2001, Kainz et al. 2004, Kelly and Scheibling 2012). Thus, consumers must obtain essential FAs from their diet. Several PUFAs are essential for a wide array of animal taxa (Bergé and Barnathan 2005) and have received intense attention, e.g., ALA (18:3n-3), PDE inhibitor EPA (20:5n-3), and DHA (22:6n-3; Guschina and Harwood 2006, 2009, Parrish 2009). Phytoplankton FA composition is determined by both genotypic and phenotypic characteristics (Dalsgaard et al. 2003). FAs are well-known taxonomic indicators at the class but not at the species level. Dalsgaard et al. (2003) compared the patterns of FA similarities among eight classes of phytoplankton. In their study, the FA composition of each algal

class was obtained by pooling FA data of different species from the same algal class. Although this comprehensive comparison showed specific FA markers for each algal class, this method omitted the information on potential effects of culture conditions on phytoplankton FA composition. Laboratory studies have shown intraspecific variation in FA profiles of phytoplankton under different culture conditions (e.g., Piorreck and Pohl 1984, Cohen et al. 1988, Thompson et al. 1990, Ahlgren and Hyenstrand 2003, Piepho et al. 2012), while variation between phytoplankton classes in response to combinations of multiple ambient

factors remains unclear. Mesocosm experiments conducted in marine (Hopavagen lagoon, Norway), brackish (Kiel Fjord, Germany) and freshwater (Lake Schöhsee, Germany) systems showed that N:P supply www.selleckchem.com/products/acalabrutinib.html ratios influenced FA contents in phytoplankton, as well as the ratio between SFAs, MUFAs, and PUFAs (Brepohl 2005). However, it has been suggested that there is no direct effect of nutrient limitation on FA synthesis of phytoplankton, but rather a direct impact of limited growth rates caused by nutrient limitation (Guschina and Harwood 2009, Piepho et al. 2012). Although Ahlgren and Hyenstrand (2003)

reported the interactive effect of N concentrations and growth rates on freshwater algae, no attempts have been made to simultaneously study responses of FA 上海皓元医药股份有限公司 composition in marine phytoplankton to wide ranges of N:P supply ratios and growth rates. In addition, the use of different units to quantify FA composition in earlier studies makes comparisons difficult, and in some cases may even have resulted in seemingly contradictory findings. The choice of unit depends on the aim of the study. For example, FAs are best quantified on a per cell basis when focusing on cell physiology, while FA data per unit biomass (often measured in carbon content) is an ideal approach when considering food quality of algae for herbivores (Piepho et al. 2012). In this study, we chose three marine phytoplankton species representing three algal classes, Rhodomonas sp. (Cryptophyceae), Isochrysis galbana (Prymnesiophyceae; Parke 1949), and Phaeodactylum tricornutum (Bacillariophyceae).

Prokinetics click here may provide symptom relief in some functional dyspepsia patients. (SeeFig. 2) Grade of evidence: moderate. Strength of recommendation: do it. Level of agreement: a: 90.0%; b: 10.0%; c: 0%; d: 0%; e: 0%; f: 0%. Prokinetic agents,

such as metoclopramide, domperidone, trimebutine, cisapride, itopride, mosapride, levosulpiride and cinitapride, can stimulate digestive tract motility via different mechanisms of action. Use of cisapride is currently restricted in most Asian countries because of its cardiovascular complications. Because delayed gastric emptying is considered a potential contributing factor to FD symptoms, prokinetic agents are often used in FD. In a meta-analysis from the Cochrane library that included 24 randomized controlled trials with 3178 patients, the efficacy of prokinetics was superior to placebo (57% vs 47%).93 However, studies on prokinetics in FD had limitations due to the high degree of heterogenicity and small sample size.93,174 The clinical trial data for the new drug acotiamide showed a clear margin of symptom improvement compared with placebo, and may I-BET-762 solubility dmso be approved for FD of the postprandial distress syndrome subtype.175,176 Statement 27. Some studies from Asia reported that herbal medications provide symptom relief in functional dyspepsia. (SeeFig. 2) Grade of evidence: moderate. Strength of recommendation: probably do it. Level of agreement: a: 60.0%; b: 40.0%; c: 0%; d: 0%; e: 0%; f: 0%. Limited

