etc. has been provided to understand plant defense responses against various pathogens. To fight against various abiotic
and biotic stress conditions, deployment plant-associated microbial population has the potential to help up to a great extent.
Last but not the least, the article describes the beneficial microbes and their applications in crop improvement. Another article
by Anupriya et al.  describes the genomics and molecular aspects of white rust disease along with how the white rust resistance
can be transferred in the susceptible varieties of oilseed Mustard. This review broadly defines the nucleotide binding
leucine rich repeat receptor (NLR) signaling and its application to exhibit oomycetes resistance in plants with special reference
to effector molecules, Albugo candida secretome. It also describes various efficient approaches such as NLR repertoire enrichment,
r-avr gene interaction, RNAi, and CRSPR-Cas technologies, which are being used to understand the pathogen-resistance
mechanism. Shukla et al.,  in their article, have reviewed biotechnological approaches for bioremediation of xenobiotics.
They specifically discuss potential extremophiles, basically microorganisms living in extreme conditions. This review provides
information on the previous studies regarding the extremophiles (microbes) and the pollutants which can been degraded. The
use of extremozymes such as amylases, proteases, etc. are highly stable and can act as good novel catalysts. There are reports of
more than 3,000 such enzymes which have been isolated from various extremophiles and have immense importance industrial uses.
Survival of life in extreme environments has always caught the attention of scientists and researchers as it can lead to understand
several mechanisms leading to humanity. A few groups of organisms, including animals, plants and microorganisms can
survive against harsh environmental conditions such as extreme temperature (cold and hot), salt, pressure, pH (acidic and alkaline)
and drought. The organisms surviving on these niches are individually called thermophiles, psychrophiles, halophiles,
piezophiles, acidophiles, alkaliphiles and xerophiles. The collective term for all these organisms is extremophiles. The study of
extremophiles has received significant interest in both environmental and industrial perspectives. It has already been reported
that microorganisms are present in a huge diversity in extreme niches. A great interest in the exploration of extreme habitats
with a diversity of extremophilic microbes and their survival mechanisms has been shown in recent years. Some microbes represented
the very ancient life forms when the environmental conditions were totally different than today, hence studying about
these microbial physiology helps to answer the evolution of life. In addition, extremophiles had also shown their role in astrobiology
The genetic and metabolic machinery of these microbes has been adapted for harsh conditions. For instance, thermophiles,
psychrophiles and piezophiles have thermostable proteins, cell wall and cell membrane that resist extreme temperature; halophiles
and xerophiles possess osmolytes and antioxidants in high concentration and; acidophiles/alkaliphiles have specific ion
transporters to pump out excess ions and maintain neutral pH. Extremophiles also maintain their cell membrane fluidity, which
protects their genetic material. They have unique genes that produce important metabolites which are stable at extreme environments
known as extremozymes. Such types of metabolites, including protein and enzymes, have proven their importance in
the field of biotechnology. For example, a DNA polymerase enzyme used in Polymerase Chain Reaction (PCR) technique is
extracted from thermophilic bacteria (Thermus aquaticus). A large number of extremozymes approximately 3000 have been
recovered from different extremophiles and are being used in several biotechnological and industrial purposes. However, there
are so many extreme niches as well as microbes and their metabolites which are needed to be explored and utilized for improving
the quality of life.
The recent advances in genomics technologies have allowed for the investigation of extremophiles diversity and their survival
mechanism as has never been seen before. Such advance genome-based studies will transform our understanding of
physiology, genetic basis and genetic mechanisms of extremophiles and will reveal the importance of extremophiles and
their products in multiple aspects of biotechnology including medicine, food technology, biofuel production, agriculture, waste
management and many more . The first part of this special issue explores genomic aspects of extremophiles including their
survival mechanisms, gene expression and their applications in agriculture and other biotechnology purposes. The extremophiles
have unique genetic material that is needed to be mined, which may be useful for genetic engineering in mesophillic microbes
and their metabolites can be used in industries. The physiology and diversity of extremophiles including halophiles, psychrophiles
and heavy metal tolerance will be presented in this special issue. Topics will also include the engineering of extremophiles
and their application in pigment production, waste management and bioenergetic purposes.
