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Animals that exhibited estrus had greater pregnancy success compared to animals that did not exhibit estrus before fixed-time AI (FTAI). Estradiol is synthesized in bovine ovarian follicles under gonadotropin regulation and can directly and indirectly regulate the uterine receptivity and luteal function. Estradiol concentrations at FTAI impacted oviductal gene expression and has been reported to play an important role in establishing the timing of uterine receptivity. These changes have been reported to impact uterine pH and sperm transport to the site of fertilization. After fertilization, preovulatory estradiol has been reported to improve embryo survival likely by mediating changes in uterine blood flow, endometrial thickness and changes in histotroph. Cows with greater estradiol concentrations at the time of GnRH-induced ovulation also had a larger dominant follicle size and greater circulating progesterone concentrations on day 7. Therefore, it is impossible to accurately determine the individual benefit of greater estradiol concentrations prior to ovulation and greater progesterone concentrations following ovulation to pregnancy establishment, as these two measurements are confounded. Research has indicated an importance in the occurrence and timing of increasing preovulatory concentrations of estradiol, but increasing estradiol concentrations by supplementation may not be sufficient to increase fertility. Increased production of estradiol by the preovulatory follicle may be required to enhance fertility through the regulation of sperm transport, fertilization, oviductal secretions, the uterine environment, and embryo survival.

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The 3' untranslated region has an important role in gene regulation through microRNAs, and it has been estimated that microRNAs regulate up to 50% of coding genes in mammals. With the aim of allelic variant identification of 3' untranslated region microRNA seed sites, the 3' untranslated region was searched for seed sites of four temperament-associated genes (CACNG4, EXOC4, NRXN3, and SLC9A4). The microRNA seed sites were predicted in the four genes, and the CACNG4 gene had the greatest number with 12 predictions. To search for variants affecting the predicted microRNA seed sites, the four 3' untranslated regions were re-sequenced in a Brahman cattle population. Eleven single nucleotide polymorphisms were identified in the CACNG4, and eleven in the SLC9A4. Rs522648682:T>G of the CACNG4 gene was located at the predicted seed site for bta-miR-191. Rs522648682:T>G evidenced an association with both exit velocity (p = 0.0054) and temperament score (p = 0.0097). The genotype TT had a lower mean exit velocity (2.93 ± 0.4 m/s) compared with the TG and GG genotypes (3.91 ± 0.46 m/s and 3.67 ± 0.46 m/s, respectively). The allele associated with the temperamental phenotype antagonizes the seed site, disrupting the bta-miR-191 recognition. The G allele of CACNG4-rs522648682 has the potential to influence bovine temperament through a mechanism associated with unspecific recognition of bta-miR-191.

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The objective of this study was to evaluate the effect of intronic single nucleotide polymorphisms (SNP) on temperament traits in a Brahman cattle population. The SNP located in CACNG4, EXOC4, NRXN3, and SLC9A4 candidate genes were genotyped in 250 animals with temperament records of exit velocity, pen score, and temperament score. Rs3423464051:G>A in the CACNG4 gene was associated with exit velocity and temperament score. An in silico analysis of the five intronic SNP showed that alternative alleles of CACNG4-rs3423464051, EXOC4-rs109393235, and SLC9A4-rs109722627 SNP could alter branch point sites during splicing, while a protein-protein interaction network analysis demonstrated a GRIA2 gene-mediated interaction between CACNG4 and NRXN3. The present results support previously reported evidence regarding bovine temperament-related candidate genes, particularly CACNG4, which is a confirmed candidate gene in need of more detailed analyses to reveal its role in temperament-related traits.(AU)

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Animals that exhibited estrus had greater pregnancy success compared to animals that did not exhibit estrus before fixed-time AI (FTAI). Estradiol is synthesized in bovine ovarian follicles under gonadotropin regulation and can directly and indirectly regulate the uterine receptivity and luteal function. Estradiol concentrations at FTAI impacted oviductal gene expression and has been reported to play an important role in establishing the timing of uterine receptivity. These changes have been reported to impact uterine pH and sperm transport to the site of fertilization. After fertilization, preovulatory estradiol has been reported to improve embryo survival likely by mediating changes in uterine blood flow, endometrial thickness and changes in histotroph. Cows with greater estradiol concentrations at the time of GnRH-induced ovulation also had a larger dominant follicle size and greater circulating progesterone concentrations on day 7. Therefore, it is impossible to accurately determine the individual benefit of greater estradiol concentrations prior to ovulation and greater progesterone concentrations following ovulation to pregnancy establishment, as these two measurements are confounded. Research has indicated an importance in the occurrence and timing of increasing preovulatory concentrations of estradiol, but increasing estradiol concentrations by supplementation may not be sufficient to increase fertility. Increased production of estradiol by the preovulatory follicle may be required to enhance fertility through the regulation of sperm transport, fertilization, oviductal secretions, the uterine environment, and embryo survival.(AU)

