Observations on the Population Genetic Structure of the Leaf Galling Nematode, Ditylenchus gallaeformans.

Ditylenchus gallaeformans is a plant parasitic nematode that induces galls on aboveground parts of Melastomataceae plants. It differs from most gall-inducing nematodes in that it is not an endoparasite and has been considered as a possible biological control agent against invasive species of Miconia. Little is known about D. gallaeformans biology, genetic differences among populations, and host preferences. This study examined the genetic differences among D. gallaeformans populations from different locations and host species and the phylogenetic relationships among them. Nematodes were collected from galls in plants from Costa Rica, Dominica, and Trinidad. The Cytochrome c oxidase 1 (cox1) region was sequenced from a total of 33 individual nematodes isolated from 33 different plant individuals, representing 21 species of Melastomataceae. Phylogenetic reconstructions, haplotype networks, and analysis of molecular variance showed that the species is monophyletic and has three major clades, which were mostly consistent with geographic location but not with host species. The first clade was composed by two subclades, one with individuals from Costa Rica and one with individuals from Dominica. The second and third clades comprised nematodes only from Trinidad. Overall, there is no evidence of host-species specialization in D. gallaeformans. Biocontrol efforts using the nematode against invasive Miconia could focus on geographical location matching but likely will not need to match host species.

First report of Meloidogyne javanica pathogenic on hybrid lavender (Lavandula ×intermedia) in the United States.

Root-knot nematodes (RKNs), Meloidogyne spp., are some of the most economically important pathogens of cultivated plants. Meloidogyne javanica is one of the most destructive RKN species and is well known for its broad host range and the severe damage it causes to plant roots (Perry et al. 2009). In Feb 2018, four mature dead and dying hybrid lavender plants (Lavandula ×intermedia 'Phenomenal') were collected in Edgefield County, South Carolina, and suspected of having Phytophthora root and crown rot (Dlugos and Jeffers 2018). Greenhouse-grown plants had been transplanted in Dec 2016 and Jan 2017 into a sandy loam soil on a site that had been fallow or in pasture for over 30 years. Some plants began to turn gray and die in summer 2017, and approximately 40% of 1230 plants were symptomatic or dead by Feb 2018. Phytophthora spp. were not isolated from the collected plants but were isolated from plants collected on subsequent visits. Instead, all four plants had small, smooth galls on the roots. Lavender roots were examined microscopically (30-70×), and egg masses of RKNs were observed on the galls. Mature, sedentary RKN females were handpicked from galled roots, and perineal patterns of 10 specimens were examined and identified as M. javanica. Juveniles and eggs were extracted from lavender roots by the method of Coolen and D'herde (1972). To confirm species identification, DNA was extracted from 10 individual juveniles, and a PCR assay was conducted using species-specific primers for M. javanica, Fjav/Rjav (Zijlstra et al. 2000). A single amplicon was produced with the expected size of approximately 720 bp, which confirmed identity as M. javanica. To determine pathogenicity, M. javanica from lavender roots were inoculated onto susceptible tomato plants for multiplication, and severe gall symptoms occurred on tomato roots 60 days later. Nematodes were extracted from tomato roots and inoculated onto healthy, rooted cuttings of 'Phenomenal' lavender plants growing in pots of soilless medium in a greenhouse. Plants were inoculated with 0, 1000, 2000, 5000, or 10000 eggs and juveniles of M. javanica. Five single-plant replicates were used for each treatment, and plants were randomized on a greenhouse bench. Plants were assessed 60 days after inoculation, and nematodes were extracted from roots and counted. The reproduction factor was 0, 43.8, 40.9, 9.1, 7.7, and 2.6 for initial nematode populations 0, 1000, 2000, 5000, and 10000, respectively, which confirmed pathogenicity (Hussey and Janssen 2002). Meloidogyne javanica also was recovered in Mar 2018 from galled roots on a 'Munstead' (L. angustifolia) lavender plant from Kentucky (provided by the Univ. of Kentucky Plant Disease Diagnostic Laboratories), and an unidentified species of Meloidogyne was isolated in Aug 2020 from a 'Phenomenal' plant grown in Florida. COI mtDNA sequences from the SC (MZ542457) and KY (MZ542458) populations were submitted to Genbank. M. javanica previously was found associated with field-grown lavender (hybrid and L. angustifolia) in Brazil, but pathogenicity was not studied (Pauletti and Echeverrigaray 2002). To our knowledge, this is the first report of M. javanica pathogenic to L. ×intermedia in the USA, and the first time RKNs have been proven to be pathogenic to Lavandula spp. following Koch's Postulates. Further studies are needed to investigate the geographic distribution of M. javanica on lavender and the potential threat this nematode poses to lavender production in the USA.

