Role of cyclin-dependent kinase 4/6 inhibitors in the current and future eras of cancer treatment.

Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib. Palbociclib and ribociclib are currently food and drug administration-approved for use in combination with aromatase inhibitors in postmenopausal women with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Palbociclib is also food and drug administration-approved for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor to gain Food and Drug Administration (FDA) approval, specifically as monotherapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer previously treated with chemotherapy and endocrine therapy. Abemaciclib also shares a similar indication with palbociclib for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Trilaciclib use remains largely investigational at this time. However, despite FDA-approval for only metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, all four cyclin-dependent kinase 4/6 inhibitors have shown promise in hematologic malignancies and non-breast solid tumors. Although further research is needed, cyclin-dependent kinase 4/6 inhibitors represent intriguing developments in the treatment of various malignancies, including those with such poor prognoses as glioblastoma multiforme, mantle cell lymphoma, and metastatic melanoma. We discuss the approved indications, current research, and areas of future exploration for palbociclib, ribociclib, abemaciclib, and trilaciclib.

Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation.

OBJECTIVE: To compare time to achieve viral load <400 copies/ml and <1000 copies/ml in HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). DESIGN: Retrospective cohort study. SETTING: Three university medical centers, USA. POPULATION: HIV-infected pregnant women initiated or restarted on HAART during pregnancy. METHODS: We calculated time to viral load <400 copies/ml and <1000 copies/ml in HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. MAIN OUTCOME MEASURES: Time to HIV viral load <400 copies/ml and <1000 copies/ml. RESULTS: We evaluated 138 HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load < 400 copies/ml during pregnancy compared with 92% of ARV-experienced women (P = 0.82). The median number of days to achieve a viral load < 400 copies/ml in the ARV-naive cohort was 25.0 (range 3.5-133; interquartile range 16-34) days compared with 27.0 (range 8-162.5; interquartile range 18.5-54.3) days in the ARV-experienced cohort (P = 0.02). In a multiple predictor analysis, women with higher adherence (adjusted relative hazard [aRH] per 10% increase in adherence 1.29, 95% confidence interval [CI] 1.08-1.54, P = 0.01) and receiving a non-nucleotide reverse transcriptase inhibitor (NNRTI) -based regimen (aRH 2.48, 95% CI 1.33-4.63, P = 0.01) were more likely to achieve viral load <400 copies/ml earlier. Increased baseline HIV log10 viral load was associated with a later time of achieving viral load <400 copies/ml (aRH 0.60, 95% CI 0.39-0.92, P = 0.02). In a corresponding model of time to achieve viral load <1000 copies/ml, adherence (aRH per 10% increase in adherence 1.79, 95% CI 1.34-2.39, P < 0.001), receipt of NNRTI (aRH 2.95, 95% CI 1.23-7.06, P = 0.02), and CD4 cell count (aRH per 50 count increase in CD4 1.12, 95% CI 1.03-1.22, P = 0.01) were associated with an earlier time to achieve viral load below this threshold. Increasing baseline HIV log10 viral load was associated with a longer time of achieving viral load <1000 copies/ml (aRH 0.54, 95% CI 0.34-0.86, P = 0.01). In multiple predictor models, previous ARV exposure was not significantly associated with time to achieve viral load below thresholds of <400 copies/ml and <1000 copies/ml. CONCLUSIONS: Pregnant women with ≥50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load <400 copies/ml within a median of 26 days and a viral load of <1000 copies/ml within a median of 14 days of HAART initiation. Increased adherence, receipt of NNRTI-based regimen and lower baseline HIV log10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml.

Membrane fusion mediated by baculovirus gp64 involves assembly of stable gp64 trimers into multiprotein aggregates.