studies have shown potential benefit of herbal medicines for symptom relief in FD patients. In a meta-analysis that included 33 studies of the efficacy of xiaoyao san (XS),177 a well-known traditional Chinese herbal formula for FD treatment, modified XS without (OR 3.26; 95% CI, 2.24 to 4.47) or with (OR 4.32; 95% CI, 2.64 to 7.08) prokinetics significantly reduced symptoms

compared with prokinetics alone. However, the reporting of quality issues in these studies was generally poor. These studies are usually non-randomized, non-blinded and without placebo control. Therefore, high-quality controlled trials are required to assess the effects of XS in comparison to placebo. Another relatively small-scaled but placebo-controlled study from Japan demonstrated the efficacy of the Japanese MCE公司 herbal medicine rikkunshito (TJ-43) in reducing GI symptoms in FD patients and accelerating gastric emptying.178 This medicine was found to improve gastric accommodation in a study using extracorporeal ultrasonography.179 Statement 28. Anti-depressant and anxiolytic agents have a role in the management of functional dyspepsia, despite the limited evidence. (SeeFig. 2) Grade of evidence: low. Strength of recommendation: probably do it. Level of agreement: a: 80.0%; b: 20.0%; c: 0%; d: 0%; e: 0%; f: 0%. Evidence supporting the use of psychotherapy in treatment of FD is inconsistent and weak.180 As for pharmacological therapies, only limited studies of anti-depressants or anxiolytic drugs are available.

Consistent with the current report, neither liver nor adipose tissue insulin resistance was different when Hispanics were compared with Caucasians, although muscle insulin-stimulated glucose disposal was somewhat lower in Hispanics. Both groups had well matched aminotransferase BAY 73-4506 ic50 levels and the same proportion of patients with increased liver aminotransferase levels. As in previous reports,3,

5, 7, 13 liver aminotransferase levels were not sensitive enough to assist in the detection of NAFLD, as the majority of patients with NASH had normal liver enzymes. Moreover, we found no correlation between plasma AST/ALT and insulin resistance at any level (i.e., hepatic, adipose tissue, or muscle). In addition, the correlation of AST/ALT with liver fat content by MRS and the overall NAS was weak and not significant, questioning the clinical value as a test for the screening of follow-up of NASH patients. This study does have

some limitations. First, African Americans were not included. This is because the ethnic mix of the San Antonio area is 61% Hispanic, 30% Caucasian and only 9% African American and other ethnicities. Therefore, we were unable to study enough African American patients to make a conclusive assessment relative to Hispanics and Caucasians. It must also be kept in mind that the Hispanic group was largely composed of patients of Mexican American ancestry, hence the findings may not apply to other Hispanic populations. BGJ398 Future work will clarify the impact of other ethnic backgrounds in NASH. Second, although there was no major insulin sensitivity

nor were there histological differences between patients of Hispanic and Caucasian ancestry, there was a trend among Hispanics to have worse hepatic insulin resistance and for diabetics to have more severe liver fibrosis on histology. This deserves further evaluation in relation to potential pharmacological treatment response, particularly insulin sensitizers such as pioglitazone. More pronounced insulin resistance or fibrosis in Hispanics may highlight a group in need of treatment at an earlier stage, either because they may be more likely to respond to thiazolidinedione therapy or be at greater risk of liver fibrosis. 上海皓元医药股份有限公司 Pioglitazone has proven to reverse hepatic insulin resistance in previous studies from our laboratory13 and others.36 Unfortunately, the relatively small number of subjects studied in our previous proof-of-concept study (n = 55 of which 50% were Hispanic)13 and the few Hispanics enrolled in the PIVENS study (37/247 [15%])36 do not allow firm conclusions at this time. Ongoing studies will likely shed light on this issue in the future.37, 38 Third, we only reported on overweight and obese subjects with NAFLD, though they represent the vast majority of patients affected.

