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PubMed2004

Did an epidemic of tularemia in Ancient Egypt affect the course of world history?

The dynamics of the spreading, and the identity of a virulent epidemic, similar to bubonic plague or typhus, which hit Ancient Egypt in the middle of the Bronze Age, are hereby presented. Documented in medical papyri as well as archaeological findings, and re-echoed in biblical texts, a plague entered Egypt's main harbor, Avaris, around 1715 BC. As a result, the country was severely weakened at a time when it was already facing serious sociopolitical issues: crumbling central government, immigration, foreign influence, and the rise in power of the army and of warlords. The Hebrews, one of the ethnic groups within the Avaris area, appeared immune amidst the devastation of the plague. This immunity was key to identify the etiological agent of the epidemic: Francisella tularensis, the Gram-negative bacterium passed by ticks, and that causes tularemia. The disease manifests itself as either an ulceroglandular or a typhoid syndrome, accounting for its similarity with bubonic plague and typhus. Cellular immunity provides the main defense against F. tularensis, and is achieved through continuous contact with avirulent strains of the bacterium. Urban dwellers of Avaris, who had a limited contact to animals, would have been defenseless against the virulent strains, unlike the Hebrews, who lived off sheep and other animals. Attempting to consolidate Egypt's central government in the aftermath of the tularemia epidemic, led among others to the internment of the Hebrews in labor camps. The repressive measures against the Hebrews left traces in the subsequent archaeological layer (stratum F) at Avaris. As a corollary, the enslavement would set the stage for the exodus of the Hebrew community from Egypt at a later time.

Communicable Diseases↗
PubMed2003

Residual water modulates QA- -to-QB electron transfer in bacterial reaction centers embedded in trehalose amorphous matrices.

The role of protein dynamics in the electron transfer from the reduced primary quinone, Q(A)(-), to the secondary quinone, Q(B), was studied at room temperature in isolated reaction centers (RC) from the photosynthetic bacterium Rhodobacter sphaeroides by incorporating the protein in trehalose water systems of different trehalose/water ratios. The effects of dehydration on the reaction kinetics were examined by analyzing charge recombination after different regimes of RC photoexcitation (single laser pulse, double flash, and continuous light) as well as by monitoring flash-induced electrochromic effects in the near infrared spectral region. Independent approaches show that dehydration of RC-containing matrices causes reversible, inhomogeneous inhibition of Q(A)(-)-to-Q(B) electron transfer, involving two subpopulations of RCs. In one of these populations (i.e., active), the electron transfer to Q(B) is slowed but still successfully competing with P(+)Q(A)(-) recombination, even in the driest samples; in the other (i.e., inactive), electron transfer to Q(B) after a laser pulse is hindered, inasmuch as only recombination of the P(+)Q(A)(-) state is observed. Small residual water variations ( approximately 7 wt %) modulate fully the relative fraction of the two populations, with the active one decreasing to zero in the driest samples. Analysis of charge recombination after continuous illumination indicates that, in the inactive subpopulation, the conformational changes that rate-limit electron transfer can be slowed by >4 orders of magnitude. The reported effects are consistent with conformational gating of the reaction and demonstrate that the conformational dynamics controlling electron transfer to Q(B) is strongly enslaved to the structure and dynamics of the surrounding medium. Comparing the effects of dehydration on P(+)Q(A)(-)-->PQ(A) recombination and Q(A)(-)Q(B)-->Q(A)Q(B)(-) electron transfer suggests that conformational changes gating the latter process are distinct from those stabilizing the primary charge-separated state.

Desiccation↗
PubMed2002

Clinical implementation of intensity-modulated arc therapy.