Identification of human miR-1839-5p by small RNA-seq, a miRNA enriched in neoplastic tissues.

BACKGROUND: MicroRNAs (miRNAs) modulate gene expression through destabilization or translational inhibition of cytoplasmic transcripts or by transcriptional regulation through binding to genomic DNA. Although miRNAs are globally down-regulated in cancer, some are overexpressed in neoplastic tissues, playing key roles in tumorigenesis (oncomiRs), sometimes behaving as effective cancer markers. METHODS: Using total RNA from human uterus adenocarcinoma and non-neoplastic uterus, we conducted a small RNA-sequencing experiment followed by prediction of novel miRNAs using MirDeep* software. Synteny analysis and whole genome alignments were performed using BLAST. We also evaluated expression by a reverse transcriptase-polymerase chain reaction (RT-PCR) in normal tissues of the FSD2 gene, which spans the human miR-1839-5p gene in the opposite direction. RESULTS: MirDeep* analysis predicted a miRNA not previously annotated in databases, identical to and likely the orthologue of mouse miR-1839-5p. Whole-genome local alignments of this miRNA revealed a single perfect hit that is indeed syntenic to mouse miR-1839-5p. Alignments with other mammalian orthologues showed considerable conservation. We validated the prediction via a stem-loop RT-PCR assay, also employed to screen RNA samples from several additional normal and cancer tissues, showing increased expression in neoplastic tissues compared to their respective non neoplastic counterparts. Human heart tissue expresses both miR-1839-5p and FSD2. CONCLUSIONS: Human tissues express an orthologue of mouse miR-1839-5p and, given its expression pattern, we suggest that this miRNA could be explored as a potential oncomiR or cancer marker. Also, according to the genomic organization of miR-1839-5p and FSD2, perfect complementarity exists between the two elements, making possible miRNA-directed cleavage in human cardiac tissue.

Bisphenol-A induces expression of HOXC6, an estrogen-regulated homeobox-containing gene associated with breast cancer.

HOXC6 is a homeobox-containing gene associated with mammary gland development and is overexpressed in variety of cancers including breast and prostate cancers. Here, we have examined the expression of HOXC6 in breast cancer tissue, investigated its transcriptional regulation via estradiol (E2) and bisphenol-A (BPA, an estrogenic endocrine disruptor) in vitro and in vivo. We observed that HOXC6 is differentially over-expressed in breast cancer tissue. E2 induces HOXC6 expression in cultured breast cancer cells and in mammary glands of Sprague Dawley rats. HOXC6 expression is also induced upon exposure to BPA both in vitro and in vivo. Estrogen-receptor-alpha (ERα) and ER-coregulators such as MLL-histone methylases are bound to the HOXC6 promoter upon exposure to E2 or BPA and that resulted in increased histone H3K4-trimethylation, histone acetylation, and recruitment of RNA polymerase II at the HOXC6 promoter. HOXC6 overexpression induces expression of tumor growth factors and facilitates growth 3D-colony formation, indicating its potential roles in tumor growth. Our studies demonstrate that HOXC6, which is a critical player in mammary gland development, is upregulated in multiple cases of breast cancer, and is transcriptionally regulated by E2 and BPA, in vitro and in vivo.

Geriatric assessment-identified deficits in older cancer patients with normal performance status.

