Auditory-visual processing represented in the human superior temporal gyrus

In natural face-to-face communication, speech perception utilizes both auditory and visual information. We described previously an acoustically responsive area on the posterior lateral surface of the superior temporal gyrus (field PLST) that is distinguishable on physiological grounds from other auditory fields located within the superior temporal plane. Considering the empirical findings in humans and non-human primates of cortical locations responsive to heard sounds and/or seen sound-sources, we reasoned that area PLST would also contain neural signals reflecting audiovisual speech interactions. To test this hypothesis, event related potentials (ERPs) were recorded from area PLST using chronically implanted multi-contact subdural surface-recording electrodes in patient-subjects undergoing diagnosis and treatment of medically intractable epilepsy, and cortical ERP maps were acquired during five contrasting auditory, visual and bimodal speech conditions. Stimulus conditions included consonant-vowel (CV) syllable sounds alone, silent seen speech or CV sounds paired with a female face articulating matched or mismatched syllables. Data were analyzed using a MANOVA framework, with the results from planned comparisons used to construct cortical significance maps. Our findings indicate that evoked responses recorded from area PLST to auditory speech stimuli are influenced significantly by the addition of visual images of the moving lower face and lips, either articulating the audible syllable or carrying out a meaningless (gurning) motion. The area of cortex exhibiting this audiovisual influence was demonstrably greater in the speech-dominant hemisphere.     

Detection of metabolites of the new synthetic cannabinoid CUMYL‐4CN‐BINACA in authentic urine samples and human liver microsomes using high‐resolution mass spectrometry

CUMYL‐4CN‐BINACA(1‐(4‐cyanobutyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H–indazole‐3‐carboxamide) is a recently introduced indazole‐3‐carboxamide‐type synthetic cannabinoid (SC) that was detected in herbal incense seized by of the Council of Forensic Medicine, Istanbul Narcotics Department, in May 2016 in Turkey. Recently introduced SCs are not detected in routine toxicological analysis; therefore, analytical methods to measure these compounds are in demand. The present study aims to identify urinary marker metabolites of CUMYL‐4CN‐BINACA by investigating its metabolism in human liver microsomes and to confirm the results in authentic urine samples (n = 80). In this study, 5 μM CUMYL‐4CN‐BINACA was incubated with human liver microsomes (HLMs) for up to 3 hours, and metabolites were identified using liquid chromatography–high‐resolution mass spectrometry (LC–HRMS). Less than 21% of the CUMYL‐4CN‐BINACA parent compound remained after 3 hours of incubation. We identified 18 metabolites that were formed via monohydroxylation, dealkylation, oxidative decyanation to aldehyde, alcohol, and carboxylic acid formation, glucuronidation or reaction combinations. CUMYL‐4CN‐BINACA N‐butanoic acid (M16) was found to be major metabolite in HLMs. In urine samples CUMYL‐4CN‐BINACA was not detected; CUMYL‐4CN‐BINACA N‐butanoic acid (M16) was major metabolite after β‐glucuronidase hydrolysis. Based on these findings, we recommend using M16 (CUMYL‐4CN‐BINACA N‐butanoic acid), M8 and M11 (hydroxylcumyl CUMYL‐4CN‐BINACA) as urinary marker metabolites to confirm CUMYL‐4CN‐BINACA intake.     

Akt Kinase Intervenes in Flavivirus Replication by Interacting with Viral Protein NS5

Arthropod-borne flaviviruses, such as Zika virus (ZIKV), Usutu virus (USUV), and West Nile virus (WNV), are a growing cause of human illness and death around the world. Presently, no licensed antivirals to control them are available and, therefore, search for broad-spectrum antivirals, including host-directed compounds, is essential. The PI3K/Akt pathway controls essential cellular functions involved in cell metabolism and proliferation. Moreover, Akt has been found to participate in modulating replication in different viruses including the flaviviruses. In this work we studied the interaction of flavivirus NS5 polymerases with the cellular kinase Akt. In vitro NS5 phosphorylation experiments with Akt showed that flavivirus NS5 polymerases are phosphorylated and co-immunoprecipitate by Akt. Polymerase activity assays of Ala- and Glu-generated mutants for the Akt-phosphorylated residues also indicate that Glu mutants of ZIKV and USUV NS5s present a reduced primer-extension activity that was not observed in WNV mutants. Furthermore, treatment with Akt inhibitors (MK-2206, honokiol and ipatasertib) reduced USUV and ZIKV titers in cell culture but, except for honokiol, not WNV. All these findings suggest an important role for Akt in flavivirus replication although with specific differences among viruses and encourage further investigations to examine the PI3K/Akt/mTOR pathway as an antiviral potential target.     

