Mucins and Their Role in Shaping the Functions of Mucus Barriers.

We review what is currently understood about how the structure of the primary solid component of mucus, the glycoprotein mucin, gives rise to the mechanical and biochemical properties of mucus that are required for it to perform its diverse physiological roles. Macroscale processes such as lubrication require mucus of a certain stiffness and spinnability, which are set by structural features of the mucin network, including the identity and density of cross-links and the degree of glycosylation. At the microscale, these same features affect the mechanical environment experienced by small particles and play a crucial role in establishing an interaction-based filter. Finally, mucin glycans are critical for regulating microbial interactions, serving as receptor binding sites for adhesion, as nutrient sources, and as environmental signals. We conclude by discussing how these structural principles can be used in the design of synthetic mucin-mimetic materials and provide suggestions for directions of future work in this field.

Susceptibility of Escherichia coli to the toxic L-proline analogue L-selenaproline is dependent on two L-cystine transport systems.

AIMS: L-Selenaproline (L-selenazolidine-4-carboxylic acid) is a toxic analogue of L-proline that inhibits the growth of the urinary tract pathogen Escherichia coli in both laboratory culture media and normal human urine. The aim of this study was to identify the transport systems involved in its uptake. METHODS AND RESULTS: Deletion mutants from the Keio collection were tested for their susceptibility to L-selenaproline (SCA) and L-selenocystine (SeCys) on minimal salts agar medium. All single-gene mutants were sensitive to both compounds, but double mutants with deletions in fliY and ydjN or in yecS and ydjN were resistant to SCA and SeCys. The YdjN transporter active in strain JW1905 (ΔfliY::kan yecC(+) yecS(+) ydjN(+)) was inhibited by both SCA and SeCys, but the FliY YecS YecC ABC transporter system active in strain JW1718 (fliY(+) yecC(+) yecS(+) ΔydjN::kan) was best inhibited by these compounds in the presence of dithiothreitol. CONCLUSIONS: L-selenaproline and L-selenocystine are accumulated by both the FliY YecC YecS and the YdjN L-cystine transporter systems in E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: Because susceptibility to selenium-containing analogues of L-proline and L-cystine is dependent on multiple transport systems, these compounds may be effective in the treatment of urinary tract infections.

Population genomic signatures of divergent adaptation, gene flow and hybrid speciation in the rapid radiation of Lake Victoria cichlid fishes.

Adaptive radiations are an important source of biodiversity and are often characterized by many speciation events in very short succession. It has been proposed that the high speciation rates in these radiations may be fuelled by novel genetic combinations produced in episodes of hybridization among the young species. The role of such hybridization events in the evolutionary history of a group can be investigated by comparing the genealogical relationships inferred from different subsets of loci, but such studies have thus far often been hampered by shallow genetic divergences, especially in young adaptive radiations, and the lack of genome-scale molecular data. Here, we use a genome-wide sampling of SNPs identified within restriction site-associated DNA (RAD) tags to investigate the genomic consistency of patterns of shared ancestry and adaptive divergence among five sympatric cichlid species of two genera, Pundamilia and Mbipia, which form part of the massive adaptive radiation of cichlids in the East African Lake Victoria. Species pairs differ along several axes: male nuptial colouration, feeding ecology, depth distribution, as well as the morphological traits that distinguish the two genera and more subtle morphological differences. Using outlier scan approaches, we identify signals of divergent selection between all species pairs with a number of loci showing parallel patterns in replicated contrasts either between genera or between male colour types. We then create SNP subsets that we expect to be characterized to different extents by selection history and neutral processes and describe phylogenetic and population genetic patterns across these subsets. These analyses reveal very different evolutionary histories for different regions of the genome. To explain these results, we propose at least two intergeneric hybridization events (between Mbipia spp. and Pundamilia spp.) in the evolutionary history of these five species that would have lead to the evolution of novel trait combinations and new species.

Probing the potential of mucus permeability to signify preterm birth risk.

