Unraveling function and diversity of bacterial lectins in the human microbiome.

The mechanisms by which commensal organisms affect human physiology remain poorly understood. Lectins are non-enzymatic carbohydrate binding proteins that all organisms employ as part of establishing a niche, evading host-defenses and protecting against pathogens. Although lectins have been extensively studied in plants, bacterial pathogens and human immune cells for their role in disease pathophysiology and as therapeutics, the role of bacterial lectins in the human microbiome is largely unexplored. Here we report on the characterization of a lectin produced by a common human associated bacterium that interacts with myeloid cells in the blood and intestine. In mouse and cell-based models, we demonstrate that this lectin induces distinct immunologic responses in peripheral and intestinal leukocytes and that these responses are specific to monocytes, macrophages and dendritic cells. Our analysis of human microbiota sequencing data reveal thousands of unique sequences that are predicted to encode lectins, many of which are highly prevalent in the human microbiome yet completely uncharacterized. Based on the varied domain architectures of these lectins we predict they will have diverse effects on the human host. The systematic investigation of lectins in the human microbiome should improve our understanding of human health and provide new therapeutic opportunities.

Co-current crossflow microfiltration in a microchannel.

Steady state crossflow microfiltration (CMF) is an important and often necessary means of particle separation and concentration for both industrial and biomedical processes. The factors controlling the performance of CMF have been extensively reviewed. A major factor is transmembrane pressure (TMP). Because microchannels have small height, they tend to have high pressure gradients in the feed-flow direction. In the extreme, these gradients may even reverse the pressure across the membrane (inciting backflow). It is therefore desirable to compensate for the effect of feed-flow on the TMP, aiming at constant transmembrane pressure (cTMP) at a value which maximizes filtrate flux. This is especially critical during filtration of deformable particles (e.g. erythrocytes) through low intrinsic resistance membranes. Filtration flux is generally taken to be directly proportional to TMP, with pressure drop along the channel decreasing in the flow direction. A co-current flow of filtrate in a suitably designed filtrate collecting channel is shown to allow the TMP to remain constant and permit the sieving surface to perform optimally, permitting up to twice as much filtration over that of a naïve configuration. Manipulation of the filtrate channel may be even more beneficial if it prevents backflow that might otherwise occur at the end of a sufficiently long channel. Experiments with erythrocyte suspensions, reported here, validate these concepts.

Normal axillary thickness thresholds as a metric for nutritional status of children.

INTRODUCTION: Childhood pneumonia is a major cause of death in the 3rd world, and undernourishment increases the severity of the condition. We considered axillary thickness as a simple measurement to evaluate nutritional status that can be performed simultaneously with lung ultrasound. Our goal was to determine the distribution of axillary thickness in a cohort of children to determine a threshold for malnutrition. METHODS: Clinical databases were scanned to identify chest computed tomograms (CT) in children between the ages of 0 and 5 years with non-debilitating disease. The bilateral axillary thicknesses of the cohort were determined using equivalent width, and these measurements were segmented by age, sex, and laterality to determine cutoff thresholds. Data was evaluated using single factor analysis of variance (ANOVA) and 5th percentile analysis to determine the lower bound thresholds of axillary thickness. RESULTS: 247 scans met inclusion criteria. ANOVA demonstrated no significant differences in the mean measurements in the 5 groups (p = 0.377). 95% confidence limits on the 5th percentile plots showed an axillary thickness of 1.5 cm was a reasonable threshold for malnutrition detection for all age groups and sexes except for males between 0 and 1 years old where a 1.1 cm threshold may be required. DISCUSSION: CT scans of the chests in a cohort of children without debilitating disease revealed a remarkably uniform axillary thickness threshold for malnutrition assessment of 1.5 cm. This suggests that there may be a threshold for nutritional assessment for children undergoing lung ultrasound scans for childhood pneumonia.

Erythrocyte fouling on micro-engineered membranes.

Crossflow microfiltration of plasma from blood through microsieves in a microchannel is potentially useful in many biomedical applications, including clinically as a wearable water removal device under development by the authors. We report experiments that correlate filtration rates, transmembrane pressures (TMP) and shear rates during filtration through a microscopically high channel bounded by a low intrinsic resistance photolithographically-produced porous semiconductor membrane. These experiments allowed observation of erythrocyte behavior at the filtering surface and showed how their unique deformability properties dominated filtration resistance. At low filtration rates (corresponding to low TMP), they rolled along the filter surface, but at higher filtration rates (corresponding to higher TMP), they anchored themselves to the filter membrane, forming a self-assembled, incomplete monolayer. The incompleteness of the layer was an essential feature of the monolayer's ability to support sustainable filtration. Maximum steady-state filtration flux was a function of wall shear rate, as predicted by conventional crossflow filtration theory, but, contrary to theories based on convective diffusion, showed weak dependence of filtration on erythrocyte concentration. Post-filtration scanning electron micrographs revealed significant capture and deformation of erythrocytes in all filter pores in the range 0.25 to 2 µm diameter. We report filtration rates through these filters and describe a largely unrecognized mechanism that allows stable filtration in the presence of substantial cell layers.

Mouse BRWD1 is critical for spermatid postmeiotic transcription and female meiotic chromosome stability.

Postmeiotic gene expression is essential for development and maturation of sperm and eggs. We report that the dual bromodomain-containing protein BRWD1, which is essential for both male and female fertility, promotes haploid spermatid-specific transcription but has distinct roles in oocyte meiotic progression. Brwd1 deficiency caused down-regulation of ∼300 mostly spermatid-specific transcripts in testis, including nearly complete elimination of those encoding the protamines and transition proteins, but was not associated with global epigenetic changes in chromatin, which suggests that BRWD1 acts selectively. In females, Brwd1 ablation caused severe chromosome condensation and structural defects associated with abnormal telomere structure but only minor changes in gene expression at the germinal vesicle stage, including more than twofold overexpression of the histone methyltransferase MLL5 and LINE-1 elements transposons. Thus, loss of BRWD1 function interferes with the completion of oogenesis and spermatogenesis through sexually dimorphic mechanisms: it is essential in females for epigenetic control of meiotic chromosome stability and in males for haploid gene transcription during postmeiotic sperm differentiation.

Acute calciphylaxis precipitated by the initiation of hemodialysis.

Calciphylaxis, or calcific uremic arteriopathy (CUA), is characterized by metastatic calcification in the media of small arteries and arterioles leading to cutaneous necrosis. It is most commonly seen in patients with end stage renal disease who have elevated serum calcium × phosphorus (Ca × P) product. Normalization of Ca × P product is considered paramount in the prevention and treatment of CUA. We describe a novel presentation of CUA in which a Stage-5 CKD patient developed signs and symptoms of CUA immediately after initiation of hemodialysis (HD). We postulate that an influx of calcium from the dialysate into the patient's blood, in addition to correction of her acidosis, led to abundant substrate in a favorable milieu for Ca-P complex formation at the time of her first HD session. Our case is the first reported case of HD associated iatrogenic acute CUA. To avoid this complication, we should maintain adequate hydration,use lower calcium dialysate, and avoid vitamin D analogues and calcium-containing medications when initiating HD in patients with high Ca-P product. Since sodium thiosulfate is known to prevent precipitation of Ca-P complexes, its empiric use during initial HD treatments may be effective in preventing CUA, a potentially fatal disease.