Dissipation, half-lives, and mass spectrometric identification of endosulfan isomers and the sulfate metabolite on three field-grown vegetables.

Endosulfan 3 EC, a mixture of α- and ß-stereo isomers, was sprayed on field-grown pepper, melon, and sweet potato plants at the recommended rate of 0.44 kg A.I. acre(-1). Plant tissue samples (leaves, fruits, or edible roots) were collected 1 h to 30 days following spraying and analyzed for endosulfan isomers (α- and ß-isomers). Analysis of samples was accomplished using a gas chromatograph (GC) equipped with a mass detector in total ion mode. The results indicated the formation of endosulfan sulfate as the major metabolite of endosulfan sulfite and the relatively higher persistence of the ß-isomers as compared to the α-isomer. The initial total residues (α- and ß-isomers plus endosulfan sulfate) were higher on leaves than on fruits. On pepper and melon fruits, the α-isomer, which is the more toxic to mammals, dissipated faster (T(1/2) = 1.22 and 0.95 d, respectively) than the less toxic ß-isomer (T(1/2) = 3.0 and 2.5 d, respectively). These results confirm the greater loss of the α-isomer compared to the ß-isomer, which can ultimately impact endosulfan dissipation in the environment. Additionally, the higher initial residues of endosulfan on pepper and sweet potato leaves should be considered of great importance for timing field operations and the safe entry of harvesters due to the high mammalian toxicity of endosulfan.

Recovery of proprioceptive feedback from nerve crush.

Sensorimotor functions are restored by peripheral nerve regeneration with greater success following injuries that crush rather than sever the nerve. Better recovery following nerve crush is commonly attributed to superior reconnection of regenerating axons with their original peripheral targets. The present study was designed to estimate the fraction of stretch reflex recovery attributable to functional recovery of regenerated spindle afferents. Recovery of the spindle afferent population was estimated from excitatory postsynaptic potentials evoked by muscle stretch (strEPSPs) in motoneurons. These events were measured in cats that were anaesthetized, so that recovery of spindle afferent function, including both muscle stretch encoding and monosynaptic transmission, could be separated from other factors that act centrally to influence muscle stretch-evoked excitation of motoneurons. Recovery of strEPSPs to 70% of normal specified the extent of overall functional recovery by the population spindle afferents that regained responsiveness to muscle stretch. In separate studies, we examined recovery of the stretch reflex in decerebrate cats, and found that it recovered to supranormal levels after nerve crush. The substantial disparity in recovery between strEPSPs and stretch reflex led us to conclude that factors in addition to recovery of spindle afferents make a large contribution in restoring the stretch reflex following nerve crush.

Some Believe, Not All Achieve: The Role of Active Learning Practices in Anxiety and Academic Self-Efficacy in First-Generation College Students.

First-generation college students face a variety of barriers in higher education compared with their continuing-generation peers. Active learning practices in STEM classrooms can potentially narrow the achievement gap by increasing academic self-efficacy, or confidence in academic abilities. However, these practices can also provoke anxiety in students. Given that anxiety can impair cognitive performance, we sought to understand how first-generation students perceive active learning practices and whether these perceptions affect the anticipated benefits of active learning. As part of a larger study on pedagogical practices in anatomy and physiology courses at the community college level, we asked students to rate various active learning techniques on how much each provoked anxiety and how much each contributed to their learning. All students (N = 186) rated some techniques as more anxiety-provoking than others (e.g., cold calling); however, compared to continuing-generation students, first-generation students' ratings tended to be higher. First-generation students anticipated doing more poorly in a course and attained lower final grades. Notably, the use of active learning practices did not improve first-generation students' academic self-efficacy: by the end of term, academic self-efficacy decreased in non-white first-generation students whereas other students showed little change. When introducing active learning strategies, instructors may need to proactively address underrepresented minority students' emotional reactions and ensure that all students experience success with these practices early in a course as a way to bolster academic self-efficacy.

The implications of force feedback for the lambda model.

