Crystal Structure Lab

This activity is concerned with crystals, the basic building units that make up rocks and minerals. Students construct a model of the silicon-oxygen tetrahedron and discover that the smallest whole unit that could form a unique crystal is called a unit cell. They learn that a unit cell would have all the properties of a large crystal such as a diamond, but would be only molecular size (submicroscopic). If a crystal starts to form from a slowly cooling magma or from a drying up pool of salty sea water, unit cells add themselves one on top of another in order to develop the large crystals we can see and handle. Educational levels: High school, Middle school

The organization of the motoneurons innervating the axial musculature of vertebrates: II. Florida water snakes ( Nerodia fasciata pictiventris )

The motor pools of axial muscles in Florida water snakes (Nerodia fasciata pictiventris) were studied by applying horseradish peroxidase (HRP) to branches of spinal nerves innervating individual muscles or groups of muscles. Motor pools of different muscles or muscle groups were located in characteristic positions in both the transverse and the longitudinal extent of the motor column. Epaxial pools were located ventromedially in the column, segregated from most hypaxial ones, which were dorsolateral. The only exception to this general rule was the motoneurons innervating the levator costae muscle. Some of the motoneurons innervating this hypaxial muscle were located in the ventral part of the motor column, like epaxial motoneurons, but they were segregated longitudinally from epaxial ones. The arrangement of the motor pools was strikingly similar to the motor pools of presumptive homologous muscles in rats Smith and Hollyday: J. Comp. Neurol. 220: 29–43, '83), even though the locomotor mechanics in the two animals are very different. The similarities may reflect a comparable relationship between the location of motoneurons in. The motor column and the location, in embryonic life, of the muscles they innervate. They also suggest that differences in the locomotor mechanics in the two species are accomplished without any dramatic reorganization of the medial motor column, in marked contrast to the substantial reorganization necessary to account for differences in the motor columns of amniotes and anamniotes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50030/1/902490409_ftp.pd

A review of the organization and evolution of motoneurons innervating the axial musculature of vertebrates

In most anamniotes the axial musculature is myomeric and is functionally subdivided into superficial red and deep white muscle. In those anamniotes that have been studied the organization of the motor column is related to this functional subdivision. The motoneurons innervating red and white muscle differ in size, distribution in the motor column, and developmental history. There is no obvious topographic relationship between the location of motoneurons in the motor column and the dorsoventral location of the muscle they innervate in the myomeres; epaxial motoneurons are not segregated from hypaxial ones.Among amniotes, the myomeres divide to form a number of discrete muscles that may be complexly arranged. This breakup of the musculature is correlated with a subdivision of the motor column into discrete motor pools serving the different muscles. Unlike anamniotes, the motor pools are topographically organized. The epaxial pools are segregated from hypaxial ones, and within the epaxial and hypaxial pools the location of motoneurons innervating any particular muscle is related to the location of the muscle's precursor in the embryonic muscle masses.Thus adjacent motor pools innervate muscles arising from adjacent positions in the myotome.These dramatic differences between the motor columns in anamniotes and amniotes imply that the medial motor column has undergone a major restructuring during the evolution of vertebrates. The available evidence -- which is tentative because of the few species that have been studied -- suggests that a topographically organized motor column was absent in early vertebrates. A motor column/myotome map appears to have arisen just prior to, or in conjunction with the origin of amniotic vertebrates. The details of this map were conserved in different amniotes in spite of major structural and functional changes in the musculature. The map may be important for the proper control of the many muscles arising from the myotomes in amniotes because it facilitates the development and evolution of motor systems in which anatomically and functionally different muscles have spatially separate motor pools in the cord.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26658/1/0000202.pd

Features of the Structure, Development, and Activity of the Zebrafish Noradrenergic System Explored in New CRISPR Transgenic Lines

The noradrenergic (NA) system of vertebrates is implicated in learning, memory, arousal, and neuroinflammatory responses, but is difficult to access experimentally. Small and optically transparent, larval zebrafish offer the prospect of exploration of NA structure and function in an intact animal. We made multiple transgenic zebrafish lines using the CRISPR/Cas9 system to insert fluorescent reporters upstream of slc6a2, the norepinephrine transporter gene. These lines faithfully express reporters in NA cell populations, including the locus coeruleus (LC), which contains only about 14 total neurons. We used the lines in combination with two‐photon microscopy to explore the structure and projections of the NA system in the context of the columnar organization of cell types in the zebrafish hindbrain. We found robust alignment of NA projections with glutamatergic neurotransmitter stripes in some hindbrain segments, suggesting orderly relations to neuronal cell types early in life. We also quantified neurite density in the rostral spinal cord in individual larvae with as much as 100% difference in the number of LC neurons, and found no correlation between neuronal number in the LC and projection density in the rostral spinal cord. Finally, using light sheet microscopy, we performed bilateral calcium imaging of the entire LC. We found that large‐amplitude calcium responses were evident in all LC neurons and showed bilateral synchrony, whereas small‐amplitude events were more likely to show interhemispheric asynchrony, supporting the potential for targeted LC neuromodulation. Our observations and new transgenic lines set the stage for a deeper understanding of the NA system

