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Lactase persistence (LP) among adults differs in frequency worldwide (Cook and Al-Torki 1975; Flatz 1987; Swallow and Hollox 2000). It is common in northern Europeans and certain African and Middle [...], The high prevalence of lactase persistence (LP) among the people of Saudi Arabia is associated with the -13915*G variant allele upstream of the lactase gene (LCT). We, therefore, examined the frequency of the commonly known LP associated SNPs among randomly collected samples from Omani and Yemeni adult populations and obtained further data on the distribution of the two most common LP-associated variants, -13910*T and -13915T*G, in the Arabian Peninsula. The DNA fragment containing all the reported LP- associated SNPs was amplified and genotyped. The frequency of the -13915*G allele was highest among Dhofari Arabs of southern Oman (0.72) followed by Yemeni Arabs (0.54) and Arabs of northern Oman (0.14). It was not detected in Omanis of Asian origin. The frequency of the -13910*T allele was extremely low in Arabs of northern and southern Oman (0.00-0.01) and Yemenis (0.002). However, it had a frequency of 0.160 among Omanis of Asian origin. Results show that the highest frequency of the LCT -13915*G variant allele appears to be in the south of the Arabian Peninsula with clinal decrease within the Peninsula and further out in surrounding countries. KEY WORDS: ARABIAN PENINSULA, OMAN, YEMEN, LACTASE PERSISTENCE.

The proton-coupled folate transporter (PCFT-SLC46A1) is required for intestinal folate absorption and is mutated in the autosomal recessive disorder, hereditary folate malabsorption (HFM). This report characterizes properties and requirements of the R376 residue in PCFT function, including a R376Q mutant associated with HFM. Gln, Cys, and Ala substitutions resulted in markedly impaired transport of 5-formyltetrahydrofolate (5-FTHF) and 5-methyltetrahydrofolate (5-MTHF) due to an increase in [K.sub.m] and decrease in [V.sub.max] in HeLa R1-11 transfectants lacking endogenous folate transport function. In contrast, although the influx [K.sub.m] for pemetrexed was increased, transport was fully preserved at saturating concentrations and enhanced for the like-charged R376K- and R376H-PCFT. Pemetrexed and 5-FTHF influx mediated by R376Q-PCFT was markedly decreased at pH 5.5 compared with wild-type PCFT. However, while pemetrexed transport was substantially preserved at low pH (4.5-5.0), 5-FTHF transport remained very low. Electrophysiological studies in Xenopus oocytes demonstrated that 1) the R376Q mutant, like wild-type PCFT, transports protons in the absence of folate substrate, and in this respect has channel-like properties; and 2) the influx [K.sub.m] mediated by R376Q-PCFT is increased for 5-MTHF, 5-FTHF, and pemetrexed. The data suggest that mutation of the R376 residue to Gin impairs proton binding which, in turn, modulates the folate-binding pocket and depresses the rate of conformational alteration of the carrier, a change that appears to be, in part, substrate dependent. reduced folate carrier; folate receptors; heme carrier protein-1; folate deficiency; folate transport; intestinal folate absorption; choroid plexus doi: 10.1152/ajpcell.00113.2010.

Angiotensin converting enzyme (ACE) has been shown to be involved in regulation of apoptosis in nonintestinal tissues. This study examined the role of ACE in the modulation of intestinal adaptation utilizing ACE knockout mice ([ACE.sup.-/-]). A 60% small bowel resection (SBR) was used, since this model results in a significant increase in intestinal epithelial cell (EC) apoptosis as well as proliferation. Baseline villus height, crypt depth, and intestinal EC proliferation were higher, and EC apoptosis rates were lower in [ACE.sup.-/-] compared with [ACE.sup.+/+] mice. After SBR, EC apoptosis rates remained significantly lower in [ACE.sup.-/-] compared with [ACE.sup.+/+] mice. Furthermore, villus height and crypt depth after SBR continued to be higher in [ACE.sup.-/-] mice. The finding of a lower bax-to-bcl-2 protein ratio in [ACE.sup.-/-] mice may account for reduced EC apoptotic rates after SBR in [ACE.sup.-/-] compared with [ACE.sup.+/+] mice. The baseline higher rate of EC proliferation in [ACE.sup.-/-] compared with [ACE.sup.+/+] mice may be due to an increase in the expression of several EC growth factor receptors. In conclusion, ACE appears to have an important role in the modulation of intestinal EC apoptosis and proliferation and suggests that the presence of ACE in the intestinal epithelium has a critical role in guiding epithelial cell adaptive response. short bowel syndrome; bax; bcl-2; intestine; adaptation

