Sex differences in spatial abilities: Methodological problems in Hoffman et al.

Hoffman et al. (1) claimed to provide evidence that “nurture” (i.e., residing in a patrilineal vs. matrilineal tribe in India) critically affects sex differences in spatial abilities. Unfortunately, their conclusion is undermined by major problems with their measures of spatial ability and sex equality. The first and biggest problem is with their measure of spatial abilities. “Spatial abilities” are a complex cognitive domain, with facets ranging from location memory (favoring women) to navigation in 3D virtual space (favoring men) (2). The puzzle used by Hoffman et al. (1) is similar to the Object Assembly subtest of the Wechsler Adult Intelligence Scale (3); sex differences on this task are extremely small (d = 0.10), at least 10-fold smaller than those found for spatial measures showing the largest sex differences. It is odd that Hoffman et al. (1) chose to investigate sex differences with this kind of sex-insensitive task. The second problem is the lack of a control task. The insensitivity of the task used by Hoffman et al. (1) suggests that their finding that men outperform women in a patrilineal tribe but not a matrilineal tribe is not related to sex differences in spatial abilities per se but to other factors instead. Education, as they noted, is likely one of these. The use of a cognitive control task tapping nonspatial abilities would have allowed for an assessment of the specificity of the effect, but, unfortunately, such a task was not included. Third, defining sex equality as matrilineality is problematic, because cross-cultural studies generally show that equality (a multidimensional construct) is not systematically correlated with descent system (4). From the descriptions of Hoffman et al. (1), it appears that women in the matrilineal Khasi have more economic power and better education, but this ignores other sex equality dimensions, such as positions of political and religious leadership, domestic authority, and autonomy. Without such measures, it is unclear whether the Khasi are, in fact, more sexegalitarian than the Karbi. Furthermore, a recent 53-nation cross-cultural study has shown that sex differences favoring men on validated, reliable, multi-item spatial measures are positively associated with United Nation indices of sex development and empowerment (5), a pattern opposite to that reported by Hoffman et al. (1). For all these reasons, the study by Hoffman et al. (1) failed to support their conclusions

Mosaic Brains? A Methodological Critique of Joel et al. (2015)

(no abstract

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Millimeter Mapping at z ∼ 1:Dust-obscured Bulge Building and Disk Growth

A randomly chosen star in today's Universe is most likely to live in a galaxy with a stellar mass between that of the Milky Way and Andromeda. Yet it remains uncertain how the structural evolution of these bulge-disk systems proceeded. Most of the unobscured star formation we observe building Andromdeda progenitors at 0.790% of their star formation is reprocessed by dust and remains unaccounted for. Here we map 500micron dust continuum emission in an Andromeda progenitor at z=1.25 to probe where it is growing through dust-obscured star formation. Combining resolved dust measurements from the NOEMA interferometer with Hubble Space Telescope Halpha maps and multicolor imaging (including new UV data from the HDUV survey), we find a bulge growing by dust-obscured star formation: while the unobscured star formation is centrally suppressed, the dust continuum is centrally concentrated, filling in the ring-like structures evident in the Halpha and UV emission. Reflecting this, the dust emission is more compact than the optical/UV tracers of star formation with r_e(dust)=3.4kpc, r_e(Halpha)/r_e(dust)=1.4, and r_e(UV)/r_e(dust)=1.8. Crucially, however, the bulge and disk of this galaxy are building simultaneously; although the dust emission is more compact than the rest-optical emission (r_e(optical)/r_e(dust)=1.4), it is somewhat less compact than the stellar mass (r_e(M_*)/r_e(dust)=0.9). Taking the 500micron emission as a tracer of star formation, the expected structural evolution of this galaxy can be accounted for by star formation: it will grow in size by Delta(r_e)/Delta(M_*)~0.3 and central surface density by Delta(Sigma_cen)/Delta(M_*)~0.9. Finally, our observations are consistent with a picture in which merging and disk instabilities drive gas to the center of galaxies, boosting global star formation rates above the main sequence and building bulges.Comment: Submitted to ApJ, key new result of paper shown in Fig.

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Gender-Related Traits in Transsexuals and Nontranssexuals

Thirty-eight male-to-female (M-to-F) transsexuals, 7 female-to-male (F-to-M) transsexuals, 13S nontranssexual men, and 225 nontranssexual women were assessed on the following: gender diagnosticity (GD) measures, which assessed male-vs. female-typical occupational and hobby preferences; instrumentality; expressiveness; self-ascribed masculinity; and self-ascribed femininity. M-to-F transsexuals differed strongly and significantly from nontranssexual men on GD and self-ascribed femininity (effect sizes from 1.84 to 3.40) and more weakly on instrumentality, expressiveness, and selfascribed masculinity (effect sizes from 0.40 to 0.56). F-to-M transsexuals differed strongly and significantly from nontranssexual women on GD and on self-ascribed masculinity and femininity (effect sizes from 2.45 to 3.97), but not on instrumentality or expressiveness (effect sizes of 0.07 and 0.39). The degree to which the six assessed gender-related traits distinguished transsexual from nontranssexuals was strongly correlated with the degree to which these same traits distinguished nontranssexual men from nontranssexual women. Using comparison data from past research, M-to-F transsexuals were quite similar to gay men on all gender-related traits except self-ascribed femininity, but F-to-M transsexuals were considerably more masculine than lesbian women on all gender-related traits except for instrumentality and expressiveness