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Strain Marseille-P3237 was isolated from a stool sample of a healthy 35-year-old Congolese pygmy female. This anaerobic, Gram-negative, non-spore-forming and non-motile coccus-shaped bacterium is a member of the order Coriobacteriales. It exhibits a 2 009 306-bp genome with a 65.46 mol% G+C content and is closely related to, but distinct from, members of the Olsenella genus. We propose the creation of the new genus Libanicoccus gen. nov. and of the new species Libanicoccus massiliensis sp. nov.
Alcohol-induced white matter (WM) degeneration is linked to cognitive-motor deficits and impairs insulin/insulin-like growth factor (IGF) and Notch networks regulating oligodendrocyte function. Ethanol downregulates Aspartyl-Asparaginyl-β-Hydroxylase (ASPH) which drives Notch. These experiments determined if alcohol-related WM degeneration was linked to inhibition of ASPH and Notch. Adult Long Evans rats were fed for 3, 6 or 8 weeks with liquid diets containing 26% ethanol (caloric) and in the last two weeks prior to each endpoint they were binged with 2 g/kg ethanol, 3×/week. Controls were studied in parallel. Histological sections of the frontal lobe and cerebellar vermis were used for image analysis. Frontal WM proteins were used for Western blotting and duplex ELISAs. The ethanol exposures caused progressive reductions in frontal and cerebellar WM. Ethanol-mediated frontal WM atrophy was associated with reduced expression of ASPH, Jagged 1, HES-1, and HIF-1α. These findings link ethanol-induced WM atrophy to inhibition of ASPH expression and signaling through Notch networks, including HIF-1α.
Hippocampal structure is particularly sensitive to trauma and other stressors. However, previous findings linking hippocampal function with trauma-related psychopathology have been mixed. Heterogeneity in psychological responses to trauma has not been considered with respect to hippocampal function and may contribute to mixed findings. To address these issues, we examined associations between data-driven symptom dimensions and episodic memory formation, a key function of the hippocampus, in a trauma-exposed sample. Symptom dimensions were defined using principal components analysis (PCA) in 3881 trauma-exposed African-American women recruited from primary care waiting rooms of a large urban hospital. Hippocampal and amygdala function were subsequently investigated in an fMRI study of episodic memory formation in a subset of 54 women. Participants viewed scenes with neutral, negative, and positive content during fMRI, and completed a delayed cued recall task. PCA analysis produced five symptom dimensions interpreted as reflecting negative affect, somatic symptoms, re-experiencing, hyper-arousal, and numbing. Re-experiencing was the only symptom type associated with hippocampal function, predicting increased memory encoding-related activation in the hippocampus as well as the amygdala. In contrast, the negative affect component predicted lower amygdala activation for subsequently recalled scenes, and lower functional coupling with other important memory-related regions including the precuneus, inferior frontal gyrus, and occipital cortex. Symptom dimensions were not related to hippocampal volume. The fMRI findings for re-experiencing versus negative affect parallel differences in behavioral memory phenomena in PTSD versus MDD, and highlight a need for more complex models of trauma-related pathology.
Hyperglycaemia remains a challenge in type 1 diabetes since current regimes used to determine meal insulin requirements prove to be ineffective. This is particularly problematic for meals containing high amounts of protein and fat. We aimed to determine the post-prandial glycaemic response and total insulin need for mixed meals, using sensor-augmented insulin pumps in children with type 1 diabetes.
The aim of this study was to understand experiences of participation in a supported self-management programme for chronic obstructive pulmonary disease (COPD). There is a wealth of clinical trials examining the outcomes of self-management interventions for individuals with COPD, but current understanding regarding patients' perspectives of such complex interventions is limited. Further insight may help to tailor self-management interventions and maximise patient engagement. Semi-structured interviews were conducted with individuals participating in a self-management programme, SPACE for COPD. Interviews took place at 6 weeks and 6 months following the programme. Data were analysed at each time point using inductive thematic analysis, and subsequently re-examined together. 40 interviews were undertaken and four themes emerged from the analysis: perceptions of the programme; lifestyle changes; social support; and disrupting factors and barriers to maintaining routines. SPACE for COPD was acceptable to participants in this study. The importance of education and social support was emphasised at both time points studied, but there were challenges such as comorbidities, ill health of family members and limited maintenance of exercise behaviours over the longer term. Further consideration of the role of carers and partners may help to improve adherence to self-management programmes once healthcare professional support has stopped.
