A global phylogenomic and metabolic reconstruction of the large intestine bacterial community of domesticated cattle.

BACKGROUND: The large intestine is a colonization site of beneficial microbes complementing the nutrition of cattle but also of zoonotic and animal pathogens. Here, we present the first global gene catalog of cattle fecal microbiomes, a proxy of the large intestine microbiomes, from 436 metagenomes from six countries. RESULTS: Phylogenomics suggested that the reconstructed genomes and their close relatives form distinct branches and produced clustering patterns that were reminiscent of the metagenomics sample origin. Bacterial taxa had distinct metabolic profiles, and complete metabolic pathways were mainly linked to carbohydrates and amino acids metabolism. Dietary changes affected the community composition, diversity, and potential virulence. However, predicted enzymes, which were part of complete metabolic pathways, remained present, albeit encoded by different microbes. CONCLUSIONS: Our findings provide a global insight into the phylogenetic relationships and the metabolic potential of a rich yet understudied bacterial community and suggest that it provides valuable services to the host. However, we tentatively infer that members of that community are not irreplaceable, because similar to previous findings, symbionts of complex bacterial communities of mammals are expendable if there are substitutes that can perform the same task. Video Abstract.

Tea crude extracts effectively inactivate severe acute respiratory syndrome coronavirus 2.

It is well known that black and green tea extracts, particularly polyphenols, have antimicrobial activity against various pathogenic microbes including viruses. However, there is limited data on the antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged rapidly in China in late 2019 and which has been responsible for coronavirus disease 2019 (COVID-19) pandemic globally. In this study, 20 compounds and three extracts were obtained from black and green tea and found that three tea extracts showed significant antiviral activity against SARS-CoV-2, whereby the viral titre decreased about 5 logs TCID50 per ml by 1·375 mg ml-1 black tea extract and two-fold diluted tea bag infusion obtained from black tea when incubated at 25°C for 10 s. However, when concentrations of black and green tea extracts were equally adjusted to 344 µg ml-1 , green tea extracts showed more antiviral activity against SARS-CoV-2. This simple and highly respected beverage may be a cheap and widely acceptable means to reduce SARS-CoV-2 viral burden in the mouth and upper gastrointestinal and respiratory tracts in developed as well as developing countries.

Therapeutic Effect of Sirolimus for Lymphangioleiomyomatosis Remaining in the Abdominopelvic Region After Lung Transplantation: A Case Report.

PURPOSE: Sirolimus (SRL) is used to treat pulmonary lymphangioleiomyomatosis (P-LAM). There is limited evidence that SRL has systemic efficacy for the patients with extrapulmonary lymphangioleiomyomatosis (E-LAM) remaining after lung transplantation (LT) for P-LAM. This report examines the efficacy of SRL treatment for the patient with E-LAM remaining after an LT for P-LAM. CASE SUMMARY: The course of the patient's recovery from an LT for P-LAM was complicated by lymphedema in the left femoral region that was caused by two E-LAM lesions remaining in the left pelvic cavity and in the retroperitoneal area. After the LT was performed, the patient started SRL treatment to reduce the E-LAM lesions. The daily SRL dose, selected based on the standard SRL dose for P-LAM, was initiated at 1 mg/d and was maintained at 2 mg/d. The remaining E-LAM lesions and lymphedema in the left femoral region improved in approximately 9 months after the LT with the administration of both SRL and the standard immunosuppressive therapy used by Okayama University Hospital, including tacrolimus, mycophenolate mofetil, and prednisolone. The SRL and tacrolimus trough concentrations in whole blood were maintained within the therapeutic window for the next 1.5 years after initiation of SRL treatment. The patient experienced no severe adverse events that required discontinuation of the SRL treatment during this time. CONCLUSION: The patients with remaining E-LAM lesions may receive SRL treatment to improve the quality of life after LT for P-LAM as effective therapy in cases where the patient's recovery is complicated by E-LAM lesions.

