The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index; 25 of the 39 sources its claims cite were checked for support.
Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS/MS
Open accessAbstract
Ceramides are the predominant lipids in the stratum corneum (SC) and are crucial components for normal skin barrier function. Although the composition of various ceramide classes in the human SC has been reported, that in mice is still unknown, despite mice being widely used as animal models of skin barrier function. Here, we performed LC/MS/MS analyses using recently available ceramide class standards to measure 25 classes of free ceramides and 5 classes of protein-bound ceramides from human and mouse SC. Phytosphingosine- and 6-hydroxy sphingosine-type ceramides, which both contain an additional hydroxyl group, were abundant in the human SC (35% and 45% of total ceramides, respectively). In contrast, in mice, phytosphingosine- and 6-hydroxy sphingosine-type ceramides were present at ∼1% and undetectable levels, respectively, and sphingosine-type ceramides accounted for ∼90%. In humans, ceramides containing α-hydroxy FA were abundant, whereas ceramides containing β-hydroxy or ω-hydroxy FA were abundant in mice. The hydroxylated β-carbon in β-hydroxy ceramides was in the ( R ) configuration. Genetic knockout of β-hydroxy acyl-CoA dehydratases in HAP1 cells increased β-hydroxy ceramide levels, suggesting that β-hydroxy acyl-CoA, an FA-elongation cycle intermediate in the ER, is a substrate for β-hydroxy ceramide synthesis. We anticipate that our methods and findings will help to elucidate the role of each ceramide class in skin barrier formation and in the pathogenesis of skin disorders.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
The paper establishes an LC/MS/MS method using deuterated standards to quantify free and protein-bound ceramides in human and mouse stratum corneum, revealing large class and species differences. Humans are rich in phytosphingosine- and 6-hydroxy sphingosine-type ceramides and α-hydroxy ceramides, whereas mice are dominated by sphingosine-type ceramides and contain more β-/ω-hydroxy and EO ceramides.
Key findings
- The method quantified 21 free ceramide classes/345 species in human SC and 16 classes/268 species in mouse SC; P-O ceramides were quantified as 5 classes/63 species in humans and 5 classes/74 species in mice.
- In human SC, NP, NH, and AH were abundant (24.2%, 23.7%, and 18.0% of total ceramides, respectively); 6-hydroxy sphingosine- and phytosphingosine-type ceramides accounted for 45.4% and 34.7%. In mouse SC, NS was highest (57.9%), sphingosine-type ceramides accounted for 87.7%, phytosphingosine-type ceramides were 1.2%, and 6-hydroxy sphingosine-type ceramides were undetectable.
- By FA type, human SC was 59.4% nonhydroxy, 32.5% α-hydroxy, 6.3% EO, 1.6% ω-hydroxy, and 0.17% β-hydroxy ceramides; mouse SC was 68.9% nonhydroxy, 16.9% EO, 8.7% ω-hydroxy, 4.9% β-hydroxy, and 0.7% α-hydroxy ceramides.
- The hydroxylated β-carbon in BS was in the (R) configuration, and HACD1/HACD2 double KO HAP1 cells showed a 15-fold increase in BS, suggesting β-hydroxy acyl-CoA from the ER FA elongation cycle is a substrate for BS synthesis.
Methods
- Human SC was collected by tape stripping from healthy volunteers (10 males and 9 females aged 20–50 y; n = 19); mouse SC was collected from the back of C57BL/6J mice on the first day after birth (n = 3), using the second tape strip for lipid extraction.
- Ceramides were analyzed by UPLC coupled to ESI tandem quadrupole MS in MRM mode with a reverse-phase C18 column and deuterium-labeled ceramide standards; matrix effects from tape extracts were tested, and P-O ceramides were released by KOH/methanol extraction.
- In vitro assays used HEK293T cells overexpressing CERS1 or CERS5 for BS synthesis and HACD1/HACD2 double KO HAP1 cells to test BS levels.
Limitations
- The paper states that it focused on and quantified ceramide species containing C18 chain-length LCBs, while LCBs with different chain lengths (C14–C26) reportedly exist in the epidermis and remain for future analysis.
- The paper states that further analyses are required for BS synthesis because (R)-β-hydroxy acyl-CoAs are also produced in peroxisomal β-oxidation and BS could alternatively be generated by β-hydroxylation of NS by an unidentified hydroxylase.
