Development of the Physiology Professional Skills Curriculum Mapping Tool (PS-MAP).

During the course of undergraduate studies, physiology (and related STEM) majors should acquire a both broad and in-depth foundation in physiological knowledge along with a distinct range of transferable (professional) skills (e.g., critical thinking, communication skills, data analysis). Previously, through a consultative and iterative process with physiology educators, the Professional Skills Committee of the Physiology Majors Interest Group (PMIG) defined and refined a consensus list of professional skills that physiology majors should acquire during their program of study. Here we describe the development and beta testing of a convenient tool to enable physiology and physiology-related program educators to map these professional skills across their curricula. The tool, referred to as PS-MAP, uses the Qualtrics platform and allows programs to collect and organize data about whether students are provided the opportunity to learn and develop the defined professional skills during their undergraduate experience. The authors have made the PS-MAP tool freely available to educators and provide practical tips for its implementation. Use of the PS-MAP tool and the data collected can help programs identify curricular strengths and gaps as well as facilitate curricular discussions among educators within the program.NEW & NOTEWORTHY In addition to foundational physiology knowledge, undergraduate physiology and related STEM majors should develop a range of transferable professional skills. However, evidence of this curricular goal has been lacking. Therefore, the Professional Skills Committee of the Physiology Majors Interest Group (PMIG) developed the freely available and convenient Physiology Professional Skills Curriculum Mapping Tool (PS-MAP) to assist educators in mapping these professional skills throughout their programs.

Relationships between prostaglandin concentrations, a single nucleotide polymorphism in HSD17B12, and reproductive performance in dairy cows.

Prostaglandins are involved in multiple processes important for fertility, with previous work in mice highlighting a potential role for the HSD17B12 gene in prostaglandin biosynthesis. This study aimed to determine the associations among circulating prostaglandin concentrations, a missense SNP in the HSD17B12 gene predicted to disrupt protein function, and fertility traits in first-lactation Holstein-Friesian dairy cows. We used a study population of approximately 500 animals specifically bred to have either a positive (POS, +5%) or negative (NEG, -5%) genetic merit for fertility (FertBV). Genotypes of a previously identified SNP (rs109711583) in HSD17B12 were determined, with 116 animals genotyped as AA, 215 genotyped as AG, and 153 genotyped as GG. Plasma concentrations of prostaglandin E2 and the PGF2α metabolite PGFM were determined at 3 time points (12 mo of age, 4 d postpartum, and 5 wk postpartum during first lactation) in a selection of animals with AA and GG genotypes from both the POS and NEG FertBV groups (n = 33-40 in each genotype for each FertBV group). Binary reproductive traits (yes or no) examined included submission for artificial breeding in the first 3 or 6 wk of the seasonal breeding period; conception to first service; conception during the first 6 wk of the breeding period; and pregnant at the end of the breeding period. Uterine health at 6 wk after calving was examined by evaluating the percentage of polymorphonuclear leukocytes following uterine cytology and by scoring vaginal discharge based on the presence of purulent material. The 3-wk submission rate was increased in animals that carried the G allele of the missense SNP in HSD17B12, but no differences were present among genotypes for 6-wk submission rate. The trait was additive, with each increase of the G allele increasing the 3-wk submission rate by 6 to 7%. We did not observe any consistent associations between SNP alleles and circulating PGE2 concentrations; however, a complex 3-way interaction among time, fertility group, and SNP allele was present for PGFM concentrations. Plasma concentrations of PGE2 were increased approximately 40% at 5 wk postpartum in animals that were submitted for breeding within 3 or 6 wk of the start of the breeding season, and in those that conceived during the first 6 wk of breeding, compared with those that did not. Plasma concentrations of PGFM were decreased approximately 20% in those animals that conceived to their first service and tended to be decreased in animals that were pregnant at the end of the breeding period, compared with those that were not. In summary, associations were observed between the SNP in HSD17B12 and submission rate by d 21 of the breeding season, as well as between circulating prostaglandin concentrations and fertility traits, but the SNP was not consistently linked to changes in prostaglandin concentrations. Thus, the association between submission rate by d 21 of the breeding season and the SNP in HSD17B12 were unlikely driven by changes in prostaglandins.

