Collective behavior can spontaneously emerge when individuals follow common rules of interaction. However, the behavior of each individual differs due to existing genetic and non-genetic variation ...within the population. It remains unclear how this individuality is managed to achieve collective behavior. We quantify individuality in bands of clonal Escherichia coli cells that migrate collectively along a channel by following a self-generated gradient of attractant. We discover that despite substantial differences in individual chemotactic abilities, the cells are able to migrate as a coherent group by spontaneously sorting themselves within the moving band. This sorting mechanism ensures that differences between individual chemotactic abilities are compensated by differences in the local steepness of the traveling gradient each individual must navigate, and determines the minimum performance required to travel with the band. By resolving conflicts between individuality and collective migration, this mechanism enables populations to maintain advantageous diversity while on the move.
Methane is an essential component of the global carbon cycle and one of the most powerful greenhouse gases, yet it is also a promising alternative source of carbon for the biological production of ...value-added chemicals. Aerobic methane-consuming bacteria (methanotrophs) represent a potential biological platform for methane-based biocatalysis. Here we use a multi-pronged systems-level approach to reassess the metabolic functions for methane utilization in a promising bacterial biocatalyst. We demonstrate that methane assimilation is coupled with a highly efficient pyrophosphate-mediated glycolytic pathway, which under oxygen limitation participates in a novel form of fermentation-based methanotrophy. This surprising discovery suggests a novel mode of methane utilization in oxygen-limited environments, and opens new opportunities for a modular approach towards producing a variety of excreted chemical products using methane as a feedstock.
The receptor for advanced glycation end products (RAGE), a multi-ligand
member of the immunoglobulin superfamily of cell surface molecules,
interacts with distinct molecules implicated in ...homeostasis, development and
inflammation, and certain diseases such as diabetes and Alzheimer's disease
3-8. Engagement of RAGE by a ligand triggers activation of key
cell signalling pathways, such as p21ras, MAP kinases,
NF-κB and cdc42/rac, thereby reprogramming cellular properties. RAGE is a central cell surface receptor for amphoterin,
a polypeptide linked to outgrowth of cultured cortical neurons derived from
developing brain. Indeed, the co-localization
of RAGE and amphoterin at the leading edge of advancing neurites indicated
their potential contribution to cellular migration, and in pathologies such
as tumour invasion. Here we demonstrate that blockade of RAGE-amphoterin
decreased growth and metastases of both implanted tumours and tumours developing
spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin
interaction suppressed activation of p44/p42, p38 and SAP/JNK MAP kinases;
molecular effector mechanisms importantly linked to tumour proliferation,
invasion and expression of matrix metalloproteinases.
Purpose
In August 2011, orthopaedic surgeons from more than 20 countries attended a summit on anatomic anterior cruciate ligament (ACL) reconstruction. The summit offered a unique opportunity to ...discuss current concepts, approaches, and techniques in the field of ACL reconstruction among leading surgeons in the field.
Methods
Five panels (with 36 panellists) were conducted on key issues in ACL surgery: anatomic ACL reconstruction, rehabilitation and return to activity following anatomic ACL reconstruction, failure after ACL reconstruction, revision anatomic ACL reconstruction, and partial ACL injuries and ACL augmentation. Panellists’ responses were secondarily collected using an online survey.
Results
Thirty-six panellists (35 surgeons and 1 physical therapist) sat on at least one panel. Of the 35 surgeons surveyed, 22 reported performing “anatomic” ACL reconstructions. The preferred graft choice was hamstring tendon autograft (53.1 %) followed by bone-patellar tendon-bone autograft (22.8 %), allograft (13.5 %), and quadriceps tendon autograft (10.6 %). Patients generally returned to play after an average of 6 months, with return to full competition after an average of 8 months. ACL reconstruction “failure” was defined by 12 surgeons as instability and pathological laxity on examination, a need for revision, and/or evidence of tear on magnetic resonance imaging. The average percentage of patients meeting the criteria for “failure” was 8.2 %.
Conclusions
These data summarize the results of five panels on anatomic ACL reconstruction. The most popular graft choice among surgeons for primary ACL reconstructions is hamstring tendon autograft, with allograft being used most frequently employed in revision cases. Nearly half of the surgeons surveyed performed both single- and double-bundle ACL reconstructions depending on certain criteria. Regardless of the technique regularly employed, there was unanimous support among surgeons for the use of “anatomic” reconstructions using bony and soft tissue remnant landmarks.
Level of evidence
V.
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the HTT gene. In addition to germline CAG expansions, somatic repeat ...expansions in neurons also contribute to HD pathogenesis. The DNA mismatch repair gene, MSH3, identified as a genetic modifier of HD onset and progression, promotes somatic CAG expansions, and thus presents a potential therapeutic target. However, what extent of MSH3 protein reduction is needed to attenuate somatic CAG expansions and elicit therapeutic benefits in HD disease models is less clear. In our study, we employed potent di-siRNAs to silence mouse Msh3 mRNA expression in a dose-dependent manner in Hdh
mice and correlated somatic Htt CAG instability with MSH3 protein levels from simultaneously isolated DNA and protein after siRNA treatment. Our results reveal a linear correlation with a proportionality constant of ~ 1 between the prevention of somatic Htt CAG expansions and MSH3 protein expression in vivo, supporting MSH3 as a rate-limiting step in somatic expansions. Intriguingly, despite a 75% reduction in MSH3 protein levels, striatal nuclear HTT aggregates remained unchanged. We also note that evidence for nuclear Msh3 mRNA that is inaccessible to RNA interference was found, and that MSH6 protein in the striatum was upregulated following MSH3 knockdown in Hdh
mice. These results provide important clues to address critical questions for the development of therapeutic molecules targeting MSH3 as a potential therapeutic target for HD.
PDF
