Sensors and transducers signal to numerous downstream cellular effectors which function primarily by substrate posttranslational modifications including phosphorylation, acetylation, methylation and ubiquitylation. In particular, the past several years
have provided important insight into the role of chromatin remodeling and histones-specific modifications to control DNA damage detection, signaling and repair. This review summarizes recently identified factors that influence this complex process and the repair of DNA DSBs in eukaryotic cells.”
“Background: Influenza is one of the oldest and deadliest infectious diseases known to man. Reassorted Crenigacestat molecular weight strains of the virus pose the greatest risk to both human and animal health and have been associated with all pandemics of the past century, with the possible exception of the 1918 pandemic, resulting in tens of millions of deaths. We have developed and tested new computer algorithms, FluShuffle and FluResort,
which enable reassorted viruses to be identified by the most rapid and direct means possible. These algorithms enable reassorted influenza, and other, viruses to be rapidly identified to allow prevention strategies and treatments to be more efficiently implemented.\n\nResults: The FluShuffle and FluResort algorithms were tested RG-7388 with both experimental and simulated mass spectra of whole virus digests. FluShuffle considers different combinations of viral protein identities that match the mass spectral data using a Gibbs sampling algorithm employing a mixed protein Markov chain Monte Carlo (MCMC) method. FluResort utilizes those identities to calculate the weighted distance of each across two or more different phylogenetic trees constructed through viral protein sequence alignments. Each weighted
mean distance value is normalized by conversion to a Z-score to establish a reassorted strain.\n\nConclusions: The new FluShuffle and FluResort algorithms can correctly identify the origins of influenza viral proteins and the number of reassortment events required to produce the strains from the high resolution Selleckchem MK-8931 mass spectral data of whole virus proteolytic digestions. This has been demonstrated in the case of constructed vaccine strains as well as common human seasonal strains of the virus. The algorithms significantly improve the capability of the proteotyping approach to identify reassorted viruses that pose the greatest pandemic risk.”
“The emergence of an influenza pandemic is of great concern globally. It is, therefore, necessary to have a better understanding of the adaptation of influenza A viruses to humans. The mutation patterns affecting host tropism may provide information on the mechanisms and determinants of the host barrier. The work by Miotto et al.
This was confirmed in rat intravital microscopy of lipopolysaccharide-induced cremasteric muscle inflammation. Intravenous pCRP administration significantly enhanced leukocyte rolling, adhesion, and transmigration via localized dissociation to mCRP in inflamed but not noninflamed cremaster muscle. This was confirmed in a rat model of myocardial infarction. Mechanistically, this process was dependent on exposure of lysophosphatidylcholine on activated
cell membranes, which is generated after phospholipase A2 activation. These membrane changes could be visualized intravitally on endothelial cells, as could the colocalized mCRP generation. Blocking Selleckchem YH25448 of phospholipase selleck kinase inhibitor A2 abrogated C-reactive protein dissociation and thereby blunted the proinflammatory effects of C-reactive protein. Identifying the dissociation process as a therapeutic target, we stabilized pCRP using 1,6-bis(phosphocholine)-hexane, which prevented dissociation in vitro and in vivo and consequently inhibited the generation and proinflammatory activity of mCRP; notably, it also inhibited mCRP deposition and inflammation in rat myocardial infarction. Conclusions-These results provide in vivo evidence for a novel mechanism that localizes and aggravates inflammation via phospholipase A2-dependent
dissociation of circulating pCRP to mCRP. mCRP is proposed as Tyrosine Kinase Inhibitor Library a pathogenic factor in atherosclerosis and myocardial infarction. Most importantly, the inhibition of pCRP dissociation represents a promising, novel anti-inflammatory therapeutic strategy.”
“Inflammatory bowel diseases are a set of complex and chronic disorders that arise in genetically predisposed
individuals due to a lack of tolerance to the gut microflora. Although the intestinal microbiota is required for the proper development of the host and the maintenance of intestinal homeostasis, its dysbiosis is associated with inflammatory bowel diseases pathogenesis. In this review, we focus the discussion on the crosstalk between the innate immune system and the microbiota. We examine new findings from genetic and functional studies investigating the critical role of the intestinal epithelial cell layer and the processes that maintain its integrity in health and disease. We further explore the mechanisms of the mucosal innate immune system including dendritic cells, macrophages, and innate-like lymphocytes in mediating immunological tolerance at the steady state or pathogenic inflammatory responses in inflammatory bowel diseases.”
