Identification of air phase retronasal and orthonasal odorant pairs

Identifications (IDs) of paired retronasal and orthonasal odorants were studied, with stimuli limited to air phase. Odorants were liquid extracts of plant materials, sold as food flavorings, matched by each subject both for retronasal-only and orthonasal-only air phase intensities and then learned to 100% correct veridical name retronasal-only and orthonasal-only IDs. Subjects were tested for ID of (a) retronasal-only and orthonasal-only odorants, (b) homogeneously paired odorant (the same odorant in retronasal and orthonasal locations), and (c) heterogeneously paired odorants (different odorants in retronasal and orthonasal locations). Paired odorants were presented in two different sequences: retronasal location odorant smelled first or orthonasal location odorant smelled first. IDs were reported after odorants were removed. Results were as follows: (a) no significant differences between correct ID of odorants when in retronasal-only versus orthonasal-only locations, although percent correct IDs were lower for half the retronasal-only location odorants; (b) correct ID of a homogeneously paired odorant equaled or exceeded its unpaired ID, with two successive, identical IDs reported on the majority of its trials; (c) with heterogeneous pairs, for all odorants when in the orthonasal location of a pair, correct ID occurred less often than when these odorants were presented orthonasal-only, but for odorants in the retronasal location, correct ID equaled or exceeded retronasal-only correct ID; and (d) perceived order of presentation of heterogeneous pairs was the reverse of the physically presented sequence for both retronasal-first and orthonasal-first conditions. The heterogeneous odorant ID outcome supports the concept that processing of retronasal and orthonasal odorants differ, and the perceived reversal of the presented sequence is in agreement with the importance of recency in odorant memory.     

Control of retinoic acid synthesis and FGF expression in the nasal pit is required to pattern the craniofacial skeleton

Endogenous retinoids are important for patterning many aspects of the embryo including the branchial arches and frontonasal region of the embryonic face. The nasal placodes express retinaldehyde dehydrogenase-3 (RALDH3) and thus retinoids from the placode are a potential patterning influence on the developing face. We have carried out experiments that have used Citral, a RALDH antagonist, to address the function of retinoid signaling from the nasal pit in a whole embryo model. When Citral-soaked beads were implanted into the nasal pit of stage 20 chicken embryos, the result was a specific loss of derivatives from the lateral nasal prominences. Providing exogenous retinoic acid residue development of the beak demonstrating that most Citral-induced defects were produced by the specific blocking of RA synthesis. The mechanism of Citral effects was a specific increase in programmed cell death on the lateral (lateral nasal prominence) but not the medial side (frontonasal mass) of the nasal pit. Gene expression studies were focused on the Bone Morphogenetic Protein (BMP) pathway, which has a well-established role in programmed cell death. Unexpectedly, blocking RA synthesis decreased rather than increased Msx1, Msx2, and Bmp4 expression. We also examined cell survival genes, the most relevant of which was Fgf8, which is expressed around the nasal pit and in the frontonasal mass. We found that Fgf8 was not initially expressed along the lateral side of the nasal pit at the start of our experiments, whereas it was expressed on the medial side. Citral prevented upregulation of Fgf8 along the lateral edge and this may have contributed to the specific increase in programmed cell death in the lateral nasal prominence. Consistent with this idea, exogenous FGF8 was able to prevent cell death, rescue most of the morphological defects and was able to prevent a decrease in retinoic acid receptorbeta (Rarbeta) expression caused by Citral. Together, our results demonstrate that endogenous retinoids act upstream of FGF8 and the balance of these two factors is critical for regulating programmed cell death and morphogenesis in the face. In addition, our data suggest a novel role for endogenous retinoids from the nasal pit in controlling the precise downregulation of FGF in the center of the frontonasal mass observed during normal vertebrate development.     

Replication protein A and gamma-H2AX foci assembly is triggered by cellular response to DNA double-strand breaks

Human replication protein A (RPA p34), a crucial component of diverse DNA excision repair pathways, is implicated in DNA double-strand break (DSB) repair. To evaluate its role in DSB repair, the intranuclear dynamics of RPA was investigated after DNA damage and replication blockage in human cells. Using two different agents [ionizing radiation (IR) and hydroxyurea (HU)] to generate DSBs, we found that RPA relocated into distinct nuclear foci and colocalized with a well-known DSB binding factor, gamma-H2AX, at the sites of DNA damage in a time-dependent manner. Colocalization of RPA and gamma-H2AX foci peaked at 2 h after IR treatment and subsequently declined with increasing postrecovery times. The time course of RPA and gamma-H2AX foci association correlated well with the DSB repair activity detected by a neutral comet assay. A phosphatidylinositol-3 (PI-3) kinase inhibitor, wortmannin, completely abolished both RPA and gamma-H2AX foci formation triggered by IR. Additionally, radiosensitive ataxia telangiectasia (AT) cells harboring mutations in ATM gene product were found to be deficient in RPA and gamma-H2AX colocalization after IR. Transfection of AT cells with ATM cDNA fully restored the association of RPA foci with gamma-H2AX illustrating the requirement of ATM gene product for this process. The exact coincidence of RPA and gamma-H2AX in response to HU specifically in S-phase cells supports their role in DNA replication checkpoint control. Depletion of RPA by small interfering RNA (SiRNA) substantially elevated the frequencies of IR-induced micronuclei (MN) and apoptosis in human cells suggestive of a role for RPA in DSB repair. We propose that RPA in association with gamma-H2AX contributes to both DNA damage checkpoint control and repair in response to strand breaks and stalled replication forks in human cells.     