MicroRNAs (miRNAs) play an essential role in tumor biological processes through interacting with specific gene targets. The involvement of miR-195-5p in cell proliferation, invasion, and migration has been demonstrated in several cancer cell lines, while its function in oral squamous cell carcinoma (OSCC) remains unclear. Here we find that miR-195-5p expression is lower in OSCC than in nontumor tissues, while its overexpression in cell lines can lead to the promotion of apoptosis and the reduction of cell growth, migration, and invasion. Moreover, we identify the tripartite motif-containing protein (TRIM14) as a target of miR-195-5p. Therefore, we reason that the tumor suppressor role of miR-195-5p in OSCC is dependent on the interaction with TRIM14.
RNA-seq has enabled in-depth analysis of the pathogenesis of psoriasis on the transcriptomic level, and many biomarkers have been discovered to be related to the immune response, lipid metabolism, and keratinocyte proliferation. However, few studies have combined analysis from various datasets. In this study, we integrated different psoriasis RNA-seq datasets to reveal the pathogenesis of psoriasis through the analysis of differentially expressed genes (DEGs), pathway analysis, and functional annotation. The revealed biomarkers were further validated through proliferation phenotypes. The results showed that DEGs were functionally related to lipid metabolism and keratinocyte differentiation dysregulation. The results also showed new biomarkers, such as AKR1B10 and PLA2G gene families, as well as pathways that include the PPAR signaling pathway, cytokine-cytokine receptor interaction, alpha-linoleic acid metabolism, and glycosphingolipid biosynthesis. Using siRNA knockdown assays, we further validated the role that the AKR1B10 gene plays in proliferation. Our study demonstrated not only the dysfunction of the AKR1B10 gene in lipid metabolizing but also its important role in the overproliferation and migration of keratinocyte, which provided evidence for further therapeutic uses for psoriasis.
Interest in bicompartmental knee arthroplasty (BKA) for the treatment of medial patellofemoral osteoarthritis (MPFOA) has grown in recent years because BKA offers a bone and ligament-preserving alternative to total knee arthroplasty (TKA). BKA only resurfaces the diseased compartments, while preserving proprioception and native knee kinematics. Therefore, the objective of this study is to assess knee function, perioperative morbidity, and implant survivability in patients undergoing BKA vs TKA for MPFOA.
To develop a three-dimensional study tool of the membranous labyrinth in order to study the pathophysiology, diagnostic workup and treatment of benign paroxysmal positional vertigo (BPPV). BPPV is the most common cause of peripheral vertigo. Its diagnosis and treatment depend on an understanding of the anatomy of the vestibular labyrinth and its position relative to the head. To date, many illustrations have been made to explain principals of diagnosis and treatment of BPPV, but few have been based on anatomical studies of the membranous labyrinth.
Parenting children with conduct problems (CP) is challenging, yet very little is known about the impact of the child's behaviour on family functioning or how parents of children with CP perceive their child. The aim of this research was to examine whether families with children with CP and high vs. low levels of callous-unemotional traits (HCU vs. LCU) experience differences in family functioning and parental perceptions. One hundred and one parents/caregivers of boys aged 11-16 [Typically developing (TD) n = 31; CP/HCU n = 35; CP/LCU n = 35] completed the McMaster Family Assessment Device, measuring multiple domains of family functioning. Parents/caregivers also completed a written statement describing their child, used for qualitative analysis. Families with CP/HCU children had poorer affective involvement than TD (p = 0.00; d = - 1.17) and CP/LCU (p = 0.03; d = - 0.62) families. Families with CP/HCU children showed significantly poorer general family functioning (p = 0.04; d = - 0.63) and more poorly defined family roles (p = 0.005; d = - 0.82) than families with TD children. Qualitative analyses indicated that parents/caregivers of CP/HCU children characterised them as having a dichotomous personality and being superficially charming. CP/LCU children were characterised as cheeky and endearing, with parents reporting good rapport. Families with CP/HCU children presented with specific difficulties in affective involvement and parents described challenges which were in line with the child's specific presentation of lack of empathy and shallow affect. These findings may be used to help clinicians identify targets for family interventions.
