The effect of valgus/varus malalignment on load distribution in total knee replacements

Valgus or varus malpositioning of the tibial component of a total knee implant may cause increased propensity for loosening or implant wear and eventually may lead to revision surgery. The aim of this study was to determine the effect of valgus/varus malalignment on tibio-femoral mechanics during surgical trial reduction and simulated gait loading. In seven cadaver legs, posterior cruciate sparing total knee replacements were implanted and tibial inserts representing a neutral alignment and 3 degrees and 5 degrees varus and valgus alignments were sequentially inserted. Each knee with each insert was loaded in a manner representative of a trial reduction performed during knee surgery and loaded in a physiological knee simulator. Simulated gait performed on the simulator demonstrated that internal/external and adduction/abduction rotations showed statistical changes with some of the angled inserts at different points in the walking cycle. Neither medial/lateral nor anterior/posterior translations changed statistically during simulated walking. The pressure distribution and total load in the medial and lateral compartments of the tibial component changed significantly with as little as a 3 degrees variation in angulation when loaded in a manner representative of a trial reduction or with a knee simulator. These results support the need for precise surgical reconstruction of the mechanical axis of the knee and proper alignment of the tibial component. These results further demonstrate that tibial contact pressures measured during a trial reduction method may be predictive of contact mechanics at the higher loading seen in the knee simulator.     

New species of Schoenobiblus (Thymelaeaceae) from Venezuela

Schoenobiblus suffruticosa andSchoenobiblus crassisepala, from the Parque Nacional “Henri Pittier” and adjacent montane forests, are described and illustrated.     

Effects of water quality and season on diatom community structure in the Damour River,Lebanon

The diatom flora in the lower Damour River, a small coastal river in Lebanon, was studied during 1981. The study area included the Damour estuary and a tributary, the el-Hamam River. Achnanthes minutissima was the most abundant diatom in the flora. Other dominant taxa included Nitzschia dissipata and Navicula cryptocephala var. veneta in the spring and Anomoeoneis vitrea in the fall. The diatom community structure was characterized by 1 or 2 dominant taxa, a few common and many rare taxa, but the taxa in these categories varied according to season and locality. The freshwater flora had a group of 20 taxa which were widely distributed in the study area throughout the study period. These taxa, in addition to a few taxa of more restricted seasonal occurrence, were the major contributers to the flora and are characteristic of this river system. Certain aspects of the flora were resistant to change. Others were more sensitive to environmental conditions. The estuarine flora reflected brackish conditions beginning in June and extending through October.     

Pinewood Nematode,Bursaphelenchus xylophilus,Associated with Red Pine, Pinus resinosa,in Western Maryland

Red pines Pinus resinosa in Garrett and Allegany counties, Maryland, were examined during 1982-84 to determine distribution of the pinewood nematode, Bursaphelenchus xylophilus, within and among trees. Approximately 25-year-old (younger) and 47-year-old (older) trees were subdivided into the following categories: 1) trees with mostly green needles; 2) trees with mostly reddish-brown needles; 3) trees lacking needles but with bark intact; 4) trees lacking both needles and bark; and 5) trees with chlorotic, bleached-green needles. Bursaphelenchus xylophilus was found infecting 68% of younger red pines and 77% of older red pines. Nematodes were not evenly distributed in trees within any given tree decadence category or in trees of the same age. Nematodes were recovered from 20% of wood samples from trunks and primary and secondary branches in younger pines and from 15 % of older red pines. On the basis of tree decadence category, the highest incidence of infection in younger trees (31%) was in bleached-green needled trees (category 5), whereas in older trees the highest infection (25%) occurred in green needled trees (category 1). At both sites trunks were infected more often than branches.     

Networking with mitogen-activated protein kinases

Mitogen activated protein (MAP) kinases and their target ribosomal protein S6 (RSK) kinases have been recognized as shared components in the intracellular signaling pathways of many diverse cytokines. Recent studies have extended this protein kinase cascade by identifying the major activator of vertebrate MAP kinases as a serine/threonine/tyrosine-protein kinase called MEK, which is related to yeast mating factor-regulated protein kinases encoded by the STE7 and byr1 genes. MEK, in turn, may be activated following its phosphorylation on serine by either of the kinases encoded by proto-oncogenesraf1 ormos, as well as by p78 ^mekk , which is related to the yeast STE11 and byr2 gene products. Isoforms of all of these protein kinases may specifically combine to assemble distinct modules for intracellular signal transmission. However, the fundamental architecture of these protein kinase cascades has been highly conserved during eukaryotic evolution.     