Tumor formation by Hep3B and Huh7 cells in nude mice was dose-dependently suppressed by CRM197 (1mg/kg), both when the inhibitor was administered beginning on the day of cell inoculation (39% of control click here for Hep3B and 42% for Huh7) or when the tumor diameter reached about 5 mm after inoculation (53% for HepB3 and 57% for Huh7). Conclusion:

These data suggest that HB-EGF is a novel molecular target for treatment of human HCC. Reference 1: Inui Y, Kawata S, et al. Expression of heparin-binding epidermal growth factor in human hepatocellular carcinoma. Gastroenterology 1994; 107: 1799–804 Reference 2: Kiso S, Kawata S, et al. Liver regeneration in heparin-binding EGF-like growth factor trans-genic mice after partial hepatectomy. Gastroenterology 2003; 124: 701–7 Reference 3: Mitamura T, Higashiyama S, et al. Diphtheria toxin binds to the epidermal growth factor (EGF)-like domain of human heparin-binding EGF-like growth factor/diphtheria toxin receptor and inhibits specifically its mitogenic activity. J Biol Chem 1995; 270: 1015–9 This study was collaborated BGB324 mouse with Prof. Eisuke Mekada, Department of Cell Biology, Research Institute for Microbial

Diseases, Osaka University. Disclosures: Yoshiyuki Ueno – Advisory Committees or Review Panels: Jansen The following people have nothing to disclose: Sumio Kawata, Satoshi Ugajin, Junji Yokozawa, Hisayoshi Watanabe, Takafumi Saito, Yoshiaki Inui Background and aims: 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a tumor suppressor in some cancers. However, no data are available regarding 15-PGDH expression in hepatocellular carcinoma

(HCC). We aimed to assess the potential role of 15-PGDH in HCC. Materials and methods: HCC cells lines were treated with EGF, HGF or different pharmacological inhibitors and vehicle as control. COX-2, mPGES-1 and 15-PGDH 上海皓元 expression were analyzed by qPCR and Western-blot. Additionally, we induced 15-PGDH overexpres-sion or silencing in a hepatoma cell line, to test in vitro cell viability, cell cycle and apoptosis markers, so as to assess tumor growth in vivo in athymic nu/nu mice. Furthermore, this study comprised a chemical model of liver cancer induced with diethylnitrosamine, a mouse model of accelerated hepatocar-cinogenesis and human HCC biopsies where 15-PGDH expression was evaluated. Results: 15-PGDH was downregulated in human hepatoma cells with a high COX-2 and mPGES-1 expression. Moreover, EGF and HGF increased COX-2 and mPGES-1 levels and suppressed 15-PGDH expression by mainly involving ERK and p38MAPK activation. Besides, 15-PGDH expression was decreased in chemical and genetic murine models of HCC and in human HCC biopsies.

We found a 55% metabolic increase over the course of pregnancy that was better explained by maternal relative reproductive

effort (relative litter mass) when compared with absolute estimates (litter mass, litter size). After parturition, female metabolism dropped below values recorded at early pregnancy and this decrease was closely related to maternal relative reproductive effort. Our estimates for MCP ranged from 13.9 to 14.7% of maternal metabolic rate, suggesting that specific energetic demands of pregnancy are significant. It appears crucial to consider both direct (MCP) and indirect (thermoregulatory shift) components to evaluate overall maternal metabolic demand during pregnancy.

Because females are already emaciated at the onset of pregnancy, these combined AUY-922 mw constraints are likely costly by inducing structural protein mobilization and altered performances after find more parturition. “
“The ability to assess and avoid predation risk is thought to be a major determinant of behavior for small mammals. We assessed the antipredator responses of three Neotropical rodent species (Heteromys desmarestianus, Peromyscus mexicanus and Melanomys caliginosus) to cues (feces or actual presence) of the snake Bothrops asper. We investigated whether rodents avoided entering or spent less time in snake-cued areas using an experimental arena, and whether rodents reduced foraging efforts (measured by giving-up density) in snake-cued areas under laboratory, 上海皓元医药股份有限公司 semi-natural and field conditions. P. mexicanus and M. caliginosus did not demonstrate any snake avoidance, and did not reduce foraging efforts under any conditions. H. desmarestianus

significantly avoided live snakes only at very short distances (<20 cm), and reduced foraging efforts in the presence of snakes only under certain experimental conditions. These results are in contrast to many studies demonstrating antipredator behavior by small mammals in temperate and desert ecosystems in response to cues of predators, including snakes, and were influenced by overall low statistical power. This discrepancy may also be explained by the complexity of tropical forest systems, as rodents must assess a myriad of sensory cues and balance risk from multiple predator groups that require different avoidance strategies. An ambush-hunting snake such as B. asper may also face strong selective pressure to avoid detection by its mammalian prey. "
“Seasonally reproducing animals show many behavioural and physiological changes during the mating period, including increased signalling for mate attraction.