The baculovirus fusogenic activity depends on the low pH conformation of virally-encoded trimeric glycoprotein, gp64. We used two experimental approaches to investigate whether monomers, trimers, and/or higher order oligomers are functionally involved in gp64 fusion machine. First, dithiothreitol (DTT)- based reduction of intersubunit disulfides was found to reversibly inhibit fusion, as assayed by fluorescent probe redistribution between gp64-expressing and target cells (i.e., erythrocytes or Sf9 cells). This inhibition correlates with disappearance of gp64 trimers and appearance of dimers and monomers in SDS-PAGE. Thus, stable (i.e., with intact intersubunit disulfides) gp64 trimers, rather than independent monomers, drive fusion. Second, we established that merger of membranes is preceded by formation of large (greater than 2 MDa), short-lived gp64 complexes. These complexes were stabilized by cell-surface cross-linking and characterized by glycerol density gradient ultracentrifugation. The basic structural unit of the complexes is stable gp64 trimer. Although DTT-destabilized trimers were still capable of assuming the low pH conformation, they failed to form multimeric complexes. The fact that formation of these complexes correlated with fusion in timing, and was dependent on (a) low pH application, (b) stable gp64 trimers, and (c) cell-cell contacts, suggests that such multimeric complexes represent a fusion machine.

Tribolium castaneum: morphology of "aureate" revealed by the scanning electron microscope.

Counts of setae in "aureate" (au), spontaneous autosomal recessive mutation of good penetrance and viability, show that the au gene causes a three-fold increase in setation over the normal in the visible abdominal sternites but not in the membranous wings of the tenebrionid flour beetle Tribolium castaneum. Micrographs taken with the scanning electron microscope demonstrate that the au gene increases setation throughout the body.

[Antiplatelet duration in the elderly patients after percutaneous coronary intervention]. / Durée du traitement antiagrégant plaquettaire chez le sujet âgé stenté.

Ischemic heart disease is a leading cause of death in Europe. At the same time, older patients are at high risk for coronary heart disease and represent an increasing proportion of patients in the catheterization laboratory in the context of an ageing population. The elderly patients are also at higher bleeding risk, and were poorly represented in major randomized trials. Duration of dual antiplatelet therapy (DAPT), after percutaneous coronary intervention (PCI) should be modulated in a personalized way taking into account hemorrhagic and ischemic risk factors, using risk scores based on the latest recommendations of the European Society of Cardiology. Even if the optimal duration of DAPT after PCI is 6 months in case of stable coronary disease and 12 months in case of an acute coronary syndrome, it can be drastically reduced, up to one month in case of high hemorrhagic risk, or can be prolonged for more than 12 months in case of high ischemic risk. The use of latest generation drug eluting stents associated with a short duration of DAPT has thus demonstrated its safety compared to these durations. In case of triple therapy treatment, associating DAPT and anticoagulation therapy, DAPT is recommended to be as short as possible, potentially reduced to 1 month. Finally, the concomitant prescription of proton pump inhibitor is essential to prevent gastrointestinal bleedings. This literature review will discuss the hemorrhagic risk stratification and choice of DAPT in elderly patients.

Vagal and recurrent laryngeal nerves neuromonitoring during thyroidectomy and parathyroidectomy: A prospective study.

OBJECTIVES: The aim of the study was to stimulate the vagal and the recurrent laryngeal nerves during and after thyroidectomy or parathyroidectomy, to record muscle responses, interpret the electrophysiological modifications and identify prognostic factors for postoperative vocal fold mobility. PATIENTS AND METHODS: A prospective study monitored 151 vagal nerves and 144 recurrent laryngeal nerves in 114 patients. Seven patients (14 vagal nerves) underwent continuous monitoring via an automatic periodic stimulation (APS®) electrode. In 15 patients (21 vagal nerves), the stimulation threshold was studied. Muscle response was recorded on direct vagal and/or recurrent laryngeal nerve stimulation by a monopolar electrode or direct repeated stimulation via an electrode on the vagal nerve. In case of signal attenuation on the first operated side, surgery was not extended to the contralateral side. RESULTS: The vagal nerve stimulation checked inferior laryngeal nerve integrity and recurrent status, without risk of false negatives. The vagal nerve stimulation threshold, before and after dissection, that induced a muscle response of at least 100µV ranged from 0.1 to 0.8mA. Similarity between pre- and post-dissection responses to supramaximal stimulation, defined as 1mA, on the one hand, and between post-dissection vagal and laryngeal recurrent nerve responses on the other correlated with normal postoperative vocal cord mobility. Conversely, muscle response attenuation below 100µV and increased latency indicated a risk of vocal fold palsy. CONCLUSION: Vagal nerve stimulation allows suspicion or elimination of lesions on the inferior laryngeal nerve upstream of the stimulation point and detection of non-recurrent inferior laryngeal nerve. Intermittent monitoring assesses nerve function at the moment of stimulation, while continuous monitoring detects the first signs of nerve injury liable to induce postoperative recurrent nerve palsy. When total thyroidectomy is indicated, signal attenuation on the first operated side casts doubt on continuing surgery to the contralateral side in the same step.

