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

Lewy Body Dementia Association\u27s Research Centers of Excellence Program: Inaugural Meeting Proceedings.

The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator\u27s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson\u27s disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics

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

Pathological Role of Peptidyl-Prolyl Isomerase Pin1 in the Disruption of Synaptic Plasticity in Alzheimer’s Disease

Synaptic loss is the structural basis for memory impairment in Alzheimer’s disease (AD). While the underlying pathological mechanism remains elusive, it is known that misfolded proteins accumulate as β-amyloid (Aβ) plaques and hyperphosphorylated Tau tangles decades before the onset of clinical disease. The loss of Pin1 facilitates the formation of these misfolded proteins in AD. Pin1 protein controls cell-cycle progression and determines the fate of proteins by the ubiquitin proteasome system. The activity of the ubiquitin proteasome system directly affects the functional and structural plasticity of the synapse. We localized Pin1 to dendritic rafts and postsynaptic density (PSD) and found the pathological loss of Pin1 within the synapses of AD brain cortical tissues. The loss of Pin1 activity may alter the ubiquitin-regulated modification of PSD proteins and decrease levels of Shank protein, resulting in aberrant synaptic structure. The loss of Pin1 activity, induced by oxidative stress, may also render neurons more susceptible to the toxicity of oligomers of Aβ and to excitation, thereby inhibiting NMDA receptor-mediated synaptic plasticity and exacerbating NMDA receptor-mediated synaptic degeneration. These results suggest that loss of Pin1 activity could lead to the loss of synaptic plasticity in the development of AD

Lewy Body Dementia Association’s Research Centers of Excellence Program: Inaugural Meeting Proceedings

Abstract The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator’s meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or other) professionals, and (4) create infrastructure for a clinical trials-ready network as well as resources to advance the study of new therapeutics.https://deepblue.lib.umich.edu/bitstream/2027.42/148286/1/13195_2019_Article_476.pd

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.