Metallization of Shock-Compressed Liquid Ammonia.

Ammonia is predicted to be one of the major components in the depths of the ice giant planets Uranus and Neptune. Their dynamics, evolution, and interior structure are insufficiently understood and models rely imperatively on data for equation of state and transport properties. Despite its great significance, the experimentally accessed region of the ammonia phase diagram today is still very limited in pressure and temperature. Here we push the probed regime to unprecedented conditions, up to ∼350 GPa and ∼40 000 K. Along the Hugoniot, the temperature measured as a function of pressure shows a subtle change in slope at ∼7000 K and ∼90 GPa, in agreement with ab initio simulations we have performed. This feature coincides with the gradual transition from a molecular liquid to a plasma state. Additionally, we performed reflectivity measurements, providing the first experimental evidence of electronic conduction in high-pressure ammonia. Shock reflectance continuously rises with pressure above 50 GPa and reaches saturation values above 120 GPa. Corresponding electrical conductivity values are up to 1 order of magnitude higher than in water in the 100 GPa regime, with possible significant contributions of the predicted ammonia-rich layers to the generation of magnetic dynamos in ice giant interiors.

Laser-driven shock compression of "synthetic planetary mixtures" of water, ethanol, and ammonia.

Water, methane, and ammonia are commonly considered to be the key components of the interiors of Uranus and Neptune. Modelling the planets' internal structure, evolution, and dynamo heavily relies on the properties of the complex mixtures with uncertain exact composition in their deep interiors. Therefore, characterising icy mixtures with varying composition at planetary conditions of several hundred gigapascal and a few thousand Kelvin is crucial to improve our understanding of the ice giants. In this work, pure water, a water-ethanol mixture, and a water-ethanol-ammonia "synthetic planetary mixture" (SPM) have been compressed through laser-driven decaying shocks along their principal Hugoniot curves up to 270, 280, and 260 GPa, respectively. Measured temperatures spanned from 4000 to 25000 K, just above the coldest predicted adiabatic Uranus and Neptune profiles (3000-4000 K) but more similar to those predicted by more recent models including a thermal boundary layer (7000-14000 K). The experiments were performed at the GEKKO XII and LULI2000 laser facilities using standard optical diagnostics (Doppler velocimetry and optical pyrometry) to measure the thermodynamic state and the shock-front reflectivity at two different wavelengths. The results show that water and the mixtures undergo a similar compression path under single shock loading in agreement with Density Functional Theory Molecular Dynamics (DFT-MD) calculations using the Linear Mixing Approximation (LMA). On the contrary, their shock-front reflectivities behave differently by what concerns both the onset pressures and the saturation values, with possible impact on planetary dynamos.

Comment on "Isochoric, isobaric, and ultrafast conductivities of aluminum, lithium, and carbon in the warm dense matter regime".

Dharma-wardana et al. [M. W. C. Dharma-wardana et al., Phys. Rev. E 96, 053206 (2017)2470-004510.1103/PhysRevE.96.053206] recently calculated dynamic electrical conductivities for warm dense matter as well as for nonequilibrium two-temperature states termed "ultrafast matter" (UFM) [M. W. C. Dharma-wardana, Phys. Rev. E 93, 063205 (2016)2470-004510.1103/PhysRevE.93.063205]. In this Comment we present two evident reasons why these UFM calculations are neither suited to calculate dynamic conductivities nor x-ray Thomson scattering spectra in isochorically heated warm dense aluminum. First, the ion-ion structure factor, a major input into the conductivity and scattering spectra calculations, deviates strongly from that of isochorically heated aluminum. Second, the dynamic conductivity does not show a non-Drude behavior which is an essential prerequisite for a correct description of the absorption behavior in aluminum. Additionally, we clarify misinterpretations by Dharma-wardana et al. concerning the conductivity measurements of Gathers [G. R. Gathers, Int. J. Thermophys. 4, 209 (1983)IJTHDY0195-928X10.1007/BF00502353].

