A minimal view of single-particle imaging with X-ray lasers

The ability to serially interrogate single biomolecules with femtosecond X-ray pulses from free-electron lasers has ushered in the possibility of determining the three-dimensional structure of biomolecules without crystallization. However, the complexity of imaging a sample''s structure from very many of its noisy and incomplete diffraction data can be daunting. In this review, we introduce a simple analogue of this imaging workflow, use it to describe a structure reconstruction algorithm based on the expectation maximization principle, and consider the effects of extraneous noise. Such a minimal model can aid experiment and algorithm design in future studies.     

Testate amoeba records indicate regional 20th‐century lowering of water tables in ombrotrophic peatlands in central‐northern Alberta,Canada

Testate amoebae are abundant in the surface layers of northern peatlands. Analysis of their fossilized shell (test) assemblages allows for reconstructions of local water‐table depths (WTD). We have reconstructed WTD dynamics for five peat cores from peatlands ranging in distance from the Athabasca bituminous sands (ABS) region in western Canada. Amoeba assemblages were combined with plant macrofossil records, acid‐insoluble ash (AIA) fluxes and instrumental climate data to identify drivers for environmental change. Two functional traits of testate amoebae, mixotrophy and the tendency to integrate xenogenic mineral matter in test construction, were quantified to infer possible effects of AIA flux on testate amoeba presence. Age–depth models showed the cores each covered at least the last ~315 years, with some spanning the last millennium. Testate amoeba assemblages were likely affected by permafrost development in two of the peatlands, yet the most important shift in assemblages was detected after 1960 CE. This shift represents a significant apparent lowering of water tables in four out of five cores, with a mean drop of ~15 cm. Over the last 50 years, assemblages shifted towards more xerophilous taxa, a trend which was best explained by increasing Sphagnum s. Acutifolia and, to a lesser extent, mean summer temperature. This trend was most evident in the two cores from the sites located farthest away from the ABS region. AIA flux variations did not show a clear effect on mineral‐agglutinating taxa, nor on S. s. Acutifolia presence. We therefore suggest the drying trend was forced by the establishment of S. s. Acutifolia, driven by enhanced productivity following regional warming. Such recent apparent drying of peatlands, which may only be reconstructed by appropriate indicators combined with high chronological control, may affect vulnerability to future burning and promote emissions of CO₂.     

Minor components of ponderosa pine oleoresin

Esters of ferulic acid with monoterpene alcohols were found in ponderosa pine oleoresin. These colorless ferulic acid esters are responsible for a yellow band seen on DEAE-Sephadex fractionation of the oleoresin. Two diterpene resin acids not previously found in pines and several resin acid artifacts were identified.     

Graduate education and the role of the physical anthropologist in biomedical teaching and research

There is a place for the physical anthropologist in biomedical teaching and research because of the special and unique skills possessed by this individual. However, eventual success in the health sciences environment requires the student to obtain the knowledge and background for functionally oriented teaching and research. Students interested in a biomedical teaching and research career must prepare themselves methodologically and theoretically. This requires: (1) teaching qualifications, (2) an increased emphasis on methodology and technology, (3) an increased emphasis on research and experimental design, (4) appropriate interdisciplinary courses which provide the background for both teaching and research, (5) increased interaction with graduate faculty active in research, and (6) the latitude to adapt the graduate program to meet these specific needs. Students who finish their graduate training with a marketable skill, and who can apply their unique talents to a specialized area, will have broad appeal in the job market and will considerably strengthen their career opportunities.     

Regulation of Nigeran Accumulation by Aspergillus aculeatus

Nigeran (mycodextran), an unbranched glucan consisting of alternating alpha,1-4 and alpha,1-3 linkages, is accumulated intracellularly by Aspergillus aculeatus, under conditions of nitrogen limitation and low pH (optimum pH 5.0). Both conditions are necessary. Nigeran is synthesized de novo from exogenous glucose and accounts for about 20% of the glucose transported by the mycelium. The polymer is diluted out but not degraded when the mycelium is transferred to fresh medium containing NH(4) (+). Cycloheximide prevents development of the nigeran biosynthetic system. The addition of substrate levels of NH(4) (+) to nigeran-accumulating mycelium immediately suppresses further nigeran buildup, presumably by diverting glucose to the biosynthesis of amino acids, nucleotides, etc.     