- The paper notes that mice deficient in a hydroxylase gene involved in hydroxylated ceramide production may not always be appropriate models for human skin disorders; evident from the text, the mouse sample was small (n = 3), from a single early time point and back skin, and no functional barrier measurements are reported.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
25 of 39 cited sources checked · 10 supported · 3 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Additionally, the fragment ion pattern of ceramides differs depending on their LCB moiety (5).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
What the sources say
- Supportedcites [5] Masukawa, 2008, Characterization of overall ceramide species in human stratum corneum, J. Lipid Res. source
The 'Characteristics of product ion spectra of authentic CERs' section (page not provided) reports different product-ion patterns for ceramides with different long-chain base moieties. It specifically contrasts the spectrum of CER[N(26)P(20)] with those of other ceramides. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The composition of ceramide classes/species in the human SC has previously been analyzed using LC/MS (5-7, 16, 17, 29, 30).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
What the sources say
- Supportedcites [5] Masukawa, 2008, Characterization of overall ceramide species in human stratum corneum, J. Lipid Res. source
The “Comprehensive profiling of CERs in human SC” section says the authors applied NPLC-ESI-MS to ceramides extracted from human stratum corneum. The Discussion reports identification of 342 species across 11 classes using NPLC-ESI-MS/MS, supporting the cited claim. (LLM, conf=0.94)
- Supportedcites [6] van Smeden, 2011, LC/MS analysis of stratum corneum lipids: ceramide profiling and discovery, J. Lipid Res. source
The Abstract states that the paper presents an LC/MS method for separating and analyzing human stratum corneum ceramide subclasses. It also reports applying the method to three human stratum corneum sample types and observing their ceramide profiles, which supports the citing sentence. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [7] t'Kindt, 2012, Profiling and characterizing skin ceramides using reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry, Anal. Chem. source
- Not checked — no full text of the sourcecites [16] Ishikawa, 2010, Changes in the ceramide profile of atopic dermatitis patients, J. Invest. Dermatol. source
- Supportedcites [17] Janssens, 2012, Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients, J. Lipid Res. source
The “Lipid extraction and ceramide analysis by LC/MS” section describes LC/MS analysis of lipids extracted from human stratum corneum tape strips. The results report that the LC/MS data were used to calculate the relative abundance of ceramide subclasses, supporting the claim about classes and species. Page numbers are not provided in our copy. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [29] Farwanah, 2005, Profiling of human stratum corneum ceramides by means of normal phase LC/APCI-MS, Anal. Bioanal. Chem. source
- Not checked — no full text of the sourcecites [30] Weerheim, 2001, Determination of stratum corneum lipid profile by tape stripping in combination with high-performance thin-layer chromatography, Arch. Dermatol. Res. source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The fragmentation pattern of this peak is consistent with that of C26:0 BS in previous reports (12,42), demonstrating that the peak detected at 12.86 min was C26:0 BS.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Establishment of the method that specifically detects ceramide species by LC/MS/MS
What the sources say
- Supportedcites [12] Tsugawa, 2017, Comprehensive identification of sphingolipid species by in silico retention time and tandem mass spectral library, J. Cheminform. source
In the Results and discussion section on β-hydroxy ceramide, Fig. 4 identifies an experimental MS/MS spectrum as Ceramide [BS] (d18:1/26:0) and describes its diagnostic fragment ions. This supports using the paper's fragmentation pattern to identify a comparable peak; the 12.86-minute retention time is the citing authors' observation. (LLM, conf=0.90)
- Supportedcites [42] Hsu, 2016, Complete structural characterization of ceramides as [M-H]– ions by multiple-stage linear ion trap mass spectrometry, Biochimie. source
Section 3.4 identifies d18:1/βh26:0-Cer as Cer[BS] and describes its characteristic fragmentation, including a dominant m/z 340 ion in the MS2 spectrum. This supports the cited comparison with a previously reported C26:0 BS fragmentation pattern; the 12.86-minute peak is the citing authors’ observation. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Therefore, more than several hundred ceramide species exist in the human SC (5)(6)(7).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
What the sources say
- Supportedcites [5] Masukawa, 2008, Characterization of overall ceramide species in human stratum corneum, J. Lipid Res. source
The Abstract reports identification of 342 ceramide species in human inner-forearm stratum corneum. The Discussion likewise concludes that at least 342 species were identified, supporting the citing sentence’s approximate count. (LLM, conf=0.90)
- Partly supportedcites [6] van Smeden, 2011, LC/MS analysis of stratum corneum lipids: ceramide profiling and discovery, J. Lipid Res. sourceExperimental — accuracy not yet measured
The Abstract reports 11 identified ceramide subclasses in human stratum corneum, and the Results and Discussion describe variation in their chain lengths. These passages support the existence of many distinct ceramides, but our copy does not establish that the number of species exceeds several hundred. (LLM, conf=0.78)