Genetic and functional analyses demonstrate a role for abnormal glycinergic signaling in autism.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Glycine receptors (GlyRs) are ligand-gated chloride channels that mediate inhibitory neurotransmission in the adult nervous system but exert an excitatory action in immature neurons. GlyRs containing the α2 subunit are highly expressed in the embryonic brain, where they promote cortical interneuron migration and the generation of excitatory projection neurons. We previously identified a rare microdeletion of the X-linked gene GLRA2, encoding the GlyR α2 subunit, in a boy with autism. The microdeletion removes the terminal exons of the gene (GLRA2(Δex8-9)). Here, we sequenced 400 males with ASD and identified one de novo missense mutation, p.R153Q, absent from controls. In vitro functional analysis demonstrated that the GLRA2(Δex8)(-)(9) protein failed to localize to the cell membrane, while the R153Q mutation impaired surface expression and markedly reduced sensitivity to glycine. Very recently, an additional de novo missense mutation (p.N136S) was reported in a boy with ASD, and we show that this mutation also reduced cell-surface expression and glycine sensitivity. Targeted glra2 knockdown in zebrafish induced severe axon-branching defects, rescued by injection of wild type but not GLRA2(Δex8-9) or R153Q transcripts, providing further evidence for their loss-of-function effect. Glra2 knockout mice exhibited deficits in object recognition memory and impaired long-term potentiation in the prefrontal cortex. Taken together, these results implicate GLRA2 in non-syndromic ASD, unveil a novel role for GLRA2 in synaptic plasticity and learning and memory, and link altered glycinergic signaling to social and cognitive impairments.

Evaluation of the level of progression of extracapsular spread for cervical lymph node metastasis in oral squamous cell carcinoma.

Only a few reports on the level of progression of extracapsular spread (ECS) have been published. The aim of this study was to evaluate the efficacy of the level of progression of ECS in identifying those patients with oral squamous cell carcinoma (OSCC) at a high risk of recurrence who would benefit most from the intensification of adjuvant therapy. The level of progression of ECS for cervical lymph node metastasis in OSCC was divided into three types (A-C), and their relationships with patient prognosis were examined. ECS was observed in 87 of 441 patients with OSCC. The recurrence rate in patients with type C, which was defined as macroscopic tumour invasion into perinodal fat or muscle tissue, was high (69.8%), with 13 cases of death due to distant metastasis. The 3-year disease-specific survival rate for patients with type C was 49.0% and these patients also had a significantly poorer prognosis (P<0.01). The results of the multivariate analysis suggested that the prognosis of ECS in OSCC patients was associated with the level of progression of ECS, especially type C (P<0.01). Overall, the results of this study suggest that the level of progression of ECS is a useful prognostic factor in OSCC patients.

Phonon dispersion of silicene on ZrB2(0 0 0 1).

We measured the phonon dispersion of silicene (monolayer Si with a honeycomb lattice) on ZrB2(0 0 0 1) using high-resolution electron energy loss spectroscopy. The measured phonon dispersion was compared with ab initio density functional theory calculations for a silicene model with [Formula: see text] periodicity of the substrate. The most stable [Formula: see text] silicene structure, which is similar to the so-called 'planar-like' model (Lee C C et al 2013 Phys. Rev. B 88 165404) reproduced the observed phonon modes very well. The recently reported soft phonon around the [Formula: see text] point (Lee C C et al 2014 Phys. Rev. B 90 241402(R)) was not reproduced, either experimentally or theoretically. The calculated electronic structure revealed that the silicene was metallic on ZrB2(0 0 0 1) and semiconducting on ZrC(1 1 1).

Occurrence of micro-organic pollutants on phosphorus recovery from urine.