In this sense, a research article by Mawad et al.  explored phenanthrene degrading bacteria Pseudomonas fluorescens AH-40
from oily sludge sample. This bacterium requires less time for degrading complete phenanthrene as compared to previously reported
bacterial cultures. Mawadand colleagues quantified the expression of phenathrene degrading genes i.e. naphthalene dioxygenase
(nahAc) and catechol 2,3-dioxygenase (C23O) in AH-40 culture and found their increased expression during the degradation
process. Authors suggested the role of nahAc and C23O as a marker gene in phenanthrene degradation and recommend to AH-40
culture for bioremediation process. In a review, specific metabolic and genomic features of thermophiles and psychrophiles are
discussed by Kohli et al. . Kohli and colleagues reported the role of hydrophobic molecules in cell membrane structure, amino
acid composition, tRNA structure, GC content in genomes and many more in the stability of extremophiles under harsh conditions.
They also described some examples of different enzymes extracted from both thermophiles and psychrophiles and their applications
for industrial purposes. Another review by Usmani et al.  described the importance of bioengineering technologies on microbes
and their uses for producing microbial pigments using agricultural wastes as substrate.
In this review, advance techniques such as Multivariate modular metabolic engineering (MMME) and Multiplex automated
genome engineering (MAGE) are reported for modulation in secondary metabolism of extremophiles. These techniques are
used for the production of carotenoid and anthocyanin compounds. In addition, use of different agro-wastes such as Apple
pomace, Rice powder, Palm date waste, Sugar-beet molasses, Orange waste and many more in production of microbial pigments
Except for mRNA that encodes proteins, there is another kind of RNA, known as non-coding RNA (ncRNAs), that does not
encode proteins. ncRNAs control various levels of gene expression in physiology and development, such as RNA splicing,
RNA translation, cell proliferation and apoptosis. Accumulated evidence have demonstrated that ncRNAs are correlated with
the progression of a series of diseases.
Besides ncRNAs, RNA modification is another layer of epigenetic regulation of gene expression. Since the first modified
RNA ribonucleic acid was found in 1957, more than 150 kinds of known RNA modifications have been reported. RNA modifications
play critical roles in a series of biological processes, such as RNA degradation, localization and degradation, and even
circadian rhythm. Recent studies revealed that RNA modifications are also associated with metabolic diseases, cancer, neurological
disorders and cardiovascular diseases.
Due to their important roles, more researchers have devoted to the researches on ncRNAs and RNA modification. However,
the biological functions and mechanisms of ncRNAs and RNA modification are still unclear. Since experimental methods are
cost-ineffective to rapidly and effectively reveal their biological functions, it is highly desirable to develop computational
methods which are good complements to experimental techniques for this aim. In recent years, a series of computational methods
have been developed to infer the regulatory functions of RNA modification and ncRNA. Therefore, the thematic issue was
proposed with the aim to collect a diverse and complementary set of articles that demonstrate new developments and applications
of machine learning methods in computational RNA epigenetics.
This thematic issue has attracted 6 papers from highly regarded researchers around the world. After the rigorous peer review,
3 of them were accepted for publication.
Guan et al.  contributed a review article, where they summarized the recent advances in pre-miRNA recognition from the
following aspects, namely the benchmark dataset, feature extraction, prediction algorithms, and the evaluation of existing models.
The challenges and future perspectives are also discussed. It is believed that this review will provide novel insights into
researches on computational identification of miRNA precursors.
In a mini review paper contributed by Li et al. , the authors reviewed available machine learning based methods for identifying
RNA 5-methylcytosine (m5C) sites. Three essential elements, namely dataset, sequence encoding scheme, and machinelearning
algorithms, required to constitute a predictor for identifying m5C sites were firstly discussed. More importantly, the
bottleneck of those predictors was also pointed out, which should be considered when developing predictors for identifying
m5C and even the other kinds of RNA modifications.