- Not checked — no full text of the sourcecites [7] t'Kindt, 2012, Profiling and characterizing skin ceramides using reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry, Anal. Chem. source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The fragmentation pattern of this peak is consistent with that of C26:0 BS in previous reports (12,42), demonstrating that the peak detected at 12.86 min was C26:0 BS.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Establishment of the method that specifically detects ceramide species by LC/MS/MS
What the sources say
- Partly supportedcites [12] Tsugawa, 2017, Comprehensive identification of sphingolipid species by in silico retention time and tandem mass spectral library, J. Cheminform. sourceExperimental — accuracy not yet measured
The Results and discussion section, under “Annotation of β-hydroxy ceramide,” identifies an experimental MS/MS spectrum as Ceramide [BS] (d18:1/26:0) and reports Ceramide [BS] in murine ear tissue. It does not identify a peak at 12.86 min or report that measurement in mouse epidermis, so those specifics are not supported by this source. (LLM, conf=0.85)
- Supportedcites [42] Hsu, 2016, Complete structural characterization of ceramides as [M-H]– ions by multiple-stage linear ion trap mass spectrometry, Biochimie. source
Section 3.4 identifies d18:1/βh26:0-Cer as Cer[BS] and describes its characteristic MS² fragmentation pattern, supporting the cited comparison. The 12.86-minute peak in mouse epidermis is the citing authors’ own identification, not a measurement attributed to this source. (LLM, conf=0.93)
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Third, during ionization, the dehydration of ceramide is often induced by in-source decay (31).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
What the sources say
- Partly supportedcites [31] Rabionet, 2013, 1-O-acylceramides are natural components of human and mouse epidermis, J. Lipid Res. sourceExperimental — accuracy not yet measured
The Materials section reports significant in-source decay of 1-O-acylceramides leading to water loss during mass spectrometry. That supports the mechanism for this ceramide subtype, but not the broader claim that ceramides generally often undergo it. Page numbers were unavailable in our copy. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“In transcriptome analysis of human skin, the fragments per kilobase of transcript per million mapped reads (FPKM) values, which indicate relative gene expression levels, of DEGS1 and DEGS2 were 186 and 32 (17% of DEGS1), respectively (51).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
What the sources say
- Could not verifycites [51] Skaug, 2020, Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile, Ann. Rheum. Dis. sourceExperimental — accuracy not yet measured
The Methods sections on skin biopsy and assignment to intrinsic subsets describe skin RNA sequencing and the use of FPKM values. Neither those passages nor the Results passage on transcript expression gives FPKM values for DEGS1 or DEGS2; searches for the gene names and the reported numbers found no matching passage in our copy. (LLM, conf=0.72)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared with the standards diluted only with methanol (external standards), the detection ratio of each d 9 ceramide mixed with tape extracts was decreased, especially in the extracts from 200 and 400 mm 2 pieces of tape (Fig. 2G).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Establishment of the method that specifically detects ceramide species by LC/MS/MS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In humans, ceramides containing -hydroxy FA were abundant, whereas ceramides containing -hydroxy or -hydroxy FA were abundant in mice.”
- Also stated in: § Different SC ceramide classes and FA composition between humans and mice · plain
“In mice, the EO, -hydroxy, and -hydroxy ceramide classes were 16.9%, 8.7%, and 4.9%, respectively, and -hydroxy ceramide, the second highest ceramide class in humans, was quite low (0.7%).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Different SC ceramide classes and FA composition between humans and mice · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In humans, ceramides containing -hydroxy FA were abundant, whereas ceramides containing -hydroxy or -hydroxy FA were abundant in mice.”
- Also stated in: § Different SC ceramide classes and FA composition between humans and mice · plain
“In mice, the EO, -hydroxy, and -hydroxy ceramide classes were 16.9%, 8.7%, and 4.9%, respectively, and -hydroxy ceramide, the second highest ceramide class in humans, was quite low (0.7%).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Different SC ceramide classes and FA composition between humans and mice · plain
- Probably not a substantial claim. 8
- It may state two separate claims as one. 26
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“In the human SC, 16 ceramide classes other than SD and -hydroxy ceramides have been identified (5)(6)(7).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
What the sources say
- Disputedcites [5] Masukawa, 2008, Characterization of overall ceramide species in human stratum corneum, J. Lipid Res. sourceExperimental — accuracy not yet measured
The Nomenclature section describes 12 ceramide classes, including classes not previously reported, rather than 16 excluding SD and β-hydroxy ceramides. The Discussion reports identifying species within 11 classes; our copy does not substantiate the claimed count of 16. (LLM, conf=0.87)
Checked by a reasoning model — may be wrong.
