The public health challenge of early growth failure in India.

Recent recognition of the early onset and high prevalence of wasting (30%) and stunting (20%) among infants 0-5 months in India draws attention to the need to understand the causes and develop prevention strategies. Such growth failure has dire consequences in the short (increased mortality) and long-term (loss of human capital and increased risk of chronic diseases). Food interventions before 6 months will increase morbidity/mortality through contamination in settings of poor sanitation and hygiene. Waiting to improve nutrition only after the initiation of complementary feeding at 6 months is a missed opportunity and may permanently alter life trajectory and potential. This underscores the importance of maternal nutrition. Iron and folic acid and protein energy supplementation during pregnancy are interventions that can improve maternal nutrition and birth outcomes. Maternal supplementation during lactation should be considered as a means to improve maternal and child outcomes, although the evidence needs strengthening. Support and counseling are also required to improve maternal diets and promote exclusive breastfeeding. Programs focused on improving maternal nutrition across the continuum of preconception, pregnancy and lactation are likely to have the greatest impact as mothers are central gatekeepers to the health and future of their children.

The human tuftelin gene: cloning and characterization.

Tuftelin has been suggested to play an important role during the development and mineralization of enamel. We isolated the full-length human tuftelin cDNA using reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (5' RACE and 3' RACE) methods. Sequence analysis of the tuftelin cDNA revealed an open reading frame of 1170 bp encoding a 390 amino acid protein with a molecular mass of 44.3 kDa and an isoelectric point of 5.7. The human tuftelin protein shares 89 and 88% amino acid sequence identity with the bovine and mouse tuftelin, respectively. It contains a coiled-coil region, recently reported to be involved with tuftelin self-assembly and with the interaction of tuftelin with TIP39 (a novel tuftelin interacting protein). Detailed DNA analysis of the cloned genomic DNA revealed that the human tuftelin gene contains 13 exons and is larger than 26 kb. Two alternatively spliced tuftelin mRNA transcripts have now been identified in the human tooth bud, one lacking exon 2, and the other lacking exon 2 and exon 3. Primer extension analysis, corroborated by RT-PCR and DNA sequencing, revealed multiple transcription initiation sites. The cloned 1.6 kb promoter region contained several GC boxes and several transcription factor binding sites such as those for activator protein 1 and stimulatory protein 1. Our blast search of the human and mouse expressed sequence tag data bases, as well as our RT-PCR and DNA sequencing results, and a previous study using Northern blot analysis revealed that tuftelin cDNA sequences are also expressed in normal and cancerous non-mineralizing soft tissues, suggesting that tuftelin has a universal function. We have now identified and characterized different alternatively spliced mouse tuftelin mRNAs in several non-mineralizing tissues. These results provide an important baseline for future understanding of the biological role of tuftelin.

Double FYVE-containing protein 1 (DFCP1): isolation, cloning and characterization of a novel FYVE finger protein from a human bone marrow cDNA library.

Double FYVE-containing protein 1 (DFCP1) encodes a 777 amino acid protein that contains: (1) an N-terminal Cys-His cluster with some homology to many zinc finger domains; (2) a consensus sequence consistent with an ATP/GTP binding site; and (3) a C-terminal domain unique because it contains two zinc-binding FYVE domains. The gene, ZNFN2A1 (GenBank accession no. AF251025) was localized to chromosome 14q22-q24 and shown to be composed of 11 exons. Northern blot analysis revealed the presence of three different mRNA transcripts (4.2, 3 and 1.2kb). The two longer transcripts appear to be expressed in a variety of different tissues, especially in endocrine tissues, while the shorter messenger is limited to testis. Both of the larger transcripts are unusual due to the presence of a 463bp long 5' UTR. Furthermore, the 4.2kb transcript contains a non-standard polyadenylation consensus sequence while the 3kb transcript contains a standard consensus sequence but within the open reading frame. Following in vitro transfection of a DFCP1-containing expression construct, confocal microscopy studies showed a vesicular distribution of DFCP1 suggesting that this protein, like other FYVE-containing proteins, might be involved in membrane trafficking.

Effect of acupuncture stimulation of the auricular sympathetic point on evoked sudomotor response.