House dust mite extract activates apical Cl− channels through protease‐activated receptor 2 in human airway epithelia

Adequate fluid secretion from airway mucosa is essential for maintaining mucociliary clearance, and fluid hypersecretion is a prominent feature of inflammatory airway diseases such as allergic rhinitis. House dust mite extract (HDM) has been reported to activate protease‐activated receptors (PARs), which play various roles in airway epithelia. However, the role of HDM in regulating ion transporters and fluid secretion has not been investigated. We examined the effect of HDM on ion transport in human primary nasal epithelial cells. The Ca²⁺‐sensitive dye Fura2‐AM was used to determine intracellular Ca²⁺ concentration ([Ca²⁺]_i) by means of spectrofluorometry in human normal nasal epithelial cells (NHNE). Short‐circuit current (Isc) was measured using Ussing chambers. Fluid secretion from porcine airway mucosa was observed by optical measurement. HDM extract (10 µg/Ml) effectively cleaved the PAR‐2 peptide and induced an increase of [Ca²⁺]_i that was abolished by desensitization with trypsin, but not with thrombin. Apical application of HDM‐induced Isc sensitive to both a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor and a Ca²⁺‐activated Cl^? channel (CaCC) inhibitor. HDM extract also stimulated fluid secretion from porcine airway mucosa. HDM extract activated PAR‐2 and apical Cl^? secretion via CaCC and CFTR, and HDM‐induced fluid secretion in porcine airway mucosa. Our results suggest a role for PAR‐2 in mucociliary clearance and fluid hypersecretion of airway mucosa in response to air‐borne allergens such as HDM. J. Cell. Biochem. 109: 1254–1263, 2010. © 2010 Wiley‐Liss, Inc.     

Evaluation of the factors affecting avicel reactivity using multi-stage enzymatic hydrolysis

Multi-stage and single-stage enzymatic hydrolysis of cellulose (Avicel PH-101) were conducted to investigate individual factors that affect the rate-reducing kinetics of enzymatic hydrolysis. Understanding factors affecting enzymatic hydrolysis of Avicel will help improve hydrolysis of various biomasses. Product inhibition, enzyme deactivation, and the changes of substrate are potential factors that can affect the hydrolysis efficiency of Avicel. Multi-stage enzymatic hydrolysis resulted in 36.9% and 25.4% higher carbohydrate conversion as compared to a single-stage enzymatic hydrolysis with an enzyme loading of 5 and 20 FPU/g in a 96 h reaction. However, a decline in carbohydrate conversion of 1.6% and 2.6% was observed through each stage with 5 and 20 FPU/g, respectively. This indicated that the substrate became more recalcitrant as hydrolysis progressed. The decreased reactivity was not due to crystallinity because no significant change in crystallinity was detected by X-ray diffraction. Product inhibition was significant at low enzyme loading, while it was marginal at high enzyme loading. Therefore, product inhibition can only partially explain this decreased conversion. Another important factor, enzyme deactivation, contributed to 20.3% and 25.4% decrease in the total carbohydrate conversion of 96 h hydrolysis with 5 and 20 FPU/g, respectively. This work shows that an important reason for the decreased Avicel digestibility is the effect of enzyme blockage, which refers to the enzymes that irreversibly adsorb on accessible sites of substrate. About 45.3% and 63.2% of the total decreased conversion at the end of the 8th stage with 5 and 20 FPU/g, respectively, was due to the presence of irreversibly adsorbed enzymes. This blockage of active sites by enzymes has been speculated by other researchers, but this article shows further evidence of this effect.     

