The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, regulates thalamocortical interactions that are critical for sensory processing, attention and cognition
. TRN ...dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders
. However, little is known about the organizational principles that underlie its divergent functions. Here we performed an integrative study linking single-cell molecular and electrophysiological features of the mouse TRN to connectivity and systems-level function. We found that cellular heterogeneity in the TRN is characterized by a transcriptomic gradient of two negatively correlated gene-expression profiles, each containing hundreds of genes. Neurons in the extremes of this transcriptomic gradient express mutually exclusive markers, exhibit core or shell-like anatomical structure and have distinct electrophysiological properties. The two TRN subpopulations make differential connections with the functionally distinct first-order and higher-order thalamic nuclei to form molecularly defined TRN-thalamus subnetworks. Selective perturbation of the two subnetworks in vivo revealed their differential role in regulating sleep. In sum, our study provides a comprehensive atlas of TRN neurons at single-cell resolution and links molecularly defined subnetworks to the functional organization of thalamocortical circuits.
Fundamental questions regarding collagen biosynthesis, especially with respect to the molecular origins of homotrimeric versus heterotrimeric assembly, remain unanswered. Here, we demonstrate that ...the presence or absence of a single cysteine in type-I collagen's C-propeptide domain is a key factor governing the ability of a given collagen polypeptide to stably homotrimerize. We also identify a critical role for Ca
in non-covalent collagen C-propeptide trimerization, thereby priming the protein for disulfide-mediated covalent immortalization. The resulting cysteine-based code for stable assembly provides a molecular model that can be used to predict, a priori, the identity of not just collagen homotrimers, but also naturally occurring 2:1 and 1:1:1 heterotrimers. Moreover, the code applies across all of the sequence-diverse fibrillar collagens. These results provide new insight into how evolution leverages disulfide networks to fine-tune protein assembly, and will inform the ongoing development of designer proteins that assemble into specific oligomeric forms.
Thalamocortical (TC) circuits are essential for sensory information processing. Clinical and preclinical studies of autism spectrum disorders (ASDs) have highlighted abnormal thalamic development and ...TC circuit dysfunction. However, mechanistic understanding of how TC dysfunction contributes to behavioral abnormalities in ASDs is limited. Here, our study on a Shank3 mouse model of ASD reveals TC neuron hyperexcitability with excessive burst firing and a temporal mismatch relationship with slow cortical rhythms during sleep. These TC electrophysiological alterations and the consequent sensory hypersensitivity and sleep fragmentation in Shank3 mutant mice are causally linked to HCN2 channelopathy. Restoring HCN2 function early in postnatal development via a viral approach or lamotrigine (LTG) ameliorates sensory and sleep problems. A retrospective case series also supports beneficial effects of LTG treatment on sensory behavior in ASD patients. Our study identifies a clinically relevant circuit mechanism and proposes a targeted molecular intervention for ASD-related behavioral impairments.
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•SHANK3 deficiency leads to increased excitability of thalamic relay neurons•HCN2 channelopathy causally links sensory hypersensitivity and sleep fragmentation•Early intervention targeting HCN2 channelopathy corrects ASD behavioral abnormalities•Lamotrigine (LTG) treatment potentially benefits the sensory symptoms in ASD patients
In a relevant mouse model of autism spectrum disorder (ASD), Guo et al. show increased excitability in thalamic neurons and disrupted phase-locking with cortical rhythms. Early intervention to restore HCN2 function with lamotrigine mitigates sensory hypersensitivity and sleep disturbances in this mouse model of ASD. This approach also holds promise for improving sensory behavior in ASD patients.
Three dimensions (3D) modeling, printing, and manufacturing can help in personalized and customized surgical reconstruction of complex defects in the craniofacial region with precision by ...manipulating tissues based on the preoperative assessment, planning the shape of metal and alloplastic materials, and reduction in the total cost and time of the surgery.
The present survey study aimed to assess the approach of treating surgeons towards the role of 3D printing in post-op rehabilitation of palatal bone loss by mucormycosis.
One thousand eyes nose and throat (ENT) and maxillofacial surgeons were given a pre-formed structured survey questionnaire to be filled by subjects themselves for their view on the role of 3D printing for rehabilitation and reconstruction of palatal bone loss due to mucormycosis.
Efficacy of 3D printing to print the pneumatic sinus design and palatal contour helping to design accurate support with a lightweight prosthesis, 67.2% (n=672) subjects whereas, exact duplication of the excised tissue, 85.4% (n=854) subjects, to detect and duplicate undercuts, 58.4% (n=584) subjects, 3D printing can be helpful as the proper extension of impression 73.2% (n=732) subjects responded positively. For reconstruction of a lost palate by prosthesis 91.2% (n=912) of study participants, in making obturators using Titanium framework and Polyetheretherketone (PEEK) was given a positive response by 82.2% (n=822) subjects, to fabricate prosthesis obturator required in palatal perforation in case of mucormycosis was given a positive response by 88.1% (n=881) subjects, the role of 3D printing to overlay zygomatic implant prosthesis was responded positively by 68.9% (n=689) study subjects.
The present survey study concludes that 3D printing is a reliable and accurate method for palatal reconstruction following bone destruction by mucormycosis as reported by the majority of ENT and maxillofacial surgeons.
Maternal health refers to the physical, mental, and emotional well-being of mothers throughout all stages of pregnancy, birth, and the postpartum period. Morbidity and death rates during pregnancy ...are significant health statistics because they provide information about the accessibility of maternal and other medical resources. The main reason of maternal mortality are hemorrhage, high blood pressure, early labor, and abortions that are performed under dangerous conditions. Machine learning algorithms play a significant role in determining maternity health risks. In this paper, Traditional Machine Learning algorithms are applied for maternal health risk prediction. Model performance has potential for improvement, thus a more robust and dependable machine learning model has been proposed to operate even in worst, average, and best scenarios and provide the robust performance by considering the performance of all scenarios. The proposed robust model turns out to be the most efficient robust model among all with an accuracy of 70.21%, which is quite satisfactory when compared to traditionally applied ML Models.
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