PURPOSE: Intensity-modulated arc therapy (IMAT) is a method for delivering intensity-modulated radiation therapy (IMRT) using rotational beams. During delivery, the field shape, formed by a multileaf collimator (MLC), changes constantly. The objectives of this study were to (1) clinically implement the IMAT technique, and (2) evaluate the dosimetry in comparison with conventional three-dimensional (3D) conformal techniques. METHODS AND MATERIALS: Forward planning with a commercial system (RenderPlan 3D, Precision Therapy International, Inc., Norcross, GA) was used for IMAT planning. Arcs were approximated as multiple shaped fields spaced every 5-10 degrees around the patient. The number and ranges of the arcs were chosen manually. Multiple coplanar, superimposing arcs or noncoplanar arcs with or without a wedge were allowed. For comparison, conventional 3D conformal treatment plans were generated with the same commercial forward planning system as for IMAT. Intensity-modulated treatment plans were also created with a commercial inverse planning system (CORVUS, Nomos Corporation). A leaf-sequencing program was developed to generate the dynamic MLC prescriptions. IMAT treatment delivery was accomplished by programming the linear accelerator (linac) to deliver an arc and the MLC to step through a sequence of fields. Both gantry rotation and leaf motion were enslaved to the delivered MUs. Dosimetric accuracy of the entire process was verified with phantoms before IMAT was used clinically. For each IMAT treatment, a dry run was performed to assess the geometric and dosimetric accuracy. Both the central axis dose and dose distributions were measured and compared with predictions by the planning system. RESULTS: By the end of May 2001, 50 patients had completed their treatments with the IMAT technique. Two to five arcs were needed to achieve highly conformal dose distributions. The IMAT plans provided better dose uniformity in the target and lower doses to normal structures than 3D conformal plans. The results varied when the comparison was made with fixed gantry IMRT. In general, IMAT plans provided more uniform dose distributions in the target, whereas the inverse-planned fixed gantry treatments had greater flexibility in controlling dose to the critical structures. Because the field sizes and shapes used in the IMAT were similar to those used in conventional treatments, the dosimetric uncertainty was very small. Of the first 32 patients treated, the average difference between the measured and predicted doses was -0.54 +/- 1.72% at isocenter. The 80%-95% isodose contours measured with film dosimetry matched those predicted by the planning system to within 2 mm. The planning time for IMAT was slightly longer than for generating conventional 3D conformal plans. However, because of the need to create phantom plans for the dry run, the overall planning time was doubled. The average time a patient spent on the table for IMAT treatment was similar to conventional treatments. CONCLUSION: Initial results demonstrated the feasibility and accuracy of IMAT for achieving highly conformal dose distributions for different sites. If treatment plans can be optimized for IMAT cone beam delivery, we expect IMAT to achieve dose distributions that rival both slice-based and fixed-field IMRT techniques. The efficient delivery with existing linac and MLC makes IMAT a practical choice.

Brain Neoplasms↗
PubMed2003

The effects of stroke and age on finger interaction in multi-finger force production tasks.

OBJECTIVE: The main purpose of this study was to investigate changes in finger interaction after stroke with strongly unilateral motor effects. Effects of age on finger interaction were also analyzed. METHODS: Sixteen stroke subjects and 16 control subjects produced maximal voluntary contractions with different finger combinations by one hand and by two hands simultaneously. Individual finger forces were measured. In multi-finger tasks, force deficit (FD) was quantified as the difference between the peak finger forces in single-finger tasks and in multi-finger tasks, while enslaving (ENSL) was quantified as forces produced by fingers that were not required to produce force. RESULTS: In stroke subjects, the peak forces produced by the fingers of the impaired hand (IH) were about 36% less than those produced by the unimpaired hand. Stroke resulted in higher ENSL and decreased FD in the IH, particularly when the index and middle fingers produced force together, while aging led to higher FD and no change in ENSL. Two-hand tasks were accompanied by an additional drop in the force of individual fingers, i.e. bilateral deficit (BD). No changes in BD were observed with age or after stroke. CONCLUSIONS: We conclude that IH function in persons after stroke is accompanied not only by a general loss of finger force but also by changes in indices of multi-finger interaction. The contrast between the significantly changed indices of one-hand multi-finger interaction and unchanged BD implies that cortical neurons mediating interhemispheric inhibition are relatively spared in unilateral stroke. SIGNIFICANCE: The study shows that stroke leads to changes not only in finger force but also in finger interaction. The conclusion on relatively spared interhemispheric projections is potentially important for therapy of hand function in stroke survivors.

Adult↗
PubMed2006

Counterion-controlled transition of a cationic gemini from submicroscopic to giant vesicles.