- Disputedcites [6] van Smeden, 2011, LC/MS analysis of stratum corneum lipids: ceramide profiling and discovery, J. Lipid Res. sourceExperimental — accuracy not yet measured
The Abstract reports 11 previously identified ceramide subclasses in human stratum corneum and identifies one additional subclass, CER [EOdS]. The Results and Discussion likewise describe 12 subclasses as the theoretical total, contrary to the attributed count of 16 even before the stated exclusions. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [7] t'Kindt, 2012, Profiling and characterizing skin ceramides using reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry, Anal. Chem. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Disputed
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“In Fa2h KO mice, neither the skin phenotype nor reduced AS levels in skin were observed (53).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
What the sources say
- Disputedcites [53] Maier, 2011, Normal fur development and sebum production depends on fatty acid 2-hydroxylase expression in sebaceous glands, J. Biol. Chem. sourceExperimental — accuracy not yet measured
In “Delayed Fur Emergence and Cyclic Alopecia in FA2H-deficient Mice” (page unavailable), the paper reports delayed fur development and repeated hair loss in Fa2h knockout mice—a skin phenotype, contrary to the claim. Its lipid analysis also reports reduced hydroxylated glucosylceramides in total skin, although hydroxylated ceramides showed no obvious change. The copy does not identify these measurements as “AS levels.” (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Disputed
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“A portion of EO ceramides are converted into protein-bound hydroxy (P-O) ceramides (Fig. 1B), which are connected to cross-linked proteins constituting the cornified envelope, a structure located beneath the surface of corneocytes (20)(21)(22).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
What the sources say
- Not checked — no full text of the sourcecites [20] Candi, 2005, The cornified envelope: a model of cell death in the skin, Nat. Rev. Mol. Cell Biol. source
- Supportedcites [21] Elias, 2014, Formation and functions of the corneocyte lipid envelope (CLE), Biochim. Biophys. Acta. source
Section 2 describes a smaller pool of acyl-(glucosyl)ceramides being converted to ω-hydroxy ceramides destined for covalent binding to the cornified envelope. Section 1 identifies the binding site as primarily involucrin in the envelope’s external portion. Page numbers are not available in our copy. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [22] Akiyama, 2017, Corneocyte lipid envelope (CLE), the key structure for skin barrier function and ichthyosis pathogenesis, J. Dermatol. Sci. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“EO ceramides are epidermisspecific ceramide classes, and their characteristic EO structure is important for the formation and stabilization of lipid organization in the lipid lamellae (18,19).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
What the sources say
- Partly supportedcites [18] Bouwstra, 2002, Phase behavior of stratum corneum lipid mixtures based on human ceramides: the role of natural and synthetic ceramide 1, J. Invest. Dermatol. sourceExperimental — accuracy not yet measured
The paper’s introductory discussion describes human ceramides 1 and 4 with the characteristic ester-linked structure as ceramides isolated from the stratum corneum. It does not establish that these classes are specific to the epidermis rather than also occurring elsewhere. (LLM, conf=0.78)
- Partly supportedcites [19] Lundborg, 2018, Human skin barrier structure and function analyzed by cryo-EM and molecular dynamics simulation, J. Struct. Biol. sourceExperimental — accuracy not yet measured
Section 4.2 (page unavailable) identifies CER EOS as a component of the human stratum corneum lipid structure, and section 4.1 reports that adding it brings the model’s lamellar periodicity closer to the observed value. The copy does not establish that EO ceramide classes are specific to the epidermis, nor does it directly show that their EO structure stabilizes the lamellae. (LLM, conf=0.83)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“EO ceramides are epidermisspecific ceramide classes, and their characteristic EO structure is important for the formation and stabilization of lipid organization in the lipid lamellae (18,19).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
What the sources say
- Partly supportedcites [18] Bouwstra, 2002, Phase behavior of stratum corneum lipid mixtures based on human ceramides: the role of natural and synthetic ceramide 1, J. Invest. Dermatol. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) concludes that human ceramide 1 plays an important role in forming the long-periodicity lamellar phase and that its acyl-chain structure affects lamellar organization. This supports the formation part of the claim, but the paper does not establish that the EO structure stabilizes an existing lipid organization. (LLM, conf=0.82)
- Partly supportedcites [19] Lundborg, 2018, Human skin barrier structure and function analyzed by cryo-EM and molecular dynamics simulation, J. Struct. Biol. sourceExperimental — accuracy not yet measured
In Results §3.1 (page not available), changing CER EOS content alters the modeled lipid lamellae’s periodicity, and a model containing 5% CER EOS best matches the cryo-EM images. Discussion §4.1 likewise says adding CER EOS helps reproduce the observed periodicity. These findings support a role in lamellar organization, but the paper does not establish that the characteristic EO structure is important for its formation or stabilization. (LLM, conf=0.83)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In that report, however, it is likely that BS, but not AS, was measured, because AS levels were determined by TLC or MS analysis without LC separation (53).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
What the sources say
- Partly supportedcites [53] Maier, 2011, Normal fur development and sebum production depends on fatty acid 2-hydroxylase expression in sebaceous glands, J. Biol. Chem. sourceExperimental — accuracy not yet measured
The Experimental Procedures (page not available) describe TLC analysis and direct injection into the mass spectrometer, supporting the claim that no LC separation preceded MS. The paper groups shorter-chain hydroxylated sphingolipids as α-hydroxy based on chain length, but does not establish that the measured material was likely BS rather than AS. (LLM, conf=0.86)
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Earlier studies have reported that ceramides with oddchain FAs exist at high levels in the SC (Fig. 3F, supplemental Table S3) (7,55).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [7] t'Kindt, 2012, Profiling and characterizing skin ceramides using reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry, Anal. Chem. source
