Seasonal Thermal Energy Storage Program

The Seasonal Thermal Energy Storage (STES) Program designed to demonstrate the storage and retrieval of energy on a seasonal basis using heat or cold available from waste or other sources during a surplus period is described. Factors considered include reduction of peak period demand and electric utility load problems and establishment of favorable economics for district heating and cooling systems for commercialization of the technology. The initial thrust of the STES Program toward utilization of ground water systems (aquifers) for thermal energy storage is emphasized

Structure of the saxiphilin:saxitoxin (STX) complex reveals a convergent molecular recognition strategy for paralytic toxins.

Dinoflagelates and cyanobacteria produce saxitoxin (STX), a lethal bis-guanidinium neurotoxin causing paralytic shellfish poisoning. A number of metazoans have soluble STX-binding proteins that may prevent STX intoxication. However, their STX molecular recognition mechanisms remain unknown. Here, we present structures of saxiphilin (Sxph), a bullfrog high-affinity STX-binding protein, alone and bound to STX. The structures reveal a novel high-affinity STX-binding site built from a "proto-pocket" on a transferrin scaffold that also bears thyroglobulin domain protease inhibitor repeats. Comparison of Sxph and voltage-gated sodium channel STX-binding sites reveals a convergent toxin recognition strategy comprising a largely rigid binding site where acidic side chains and a cation-π interaction engage STX. These studies reveal molecular rules for STX recognition, outline how a toxin-binding site can be built on a naïve scaffold, and open a path to developing protein sensors for environmental STX monitoring and new biologics for STX intoxication mitigation

Biochemical Properties of Cytochrome P-450 in Relation to Steroid Oxygenation a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73858/1/j.1749-6632.1985.tb14606.x.pd

Using Lexical Analysis to Link Depression in Schizotypy

poster abstractIntroduction: Previous research has suggested that depression is a major symptom of schizophrenia, and, moreover, schizotypy. Speech has also been heavily studied within the schizophrenia-spectrum. Compared to healthy populations, those with schizotypy tend to show greater depression and use negative affect (emotion) words more frequently. Speech containing negative affect words has also been shown to correlate with depression in both the healthy population and the schizophrenia-spectrum. This study aimed to examine any differences in depression level and negative affect words between a schizotypy and control sample, and also if depression level can be linked to speech within schizotypy. Methods: 38 participants partook in an open-ended, semi-structured interview-25 making up the schizotypy group, and 13 in the non-schizotypy group. The interview was recorded, transcribed, and ran through Lexical Inquiry Word Count (LIWC), a computerized measure that evaluates speech content using a dictionary that contains over 4500 words/word stems across 68 categories. Participants were also administered two depression questionnaires. Results: The schizotypy sample showed significantly greater depression than controls (p.05, d= -.54).Within schizotypy, a trend level relationship between depression and negative affect words was observed (r= -.31, p>.05). Conclusion: These findings are consistent with previous studies reporting higher depression levels in the schizophrenia-spectrum compared to healthy populations. It is inconsistent, however, with regards to schizotypy and use of negative emotion words, which may be due in part to low power. Furthermore, this study shows that lexical analysis software has the potential to assist in the measurement of depression in schizotypy

The role of lrp-2 in C. elegans vulval cell lineage polarity

We investigated the role of the low-density lipoprotein receptor lrp-2 in C. elegans vulval cell lineage polarity. We find that despite the high conservation of the Wnt signaling component, LRP5/6, in higher order organisms it appears to have evolved after the split of Nematoda due to its absence in all nematode genomes examined. C. elegans contains multiple low-density lipoprotein receptors within its genome, two of which are lrp-1 and lrp-2. Due to the position in the genome and high sequence similarity we believe that lrp-2 is the product of a recent duplication of lrp-1 within the Caenorhabditis lineage (Minor and Sternberg, 2019d). To understand the potential role of lrp-1 and lrp-2, we sought to score the vulval phenotypes of these mutants during L4 stage. lrp-1(ku156) mutants are sick and arrest during an early larval stage. For this reason we were not able to examine the role of lrp-1 in vulval formation. Despite high sequence similarity and proposed functional redundancy with lrp-1, lrp-2 mutants are remarkably wild-type. lrp-2 is expressed in the developing vulva at the same time as both cam-1 and vang-1. By examining double and triple mutant strains we find that lrp-2 is likely to function downstream of egl-20 along with transmembrane proteins cam-1 and vang-1 (Minor and Sternberg, 2019b; Minor and Sternberg, 2019c). All three genes antagonize the lin-17/Frizzled pathway by directing the aberrant localization of SYS-1 to the posterior daughter cell of P7.p, thereby leading to the posterior orientation of the P7.p lineage (Minor and Sternberg, 2019a). These observations suggest the simple model shown in Figure 1, in which LRP-2 cooperates with CAM-1 and VANG-1 to respond to EGL-20. This work provides evidence that despite lacking a true LRP5/6 ortholog, the formation of the C. elegans vulva is controlled by another member of the low-density lipoprotein superfamily, lrp-2. This data could potentially lead to insight into the evolution of both structure and function of the highly important Wnt pathway component, LRP5/6. Despite strong genetic evidence, this work does not describe the physical interaction between LRP-2 and CAM-1, VANG-1, EGL-20. Can LRP-2 bind with the other transmembrane proteins, CAM-1 and VANG-1, involved in this pathway? Can LRP-2 physically bind the Wnt ligand, EGL-20? Future work should focus on the biochemistry of this pathway. Answers to these questions could provide interesting insights into the evolution of low-density lipoprotein receptors, including LRP5/6, as well as how Wnt signaling has evolved within nematodes without the presence of one of the most important and highly conserved transmembrane proteins