“Background: Obesity during pregnancy is associated with adverse outcomes for the offspring and mother. interventions in pregnancy such as antenatal exercise, are proposed to improve both short-and long-term health of mother and child.
“Is complexity growth the result of a continuous process or a sudden breakthrough? An increased energy density rate is the effect or the cause of a complexity leap? Should we approach complexity change by the perspective of components
behaviour or system’s space geometry? In this work we address some of the questions regarding the theoretical approach to complexity MLN2238 nmr change. For this purpose a case study drawn by the productive structure and the transport system is considered. We would like here to propose an example in which the system structure is reshaped in a more energy intensive fashion as to increase the components’ interactions due to a symmetry rupture in the space. Flows throughout the system are thereby incremented in a discontinuous way by a complexity leap. In the case study, we analyze how the productive system evolved its structure, between 1970s and 1990s, to increase interactions among its parts and thus further develop the transport sub-system. A two-stage shift has been considered:
the fordian and the post-fordian productive structure. The second structure, given the same amount of parts, has been shown to increase the degree of freedom (path PCI-34051 in vivo length and path diversity) of the system. The underlying evolutionary pattern is then analyzed. This evolutionary pattern relies on the hypothesis that thermodynamic evolutionary systems are characterized by an ever growing influx of energy driven into the system by self-catalytic processes that must find their way through the constraints of the system. The system initially disposes of the energy by expanding, in extent and in the number of components, up to saturation due to inner or outer constraints. The two counteractive forces, constraints and growing energy flux, expose the system to new gradients. Every new (spatial) gradient upon the system
represents a symmetry rupture in the components’ space. By exploring a new gradient, the system imposes further restrictions on its components and increases its overall degree of freedom. The counteractive effects of reduction/increase of degree Ferroptosis inhibitor clinical trial of freedom concern two different hierarchical levels and occur at two different space and time scales. (C) 2009 Elsevier B.V. All rights reserved.”
“Aims: Cisplatin (CDDP) is a platinum-based drug that is widely used in cancer chemotherapy, but the development of resistance in tumor cells is a major weakness of these treatments. Several mechanisms have been proposed to explain cisplatin resistance, and disruption of certain cellular pathways could modulate drug sensitivity to cisplatin. A lower level of cross-resistance to cisplatin leads to better outcomes in clinical use. Main methods: Cross-resistance was assessed using cisplatin resistant lung cancer cell line A549/CDDP.
5% of cases, in 95.9% of squamous cell carcinomas and 84.3% of adenocarcinomas. The five most prevalent high-risk HPV genotypes were HPV 16 (68.2%), 18 (40%), 58 (10.7%), 33 (10.4%) and 52 (10.4%). Multiple HPV infections were more prevalent (55.7%) than single HPV infections (36.8%). The percentage of HPV positive cases in Chinese, Malays and Indians were 95.5%, 91.9% and 80.0%, respectively. DAPT solubility dmso HPV 16 and 18 genotypes were the commonest in all ethnic groups. We found that the percentage of HPV 16 infection was significantly higher in Chinese (75.9%) compared to Malays (63.7%) and Indians (52.0%) (p<0.05), while HPV 18 was significantly higher in Malays (52.6%) compared to Chinese
(25.0%) and Indians (28%) (p<0.05). Meanwhile, HPV 33 (17.9%) and 52 (15.2%) were also more commonly detected in the Chinese
(p<0.05). Conclusions: This study showed that the distribution of HPV genotype in Malaysia is similar to other Asian countries. Importantly, we found that different ethnic groups in Malaysia have different HPV genotype infection rates, which is a point to consider during the implementation GDC-0973 datasheet of HPV vaccination.”
