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Patient-derived iPSCs show premature neural differentiation and neuron type-specific phenotypes relevant to neurodevelopment.
Ras/MAPK pathway signaling is a major participant in neurodevelopment, and evidence suggests that BRAF, a key Ras signal mediator, influences human behavior. We studied the role of the mutation BRAFQ257R, the most common cause of cardiofaciocutaneous syndrome (CFC), in an induced pluripotent stem cell (iPSC)-derived model of human neurodevelopment. In iPSC-derived neuronal cultures from CFC subjects, we observed decreased p-AKT and p-ERK1/2 compared to controls, as well as a depleted neural progenitor pool and rapid neuronal maturation. Pharmacological PI3K/AKT pathway manipulation recapitulated cellular phenotypes in control cells and attenuated them in CFC cells. CFC cultures displayed altered cellular subtype ratios and increased intrinsic excitability. Moreover, in CFC cells, Ras/MAPK pathway activation and morphological abnormalities exhibited cell subtype-specific differences. Our results highlight the importance of exploring specific cellular subtypes and of using iPSC models to reveal relevant human-specific neurodevelopmental events
Lp Fourier multipliers on compact Lie groups
In this paper we prove Lp multiplier theorems for invariant and non-invariant
operators on compact Lie groups in the spirit of the well-known
Hormander-Mikhlin theorem on Rn and its variants on tori Tn. We also give
applications to a-priori estimates for non-hypoelliptic operators. Already in
the case of tori we get an interesting refinement of the classical multiplier
theorem.Comment: 22 pages; minor correction
Dobbs Was Not The Beginning: A Guide on Pregnancy Criminalization
Community Justice Exchange partnered with Repro Legal Defense Fund to produce this guide for anyone interested in understanding the ways criminalization of abortion has manifested and harmed people in the past as a way to understand what we might expect in the post-Dobbs era. The guide specifically focuses on the current and anticipated increase of the criminalization of individuals who self-manage their abortion or are suspected of self-managing their abortion. We also identify and provide guidance for possible points of intervention and support that would benefit people being criminalized for self-managed abortion, as well as further resources for understanding and intervening in the criminalization of self-managed abortion
Scoliosis in patients with Prader Willi Syndrome – comparisons of conservative and surgical treatment
In children with Prader Willi syndrome (PWS), besides growth hormone (GH) therapy, control of the food environment and regular exercise, surgical treatment of scoliosis deformities seems the treatment of choice, even though the risks of spinal surgery in this specific population is very high. Therefore the question arises as to whether the risks of spinal surgery outweigh the benefits in a condition, which bears significant risks per se. The purpose of this systematic review of the Pub Med literature was to find mid or long-term results of spinal fusion surgery in patients with PWS, and to present the conservative treatment in a case study of nine patients with this condition
Molecular Gas in the Host Galaxy of a Quasar at Redshift z=6.42
Observations of the molecular gas phase in quasar host galaxies provide
fundamental constraints on galaxy evolution at the highest redshifts. Molecular
gas is the material out of which stars form; it can be traced by spectral line
emission of carbon--monoxide (CO). To date, CO emission has been detected in
more than a dozen quasar host galaxies with redshifts (z) larger 2, the record
holder being at z=4.69. At these distances the CO lines are shifted to longer
wavelengths, enabling their observation with sensitive radio and millimetre
interferometers. Here we present the discovery of CO emission toward the quasar
SDSS J114816.64+525150.3 (hereafter J1148+5251) at a redshift of z=6.42, when
the universe was only 1/16 of its present age. This is the first detection of
molecular gas at the end of cosmic reionization. The presence of large amounts
of molecular gas (M(H_2)=2.2e10 M_sun) in an object at this time demonstrates
that heavy element enriched molecular gas can be generated rapidly in the
earliest galaxies.Comment: 12 pages, 2 figures. To appear in Nature, July, 200
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