Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Complete Sequencing of the blaNDM-1-Positive IncA/C Plasmid from Escherichia coli ST38 Isolate Suggests a Possible Origin from Plant Pathogens

The complete sequence of the plasmid pNDM-1_Dok01 carrying New Delhi metallo-β-lactamase (NDM-1) was determined by whole genome shotgun sequencing using Escherichia coli strain NDM-1_Dok01 (multilocus sequence typing type: ST38) and the transconjugant E. coli DH10B. The plasmid is an IncA/C incompatibility type composed of 225 predicted coding sequences in 195.5 kb and partially shares a sequence with blaCMY-2-positive IncA/C plasmids such as E. coli AR060302 pAR060302 (166.5 kb) and Salmonella enterica serovar Newport pSN254 (176.4 kb). The blaNDM-1 gene in pNDM-1_Dok01 is terminally flanked by two IS903 elements that are distinct from those of the other characterized NDM-1 plasmids, suggesting that the blaNDM-1 gene has been broadly transposed, together with various mobile elements, as a cassette gene. The chaperonin groES and groEL genes were identified in the blaNDM-1-related composite transposon, and phylogenetic analysis and guanine-cytosine content (GC) percentage showed similarities to the homologs of plant pathogens such as Pseudoxanthomonas and Xanthomonas spp., implying that plant pathogens are the potential source of the blaNDM-1 gene. The complete sequence of pNDM-1_Dok01 suggests that the blaNDM-1 gene was acquired by a novel composite transposon on an extensively disseminated IncA/C plasmid and transferred to the E. coli ST38 isolate

Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies

Anaplastic thyroid carcinoma (ATC) is a rare malignancy, accounting for 1-2% of all thyroid cancers. Although rare, ATC accounts for the majority of deaths from thyroid carcinoma. ATC often originates in a pre-existing thyroid cancer lesion, as suggested by the simultaneous presence of areas of differentiated or poorly differentiated thyroid carcinoma. ATC is characterized by the accumulation of several oncogenic alterations, and studies have shown that an increased number of oncogenic alterations equates to an increased level of dedifferentiation and aggressiveness. The clinical management of ATC requires a multidisciplinary approach; according to recent American Thyroid Association guidelines, surgery, radiotherapy and/or chemotherapy should be considered. In addition to conventional therapies, novel molecular targeted therapies are the most promising emerging treatment modalities. These drugs are often multiple receptor tyrosine kinase inhibitors, several of which have been tested in clinical trials with encouraging results so far. Accordingly, clinical trials are ongoing to evaluate the safety, efficacy and effectiveness of these new agents. This Review describes the updated clinical and pathological features of ATC and provides insight into the molecular biology of this disease. The most recent literature regarding conventional, newly available and future therapies for ATC is also discussed