Govindaraj et al.  proposed a novel computational predictor termed as ERT-m6Apred based on extremely randomized
tree to identify N6-methyladenosine (m6A), in which a two-step feature selection technique was used to obtain the optimal feature
Finally, the guest editor would like to thank all the authors who contributed their original works to the thematic issue and to
the reviewers for their valuable comments on those works. The guest editor would also like to express sincere gratitude to the
Editor in Chief, Dr. Christian Néri, of Current Genomics and the Assistant Manager Publications, Ms. Iqra Shafi for their excellent
supports and providing the opportunity to organize the thematic issue.
With systems genomics burgeoning, there is always a need to prioritise candidates post bioinformatics
analyses. This is where machine learning approaches have steadfastly been in use. While the
articles in part I have seen a seminal research on the applications of the genes, this second part constituting
three articles emphasizing the need for machine learning heuristics.
Roy et al. in their article entitled, “Deciphering the novel target genes involved in the epigenetics
of hepatocellular carcinoma using graph theory approach”  applied graph theory approaches for
drawing a network of genes in identifying novel targets for hepatocellular carcinoma epigenetic therapy.
The candidates they found were statistically coherent for the therapeutic use.
Natarajan et al., in their article entitled, “Helicobacter pylori reactivates Human Immunodeficiency
Virus-1 in latently infected monocytes with increased expression of IL-1β and CXCL8”  have aptly used HIV infected
monocytes for measuring the expression of genes reactivated by H. Pylori.
Parveen et al. emphasized a review on “Applications of machine learning in miRNA discovery and target prediction” 
which brings a subtle understanding of these approaches for miRNA target prediction and early phase discovery.
In conclusion, systems genomics has shaped up from nascent stage to a phase where we set actions to prevent diseases,
thanks to machine learning approaches.
“The goal of getting your genome done is not to tell you what you will die from, but it's how to learn how to take action to
prevent disease”. George M. Church.
In the last years, research efforts have been focused on the understanding of the evolutionary mechanisms linked to the control
of the transcriptional activity and developmental processes. The study of developmental mechanisms has advanced significance
over the last decade, and developmental programs that have undergone evolutionary specialization among species have
recently been characterized. Epigenetics, which includes analysis of DNA methylation, histone code (i.e., histone methylation/
demethylation, acetylation/deacetylation, phosphorylation, ubiquitination, etc.), noncoding RNA (ncRNA) pathways and
3D genome organization, has made important progress towards understanding of the complexity of developmental processes.
Epigenetic factors involved in the regulation of development are increasingly being identified in organisms ranging from yeast
to humans, and it has been shown that epigenetic phenomena such as genomic imprinting, paramutation and transgenerational
epigenetic inheritance are often closely linked to these processes. The main objective of this thematic issue is to present current
research into the epigenetic mechanisms involved in developmental programming, their evolution and their roles in disease
In the first article of this issue, Vaschetto and Ortiz  provide an opinion on the role of the duplication of sequence in
the mechanisms of gene regulation and its importance in genome evolution and developmental programming. By the analysis
of information based on master developmental genes (i.e., HOX genes), repetitive ribosomal DNA (rDNA) arrays, sequences
encoding noncoding RNAs (ncRNAs,) and distinct classes of Transposable Elements (i.e., MITEs, SINEs, R2, etc.),
the authors explain how sequence duplication may function as an evolutionary strategy to regulate the transcriptional expression
at genome-level. In the next article, Csaba  provides a review on the mechanisms associated with the hormonal
imprinting, an epigenetic phenomenon that involves the first encounter between a hormone and the target receptor, which
occurs in the perinatal period. Remarkably, Dr. Csaba postulated the theory of hormonal imprinting , and his laboratory
has made important research efforts to understand the faulty hormonal imprinting in the Developmental Origin of Health and
In the third article, Şanlı and Kabaran  examine the consequences of the maternal obesity and maternal overnutrition on
fetal programming. In this article, the authors analyze how maternal obesity is associated with epigenetic modifications that
influence fetal growth and underlie metabolic diseases during adulthood. Next, Lecoutre et al. review the mechanisms for
which maternal obesity may induce adipose tissue remodeling of offspring and explore the role of the epigenetic inheritance in
developmental programming of obesity .