Vestibular paroxysmia (VP) is characterized by short, often oligosymptomatic attacks of vertigo which occur spontaneously or are sometimes provoked by turning the head. Despite the description of the disease almost 40 years ago (first termed "disabling positional vertigo"), no controlled treatment trial has been published to date. The Vestparoxy trial was designed as a randomized, placebo-controlled, double-blind cross-over trial to examine the therapeutic effect of oxcarbazepine (OXA) in patients with definite or probable VP.
Interstitial cells of Cajal (ICC) from murine colonic muscles express genes encoding inwardly rectifying K+ channels. Transcripts of Kcnj2 (Kir2.1), Kcnj4 (Kir2.3), Kcnj14 (Kir2.4), Kcnj5 (Kir3.4), Kcnj8 (Kir 6.1) and Kcnj11 (Kir6.2) were found in colonic ICC. A conductance with properties consistent with Kir2 channels was observed in ICC but not in smooth muscle cells (SMC). Despite expression of gene transcripts, G-protein gated K+ channel (Kir3) and KATP (Kir6) currents were not resolved in ICC. KATP is a conductance prominent in SMC. Kir2 antagonist caused depolarization of freshly dispersed ICC and colonic smooth muscles, suggesting that this conductance is active under resting conditions in colonic muscles. The conclusion of the present study is that ICC express the Ba2+ -sensitive, inwardly rectifying K+ conductance in colonic muscles. This conductance is most probably a result of heterotetramers of Kir2 gene products, with this regulating resting potentials and the excitability of colonic muscles.
A new cellulolytic strain of Chryseobacterium genus was screened from the dung of a cattle fed with cereal straw. A putative cellulase gene (cbGH5) belonging to glycoside hydrolase family 5 subfamily 46 (GH5_46) was identified and cloned by degenerate PCR plus genome walking. The CbGH5 protein was overexpressed in Pichia pastoris, purified and characterized. It is the first bifunctional cellulase-xylanase reported in GH5_46 as well as in Chryseobacterium genus. The enzyme showed an endoglucanase activity on carboxymethylcellulose of 3237 μmol min-1 mg-1 at pH 9, 90 °C and a xylanase activity on birchwood xylan of 1793 μmol min-1 mg-1 at pH 8, 90 °C. The activity level and thermophilicity are in the front rank of all the known cellulases and xylanases. Core hydrophobicity had a positive effect on the thermophilicity of this enzyme. When similar quantity of enzymatic activity units was applied on the straws of wheat, rice, corn and oilseed rape, CbGH5 could obtain 3.5-5.0× glucose and 1.2-1.8× xylose than a mixed commercial cellulase plus xylanase of Novozymes. When applied on spent mushroom substrates made from the four straws, CbGH5 could obtain 9.2-15.7× glucose and 3.5-4.3× xylose than the mixed Novozymes cellulase+xylanase. The results suggest that CbGH5 could be a promising candidate for industrial lignocellulosic biomass conversion.
Central among the fetotoxic responses to in utero ethanol (E) exposure is redox-shift related glutathione (GSH) loss and apoptosis. Previously, we reported that despite an E-generated Nrf2 upregulation, fetal neurons still succumb. In this study, we investigate if the compromised GSH results from an impaired inward transport of cysteine (Cys), a precursor of GSH in association with dysregulated excitatory amino acid carrier1 (EAAC1), a cysteine transporter. In utero binge model involves administration of isocaloric dextrose or 20% E (3.5 g/kg)/ by gavage at 12 h intervals to pregnant Sprague Dawley (SD) rats, starting gestation day (gd) 17 with a final dose on gd19, 2 h prior to sacrifice. Primary cerebral cortical neurons (PCNs) from embryonic day 16-17 fetal SD rats were the in vitro model. E reduced both PCN and cerebral cortical GSH and Cys up to 50% and the abridged GSH could be blocked by administration of N-acetylcysteine. E reduced EAAC1 protein expression in utero and in PCNs (p < 0.05). This was accompanied by a 60-70% decrease in neuron surface expression of EAAC1 along with significant reductions of EAAC1/Slc1a1 mRNA (p < 0.05). In PCNs, EAAC1 knockdown significantly decreased GSH but not oxidized glutathione (GSSG) illustrating that while not the sole provider of Cys, EAAC1 plays an important role in neuron GSH homeostasis. These studies strongly support the concept that in both E exposed intact fetal brain and cultured PCNs a mechanism underlying E impairment of GSH homeostasis is reduction of import of external Cys which is mediated by perturbations of EAAC1 expression/function.