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BACKGROUND: Tau hyperphosphorylation at several sites, including those close to its microtubule domain (MD), is considered a key pathogenic event in the development of tauopathies. Nevertheless, we recently demonstrated that at the very early disease stage, tau phosphorylation (pTau) at MD sites promotes neuroprotection by preventing seizure-like activity. OBJECTIVE: To further support the notion that very early pTau is not detrimental, the present work evaluated the young rTg4510 mouse model of tauopathy as a case study. Thus, in mice at one month of age (PN30-35), we studied the increase of pTau within the hippocampal area as well as hippocampal and locomotor function. METHODS: We used immunohistochemistry, T-maze, nesting test, novel object recognition test, open field arena, and electrophysiology. RESULTS: Our results showed that the very young rTg4510 mouse model has no detectable changes in hippocampal dependent tasks, such as spontaneous alternation and nesting, or in locomotor activity. However, at this very early stage the hippocampal neurons from PN30-35 rTg4510 mice accumulate pTau protein and exhibit changes in hippocampal oscillatory activity. Moreover, we found a significant reduction in the somatic area of pTau positive pyramidal and granule neurons in the young rTg4510 mice. Despite this, improved memory and increased number of dendrites per cell in granule neurons was found. CONCLUSION: Altogether, this study provides new insights into the early pathogenesis of tauopathies and provides further evidence that pTau remodels hippocampal function and morphology.

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Although protocols exist for the recovery of ancient DNA from land snail and marine bivalve shells, marine conch shells have yet to be studied from a paleogenomic perspective. We first present reference assemblies for both a 623.7 Mbp nuclear genome and a 15.4 kbp mitochondrial genome for Strombus pugilis, the West Indian fighting conch. We next detail a method to extract and sequence DNA from conch shells and apply it to conch from Bocas del Toro, Panama across three time periods: recently-eaten and discarded (n = 3), Late Holocene (984-1258 before present [BP]) archaeological midden (n = 5), and mid-Holocene (5711-7187 BP) paleontological fossil coral reef (n = 5). These results are compared to control DNA extracted from live-caught tissue and fresh shells (n = 5). Using high-throughput sequencing, we were able to obtain S. pugilis nuclear sequence reads from shells across all age periods: up to 92.5 thousand filtered reads per sample in live-caught shell material, 4.57 thousand for modern discarded shells, 12.1 thousand reads for archaeological shells, and 114 reads in paleontological shells. We confirmed authenticity of the ancient DNA recovered from the archaeological and paleontological shells based on 5.7× higher average frequency of deamination-driven misincorporations and 15% shorter average read lengths compared to the modern shells. Reads also mapped to the S. pugilis mitochondrial genome for all but the paleontological shells, with consistent ratios of mitochondrial to nuclear mapped reads across sample types. Our methods can be applied to diverse archaeological sites to facilitate reconstructions of the long-term impacts of human behaviour on mollusc evolutionary biology.

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Publishing articles in international scientific journals is the primary method for the communication of validated research findings and ideas. Journal articles are commonly used as a major input for evaluations of researchers and institutions. Few articles have been published previously about the different aspects needed for writing high-quality articles. In this manuscript, we provide an updated and brief guide for the multiple dimensions needed for writing manuscripts in the health and biological sciences, from current, international and interdisciplinary perspectives and from our expertise as authors, peer reviewers and editors. We provide key suggestions for writing major sections of the manuscript (e.g. title, abstract, introduction, methods, results and discussion), for submitting the manuscript and bring an overview of the peer review process and  of the post-publication impact of the articles.