We found a 55% metabolic increase over the course of pregnancy that was better explained by maternal relative reproductive

effort (relative litter mass) when compared with absolute estimates (litter mass, litter size). After parturition, female metabolism dropped below values recorded at early pregnancy and this decrease was closely related to maternal relative reproductive effort. Our estimates for MCP ranged from 13.9 to 14.7% of maternal metabolic rate, suggesting that specific energetic demands of pregnancy are significant. It appears crucial to consider both direct (MCP) and indirect (thermoregulatory shift) components to evaluate overall maternal metabolic demand during pregnancy.

Because females are already emaciated at the onset of pregnancy, these combined PLX4032 datasheet constraints are likely costly by inducing structural protein mobilization and altered performances after Maraviroc mw parturition. “
“The ability to assess and avoid predation risk is thought to be a major determinant of behavior for small mammals. We assessed the antipredator responses of three Neotropical rodent species (Heteromys desmarestianus, Peromyscus mexicanus and Melanomys caliginosus) to cues (feces or actual presence) of the snake Bothrops asper. We investigated whether rodents avoided entering or spent less time in snake-cued areas using an experimental arena, and whether rodents reduced foraging efforts (measured by giving-up density) in snake-cued areas under laboratory, medchemexpress semi-natural and field conditions. P. mexicanus and M. caliginosus did not demonstrate any snake avoidance, and did not reduce foraging efforts under any conditions. H. desmarestianus

significantly avoided live snakes only at very short distances (<20 cm), and reduced foraging efforts in the presence of snakes only under certain experimental conditions. These results are in contrast to many studies demonstrating antipredator behavior by small mammals in temperate and desert ecosystems in response to cues of predators, including snakes, and were influenced by overall low statistical power. This discrepancy may also be explained by the complexity of tropical forest systems, as rodents must assess a myriad of sensory cues and balance risk from multiple predator groups that require different avoidance strategies. An ambush-hunting snake such as B. asper may also face strong selective pressure to avoid detection by its mammalian prey. "
“Seasonally reproducing animals show many behavioural and physiological changes during the mating period, including increased signalling for mate attraction.

This distinguishes this signature with regard to long-term outcome, compared to the clinical situation early post-OLT. Acute cellular rejection (ACR) is difficult to distinguish from HCV recurrence, based on analysis of patient liver biopsies, as a result of common histological features. Previous studies comparing HCV

patients with and without ACR demonstrate that many of the BIBW2992 mouse repressed genes are significantly up-regulated during ACR in HCV patients.3, 14 Additionally, repression of innate and inflammatory genes was characteristic of HCV recurrence, rather than ACR, in HCV transplant patients.15 This indicates that though short-term clinical factors, such as ACR, may confound long-term efforts to develop molecular signatures of liver disease pathogenesis, repression

of these innate immune genes is more widespread and of greater magnitude. Immune repression early in infection see more may contribute to increased hepatocyte infection during HCV recurrence and thus may create a more favorable environment for progression to severe disease. Although antigen presentation has been associated with HCV pathogenesis,16-18 these pathways are normally suppressed by allograft rejection drugs, causing impaired T-cell responses in HCV transplant patients. However, it is difficult to determine the effect of specific immunosuppressive regimens, because patients are routinely treated with different drugs and dosing regimens. Generally, the immunosuppressive regimens used are less likely to repress innate immune responses that could attenuate the severity of HCV recurrence. Innate immune

antagonism by HCV infection may result in the virus eliciting a transcriptional program that eventually results in fibrosis and disease progression, which is partially reflected by the increase in inflammatory genes over time caused by infiltrating leukocytes. HCV facilitates its replication by antagonizing the induction of antiviral interferons, ISGs, and antiviral cytokines through the action of the viral nonstructural protein (NS)3/4 protease and NS5A.19-22 Clinicians have not routinely treated HCV patients with post-OLT ribavirin and pegylated interferon, primarily because the high expense and harsh side effects of this treatment regimen do not justify its use in patients recovering from organ transplantation. However, MCE公司 a recent study demonstrated that post-OLT treatment resulted in stable or improved fibrosis scores, even in some patients who did not demonstrate sustained virologic response.23 Our data indicating that repressed antiviral gene expression early in infection determines transition to severe disease suggests that patients may benefit from early therapeutic intervention during HCV recurrence to boost innate immune genes not effected by immunosuppressant drugs during the first 3 months post-OLT. Early repression of cell-division mediators in patients who progress also indicates that these transcriptional profiles are altered.