Weaning practices in phenylketonuria vary between health professionals in Europe.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Early feeding practices in infants with phenylketonuria across Europe.

BACKGROUND: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. METHODS: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. RESULTS: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%. DISCUSSION: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.

Intraoperative dexamethasone alters immune cell populations in patients undergoing elective laparoscopic gynaecological surgery.

BACKGROUND: Anaesthetists use dexamethasone principally for its anti-emetic effect. The purpose of this study was to characterize the effects of a single intraoperative dose of dexamethasone on cellular and metabolic components of the immune system in patients undergoing laparoscopic surgical procedures. METHODS: In this prospective double-blind trial, female patients undergoing elective major laparoscopic surgery were randomized to receive saline (Control group, n =16) or dexamethasone 4 mg (Dexamethasone group, n =16) i.v. after the induction of anaesthesia. Inflammatory markers and immune cell counts were examined at 24 and 48 h and 6 weeks after surgery. The changes from baseline preoperative values were compared between groups using a Mann-Whitney U -test, and linear mixed models were used to validate the findings. RESULTS: No differences in concentrations of serum glucose and interleukin-6 were observed between groups after surgery. The increase in C-reactive protein concentration at 24 h after surgery was greater in the control group [median (interquartile range), 33 (25-65) vs 17 (7-26) mg dl -1 ; P =0.018]. Extensive changes in the counts of white cells, including most lymphocyte subsets, were observed 24 h after surgery, and dexamethasone appeared to attenuate most of these changes. Changes at 48 h and 6 weeks did not differ between groups. CONCLUSIONS: In female patients undergoing elective laparoscopic gynaecological surgery, dexamethasone administration appears to attenuate inflammation and to alter immune cell counts at 24 h, with no effects identified after this time. The importance of these changes for postoperative immune function is unknown. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ACTRN12608000340336).

NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis.

Nod-like receptor, pyrin containing 3 (NLRP3) is characterized primarily as a canonical caspase-1 activating inflammasome in macrophages. NLRP3 is also expressed in the epithelium of the kidney and gut; however, its function remains largely undefined. Primary mouse tubular epithelial cells (TEC) lacking Nlrp3 displayed reduced apoptosis downstream of the tumor necrosis factor (TNF) receptor and CD95. TECs were identified as type II apoptotic cells that activated caspase-8, tBid and mitochondrial apoptosis via caspase-9, responses that were reduced in Nlrp3-/- cells. The activation of caspase-8 during extrinsic apoptosis induced by TNFα/cycloheximide (TNFα/CHX) was dependent on adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and completely independent of caspase-1 or caspase-11. TECs and primary human proximal tubular epithelial cells (HPTC) did not activate a canonical inflammasome, caspase-1, or IL-1ß secretion in response to TNFα/CHX or NLRP3-dependent triggers, such as ATP or nigericin. In cell fractionation studies and by confocal microscopy, NLRP3 colocalized with ASC and caspase-8 in speck-like complexes at the mitochondria during apoptosis. The formation of NLRP3/ASC/caspase-8 specks in response to TNFα/CHX was downstream of TNFR signaling and dependent on potassium efflux. Epithelial ASC specks were present in enteroids undergoing apoptosis and in the injured tubules of wild-type but not Nlrp3-/- or ASC-/- mice following ureteric unilateral obstruction in vivo. These data show that NLRP3 and ASC form a conserved non-canonical platform for caspase-8 activation, independent of the inflammasome that regulates apoptosis within epithelial cells.

Urogenital schistosomiasis in women of reproductive age and pregnant mothers in Kwale County, Kenya.

