The management of sodium intake is clinically important in many disease states including heart failure, kidney disease, and hypertension. Tenapanor is an inhibitor of the sodium-proton (Na(+)/H(+)) ...exchanger NHE3, which plays a prominent role in sodium handling in the gastrointestinal tract and kidney. When administered orally to rats, tenapanor acted exclusively in the gastrointestinal tract to inhibit sodium uptake. We showed that the systemic availability of tenapanor was negligible through plasma pharmacokinetic studies, as well as autoradiography and mass balance studies performed with (14)C-tenapanor. In humans, tenapanor reduced urinary sodium excretion by 20 to 50 mmol/day and led to an increase of similar magnitude in stool sodium. In salt-fed nephrectomized rats exhibiting hypervolemia, cardiac hypertrophy, and arterial stiffening, tenapanor reduced extracellular fluid volume, left ventricular hypertrophy, albuminuria, and blood pressure in a dose-dependent fashion. We observed these effects whether tenapanor was administered prophylactically or after disease was established. In addition, the combination of tenapanor and the blood pressure medication enalapril improved cardiac diastolic dysfunction and arterial pulse wave velocity relative to enalapril monotherapy in this animal model. Tenapanor prevented increases in glomerular area and urinary KIM-1, a marker of renal injury. The results suggest that therapeutic alteration of sodium transport in the gastrointestinal tract instead of the kidney--the target of current drugs--could lead to improved sodium management in renal disease.
Embryonic muscle forces are necessary for normal vertebral development and spinal curvature, but their involvement in intervertebral disc (IVD) development remains unclear. The aim of the current ...study was to determine how muscle contractions affect (1) notochord involution and vertebral segmentation, and (2) IVD development including the mechanical properties and morphology, as well as collagen fibre alignment in the annulus fibrosus. Muscular dysgenesis (mdg) mice were harvested at three prenatal stages: at Theiler Stage (TS)22 when notochord involution starts, at TS24 when involution is complete, and at TS27 when the IVD is formed. Vertebral and IVD development were characterised using histology, immunofluorescence, and indentation testing. The results revealed that notochord involution and vertebral segmentation occurred independently of muscle contractions between TS22 and TS24. However, in the absence of muscle contractions, we found vertebral fusion in the cervical region at TS27, along with (i) a displacement of the nucleus pulposus towards the dorsal side, (ii) a disruption of the structural arrangement of collagen in the annulus fibrosus, and (iii) an increase in viscous behaviour of the annulus fibrosus. These findings emphasise the important role of mechanical forces during IVD development, and demonstrate a critical role of muscle loading during development to enable proper annulus fibrosus formation. They further suggest a need for mechanical loading in the creation of fibre-reinforced tissue engineering replacement IVDs as a therapy for IVD degeneration.
This study assessed the effects of amino acid additives, aspartic acid, leucine, lysine, and methionine, on the pasting and thermal characteristics of white- and orange-fleshed Beauregard sweet ...potato starches. A rapid visco analyzer 3D was used to determine pasting properties. In comparing pasting characteristics, starch from orange-fleshed sweet potato was found to be easier to cook, had a lower potential for retrogradation, and was less stable during heating than the white-fleshed sweet potato starch. The RVA analysis showed that the charged amino acids, aspartic acid and lysine, altered pasting characteristics of the 2 starches more than the neutral amino acids, leucine and methionine. Aspartic acid had similar effects on both starches, making them less stable during cooking and lowering the potential for retrogradation. Lysine, when added to the orange-fleshed sweet potato starch, decreased the breakdown, allowing for more stability during cooking. This study showed that pasting properties of sweet potato starches can be altered by the addition of amino acids.
Personal products, such as toothbrushes, have been used as both known reference and evidentiary samples for forensic DNA analysis. This study examined the viability of a broad selection of cosmetic ...applicators for use as targets for human DNA extraction and short tandem repeat (STR) analysis using standard polymerase chain reaction (PCR) conditions. Applicator types included eyeliner smudgers, pencils and crayons, eye shadow sponges, mascara wands, concealer wands, face makeup sponges, pads and brushes, lipsticks and balms, and lip gloss wands. The quantity and quality of DNA extracted from each type of applicator were examined by assessing the number of loci successfully amplified and the peak balance of the heterozygous alleles in each full STR profile. While degraded DNA, stochastic amplification, and PCR inhibition were observed for some items, full STR profiles were developed for 14 of 76 applicators. The face makeup sponge applicators yielded the highest proportional number of full STR profiles (4/7).