It is argued here that length and force feedback play important but distinct roles in motor coordination. Length feedback compensates for several nonlinear properties of muscle and therefore simplifies its behavior, but in addition promotes the nonlinear relationship between force and stiffness that is essential to the mechanism for modulating joint stiffness. Excitatory force feedback is also primarily autogenic. Under conditions of level treadmill stepping in cat walking, positive force feedback is restricted in the distal hindlimb to a few and perhaps only one ankle extensor, the gastrocnemius muscle group. Based on the anatomy of this group, positive force feedback provides a stiff linkage that reinforces proportional coordination between ankle and knee joints. In terms of the lambda model, excitatory force feedback can reinforce muscular force generation and stiffness, but should have no significant effect on activation threshold. Inhibitory force feedback projects mainly to muscles that span different joints and axes of rotation than the parent muscle. This heterogenic force feedback is thought to promote interjoint coordination and thought to influence stiffness of the joints and limbs. During locomotion, the inhibitory influences appear to be focused on the distal musculature. Since the inhibitory force feedback is heterogenic, it also influences the threshold for activation of relevant musculature. Threshold is therefore not entirely a control variable and independent of feedback. It is proposed that the actuators for movement consist of systems of muscles or motor units that are linked by feedback and that receive control signals from elsewhere in the nervous system.

The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops.

HIV-1 protease (PR) is a 99 amino acid protein responsible for proteolytic processing of the viral polyprotein - an essential step in the HIV-1 life cycle. Drug resistance mutations in PR that are selected during antiretroviral therapy lead to reduced efficacy of protease inhibitors (PI) including darunavir (DRV). To identify the structural mechanisms associated with the DRV resistance mutation L33F, we performed X-ray crystallographic studies with a multi-drug resistant HIV-1 protease isolate that contains the L33F mutation (MDR769 L33F). In contrast to other PR L33F DRV complexes, the structure of MDR769 L33F complexed with DRV reported here displays the protease flaps in an open conformation. The L33F mutation increases noncovalent interactions in the hydrophobic pocket of the PR compared to the wild-type (WT) structure. As a result, L33F appears to act as a molecular anchor, reducing the flexibility of the 30s loop (residues 29-35) and the 80s loop (residues 79-84). Molecular anchoring of the 30s and 80s loops leaves an open S1/S1' subsite and distorts the conserved hydrogen-bonding network of DRV. These findings are consistent with previous reports despite structural differences with regards to flap conformation.

The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics.

Treatment of Human Immunodeficiency Virus remains challenging due to the emergence of drug resistant strains under the selective pressure produced by standard anti-retroviral therapy. To explore the structural mechanisms of drug resistance, we performed 40 ns molecular dynamics simulations on three multi-drug resistant HIV-1 protease clinical isolates from patients attending an infectious diseases clinic in Detroit, MI. We identify a novel structural role for the I47V, V32I, I54M and L90M major resistance mutations in flap opening and closure of MDR-PR isolates. Our studies suggest I47V is involved in flap opening and the interaction between I47V and V32I tethers the flaps to the active site. Also, I54M and L90M may be responsible for asymmetric movement of the protease flaps. These findings can be utilized to improve drug design strategies against MDR HIV-1 PR variants.

Heterogenic feedback between hindlimb extensors in the spontaneously locomoting premammillary cat.

Electrophysiological studies in anesthetized animals have revealed that pathways carrying force information from Golgi tendon organs in antigravity muscles mediate widespread inhibition among other antigravity muscles in the feline hindlimb. More recent evidence in paralyzed or nonparalyzed decerebrate cats has shown that some inhibitory pathways are suppressed and separate excitatory pathways from Golgi tendon organ afferents are opened on the transition from steady force production to locomotor activity. To obtain additional insight into the functions of these pathways during locomotion, we investigated the distribution of force-dependent inhibition and excitation during spontaneous locomotion and during constant force exertion in the premammillary decerebrate cat. We used four servo-controlled stretching devices to apply controlled stretches in various combinations to the gastrocnemius muscles (G), plantaris muscle (PLAN), flexor hallucis longus muscle (FHL), and quadriceps muscles (QUADS) during treadmill stepping and the crossed-extension reflex (XER). We recorded the force responses from the same muscles and were therefore able to evaluate autogenic (intramuscular) and heterogenic (intermuscular) reflexes among this set of muscles. In previous studies using the intercollicular decerebrate cat, heterogenic inhibition among QUADS, G, FHL, and PLAN was bidirectional. During treadmill stepping, heterogenic feedback from QUADS onto G and G onto PLAN and FHL remained inhibitory and was force-dependent. However, heterogenic inhibition from PLAN and FHL onto G, and from G onto QUADS, was weaker than during the XER. We propose that pathways mediating heterogenic inhibition may remain inhibitory under some forms of locomotion on a level surface but that the strengths of these pathways change to result in a proximal to distal gradient of inhibition. The potential contributions of heterogenic inhibition to interjoint coordination and limb stability are discussed.