Extensor tendon: anatomy, injury, and reconstruction

Although seemingly simple in its anatomy and function, the extensor mechanism of the hand is actually a complex set of interlinked muscles, tendons, and ligaments. A thorough understanding of the extensor anatomy is required to understand the consequences of injury at various levels. Reconstructive options must restore normal function. Whereas primary repair of anatomic structures is frequently possible in acute injury, it is rarely possible in chronic situations. Technically exacting procedures may be necessary to restore function.     

Use of soybean oil and ammonium sulfate additions to optimize secondary metabolite production

A valine-overproducing mutant (MA7040, Streptomyces hygroscopicus) was found to produce 1.5 to 2.0 g/L of the immunoregulant, L-683,590, at the 0.6 m3 fermentation scale in a simple batch process using soybean oil and ammonium sulfate-based GYG5 medium. Levels of both lower (L-683,795) and higher (HH1 and HH2) undesirable homolog levels were controlled adequately. This batch process was utilized to produce broth economically at the 19 m3 fermentation scale. Material of acceptable purity was obtained without the multiple pure crystallizations previously required for an earlier culture, MA6678, requiring valine supplementation for impurity control. Investigations at the 0.6 m3 fermentation scale were conducted, varying agitation, pH, initial soybean oil/ammonium sulfate charges, and initial aeration rate to further improve growth and productivity. Mid-cycle ammonia levels and lipase activity appeared to have an important role. Using mid-cycle soybean oil additions, a titer of 2.3 g/L of L-683,590 was obtained, while titers reached 2.7 g/L using mid-cycle soybean oil and ammonium sulfate additions. Both higher and lower homolog levels remained acceptable during this fed-batch process. Optimal timing of mid-cycle oil and ammonium sulfate additions was considered a critical factor to further titer improvements.     

Seasonal mortality trends in tree‐feeding insects: a field experiment

Abstract 1. The majority of general life‐history models treat the environment as being invariable through time, even though temporal variation in selective agents could dramatically change the outcomes, e.g. in terms of optimal size and time at maturity. For herbivorous insects, seasonal differences in food quality are reasonably well described, but seasonal dynamics of top‐down selective forces are poorly documented. 2. The present study attempted to quantify seasonal changes in predation risk of folivorous insect larvae in temperate forest habitats. In a series of field experiments, artificial larvae were exposed to predators, and the resulting bird‐inflicted damage was recorded. The trials were repeated regularly throughout the course of two summers. 3. A distinct peak of larval mortality was recorded in mid‐June (the nestling period for most insectivorous passerine birds), after which predation risk declined to a plateau of 20–30% below the peak value. 4. The recorded pattern is interpreted as a consequence of seasonal changes in the number and behaviour of insectivorous birds, and the abundance of alternative food resources for these predators. 5. A quantitative analysis based on field data indicated that considering temporal variation in mortality in life‐history models is crucial for obtaining realistic predictions concerning central life‐history traits, such as final body size in different generations.     

Spectral information as an orientation cue in dung beetles

During the day, a non-uniform distribution of long and short wavelength light generates a colour gradient across the sky. This gradient could be used as a compass cue, particularly by animals such as dung beetles that rely primarily on celestial cues for orientation. Here, we tested if dung beetles can use spectral cues for orientation by presenting them with monochromatic (green and UV) light spots in an indoor arena. Beetles kept their original bearing when presented with a single light cue, green or UV, or when presented with both light cues set 180° apart. When either the UV or the green light was turned off after the beetles had set their bearing in the presence of both cues, they were still able to maintain their original bearing to the remaining light. However, if the beetles were presented with two identical green light spots set 180° apart, their ability to maintain their original bearing was impaired. In summary, our data show that ball-rolling beetles could potentially use the celestial chromatic gradient as a reference for orientation.     

Compartmentalization of membrane trafficking,glucose transport,glycolysis, actin,tubulin and the proteasome in the cytoplasmic droplet/Hermes body of epididymal sperm

Discovered in 1909 by Retzius and described mainly by morphology, the cytoplasmic droplet of sperm (renamed here the Hermes body) is conserved among all mammalian species but largely undefined at the molecular level. Tandem mass spectrometry of the isolated Hermes body from rat epididymal sperm characterized 1511 proteins, 43 of which were localized to the structure in situ by light microscopy and two by quantitative electron microscopy localization. Glucose transporter 3 (GLUT-3) glycolytic enzymes, selected membrane traffic and cytoskeletal proteins were highly abundant and concentrated in the Hermes body. By electron microscope gold antibody labelling, the Golgi trafficking protein TMED7/p27 localized to unstacked flattened cisternae of the Hermes body, as did GLUT-3, the most abundant protein. Its biogenesis was deduced through the mapping of protein expression for all 43 proteins during male germ cell differentiation in the testis. It is at the terminal step 19 of spermiogenesis that the 43 characteristic proteins accumulated in the nascent Hermes body.     

First Administration of the Fc-Attenuated Anti-β Amyloid Antibody GSK933776 to Patients with Mild Alzheimer’s Disease: A Randomized,Placebo-Controlled Study

Objective

To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the Fc-inactivated anti-β amyloid (Aβ) monoclonal antibody (mAb) GSK933776 in patients with mild Alzheimer’s disease (AD) or mild cognitive impairment (MCI).

Methods

This was a two-part, single blind, placebo-controlled, first-time-in-human (FTIH) study of single (n = 18) and repeat dose (n = 32) intravenous GSK933776 0.001–6 mg/kg (ClinicalTrials.gov: NCT00459550). Additional safety data from an open-label, uncontrolled, single dose study of intravenous GSK933776 1–6 mg/kg (n = 18) are included (ClinicalTrials.gov: NCT01424436).

Results

There were no cases of amyloid-related imaging abnormalities-edema (ARIA-E) or –hemorrhage (ARIA-H) after GSK933776 administration in both studies. Three patients across the two studies developed anti-GSK933776 antibodies. Plasma GSK933776 half-life (t_1/2) was 10–15 days after repeat dosing. After each of three administrations of GSK933776, plasma levels of total Aβ42 and Aβ increased whereas plasma levels of free Aβ decreased dose dependently; no changes were observed for placebo. For total Aβ42 the peak:trough ratio was ≤2 at doses ≥3 mg/kg; for total Aβ the ratio was ≤2 at 6 mg/kg. CSF concentrations of Aβ showed increases from baseline to week 12 for Aβ X–38 (week 12:baseline ratio: 1.65; 95%CI: 1.38, 1.93) and Aβ X–42 (week 12:baseline ratio: 1.18; 95%CI: 1.06, 1.30) for values pooled across doses.

Conclusion

In this FTIH study the Fc-inactivated anti-Aβ mAb GSK933776 engaged its target in plasma and CSF without causing brain ARIA-E/H in patients with mild AD or MCI.

Trial Registration

ClinicalTrials.gov NCT00459550