Generation and expression of a Hoxa11eGFP targeted allele in mice

Hox genes are crucial for body axis specification during embryonic development. Hoxa11 plays a role in anteroposterior patterning of the axial skeleton, development of the urogenital tract of both sexes, and proximodistal patterning of the limbs. Hoxa11 expression is also observed in the neural tube. Herein, we report the generation of a Hoxa11eGFP targeted knock‐in allele in mice in which eGFP replaces the first coding exon of Hoxa11 as an in‐frame fusion. This allele closely recapitulates the reported mRNA expression patterns for Hoxa11. Hoxa11eGFP can be visualized in the tail, neural tube, limbs, kidneys, and reproductive tract of both sexes. Additionally, homozygous mutants recapitulate reported phenotypes for Hoxa11 loss of function mice, exhibiting loss of fertility in both males and females. This targeted mouse line will prove useful as a vital marker for Hoxa11 protein localization during control (heterozygous) or mutant organogenesis. Developmental Dynamics 237:3410–3416, 2008. © 2008 Wiley‐Liss, Inc.     

Annular elastolytic giant cell granuloma of conjunctiva: A case report

Annular elastolytic giant cell granuloma is a condition characterized histologically by damaged elastic fibers associated with preponderance of giant cells along with absence of necrobiosis, lipid, mucin, and pallisading granuloma. It usually occurs on sun-damaged skin and hence the previous name actinic granuloma. A similar process occurs on the conjunctiva. Over the past three decades only four cases of conjunctival actinic granuloma have been documented. All the previous patients were females with lesions in nasal or temporal bulbar conjunctiva varying 2-3 mm in size. We report a male patient aged 70 years presenting with a 14 mm × 7 mm fleshy mass on right lower bulbar conjunctiva. Clinical differential diagnoses were lymphoma, squamous cell carcinoma in situ and amyloidosis. Surgical excision followed by histopathology confirmed it to be a case of actinic granuloma. This is the first case of isolated conjunctival actinic granuloma of such a large size reported from India.     

Ideal,catch, and slip bonds in cadherin adhesion

Classical cadherin cell-cell adhesion proteins play key morphogenetic roles during development and are essential for maintaining tissue integrity in multicellular organisms. Classical cadherins bind in two distinct conformations, X-dimer and strand-swap dimer; during cellular rearrangements, these adhesive states are exposed to mechanical stress. However, the molecular mechanisms by which cadherins resist tensile force and the pathway by which they convert between different conformations are unclear. Here, we use single molecule force measurements with an atomic force microscope (AFM) to show that E-cadherin, a prototypical classical cadherin, forms three types of adhesive bonds: catch bonds, which become longer lived in the presence of tensile force; slip bonds, which become shorter lived when pulled; and ideal bonds that are insensitive to mechanical stress. We show that X-dimers form catch bonds, whereas strand-swap dimers form slip bonds. Our data suggests that ideal bonds are formed as X-dimers convert to strand-swap binding. Catch, slip, and ideal bonds allow cadherins to withstand tensile force and tune the mechanical properties of adhesive junctions.     

Antinutritional factors and in vitro protein digestibility of improved haricot bean (Phaseolus vulgaris L.) varieties grown in Ethiopia

The antinutrient (raffinose oligosaccharides, tannins, phytic acid and trypsin inhibitors) composition and in vitro protein digestibility of eight improved varieties of Phaseolus vulgaris grown in Ethiopia were determined. Stachyose was the predominant alpha-galactosides in all haricot bean samples. Raffinose was also present in significant quantities but verbascose, glucose and fructose were not detected at all in the samples. The concentrations observed for the protein digestibility and antinutritional factors, varied significantly (P<0.05) between varieties investigated in this study. Mean values for protein digestibility ranged from 80.66% (in Roba variety) to 65.64% (in Beshbesh variety). Mean values for raffinose, stachyose, sucrose, trypsin inhibitors, tannins and phytic acid were 3.14 mg/g, 14.86 mg/g, 24.22 mg/g, 20.68 TUIx10(3)/g, 17.44 mg, catechin equivalents/g and 20.54 mg/g respectively. Statistical analyses of data revealed that antinutritional factors and protein digestibility were influenced by variety (genotype). Relationships between antinutritional factors and protein digestibility were also observed. The possibility of selecting varieties to be used for large-scale cultivation in Ethiopia on the basis of these data is discussed. Among the improved varieties studied, Roba, Redwolaita, Mexican and Awash were found to be the best food and export type of haricot beans in the Ethiopian context, because of their higher protein digestibility, lower antinutrtional factors and other beneficial nutritional parameters. Roba variety can be used by local food processors for the production of value-added bean-based products especially to combat the problem of protein energy malnutrition and related diseases which are very common in developing countries.     

Super-Optimal NPK Along with Foliar Iron Application Influences Bioavailability of Iron and Zinc of Wheat

Deficiency of wheat grain iron (Fe) and zinc (Zn) is common nutritional problem in the developing countries and thus increasing their concentrations is a major challenge. Field experiments were conducted to investigate the effect of different levels of fertilizer nitrogen, phosphorus, potassium (100–200 % NPK) and foliar Fe application (3 % FeSO₄.7H₂O at 40, 60, and 75 days after sowing) on improving Fe and Zn concentrations in grain and molar ratio of phosphorus/iron (P/Fe) and phosphorus/zinc (P/Zn). Data obtained during the two year (2010–2011 and 2011–2012) field experiment reveals that foliar Fe spray along with fertilizer NPK significantly increased the grain Fe concentration by 6–15 %; whereas a sharp decrease in the grain Zn concentration under super optimal fertilization is attributed to the depressive effect of excessive phosphorus in the treatments. Molar ratio of P/Fe in wheat grains signifies the increased bioavailability of Fe in wheat grains but P/Zn increase under super-optimal NPK application calls for P management to correct the reduced level of Zn in wheat grains.     

Mean perfusion pressure deficit during the initial management of shock—an observational cohort study

Purpose

It is unclear if blood pressure targets for patients with shock should be adjusted to pre-morbid levels. We aimed to investigate mean deficit between the achieved mean perfusion pressure (MPP) in vasopressor-treated patients and their estimated basal (resting) MPP, and assess whether MPP deficit has any association with subsequent acute kidney injury (AKI).

Materials and Methods

Fifty-one consecutive, non-trauma patients, aged ≥ 40 years, with ≥ 2 organ dysfunction and requiring vasopressor ≥ 4 hours were observed at an academic intensive care unit. Mean MPP deficit [=%(basal MPP − achieved MPP)/basal MPP] and % time spent with > 20% MPP deficit were assessed during initial 72 vasopressor hours (T0-T72) for each patient.

Results

Achieved MPP was unrelated to basal MPP (P = .99). Mean MPP deficit was 18% (95% CI 15-21). Patients spent 48% (95% CI 39-57) time with > 20% MPP deficit. Despite similar risk scores at T0, subsequent AKI (≥ 2 RIFLE class increase from T0) occurred more frequently in patients with higher (> median) MPP deficit compared to patients with lower MPP deficit (56% vs 28%; P = .045). Incidence of subsequent AKI was also higher among patients who spent greater % time with > 20% MPP deficit (P = .04).

Conclusions

Achieved blood pressure during vasopressor therapy had no relationship to the pre-morbid basal level. This resulted in significant and varying degree of relative hypotension (MPP deficit), which could be a modifiable risk factor for AKI in patients with shock.