BACKGROUND: We investigated whether a brief geriatric assessment (GA) would identify important patient deficits that could affect treatment tolerance and care outcomes within a sample of older cancer patients rated as functionally normal (80%-100%) on the Karnofsky performance status (KPS) scale. METHODS: Cancer patients aged ≥65 years were assessed using a brief GA that included both professionally and patient-scored KPS and measures of comorbidity, polypharmacy, cognition, function, nutrition, and psychosocial status. Data were analyzed using descriptive statistics and multivariable logistic regression. RESULTS: The sample included 984 patients: mean age was 73 years (range: 65-99 years), 74% were female, and 89% were white. GA was conducted before (23%), during (41%), or after (36%) treatment. Overall, 54% had a breast cancer diagnosis (n = 528), and 46% (n = 456) had cancers at other sites. Moreover, 81% of participants (n = 796) had both professionally and self-rated KPS ≥80, defined as functionally normal, and those patients are the focus of analysis. In this subsample, 550 (69%) had at least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits, and 188 (24%) had ≥3 deficits. Specifically, 43% reported taking ≥9 medications daily, 28% had decreased social activity, 25% had ≥4 comorbidities, 23% had ≥1 impairment in instrumental activities of daily living, 18% had a Timed Up and Go time ≥14 seconds, 18% had ≥5% unintentional weight loss, and 12% had a Mental Health Index score ≤76. CONCLUSION: Within this sample of older cancer patients who were rated as functionally normal by KPS, GA identified important deficits that could affect treatment tolerance and outcomes.

Myofibroma of the oral mucosa: a case report.

OBJECTIVE: To report a case of coexisting irritation fibroma and myofibroma in oral mucosa. CLINICAL PRESENTATION AND INTERVENTION: One case with two painless, nodular masses, adjacent to each other in the buccal mucosa, was clinically examined with a provisional diagnosis of irritation fibroma, salivary gland tumors, neurofibroma and schwannoma. Histological examination of the smaller swelling showed features of irritation fibroma, while the features of the other mass were compatible with myofibroma or leiomyoma. Additional immunohistochemical examination established the diagnosis of myofibroma. CONCLUSION: This was a case of a myofibroma that was clinically similar to an adjacent irritation fibroma, which highlights the possibility of misdiagnosis of a myofibroblastic tumor and underlines the importance of histologic examination together with immunohistochemical and/or histochemical analysis if necessary to establish the accurate diagnosis.

Study of wide bandgap SnOx thin films grown by a reactive magnetron sputtering via a two-step method.

In the present work, we report on the microstructural and optoelectronic properties of SnOx thin films deposited by a reactive radio frequency magnetron sputtering. After SnOx growth by sputtering under O2/Ar flow, we have used three different treatment methods, namely (1) as deposited films under O2/Ar, (2) vacuum annealed films ex-situ, and (3) air annealed films ex-situ. Effects of the O2/Ar ratios and the growth temperature were investigated for each treatment method. We have thoroughly investigated the structural, optical, electrical and morphology of the different films by several advanced techniques. The best compromise between electrical conductivity and optical transmission for the use of these SnOx films as an n-type TCO was the conditions O2/Ar = 1.5% during the growth process, at 250 °C, followed by a vacuum post thermal annealing performed at 5 × 10-4 Torr. Our results pointed out clear correlations between the growth conditions, the microstructural and optoelectronic properties, where highly electrically conductive films were found to be associated to larger grains size microstructure. Effects of O2/Ar flow and the thermal annealing process were also analysed and discussed thoroughly.

Proteomics reveal rat hippocampal lateral asymmetry.

Brain laterality has been observed in animals and humans structurally, functionally, and behaviorally. MRI and CT scans have revealed pathological and normal brain asymmetry. A coarse assessment of rat or human brain fails to expose profound left/right differences, while a finer examination of its structure reveals an array of asymmetric features. This lateralization may be derived from evolutionary, genetic, developmental, epigenetic, and pathologic factors. However, brain structure and function is complex and macroscopic or microscopic asymmetries may be hard to discern from random fluctuations. This study concentrated on the hippocampus and we explored lateralization employing a molecular high-throughput approach. Using proteomic analysis based on a combined approach of 2-D PAGE and MS, we examined differential protein expression in the hippocampi (left vs. right) of young adult male rats. Initial proteomic analysis demonstrated quantitative differences of approximately eighty proteins between the right (RH) and left hippocampus (LH). These were primarily energy-, cell metabolism-, stress-inducible chaperone proteins and cytoskeleton- proteins. Analysis revealed higher abundance of metabolic enzymes related to cellular energy metabolism, in the RH than the LH. In contrast, higher concentrations of proteins which are located mainly in astrocytes were shown in the LH than the RH. Immunoblotting of brain-specific proteins, on single animal hippocampal lysates confirmed the expression of Dynamin-1, DRP2, synapsin-1 and others, to be higher in the RH than LH lysates. These findings demonstrate major laterality in the expression of protein molecules between the two hippocampi providing a fertile field for mapping studies relating molecular, neuroimaging and functional data. Undoubtedly, asymmetries found at the animal level are hard to extrapolate to humans; however, studies in animal models will increase our understanding of the developing and adult brain and the healthy and diseased brain.