Increased population growth and food prices have resulted in more demand for fertilizers, especially phosphorus (P), to be used in agriculture and production of food crops. Phosphorus is one of the important natural resources and will be exhausted in the near future. Nowadays, struvite production is a good method to recover P from urine. However, the natural urines contain high amounts of micro-organic pollutants which may cause health risks. Therefore, in this contribution, we investigated the amount of micro-organic pollutants in struvite from urine. There are various kinds of pharmaceuticals and hormones which are used in the world. Nevertheless, we focused on 10 pharmaceuticals (amoxycillin, carbamazepine, erythromycin, furosemide, atenolol, ibuprofen, norfloxacin, trimethoprim, tetracycline, and acetylsalicylic acid) and one hormone (17ß-estradiol) as representatives. The experiments were carried out with synthetic and natural urines. After the production of struvite, the results from synthetic and natural urine samples showed that only tetracycline, erythromycin, and norfloxacin remained in the struvite, and, especially, tetracycline remained in struvite with quite a high amount.

Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells.

Statins are 3-hydroxy-3-methylglutaryl-co-enzyme A reductase inhibitors of cholesterol biosynthesis, and have been reported to exert pleiotropic effects on cellular signalling and cellular functions involved in inflammation. Recent reports have demonstrated that previous statin therapy reduced the risk of pneumonia or increased survival in patients with community-acquired pneumonia. However, the precise mechanisms responsible for these effects are unclear. In the present study, we examined the effects of statins on cytokine production from lipopolysaccharide (LPS)-stimulated human bronchial epithelial cells (BEAS-2B). Interleukin (IL)-6 and IL-8 mRNA expression and protein secretion in LPS-stimulated cells were inhibited significantly by the lipophilic statin pitavastatin and the hydrophilic statin pravastatin. As these inhibitory effects of statin were negated by adding mevalonate, the anti-inflammatory effects of statins appear to be exerted via the mevalonic cascade. In addition, the activation levels of Ras homologue gene family A (RhoA) in BEAS-2B cells cultured with pitavastatin were significantly lower than those without the statin. These results suggest that statins have anti-inflammatory effects by reducing cytokine production through inhibition of the mevalonic cascade followed by RhoA activation in the lung.

Phase II study of S-1 monotherapy in patients with previously treated, advanced non-small-cell lung cancer.

BACKGROUND: In this phase II clinical trial, we evaluated the efficacy and safety of S-1 monotherapy in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We also measured plasma concentrations of 5-fluorouracil (5-FU) and 5-chloro-2,4-dihydroxypyridine components of S-1 and examined correlation with effectiveness and toxicity. METHODS: S-1 was given orally at a dose of 80 mg/m(2)/day for 14 consecutive days, followed by a 7-day rest period. This treatment course was repeated until disease progression or intolerable toxicity. RESULTS: We enrolled 30 patients. The response rate was 26.7% (8/30), and the disease control rate was 70% (21/30). Median progression-free survival (PFS) was 3.1 months, and median overall survival (OS) was 11.2 months. Mutations in the epidermal growth factor receptor (EGFR) gene were analyzed in 27 patients. The response rate was higher in patients with mutant EGFR (50.0%) than in those with wild-type EGFR (11.8%, P = 0.0288). Median PFS was 4.8 and 2.5 months (P = 0.038), and median OS was 22.4 and 8.4 months (P = 0.071). There was no grade 4 toxicity in this study. Five patients had grade 3 non-hematologic toxicity, and there was a trend toward higher plasma concentrations of 5-FU in those patients than in another patients. CONCLUSIONS: S-1 monotherapy is effective and well-tolerated treatment for previously treated advanced NSCLC.

[Electroablation for the treatment of spontaneous pneumothorax using SOFT COAG electrosurgical output system].

We evaluated the validity of the SOFT COAG electrosurgical output system for the treatment of spontaneous pneumothorax. From April 2008 to May 2010, we compared 64 patients who had undergone bullae resection using endoscopic linear staplers, to 20 patients subjected to electroablation of the bullae using the SOFT COAG output system. There was no significant difference between the 2 groups in terms of operation time, bleeding, and mean duration of postoperative chest tube drainage. Postoperative recurrence was apparent in 3 cases for the linear stapler, and in 2 cases for SOFT COAG. Electroablation using the SOFT COAG output system was suggested to be valid for treatment of spontaneous pneumothorax.