Proteomic analysis of secretion from human transplanted submandibular gland replacing lacrimal gland with severe keratoconjunctivitis sicca

Purpose: Proteomic analysis of secretions from transplanted or non-transplanted submandibular glands in patients with severe keratoconjunctivitis sicca and tears from normal eyes. Experimental design: Secretions from submandibular glands transplanted to replace lacrimal glands and non-transplanted submandibular glands were collected at 1 year from 5 patients with severe keratoconjunctivitis sicca undergoing transplantation, and tears were collected from 3 normal subjects. 2-D electrophoresis (2-DE), then mass spectrometry was used to identify proteins. Western blot analysis was used to confirm protein expression. Results: We identified 34 and 11 distinct proteins in the saliva from transplanted submandibular glands and tears, respectively. The saliva from transplanted submandibular glands contained almost all the proteins abundant in tear fluid. The functions of identified proteins in the saliva from transplanted submandibular gland were mainly immune response and anti-bacterial. In total, 7 proteins showed differential expression between the saliva of transplanted and non-transplanted submandibular glands. The upregulation of short palate, lung and nasal epithelium carcinoma-associated protein 2 and carbonic anhydrase VI was confirmed by Western blot analysis. Conclusions: Identified proteins in saliva from transplanted submandibular glands may protect ocular structures. These findings can help in understanding the functional status of transplanted submandibular glands.     

难辨认孢子丝菌病临床分析

探讨孢子丝菌病不典型的临床表现.孢子丝菌病是皮肤科常见的一种深部真菌病,典型的皮肤科特征是慢性肉芽肿、溃疡性损害、炎性结节等.而部分孢子丝菌病的患者由于各种各样的原因导致皮损丧失特征性临床表现,给皮肤科医生尤其是临床经验尚不丰富的年轻医师于该病的诊断带来了一定的困难.本文所讨论的8例患者均为就诊于我科门诊并已确诊为孢子丝菌病病例,皮损与典型的孢子丝菌病皮损表现不相符,希望皮肤科医师在以后的临床工作中遇到一些不典型皮损但是综合患者病史、生活环境、诊治过程等情况可考虑到此种疾病,及时给予明确的诊断,使患者能够得到及时、有效的治疗.     

What determines nasal carriage of Staphylococcus aureus?

Nasal carriage of Staphylococcus aureus is an important risk factor for infection by this organism in both community and hospital settings; this article reviews the role of host and bacterial factors in carriage. A host genetic influence appears likely but the phenotypic determinants are unknown. Possibilities include variability in host adhesins, immune response or secretion of antimicrobial molecules. Colonization resistance by S. aureus, together with the observation that persistent carriers often carry a single strain whereas intermittent carriers can be colonized with unrelated strains over time, suggests that bacterial factors could also be involved.     

The ethmoid and presphenoid of cetaceans

A cribriform plate, a perpendicular plate, and two lateral masses are major components of the ethmoid bone of mammals. Notwithstanding the noticeable bone, virtually sitting in the center of the skull, extensive modifications of the skull of modern cetaceans, especially odontocetes (toothed whales), and the lack of clarity as to what characteristics delimit each element of the ethmoid has made the problem of the nature of the cetacean ethmoid more complicated and elusive than in other, less modified mammals. Furthermore, contention as to whether a perpendicular plate of the ethmoid, or the mesethmoid, exists in all mammals including cetaceans has remained unsettled. In odontocetes, the mesethmoid has been variably identified not only as the osseous nasal septum but also as the mediodorsal region of the posterior wall of the nasal passage below the nasals, as a mass of bone encased by the vomer in front of the osseous nasal cavity at the base of the rostrum, and as a combination of some portions mentioned above. The presence or absence of the mesethmoid in various groups of mammals has attracted the attention of some biologists, and here, I demonstrate that cetaceans have no mesethmoid. The close inspection of the ontogenetic changes of the basicranial elements in cetaceans reveals that a mass of bone ensheathed by the vomer in front, or at the level of the osseous nasal cavity is actually the presphenoid. It is highly likely that in odontocetes the posterior wall of the nasal passages below the nasals consists of the combination of the frontal, the imperforated cribriform plate, the paired ectethmoids, and the vomer, the latter three of which partially concealing the presphenoid dorsally and laterally as the ontogeny proceeds. In contrast, mysticetes clearly display ethmoturbinates and a cribriform plate, which are morphologically similar to those in terrestrial mammals. J. Morphol. 277:1661–1674, 2016. © 2016 Wiley Periodicals, Inc.     

Blockage errors in studies of the effect of wind on thermoregulatory responses

1. 1.The presence of an animal in a wind tunnel increases the effective wind velocity, and so increases heat transfer rates.

2. 2.Potentially significant errors in thermal conductance and thermoregulatory metabolism measurements may result.

3. 3.In a given wind tunnel metabolism chamber, these errors are size dependent and thus may lead to invalid allometric or adaptive interpretations of data.

4. 4.The errors are also sensitive to the shape, orientation, and characteristics of the fur or feather insulation of the animal. Thus, only approximate guidelines can be given for choosing correction factors.