This distinguishes this signature with regard to long-term outcome, compared to the clinical situation early post-OLT. Acute cellular rejection (ACR) is difficult to distinguish from HCV recurrence, based on analysis of patient liver biopsies, as a result of common histological features. Previous studies comparing HCV

patients with and without ACR demonstrate that many of the Talazoparib chemical structure repressed genes are significantly up-regulated during ACR in HCV patients.3, 14 Additionally, repression of innate and inflammatory genes was characteristic of HCV recurrence, rather than ACR, in HCV transplant patients.15 This indicates that though short-term clinical factors, such as ACR, may confound long-term efforts to develop molecular signatures of liver disease pathogenesis, repression

of these innate immune genes is more widespread and of greater magnitude. Immune repression early in infection RAD001 cost may contribute to increased hepatocyte infection during HCV recurrence and thus may create a more favorable environment for progression to severe disease. Although antigen presentation has been associated with HCV pathogenesis,16-18 these pathways are normally suppressed by allograft rejection drugs, causing impaired T-cell responses in HCV transplant patients. However, it is difficult to determine the effect of specific immunosuppressive regimens, because patients are routinely treated with different drugs and dosing regimens. Generally, the immunosuppressive regimens used are less likely to repress innate immune responses that could attenuate the severity of HCV recurrence. Innate immune

antagonism by HCV infection may result in the virus eliciting a transcriptional program that eventually results in fibrosis and disease progression, which is partially reflected by the increase in inflammatory genes over time caused by infiltrating leukocytes. HCV facilitates its replication by antagonizing the induction of antiviral interferons, ISGs, and antiviral cytokines through the action of the viral nonstructural protein (NS)3/4 protease and NS5A.19-22 Clinicians have not routinely treated HCV patients with post-OLT ribavirin and pegylated interferon, primarily because the high expense and harsh side effects of this treatment regimen do not justify its use in patients recovering from organ transplantation. However, 上海皓元 a recent study demonstrated that post-OLT treatment resulted in stable or improved fibrosis scores, even in some patients who did not demonstrate sustained virologic response.23 Our data indicating that repressed antiviral gene expression early in infection determines transition to severe disease suggests that patients may benefit from early therapeutic intervention during HCV recurrence to boost innate immune genes not effected by immunosuppressant drugs during the first 3 months post-OLT. Early repression of cell-division mediators in patients who progress also indicates that these transcriptional profiles are altered.

3). For example, brain growth in precocial sheep (Ovis aries) and altricial wolves (Canis lupus) proceeds according to the same general pattern (Fig. 3, Table 3), but in the sheep, a larger proportion of brain growth is completed

in utero (Mangold-Wirz 1966, Schleifenbaum 1973, Kruska 2005, Watson et al. 2006). The pattern of brain growth in the Weddell seal and other pinnipeds is presumably similar to that of sheep, but with an even greater proportion of growth completed prenatally. Thus Weddell seals attain ca. 70% of adult brain size at the time of birth, Trametinib cell line a relative size attained in sheep at ca. 30 d and in wolves at ca. 60 d postnatum (Fig. 3). Neurophysiological studies also indicate that brain function is exceptionally advanced in newborn Weddell seals compared with other mammals (Gruenau et al. 1975). The growth of the mammalian brain is generally complete (Fig. 3) before adult body size is reached (Kruska 2005), and cessation of cranial growth is evident in the closure of cranial sutures. The same pattern of suture closure appears to occur in pinnipeds including Weddell seals (Lindsey 1937, Tedman 2003, Brunner et al. 2004), but actual brM data are needed to confirm this assumption. 0.336 0.363c 9.75 10.36c 7.65

