Sex differences in variability across timescales in BALB/c mice.

BackgroundFemales are markedly underinvestigated in the biological and behavioral sciences due to the presumption that cyclic hormonal changes across the ovulatory cycle introduce excess variability to measures of interest in comparison to males. However, recent analyses indicate that male and female mice and rats exhibit comparable variability across numerous physiological and behavioral measures, even when the stage of the estrous cycle is not considered. Hormonal changes across the ovulatory cycle likely contribute cyclic, intra-individual variability in females, but the source(s) of male variability has, to our knowledge, not been investigated. It is unclear whether male variability, like that of females, is temporally structured and, therefore, quantifiable and predictable. Finally, whether males and females exhibit variability on similar time scales has not been explored.MethodsThese questions were addressed by collecting chronic, high temporal resolution locomotor activity (LA) and core body temperature (CBT) data from male and female BALB/c mice.ResultsContrary to expectation, males are more variable than females over the course of the day (diel variability) and exhibit higher intra-individual daily range than females in both LA and CBT. Between mice of a given sex, variability is comparable for LA but the inter-individual daily range in CBT is greater for males. To identify potential rhythmic processes contributing to these sex differences, we employed wavelet transformations across a range of periodicities (1-39 h).ConclusionsAlthough variability in circadian power is comparable between the sexes for both LA and CBT, infradian variability is greater in females and ultradian variability is greater in males. Thus, exclusion of female mice from studies because of estrous cycle variability may increase variance in investigations where only male measures are collected over a span of several hours and limit generalization of findings from males to females

A New Archaeoastronomical Investigation of the Irish Axial-Stone Circles

This paper presents the preliminary results of a project undertaken in 1994 to investigate the astronomical potential of the axial-stone circles (ASCs) of seven or more stones in Counties Cork and Kerry, south-west Ireland. This group of sites is of particular interest in that the monuments in the group bear a striking resemblance to the recumbent stone circles (RSCs) of Aberdeenshire, eastern Scotland, which appear to exhibit a strong pattern of alignment in relation to prominent hilltop summits and the rising and setting position of the moon. The first indications from the Irish data are that similar patterns of alignment are not evident in the Irish ASCs. The Irish sites show no preference for orientation upon prominent hilltops and no clear astronomical trends

ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors

\ua9 The Author(s) 2024.Purpose: PARP inhibitors (PARPi) are effective in homologous recombination repair (HRR) defective (HRD) cancers. To (re)sensitise HRR proficient (HRP) tumours to PARPi combinations with other drugs are being explored. Our aim was to determine the mechanism underpinning the sensitisation to PARPi by inhibitors of cell cycle checkpoint kinases ATR, CHK1 and WEE1. Experimental design: A panel of HRD and HRP cells (including matched BRCA1 or 2 mutant and corrected pairs) and ovarian cancer ascites cells were used. Rucaparib (PARPi) induced replication stress (RS) and HRR (immunofluorescence microscopy for γH2AX and RAD51 foci, respectively), cell cycle changes (flow cytometry), activation of ATR, CHK1 and WEE1 (Western Blot for pCHK1S345, pCHK1S296 and pCDK1Y15, respectively) and cytotoxicity (colony formation assay) was determined, followed by investigations of the impact on all of these parameters by inhibitors of ATR (VE-821, 1 \ub5M), CHK1 (PF-477736, 50 nM) and WEE1 (MK-1775, 100 nM). Results: Rucaparib induced RS (3 to10-fold), S-phase accumulation (2-fold) and ATR, CHK1 and WEE1 activation (up to 3-fold), and VE-821, PF-477736 and MK-1775 inhibited their targets and abrogated these rucaparib-induced cell cycle changes in HRP and HRD cells. Rucaparib activated HRR in HRP cells only and was (60-1,000x) more cytotoxic to HRD cells. VE-821, PF-477736 and MK-1775 blocked HRR and sensitised HRP but not HRD cells and primary ovarian ascites to rucaparib. Conclusions: Our data indicate that, rather than acting via abrogation of cell cycle checkpoints, ATR, CHK1 and WEE1 inhibitors cause an HRD phenotype and hence “induced synthetic lethality” with PARPi

Young Children with ASD Use Lexical and Referential Information During On-line Sentence Processing