Comparison of Hippocampal Subfield Segmentation Agreement between 2 Automated Protocols across the Adult Life Span.

BACKGROUND AND PURPOSE: The hippocampus is a frequent focus of quantitative neuroimaging research, and structural hippocampal alterations are related to multiple neurocognitive disorders. An increasing number of neuroimaging studies are focusing on hippocampal subfield regional involvement in these disorders using various automated segmentation approaches. Direct comparisons among these approaches are limited. The purpose of this study was to compare the agreement between two automated hippocampal segmentation algorithms in an adult population. MATERIALS AND METHODS: We compared the results of 2 automated segmentation algorithms for hippocampal subfields (FreeSurfer v6.0 and volBrain) within a single imaging data set from adults (n = 176, 89 women) across a wide age range (20-79 years). Brain MR imaging was acquired on a single 3T scanner as part of the IXI Brain Development Dataset and included T1- and T2-weighted MR images. We also examined subfield volumetric differences related to age and sex and the impact of different intracranial volume and total hippocampal volume normalization methods. RESULTS: Estimated intracranial volume and total hippocampal volume of both protocols were strongly correlated (r = 0.93 and 0.9, respectively; both P < .001). Hippocampal subfield volumes were correlated (ranging from r = 0.42 for the subiculum to r = 0.78 for the cornu ammonis [CA]1, all P < .001). However, absolute volumes were significantly different between protocols. volBrain produced larger CA1 and CA4-dentate gyrus and smaller CA2-CA3 and subiculum volumes compared with FreeSurfer v6.0. Regional age- and sex-related differences in subfield volumes were qualitatively and quantitatively different depending on segmentation protocol and intracranial volume/total hippocampal volume normalization method. CONCLUSIONS: The hippocampal subfield volume relationship to demographic factors and disease states should undergo nuanced interpretation, especially when considering different segmentation protocols.

Recovery of transient pericardial constriction following steroid administration.

A case of transient idiopathic constrictive pericarditis is presented. Following steroid treatment there was resolution of the pericardial effusion, resolution of constriction and disappearance of the fibrin layer. The patient was followed-up for one year without any need for further treatment. Transient pericardial constriction is a rare outcome of acute pericarditis and should be promptly diagnosed before any consideration for pericardectomy.

Longitudinal Assessment of Neuroradiologic Features in Wolfram Syndrome.

BACKGROUND AND PURPOSE: Wolfram syndrome is a rare genetic disease with characteristic brain involvement. We reviewed the brain MR images of patients with Wolfram syndrome to determine the frequency and characteristics of common neuroradiologic findings. MATERIALS AND METHODS: We retrospectively reviewed the imaging data of patients with genetically-confirmed Wolfram syndrome who had been recruited to the Washington University Wolfram Syndrome Research Clinic. These patients were evaluated between 2010 and 2019 with annual MRIs, along with other measures. MR images were assessed for clinical neuroradiologic signs at each individual's first and last follow-up visits to characterize the frequency, rate of progression, and clinical correlations of these signs. RESULTS: We included 30 patients (13 males/17 females; average age at first visit, 14 years; average age at last visit, 19 years). The median duration of follow-up was 5 years (range, 2-9 years). The most common findings were an absent or diminished posterior pituitary bright spot (first, 53%; last, 70%), T1/T2 pons signal abnormalities (first, 53%; last, 67%), optic nerve atrophy (first, 30%; last, 80%), white matter T2 hyperintensities (first, 27%; last, 35%), and cerebellar atrophy (first, 23%; last, 70%). CONCLUSIONS: Patients with Wolfram syndrome present characteristic neuroradiologic findings that involve the posterior pituitary gland, optic nerves, white matter, brain stem, and cerebellum. These abnormal findings appear at an early age and tend to increase in frequency with time. However, the neurologic significance and neuropathologic mechanisms of each sign require more investigation. Neuroradiologists should be aware of the pattern of these features in Wolfram syndrome.

HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol.

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERß downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

Association of human cathelicidin (hCAP-18/LL-37) gene expression with cardiovascular disease risk factors.