The human folate transporter of the small intestine has been identified and characterized. It functions optimally at the low pH (6.0-6.2) characteristic of the microenvironment of the duodenal brush border membrane, where dietary folates are mainly absorbed. The transporter, named PCFT/HCP1, is a protein of approximately 50 kDa and functions as a reversible, electrogenic, proton-coupled high-affinity folate transporter (PCFT). It shows high specificity for folates and anti-folates. This protein was previously identified as an intestinal heme carrier protein HCP1. Patients suffering from hereditary familial folate malabsorption were found to be homozygous for a mutation of the PCFT/HCP1 gene due to loss of a particular exon coding for 28 amino acids. Key words: folic acid, methotrexate, folates, duodenum, reduced folate carrier, heme carrier protein, electrogenic, Caco2 cells, folate malabsorption doi: 10.1301/nr.2007.dec.554-557

The identification of a proton-coupled, electrogenic, high-affinity folate transporter with properties that are similar to folate transport in intestinal and other cells at low pH is described. It is established that a major function of pH-independent heme carrier protein, HCP1 gene product is proton-coupled folate transport required for folate homeostasis in man, named PCFT/HCP1.

Byline: Barbara E. Wildhaber (1), Hua Yang (1), Arnold G. Coran (1), Daniel H. Teitelbaum (1) Keywords: Short bowel syndrome; Intraepithelial lymphocytes; Apoptosis; Proliferation; Microarray Abstract: Background The intestinal adaptive response [increased epithelial cell (EC) proliferation and apoptosis] after massive small bowel resection (SBR) is partially controlled by intraepithelial lymphocytes (IEL). To identify IEL factors contributing to EC adaptation post-SBR we utilized microarray assays. Methods Mice underwent a 70% SBR (SBR1w/SBR4w) or sham operation (Sham1w/Sham4w). After 1 or 4 weeks (1w, 4w) small bowel was harvested, and IEL isolated. Determination of the EC-proliferation rate used BrdU incorporation, and of the EC-apoptotic rate used Annexin V staining. Affymetrix system microarrays (12,491 genes) were performed to examine IEL-mRNA expression. Results were considered significant if fold-change (FC) between groups was &gt 2 and P &lt 0.05 (F-test), or FC&gt 3 and 0.05&gt P &gt 0.01, or FC&gt 4 and P &gt 0.05. Significant genes were confirmed by conventional RT-PCR. Results The SBR EC-proliferation rate increased significantly in both 1w and 4w groups compared to Sham: SBR1w 0.24+-0.07 vs. Sham1w 0.12+-0.02 ( P =0.03) SBR4w 0.35+-0.04 vs. Sham4w 0.19+-0.02 ( P &lt 0.01). The EC-apoptotic rate was unchanged in the 1w group, but significantly differed from controls after 4 weeks: SBR4w 39.92+-6.78 vs. Sham4w 12.56+-6.44 ( P &lt 0.01). Microarray results were analyzed to identify potential growth-modifying IEL genes. The following were identified (function in parenthesis A, apoptosis P, proliferation): lipocalin 2 (promotes A), angiotensin converting enzyme (increases A), Rap2 interacting protein (reduces A, promotes P), amphiregulin (promotes P) and leucine-rich-[alpha]2-glycoprotein (promotes A, reduces P). Based on RT-PCR results these genes showed significant changes between groups. The increase in ACE at 1w preceded the observed apoptotic changes. The alterations in lipocalin 2, Rap2 and amphiregulin at 4w coincided with the marked changes in growth and apoptosis in the SBR mice. Conclusions IEL undergo temporal changes after SBR. These findings provide profound insight into potential IEL-dependent regulation of EC homeostasis post-SBR. Author Affiliation: (1) Department of Surgery, Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan, Mott F3970, Box 0245, Ann Arbor, Michigan, 48109, USA Article History: Accepted Date: 10/12/2002 Online Date: 01/05/2003

Glucose galactose malabsorption is a genetic disease due to a malfunction in glucose and galactose transport across the intestinal brush border. During normal situations, lactose in milk is separated into glucose and galactose by lactase, an ectoenzyme on the brush border, and the hexoses are moved into the cell by the Na+-glucose cotransporter SGLT1. The mutations responsible for the malfunction in sugar transport were determined in patients from 33 families and functional investigations were used to determine how the mutations cause the disorder.

The gene that causes a rare fat-developmental disorder has been identified. Researchers at the University of Texas (UT) Southwestern Medical Center at Dallas--along with a panel of their colleagues from [...]