Age-related differences in corticomotor excitability and inhibitory processes during a visuomotor RT task

This study tested the postulation that change in the ability to modulate corticospinal excitability and inhibitory processes underlie age-related differences in response preparation and generation during tasks requiring either rapid execution of a motor action or actively withholding that same action. Younger (n = 13, mean age = 26.0 years) and older adults (n = 13, mean age = 65.5 years) performed an RT task in which a warning signal (WS) was followed by an imperative signal (IS) to which participants were required to respond with a rapid flexion of the right thumb (go condition) or withhold their response (no-go condition). We explored the neural correlates of response preparation, generation, and inhibition using single- and paired-pulse TMS, which was administered at various times between WS and IS (response preparation phase) and between IS and onset of response-related muscle activity in the right thumb (response generation phase). Both groups exhibited increases in motor-evoked potential amplitudes (relative to WS onset) during response generation; however, this increase began earlier and was more pronounced for the younger adults in the go condition. Moreover, younger adults showed a general decrease in short-interval intracortical inhibition during response preparation in both the go and no-go conditions, which was not observed in older adults. Importantly, correlation analysis suggested that for older adults the task-related increases of corticospinal excitability and intracortical inhibition were associated with faster RT. We propose that the declined ability to functionally modulate corticospinal activity with advancing age may underlie response slowing in older adults

Gender- and gamete-specific patterns of X chromosome segregation in a three-gendered nematode

Meiosis is at the core of sexual reproduction and alterations to its program can have dramatic effects. In this study, we investigate the segregation pattern of the X chromosome in Auanema rhodensis, a three-gendered nematode. This species has an atypical pattern of X chromosome segregation during male spermatogenesis that results in the exclusive production of haplo-X sperm. Here we use a combination of genetic and cytological approaches to show that while XX females undergo conventional meiosis to produce mostly haplo-X oocytes, hermaphrodites undergo atypical meiosis to produce nullo-X oocytes and mostly diplo-X sperm. Gender- and gamete-specific alterations of the normal meiotic program include non-pairing of the X homologs and precocious separation of X chromatids. Given these intra-species, intra-individual and intra-gametogenesis variations in meiotic program of A. rhodensis, we argue that it is an ideal model to study the plasticity of meiosis and how it can be modulated

Sex- and Gamete-Specific Patterns of X Chromosome Segregation in a Trioecious Nematode

Three key steps in meiosis allow diploid organisms to produce haploid gametes: (1) homologous chromosomes (homologs) pair and undergo crossovers; (2) homologs segregate to opposite poles; and (3) sister chromatids segregate to opposite poles. The XX/XO sex determination system found in many nematodes [1] facilitates the study of meiosis because variation is easily recognized [2, 3, 4]. Here we show that meiotic segregation of X chromosomes in the trioecious nematode Auanema rhodensis [5] varies according to sex (hermaphrodite, female, or male) and type of gametogenesis (oogenesis or spermatogenesis). In this species, XO males exclusively produce X-bearing sperm [6, 7]. The unpaired X precociously separates into sister chromatids, which co-segregate with the autosome set to generate a functional haplo-X sperm. The other set of autosomes is discarded into a residual body. Here we explore the X chromosome behavior in female and hermaphrodite meioses. Whereas X chromosomes segregate following the canonical pattern during XX female oogenesis to yield haplo-X oocytes, during XX hermaphrodite oogenesis they segregate to the first polar body to yield nullo-X oocytes. Thus, crosses between XX hermaphrodites and males yield exclusively male progeny. During hermaphrodite spermatogenesis, the sister chromatids of the X chromosomes separate during meiosis I, and homologous X chromatids segregate to the functional sperm to create diplo-X sperm. Given these intra-species, intra-individual, and intra-gametogenesis variations in the meiotic program, A. rhodensis is an ideal model for studying the plasticity of meiosis and how it can be modulated

Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial

Purpose Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B). Materials and Methods Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B. The primary end point was best overall response (complete or partial) rate (ORR) during the first six courses, by RECIST or International Neuroblastoma Response Criteria for patients with measurable or evaluable disease, respectively. Safety, progression-free survival (PFS), and overall survival (OS) time were secondary end points. Results One hundred sixty patients with RR-HRNB were included. For B random assignment (n = 160), the ORR was 26% (95% CI, 17 to 37) with B and 18% (95% CI, 10 to 28) without B (risk ratio [RR], 1.52 [95% CI, 0.83 to 2.77]; P = .17). Adjusted hazard ratio for PFS and OS were 0.89 (95% CI, 0.63 to 1.27) and 1.01 (95% CI, 0.70 to 1.45), respectively. For irinotecan ([I]; n = 121) and topotecan (n = 60) random assignments, RRs for ORR were 0.94 and 1.22, respectively. A potential interaction between I and B was identified. For patients in the bevacizumab-irinotecan-temozolomide (BIT) arm, the ORR was 23% (95% CI, 10 to 42), and the 1-year PFS estimate was 0.67 (95% CI, 0.47 to 0.80). Conclusion The addition of B met protocol-defined success criteria for ORR and appeared to improve PFS. Within this phase II trial, BIT showed signals of antitumor activity with acceptable tolerability. Future trials will confirm these results in the chemoimmunotherapy era

On the limited effect of stimulus boundaries on saccade metrics

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Age-related differences in corticospinal excitability during a Go/NoGo task

Age-related slowing of reaction times (RTs) is well documented but whether the phenomenon reflects deficits in movement preparation and/or response generation processes is unclear. To gain further insight into this issue, transcranial magnetic stimulation (TMS) was used to investigate motor cortex (M1) excitability and short-interval intracortical inhibitory (SICI) processes during a Go/NoGo RT task in younger and older adults. Single- and paired-pulse TMS was delivered over the left M1 during preparation and response generation periods in a right-hand muscle. Younger adults had shorter RTs and a larger increase in corticospinal excitability at response generation period than older adults. SICI modulation for both groups showed a large reduction in inhibition immediately prior to EMG onset. These findings indicate age-related differences in corticospinal excitability during the response generation stage of sensorimotor information processing

Larger stimuli do not attract more the gaze

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On the limited effect of stimulus boundaries on saccade metrics.

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