The role of lrp-2 in C. elegans vulval cell lineage polarity

We investigated the role of the low-density lipoprotein receptor lrp-2 in C. elegans vulval cell lineage polarity. We find that despite the high conservation of the Wnt signaling component, LRP5/6, in higher order organisms it appears to have evolved after the split of Nematoda due to its absence in all nematode genomes examined. C. elegans contains multiple low-density lipoprotein receptors within its genome, two of which are lrp-1 and lrp-2. Due to the position in the genome and high sequence similarity we believe that lrp-2 is the product of a recent duplication of lrp-1 within the Caenorhabditis lineage (Minor and Sternberg, 2019d). To understand the potential role of lrp-1 and lrp-2, we sought to score the vulval phenotypes of these mutants during L4 stage. lrp-1(ku156) mutants are sick and arrest during an early larval stage. For this reason we were not able to examine the role of lrp-1 in vulval formation. Despite high sequence similarity and proposed functional redundancy with lrp-1, lrp-2 mutants are remarkably wild-type. lrp-2 is expressed in the developing vulva at the same time as both cam-1 and vang-1. By examining double and triple mutant strains we find that lrp-2 is likely to function downstream of egl-20 along with transmembrane proteins cam-1 and vang-1 (Minor and Sternberg, 2019b; Minor and Sternberg, 2019c). All three genes antagonize the lin-17/Frizzled pathway by directing the aberrant localization of SYS-1 to the posterior daughter cell of P7.p, thereby leading to the posterior orientation of the P7.p lineage (Minor and Sternberg, 2019a). These observations suggest the simple model shown in Figure 1, in which LRP-2 cooperates with CAM-1 and VANG-1 to respond to EGL-20. This work provides evidence that despite lacking a true LRP5/6 ortholog, the formation of the C. elegans vulva is controlled by another member of the low-density lipoprotein superfamily, lrp-2. This data could potentially lead to insight into the evolution of both structure and function of the highly important Wnt pathway component, LRP5/6. Despite strong genetic evidence, this work does not describe the physical interaction between LRP-2 and CAM-1, VANG-1, EGL-20. Can LRP-2 bind with the other transmembrane proteins, CAM-1 and VANG-1, involved in this pathway? Can LRP-2 physically bind the Wnt ligand, EGL-20? Future work should focus on the biochemistry of this pathway. Answers to these questions could provide interesting insights into the evolution of low-density lipoprotein receptors, including LRP5/6, as well as how Wnt signaling has evolved within nematodes without the presence of one of the most important and highly conserved transmembrane proteins

C. elegans LRP-2 functions in vulval precursor cell polarity

The C. elegans vulva is formed from divisions of three vulval precursor cells (VPCs) – P5.p, P6.p, and P7.p – arranged along the anteroposterior axis in the ventral epithelium (Sulston and Horvitz, 1977). Previous analyses show the orientation of P5.p and P7.p descendants is determined by the interaction of multiple Wnt signals. Specifically, in the absence of all Wnts, the VPCs display a randomized orientation, which is likely the default (Green et al., 2008; Minor et al. 2013). Two separate Wnts from the anchor cell, LIN-44 and MOM-2 acting through receptors LIN-17/Frizzled and LIN-18/Ryk, respectively, regulate P7.p orientation (Ferguson et al., 1987; Sternberg and Horvitz, 1988; Sawa et al., 1996; Inoue et al., 2004; Gleason et al., 2006). In the absence of these signals the orientation of the progeny of P7.p mimic those of P5.p and face toward the posterior of the worm, a phenotype referred to as posterior-reversed vulval lineage (P-Rvl). This posterior orientation is dependent on the instructive signal EGL-20, a Wnt expressed in the tail acting through CAM-1/ROR and VANG-1/Van Gogh, and is referred to as “ground polarity” (Green et al., 2008). Here we examine the role of a low-density lipoprotein receptor, lrp-2, and its role in controlling the orientation of P7.p daughter cells. To investigate this interaction double mutants were constructed with both alleles of lrp-2 and lin-17(n671) (Table 1). Much like cam-1(gm122) and vang-1(ok1142), both alleles of lrp-2 suppress the lin-17(n671) phenotype from 74 to approximately 50% P-Rvl leading us to hypothesize that lrp-2 functions in the same pathway as cam-1 and vang-1. Furthering this hypothesis we have shown that, like cam-1 and vang-1, lrp-2 controls the localization of SYS-1/b-catenin (Minor and Sternberg, 2019). To ensure that this phenotype was a result of loss of lrp-2 function as opposed to background effects we injected a fosmid (WRM0617cA02) containing the full-length sequence of lrp-2 and found that it does rescue the double mutant phenotype of lin-17(n671); lrp-2(gk272) from 55 to 73%. In order to better test this hypothesis a triple mutant was constructed between lin-17(n671), lrp-2(gk272), and cam-1(gm122) (Table 1). This triple mutant displays the same P-Rvl penetrance as both the lin-17(n671); lrp-2(gk272) and lin-17(n671); cam-1(gm122) double mutants confirming that lrp-2 functions in the same pathway as cam-1

Neonatal Calf Care

Calf mortality is important economically in dairy and beef herds. Calf losses substantially reduce the returns from cattle raising. The economic losses are those derived from the loss of the calf, planning and labor already invested by the herdsman, and veterinary expenses from obstetric and post-natal care. Indirect losses are infertility, chronic disease, and impaired development of the calf