“Ethnic minorities are disproportionately impacted by prostate cancer (PCa) and are at risk for not receiving informed decision making (IDM). We conducted a systematic literature review on interventions to improve: (1) IDM about PCa in screening-eligible minority men, and (2) quality of life (QOL) in minority PCa survivors.\n\nMeSH headings for PCa, ethnic minorities, and interventions were searched in MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO.\n\nWe identified U.S.-based, English-language articles (1985 -aEuro parts per thousand 2010) on interventions to improve PCa IDM and QOL that
included 50 % or more minority patients or analyses stratified by race/ethnicity.\n\nArticles (n = 19) were evaluated and scored for quality using a Downs and Black (DB) system. Interventions were organized by those enhancing 1) IDM about PCa screening and 2) improving QOL and symptom among PCa survivors. Outcomes were reported by intervention type (educational seminar, printed material, telephone-based, Selleck BAY 73-4506 video and web-based).\n\nFourteen studies evaluated interventions for enhancing IDM about PCa screening and five evaluated programs to improve outcomes for PCa survivors. Knowledge scores were statistically significantly increased in 12 of 13 screening studies that measured knowledge, with ranges of effect varying across intervention types: educational programs (13 % -aEuro parts per thousand 48 % increase), print (11 % -aEuro parts per thousand 18 %), videotape/DVD (16 %), and web-based (7 % -aEuro parts per thousand 20 %). In the final screening study, an intervention to improve decision-making about screening increased decisional self-efficacy by 9 %.
“Introduction: Double antiplatelet therapy with clopidogrel and acetylsalicylic acid is a standard procedure after acute coronary syndrome. This treatment carries a higher risk of complications. The main goal of this research was to assess the patients’ quality of life after undergoing antiplatelet therapy with clopidogrel after acute coronary syndrome (ACS).\n\nMaterial and methods: In the questionnaire research 3220 patients after ACS and treated with clopidogrel were included. The evaluation was carried out with the quality of life questionnaire SF-12.\n\nResults:
LY3023414 purchase 37.9% of the interviewees experienced ACS-ST-elevation myocardial infarction (STEMI), 62.1% non-ST-elevation myocardial Infarction (NSTEMI), on average within 23 +/-42 weeks (p Selleck NU7026 < 0.05). 7.2% of the interviewees were receiving non-invasive treatment and in 2.4% cases it was fibrinolysis. 90.4% were treated with primary angioplasty and stenting. In 53.8% of cases a covered stent (DES) was implanted. 95.6% of the patients received, besides clopidogrel, acetylsalicylic acid. The lowest quality of life was observed after non-invasive treatment or fibrinolytic only (p < 0.05). The quality of life in those
patients who underwent angioplasty and stent implantation was similar (p < 0.05). With time, a progressive improvement of all assessed quality of life aspects was observed (p < 0.05). The improvement was noted regardless of the ACS treatment method (p < 0.001). The differences between the patients were smaller at each successive evaluation
(p < 0.05). In the case of vitality, emotional and psychic condition, they disappeared completely (p < 0.05).\n\nConclusions: The quality of life rises along with time passed after acute coronary syndrome. Invasive methods provide better quality of life than fibrinolysis and non-invasive treatment in the acute coronary syndrome patients.”
“Objective: T-cell lymphoma is a highly aggressive malignant lymphoma that is rare in Caucasians but relatively common in Asian populations. Factors regulating T-cell proliferation and function may play an important role in the pathogenesis of T-cell lymphoma. Methods: A total of 8 single nucleotide polymorphisms Compound C mouse in cytotoxic T lymphocyte antigen-4 (CTLA-4), tumor necrosis factor-alpha (TNF-alpha), and lymphotoxin-alpha (LTA) genes were detected by polymerase chain reaction-ligation detection reaction analysis in a Chinese population of 291 patients with T-cell lymphoma and 300 healthy controls. Logistic regression was used to determine the odds ratios (ORs) and 95% confidence intervals for the associations of genotypes and haplotypes with T-cell lymphoma risk. Results: Among these polymorphisms, the LTA +252AA genotype was significantly associated with T-cell lymphoma risk (OR, 2.3; P = 0.002). Furthermore, the TNF-alpha/LTA haplotype C-G-G-A (TNF-alpha -857C, -308G, and -238G and LTA +252A) showed a significantly increased risk for T-cell lymphoma (OR, 1.6; P = 0.001).
These changes may be partially mediated by oxidative stress. Oxidative damage is a major factor in neurodegenerative disorders and aging. A decline in the respiratory control ratio suggesting mitochondrial dysfunction was found in the brain of SAMP8.
The rise in oxidative stress following mitochondrial dysfunction may trigger neuropathological and neurochemical changes, disrupting the development of neural networks in the brain in SAMP8.”