Generally, women residing in areas endemic for urinary schistosomiasis may suffer from female genital schistosomiasis which is acquired during childhood. The objective of this cross-sectional study was to estimate the prevalence and intensity of infection of Schistosoma haematobium in women of reproductive age (16-45 years) and to investigate whether S. haematobium had any effect on kidney function. A total of 394 women of known pregnancy status (158 pregnant and 236 non-pregnant) were recruited from five villages (known for their high prevalence of infection of S. haematobium) in Kwale County. Serum samples were analysed to determine levels of urea and creatinine as proxy indicators of kidney function. Data revealed that pregnant women did not, on average, have a higher prevalence or intensity of infection of urinary schistosomiasis than non-pregnant women. During pregnancy, the level of prevalence and intensity of infection of S. haematobium was highest in the first trimester (0-13 weeks), dropped in the second trimester (14-26 weeks) and rose again in the third trimester (27-40 weeks). In addition, 24.8% of women were infected with hookworm, while none were diagnosed with malaria parasites. Of 250 samples analysed for serum urea and creatinine, none had significant levels of pathology, either in pregnant or non-pregnant women. Despite World Health Organization (WHO) recommendations that pregnant women should be treated with praziquantel after the first trimester, in practice this has not been the case in many countries, including Kenya. In view of this, healthcare providers should be informed to consider treatment of pregnant women infected with schistosomiasis during antenatal visits and whenever there is mass drug administration as recommended by the WHO.

Circulating mycobacterial-reactive CD4+ T cells with an immunosuppressive phenotype are higher in active tuberculosis than latent tuberculosis infection.

BACKGROUND: Previous studies suggest that control of Mycobacterium tuberculosis infection is compromised by the activity of regulatory T cells, including those that express CD39, an ectonucleotidase with immunosuppressive properties. Here, we examine the role of CD39 on CD4+ T cells reacting to M. tuberculosis antigens. METHODS: Cryopreserved PBMC from patients with active TB (n = 31) or individuals with LTBI (n = 30) were cultured with PPD, ESAT-6 or CFP-10 and antigen-reactive CD4+ T cells assessed by: A) intracellular expression of interferon-gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) and interleukin (IL)-2, B) co-expression of CD25 and CD134 with or without CD39, and C) production of IFN-γ, TNF-α and IL-10 in culture supernatants. RESULTS: Active TB patients were not differentiated from individuals with LTBI by intracellular expression of IFN-γ, TNF-α or IL-2 (alone or together), nor by co-expression of CD25 and CD134. However, active TB patients exhibited higher proportions of CD25+, CD134+, CD4+ T cells expressing CD39 in response to all antigens (p ≤ 0.022). Furthermore, in response to PPD, CD39 expression on CD25+, CD134+, CD4+ T cells correlated with IL-10 production (r = 0.41, p = 0.005) and inhibition of CD39 decreased IL-10 production. CONCLUSIONS: Antigen-reactive CD4+ T cells expressing CD39 are more abundant in active TB than LTBI and are associated with production of the immunosuppressive cytokine IL-10. Modulating the effects of CD39 might enhance cellular immune responses against M. tuberculosis.

Immune reconstitution disorders in patients with HIV infection: from pathogenesis to prevention and treatment.

An immune reconstitution disorder occurs in up to 40 % of severely immunodeficient HIV patients who commence antiretroviral therapy (ART), with an immune reconstitution inflammatory syndrome (IRIS) being encountered most commonly. Differences in the immunopathogenesis of an IRIS associated with different types of pathogen have become apparent but common features have also been defined. These include severe immunodeficiency prior to commencing ART associated with a high pathogen load and 'compensatory' immune responses, particularly innate immune responses, which inadequately control the pathogen and increase the risk of immunopathology as the immune system recovers on ART. Prevention of an IRIS may be achieved by optimising therapy for opportunistic infections before ART is commenced, delaying ART or using immunomodulatory therapy to prevent or suppress the immune response that causes the immunopathology. However, further clinical studies are required to examine these options in a systematic manner for the various types of IRIS.