MITOCHONDRIAL STRUCTURE IN SITES OF STEROID SECRETION

1. Mitochondria of the adrenal gland, corpus luteum, theca interna and granulosa of the graafian follicle, interstitial cells of the testis, and placenta of the rat have been studied with the electron microscope. 2. In most sites of steroid secretion, the internal structure of the mitochondria is in the form of tubular reflections of the internal mitochondrial membrane, rather than plate-like cristae. 3. The mitochondria of the adrenal gland have a highly variable size, even within a single cell; they may reach 2 to 3 µ in diameter, and are nearly filled with tubules. 4. It is suggested that while mitochondria in many places have a tubular component, those in the adrenal gland are highly specialized by virtue of their giant size and their internal structure.     

HEMOLYTIC ANEMIAS,Recent Advances in Diagnosis and Treatment

The hemolytic anemias of unknown cause can be separated into two main groups: (1) those produced by a defect in cell structure, which is usually hereditary, and (2) those due to a hemolysin of immune-body type.The hemolytic anemias associated with hypersensitivity to drugs and disease processes such as leukemia are less well understood and need further investigation.Splenectomy is the only effective treatment in congenital hemolytic jaundice and in acquired hemolytic anemia; the operation should be carried out promptly in most cases. Transfusion may be used in all varieties of hemolytic disease and is the only effective form of therapy in sickle-cell anemia and paroxysmal nocturnal hemoglobinuria.     

Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation of LPA(1), p42 and p38alpha

Prostate cancer cell migration is an essential event both in the progression of prostate cancer and in the steps leading to metastasis. We report here that lysophosphatidic acid (LPA), a potent bioactive phospholipid, induces prostate cancer PC3 cell migration via the activation of the LPA(1) receptor, which is linked to a PTX-sensitive activation mechanism of the mitogen-activated protein kinases (MAPK). Our results demonstrate that parallel activation of ERK1/2 and p38, but not JNK, is responsible for LPA-stimulated PC3 cell migration. Furthermore, using small interfering RNA (siRNA) technology, and overexpressing dominant-negative mutants of p38 MAPK isotypes of alpha, beta, gamma and delta, we have identified that the activation of ERK2 (p42) and p38alpha, but not of ERK1 and the other isoforms of p38 MAPK, is required for LPA-induced migration. Our study provides the first evidence for a functional role of p42 and p38alpha in LPA-induced mammalian cell migration, and also demonstrates, for the first time, that the receptor LPA(1) mediates prostate cancer cell migration. The results of the present study suggest that LPA, the receptor LPA(1), ERK2 and p38alpha are important regulators for prostate cancer cell invasion and thus could play a significant role in the development of metastasis.     

The CRL4DTL E3 ligase induces degradation of the DNA replication initiation factor TICRR/TRESLIN specifically during S phase

A DNA replication program, which ensures that the genome is accurately and wholly replicated, is established during G1, before the onset of S phase. In G1, replication origins are licensed, and upon S phase entry, a subset of these will form active replisomes. Tight regulation of the number of active replisomes is crucial to prevent replication stress-induced DNA damage. TICRR/TRESLIN is essential for DNA replication initiation, and the level of TICRR and its phosphorylation determine the number of origins that initiate during S phase. However, the mechanisms regulating TICRR protein levels are unknown. Therefore, we set out to define the TICRR/TRESLIN protein dynamics throughout the cell cycle. Here, we show that TICRR levels are high during G1 and dramatically decrease as cells enter S phase and begin DNA replication. We show that degradation of TICRR occurs specifically during S phase and depends on ubiquitin ligases and proteasomal degradation. Using two targeted siRNA screens, we identify CRL4^DTL as a cullin complex necessary for TICRR degradation. We propose that this mechanism moderates the level of TICRR protein available for replication initiation, ensuring the proper number of active origins as cells progress through S phase.