Synthesis and antifungal activity of novel amide derivatives from quinic acid against the sweet potato pathogen Ceratocystis fimbriata.

Background: Ceratocystis fimbriata is a fungal pathogen that infects sweet potato roots, producing enormous economic losses. Cyclic polyhydroxy compound quinic acid is a common metabolite synthesized in plant tissues, including sweet potato tubers, showing weak antifungal properties. Although several O-acylated quinic acid derivatives have been synthesized and found in nature and their antifungal properties have been explored, derivatives based on modification of the carboxylic acid have never been evaluated.

Mechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is caused by loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain.

Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.

Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes.

Transcriptional Determinism and Stochasticity Contribute to the Complexity of Autism Associated Family Genes.

Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. is one of the most common autism causative genes.

Patterns of Cytogenomic Findings from a Case Series of Recurrent Pregnancy Loss Provide Insight into the Extent of Genetic Defects Causing Miscarriages.

 A retrospective study was performed to evaluate the patterns of cytogenomic findings detected from a case series of products of conception (POC) in recurrent pregnancy loss (RPL) over a 16-year period from 2007 to 2023.  This case series of RPL was divided into a single analysis (SA) group of 266 women and a consecutive analysis (CA) group of 225 women with two to three miscarriages analyzed. Of the 269 POC from the SA group and the 469 POC from the CA group, a spectrum of cytogenomic abnormalities of simple aneuploidies, compound aneuploidies, polyploidies, and structural rearrangements/pathogenic copy number variants (pCNVs) were detected in 109 (41%) and 160 cases (34%), five (2%) and 11 cases (2%), 35 (13%) and 36 cases (8%), and 10 (4%) and 19 cases (4%), respectively.

Intrathecal Injection of Newborn Mouse for Genome Editing and Drug Delivery.

Intrathecal injection is a commonly employed procedure in both pediatric and adult clinics, serving as an effective means to administer medications and treatments. By directly delivering medications and treatments into the cerebrospinal fluid of the central nervous system, this method achieves higher localized drug concentrations while reducing systemic side-effects compared to other routes such as intravenous, subcutaneous, or intramuscular injections. Its importance extends beyond clinical settings, as intrathecal injection plays a vital role in preclinical studies focused on treating neurogenetic disorders in rodents and other large animals, including non-human primates.

Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs.

Background: SHANK3 gene is a highly replicated causative gene for autism spectrum disorder and has been well characterized in multiple Shank3 mutant rodent models. When compared to rodents, domestic dogs are excellent animal models in which to study social cognition as they closely interact with humans and exhibit similar social behaviors. Using CRISPR/Cas9 editing, we recently generated a dog model carrying Shank3 mutations, which displayed a spectrum of autism-like behaviors, such as social impairment and heightened anxiety.

Identifying critical windows of air pollution exposure during preconception and gestational period on birthweight: a prospective cohort study.

Background: Few studies have assessed air pollution exposure association with birthweight during both preconception and gestational periods.

Methods: Leveraging a preconception cohort consisting of 14220 pregnant women and newborn children in Shanghai, China during 2016-2018, we aim to assess associations of NO and PM exposure, derived from high-resolution spatial-temporal models, during preconception and gestational periods with outcomes including term birthweight, birthweight Z-score, small-for-gestational age (SGA) and large-for-gestational age (LGA). Linear and logistic regressions were used to estimate 3-month preconception and trimester-averaged air pollution exposure associations; and distributed lag models (DLM) were used to identify critical exposure windows at the weekly resolution from preconception to delivery.

Modeling SHANK3-associated autism spectrum disorder in Beagle dogs via CRISPR/Cas9 gene editing.

Despite intensive studies in modeling neuropsychiatric disorders especially autism spectrum disorder (ASD) in animals, many challenges remain. Genetic mutant mice have contributed substantially to the current understanding of the molecular and neural circuit mechanisms underlying ASD. However, the translational value of ASD mouse models in preclinical studies is limited to certain aspects of the disease due to the apparent differences in brain and behavior between rodents and humans.

Antifungal and elicitor activities of p-hydroxybenzoic acid for the control of aflatoxigenic Aspergillus flavus in kiwifruit.

Aspergillus flavus not only reduces kiwifruit production but also synthesizes carcinogenic aflatoxins, resulting in a relevant threat to human health. p-Hydroxybenzoic acid (pHBA) is one of the most abundant phenolics in kiwifruit. In this study, pHBA was found to reduce A.

Novel epigenetic molecular therapies for imprinting disorders.

Genomic imprinting disorders are caused by the disruption of genomic imprinting processes leading to a deficit or increase of an active allele. Their unique molecular mechanisms underlying imprinted genes offer an opportunity to investigate epigenetic-based therapy for reactivation of an inactive allele or reduction of an active allele. Current treatments are based on managing symptoms, not targeting the molecular mechanisms underlying imprinting disorders.

Shank3 deficits in the anteromedial bed nucleus of the stria terminalis trigger an anxiety phenotype in mice.

Anxiety disorders are the most prevalent co-morbidity factor associated with the core domains of autism spectrum disorders (ASD). Investigations on potential common neuronal mechanisms that may explain the co-occurrence of ASD and anxiety disorders are still poorly explored. One of the key questions that remained unsolved is the role of Shank3 protein in anxiety behaviours.

Dipicolinic acid enhances kiwifruit resistance to Botrytis cinerea by promoting phenolics accumulation.

Background: Kiwifruit is highly susceptible to fungal pathogens, such as Botrytis cinerea, which reduce crop production and quality. In this study, dipicolinic acid (DPA), which is one of the main components of Bacillus spores, was evaluated as a new elicitor to enhance kiwifruit resistance to B. cinerea.

Estimation on risk of spontaneous abortions by genomic disorders from a meta-analysis of microarray results on large case series of pregnancy losses.

A meta-analysis on seven large case series (>1000 cases) of chromosome microarray analysis (CMA) on products of conceptions (POC) evaluated the diagnostic yields of genomic disorders and syndromic pathogenic copy number variants (pCNVs) from a collection of 35,130 POC cases. CMA detected chromosomal abnormalities and pCNVs in approximately 50% and 2.5% of cases, respectively.

CHD8 mutations increase gliogenesis to enlarge brain size in the nonhuman primate.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that affects social interaction and behavior. Mutations in the gene encoding chromodomain helicase DNA-binding protein 8 (CHD8) lead to autism symptoms and macrocephaly by a haploinsufficiency mechanism. However, studies of small animal models showed inconsistent findings about the mechanisms for CHD8 deficiency-mediated autism symptoms and macrocephaly.