While much is known about the self-assembly of lipids on nanoscale, our understanding of their biologically relevant mesoscale organization remains incomplete. Here, we show for a cationic gemini lipid a sharp and reversible transition from small vesicles with an average diameter of approximately 40 nm to giant vesicles (GVs) with an average diameter of approximately 11 microm. This transition is dependent on proper [NaCl] and specific temperature. Below this transition and in the vicinity of the air/water interface, a series of mesoscale morphological transitions was observed, revealing complex structures resembling biological membranes. On the basis of microscopy experiments, a tentative [NaCl] versus temperature shape/size phase diagram was constructed. To explain this unprecedented transition, we propose a novel mechanism whereby a specific interaction of Cl(-) counterion with the cationic gemini surfactant initiates the formation of a commensurate solute counterion lattice with low spontaneous curvature. In keeping with the high bending rigidity of NaCl crystal, this tightly associated ionic lattice enslaves membrane curvature and the mesoscale 3-D organization of this lipid.

Cations↗
PubMed1999

Utility of an African-centered support group for African American men confronting societal racism and oppression.

African American men suffer from the chronic stressor of living in a racist and oppressive society. This condition has historical roots dating back to enslavement and deportation from Africa to America. The psychological and physical difficulties that this group suffers from as a result of both the direct and the indirect influences of this chronic stressor have been well documented. However, a recent review of the literature revealed that not one article has been published in any of the major psychology journals that describes treatment issues or case studies focusing on this issue. This case study outlines the use of an African-centered group approach to helping African American men develop effective coping skills to successfully ameliorate the impact of societal racism and oppression on their lives.

Adaptation, Psychological↗
PubMed2002

The Yersinia Ysc-Yop 'type III' weaponry.

'Type III secretion'--the mechanism by which some pathogenic bacteria inject proteins straight into the cytosol of eukaryotic cells to 'anaesthetize' or 'enslave' them--was discovered in 1994. Important progress has been made in this area during the past few years: the bacterial organelles responsible for this secretion--called 'injectisomes'--have been visualized, the structures of some of the bacterial protein 'effectors' have been determined, and considerable progress has been made in understanding the intracellular action of the effectors. Type III secretion is key to the pathogenesis of bacteria from the Yersinia genus.

Animals↗
PubMed2002

The single, ancient origin of chromist plastids.

Algae include a diverse array of photosynthetic eukaryotes excluding land plants. Explaining the origin of algal plastids continues to be a major challenge in evolutionary biology. Current knowledge suggests that plastid primary endosymbiosis, in which a single-celled protist engulfs and "enslaves" a cyanobacterium, likely occurred once and resulted in the primordial alga. This eukaryote then gave rise through vertical evolution to the red, green, and glaucophyte algae. However, some modern algal lineages have a more complicated evolutionary history involving a secondary endosymbiotic event, in which a protist engulfed an existing eukaryotic alga (rather than a cyanobacterium), which was then reduced to a secondary plastid. Secondary endosymbiosis explains the majority of algal biodiversity, yet the number and timing of these events is unresolved. Here we analyzed a five-gene plastid data set to show that a taxonomically diverse group of chlorophyll c(2)-containing protists comprising cryptophyte, haptophyte, and stramenopiles algae (Chromista) share a common plastid that most likely arose from a single, ancient ( approximately 1,260 million years ago) secondary endosymbiosis involving a red alga. This finding is consistent with Chromista monophyly and implicates secondary endosymbiosis as an important force in generating eukaryotic biodiversity.

Algal Proteins↗
PubMed2005

Economy, speed and size matter: evolutionary forces driving nuclear genome miniaturization and expansion.