Preterm birth is the leading cause of neonatal mortality, and is frequently associated with intra-amniotic infection hypothesized to arise from bacterial ascension across a dysfunctional cervical mucus plug. To study this dysfunction, we assessed the permeability of cervical mucus from non-pregnant ovulating (n = 20) and high- (n = 9) and low-risk (n = 16) pregnant women to probes of varying sizes and surface chemistries. We found that the motion of negatively charged, carboxylated microspheres in mucus from pregnant patients was significantly restricted compared to ovulating patients, but not significantly different between high- and low-risk pregnant women. In contrast, charged peptide probes small enough to avoid steric interactions, but sensitive to the biochemical modifications of mucus components exhibited significantly different transport profiles through mucus from high- and low-risk patients. Thus, although both microstructural rearrangements of the components of mucus as well as biochemical modifications to their adhesiveness may alter the overall permeability of the cervical mucus plug, our findings suggest that the latter mechanism plays a dominant role in the impairment of the function of this barrier during preterm birth. We expect that these probes may be readily adapted to study the mechanisms underlying disease progression on all mucosal epithelia, including those in the mouth, lungs, and gut.

1-Boraadamantane blows its top, sometimes. The mono- and polyhomologation of 1-boraadamantane.

[reaction: see text] 1-Boraadamantane.THF (3) reacts with 1 equiv of dimethylsulfoxonium methylide (4) to afford a monohomologated product. The polyhomologation of 1-boraadamantane.THF by ylide 4 followed by oxidative cleavage generates star polymethylene polymers incorporating a cyclohexane core. However, only one-third of the initiators lead to product formation, resulting in an observed degree of polymerization three times higher than expected. The polyhomologation of 3 was found to contain branch points after the fourth and fifth methylene insertions. At the branch points, the propagating species either terminate in tricyclic trialkylborane cages with collapsed, pyramidal inverted boron centers that are unreactive toward ylide or they continue in uninterrupted polymerization and eventually result in the formation of giant "tube-like" structures such as 5.

An unusually long ligamentum arteriosum.

During routine laboratory dissections an unusually long ligamentum arteriosum, measuring 40 mm, was observed. Apparently, such a length for an otherwise normal ligamentum has not been reported previously. Forty-three other ligamenta in adults and three in newborn or stillborn infants were also measured having a range of 8 mm to 24 mm (mean 15.47 mm) and 7.5 mm to 11 mm (mean 9.5 mm) respectively. Since short and long ligaments have been reported previously, both in the newborn as well as in the adult, the variability in length of this structure appears normal and without any functional significance.

Right-sided aorta: a cadaver report and brief discussion of human aortic arch anomalies.

We observed an unusual right-sided aorta during routine laboratory dissection. The short aortic arch passed to the right side of the esophagus and trachea and had four branches, from proximal to distal: left common carotid, right common carotid, right subclavian, left subclavian arteries. The ligamentum arteriosum connected the pulmonary trunk to the left subclavian artery and lay to the left of the esophagus and trachea. The left recurrent laryngeal nerve passed under the ligamentum arteriosum while the right recurrent laryngeal nerve passed under the aortic arch. The descending thoracic aorta was situated near the midline, anterior to the vertebral bodies; consequently, the right posterior intercostal arteries were shorter than normal. The large veins of the thorax and the other thoracic organs appeared normal.

Thrombocytopenia in Patients with Gastric Varices and the Effect of Balloon-occluded Retrograde Transvenous Obliteration on the Platelet Count.