10.3c 1.196 1.876c 23 28 4.4 3.5 430j 480j 222.5j 343.2j 302j 355j 40.68q 227.0j 362j 405j 91.00j 300.0j 196r 213r 4,900r 5,800r 324r 365j,r 34.10r 140.0r Comparing brM among mammalian neonates is complicated by the fact that species are born at different medchemexpress stages of developmental maturity. A common metric for assessment of neonatal brain size is the multiplication factor (MF), i.e., the ratio of adult mTOR inhibitor brain mass: neonatal brain mass (Mangold-Wirz 1966). Generally, species with brain MF values of 6 or greater are classified as altricial, whereas species with MF values of <5 are considered precocial (Mangold-Wirz 1966, Kruska 2005). Terrestrial carnivores typically give birth to altricial neonates with high MF values ranging from ~6 in the domestic cat (Felis silvestris f. dom.) to 35–58 in the Ursidae (Mangold-Wirz 1966; Table 3

and references therein). By contrast, pinnipeds are morphologically precocial at birth, with MF values <2. Based on the results reported here and previously (Table 2, 3), neonatal Weddell seals have an MF of 1.4, the lowest value reported to date for any mammal. Due to the paucity of neonatal brM data, it is difficult to determine the extent to which brain development in Weddell seals is representative of pinnipeds in general (Table 3). However, a comparison to hooded seals (Phocidae: Cystophora cristata) is instructive. Considering metrics other than MF, newborn hooded seals pups are among the most precocial of mammals: they are large (10%–12% of maternal BM compared to the phocid average of ~9%; Oftedal et al. 1993, Mellish et al. 1999, Schulz and Bowen 2005), close to chemically mature, as indicated by the water content of fat-free mass (Moulton 1923, Widdowson 1950, Oftedal et al.

3). For example, brain growth in precocial sheep (Ovis aries) and altricial wolves (Canis lupus) proceeds according to the same general pattern (Fig. 3, Table 3), but in the sheep, a larger proportion of brain growth is completed

in utero (Mangold-Wirz 1966, Schleifenbaum 1973, Kruska 2005, Watson et al. 2006). The pattern of brain growth in the Weddell seal and other pinnipeds is presumably similar to that of sheep, but with an even greater proportion of growth completed prenatally. Thus Weddell seals attain ca. 70% of adult brain size at the time of birth, CP-690550 a relative size attained in sheep at ca. 30 d and in wolves at ca. 60 d postnatum (Fig. 3). Neurophysiological studies also indicate that brain function is exceptionally advanced in newborn Weddell seals compared with other mammals (Gruenau et al. 1975). The growth of the mammalian brain is generally complete (Fig. 3) before adult body size is reached (Kruska 2005), and cessation of cranial growth is evident in the closure of cranial sutures. The same pattern of suture closure appears to occur in pinnipeds including Weddell seals (Lindsey 1937, Tedman 2003, Brunner et al. 2004), but actual brM data are needed to confirm this assumption. 0.336 0.363c 9.75 10.36c 7.65

10.3c 1.196 1.876c 23 28 4.4 3.5 430j 480j 222.5j 343.2j 302j 355j 40.68q 227.0j 362j 405j 91.00j 300.0j 196r 213r 4,900r 5,800r 324r 365j,r 34.10r 140.0r Comparing brM among mammalian neonates is complicated by the fact that species are born at different 上海皓元医药股份有限公司 stages of developmental maturity. A common metric for assessment of neonatal brain size is the multiplication factor (MF), i.e., the ratio of adult ABT-199 concentration brain mass: neonatal brain mass (Mangold-Wirz 1966). Generally, species with brain MF values of 6 or greater are classified as altricial, whereas species with MF values of <5 are considered precocial (Mangold-Wirz 1966, Kruska 2005). Terrestrial carnivores typically give birth to altricial neonates with high MF values ranging from ~6 in the domestic cat (Felis silvestris f. dom.) to 35–58 in the Ursidae (Mangold-Wirz 1966; Table 3

and references therein). By contrast, pinnipeds are morphologically precocial at birth, with MF values <2. Based on the results reported here and previously (Table 2, 3), neonatal Weddell seals have an MF of 1.4, the lowest value reported to date for any mammal. Due to the paucity of neonatal brM data, it is difficult to determine the extent to which brain development in Weddell seals is representative of pinnipeds in general (Table 3). However, a comparison to hooded seals (Phocidae: Cystophora cristata) is instructive. Considering metrics other than MF, newborn hooded seals pups are among the most precocial of mammals: they are large (10%–12% of maternal BM compared to the phocid average of ~9%; Oftedal et al. 1993, Mellish et al. 1999, Schulz and Bowen 2005), close to chemically mature, as indicated by the water content of fat-free mass (Moulton 1923, Widdowson 1950, Oftedal et al.