Role of monocytes in mediating HIV-specific antibody-dependent cellular cytotoxicity.

Antibodies (Abs) that mediate antibody-dependent cellular cytotoxicity (ADCC) activity against HIV-1 are of major interest. A widely used method to measure ADCC Abs is the rapid and fluorometric antibody-dependent cellular cytotoxicity (RFADCC) assay. Antibody-dependent killing of a labelled target cell line by PBMC is assessed by loss of intracellular CFSE but retention of membrane dye PKH26 (CFSE-PKH26+). Cells of this phenotype are assumed to be derived from CFSE+PKH26+ target cells killed by NK cells. We assessed the effector cells that mediate ADCC in this assay. Backgating analysis and phenotyping of CFSE-PKH26+ revealed that the RFADCC assay's readout mainly represents CD3-CD14+ monocytes taking up the PKH26 dye. This was confirmed for 53 HIV+plasma-purified IgG samples when co-cultured with PBMC from three separate healthy donors. Emergence of the CFSE-PKH26+ monocyte population was observed upon co-culture of targets with purified monocytes but not with purified NK cells. Image flow cytometry and microscopy showed a monocyte-specific interaction with target cells without typical morphological changes associated with phagocytosis, suggesting a monocyte-mediated ADCC process. We conclude that the RFADCC assay primarily reflects Ab-mediated monocyte function. Further studies on the immunological importance of HIV-specific monocyte-mediated ADCC are warranted.

Probing the interiors of the ice giants: shock compression of water to 700 GPa and 3.8 g/cm³.

Recently, there has been a tremendous increase in the number of identified extrasolar planetary systems. Our understanding of their formation is tied to exoplanet internal structure models, which rely upon equations of state of light elements and compounds such as water. Here, we present shock compression data for water with unprecedented accuracy that show that water equations of state commonly used in planetary modeling significantly overestimate the compressibility at conditions relevant to planetary interiors. Furthermore, we show that its behavior at these conditions, including reflectivity and isentropic response, is well-described by a recent first-principles based equation of state. These findings advocate that this water model be used as the standard for modeling Neptune, Uranus, and "hot Neptune" exoplanets and should improve our understanding of these types of planets.

Novel sensitive real-time PCR for quantification of bacterial 16S rRNA genes in plasma of HIV-infected patients as a marker for microbial translocation.

We developed a real-time PCR to quantify 16S rRNA gene levels in plasma from HIV-infected patients as a marker of microbial translocation. The assay uses shrimp nuclease (SNuc) to eliminate DNA contamination, giving high sensitivity and low variability. The 16S rRNA gene levels measured in plasma from HIV patients correlated significantly with lipopolysaccharide levels.

A linkage map of sheep chromosome X (OARX) aligned to human chromosome X (HSAX).

We have constructed a genetic linkage map of the sheep X chromosome (OARX) containing 22 new gene loci from across the human X chromosome (HSAX). The female OARX linkage map has a total length of 152.6 cM with average gene spacing of 5.5 cM. Comparison with HSAX confirms one previously reported major breakpoint and inversion, and other minor rearrangements between OARX and HSAX. Comparison of the linkage map with sheep sequence data OAR 1.0 reveals a different arrangement of markers on the q arm, which may more accurately reflect the genuine arrangement of this region.

The multidimensionality of sleep quality and its relationship to fatigue in older adults with painful osteoarthritis.