“Clinical and experimental evidence indicates that intestinal inflammatory Nepicastat order conditions can be exacerbated by behavioral conditions such as depression. The recent demonstration of a tonic counterinflammatory influence mediated by the vagus nerve in experimental colitis provides a potential link between behavior and gut inflammation. Here we show that experimental conditions that induced depressive-like behaviors selleck kinase inhibitor in mice increased susceptibility to intestinal inflammation by interfering with the tonic vagal inhibition of proinflammatory macrophages and that tricyclic
antidepressants restored vagal function and reduced intestinal inflammation. These results show that reserpine-induced monoamine depletion and maternal separation, 2 models for depression, produced a vulnerability to colitis by a mechanism involving parasympathetic transmission and the presence of gut macrophages. The tricyclic antidepressant desmethylimipramine protected against this vulnerability by a vagal-dependent mechanism. Together these results illustrate
the critical role of the vagus in both the vulnerability to inflammation induced by depressive-like conditions and the protection afforded by tricyclic antidepressants and rationalize a clinical evaluation of both parasympathomimetics and tricyclic antidepressants in treatment of inflammatory bowel disease.”
“The avian hippocampal formation (HF) is reported to have a role equivalent to that of the mammalian hippocampus, which may involve the glutamatergic system as well. In the present paper we offer evidence of the occurrence and distribution of the subunits composing AMPA-type glutamate receptors on neurons in the hippocampus region of the pigeon brain. The experiment analyzed the immunolabeling of glutamate receptor (GluR)(1), GluR(4), and GluR(2/3) receptor subunits in adult pigeons and found RSL3 inhibitor consistent evidence that neurons located in the five main areas of the avian HF have these AMPA-type subunits, but their incidence varies according to position and neuro-type. About 20%-35% of the irregular and 35%-70% of the triangular neurons on the lateral and medial “V” arms contain GluR(1) and GluR(2/3), while GluR(4) Was found only at rounded neurons. The majority of the triangular neurons (over 90%) and about half of the irregular neurons in the medial area contain GluR, and GluR(2/3), whereas the rounded neurons contain primarily GluR(4) (95%).
The canonical correlation redundancy analysis showed that coat reflectance as well as hair length and number of hairs per unit area were the most useful in explaining changes in physiological traits. Skin and coat traits such as hair length, coat reflectance, percentage of epithelial area occupied by sweat glands, skin reflectance and thickness, as well as heart and breathing rates were the most important in separating these groups.”
“Collisions between planetesimals were common during the first approximately
100Myr of solar system formation. Such collisions click here have been suggested to be responsible for thermal processing seen in some meteorites, although previous work has demonstrated that such events could not be responsible for the global thermal evolution of a meteorite parent body. At this early epoch in solar system history, however, meteorite parent bodies would have been heated or retained heat from the decay of short-lived radionuclides, most notably PXD101 research buy Al-26. The postimpact structure of an impacted body is shown here to be a strong function of the internal temperature structure of the target body. We calculate the temperature-time history of all mass
in these impacted bodies, accounting for their heating in an onion-shell-structured body prior to the collision event and then allowing for the postimpact thermal evolution as heat from both radioactivities and the impact is diffused through the resulting planetesimal and radiated to space. The thermal histories of materials in these bodies are compared
with what they would be in an unimpacted, onion-shell body. We find that while collisions in the early solar system led to the heating of a target body around the point of impact, a greater amount of mass had its cooling rates accelerated as a result of the flow of heated materials to the surface during the cratering event.”
“Two-way wavelength conversion was achieved for visible and infrared signal pulses by using a phosphorescent disk. When a visible (530 nm) or infrared (980 nm) laser beam was focused on the disk, absorbed photons created bright spots that emitted both visible and infrared phosphorescence (upconversion and downconversion). Although the phosphorescence lasted https://www.selleckchem.com/products/GDC-0941.html for 1 ms, a pulse signal of 1 MHz (1 mu s period) was detected successfully by circulating the bright spots on the disk (a time-space conversion method). In comparison with downconversion, upconversion was easier to achieve for high-frequency signals, since the two-photon absorption process prevented overlapping of adjacent spots by restricting the phosphorescence spot size. (C) 2013 Elsevier B.V. All rights reserved.”
