We were there..

Polyamine block of inwardly rectifying potassium (Kir) channels underlies their steep voltage dependence observed in vivo. We have examined the potency, voltage dependence, and kinetics of spermine block in dimeric Kir2.1 constructs containing one nonreactive subunit and one cysteine-substituted subunit before and after modification by methanethiosulfonate (MTS) reagents. At position 169C (between the D172 “rectification controller” and the selectivity filter), modification by either 2-aminoethyl MTS (MTSEA) or 2-(trimethylammonium)ethyl MTS (MTSET) reduced the potency and voltage dependence of spermine block, consistent with this position overlapping the spermine binding site. At position 176C (between D172 and the M2 helix bundle crossing), modification by MTSEA also weakened spermine block. In contrast, MTSET modification of 176C dramatically slowed the kinetics of spermine unblock, with almost no effect on potency or voltage dependence. The data are consistent with MTSET modification of 176C introducing a localized barrier in the inner cavity, resulting in slower spermine entry into and exit from a “deep” binding site (likely between the D172 rectification controller and the selectivity filter), but leaving the spermine binding site mostly unaffected. These findings constrain the location of deep spermine binding that underlies steeply voltage-dependent block, and further suggest important chemical details of high affinity binding of spermine in Kir2.1 channels—the archetypal model of strong inward rectification.     

How large were the australopithecines?

Stature of the African early hominids is estimated from most of the available fragments of fossil long bones by means of regression analysis. The average height of the South African gracile australopithecines is predicted to be 145.1 cm (4′9″) where n = 4 and of the South African robust forms, 152.7 cm (5′) where n = 3. The East African early hominids are somewhat taller (x = 163.0 cm or 5′4″, where n = 7). Variability in stature is high even within the same site which is probably a reflection of fairly strong sexual dimorphism in body size. Evidence is presented which suggests that at least in one form of early hominid the size proportions of fore- and hindlimbs are different than in modern man. There is also evidence that average stature may have increased through time. The most significant of these findings is that the two forms of early hominids in South Africa are possibly more similar in stature than is usually cited. This does not imply necessarily that the two forms did not differ significantly in robustness or weight.     

These motors were made for walking

Kinesins are a diverse group of adenosine triphosphate (ATP)‐dependent motor proteins that transport cargos along microtubules (MTs) and change the organization of MT networks. Shared among all kinesins is a ~40 kDa motor domain that has evolved an impressive assortment of motility and MT remodeling mechanisms as a result of subtle tweaks and edits within its sequence. Several elegant studies of different kinesin isoforms have exposed the purpose of structural changes in the motor domain as it engages and leaves the MT. However, few studies have compared the sequences and MT contacts of these kinesins systematically. Along with clever strategies to trap kinesin–tubulin complexes for X‐ray crystallography, new advancements in cryo‐electron microscopy have produced a burst of high‐resolution structures that show kinesin–MT interfaces more precisely than ever. This review considers the MT interactions of kinesin subfamilies that exhibit significant differences in speed, processivity, and MT remodeling activity. We show how their sequence variations relate to their tubulin footprint and, in turn, how this explains the molecular activities of previously characterized mutants. As more high‐resolution structures become available, this type of assessment will quicken the pace toward establishing each kinesin's design–function relationship.     

Trichosanthin-induced specific changes of cytoskeleton configuration were associated with the decreased expression level of actin and tubulin genes in apoptotic Hela cells

Trichosanthin (TCS) possesses a broad spectrum of biological and pharmacological activities, including anti-cancer activities through apoptosis pathway. However, little is known about the effects of TCS on the cytoskeleton configuration and expression of actin and tubulin genes in Hela cell apoptosis. In the present study, apoptotic cytoskeleton structures were observed by confocal immunofluorescence microscopy, absolute amounts of actin and tubulin subunit mRNAs were determined by quantitative real-time PCR assays (QRT-PCR). Our results showed that the execution phase of cell apoptosis was a highly coordinated process of cellular reorganization, depolymerized microfilaments (MFs) accumulated in the coarsened cytoplasm and apoptotic bodies, followed by the formation of a ring microtubule (MT) structure beneath the plasma membrane. Importantly, apoptosis occurred by a suppression of actin and tubulin subunit gene expression. In particular, a rapid decrease in the amounts of gamma-actin mRNA preceded that of beta-actin; alpha- and beta-tubulin mRNAs were subsequently down-regulated in the later stage of Hela cell apoptosis. These results suggested that the execution of Hela cell apoptosis induced by TCS accompanied the specific changes of cytoskeleton configuration and, significantly, decreased the expression level of actin and tubulin subunit genes in different stages.     

Why were the first anthropologists creationists?

Anthropologists in every generation have been tarred as creationists by radical Darwinians. In only the very first generation of scholarly anthropology, however, does the charge really stick; that is, in the founding tradition of liberal German humanistic anthropology from about 1860–1890. This paper explores the ideas that may have motivated their rejection of evolution.