[The role of extracorporeal removal of CO2 (ECCO2R) in the management of respiratory diseases]. / Place de l'épuration extracorporelle de CO2 (ECCO2R) dans la prise en charge des pathologies respiratoires.

INTRODUCTION: The aim of extracorporeal removal of CO2 (ECCO2R) is to ensure the removal of CO2 without any significant effect on oxygenation. ECCO2R makes use of low to moderate extracorporeal blood flow rates, whereas extracorporeal membrane oxygenation (ECMO) requires high blood flows. STATE OF THE ART: For each ECCO2R device it is important to consider not only performance in terms of CO2 removal, but also cost and safety, including the incidence of hemolysis and of hemorrhagic and thrombotic complications. In addition, it is possible that the benefits of such techniques may extend beyond simple removal of CO2. There have been preliminary reports of benefits in terms of reduced respiratory muscle workload. Mobilization of endothelial progenitor cells could also occur, in analogy to the data reported with ECMO, with a potential benefit in term of pulmonary repair. The most convincing clinical experience has been reported in the context of the acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (COPD), especially in patients at high risk of failure of non-invasive ventilation. PERSPECTIVES: Preliminary results prompt the initiation of randomized controlled trials in these two main indications. Finally, the development of these technologies opens new perspectives in terms of long-term ventilatory support.

[Characteristics and management of ST-elevation myocardial infarction in France: Regional variations in 2010]. / Prise en charge du syndrome coronaire aigu avec sus-décalage de ST en France : variations régionales en 2010.

Data on regional variations in the characteristics, management and early outcome of patients admitted with ST-elevation myocardial infarction (STEMI) in France are limited. We used data from the FAST-MI 2010 registry to determine whether regional specificities existed, dividing the French territory into 6 larger geographical regions. Variations in the patients' characteristics were found, partly related to regional variations in demography. Acute reperfusion strategy showed more use of primary percutaneous coronary intervention in the greater Paris area, compared to other regions, which would be expected owing to geography and local availability of catheterization laboratories. Overall, however, in-hospital management showed more similarities than differences across regions. Complications, and in particular in-hospital mortality, did not differ significantly among regions.

Ca(2+)-mediated interaction between negatively charged and neutral liposomes.

In the present work it is shown that large unilamellar lecithin/cholesterol liposomes are able to sequester small negatively charged liposomes in the presence of divalent cations. Evidence is presented suggesting that the sequestration occurs via the formation of membrane invaginations transformed further into intraliposomal vesicles.

Lysolipids reversibly inhibit Ca(2+)-, GTP- and pH-dependent fusion of biological membranes.

Membrane fusion in exocytosis, intracellular trafficking, and enveloped viral infection is thought to be mediated by specialized proteins acting to merge membrane lipid bilayers. We now show that one class of naturally-occurring phospholipids, lysolipids, inhibits fusion between cell membranes, organelles, and between organelles and plasma membrane. Inhibition was reversible, did not correlate with lysis, and could be attributed to the molecular shape of lysolipids rather than to any specific chemical moiety. Fusion was arrested at a stage preceding fusion pore formation. Our results are consistent with the hypothesis that biological fusion, irrespective of trigger, involves the formation of a highly bent intermediate between membranes, the fusion stalk.

Musculotopic organization of the hypoglossal nucleus in the grass frog, Rana pipiens.

Recent neural tracer studies in several mammalian species have demonstrated a similar musculotopic organization of the hypoglossal motoneurons which innervate individual tongue muscles. The distribution of this musculotopic organization in nonmammalian tetrapods, however, has not received detailed investigation. As part of an ongoing study on the comparative organization of the vertebrate hypoglossal nucleus, the musculotopic organization of the hypoglossal nucleus of Rana pipiens was studied by injection of lectin-conjugated horseradish peroxidase into four distinct tongue muscles and the geniohyoid muscle. Injections into the hyoglossus muscle label neurons in dorsal regions of the hypoglossal nucleus in middle and rostral nucleus levels. Injections into the genioglossus basalis muscle label neurons in ventral and lateral regions of the hypoglossal nucleus in caudal nucleus levels. Injections into the genioglossus medialis muscle label neurons in dorsal regions in caudal levels, throughout the nucleus in middle levels, and in ventral regions in more rostral levels. Injections into the geniohyoid muscle label neurons in the ventral tip of the hypoglossal nucleus and in the ventromedial corner of the medullary gray matter in middle and rostral nucleus levels. These results demonstrate that the organization of the hypoglossal nucleus in Rana pipiens is more complex than previous tracer studies indicated. Similarities in the musculotopic organization of the amphibian and mammalian hypoglossal nuclei suggest an evolutionary conservatism of the motor system controlling tongue movement.

