SLO-2 isoforms with unique Ca2+- and voltage-dependence characteristics confer sensitivity to hypoxia in C. elegans

Slo channels are large conductance K⁺ channels that display marked differences in their gating by intracellular ions. Among them, the Slo1 and C. elegans SLO-2 channels are gated by calcium (Ca²⁺), while mammalian Slo2 channels are activated by both sodium (Na⁺) and chloride (Cl⁻). Here, we report that SLO-2 channels, SLO-2a and a novel N-terminal variant isoform, SLO-2b, are activated by Ca²⁺ and voltage, but in contrast to previous reports they do not exhibit Cl⁻ sensitivity. Most importantly, SLO-2 provides a unique case in the Slo family for sensing Ca²⁺ with the high-affinity Ca²⁺ regulatory site in the RCK1 but not the RCK2 domain, formed through interactions with residues E319 and E487 (that correspond to D362 and E535 of Slo1, respectively). The SLO-2 RCK2 domain lacks the Ca²⁺ bowl structure and shows minimal Ca²⁺ dependence. In addition, in contrast to SLO-1, SLO-2 loss-of-function mutants confer resistance to hypoxia in C. elegans. Thus, the C. elegans SLO-2 channels possess unique biophysical and functional properties.     

Current progress in use of adipose derived stem cells in peripheral nerve regeneration

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental model shave been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells(ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury(PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair.     

Effects of aflatoxin B1 and caffeine on viability in natural strains of Drosophila melanogaster

Thirty-five natural populations of Drosophila melanogaster from Virginia were tested for their degree of sensitivity to the carcinogen Aflatoxin B₁ (AFB₁) and to caffeine. Significant variations in sensitivity to each was demonstrated among these strains, but no correlation existed for relative degrees of sensitivity to AFB₁ or caffeine when strains were compared, although most strains were more severely affected by AFB₁. Eight of these strains were tested for the effects of simultaneous administration of AFB₁ and caffeine. Generally, caffeine demonstrated both a significant protective effect in preventing the high degree of egg-adult mortality produced by AFB₁ alone and a retardation of the significant decrease in body length shown by adults which survive in the AFB₁ treatments.     

How ancestral subsistence strategies solve salmon starvation and the “protein problem” of Pacific Rim resources

This article provides a theoretical treatment of hunter–gatherer diet and physiology. Through a synthesis of nutritional studies, informed by ethno-archaeological data, we examine the risk of protein-rich diets for human survival, and how societies circumvent "salmon starvation" in the northeastern Pacific Rim. Fundamental nutritional constraints associated with salmon storage and consumption counter long-standing assumptions about the engine of cultural evolution in the region. Excess consumption of lean meat can lead to protein poisoning, termed by early explorers “rabbit starvation.” While consumption of fats and carbohydrates is widely portrayed as a pathway to “offsetting” protein thresholds, there are true limits to the amount of protein individuals can consume, and constraints are most extreme for smaller individuals, children, and pregnant/nursing mothers. While this problem is not usually perceived as associated with fish, the risk of protein poisoning limits the amount of low-fat fish that people can eat safely. Compared with smaller, mass-harvested species (e.g., eulachon), dried salmon are exceedingly lean. Under certain circumstances fattier foods (small forage fish, marine mammals, whales, and even bears) or carbohydrate-rich plants may have been preferred not just for taste but to circumvent this “dietary protein ceiling.” Simply put, “salmon specialization” cannot evolve without access to complimentary caloric energy through fat-rich or carbohydrate-rich resources. By extension, the evolution of storage-based societies requires this problem be solved prior to or in tandem with-salmon intensification. Without such solutions, increased mortality and reproductive rates would have made salmon reliance unsustainable. This insight is in line with genomic research suggesting protein toxicity avoidance was a powerful evolutionary force, possibly linked to genetic adaptations among First Americans. It is also relevant to evaluating the plausibility of other purportedly “focal” economies and informs understanding of the many solutions varied global societies have engineered to overcome physiological protein limits.     

Further evidence for a partially folded intermediate in penicillinase secretion by Bacillus licheniformis.

Protoplasis of Bacillus licheniformis 749/C (a mutant constitutive for penicillinase production) continued to synthesize and release penicillinase in hypertonic growth medium in the presence of trypsin and chymotrypsin at 25 mug each per ml. When the protoplasts were stripped of about half of their membrane-bound penicillinase by pretreatment at pH 9.5 or with a higher level of trypsin, penicillinase activity no longer increased in the presence of the proteases. This effect was immediately eliminated after addition of soybean trypsin inhibitor. These proteases do not significantly inhibit general protein synthesis. Stripped protoplasts of strain 749/C and of uninduced strain 749 (unable to synthesize penicillinase) were incubated with 50 mug of chymotrypsin per ml, and the supernatent fluids were examined immunochemically for peptides derived from the penicillinase chain. Such fargments were found only with the protoplasts capable of synthesizing penicillinase (strain 749/C). The direct detection of the products of protease degradation of a susceptible form of penicillinase provides strong evidence that, in stripped protoplasts of B. licheniformis 749/C, penicillinase synthesis continues in the presence of trypsin or chymotrypsin and that, in these modified membranes, the protease is able to act on an early form of the enzyme that has not yet attained the protease-resistant conformation characteristic of the membrane-bound and exopenicillinases. This finding is discussed in terms of the current models of penicillinase secretion.     

Effects of the Bow on Social Organization in Western North America

The bow more than doubled, likely tripled, the success of individuals bent on killing animal or human targets (Box 1 ). The advent of this revolutionary technology generated different responses in western North America depending on subsistence and sociopolitical organization at the time of its arrival, roughly 2300 ‐ 1300 B.P. 1 Its effect was substantial in California and the Great Basin, particularly on group size, which in many places diminished as a consequence of the bow's reliability. The counter‐intuitive result was to increase within group‐relatedness enough to encourage intensification of plant resources, previously considered too costly. The bow rose to greatest direct economic importance with the arrival of the horse, and was put to most effective use by former Great Basin groups who maintained the family band system that had developed around intensive Great Basin plant procurement, adapting the same organization to a lifestyle centered on the equestrian pursuit of buffalo and warfare.     

Affinity chromatography purification of penicillinase of Bacillus licheniformis 749-C and its use to measure tuurnover of the cell bound enzyme

Affinity chromatography purification of small amounts of penicillinase using cephalosporin C covalently linked to Sepharose 4B has been used in examining the turnover of cell-bound penicillinase by B. licheniformis 749/C. Under conditions in which most of the nascent penicillinase is retained by the cells, turnover could be demonstrated (15% of the cell-bound enzyme in 2.5 hours), although most of the secreted enzyme is derived from newly-formed molecules.