- Could not verifycites [55] Masukawa, 2009, Comprehensive quantification of ceramide species in human stratum corneum, J. Lipid Res. sourceExperimental — accuracy not yet measured
The Methods passage lists an odd-chain ceramide, CER[N(17)S(18)], as an internal standard, not as a ceramide found at high levels in stratum corneum. Searches for odd-chain fatty acids and their abundance found no passage in our copy reporting the claimed high levels; the paper discusses quantifying ceramide species generally. (LLM, conf=0.72)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Sphingosine-and phytosphingosine-type ceramides are generated either via desaturation between the 4 and 5 positions of the LCB moiety of dihydroceramides (DS ceramides) by the desaturase DEGS1, or via hydroxylation of the same moiety at the 4 position by the hydroxylase DEGS2 (49,50).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
What the sources say
- Supportedcites [49] Omae, 2004, DES2 protein is responsible for phytoceramide biosynthesis in the mouse small intestine, Biochem. J. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [50] Ternes, 2002, Identification and characterization of a sphingolipid Δ4-desaturase family, J. Biol. Chem. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Although we focused on and quantified ceramide species containing LCBs with a C18 chain length, LCBs with different chain lengths (C14-C26) reportedly exist in the epidermis (57).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
What the sources say
- Partly supportedcites [57] Pons, 2002, Gas-chromatography/mass-spectrometry analysis of human skin constituents as heptafluorobutyrate derivatives with special reference to long-chain bases, J. Lipid Res. sourceExperimental — accuracy not yet measured
Table 2 (shown under “Conclusion and Perspectives”; page unavailable) identifies LCBs with multiple chain lengths, including C16 through C26, in a human skin extract. It does not identify a C14 LCB, and the analysis is of skin extracts rather than the epidermis specifically. The claimed C14–C26 range in the epidermis is therefore only partly supported. (LLM, conf=0.88)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dehydrated AS was also detected predominantly, whereas nondehydrated OS was detected at the same levels as dehydrated OS.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Establishment of the method that specifically detects ceramide species by LC/MS/MS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In LC/MS/MS analysis using the MRM setting to detect C26:0 AS, C26:0 AS was detected in the human SC (13.20 min), while a large peak at an earlier retention time (12.86 min), instead of C26:0 AS, was detected in the mouse epidermis (Fig. 2D).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Establishment of the method that specifically detects ceramide species by LC/MS/MS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Product ions of m/z 266 and 284 were mainly produced by the fragmentation of NDS, and neither were detected in other ceramide classes.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Establishment of the method that specifically detects ceramide species by LC/MS/MS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ceramide classes with double bond(s) in their LCB (NS, NH, and NSD) were highly dehydrated, while those without double bonds (NDS and NP) were not (Fig. 2F).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Establishment of the method that specifically detects ceramide species by LC/MS/MS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The FA compositions of the human AH, AP, and mouse BS were C26:0 > C24:0 > C25:0; C24:0 > C26:0 > C25:0; and C26:0 > C28:0 > C25:0, respectively.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Different SC ceramide classes and FA composition between humans and mice
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Generally, the FA chain length of -hydroxylated ceramides (EO and -hydroxy) was C30-C34, and that of the other ceramides was C16-C30.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Different SC ceramide classes and FA composition between humans and mice
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The amounts of EO ceramides were comparable between EOS, EOH, and EOP in the human SC (Fig. 3A), whereas those of P-O ceramides were different: P-OS was the most abundant, and P-OH and P-OP were half and 1/10 of P-OS, respectively (Fig. 4A).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“C26:0 and C24:0 were the top two FAs in most ceramide classes, other than -hydroxy or EO ceramides, although C16:0 was the principal ceramide present in human AS (C16:0 > C26:0 > C24:0).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Different SC ceramide classes and FA composition between humans and mice
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Major FAs of nonhydroxy ceramides were C26:0 > C24:0 > C28:0 both in human and mouse SC (except for human NDS, which was C24:0 > C26:0 > C28:0).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Different SC ceramide classes and FA composition between humans and mice
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“FA species that constituted P-OS were C30-C34 (C30:0 > C32:0 > C32:1 in humans and C34:1 ≈ C32:0 > C32:1 in mice) (Fig. 4B).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Protein-bound ceramides in human and mouse SC
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the LC chromatogram of the synthesized (R, S) C18:0 BS, two peaks were observed at 8.63 and 8.78 min, and the latter peak was identical with C18:0 BS in the mouse epidermis (Fig. 5A).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > (R) configuration of the hydroxylated -carbon in BS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ratio of each ceramide class to total ceramides in this study was not largely different from earlier studies (supplemental Table S6).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the current study, we performed LC/MS/MS analyses and quantified free ceramides (21 classes/345 species in humans; 16 classes/268 species in mice) and P-O ceramides (5 classes/63 species in humans; 5 classes/74 species in mice) (Figs. 3, 4; supplemental Tables S2-S5), revealing the in-depth ceramide profiles of human and mouse SC.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although semiquantitative analysis of P-O ceramides by TLC and quantification of limited P-O ceramide species by LC/MS/MS have already been conducted (44-46), we successfully quantified 63 and 74 P-O ceramide species in humans and mice, respectively, leading to the elucidation of the detailed composition of P-O ceramides.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Protein-bound ceramides in human and mouse SC