Musculotopic organization of the hypoglossal nucleus in the cynomolgus monkey, Macaca fascicularis.

The movements of the tongue in feeding and vocalization are enabled by a complex system of interdigitated muscle fibers in the tongue body. Because of this complexity, the detailed anatomical connections between individual intrinsic tongue muscles and corresponding motoneurons in the hypoglossal nucleus have not been described for any mammal. In this study we describe the distribution of retrogradely labeled neurons in the hypoglossal nucleus, following injections of wheat-germ agglutinin-horseradish peroxidase into different regions of the tongue of 21 cynomolgus monkeys. These experiments demonstrate a spatial organization of hypoglossal motoneurons that reflects the anatomical and functional organization of tongue body muscles: motoneurons innervating the transversus and verticalis muscles are located in medial hypoglossal nucleus regions, motoneurons innervating the genioglossus are located in intermediate hypoglossal nucleus regions, motoneurons innervating the hyoglossus and inferior longitudinalis are located in ventrolateral hypoglossal nucleus regions, and motoneurons innervating the styloglossus and superior longitudinalis are located in dorsolateral hypoglossal nucleus regions. Motoneurons innervating the suprahyoid muscle, the geniohyoid, are situated in a cell column separated ventrally from the main body of the hypoglossal nucleus. Motoneurons innervating the palatoglossus are located in the nucleus ambiguus and, possibly, in dorsolateral hypoglossal nucleus regions. Motoneurons of the medial divisions of the hypoglossal nucleus innervate tongue muscles that are oriented in planes transverse to the long axis of the tongue whereas motoneurons of the lateral divisions innervate tongue muscles that are oriented parallel to this axis. These results suggest that the segregation of motoneurons corresponds to the functional distinction between tongue protrusion and retrusion.

Orderly recruitment among motoneurons supplying different muscles.

Virtually all movements involve the recruitment of motor units from multiple muscles. Given the functional diversity of motor units (motoneurons and the muscle fibers they supply), the effective production of specific movements undoubtedly depends upon some principle(s) to organize the ensemble of active motor units. The principle acting to organize the recruitment of motor units within muscles is the size principle, whereby the first motor units to be recruited have the smallest values for axonal conduction velocity and contractile force, and are the slowest to contract and fatigue. Here we consider the possibility that the size principle applies in the recruitment of motor units across muscles, i.e., that regardless of their muscles of origin, active motor units are recruited in rank order, for example, from low to high conduction velocity. The benefits of orderly recruitment across muscles could be similar to the acknowledged advantages of orderly recruitment within muscles. One benefit is that the neural process involved in organizing active motor units would be simplified. In a muscle-based scheme, the size principle would organize only those motor units within individual muscles, leaving the nervous system with the additional task of coordinating the relative activities of motor units from different muscles. By contrast, in an ensemble-based scheme, orderly recruitment of all motor units according to the size principle would automatically coordinate motor units both within and across motor nuclei. Another potential benefit is the provision for movements with smooth trajectory, the result of interleaving the divergent torque contributions made by motor units from muscles that differ in their orientations about joints. Otherwise, if order were restricted within muscles, the torque trajectory of a joint would change unevenly as participating muscles begin contracting at different times and grade activity at different rates. These considerations support speculation that motor units recruited from co-contracting muscles are collectively recruited according to the size principle.

Topographic segregation of genioglossus motoneurons in the neonatal rat.

The location of the motoneurons that innervate the main tongue protrusor muscle, genioglossus, was studied in the 1-2 day old, 10-14 day old and adult rat. Following injection of the retrograde axonal tracer WGA-HRP into the genioglossus muscle, labeled neurons were localized to a discrete column within the ventral division of the hypoglossal nucleus in both the neonatal and adult rats. These results demonstrate an adult pattern of genioglossus innervation in the neonatal rat.