In the next article, Alsayegh et al.  examine the potential of pluripotent stem cells (PSCs) as de novo source of Hematopoietic
Stem Cells (HSCs), and the mechanism of regulation of HOX and GATA factors in hematopoiesis. In this review,
the authors also evaluate the relationships existing between the HOX and GATA master regulators and microRNA (miRNA)
pathways. Lastly, Kadayifci et al.  discuss the importance of the epigenetic mechanisms for the nutritional programming
of Type 2 Diabetes Mellitus and their roles in the developmental origin of this worldwide chronic disease.
As anticipated in the editorial of the Part I of this special issue, Early Life Stress (ELS) profoundly impairs child’s brain
development and behavior giving rise to either temporary or permanent effects on cognitive, behavioral and psychological
functions. Furthermore, possible long-term cumulative effects of various types of early adversity may show up in adulthood .
ELS-related pathological consequences greatly vary among individuals and depend upon genetic and environmental factors.
This second part of the issue includes four additional reviews and provides novel exciting aspects linking genomics and epigenomics
to neuropsychiatric disorders associated to Early-Life Stress. A natural extension of this second part of the thematic
issue is the double-edged sword of epigenetic processes: their potential reversibility and long-term stability via non-Mendelian
inheritance mechanisms. A growing amount of evidence has showed that our DNA remembers past traumatic experiences
through the storage of epigenetic marks that can be transmitted into subsequent generations. Epigenetic alterations may cause a
variety of latent biological dysfunctions in the stress system of the offspring and result as pre-traumatic vulnerable factors [2,
3]. These novel and exciting mechanisms of trans-generational inheritance suggest the possibility to deliver integrative solutions
in the clinical diagnosis and therapeutic approach against various long-term consequences to ELS, and in later family life.
Based on these observations, the paper by Lux highlights the role of a parallel synaptic and hormonal activation of epigenetic
programming in human and rodent models. Liu et al. elucidate both genomic and non-genomic mechanisms related to stress
modulation of the hypothalamic-pituitary-adrenal (HPA) axis leading to methylation of the glucocorticoid receptor gene
(NR3C1) and activation of lifelong impairments. Bearer et al. provide an in-depth introduction to genome-wide changes in the
child's methylome pattern induced by early adversity in life, potentially linked to the development and function of brain circuits,
immune and endocrine system. Stenz et al. describe the still largely unexplored concept of the intergenerational transmission
of DNA methylation signatures associated to the increased risk for developmental psychopathology. The aforementioned
reviews are mostly focused on genomic and epigenomic variations in neuropsychiatric disorders associated to ELS phenomena.
Moving these advanced findings into the routine medical practice will offer a revolutionary care and rehabilitation approach for
patients, either adults or children generally poorly managed, who suffer from psychopathologies following ELS exposure. The
overall aim of this Special Issue is to prove how the developmental age may represent a window of opportunity to implement
novel early interventions in the diagnosis and treatment of individuals subjected to ELS. Likewise, the resulting collection of
the present reviews examines wider strategic significance. A greater understanding of neuroplasticity and the brain interactions
with the social environment will promote a fertile ground of investigations to the pathogenesis of neurodegenerative disorders
and other psychiatric illnesses (e.g. schizophrenia), characterized by disruptive processes of cerebral growth and synaptic plasticity
Early Life Stress (ELS) profoundly impairs child’s brain development and behaviour giving rise to either temporary or permanent
effects on cognitive, behavioural and psychological functions. Furthermore, possible long-term cumulative effects of
various types of early adversity may show up in adulthood . ELS-related pathological consequences greatly vary among individuals
and depend on genetic and environmental factors. With regard to the onset of neurodevelopmental and psychiatric
disorders associated to ELS exposure, great emphasis must be laid on the influence of various pre-, peri- and post-traumatic
components in the environmental social context in which childhood abuse occurs. Namely, other influence factors related to the
nature of the early trauma, such as its duration, chronicity, and severity, strongly predispose towards either pathological outcomes
or resilient reactions. Together, genetic and environmental factors influence the individual stress responses although the
most remarkable effects of such an interplay are those concerning a critical period of vulnerability spanning from fetal to postnatal
development and adolescence. During this developmental window, the genome within neurons appears to be more plastic
and sensitive to both positive and negative environmental stimuli. These gene-environment interactions contribute to optimal
brain development, establishing a proper neural and behavioural developmental trajectory . As previously anticipated, it is
now clear that there is a causal link between ELS and the onset of neuropsychiatric and behavioural consequences, both with
short- and long-term effects .
