Modern sugarcanes are polyploid interspecific hybrids, combining high sugar content from Saccharum officinarum with hardiness, disease resistance and ratooning of Saccharum spontaneum. Sequencing of a haploid S. spontaneum, AP85-441, facilitated the assembly of 32 pseudo-chromosomes comprising 8 homologous groups of 4 members each, bearing 35,525 genes with alleles defined. The reduction of basic chromosome number from 10 to 8 in S. spontaneum was caused by fissions of 2 ancestral chromosomes followed by translocations to 4 chromosomes. Surprisingly, 80% of nucleotide binding site-encoding genes associated with disease resistance are located in 4 rearranged chromosomes and 51% of those in rearranged regions. Resequencing of 64 S. spontaneum genomes identified balancing selection in rearranged regions, maintaining their diversity. Introgressed S. spontaneum chromosomes in modern sugarcanes are randomly distributed in AP85-441 genome, indicating random recombination among homologs in different S. spontaneum accessions. The allele-defined Saccharum genome offers new knowledge and resources to accelerate sugarcane improvement.

Gelsolin consists of six homologous domains (G1-G6), each containing a conserved Ca-binding site. Occupation of a subset of these sites enables gelsolin to sever and cap actin filaments in a Ca-dependent manner. Here, we present the structures of Ca-free human gelsolin and of Ca-bound human G1-G3 in a complex with actin. These structures closely resemble those determined previously for equine gelsolin. However, the G2 Ca-binding site is occupied in the human G1-G3/actin structure, whereas it is vacant in the equine version. In-depth comparison of the Ca-free and Ca-activated, actin-bound human gelsolin structures suggests G2 and G6 to be cooperative in binding Ca 2؉ and responsible for opening the G2-G6 latch to expose the F-actin-binding site on G2. Mutational analysis of the G2 and G6 Ca-binding sites demonstrates their interdependence in maintaining the compact structure in the absence of calcium. Examination of Ca binding by G2 in human G1-G3/actin reveals that the Ca 2؉ locks the G2-G3 interface. Thermal denaturation studies of G2-G3 indicate that Ca binding stabilizes this fragment, driving it into the active conformation. The G2 Ca-binding site is mutated in gelsolin from familial amyloidosis (Finnish-type) patients. This disease initially proceeds through protease cleavage of G2, ultimately to produce a fragment that forms amyloid fibrils. The data presented here support a mechanism whereby the loss of Ca binding by G2 prolongs the lifetime of partially activated, intermediate conformations in which the protease cleavage site is exposed.actin ͉ calcium activated ͉ calcium dependent ͉ TIRF

No abstract

No abstract

ParticipantsA total of 1,558 participants, including 782 patients with major depressive disorder (MDD) and 776 healthy controls (HCs), were recruited from 5 research centers in China (The Second Xiangya Hospital, ). The detailed inclusion and exclusion criteria for each center are listed below. CMU dataset:Four hundred thirty-one participants were recruited for participation in this study, including 155 patients with MDD and 276 HCs. All patients with MDD were recruited from the outpatient clinic at the Department of Psychiatry, First Affiliated Hospital of China Medical University and the Mental Health Center of Shenyang. Patients with MDD were diagnosed by two trained psychiatrists using the Structured Clinical Interview for DSM-IV Disorders. Participants with MDD met the DSM-IV diagnostic criteria for MDD but not for any other Axis I disorders. The severity of depression was rated using the 17-item HDRS (Williams, 1988) and the Clinical Global Impression of Severity Scale (Guy, 1976). The control group was recruited from the local community. HC participants did not have a current or lifetime history of Axis I disorders or a history of psychotic, mood, or other Axis I disorders in first-degree relatives as determined from the detailed family history. The participants were excluded for the following reasons: 1) a lifetime history of substance/alcohol abuse or dependence, 2) a concomitant major medical disorder, 3) any MRI contraindications, 4) a history of head trauma with loss of consciousness ≥5 minutes or any neurological disorder, and 5) suboptimal imaging data quality. The study was approved by the Institutional Review Board of China Medical University. Among these participants, 1 patient and 5 HCs were excluded because of duplicate data in the data transfer, 1 HC was excluded due to errors in raw DICOM data, 6 patients were excluded due to the use of different scanning parameters, 3 HCs were excluded due to abnormalities in anatomical brain images, 6 patients and 6 HCs were excluded for large head motion during the R-fMRI scan (exceeding 3 mm of translational movements or 3° of rotational movements), 13 patients and 8 HCs were excluded because the MRI scan did not cover the entire brain, 4 patients and 2 HCs were excluded due to a change in the diagnosis in follow-up interviews, 1 HC was excluded due to a lack of demographic information, and 1 HC was excluded because of his young age. Finally, data from the remaining 125 patients with MDD and 249 HCs were used in the present study. CSU dataset:Patients with MDD were recruited from inpatient or outpatient departments of the Psychiatry Hospital of Zhumadian, Henan Province, China. The diagnosis of MDD was confirmed by

Psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), share clinical and neurobiological features. Because previous investigations of functional dysconnectivity have mainly focused on single disorders, the transdiagnostic alterations in the functional connectome architecture of the brain remain poorly understood. We collected resting-state functional magnetic resonance imaging data from 512 participants, including 121 with SCZ, 100 with BD, 108 with MDD, and 183 healthy controls. Individual functional brain connectomes were constructed in a voxelwise manner, and the modular architectures were examined at different scales, including (1) global modularity, (2) module-specific segregation and intra- and intermodular connections, and (3) nodal participation coefficients. The correlation of these modular measures with clinical scores was also examined. We reliably identify common alterations in modular organization in patients compared to controls, including (1) lower global modularity; (2) lower modular segregation in the frontoparietal, subcortical, visual, and sensorimotor modules driven by more intermodular connections; and (3) higher participation coefficients in several network connectors (the dorsolateral prefrontal cortex and angular gyrus) and the thalamus. Furthermore, the alterations in the SCZ group are more widespread than those of the BD and MDD groups and involve more intermodular connections, lower modular segregation and higher connector integrity. These alterations in modular organization significantly correlate with clinical scores in patients. This study demonstrates common hyper-integrated modular architectures of functional brain networks among patients with SCZ, BD, and MDD. These findings reveal a transdiagnostic mechanism of network dysfunction across psychiatric disorders from a connectomic perspective.

No abstract

No abstract