BACKGROUND: Nuclear genome size varies 300 000-fold, whereas transcriptome size varies merely 17-fold. In the largest genomes nearly all DNA is non-genic secondary DNA, mostly intergenic but also within introns. There is now compelling evidence that secondary DNA is functional, i.e. positively selected by organismal selection, not the purely neutral or 'selfish' outcome of mutation pressure. The skeletal DNA theory argued that nuclear volumes are genetically determined primarily by nuclear DNA amounts, modulated somewhat by genes affecting the degree of DNA packing or unfolding; the huge spread of nuclear genome sizes is the necessary consequence of the origin of the nuclear envelope and the nucleation of its assembly by DNA, plus the adaptively significant 300 000-fold range of cell volumes and selection for balanced growth by optimizing karyoplasmic volume ratios (essentially invariant with cell volume in growing/multiplying cells). This simple explanation of the C-value paradox is refined here in the light of new insights into the nature of heterochromatin and the nuclear lamina, the genetic control of cell volume, and large-scale eukaryote phylogeny, placing special emphasis on protist test cases of the basic principles of nuclear genome size evolution. GENOME MINIATURIZATION: and Expansion Intracellular parasites (e.g. Plasmodium, microsporidia) dwarfed their genomes by gene loss and eliminating virtually all secondary DNA. The primary driving forces for genome reduction are metabolic and spatial economy and cell multiplication speed. Most extreme nuclear shrinkage yielded genomes as tiny as 0.38 Mb (making the nuclear genome size range effectively 1.8 million-fold!) in some minute enslaved nuclei (nucleomorphs) of cryptomonads and chlorarachneans, chimaeric cells that also retain a separate normal large nucleus. The latter shows typical correlation between genome size and cell volume, but nucleomorphs do not despite co-existing in the same cell for >500 My. Thus mutation pressure does not inexorably increase genome size; selection can eliminate essentially all non-coding DNA if need be. Nucleomorphs and microsporidia even reduced gene size. Expansion of secondary DNA in the main nucleus, and in large-celled eukaryotes generally, must be positively selected for function. Ciliate nuclear dimorphism provides a key test that refutes the selfish DNA and strongly supports the skeletal DNA/karyoplasmic ratio interpretation of genome size evolution. GENETIC CONTROL OF CELL VOLUME IS MULTIGENIC: The quantitatively proportional correlation between genome size and cell size cannot be explained by purely mutational theories, as eukaryote cell volumes are causally determined by cell cycle control genes, not by DNA amounts.

Animals↗
PubMed2003

Plant culture: thirteen seasonal pieces. February--constructing a corymb.

According to Robert Graves' mythological interpretation of the seasonal cycle, February is associated with the rowan tree. Corymb is the systematic name for the rowan inflorescence that produces the distinctive group of orange berries. The corymb, a gently domed cluster, is related to a panicle and an anthela, differing from them in the extent of upgrowth of the inflorescence branches. Soon, molecular biology will provide a gene-driven description of each inflorescence structure. This advance illustrates the progress of science: previous issues of inflorescence classification are not resolved, but a new system, reflecting the availability of new technology, is established. The artist and poet William Blake remarked that it is better to invent a system, than be enslaved by that of another. He also railed against science for its improper restriction to the imagination.

Culture Techniques↗
PubMed2006

Patterns of intron loss and gain in plants: intron loss-dominated evolution and genome-wide comparison of O. sativa and A. thaliana.

Numerous previous studies have elucidated 2 surprising patterns of spliceosomal intron evolution in diverse eukaryotes over the past roughly 100 Myr. First, rates of recent intron gain in a wide variety of eukaryotic lineages have been surprisingly low, far too low to explain modern intron densities. Second, intron losses have outnumbered intron gains over a variety of lineages. For several reasons, land plants might be expected to have comparatively high rates of intron gain and thus to represent a possible exception to this pattern. However, we report several studies that indicate low rates of intron gain and an excess of intron losses over intron gains in a variety of plant lineages. We estimate that intron losses have outnumbered intron gains in recent evolution in Arabidopsis thaliana (roughly 12.6 times more losses than gains), Oryza sativa (9.8 times), the green alga Chlamydomonas reinhardtii (5.1 times), and the Bigelowiella natans nucleomorph, an enslaved green algal nucleus (2.8 times). We estimate that during recent evolution, A. thaliana and O. sativa have experienced very low rates of intron gain of around one gain per gene per 2.6-8.0 billion years. In addition, we compared 8,258 pairs of putatively orthologous A. thaliana-O. sativa genes. We found that 5.3% of introns in conserved coding regions are species-specific. Observed species-specific A. thaliana and O. sativa introns tend to be exact and to lie adjacent to each other along the gene, in a pattern suggesting mRNA-mediated intron loss. Our results underscore that low intron gain rates and intron number reduction are common features of recent eukaryotic evolution. This pattern implies that rates of intron creation were higher during earlier periods of evolution and further focuses attention on the causes of initial intron proliferation.