Capacity analysis, cycle time optimization, and supply chain strategy in multi-product biopharmaceutical manufacturing operations

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering; in conjunction with the Leaders for Global Operations Program at MIT, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 99-104).Application of system optimization theory, supply chain principles, and capacity modeling are increasingly valuable tools for use in pharmaceutical manufacturing facilities. The dynamics of the pharmaceutical industry - market exclusivity, high margins, product integrity and contamination constraints - coupled with increasing cost pressures, demand for specialized products increase, and growing industry complexity makes analytical business decisions necessary to sustain competitive advantage. The united application of capacity modeling, system optimization, and supply chain analysis tools, paired with implementation strategies on a multi-product vaccine production system are detailed to address important business difficulties.by Kacey L. Fetcho-Phillips.S.M.M.B.A

Secondary motoneurons in juvenile and adult zebrafish: Axonal pathfinding errors caused by embryonic nicotine exposure

Nicotine is a drug of abuse that has been reported to have many adverse effects on the developing nervous system. We previously demonstrated that embryonic exposure to nicotine alters axonal pathfinding of spinal secondary motoneurons in zebrafish. We hypothesize that these changes will persist into adulthood. The Tg(isl1:GFP) line of zebrafish, which expresses green fluorescent protein (GFP) in a subtype of spinal secondary motoneurons, was used to investigate potential long-term consequences of nicotine exposure on motoneuron development. Anatomical characterization of Tg(isl1:GFP) zebrafish ranging between 3 and 30 days postfertilization (dpf) was initially performed in fixed tissue to characterize axonal trajectories in larval and juvenile fish. Tg(isl1:GFP) embryos were transiently exposed to 5–30 μM nicotine. They were then rescued from nicotine and raised into later stages of life (3–30 dpf) and fixed for microscopic examination. Morphological analysis revealed that nicotine-induced abnormalities in secondary motoneuron anatomy were still evident in juvenile fish. Live imaging of Tg(isl1:GFP) zebrafish using fluorescent stereomicroscopy revealed that the nicotine-induced changes in motoneuron axonal pathfinding persisted into adulthood. We detected abnormalities in 37-dpf fish that were transiently exposed to nicotine as embryos. These fish were subsequently imaged over a 7-week period of time until they were ≈3 months of age. These pathfinding errors of spinal secondary motoneuron axons detected at 37 dpf persisted within the same fish until 86 dpf, the latest age analyzed. These findings indicate that exposure to nicotine during embryonic development can have permanent consequences for motoneuron anatomy in zebrafish. J. Comp. Neurol. 512:305–322, 2009. © 2008 Wiley-Liss, Inc

Distribution and projection pattern of motoneurons that innervate hindlimb muscles in the quail

We characterized the motoneuron pool positions and projection patterns in the embryonic quail hindlimb and compared them to those in the chick to determine the degree of similarity and to form a baseline for future chimeric experiments. We find that the most similar parameters of pool position correlate with the major axonal pathway choices. First, the medial-lateral pool position, which is highly conserved among birds and mammals, is identical in the quail and chick and correlates with the dorsal-ventral pathway choice, the first and least plastic of the choices within the limb. Second, although quail pools were known to be compressed into seven rather than eight segments, we show that the map of pools is compressed about a central point (segment three) that preserves the spatial relationships between anterior pools and the crural plexus, and between posterior pools and the sciatic plexus. Access to guidance cues that are restricted to each plexus region is thus maintained between species. Third, pool position along the anterior-posterior axis is the least similar parameter between species. In fact, the entire lumbosacral motor complex may shift by ± half a segment in individual quail. Despite the consequent differences in segmental projections, the specific projection pattern within each quail hindlimb is identical to that in the chick. There is no need to preserve the exact segmental pattern either phylogenetically or during development, because motoneurons accommodate to modest variations in their position along the anterior-posterior axis by sorting out at the limb base. The contrast between variable segmental and constant limb projections also demonstrates that neither the specification nor the precise projection of motoneurons is dependent upon the specification or development of somites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50047/1/902980404_ftp.pd