OBJECTIVE: To evaluate subjective sleep quality and its relationship to fatigue in older adults with osteoarthritis (OA). METHOD: In a community cohort with hip/knee OA, subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and fatigue was measured by the Profile of Mood States - Fatigue subscale (POMS-F). Correlates of sleep quality and fatigue were determined by standardized interviews including socio-demographics, OA severity (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) summary score), comorbidity, depression (Center for Epidemiologic Studies Depression Scale, CES-D), stressful life events, daytime napping, symptoms of restless legs syndrome (RLS) and prior sleep disorder diagnoses. Logistic regression examined correlates of poor sleep (PSQI score>5). Linear regression evaluated the relationship between poor sleep and fatigue, and the effect of napping on this relationship. RESULTS: In 613 respondents, mean age was 78 years, 78% were female, 11% had concomitant fibromyalgia, and 26% had 3+ comorbid conditions. Responses indicated moderate OA severity. Seventy percent reported poor sleep; 25% met criteria for RLS and 6.5% reported a diagnosed sleep disorder. Independent correlates of poor sleep were: greater arthritis severity (adjusted odds ratio (OR) per unit increase in WOMAC score=1.03, P<0.0001), 3+ comorbid conditions (adjusted OR=1.88; P=0.03), depressed mood (adjusted OR per unit increase in CES-D score=1.09, P<0.0001), and RLS (adjusted OR=1.87; P=0.02). Controlling for previously reported fatigue correlates, poor sleep was significantly associated with greater fatigue (parameter estimate=1.63, P=0.0003) and napping did not moderate this relationship (P=0.55 for the interaction between napping and poor sleep). CONCLUSIONS: Among older people with OA, poor sleep is highly prevalent and significantly linked with fatigue. Identifying the nature of sleep disturbances in OA is important as treatment of sleep disturbances may reduce OA-related fatigue.

Directional field-induced metallization of quasi-one-dimensional Li0.9Mo6O17.

We report a detailed magnetotransport study of the highly anisotropic quasi-one-dimensional oxide Li(0.9)Mo(6)O(17) whose in-chain electrical resistivity diverges below a temperature T_{min} approximately 25 K. For T < T_{min}, a magnetic field applied parallel to the conducting chain induces a large negative magnetoresistance and, ultimately, the recovery of a metallic state. We show evidence that this insulator-metal crossover is a consequence of field-induced suppression of a density-wave gap in a highly one-dimensional conductor. At the highest fields studied, there is evidence for the possible emergence of a novel superconducting state with an onset temperature T_{c} > 10 K.

Synthesis of specific fatty acids contributes to VLDL-triacylglycerol composition in humans with and without type 2 diabetes.

AIMS/HYPOTHESIS: It is recommended that patients with diabetes reduce their intake of saturated fat and increase their intake of monounsaturated fat or carbohydrate. However, high-carbohydrate diets may result in higher saturated fatty acids in VLDL-triacylglycerol. This is attributed to de novo lipogenesis, although synthesis of specific fatty acids is rarely measured. The objective of this study was to examine the contribution of de novo fatty acid synthesis to VLDL-triacylglycerol composition. It was hypothesised that levels of total and de novo synthesised fatty acids would increase with increased carbohydrate intake in diabetic participants. METHODS: Seven individuals with type 2 diabetes mellitus and seven matched non-diabetic controls consumed two diets differing in fat energy (lower fat <25%, higher fat >35%) for 3 days in a randomised crossover design. Blood samples were drawn before and 24 h after the ingestion of (2)H-labelled water. RESULTS: In the control participants, the higher-fat diet resulted in a 40% reduction in VLDL-triacylglycerol fatty acids because of decreases in myristic, palmitic, palmitoleic and linoleic acids, but the opposite trend occurred in participants with diabetes. The lower-fat diet increased the fractional synthesis rate by 35% and 25% in the control and diabetes participants, respectively (range: 0-33%). Palmitate accounted for 71% of fatty acids synthesised (range: 44-84% total de novo synthesised fatty acids). CONCLUSIONS/INTERPRETATION: (2)H incorporation was used for the first time in humans showing variability in the synthesis rate of specific fatty acids, even palmitic acid. A lower-fat diet stimulated saturated fatty acid synthesis at high rates, but no net stimulation of synthesis of any fatty acid occurred in the diabetes group. The implications of this finding for our understanding of lipid metabolism in diabetes require further investigation.