Dorsal-ventral distinction of chronic stress-induced electrophysiological alterations in the rat medial prefrontal cortex.

Chronic stress causes neuronal adaptation and maladaptation in the widespread brain regions including the prefrontal cortex (PFC) and limbic structures, resulting in cognitive and affective dysfunctions. In this study, we examined the impacts of chronic stress on functional interaction between the medial PFC and limbic structures in rats. In vivo electrophysiological recordings in rats exposed to chronic stress unveiled disturbance of correlated local field potential activity between the PFC and limbic structures as well as impairment of synaptic plasticity induction in the limbic-PFC pathways. However, these stress-induced alterations in limbic-PFC interaction were distinct along with the dorsal-ventral axis within the PFC, with greater stress vulnerability in the dorsal than the ventral PFC, such that alterations in the dorsal PFC became evident with much shorter duration of repeated stress exposure than those occurring in the ventral PFC. In agreement with the stress-induced alterations in limbic-PFC interaction, spike firing patterns of neurons in the dorsal and ventral PFC were also differently modulated by chronic stress. These results suggest that chronic stress produces heterogeneous cellular and neural network adaptation and maladaptation within the PFC that affect limbic information integration mechanisms.

Mechanisms underlying ketamine-induced synaptic depression in rat hippocampus-medial prefrontal cortex pathway.

The non-competitive N-methyl-D-aspartate NMDA receptor antagonist ketamine, a dissociative anesthetic capable of inducing analgesia, is known to have psychotomimetic actions, but the detailed mechanisms remain unclear because of its complex properties. The present study elucidated neural mechanisms of the effect of ketamine, at doses that exert psychotomimetic effects without anesthetic and analgesic effects, by evaluating cortical synaptic responses in vivo. Systemic administration (i.p.) of low (1 and 5 mg/kg), subanesthetic (25 mg/kg) and anesthetic (100 mg/kg) doses of ketamine dose-dependently decreased hippocampal stimulation-evoked potential in the medial prefrontal cortex (mPFC) in freely moving rats. The behavioral analysis assessed by prepulse inhibition (PPI) of acoustic startle response showed that ketamine (5 and 25 mg/kg, i.p.) produced PPI deficit. Thus, the psychotomimetic effects observed in ketamine-treated groups (5 and 25 mg/kg, i.p.) are associated with the induction of synaptic depression in the hippocampus-mPFC neural pathway. Based on these results, we further examined the underlying mechanisms of the ketamine-induced synaptic depression under anesthesia. Ketamine (5 and 25 mg/kg, i.p.) caused increases in dialysate dopamine in the mPFC in anesthetized rats. Moreover, the ketamine-induced decreases in the evoked potential, at the dose 5 mg/kg which has no anesthetic and analgesic effects, were indeed absent in dopamine-lesioned rats pretreated with 6-hydroxydopamine (6-OHDA; 150 µg/rat, i.c.v.). Ketamine (5 mg/kg, i.p.)-induced synaptic depression was blocked by pretreatment with dopamine D1 receptor antagonist SCH 23390 (10 µg/rat, i.c.v.) but not dopamine D2 receptor antagonist haloperidol (1.5 mg/kg, i.p.), suggesting that dopaminergic modulation mediated via D1 receptors are involved in the synaptic effects of ketamine. Furthermore, ketamine (5 mg/kg, i.p.)-induced synaptic depression was prevented also by GABAA receptor antagonist bicuculline (0.2 or 2 µg/rat, i.c.v.). These findings suggest that ketamine at the dose that exerts psychotomimetic symptoms depresses hippocampus-mPFC synaptic transmission through mechanisms involving dopaminergic modulation mediated via D1 receptors, which may lead to a net augmentation of synaptic inhibition mediated via GABAA receptors.