Localization and contractile properties of intrinsic longitudinal motor units of the rat tongue.

Tongue dysfunction is a hallmark of many human clinical disorders, yet we lack even a rudimentary understanding of tongue neural control. Here, the location and contractile properties of intrinsic longitudinal motor units (MUs) of the rat tongue body are described to provide a foundation for developing and testing theories of tongue motor control. One hundred and sixty-five MUs were studied by microelectrode penetration and stimulation of individual motor axons coursing in the terminal portion of the lateral (retrusor) branch of the hypoglossal nerve in the rat. Uniaxial MU force was recorded by a transducer attached to the protruded tongue tip, and MU location was estimated by electromyographic (EMG) electrodes implanted into the anterior, middle, and posterior portions of the tongue body. All MUs produced retrusive force. MU twitch force ranged from 2-129 mg (mean = 35 mg) and tetanic force ranged from 9-394 mg (mean = 95 mg). MUs reached maximal twitch force in 8-33 ms (mean = 15 ms) and were resistant to fatigue; following 2 min of stimulation, MUs (n = 11) produced 78-131% of initial force. EMG data were collected for 105 MUs. For 65 of these MUs, the EMG response was confined to a single electrode location: for 26 MUs to the anterior, 21 MUs to the middle, and 18 MUs to the posterior portion of the tongue. Of the remaining MUs, EMG responses were observed in two (38/40) or all three (2/40) tongue regions. These data provide the first contractile measures of identified intrinsic tongue body MUs and the first evidence that intrinsic longitudinal MUs are restricted to a portion of tongue length. Localization of MU territory suggests a role for intrinsic MU in the regional control of the mammalian tongue observed during feeding and speech.

The N-ethylmaleimide-sensitive protein thiol groups necessary for sea-urchin egg cortical-granule exocytosis are highly exposed to the medium and are required for triggering by Ca2+.

It is known that sea-urchin egg cortical-granule exocytosis is inhibited by agents such as N-ethylmaleimide (NEM) which modify thiol groups. The fusion-related proteins modified by these agents have yet to be identified, nor is there information regarding the topography of these thiol groups. Furthermore, the step in cortical-granule exocytosis at which these thiol groups participate is unknown. In this study we have investigated the topological properties of, and the temporal requirement for the function of, the fusion-related thiol groups by treating the isolated exocytotic apparatus with high-molecular-mass dextrans and BSA carrying thiol-reactive 3-(2-pyridyldithio)propionate groups. The dextran derivatives inhibited exocytosis. The BSA derivative was much less inhibitory. Inhibition was reversed by treatment with dithiothreitol. When NEM was added to the dextran-derivative-treated exocytotic apparatus, treatment with dithiothreitol completely reversed inhibition, indicating that the dextran derivatives inhibit by reacting at the NEM-sensitive sites. A pulse of Ca2+ applied in the presence of inhibitors did not trigger any fusion following the removal of the inhibitor by dithiothreitol. These data show that the thiol groups, the modification of which by NEM inhibits exocytosis, are exposed to the medium in terms of their accessibility to macromolecules. They also show that the fusion-related thiol groups are required during the Ca(2+)-dependent stage of exocytosis.

Innervation of propatagial musculature in a flying squirrel, Glaucomys volans (Rodentia, Sciuridae).

The propatagium of gliding and flying mammals is of both functional and phylogenetic interest. The innervation of the propatagial muscle, platysma II, was studied with the axonal tracer wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) in a flying squirrel, Glaucomys volans. Injections of WGA-HRP into the proximal third of platysma II labeled motoneurons in the lateral part of the medial subdivision of the ipsilateral facial nucleus and in the ipsilateral ventral horn of the brachial enlargement. Injections into distal regions of platysma II labeled motoneurons in the ipsilateral ventral horn of spinal segments C5-C8 but not in the facial nucleus. Injections along the whole length of the muscle labeled afferent axons in the ipsilateral dorsal horn of spinal segments C4-T1. These results demonstrate a mixed facial and spinal motor innervation of propatagial musculature in the flying squirrel and indicate that this pattern of mixed innervation is more widespread among flying and gliding mammals than previously reported. Mixed facial and cervical propatagial innervation, independently derived in different flying and gliding mammals, may represent a common solution in the design of the propatagium. These findings complicate the use of propatagial muscle innervation patterns for the establishment of phylogenetic relationships among flying and gliding mammals.