“Corneal epithelium is maintained throughout life by well-orchestrated proliferation of limbal epithelial stem cells, followed by migration and maturation centripetally across the ocular surface.
A PFA100 closure time less than 190 seconds was defined as residual platelet reactivity. Eighty-six patients (43%) showed residual platelet reactivity. The mean follow-up time was 32 +/- 10 months and was 100% complete.\n\nResults. A total of 75 cardiovascular events have been registered. The majority of these events were among patients with residual platelet activity (p = 0.001). Out of this number, graft failure was documented in 25 patients. The 42-month
freedom from major cardiovascular events was significantly better for patients with adequate platelet inhibition (p = 0.001). At multivariable analysis residual platelet Ferroptosis mutation reactivity (p = 0.012), incomplete revascularization (p = 0.029), and diabetes (p = 0.0009) were independently associated with occurrence of negative events.\n\nConclusions. Our results demonstrate that high residual platelet reactivity independently correlates with a worst clinical outcome
in patients treated by coronary artery bypass surgery. The PFA-100 point care test could cheaply and simply discover this condition and contribute to improve the outcome of this subset of patients.”
“Background. Lung transplantation activity is frustrated by donor lung availability. We sought to examine the effect SNX-5422 Cytoskeletal Signaling inhibitor of active donor management and hormone administration on pulmonary function and yield in cadaveric heart-beating potential lung donors.\n\nMethods. We studied 182 potential lung donors (arterial oxygen tension [PaO2]/fractional inspired oxygen GNS-1480 mw [FIO2] ratio >
230). From this group, 60 patients (120 lungs) were allocated, within a randomized trial, to receive methylprednisolone (1 g), triiodothyronine (0.8 mu g/ kg bolus and 0.113 mu g/ kg/h infusion), both methylprednisolone and triiodothyronine, or placebo as soon as feasible after consent and initial assessment. Trial donors underwent protocol-guided optimization of ventilation and hemodynamics, lung water assessment, and bronchoscopy. Function was assessed by PaO2/FIO2 ratio, extravascular lung water index (EVLWI), and pulmonary vascular resistance (PVR). A nontrial group of 122 donors (244 lungs) received similar management without bronchoscopy, pulmonary artery flotation catheter monitoring, or lung water assessment.\n\nResults. Within the trial, management commenced within a median of 2 hours (interquartile range, 0.5 to 3.5 hours) of consent and continued for an average of 6.9 +/- 1.2 hours. The PaO2/FIO2 ratio deteriorated (p = 0.028) from 397 +/- 78 (95% CL, 376 to 417) to 359 +/- 126 (95% CL, 328 to 390) and EVLWI from 9.7 +/- 4.5 mL/ kg (95% CL, 8.6 to 10.9 mL/ kg) to 10.8 +/- 5.2 mL/ kg (95% CL, 9.4 to 12.2 mL/ kg; p = 0.009). PVR remained unchanged (p = 0.28). At end management, 48 of 120 trial lungs (40%) were transplanted versus 66 of 244 nontrial lungs (27%; p = 0.016).
The 5-year event-free-survival (EFS) and overall survival (OS) for all patients was 35% and 50% respectively. Furthermore, at 66-months median follow-up, the 5-year EFS and OS for patients who received consolidative auto-HSCT was 54% and 75% respectively. Patients who received auto-HSCT had improved outcomes compared to no auto-HSCT (EFS P = 0.001; OS P = 0.0002). CTAP/VMAC induction followed by consolidative auto-HSCT for newly diagnosed Caspase-3 Inhibitor MCL is associated with high ORR and durable survival.”
“This study focuses on analyzing the effects of several factors on the rate of decay of inherent viscosity (iv) during hydrolytic degradation. The analysis was made for oriented PLLA, 96L/4D PLA and 80L/20D,L
PLA. The analyzed polymers were found to have identical rate of iv loss (P < 0.05), given that the materials have otherwise similar initial material properties. The effect of the post-processing residual monomer was dose dependent, i.e. the higher the monomer content the faster the degradation (P < 0.05). Smoothened Agonist ic50 Samples with a smaller diameter (1.1 mm) were found to have a faster rate of iv loss than the samples with a larger diameter (4 mm) (P < 0.05). A multiple linear regression analysis was used to create a five-component linear model to predict changes in the materials’ inherent viscosity. This model yielded accurate predictions during
the initial stages of the hydrolytic degradation process where the iv loss was virtually linear.”