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although two peaks (6.79 and 6.96 min) were also observed in (R) C14:0 BS, the latter peak was larger than the former, indicating that the former and latter peaks corresponded to (S) BS and (R) BS, respectively.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > (R) configuration of the hydroxylated -carbon in BS
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the current study, we performed LC/MS/MS analyses and quantified free ceramides (21 classes/345 species in humans; 16 classes/268 species in mice) and P-O ceramides (5 classes/63 species in humans; 5 classes/74 species in mice) (Figs. 3, 4; supplemental Tables S2-S5), revealing the in-depth ceramide profiles of human and mouse SC.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, phytosphingosine-and 6-hydroxy sphingosine-type ceramides were at very low and undetectable levels, respectively, in the mouse SC (Fig. 3; supplemental Tables S2, S3).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Consistent with earlier reports (43,44), in humans, P-OS was predominant (64% of total P-O ceramides), followed by P-OH (28%) (Fig. 4A; supplemental Tables S4, S5).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Protein-bound ceramides in human and mouse SC
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mouse EOS and OS contained C32:0 > C30:0 > C34:1 and C32:0 > C34:1 > C30:0, respectively.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Different SC ceramide classes and FA composition between humans and mice
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The main constituents of lipid lamellae are ceramides, cholesterol, and FFAs, of which ceramides account for 50% by weight (4).”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Abstract
What the sources say
- Not checked — no full text of the sourcecites [4] Yardley, 1981, Lipid composition and metabolism in normal and diseased epidermis, Pharmacol. Ther. source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“From this result, although a matrix effect (suppression of ionization) is caused by the tape-derived coextracts, this effect can be nullified by reducing the tape size to 50 mm 2 or less.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > Establishment of the method that specifically detects ceramide species by LC/MS/MS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because P-O ceramides are derived from EO ceramides, the difference in LCB composition between EO and P-O ceramides indicates that the conversion efficiency of EO to P-O ceramides varies depending on the LCB structure (the presence of hydroxylation), presumably due to the low activities against EOP and EOH of the enzymes involved in the production of P-O ceramides.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: P-O ceramides are derived from EO ceramides.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the gene responsible for the production of 6-hydroxy sphingosine-type ceramide has not yet been identified, the absence of 6-hydroxy sphingosine-type ceramide in mice suggests that the gene involved does not exist in mice or is not expressed in the skin of mice.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > DISCUSSION
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although two peaks (6.79 and 6.96 min) were also observed in (R) C14:0 BS, the latter peak was larger than the former, indicating that the former and latter peaks corresponded to (S) BS and (R) BS, respectively.”
§ Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC/MS > (R) configuration of the hydroxylated -carbon in BS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The appropriate maintenance of the amount and composition of stratum corneum ceramides is important for normal skin barrier function.
“The appropriate maintenance of the amount and composition of SC ceramides is important for normal skin barrier function.”
The paper relies on this without support.
It is currently unclear whether 4E,14Z-sphingadiene is present in the epidermis.
“It is currently unclear whether SD is present in the epidermis.”
The paper relies on this without support.
The presence of β-hydroxy ceramides in human skin has not yet been determined.
“Although ceramides containing -hydroxy FA have recently been identified in the mouse epidermis (11,12), their presence in human skin has not yet been determined.”
The paper relies on this without support.
The degree of dehydration of each ceramide class has not yet been determined.
“However, the degree of dehydration of each ceramide class has not yet been determined.”
The paper relies on this without support.
The amounts of ceramide classes other than sphingosine-type ceramides in mice have not yet been elucidated.
“Thus, although mice have been generally utilized as a model animal for studying skin barrier function, the ceramide classes measured have primarily been sphingosine-type ceramides such as NS and EOS, and the amounts of other ceramide classes have not yet been elucidated.”
The paper relies on this without support.
The matrix effect caused by coextracted compounds from the tape is unknown.
“Although an SC sample is often collected by tape stripping, the matrix effect caused by coextracted compounds from the tape is unknown.”
The paper relies on this without support.
It is difficult to separately detect and precisely quantify a tremendous number of ceramide species by LC/MS.
“However, it is difficult to separately detect and precisely quantify such a tremendous number of ceramide species by LC/MS.”
The paper relies on this without support.
P-O ceramides are derived from EO ceramides.
“Because P-O ceramides are derived from EO ceramides, the difference in LCB composition between EO and P-O ceramides indicates that the conversion efficiency of EO to P-O ceramides varies depending on the LCB structure (the presence of hydroxylation), presumably due to the low activities against EOP and EOH of the enzymes involved in the production of P-O ceramides.”
The paper relies on this without support.
The amounts of SD-type ceramides and BS were previously unknown.
“Although the amounts of SDtype ceramides and BS were previously unknown, we determined them for the first time (Fig. 3; supplemental Tables S2, S3).”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
NSD synthesis incubation time differs between Methods and Fig. 2
MinorThe Methods specify a 30-minute incubation for NSD synthesis, while the Fig. 2 caption specifies 1 hour for the same synthesis.
“For NSD synthesis, the membrane fraction (50 µg) prepared from the cells overexpressing CERS5 was mixed with 1 µM SD and 1 µM C16:0-CoA (Merck) (total volume: 50 µl) and incubated (37°C, 30 min).”