The tight junction of pancreatic exocrine cells is a morphometrically dynamic structure altered by intraductal hypertension

The tight junction of pancreatic exocrine cells is thought to regulate paracellular permeability, and is a possible reflux route of pancreatic juice into the blood flow. Morphological changes in the tight junction of canine pancreatic acinar cells following intraductal hypertension and secretin stimulation were morphometrically analyzed to obtain evidence of the control of the paracellular reflux. Pancreatic tissues obtained from 25 dogs after intraductal hypertension, 3 dogs after secretin stimulation, and 5 control dogs were studied. Intraductal pressure was either 20 cmH2O, 30 cmH2O, or 40 cmH2O. Freeze fracture replicas of these pancreatic tissues were observed by electron microscopy. Tight junctions were classified into six morphometric types. Reticular type, parallel type, and mixed type comprised the common types predominantly found in all groups, and three special types were found, infrequently, only after intraductal hypertension. The percentages of the common types were significantly different between the groups. The areas of the tight junctions, and other morphometric parameters, were significantly less after 20 cmH2O intraductal hypertension and secretin stimulation than in the controls. However, these findings after 30 cmH2O or 40 cmH2O intraductal hypertension did not differ from those in the controls. The areas of the three special types of tight junctions were larger than those of the common types. These results suggest that the tight junction of pancreatic exocrine cells is a morphologically dynamic structure that is altered by the extent of intraductal hypertension, and support the hypothesis that paracellular permeability is the mechanism of the reflux of pancreatic juice. Received: November 10, 1999 / Accepted: April 28, 2000     

Characterization of peptide YY receptors in the brain

We studied the pharmacological and structural characteristics of peptide YY (PYY) receptors in porcine brain. PYY and neuropeptide Y (NPY) bound with high affinity to crude membrane preparations from the hippocampus, but their C-terminal fragments bound with 30- to 450-fold lower affinity Guanine nucleotides, especially the nonhydrolyzable GTP analog GTP gammas inhibited the binding of [125I]PYY, but other transmitters, hormones, and central nervous system-acting drugs did not, except for gangliosides at high concentrations. These results suggest that PYY receptor binding resides in the N-terminal part of the PYY molecule and is coupled to a guanine nucleotide regulatory protein. To elucidate PYY receptor structure, we used the cross-linking reagent disuccinimidyl suberate to covalently attach [125I]PYY to its receptors in the hippocampus membrane. Gel electrophoresis followed by autoradiography revealed a band centered at the mol wt of 50,000. Competitive inhibition of binding by unlabeled PYY resulted in a parallel inhibition of labeling of the 50,000 mol wt protein. The reducing agent 2-mercaptoethanol did not affect the appearance of this band, suggesting that the PYY receptor does not have subunits connected by sulfhydryl bonds. Furthermore, cross-linking [125I]NPY to its receptors in the porcine hippocampus produced the same 50,000 mol wt band regardless of 2-mercaptoethanol. The identity in the size of NPY and PYY receptors together with their similarities in binding properties including regional distribution and peptide specificity, indicate that NPY and PYY regulate brain function through interaction at a common receptor site.     

Dental technician's pneumoconiosis; a case report

Since 1939, it has been known that, silicosis and extrinsic allergic alveolitis can be seen among dental technicians. The interstitial disease caused by the exposure to complex substances used by dental technicians is classified as a special group called dental technician's pneumoconiosis. A 36-year-old man, who has no smoking history, presented with severe dyspnea. He had worked in different dental laboratories for 22 years, but he did not have respiratory symptoms until five years ago. After that date, he had hospitalized and had been examined for respiratory pathologies for many times. He had came to our clinic, because of the progression of his dyspnea. Diffuse pulmonary parenchymal infiltrates which can be related with pneumoconiosis and chronic type 1 respiratory deficiency had been diagnosed as the result of the examinations. While he has no history of smoking or any other risk factors or diseases in his medical history, the case was accepted as dental technician's pneumoconiosis. The factors related with the pathogenesis of dental technician's pneumoconiosis are; the complex compound of the substances (metal dusts, silica, plaster, wax and resins, chemical liquids, methyl methacrylate) used in this sector and their effects on the lung parenchyma. Extrinsic allergic alveolitis related with methyl methacrylate has been reported. The most important factor to acquire an occupational lung disease is a complex occupational exposure. The insufficient workplace airing and the lack of preventive measures added on this exposure, the risks become much more greater.     

Rectal submucosal tumor-like lesion originating from intestinal tuberculosis

We present the case of a 55-year-old man who underwent transsacral local excision for a rectal submucosal tumor-like lesion suspected to originate from tuberculosis. The lesion, 2 cm in size, was found incidentally in the posterior wall of the lower rectum during anal fistulectomy. The lesion was apart from the primary crypt of the anal fistula. Barium enema and colonoscopy revealed a protuberant submucosal growth with a shallow depression of the overlying mucosa. Although computed tomography and magnetic resonance imaging showed a well defined round mass within the rectal wall, digital rectal examination suggested extramural origin. Since repeated endoscopic biopsies were negative, we selected the transsacral approach for excisional biopsy to achieve histological diagnosis. The lesion was confined to the rectal wall and the full-thickness rectal wall was excised. Histologically, a foreign-body granuloma with acute inflammation was the main component of the lesion. Caseating granulomas and Langhans' giant cells, consistent with tuberculosis, were also found.