Recruitment of triceps surae motor units in the decerebrate cat. II. Heterogeneity among soleus motor units.

1. On the basis of the orderly activation of motoneurons in a pool, one would predict that motor unit activity and whole muscle force will change at least roughly in parallel: active motor units should continue to fire as net muscle force increases and quiescent motor units should remain inactive as muscle force decreases. We have consistently observed this relationship in our studies of the medial gastrocnemius (MG) muscle, but here we report an uncoupling of the soleus muscle and some of its motor units. 2. Physiological properties and firing behaviors of 20 soleus motor units were characterized in five decerebrate cats with the use of intra-axonal stimulation and recording. Motor unit firing was elicited in reflexes initiated by muscle stretch, nerve stimulation, and mechanical stimulation of the heel. Particular emphasis was placed on the heterogenic reflexes produced in soleus by ramphold-release stretches of the MG muscle. In agreement with previous reports, either net heterogenic excitation or inhibition of the soleus muscle was produced in separate trials of MG stretch. 3. During excitation of soleus in autogenic stretch reflexes and in crossed-extension reflexes, all 20 units were recruited or increased firing, i.e., unit firing was coupled with soleus force. In the other reflexes, however, unit firing and muscle force were uncoupled for 10 of these units. Six tonically active motor units were inhibited during an increase in soleus force produced by MG stretch or by mechanical stimulation of the heel. Four motor units were activated during a decrease in soleus force produced by the same stimuli. 4. Six motor units were studied during both soleus inhibition and excitation evoked by MG stretches. One motor unit was consistently coupled to the soleus muscle response; firing increased during soleus excitation and decreased during inhibition. However, four soleus motor units were inhibited under both conditions, and one unit was excited under both conditions. Thus the firing behavior of five of these six motor units was the same in response to MG stretch, irrespective of the soleus response. 5. The uncoupling was most clearly recognized when tonically active units ceased firing during net excitation of the soleus muscle and when silent units began firing during net inhibition of the soleus muscle. Unit responses were not as striking in all trials of MG stretch (spike number increased or decreased relative to prestretch values by 1-4 spikes), but the responses were consistent across trials; in multiple stretches, spike number commonly either increased or decreased. Intertrial regularity was also observed in units for which firing was coupled with the net reflex response of the soleus muscle. 6. Divergence in the firing of soleus motor units was also observed in three cases in which records were taken simultaneously from two motor units. In one pair, one unit increased and the other decreased firing during MG stretch-evoked inhibition of soleus. In the other two pairs, one unit increased and the other decreased firing when soleus was excited by heel stimulation. In all pairs, the unit that decreased firing under these conditions had the lowest recruitment threshold in response to the soleus stretch. 7. Although all soleus motor units were classified as slow-twitch (type S), variation in their physiological properties bore some relation to firing behavior. Those units recruited during periods of soleus inhibition exhibited among the fastest conduction velocities and contraction times in our sample. In all three unit pairs sampled, the unit expressing decreases in firing had the slower conduction velocity and contraction time. 8. These findings demonstrate that soleus motor units are differentially activated and deactivated by peripheral afferents. (ABSTRACT TRUNCATED)

Horned gena, an atavistic sex-linked dominant mutation in Tribolium confusum.

Horned gena (Hg), a sex-linked dominant mutation with semilethal effects in the imago stage, was found in Tribolium confusion. The Hg mutant is characterized by a pair of horns of variable size and shape that arises from the genoclypeal suture in mildly expressed beetles or a more pronounced horn-like structure resulting from a folding of the genal shelf near the compound eyes. In these beetles there is considerable stress on the exoskeleton of the head so that the cranium is fragmented between the eyes, leaving large, irregularly shaped areas of the head unprotected by cranial exoskeleton. These beetles die presumably because of bacterial infection or because they cannot retain moisture within their bodies. This mutation differs from the mutation V-Grube found in another tenebrionid, Tenebrio molitor. Taxonomic, genetic, and cytological evidence is presented suggesting that Hg is a gene of ancient origin, having existed at least since the genera of Tenebrionidae were being evolved.