Amino Acid Sequence↗
PubMed2003

Genetic evidence for intra- and interspecific slavery in honey ants (genus Myrmecocystus).

The New World honey ant species Myrmecocystus mimicus is well known for its highly stereotyped territorial tournaments, and for the raids on conspecific nests that can lead to intraspecific slavery. Our results from mitochondrial and nuclear markers show that the raided brood emerges in the raiding colony and is subsequently incorporated into the colony's worker force. We also found enslaved conspecifics in a second honey ant species, M. depilis, the sister taxon of M. mimicus, which occurs in sympatry with M. mimicus at the study site. Colonies of this species furthermore contained raided M. mimicus workers. Both species have an effective mating frequency that is not significantly different from 1. This study provides genetic evidence for facultative intra- and interspecific slavery in the genus Myrmecocystus. Slavery in ants has evolved repeatedly and supposedly by different means. We propose that, in honey ants, secondary contact between two closely related species that both exhibit intraspecific slavery gave rise to an early form of facultative interspecific slavery.

Animals↗
PubMed2005

Isotropic-nematic spinodal decomposition kinetics.

The initial stage of isotropic-nematic spinodal demixing kinetics of suspensions of very long and thin, stiff, repulsive rods is analyzed on the basis of the N-particle Smoluchowski equation. Equations of motion for the reduced probability density function of the position and orientation of a rod are expanded up to second order in spatial gradients and leading order in orientational order parameter. The resulting equation of motion is solved analytically, from which the temporal evolution of light-scattering patterns are calculated. It is shown that inhomogeneities in number density are enslaved by the temporal development of inhomogeneities in orientational order. Furthermore, demixing due to rotational diffusion is shown to be much faster as compared to translational diffusion. This results in an instable mode that is rotational, for which the corresponding eigenvector remains finite at zero wave vector. The scattered intensity nevertheless exhibits a maximum at a finite wave vector due to the wave-vector dependence of time-exponential prefactors. The wave vector where the intensity exhibits a maximum is therefore predicted to be a function of time even during the initial stage of demixing.

Journal Article↗
PubMed2002

Two- and three-dimensional oscillons in nonlinear faraday resonance.

We study 2D and 3D localized oscillating patterns in a simple model system exhibiting nonlinear Faraday resonance. The corresponding amplitude equation is shown to have exact soliton solutions which are found to be always unstable in 3D. On the contrary, the 2D solitons are shown to be stable in a certain parameter range; hence the damping and parametric driving are capable of suppressing the nonlinear blowup and dispersive decay of solitons in two dimensions. The negative feedback loop occurs via the enslaving of the soliton's phase, coupled to the driver, to its amplitude and width.

Journal Article↗
PubMed1992

Mitochondrial DNA polymorphisms in Khoisan populations from southern Africa.

Mitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) were investigated in 95 individuals, consisting of 49 San ('Bushmen') and 46 Nama ('Hottentot') individuals from Namibia, using the restriction enzymes HpaI, BamHI, HaeII, MspI, AvaII and HincII. Six of the eleven types found in the pooled Khoisan sample are shared, albeit at varying frequencies, suggesting that both the San and Nama have evolved from a recent common ancestor. However, San and Nama groups differ appreciably, in particular, type 3-2 (3-1-1-2-2-2) was found in 7/49 Sekele and 25/46 Nama (chi 2 [1] = 15.3, P = 9.17 x 10(-5)). In addition, type 4 makes up 42.8% of the types found in the San, and is not found in the Nama group. This suggests that the San and Nama have evolved along separate lineages, with little gene flow between them, following their proposed separation from a common Khoisan ancestor. Type 7-2 (3-1-1-1-1-2), most common in Negroid populations, is found at a higher frequency in the San (20.4%) than the Nama (6.5%), suggesting that miscegenation involving Negroid females and San males is more common than that between Negroid females and Nama men. The higher frequency of type 21-2 (2-1-1-1-2-2) in the Nama (13%) than in the San (4.1%), may be attributable to gene flow from the Dama into the Nama, consistent with the consequences of enslavement of the Dama by the Nama.

Adult↗
PubMed2002

Respiratory mechanical unloading and proportional assist ventilation in infants.