OBJECTIVES: Gastric varices primarily occur in cirrhotic patients with portal hypertension and splenomegaly and thus are probably associated with thrombocytopenia. However, the prevalence and severity of thrombocytopenia are unknown in this clinical setting. Moreover, one-third of patients after balloon-occluded retrograde transvenous obliteration (BRTO) have aggravated splenomegaly, which potentially may cause worsening thrombocytopenia. The aim of the study is to determine the prevalence and degree of thrombocytopenia in patients with gastric varices associated with gastrorenal shunts undergoing BRTO, to determine the prognostic factors of survival after BRTO (platelet count included), and to assess the effect of BRTO on platelet count over a 1-year period. MATERIALS AND METHODS: This is a retrospective review of 35 patients who underwent BRTO (March 2008-August 2011). Pre- and post-BRTO platelet counts were noted. Potential predictors of bleeding and survival (age, gender, liver disease etiology, platelet count, model for end stage liver disease [MELD]-score, presence of ascites or hepatocellular carcinoma) were analyzed (multivariate analysis). A total of 91% (n = 32/35) of patients had thrombocytopenia (<150,000 platelet/cm(3)) pre-BRTO. Platelet counts at within 48-h, within 2 weeks and at 30-60 days intervals (up to 6 months) after BRTO were compared with the baseline pre-BRTO values. RESULTS: 35 Patients with adequate platelet follow-up were found. A total of 92% and 17% of patients had a platelet count of <150,000/cm(3) and <50,000/cm(3), respectively. There was a trend for transient worsening of thrombocytopenia immediately (<48 h) after BRTO, however, this was not statistically significant. Platelet count was not a predictor of post-BRTO rebleeding or patient survival. However, MELD-score, albumin, international normalized ratio (INR), and etiology were predictors of rebleeding. CONCLUSION: Thrombocytopenia is very common (>90% of patients) in patients undergoing BRTO. However, BRTO (with occlusion of the gastrorenal shunt) has little effect on the platelet count. Long-term outcomes of BRTO for bleeding gastric varices using sodium tetradecyl sulfate in the USA are impressive with a 4-year variceal rebleed rate and transplant-free survival rate of 9% and 76%, respectively. Platelet count is not a predictor of higher rebleeding or patient survival after BRTO.

Do electroweak precision data and Higgs-mass constraints rule out a scalar bottom quark with mass of order 5 GeV?

We study the implications of a scalar bottom quark, with a mass of O (5 GeV), within the minimal supersymmetric standard model. Light sbottoms may naturally appear for large tan(beta) and, depending on the decay modes, may have escaped experimental detection. We show that a light sbottom cannot be ruled out by electroweak precision data and the bound on the lightest CP-even Higgs-boson mass. We infer that a light b scenario requires a relatively light scalar top quark whose mass is typically about the top-quark mass. In this scenario the lightest Higgs boson decays predominantly into b pairs and obeys the mass bound m(h) less, similar 123 GeV.

Subisthmic accessory thyroid gland in man: a case report and a review of thyroid anomalies.

Morphological variations of the thyroid gland are common and generally occur superior to the gland, reflecting its developmental origin. In this report we describe an accessory lobe located inferior to both lateral lobes and the isthmus. The accessory lobe was supplied by a branch of the right inferior thyroid artery and its vein drained via the plexus thyroideus impar. A discussion of thyroid anomalies is presented and a system for classifying variations of thyroid anatomy is proposed.

Low-energy supersymmetry and the Tevatron bottom-quark cross section.

A long-standing discrepancy between the bottom-quark production cross section and predictions of perturbative quantum chromodynamics is addressed. We show that pair production of light gluinos, of mass 12 to 16 GeV, with two-body decays into bottom quarks and light bottom squarks, yields a bottom-quark production rate in agreement with hadron collider data. We examine constraints on this scenario from low-energy data and make predictions that may be tested at the next run of the Fermilab Tevatron collider.

Metallic dissolution of a civil war bullet embedded in a sternum.

The contemporary trend of converting departments of anatomy into departments of cell biology has brought with it the task of examining archive collections and storage facilities to figure out how to best utilize the available space. During one such inspection at the University of Louisville School of Medicine, a human sternum containing a dull metal projectile was uncovered. The projectile was easy to characterize as a bullet that had been deeply embedded in the bone. Less clear, however, were the circumstances detailing how the bullet had become lodged in the sternum, or how long the sternum might have been in storage at the University of Louisville. Radiographs of the sternum revealed a halo of surrounding density that dissipated in intensity from the margins of the bullet. Our initial hypothesis was that lead had been leached from the bullet into the bone matrix. To better assess what in fact contributed to this density, the sternum and the bullet were analyzed by energy-dispersive spectroscopy (EDS) to determine their elemental composition. That the bullet was composed of lead and aluminum was not surprising, but the extent to which the presence and dissolution of the bullet had affected the composition of the bony sternum was not entirely expected. The contribution of metal ions from the bullet to the inorganic matrix of bone was most notable for aluminum but nearly negligible for lead. This finding confirmed that bone affinity for metals is dependent upon the metal and supports previous reports that have suggested that lead is released from bone as soluble blood product during bony remodeling, whereas aluminum results in a significant elevation of bone density.