Cellular mechanisms of long-term depression induced by noradrenaline in rat prefrontal neurons.

Noradrenaline (NA) is released in the prefrontal cortex (PFC) during salient behavioral phases and thought to modulate PFC-mediated cognitive functions. However, cellular actions of NA in PFC neurons are still not well understood. In the present study, we investigated long-term effects of bath-applied NA (12.5 min) on glutamatergic synaptic transmission in rat PFC pyramidal neurons maintained in vitro. We found that NA concentration-dependently (5 microM< or =[NA]< or =20 microM) induces long-term depression (LTD) of layer I-II to layer V pyramidal neuron glutamatergic synapses. NA acts through alpha1- and alpha2-adrenoceptors, but not beta-adrenoceptors, to induce LTD. This NA-induced LTD depends on concurrent single synaptic activations of N-methyl-d-aspartate (NMDA) receptors and requires the activation of protein kinase C and postsynaptic Extracellular signal-Regulated Kinases (ERK1/2). Western blot analyses showed that NA (20 microM for 12.5 min) indeed induces transient increases of ERK1/2 phosphorylation in PFC neurons, which is dependent at least in part on the activation of NMDA receptors and alpha1-adrenoceptors. Together, these results demonstrate that NA can lastingly depress glutamatergic synapses in rat PFC neurons through mechanisms involving alpha-adrenoceptors, NMDA receptors, and the activation of postsynaptic ERK1/2.

[Video-assisted thoracoscopic removal for mediastinal mature teratoma following extraction of cystic components].

Video-assisted thoracoscopic resection for mediastinal mature teratoma is sometimes converted to open thoracotomy. Because it has rich components including pancreatic tissue and dense adhesion, even when it is asymptomatic. Prior to thoracoscopic resection, extraction of the cystic components with the aid of a 20 Fr tube can provide a wide thoracoscopic view leading to easier complete removal. Between October 1998 and June 2008, 6 patients (1 man and 5 women) with benign mediastinal mature teratoma underwent the thoracoscopic operations. The average age was 36.3 (range, 24-54). The mean diameter was 9.0 cm (range, 5-11 cm). The mean operation time was 143 minutes and the mean blood loss was 103 ml. Neither complications nor tumor recurrences developed during the mean follow-up period of 3.4 years. The presented thoracoscopic surgery for benign mature teratoma is a feasible procedure.

Background dopamine concentration dependently facilitates long-term potentiation in rat prefrontal cortex through postsynaptic activation of extracellular signal-regulated kinases.

Altered levels of tonic/background dopamine in prefrontal cortex (PFC) may underlie modifications of executive cognitive function. We showed previously in rat PFC slices that exogenously supplied background dopamine facilitates induction of long-term potentiation (LTP), a possible cellular substrate for the long-term component of executive cognitive function. In the present study, we characterized cellular and molecular mechanisms underlying this modulatory dopamine effect. We show first that the LTP-facilitating effect of tonic/background dopamine follows an inverted-U shape concentration curve and that the effective level of background dopamine slowly activates postsynaptic extracellular signal-regulated kinases (ERKs) to facilitate LTP. Furthermore, we show the evidence that LTP-inducing high-frequency stimulation evokes endogenous release of dopamine in PFC slices. This fast dopamine serves as a trigger for LTP in the presence of the background dopamine. In its absence, the endogenous dopamine triggered, instead, long-term depression. These results indicate that appropriate levels of tonic/background dopamine serve to activate critical molecular factors in PFC neurons and thereby facilitate induction of synaptic potentiation.

Comparison of postoperative surface light scattering of different intraocular lenses.