With the advent of Omic technologies, we are getting a considerable amount of information on the gene-environment interplay
mechanisms, and learning biological underpinnings of those long-lasting changes that influence the pathological effects of
ELS during the development of brain and behavioural traits . In recent years, we have witnessed the rapid evolution of
knowledge about several potential mediators responsible for the high phenotypic heterogeneity observed among individuals
exposed to ELS. Ultimately, epigenetic changes in response to stress signalling are also known to influence the development
and susceptibility to early trauma-related pathologies. Epigenetic variations depict potentially reversible and transitory biochemical
changes that cause altered gene expression without modifying the DNA sequence and dynamically switch transcription
rates in response to a multitude of environmental stimuli and developmental states. These epigenetic changes mirror the
great flexibility of diverse biological processes of the organism including the modulation of proper and adaptive neurobiological
responses to various stressor agents throughout the life. However, experiencing prematurely a stress challenge causes widespread
alterations in brain plasticity and neuroendocrine system that correlate with marked and persistent changes in functional
activity of a large number of stress responsive genes . It follows that the epigenetic deregulation may be implicated in many
long-term pathological consequences of physical and mental health.
The above key concepts are well represented by the seven reviews selected for the present Special Issue, which aims to provide
an extensive overview of the interplay between ELS and the genome. This Special Issue is divided into two parts: the first
comprises two papers and features a very constructive analysis of ELS-driven processes that program the cerebral decline to
neurodevelopment and neuropsychiatric disorders. To this end, Drake et al. examine the intriguing and relatively little-known
mechanisms linking preterm birth with neurodevelopmental effects. From the viewpoint of clinical neuroscience, there is substantial
interest in studying the delayed effects of ELS in neurodegeneration. Therefore, the scope of the paper by Lemche is to
provide a highly informative overview of genomic association studies supporting the relevance of ELS as a powerful mediator
of Late-Onset Alzheimer’s Disease (LOAD).
Taken as a whole, the pioneering works of this first part of the Issue invite the readers to discover some interesting genomics
and epigenomics insights into the programming of the neuronal cell fate during the developmental age. These new findings
build the foundation for precision medicine to improve the treatment of neuropathological sequelae induced by ELS injury,
develop preclinical screening and, possibly, offer more reliable and integrative therapeutic models.
The past twenty-five years significantly expanded our knowledge of Copy Number Variants (CNVs), genomic imbalances
belonging to structural genetic variations, and their role in both human health and disease, particularly in the neurological field.
In 1991, Lupski was the first to associate a CNV (a DNA duplication) to a human autosomal dominant neurodegenerative disease,
the Charcot-Marie-Tooth Disease Type 1A . In the last years, different technologies succeeded one another, increasing
the power of resolution and the regions of application. However, technological and conceptual barriers have hampered the investigation
of neurodegenerative diseases from a polygenic point of view, not only for complex neurodegenerative diseases but
also for monogenic ones. For example, even if Neurofibromatosis type 1 represents a monogenic autosomal dominant disorder
with complete penetrance, it is characterized by a variable expressivity that is hard to address in a genotype-phenotype correlation
In this mini-thematic issue, we aim to describe the progress in the study of these important types of structural variations in
medicine, exploring the use of CNVs analysis in neurological disorders, as recently reviewed for Alzheimer’s Disease, Parkinson’s
Disease and Amyotrophic Lateral Sclerosis studies [4-6]. Taken together, the three manuscripts published in the present
mini-thematic issue provide the reader an overview of the recent findings regarding inherited neuropathies (Salpietro et al.) and
adult-onset neuropsychiatric disorders, i.e. Schizophrenia and Alzheimer’s disease (Lew et al.), and emphasize the need of custom
technologies, such as a customized exon-centric aCGH, to detect overlapping gene signatures among neurological conditions
(La Cognata et al.).
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