“C16:0 NSD was synthesized by incubating 1 µM SD and 1 µM C16:0-CoA with membrane fractions (50 µg) prepared from HEK 293T cells overexpressing CERS5 at 37°C for 1 h (B).”
Citations
Cites
The cornified envelope: a model of cell death in the skin
Candi, E., Schmidt, R., & Melino, G. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1619 · Cited by 1,776
Ebola virus entry requires the cholesterol transporter Niemann–Pick C1
Carette, J. E., Raaben, M., Wong, A., Herbert, A. S., Obernosterer, G., Mulherkar, N., Kuehne, A. I., Kranzusch, P. J., Griffin, A. M., Ruthel, G. T., et al. (2011) · Nature · doi:10.1038/nature10348 · Cited by 1,327
Imokawa, G., Abe, A., Jin, K., Higaki, Y., Kawashima, M., & Hidano, A. (1991) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12470233 · Cited by 1,040
Janssens, M., van Smeden, J., Gooris, G. S., Bras, W., Portale, G., Caspers, P. J., Vreeken, R. J., Hankemeier, T., Kezic, S., Wolterbeek, R., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p030338 · Cited by 488
Very long-chain fatty acids: elongation, physiology and related disorders
Kihara, A. (2012) · The Journal of Biochemistry · doi:10.1093/jb/mvs105 · Cited by 453
Self-citationPruett, S. T., Bushnev, A. S., Hagedorn, K., Adiga, M., Haynes, C. A., Sullards, M. C., Liotta, D. C., & Merrill, A. H. (2008) · Journal of Lipid Research · doi:10.1194/jlr.r800012-jlr200 · Cited by 450
Changes in the Ceramide Profile of Atopic Dermatitis Patients
Ishikawa, J., Narita, H., Kondo, N., Hotta, M., Takagi, Y., Masukawa, Y., Kitahara, T., Takema, Y., Koyano, S., Yamazaki, S., et al. (2010) · Journal of Investigative Dermatology · doi:10.1038/jid.2010.161 · Cited by 372
Characterization of overall ceramide species in human stratum corneum
Masukawa, Y., Narita, H., Shimizu, E., Kondo, N., Sugai, Y., Oba, T., Homma, R., Ishikawa, J., Takagi, Y., Kitahara, T., et al. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800014-jlr200 · Cited by 322
Metabolism of Very Long-Chain Fatty Acids: Genes and Pathophysiology
Sassa, T., & Kihara, A. (2014) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2014.017 · Cited by 302
Self-citationWeerheim, A., & Ponec, M. (2001) · Archives of Dermatological Research · doi:10.1007/s004030100212 · Cited by 302
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–129 of 129
Williams, S. F., Andrew, P., Brown, K., Chittock, J., Pinnock, A., Poyner, A., Cork, M. J., & Danby, S. G. (2025) · Experimental Dermatology · doi:10.1111/exd.70192 · Cited by 6
Ge, F., Jian, J., Li, N., Yang, J., Chao, Y., & Dong, X. W. (2025) · Analytica Chimica Acta · doi:10.1016/j.aca.2025.344099 · Cited by 2
Kato, S., Takeichi, T., Jojima, K., Kato, M., Omi, M., Tanahashi, K., Otsuka, A., Muro, Y., Kihara, A., & Akiyama, M. (2025) · Experimental Dermatology · doi:10.1111/exd.70130 · Cited by 2
Self-citationGut bacterial sphingolipid production modulates dysregulated skin lipid homeostasisPreprint
Lee, M.-T., Tan, X., Le, H. H., Besler, K. R., Thompson, S. D., Harris-Tryon, T. A., & Johnson, E. L. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.29.629238 · Cited by 2
Hua, X., Ficaro, M. K., Wallace, N. L., & Dai, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910698 · Cited by 1
Schoenfelder, H., Reuter, M., Evers, D.-H., Herbig, M. E., & Lunter, D. J. (2025) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.4c01245 · Cited by 1
Naylor, C. N., & Nagy, G. (2025) · International Journal of Mass Spectrometry · doi:10.1016/j.ijms.2025.117459 · Cited by 1
Batista, J. N., Lopes, D., Neves, B., Pais, R., Pinho, M., Moreira, A. S. P., Conde, T., Bonciarelli, S., Goracci, L., Dias, J., et al. (2025) · Journal of Applied Phycology · doi:10.1007/s10811-025-03641-7 · Cited by 1
Tajiri, M., Takeichi, T., Teye, K., Fukaura, R., Sugiyama, T., Ohno, Y., Shimauchi, K., Yamashiro, C., Tsutsumi, M., Natsuaki, Y., et al. (2025) · The Journal of Dermatology · doi:10.1111/1346-8138.70048 · Cited by 1
Self-citationMuller, A., Grove, K. J., Christen, I., Kreider, J., Santos, C., Hoque, S., Bidinosti, M., Hatakeyama, S., & Zhang, J. (2026) · Scientific Reports · doi:10.1038/s41598-025-31633-7 · Cited by 1
Impact of Ceramide Acyl Chain Length on Human Skin Barrier Recovery and Hydration
Gwon, D.-H., Choi, H. K., Lee, E. O., Hong, S., Park, C. S., Kim, J. W., & Liu, K. (2026) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.70795 · Cited by 1