AIMS: This retrospective study was conducted to compare postoperative surface scattering of four kinds of intraocular lens (IOL). METHODS: Sixty-seven eyes of 67 patients who had undergone cataract surgery were enrolled in this study. One of four IOLs was used in the patients; MA60BM in 17 patients (MA group), SA60AT in 17 patients (SA group), AR40 in 16 patents (AR group) and ClariFlex in 17 patients (CL group). Measurement of scattering from the anterior surface of the IOL was measured with area densitometry using a Scheimpflug camera (EAS-1000, Nidek, Aichi) for 3 years after the surgery. RESULTS: The density of IOL surface scattering increased starting 1 year after surgery and throughout the 3-year period in the MA group and starting at 6 months through 3 years in the SA group, whereas the density was stable in the AR and CL groups. The density of surface scattering in the MA and SA groups at 3 years after surgery was significantly higher than in the AR and CL groups. CONCLUSION: The surface scattering of MA60BM and SA60AT is higher than that of AR40 and ClariFlex. The grades of surface scattering differ among the manufacturers, even with the same acrylic material.

[Surgical outcome of tracheobronchial reconstruction for lung cancer].

We retrospectively evaluated the surgical outcome after sleeve lobectomy and pneumonectomy with tracheobronchial reconstruction for lung cancer. From 1993 to 2008, 46 patients with primary lung cancer underwent these surgical procedures. Seventeen patients (37%) received induction therapy, 15 received chemotherapy, while chemoradiotherapy or radiotherapy alone were received by one patient each. Sleeve lobectomy without carinal resection was performed in 41 patients. Carinal resection with 2 sleeve pneumonectomies was performed in 5 patients. There were no operative deaths. Bronchopleural fistula occurred in one patient, who required completion pneumonectomy. One patient presented local mucosal necrosis in the anastomotic site and was managed conservatively. Two patients had bronchial strictures as late complications and successfully dilated by a balloon using bronchoscopy. Overall 5-year and 10-year survival rates were 54% and 48%, respectively. No recurrence developed at any anastomotic site. The results showed that sleeve lobectomy and pneumonectomy with tracheobronchial reconstruction can be performed with low mortality and bronchial anastomotic complication rates. As well, local control of the tumor was satisfactory.

[Atypical pulmonary carcinoid tumor with abnormal elevation of serum gastrin-releasing peptide precursor: report of a case].

We report a rare case of atypical pulmonary carcinoid tumor accompanied by elevation of serum gastrin-releasing peptide precursor (ProGRP). A 55-year-old male presented to our hospital with a history of bloody sputum. The level of serum ProGRP was elevated to 781 pg/ml (normal < 46 pg/ml). Chest computed tomography (CT) revealed a solitary pulmonary tumor in the left lower lobe with sub-carinal lymph node enlargement. Transbronchial lung biopsy showed a pulmonary carcinoid, therefore left lower lobectomy with mediastinal lymph node dissection was performed. ProGRP decreased to normal level 1 month after operation. Histopathological diagnosis showed an atypical pulmonary carcinoid tumor.

[Surgical treatment of an endobronchial inflammatory pseudotumor].

A 62-year old man with an abnormal chest radiograph was referred to our hospital for further evaluation. Chest computed tomography (CT) revealed a 3.0 cm tumor on the hilum of the right S3 segment. Bronchofiberscopic findings showed a polypoid tumor arising from right B3. Brushing cytology under bronchofiberscopy couldnot diagnose the tumor. The tentative preoperative diagnosis was primary lung cancer or a metastatic lung tumor. To confirm the histopathological diagnosis, a right upper lobectomy was performed. Intraoperative histopathological examination showed a pulmonary inflammatory pseudotumor.

Surface phonon dispersion of [Formula: see text].

Surface phonon dispersion of [Formula: see text]-B was measured using high resolution electron energy loss spectroscopy. With adsorption of excess boron, an ordered structure of [Formula: see text] is found at the B coverage of about 0.8 ML. Another structure of 4 × 4 appears mixed with the [Formula: see text] phase at a higher coverage. Using the phonon dispersion relations, the [Formula: see text] structure is inferred to consist of a planar boron network, as in the bulk. In contrast to the NbB(2)(0001) case, no surface core level shift of B 1s is observed on this [Formula: see text] surface, suggesting that the planar boron is not outermost.