Reproduction of Heterodera zeae and Its Suppression of Corn Plant Growth as Affected by Temperature

Reproduction of the corn cyst nematode (Heterodera zeae) and its effect on growth of corn (Zea mays) was studied in plant growth chambers at 24, 27, 30, 33, and 36 C. Reproduction of H. zeae increased directly with increase in temperature from 24 to 36 C. Fifteen-cm-d pots of corn seedlings inoculated with a mixture of 5,000 eggs + J2 and maintained for 8 weeks in growth chambers contained an average of 7,042 cysts + females at 36 C, but only 350 cysts + females at 24 C. Fresh weights of plants without nematodes were highest at 27 C and lowest at 36 C. Nematodes suppressed plant fresh weight by an average of 30% at 27 C and by 27% at 33 C but did not suppress plant weight at 36 C. Heterodera zeae has the highest reported temperature optimum for reproduction of any cyst nematode.     

A HISTOCHEMICAL STUDY OF CALLUS INITIATION FROM CARROT TAPROOT PHLOEM CULTIVATED IN VITRO

Cylinders of carrot taproot secondary phloem were cultured on one of four media: 1) 2% sucrose + 1% agar (SA); 2) Heller's basal medium (NA); 3) NA + 10^-5 g/liter 2,4-D (H4); and 4) NA + H4 + 15% coconut milk (HW). Samples were taken from the cultured explants at 3-day intervals. A morphological study of the cultured explants revealed no differences between callus-initiating explants (cultured on HW medium) and noncallus-initiating explants (cultured on SA, NA, and H4 media) within the first 3 days of culture. All explants exhibited a typical wound response. Cell division ceased in the NA and SA explants after the sixth day in culture. Extensive cell division occurred in the subsurface layer of dividing cells in the HW explants and resulted in the formation of callus by the ninth day in culture. Histochemical staining revealed that the activity of NAD diaphorase, succinic dehydrogenase, and cytochrome oxidase were closely correlated with the wound response and with callus initiation in the cultured explants. The activity of these enzymes was high in the layer of dividing cells of all explants after 3 days of culture, but with longer periods of culture the activity of these enzymes was closely correlated with the extent of cell division. Acid phosphatase activity was associated with the dividing cell layers of all explants, but comparatively little acid phosphatase activity was observed in the NA, SA, and H4 explants as compared to the HW explants, and acid phosphatase was strongly correlated with callus initiation by the HW explants. Using the nitroso reaction, “catechol tannins” were found in the surface layers of the NA, SA, and H4 explants, while no nitroso-reaction-positive substances were detected in the HW explants during the period of callus initiation.     

Fate and action of ricin in rat liver in vivo: translocation of endocytosed ricin into cytosol and induction of intrinsic apoptosis by ricin B‐chain

Cytotoxicity of many plant and bacterial toxins requires their endocytosis and retrograde transport from endosomes to the endoplasmic reticulum. Using cell fractionation and immunoblotting procedures, we have assessed the fate and action of the plant toxin ricin in rat liver in vivo, focusing on endosome‐associated events and induction of apoptosis. Injected ricin rapidly accumulated in endosomes as an intact A/B heterodimer (5–90 min) and was later (15–90 min) partially translocated to cytosol as A‐ and B‐chains. Unlike cholera and diphtheria toxins, which also undergo endocytosis in liver, neither in cell‐free endosomes loaded by ricin in vivo nor upon incubation with endosomal lysates did ricin undergo degradation in vitro. A time‐dependent translocation of ricin across the endosomal membrane occurred in cell‐free endosomes. Endosome‐located thioredoxin reductase‐1 was required for translocation as shown by its physical association with ricin chains and effects of its removal and inhibition. Ricin induced in vivo intrinsic apoptosis as judged by increased cytochrome c content, activation of caspase‐9 and caspase‐3, and enrichment of DNA fragments in cytosol. Furthermore, reduced ricin and ricin B‐chain caused cytochrome c release from mitochondria in vivo and in vitro, suggesting that the interaction of ricin B‐chain with mitochondria is involved in ricin‐induced apoptosis.     

Multi-scale inference of genetic trait architecture using biologically annotated neural networks

In this article, we present Biologically Annotated Neural Networks (BANNs), a nonlinear probabilistic framework for association mapping in genome-wide association (GWA) studies. BANNs are feedforward models with partially connected architectures that are based on biological annotations. This setup yields a fully interpretable neural network where the input layer encodes SNP-level effects, and the hidden layer models the aggregated effects among SNP-sets. We treat the weights and connections of the network as random variables with prior distributions that reflect how genetic effects manifest at different genomic scales. The BANNs software uses variational inference to provide posterior summaries which allow researchers to simultaneously perform (i) mapping with SNPs and (ii) enrichment analyses with SNP-sets on complex traits. Through simulations, we show that our method improves upon state-of-the-art association mapping and enrichment approaches across a wide range of genetic architectures. We then further illustrate the benefits of BANNs by analyzing real GWA data assayed in approximately 2,000 heterogenous stock of mice from the Wellcome Trust Centre for Human Genetics and approximately 7,000 individuals from the Framingham Heart Study. Lastly, using a random subset of individuals of European ancestry from the UK Biobank, we show that BANNs is able to replicate known associations in high and low-density lipoprotein cholesterol content.