River Restoration to Achieve a Stage 0 Condition: Summary of a Workshop Held November 5-6, 2020

Restoration to achieve Stage 0 is a valley-scale, process-based (hydrologic, geologic and biological) approach that aims to reestablish stream depositional environments to maximize longitudinal, lateral, and vertical connectivity at base flows and facilitate development of dynamic, self-formed and self-sustaining wetland-stream complexes. The term Stage 0 originally described complex multi-channel conditions and wider floodplains that evidence suggests were common when Euro-Americans arrived. Stage 0 is one stage in a 9-stage stream channel evolution model. Stage 0 is now also more broadly used to describe stream restoration projects aimed at changing the current condition and future evolution of incised, single-channel streams to achieve those multi-channel and wider floodplain conditions. The Stage 0 approach has generated excitement among restoration practitioners and researchers. It is seen as an action on a scale commensurate with past impacts; potentially capable of putting streams and their floodplains on a trajectory to recovery that is sustainable with minimal future intervention. Projects that reset the valley surface elevation may include the transfer of large amounts of sediment into incised channels from adjacent terraces using heavy machinery, and placement of logs and boulders to create structure across the resulting floodplain. Recreating expanded, complex and resilient stream and floodplain habitats over the longer term may involve considerable short-term disturbance of existing stream environments. Because some of these streams currently support sensitive populations of focal or endangered species (most notably salmonids) projects designed to achieve a Stage 0 condition have raised some questions and concerns among land managers and regulators charged with recovering those species. The approach is relatively new, so there are also questions regarding terminology, implementation and monitoring approaches, and appropriate sites and scale for these projects. In this science and policy context, a Stage 0 Stream Restoration Workshop was held on November 5-6, 2020 with the goal to bring together practitioners, researchers, regulators and other stakeholders to discuss current topics and data gaps related to implementing and monitoring restoration projects intended to achieve a Stage 0 condition. The online workshop included expert presentations, questions and discussions during plenary sessions, and smaller breakout groups. This document summarizes the workshop proceedings

A randomized, open-label study of the tolerability and efficacy of one or three daily doses of ivermectin plus diethylcarbamazine and albendazole (IDA) versus one dose of ivermectin plus albendazole (IA) for treatment of onchocerciasis

BACKGROUND: Onchocerciasis ( river blindness ) has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis. METHODS AND FINDINGS: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with two oral doses of ivermectin (150 μg/kg) separated by at least 6 months prior to treatment with either a single oral dose of ivermectin 150 μg/kg plus albendazole 400 mg (IA), a single oral dose of IDA (IDA1, IA plus diethylcarbamazine (DEC. 6 mg/kg) or three consecutive daily doses of IDA (IDA3). These treatments were tolerated equally well. While adverse events were common (approximately 30% overall), no severe or serious treatment-emergent adverse events were observed. Skin microfilariae were absent or present with very low densities after all three treatments through 18 months, at which time nodules were excised for histological assessment. Nodule histology was evaluated by two independent assessors who were masked regarding participant infection status or treatment assignment. Significantly lower percentages of female worms were alive and fertile in nodules recovered from study participants after IDA1 (40/261, 15.3%) and IDA3 (34/281, 12.1%) than after IA (41/180, 22.8%). This corresponds to a 40% reduction in the percentage of female worms that were alive and fertile after IDA treatments relative to results observed after the IA comparator treatment (P = 0.004). Percentages of female worms that were alive (a secondary outcome of the study) were also lower after IDA treatments (301/574, 52.4%) than after IA (127/198, 64.1%) (P = 0.004). Importantly, some comparisons (including the reduced % of fertile female worms after IDA1 vs IA treatment, which was the primary endpoint for the study) were not statistically significant when results were adjusted for intraclass correlation of worm fertility and viability for worms recovered from individual study participants. CONCLUSIONS: Results from this pilot study suggest that IDA was well tolerated after ivermectin pretreatment. They also suggest that IDA was more effective than the comparator treatment IA for killing or sterilizing female O. volvulus worms. No other short-course oral treatment for onchocerciasis has been demonstrated to have macrofilaricidal activity. However, this first study was too small to provide conclusive results. Therefore, additional studies will be needed to confirm these promising findings. TRIAL REGISTRATION: The study is registered at Cinicaltrials.gov under the number NCT04188301