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COVID-19 has catastrophically affected the world's panoramic view of human well-being in terms of healthcare and management. With the increase in the number of cases worldwide, neurological symptoms and psychological illnesses from COVID-19 have increasingly upsurged. Mental health illness and affective disorders, including depression, obsessive-compulsive disorder, anxiety, phobia, and panic disorders, are highly impacted due to social distress. The COVID-19 pandemic not only affected people with pre-existing mental and affective illnesses, but also healthy individuals with anxiety, worrying, and panic symptoms, and fear conditioning. In addditon, the novel coronavirus is known to impact the central nervous system in the brain, resulting in severe and certain long-lasting neurological issues. Owing to the significance of neurological and psychological events, the present perspective has been an attempt to disseminate the impact of COVID-19 on neural injury through inflammation, and its interrelation with psychological symptoms. In this current review, we synthesize the literature to highlight the critical associations between SARS-CoV-2 infection and the nervous system, and mental health illness, and discuss potential mechanisms of neural injury through psycho-neuroimmunity.

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The objectives of the study were to determine the effect of steroidal implants on growth performance, carcass characteristics, and estradiol-17ß (E2) concentrations in the blood and longissimus muscle of Holstein steers fed a grain-based diet. Seventy Holstein steers (average initial BW = 275 ± 6.4 kg, 10 to 12 mo of age) were assigned to treatments: (i) implanted with 80 mg of trenbolone acetate (TBA) and 16 mg of E2 (Component TE-IS with Tylan; Elanco Animal Health, Greenfield, IN) at the start of the trial (day 0), and reimplanted with 120 mg of TBA and 24 mg of E2 (Component TE-S with Tylan; Elanco Animal Health) on day 84 of the experiment; or (ii) no implant. Implanted Holstein steers were heavier (P ≤ 0.01) than nonimplanted Holstein steers in the middle (day 84) and at the end of the experiment (day 186). Implanting Holstein steers increased (P < 0.01) average daily gain (ADG) and dry matter intake (DMI) without affecting gain-to-feed ratio compared with nonimplanted animals. Carcasses from implanted Holstein steers had greater (P < 0.01) hot carcass weight (HCW) and longissimus muscle (LM) area than carcasses from nonimplanted steers. Implanting did not affect (P ≥ 0.21) other carcass characteristics. There was an increase (P = 0.03) of 1.3 pg of E2/g of muscle in implanted Holstein steers compared with that from nonimplanted Holstein steers. There was an implant × day interaction (P < 0.01) in serum E2 concentrations. Serum E2 concentrations were not altered in nonimplanted Holstein steers, whereas E2 concentration increased (P < 0.01) after steers were implanted, regardless of implant characteristics. Serum E2 peaked at 28 days after the first implant and then rapidly declined after day 56. In summary, steroidal implants administered on days 0 and 84 increased DMI, ADG, HCW, and LM area in Holstein steers compared with nonimplanted steers due to increased serum E2 concentrations. However, these changes did not improve feed efficiency or other carcass characteristics.

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We recently developed the National Dementia Biobank in México (BioBanco Nacional de Demencias, BND) as a unit for diagnosis, research, and tissue transfer for research purposes. BND is associated with the Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de Mexico (UNAM), Mexico. The donation of fluids, brain, and other organs of deceased donors is crucial for understanding the underlying mechanisms of neurodegenerative diseases and for the development of successful treatment. Our laboratory research focuses on 1) analysis of the molecular processing of the proteins involved in those neurodegenerative diseases termed tauopathies and 2) the search for biomarkers for the non-invasive and early diagnosis of Alzheimer's disease.

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Several taxonomically distinct mammalian groups-certain microbats and cetaceans (e.g., dolphins)-share both morphological adaptations related to echolocation behavior and strong signatures of convergent evolution at the amino acid level across seven genes related to auditory processing. Aye-ayes (Daubentonia madagascariensis) are nocturnal lemurs with a specialized auditory processing system. Aye-ayes tap rapidly along the surfaces of trees, listening to reverberations to identify the mines of wood-boring insect larvae; this behavior has been hypothesized to functionally mimic echolocation. Here we investigated whether there are signals of convergence in auditory processing genes between aye-ayes and known mammalian echolocators. We developed a computational pipeline (Basic Exon Assembly Tool) that produces consensus sequences for regions of interest from shotgun genomic sequencing data for nonmodel organisms without requiring de novo genome assembly. We reconstructed complete coding region sequences for the seven convergent echolocating bat-dolphin genes for aye-ayes and another lemur. We compared sequences from these two lemurs in a phylogenetic framework with those of bat and dolphin echolocators and appropriate nonecholocating outgroups. Our analysis reaffirms the existence of amino acid convergence at these loci among echolocating bats and dolphins; some methods also detected signals of convergence between echolocating bats and both mice and elephants. However, we observed no significant signal of amino acid convergence between aye-ayes and echolocating bats and dolphins, suggesting that aye-aye tap-foraging auditory adaptations represent distinct evolutionary innovations. These results are also consistent with a developing consensus that convergent behavioral ecology does not reliably predict convergent molecular evolution.