Research with adults and older children indicates that verb biases are strong influences on listeners’ interpretations when processing sentences, but they can be overruled. In this paper, we ask two questions: (i) are children with Autism Spectrum Disorder (ASD) who are high functioning sensitive to verb biases like their same age typically developing peers?, and (ii) do young children with ASD and young children with typical development (TD) override strong verb biases to consider alternative interpretations of ambiguous sentences? Participants were aged 5–9 years (mean age 6.65 years): children with ASD who were high functioning and children with TD. In task 1, biasing and neutral verbs were included (e.g., eat cake versus move cake). In task 2, the focus was on whether the prepositional phrase occurring with an instrument biasing verb (e.g., ‘Chop the tree with the axe’) was interpreted as an instrument even if the named item was an implausible instrument (e.g., candle in ‘Cut the cake with the candle’). Overall, the results showed similarities between groups but the ASD group was generally slower. In task 1, both groups looked at the named object faster in the biasing than the non-biasing condition, and in the biasing condition the ASD group looked away from the target more quickly than the TD group. In task 2, both groups identified the target in the prepositional phrase. They were more likely to override the verb instrument bias and consider the alternative (modification) interpretation in the implausible condition (e.g., looking at the picture of a cake with a candle on it’). Our findings indicate that children of age 5 years and above can use context to override verb biases. Additionally, an important component of the sentence processing mechanism is largely intact for young children with ASD who are high functioning. Like children with TD, they draw on verb semantics and plausibility in integrating information. However, they are likely to be slower in processing the language they hear. Based on previous findings of associations between processing speed and cognitive functioning, the implication is that their understanding will be negatively affected, as will their academic outcomes

Biology-specific vocabulary: students’ understanding and lecturers’ expectations of student understanding

The current A-level biology curriculum includes a broad coverage of all the biosciences which demands knowledge of a wide range of biological vocabulary. Students (n = 184) from two UK universities were presented with a list of vocabulary, associated with a ‘Revise Biology’ text which highlighted key terms that students should know. Lecturers (n = 26) were asked which of these terms they expected students to know, or be aware of. Findings revealed that students’ claimed knowledge of vocabulary exceeded lecturer expectations. In addition, there were a number of terms which students did not understand and lecturers did not expect them to know, which could be removed from A-level biology courses. This is discussed in relation to whether A-level curricula need to be so content heavy and whether lecturers would benefit from knowing more about their students’ knowledge of discipline-specific terms

Biology-specific vocabulary: students’ understanding and lecturers’ expectations of student understanding

The current A-level biology curriculum includes a broad coverage of all the biosciences which demands knowledge of a wide range of biological vocabulary. Students (n = 184) from two UK universities were presented with a list of vocabulary, associated with a ‘Revise Biology’ text which highlighted key terms that students should know. Lecturers (n = 26) were asked which of these terms they expected students to know, or be aware of. Findings revealed that students’ claimed knowledge of vocabulary exceeded lecturer expectations. In addition, there were a number of terms which students did not understand and lecturers did not expect them to know, which could be removed from A-level biology courses. This is discussed in relation to whether A-level curricula need to be so content heavy and whether lecturers would benefit from knowing more about their students’ knowledge of discipline-specific terms

Super-Eddington Atmospheres that Don't Blow Away

We show that magnetized, radiation dominated atmospheres can support steady state patterns of density inhomogeneity that enable them to radiate at far above the Eddington limit, without suffering mass loss. The inhomogeneities consist of periodic shock fronts bounding narrow, high-density regions, interspersed with much broader regions of low density. The radiation flux avoids the regions of high density, which are therefore weighed down by gravity, while gas in the low-density regions is slammed upward into the shock fronts by radiation force. As the wave pattern moves through the atmosphere, each parcel of matter alternately experiences upward and downward forces, which balance on average. Magnetic tension shares the competing forces between regions of different densities, preventing the atmosphere from blowing apart. We calculate the density structure and phase speed of the wave pattern, and relate these to the wavelength, the density contrast, and the factor by which the net radiation flux exceeds the Eddington limit. In principle, this factor can be as large as the ratio of magnetic pressure to mean gas pressure, or the ratio of radiation pressure to gas pressure, whichever is smaller. Although the magnetic pressure must be large compared to the mean gas pressure in order to support a large density contrast, it need not be large compared to the radiation pressure. These highly inhomogeneous flows could represent the nonlinear development of the "photon bubble" instability discovered by Gammie. We briefly discuss the applicability of these solutions to astrophysical systems.Comment: 11 pages, 1 figure, accepted for publication in The Astrophysical Journa