UNLABELLED: Conventional patient-triggered ventilation attempts to synchronize the upstroke in ventilator pressure with the onset of spontaneous inspiration. Other parameters of the mechanical cycle such as the peak inspiratory pressure are preset by the clinician. They will be imposed on the infant regardless of the actual spontaneous respiratory drive. Proportional assist ventilation (PAV) and respiratory mechanical unloading of spontaneous breathing (RMU, resistive and elastic unloading) are based on fundamentally different concepts. In contrast to the conventional perception of the ventilator being a pump, RMU/PAV servo-controls the applied ventilator pressure continuously throughout each inspiration. These modalities proportionally enhance the effect on ventilation of each respiratory effort. They rely on rather than interfere with the subject's respiratory control system. The patient controls all variables of the respiratory pattern while the ventilator works fully enslaved as a proportional amplifier. Back-up conventional mechanical ventilation is initiated during episodes of hypoventilation and apnoea. The clinician sets the degree of the assist during RMU/PAV in terms of "gains". Selecting specific gains for the elastic and resistive unloading components allows the ventilator pressure waveform to be tailored to the individual degree of restrictive and obstructive pulmonary disease. This results in a reduction in the transpulmonary pressure cost of ventilation compared with conventional modes. CONCLUSION: Further studies on RMU/PAV are required to evaluate clinically important long-term outcome variables in infants and to determine whether the benefits outweigh potential drawbacks and the complexity involved in these new modes of mechanical ventilation.

Airway Resistance↗
PubMed2006

The medical ethics of Dr J Marion Sims: a fresh look at the historical record.

Vesicovaginal fistula was a catastrophic complication of childbirth among 19th century American women. The first consistently successful operation for this condition was developed by Dr J Marion Sims, an Alabama surgeon who carried out a series of experimental operations on black slave women between 1845 and 1849. Numerous modern authors have attacked Sims's medical ethics, arguing that he manipulated the institution of slavery to perform ethically unacceptable human experiments on powerless, unconsenting women. This article reviews these allegations using primary historical source material and concludes that the charges that have been made against Sims are largely without merit. Sims's modern critics have discounted the enormous suffering experienced by fistula victims, have ignored the controversies that surrounded the introduction of anaesthesia into surgical practice in the middle of the 19th century, and have consistently misrepresented the historical record in their attacks on Sims. Although enslaved African American women certainly represented a "vulnerable population" in the 19th century American South, the evidence suggests that Sims's original patients were willing participants in his surgical attempts to cure their affliction-a condition for which no other viable therapy existed at that time.

Black or African American↗
PubMed2004

Dynamics of living polymers.

We study theoretically the dynamics of living polymers which can add and subtract monomer units at their live chain ends. The classic example is ionic living polymerization. In equilibrium, a delicate balance is maintained in which each initiated chain has a very small negative average growth rate ("velocity") just sufficient to negate the effect of growth rate fluctuations. This leads to an exponential molecular weight distribution (MWD) with mean N. After a small perturbation of relative amplitude epsilon, e.g. a small temperature jump, this balance is destroyed: the velocity acquires a boost greatly exceeding its tiny equilibrium value. For epsilon > epsilonc approximately equal to 1/N(1/2) the response has 3 stages: (1) Coherent chain growth or shrinkage, leaving a highly non-linear hole or peak in the MWD at small chain lengths. During this episode, lasting time tau(fast) approximately N, the MWD's first moment and monomer concentration m relax very close to equilibrium. (2) Hole-filling (or peak decay) after tau(fill) approximately epsilon2N2. The absence or surfeit of small chains is erased. (3) Global MWD shape relaxation after tau(slow) approximately N2. By this time second and higher MWD moments have relaxed. During episodes (2) and (3) the fast variables (N, m) are enslaved to the slowly varying number of free initiators (chains of zero length). Thus fast variables are quasi-statically fine-tuned to equilibrium. The outstanding feature of these dynamics is their ultrasensitivity: despite the perturbation's linearity, the response is non-linear until the late episode (3). For very small perturbations, epsilon < epsilonc, response remains non-linear but with a less dramatic peak or hole during episode (1). Our predictions are in agreement with viscosity measurements on the most widely studied system, alpha-methylstyrene.

Binding Sites↗