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Alzheimer's disease is a common tauopathy where fibril formation and aggregates are the hallmark of the disease. Efforts targeting amyloid-ß plaques have succeeded to remove plaques but failed in clinical trials to improve cognition; thus, the current therapeutic strategy is at preventing tau aggregation. Here, we demonstrated that four phenolic diterpenoids and rosmarinic acid inhibit fibrillization. Since, rosmarinic acid was the most active compound, we observe morphological changes in atomic force microscopy images after treatment. Hence, rosmarinic acid leads to a decrease in amide regions I and III, indicating that rosmarinic acid prevents ß-sheet assembly. Molecular docking study inside the steric zipper model of the hexapeptide 306VQIVYK311 involved in fibrillization and ß sheet formation, suggests that rosmarinic acid binds to the steric zipper with similar chemical interactions with respect to those observed for orange G, a known pharmacofore for amyloid.

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BACKGROUND: In recent years, a large number of studies around the world have led to the identification of causal genes for hereditary types of common and rare neurological and psychiatric disorders. OBJECTIVE: To explore the functional and genomic features of known human genes mutated in neuropsychiatric disorders. METHODS: A systematic search was used to develop a comprehensive catalog of genes mutated in neuropsychiatric disorders (NPD). Functional enrichment and protein-protein interaction analyses were carried out. A false discovery rate approach was used for correction for multiple testing. RESULTS: We found several functional categories that are enriched among NPD genes, such as gene ontologies, protein domains, tissue expression, signaling pathways and regulation by brain-expressed miRNAs and transcription factors. Sixty six of those NPD genes are known to be druggable. Several topographic parameters of protein-protein interaction networks and the degree of conservation between orthologous genes were identified as significant among NPD genes. CONCLUSION: These results represent one of the first analyses of enrichment of functional categories of genes known to harbor mutations for NPD. These findings could be useful for a future creation of computational tools for prioritization of novel candidate genes for NPD.

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BACKGROUND: Alzheimer's disease (AD) is a common and severe neurodegenerative disorder. Human telomeres are fundamental for the maintenance of genomic stability and play prominent roles in both cellular senescence and organismal aging. Regulation of telomere length (TL) is the result of the complex interplay between environmental and genetic factors. Alterations in TL are increasingly being studied as a possible risk factor for AD, and published studies on TL in AD show discrepant results, highlighting the need for a meta-analysis. METHODS: In the current study, we carried out a meta-analysis of published studies of TL in AD patients and healthy controls. PubMed, Web of Science and Google Scholar databases (from inception to September 2015) were used to identify relevant articles reporting TL in humans with AD, from which we retrieved data such as sample size, experimental methods, and mean TL for cases and controls. A random-effects model was used for meta-analytical procedures. RESULTS: The meta-analysis included 13 primary studies and demonstrated a significant difference in TL between 860 AD patients and 2,022 controls, with a standardized mean difference of -0.984 (confidence interval: -1.433 to -0.535; p value: <.001). CONCLUSIONS: Our results show a consistent evidence of shorter telomeres in AD patients and highlight the importance of the analysis of epigenomic markers associated with neurodegeneration and with the risk for common and severe neurological diseases, such as AD.

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Millions of urban children are chronically exposed to high concentrations of air pollutants, i.e., fine particulate matter (PM2.5) and ozone, associated with increased risk for Alzheimer's disease. Compared with children living with clear air those in Mexico City (MC) exhibit systemic, brain and intrathecal inflammation, low CSF Aß42, breakdown of the BBB, attention and short-term memory deficits, prefrontal white matter hyperintensities, damage to epithelial and endothelial barriers, tight junction and neural autoantibodies, and Alzheimer and Parkinson's hallmarks. The prefrontal white matter is a target of air pollution. We examined by light and electron microscopy the prefrontal white matter of MC dogs (n: 15, age 3.17±0.74 years), children and teens (n: 34, age: 12.64±4.2 years) versus controls. Major findings in MC residents included leaking capillaries and small arterioles with extravascular lipids and erythrocytes, lipofuscin in pericytes, smooth muscle and endothelial cells (EC), thickening of cerebrovascular basement membranes with small deposits of amyloid, patchy absence of the perivascular glial sheet, enlarged Virchow-Robin spaces and nanosize particles (20-48nm) in EC, basement membranes, axons and dendrites. Tight junctions, a key component of the neurovascular unit (NVU) were abnormal in MC versus control dogs (χ(2)<0.0001), and white matter perivascular damage was significantly worse in MC dogs (p=0.002). The integrity of the NVU, an interactive network of vascular, glial and neuronal cells is compromised in MC young residents. Characterizing the early NVU damage and identifying biomarkers of neurovascular dysfunction may provide a fresh insight into Alzheimer pathogenesis and open opportunities for pediatric neuroprotection.