ABSTRACT
Sweetpotato Ipomoea batatas (L.) Lam farmer varieties are still the backbone of production and breeding programs in Sub‐Sahara Africa. Usually, farmer varieties in Sub‐Sahara Africa are ...white‐ or cream‐fleshed sweetpotato (WFSP), but recently orange‐fleshed sweetpotato (OFSP) were found in East Africa. The objective of the study was to characterize WFSP and OFSP germplasm from East Africa. Eighty‐five East African farmer varieties (29 OFSPs and 56 WFSPs) and seven varieties of non‐African origin as check clones were analyzed for diversity using 26 simple sequence repeat (SSR) markers. A total of 158 alleles were scored with an average of 6.1 alleles per SSR loci. The mean of Jaccard's similarity coefficients was 0.54. The unweighted pair group method analysis (UPGMA) revealed a main cluster for East Africa germplasm at a similarity coefficient of 0.52. At a similarity coefficient of about 0.55 subclusters within the East African germplasm were observed, but these were neither country nor flesh color specific. Analysis of molecular variance (AMOVA) found a significant difference between East African and non‐African germplasm and a nonsignificant difference between OFSP and WFSP germplasm. In conclusion, the East African germplasm appears to be distinct from non‐African germplasm, and OFSP and WFSP farmer varieties from East Africa are closely related. Orange‐fleshed sweetpotato farmer varieties from East Africa might show similar adaptation to Sub‐Sahara African environments as WFSP and a big potential in alleviating vitamin A deficiency.
Synopsis
Jumping is a rapid locomotory mode widespread in terrestrial organisms. However, it is a rare specialization in ants. Forward jumping has been reported within four distantly related ant ...genera: Gigantiops, Harpegnathos, Myrmecia, and Odontomachus. The temporal engagement of legs/body parts during jump, however, varies across these genera. It is unknown what morphological adaptations underlie such behaviors and whether jumping in ants is solely driven directly by muscle contraction or additionally relies on elastic recoil mechanism. We investigated the morphological adaptations for jumping behavior by comparing differences in the locomotory musculature between jumping and non-jumping relatives using X-ray micro-CT and 3D morphometrics. We found that the size-specific volumes of the trochanter depressor muscle (scm6) of the middle and hind legs are 3–5 times larger in jumping ants, and that one coxal remotor muscle (scm2) is reduced in volume in the middle and/or hind legs. Notably, the enlargement in the volume of other muscle groups is directly linked to the legs or body parts engaged during the jump. Furthermore, a direct comparison of the muscle architecture revealed two significant differences between jumping vs. non-jumping ants: First, the relative Physiological Cross-Sectional Area (PCSA) of the trochanter depressor muscles of all three legs were larger in jumping ants, except in the front legs of Odontomachus rixosus and Myrmecia nigrocincta; second, the relative muscle fiber length was shorter in jumping ants compared to non-jumping counterparts, except in the front legs of O. rixosus and M. nigrocincta. These results suggest that the difference in relative muscle volume in jumping ants is largely invested in the area (PCSA), and not in fiber length. There was no clear difference in the pennation angle between jumping and non-jumping ants. Additionally, we report that the hind leg length relative to body length was longer in jumping ants. Based on direct comparison of the observed vs. possible work and power output during jumps, we surmise that direct muscle contractions suffice to explain jumping performance in three species, except for O. rixosus, where the lack of data on jumping performance prevents us from drawing definitive conclusions for this particular species. We suggest that increased investment in jumping-relevant musculature is a primary morphological adaptation that separates jumping from non-jumping ants. These results elucidate the common and idiosyncratic morphological changes underlying this rare adaptation in ants.