Takada, M., Sashikawa, M., Ohno, Y., Hossain, M. R., Xie, X., Iwabuchi, K., Komine, M., Ohtsuki, M., & Imokawa, G. (2026) · The Journal of Pathology · doi:10.1002/path.70050 · Cited by 1
Self-citationSkin Lipid Dysregulation in Atopic Dermatitis and Related Inflammatory Skin Diseases
Kim, H. B., Park, J. S., Lim, C. S., Um, J., Chung, B. Y., Park, C. W., Lee, D., & Kim, H. O. (2026) · Allergy Asthma and Immunology Research · doi:10.4168/aair.2026.18.4.485 · Cited by 1
Fan, Y., Wei, C., Su, N., Ma, Y., Liu, W., Sun, P., & Shan, S. (2025) · International Journal of Cosmetic Science · doi:10.1111/ics.13065 · Cited by 2
CYP4F22 p. V215D is a novel variant causative for lamellar ichthyosis
Ishida, Y., Saeki, K., Ueda, M., et al. (2023) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.19680
Lipidomic profiling of cutaneous surface lipid alterations in sensitive scalp in Beijing
Li, R., Jiao, Q., Song, L., He, Y., He, H., Zhou, C., & Jia, Y. (2025) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2025.105551
Frame, C. O., Iacovella, C. R., Moore, D. J., Bunge, A. L., & McCabe, C. (2026) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2026.126573
Sodium ion-assisted structural lipidomics for sphingolipid profilingPreprint
Takeda, H., Asakawa, D., Takeuchi, M., & Tsugawa, H. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.02.703417
Yadav, N., Nautiyal, V., Widyowati, R., Ekasari, W., Asif, A. H., & Bhatt, H. (2026) · Springer eBooks · doi:10.1007/978-981-95-7358-5_2
Kang, B.-G., Wu, Z., Lee, D., Cho, Y., Lee, T., & Liu, K. (2026) · Journal of Analytical Science & Technology · doi:10.1186/s40543-026-00542-3
Xu, F., Li, Y., He, T.-Y., et al. (2026) · ACS Omega · doi:10.1021/acsomega.6c00065
Carreras, J. G., Caballé, M., Leivar, P., et al. (2026) · New Biotechnology · doi:10.1016/j.nbt.2026.06.005
Bouayadi, S., Arbey, E., Raynaud, E., Ávila, J., Rolland, G., Lynch, B., Baltenneck, C., Rieux, E., Saussine, A., Bourland, J., et al. (2026) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2026.07.007
Beres, R. L., Setchell, K. D. R., Mouzaki, M., & Zhao, X. (2026) · Journal of Personalized Medicine · doi:10.3390/jpm16070391
Chemogenetic Activation of G 12 Signaling Thickens the Epidermis With Enhanced Barrier Function
Kamakura, N., Hirai, N., Arai, K., Du, Y., Kogame, T., Ohno, Y., Kihara, A., Kabashima, K., & Inoue, A. (2026) · FASEB BioAdvances · doi:10.1096/fba.2026-00042
Self-citationKojima, A., Sugiyama, T., Ito, Y., Otsuka, K., Ohno, Y., & Kihara, A. (2026) · The FASEB Journal · doi:10.1096/fj.202602245r
Self-citationZheng, Y., Li, J., Wang, J., Zhang, J., Tang, Z., Chen, S., Wu, Z., An, Q., Wu, H., Wang, Y., et al. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158768
Yang, Q., & Zhang, W. (2026) · Acta Dermatovenerologica Alpina Pannonica et Adriatica · doi:10.15570/actaapa.2026.33
Eichner, A., Hauß, T., Havrišák, T., Demé, B., & Opálka, L. (2026) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2026.127469
Metadata
- Authors
- Kawana, M., Miyamoto, M., Ohno, Y., & Kihara, A.
- Affiliations
- Hokkaido University (JP)
- Corresponding author
- Ohno, Yusuke
- Kihara, Akio
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 61
- Issue
- 6
- Pages
- 884-895
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC7269764
- OpenAlex
- W3015053316
- Semantic Scholar
- d636fe0987fbf6e6a53d593f9c3e15494bebdae9
- Cited by
- 129
- References
- 57
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 31 · 2023: 23 · 2022: 17 · 2021: 19 · 2020: 2
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- PubMed Central (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion, cc-by)
- Funders
- Japan Agency for Medical Research and Development (JP18H03976, JP15H05589)
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- ceramide, stratum corneum, skin barrier function, human-mouse comparison, phytosphingosine, fatty acid elongation, HAP1 cells
- MeSH terms
- Lipidomics, Animals, Ceramides, Chromatography, Liquid, Epidermis, Humans, Mice, Tandem Mass Spectrometry
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-23, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-23 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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