“Information on the phenotypic variations seen in patients
with type 3 (chronic neuronopathic) Gaucher disease (GD) is still limited compared with type I GD. We retrospectively investigated the clinical features of 42 Japanese patients with type 3 GD. The 42 patients classified as type 3 fell into two groups: A-1155463 cell line those diagnosed as having type 3 GD at diagnosis (group A; n = 24) and those thought to have type 1 at diagnosis but who later developed neurological symptoms (group B; n = 18). The genotype of group A patients varied widely: however, L444P/L444P and L444P/F213I genotypes accounted for 83% in group B. All the patients who did not receive enzyme replacement with alglucerase or imiglucerase (4 in group A, 2 in group B) died. Nineteen patients received enzyme replacement in group A; however, 7 of these died despite the therapy. On the other hand, 14 patients received enzyme replacement alone in group B and 13 of them survived. Among the ERT-treated patients who survived, only one of 12 in group A and 12 out of 13 in group B can walk unaided. In conclusion, some Japanese GD patients who are thought to have type 1 at diagnosis develop neurological symptoms during their clinical course, and careful observation is essential for patients with characteristic genotypes. Moreover, enzyme replacement alone might not have a sufficient effect on the early onset neurological symptoms in type 3 patients. A different treatment strategy is needed to improve the prognosis of these patients.
Results showed a high radical scavenging activity and antioxidant capacity of QFE similar to those of the pure flavonoid quercetin.”
“Background: We investigated the applicability and feasibility of perceptive computing assisted gait analysis in multiple sclerosis (MS) patients using Microsoft
Kinect (TM). To detect the maximum walking speed and the degree of spatial sway, we established a computerized and observer-independent measure, which we named Short Maximum Speed Walk (SMSW), and compared it to established clinical measures of gait disability in MS, namely the Expanded Disability Status Scale (EDSS) and the Timed 25-Foot Walk (T25FW). Methods: Cross-sectional study of 22 MS patients (age mean +/- SD 43 +/- 9 years, 13
female) and 22 age and gender matched www.selleckchem.com/products/geneticin-g418-sulfate.html healthy control subjects (HC) (age 37 +/- 11 years, 13 female). The disability level of each MS patient was graded using the EDSS (median 3.0, range 0.0-6.0). All subjects then performed the SMSW and the Timed 25-Foot Walk (T25FW). The SMSW comprised five gait parameters, which together assessed average walking speed and gait stability in different dimensions (left/right, up/down and 3D deviation). Results: SMSW average Blebbistatin cost walking speed was slower in MS patients (1.6 +/- 0.3 m/sec) than in HC (1.8 +/- 0.4 m/sec) (p = 0.005) and correlated well with EDSS (Spearman’s Rho 0.676, p smaller than 0.001). Furthermore, SMSW revealed higher left/right deviation in MS patients compared to HC. SMSW showed high recognition quality and retest-reliability (covariance GS-1101 nmr 0.13 m/sec, ICC 0.965, p smaller than 0.001). There was a significant correlation between SMSW average walking speed and T25FW (Pearson’s R = -0.447, p = 0.042). Conclusion: Our data suggest that ambulation tests using Microsoft Kinect (TM) are feasible,
well tolerated and can detect clinical gait disturbances in patients with MS. The retest-reliability was on par with the T25FW.”
“We present case of oral and skin anaplastic T-cell lymphoma in a 68-year-old woman. The patient presented with extensive ulcerations and necrotic tissue on the left mandibular gingiva. Orthopantomogram finding showed extensive necrolytic lesions of the adjacent mandible. Biopsy finding of oral lesions and subsequently of the skin confirmed the diagnosis of anaplastic T-cell lymphoma. The bridge on the teeth 35-37 was taken out. After three cycles of chemotherapy, oral lesions subsided, unlike skin lesions. Dentists should be aware that differential diagnosis when dealing with oral ulcerations might be the result of certain malignant hematologic diseases.”
“Cutaneous mucinoses are a heterogeneous group of disorders characterized by an abnormal amount of mucin in the skin. However, the pathomechanism of an excessive mucin deposition in the skin is still unknown.