まとぅみ (Okinawan language—Uchinaaguchi)
要旨 (Japanese)
РЕЗЮМЕ (Kazakh)
ZUSAMMENFASSUNG (German)
“Cuttlebone,” the internalized shell found in all members of the cephalopod family
Sepiidae, is a sophisticated buoyancy device combining high porosity
with considerable strength. Using a ...complementary suite of characterization tools, we
identified significant structural, chemical, and mechanical variations across the
different structural units of the cuttlebone: the dorsal shield consists of two stiff and
hard layers with prismatic mineral organization which encapsulate a more ductile and
compliant layer with a lamellar structure, enriched with organic matter. A similar
organization is found in the chambers, which are separated by septa, and supported by
meandering plates (“pillars”). Like the dorsal shield, septa contain two layers with
lamellar and prismatic organization, respectively, which differ significantly in their
mechanical properties: layers with prismatic organization are a factor of three stiffer
and up to a factor of ten harder than those with lamellar organization. The combination of
stiff and hard, and compliant and ductile components may serve to reduce the risk of
catastrophic failure, and reflect the role of organic matter for the growth process of the
cuttlebone. Mechanically “weaker” units may function as sacrificial structures, ensuring a
stepwise failure of the individual chambers in cases of overloading, allowing the animals
to retain near-neutral buoyancy even with partially damaged cuttlebones. Our findings have
implications for our understanding of the structure-property-function relationship of
cuttlebone, and may help to identify novel bioinspired design strategies for light-weight
yet high-strength foams.
The objectives of the present study were to evaluate the inheritance and nucleotide sequence profiles of microsatellite genetic markers in hexaploid sweetpotato Ipomoea batatas (L.) Lam. and its ...putative tetraploid and diploid ancestors, and to test possible microsatellite mutation mechanisms in polyploids by direct sequencing of alleles. Sixty three microsatellite loci were isolated from genomic libraries of I. batatas and sequenced. PCR primers were designed and used to characterize microsatellite loci in two hexaploid I. batatas populations, a tetraploid Ipomoea trifida population, and a diploid I. trifida population. Nine out of the sixty three primer pairs tested yielded a clearly discernible, heritable banding pattern; five showed Mendelian segregation. All other primer pairs produced either smeared banding patterns, which could not be scored, or no bands at all in I. batatas. All of the primers which produced discernible banding patterns from I. batatas also amplified products of similar size in tetraploid and diploid I. trifida accessions. The sequence analysis of several alleles in the three species showed differences due to mutations in the repeat regions consistent with small differences in the repeat number. However, in some cases insertions/deletions and base substitutions in the microsatellite flanking regions were responsible for polymorphisms in both polyploid and diploid species. These results provide strong empirical evidence that complex genetic mechanisms are responsible for SSR allelic variation in Ipomoea. Four I. batatas microsatellite loci showed polysomic segregation fitting tetraploid segregation ratios. To our knowledge this is the first report of segregation ratios for microsatellites markers in polyploids.
In CKD, phosphate retention arising from diminished GFR is a key early step in a pathologic cascade leading to hyperthyroidism, metabolic bone disease, vascular calcification, and cardiovascular ...mortality. Tenapanor, a minimally systemically available inhibitor of the intestinal sodium-hydrogen exchanger 3, is being evaluated in clinical trials for its potential to (1) lower gastrointestinal sodium absorption, (2) improve fluid overload-related symptoms, such as hypertension and proteinuria, in patients with CKD, and (3) reduce interdialytic weight gain and intradialytic hypotension in ESRD. Here, we report the effects of tenapanor on dietary phosphorous absorption. Oral administration of tenapanor or other intestinal sodium-hydrogen exchanger 3 inhibitors increased fecal phosphorus, decreased urine phosphorus excretion, and reduced (33)Porthophosphate uptake in rats. In a rat model of CKD and vascular calcification, tenapanor reduced sodium and phosphorus absorption and significantly decreased ectopic calcification, serum creatinine and serum phosphorus levels, circulating phosphaturic hormone fibroblast growth factor-23 levels, and heart mass. These results indicate that tenapanor is an effective inhibitor of dietary phosphorus absorption and suggest a new approach to phosphate management in renal disease and associated mineral disorders.
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