Phelipanche aegyptiaca parasitizes a wide range of plants, including important crops, and causes serious damage to their production. P. aegyptiaca develops a specialized intrusive organ called a haustorium that establishes connections to the host's xylem and phloem. In parallel with the development of xylem vessels, the differentiation of phloem-conducting cells has been demonstrated by the translocation of symplasmic tracers from the host to the parasite. However, it is unclear yet whether haustorial phloem-conducting cells are sieve elements. In this study, we identified phloem-conducting cells in haustoria by the host-to-parasite translocation of green fluorescent protein (GFP) from AtSUC2pro::GFP tomato sieve tubes. Haustorial GFP-conducting cells contained nuclei but not callose-rich sieve plates, indicating that phloem-conducting cells in haustoria differ from conventional sieve elements. To ascertain why the nuclei were not degenerated, expression of the P. aegyptiaca homologs NAC-domain containing transcription factor (NAC45), NAC45/86-dependent exonuclease-domain protein 1 (NEN1), and NEN4 was examined. However, these genes were more highly expressed in the haustorium than in tubercle protrusion, implying that nuclear degradation in haustoria may not be exclusively controlled by the NAC45/86-NEN regulatory pathway. Our results also suggest that the formation of plasmodesmata with large size exclusion limits is independent of nuclear degradation and callose deposition.
Small RNAs play an important role in regulating plant responses to abiotic stress. Depending on the method of salt application, whether sudden or gradual, plants may experience either salt shock or salt stress, respectively. In this study, small RNA expression in response to salt shock and long-term salt stress in parallel experiments was described. Cotton small RNA libraries were constructed and sequenced under normal conditions, as well as sudden and gradual salt application. A total of 225 cotton microRNAs (miRNAs) were identified and of these 24 were novel miRNAs. There were 88 and 75 miRNAs with differential expression under the salt shock and long-term salt stress, respectively. Thirty one transcripts were found to be targets of 20 miRNA families. Eight targets showed a negative correlation in expression with their corresponding miRNAs. We also identified two TAS3s with two near-identical 21-nt trans-acting small interfering RNA (tasiRNA)-Auxin Response Factors (ARFs) that coaligned with the phases D7(+) and D8(+) in three Gossypium species. The miR390/tasiRNA-ARFs/ARF4 pathway was identified and showed altered expression under salt stress. The identification of these small RNAs as well as elucidating their functional significance broadens our understanding of post-transcriptional gene regulation in response to salt stress.
Single-cell RNA sequencing (scRNA-Seq) is rapidly becoming a powerful tool for high-throughput transcriptomic analysis of cell states and dynamics at the single cell level. Both the number and quality of scRNA-Seq datasets have dramatically increased recently. A database that can comprehensively collect, curate, and compare expression features of scRNA-Seq data in humans has not yet been built. Here, we present scRNASeqDB, a database that includes almost all the currently available human single cell transcriptome datasets (n = 38) covering 200 human cell lines or cell types and 13,440 samples. Our online web interface allows users to rank the expression profiles of the genes of interest across different cell types. It also provides tools to query and visualize data, including Gene Ontology and pathway annotations for differentially expressed genes between cell types or groups. The scRNASeqDB is a useful resource for single cell transcriptional studies. This database is publicly available at bioinfo.uth.edu/scrnaseqdb/.
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