BACKGROUND AND AIMS: Antimicrobial peptides (AMPs) are components of the innate immune system. In addition, evidence suggests that these peptides are associated with various inflammatory diseases. We examined whether expression of the cathelicidin LL-37 in peripheral blood mononuclear cells (PBMCs) is associated with cardiovascular risk factors. METHODS AND RESULTS: A total of 90 men and 87 women selected from STANISLAS cohort were studied. Expression of LL-37 mRNA isolated from PBMCs of these subjects was quantified by quantitative RT-PCR. Anthropometric measurements and biochemical profiles were assessed for each individual. In women, LL-37 mRNA expression was significantly and positively correlated with body mass index (BMI) (p

Sex differences in the expression of morphine withdrawal symptoms and associated activity in the tail of the ventral tegmental area.

Recent studies, in male rodents, have begun to elucidate a role for the GABAergic neurons in the tail of the ventral tegmental area (tVTA) in morphine withdrawal. To date, the mechanisms underlying morphine withdrawal have been studied almost exclusively in male animals. As a result, there is a considerable gap in our current understanding of the processes underlying sex differences in morphine withdrawal behaviors and its effects on cellular activity in the tVTA in females. The purpose of the present study was to investigate the influence of sex on the expression and duration of spontaneous somatic morphine withdrawal syndrome, and to characterize the relationship between spontaneous somatic withdrawal symptoms and cellular activation (measured as phosphorylated CREB; pCREB), in the GABAergic tVTA in male and female rats. Morphine-dependent adult male and female Long Evans rats underwent 72 h of spontaneous withdrawal, and somatic withdrawal symptoms were assessed every 12 h. Male morphine-dependent rats expressed more severe symptoms during the early phases of withdrawal compared to females. Although, females demonstrated lower overall symptom severity, their symptoms persisted for a longer period of time, thus demonstrating higher withdrawal-symptom severity than males during late withdrawal. pCREB activity in the tVTA was elevated in morphine-withdrawn rats and was positively correlated with the severity of withdrawal symptoms. These results demonstrate sex differences in the timing of the expression of somatic withdrawal. Our data add to the growing body of evidence demonstrating a role for the tVTA in morphine withdrawal and begin to establish a sex-dependent behavioral and molecular profile within this brain region.

Antioxidant and Antiulcerogenic Activity of the Dry Extract of Pods of Libidibia ferrea Mart. ex Tul. (Fabaceae).

Ethnomedicinal studies in the Amazon community and in the Northeast region of Brazil highlight the use of Libidibia ferrea fruits for the treatment of gastric problems. However, there are no data in the literature of this pharmacological activity. Thus, the aim of this paper is to provide a scientific basis for the use of the dry extract of L. ferrea pods (DELfp) for the treatment of peptic ulcers. Phytochemical characterization was performed by HPLC/MS. In vitro antioxidant activity was assessed using DPPH, ABTS, phosphomolybdenum, and superoxide radical scavenging activity. The gastroprotective activity, the ability to stimulate mucus production, the antisecretory activity, and the influence of -SH and NO compounds on the antiulcerogenic activity of DELfp were evaluated. The healing activity was determined by the acetic acid-induced chronic ulcer model. Anti-Helicobacter pylori activity was investigated. HPLC/MS results identified the presence of phenolic compounds, gallic acid and ellagic acid, in DELfp. The extract showed antioxidant activity in vitro. In ulcers induced by absolute ethanol and acidified ethanol, the ED50 values of DELfp were 113 and 185.7 mg/kg, respectively. DELfp (100, 200, and 400 mg/kg) inhibited indomethacin-induced lesions by 66.7, 69.6, and 65.8%, respectively. DELfp (200 mg/kg) reduced gastric secretion and H+ concentration in the gastric contents and showed to be independent of nitric oxide (NO) and dependent on sulfhydryl (-SH) compounds in the protection of the gastric mucosa. In the chronic ulcer model, DELfp reduced the area of the gastric lesion. DELfp also showed anti-H. pylori activity. In conclusion, DELfp showed antioxidant, gastroprotective, healing, and antiulcerogenic activities. The mechanism of these actions seems to be mediated by different pathways and involves the reduction of gastric secretion and H+ concentration, dependence on sulfhydryl compounds, and anti-H. pylori activity. All these actions support the medicinal use of this species in the management of peptic ulcers.