OBJECTIVES: To investigate whether stimulation of the auricular sympathetic acupuncture point would affect the mean maximum amplitude of evoked sudomotor responses. DESIGN: A placebo-controlled trial. Two types of controls were used: no acupuncture and acupuncture of an alternate "non-sympathetic nervous system" related (i.e., a non-sympathetic, placebo) point. Subjects were included in either the placebo or the test group. Each subject would have one session of acupuncture and one session without acupuncture, the acupuncture was applied in either the first or the second session. Initially, each group was unaware in which of the two sessions they would receive acupuncture (cross-over design). Each individual was unaware of which group they were to participate in. SETTINGS/LOCATION: A quiet, sealed room with a constant temperature, in the research department of the Anglo-European College of Chiropractic. SUBJECTS: Thirty-eight asymptomatic male, white volunteers (18 to 40 years old). INTERVENTIONS: The two groups underwent two electrodermal response (EDR) recording sessions, at an interval of 5 weeks. During each session, they were also presented with eight stimuli, each of which was designed to stimulate the sympathetic nervous system. In each session, subjects either received auricular acupuncture (AA) or did not. OUTCOME MEASURES: The maximum amplitude of the EDR for each stimulus. RESULTS: AA at the non-sympathetic, placebo point significantly increased EDR both with respect to the individual stimuli (p < or = 0.05 to < or = 0.001) and for the pooled data (p = 0.0001). AA to the sympathetic point produced no significant change in EDR for either individual stimuli (p range > or = 0.8 to > or = 0.1) or for the pooled data (p > 0.8). A significant difference was found between the results from placebo and sympathetic point stimulated groups during AA for 2 of the 8 stimuli (p < 0.05), and for the pooled data from all 8 stimuli (p = 0.0006). CONCLUSION: Stimulation of the sympathetic AA point significantly decreased the stimulus-evoked EDR when compared with an AA stimulation to a non-sympathetic (placebo) point. However, it did not significantly alter EDR compared with no treatment. This implies that the increase in response as a result of inserting the needles was negated by placing the electrodes in the AA sympathetic point. Consequently, one might surmise that there may be a specific action of AA in respect to hyperhidrosis resulting from an increase in sympathetic activity.

Cloning and expression analysis of the bovine dentin matrix acidic phosphoprotein gene.

The dentin matrix acidic phosphoprotein gene has been mapped to human chromosome 4q21 and mouse chromosome 5q21. Expression studies have implicated a role for this gene in the mineralization of dentin. In the current investigation, a cDNA encoding bovine dentin matrix acidic phosphoprotein has been cloned and sequenced. A comparison of the bovine gene with its rat counterpart has indicated that the genes are conserved (67.4% identity; 79.5% similarity), particularly in the region of presumed functional elements such as the hydrophobic signal peptide sequence, the cell attachment Arg-Gly-Asp tripeptide, and numerous serine residues which are likely candidates for phosphorylation. Zoo blot analysis further indicated that a similar gene is found in all mammalian species tested, but not in chicks. However, Northern analysis has indicated that in the cow the message is detectable at high levels in fetal bovine brain and cultured long bone as well as in odontoblasts. These results support a potential role for dentin matrix acidic phosphoprotein in dentinogenesis.

Mouse tetranectin: cDNA sequence, tissue-specific expression, and chromosomal mapping.

Tetranectin is a plasminogen-binding tetrameric protein originally isolated from plasma. Expression of tetranectin appears ubiquitous, although particularly high expression is noted in the stroma of malignant tumors and during mineralization. To dissect the molecular basis of tetranectin gene regulation, mouse tetranectin cDNA was cloned from a 16-day-old mouse embryo library. Sequence analysis revealed a 992-bp cDNA with an open reading frame of 606 bp, which is identical in length to the human tetranectin cDNA. The deduced amino acid sequence showed high homology to the human cDNA with 76% identity and 87% similarity at the amino acid level. Sequence comparisons between mouse and human tetranectin and some C-type lectins confirmed a complete conservation in the position of six cysteines as well as numerous other amino acid residues, indicating an essential structure for potential function(s) of tetranectin. The sequence analysis revealed a difference in both sequence and size of the noncoding regions between mouse and human cDNAs. Northern analysis of the various tissues from mouse, rat, and cow showed the major transcript(s) to be approximately 1 kb, which is similar in size to that observed in human. Although additional minor bands of 1.5 and 3.3 kb were found in Northern blots, RT-PCR (reverse transcription polymerase chain reaction) analysis failed to provide evidence that these minor bands are products of the tetranectin gene. Finally, the genetic map location for this gene, Tna, was determined to be on distal mouse Chromosome (Chr) 9 by analysis of two sets of multilocus crosses.

Cloning and sequence analysis of bovine bone sialoprotein cDNA: conservation of acidic domains, tyrosine sulfation consensus repeats, and RGD cell attachment domain.

We isolated and sequenced a cDNA encoding bovine bone sialoprotein (BSP) using a bovine cDNA library made from mRNA isolated from bone-derived cell cultures and ligated to a phage lambda gt11. One of the cDNA clones isolated from this library had a 1800 base pair long insert and was found to contain the entire protein-encoding region. The deduced protein sequence revealed a 310 amino acid protein containing a signal peptide sequence of 16 hydrophobic amino acids. The protein sequence shows remarkable conservation with previously published human and rat sequences (more than 80% similarity for both species). The potential functional domains of BSP, including three acid amino acid-rich sequences, tyrosine sulfation consensus repeats, and the RGD cell binding sequence, are all present in the bovine sequence. Northern analysis of RNA from different bovine tissues indicated the presence of BSP message in bone but not in other nonmineralized tissues, confirming that bone is the major site of BSP message production.