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Millions of Mexico, US and across the world children are overweight and obese. Exposure to fossil-fuel combustion sources increases the risk for obesity and diabetes, while long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with increased risk of Alzheimer's disease (AD). Mexico City Metropolitan Area children are chronically exposed to PM2.5 and O3 concentrations above the standards and exhibit systemic, brain and intrathecal inflammation, cognitive deficits, and Alzheimer disease neuropathology. We investigated adipokines, food reward hormones, endothelial dysfunction, vitamin D and apolipoprotein E (APOE) relationships in 80 healthy, normal weight 11.1±3.2 year olds matched by age, gender, BMI and SES, low (n: 26) versus high (n:54) PM2.5 exposures. Mexico City children had higher leptin and endothelin-1 (p<0.01 and p<0.000), and decreases in glucagon-like peptide-1 (GLP 1), ghrelin, and glucagon (<0.02) versus controls. BMI and leptin relationships were significantly different in low versus high PM2.5 exposed children. Mexico City APOE 4 versus 3 children had higher glucose (p=0.009). Serum 25-hydroxyvitamin D<30 ng/mL was documented in 87% of Mexico City children. Leptin is strongly positively associated to PM 2.5 cumulative exposures. Residing in a high PM2.5 and O3 environment is associated with 12h fasting hyperleptinemia, altered appetite-regulating peptides, vitamin D deficiency, and increases in ET-1 in clinically healthy children. These changes could signal the future trajectory of urban children towards the development of insulin resistance, obesity, type II diabetes, premature cardiovascular disease, addiction-like behavior, cognitive impairment and Alzheimer's disease. Increased efforts should be made to decrease pediatric PM2.5 exposures, to deliver health interventions prior to the development of obesity and to identify and mitigate environmental factors influencing obesity and Alzheimer disease.

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Neuropsychiatric disorders (NPDs) constitute a heavy burden on public health systems around the world and studies have demonstrated that the negative impact of NPDs is larger in Low and Middle Income Countries (LMICs). In recent decades, several studies have come to the understanding that genetic factors play a major role in the risk for a large number of NPDs. However, few neuropsychiatric genetics studies have been published from LMICs. In this Editorial, we discuss important issues impinging on advances in neuropsychiatric genetics research in LMICs. It is essential that scientists educate policymakers and officials of funding agencies on the importance of providing adequate funding for research in these areas. Development of local well-supported research programs focused on NPD genetics should be an important asset to develop; it would facilitate the establishment of sustainable research efforts that could lead to appropriate diagnosis and specific, affordable and feasible interventions in LMICs. It is important to point out that research into the biological basis of human NPDs is not only an academic effort reserved for a few elite institutions in economically developed countries, but it is vitally important for the mental health of people around the world.

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Alzheimer's disease (AD) exhibits a complex etiology that simultaneously manifests as a complex cellular, neurobiological, molecular, anatomic-physiological and clinical entity. Other significant psychiatric conditions, such as depression and schizophrenia, may also present with complex and concurrent clinical and/or molecular phenotypes. These neuropsychiatric pathologies also originate from both environmental and genetic factors. We analyzed the molecular phenotypes of AD and discuss them with respect to the classical theories, which we integrated into mechanisms that share molecular and/or anatomical connections. Based on these mechanisms, we propose an interaction model and discuss the model in light of studies that refute or support it. Given the spectrum of AD phenotypes, we limit the scope of our discussion to a few, which facilitates concrete analysis. In addition, the study of specific, individual pathogenic phenotypes may be critical to defining the complex mechanisms leading to AD, thereby improving strategies for developing novel therapies.