Neuromuscular control of wingbeat kinematics in Anna's hummingbirds (Calypte anna)

Hummingbirds can maintain the highest wingbeat frequencies of any flying vertebrate – a feat accomplished by the large pectoral muscles that power the wing strokes. An unusual feature of these muscles is that they are activated by one or a few spikes per cycle as revealed by electromyogram recordings (EMGs). The relatively simple nature of this activation pattern provides an opportunity to understand how motor units are recruited to modulate limb kinematics. Hummingbirds made to fly in low-density air responded by moderately increasing wingbeat frequency and substantially increasing the wing stroke amplitude as compared with flight in normal air. There was little change in the number of spikes per EMG burst in the pectoralis major muscle between flight in normal and low-density heliox (mean=1.4 spikes cycle^(–1)). However the spike amplitude, which we take to be an indication of the number of active motor units, increased in concert with the wing stroke amplitude, 1.7 times the value in air. We also challenged the hummingbirds using transient load lifting to elicit maximum burst performance. During maximum load lifting, both wing stroke amplitude and wingbeat frequency increased substantially above those values during hovering flight. The number of spikes per EMG burst increased to a mean of 3.3 per cycle, and the maximum spike amplitude increased to approximately 1.6 times those values during flight in heliox. These results suggest that hummingbirds recruit additional motor units (spatial recruitment) to regulate wing stroke amplitude but that temporal recruitment is also required to maintain maximum stroke amplitude at the highest wingbeat frequencies

The Management of Perioperative Immunosuppressant Medications for Rheumatoid Arthritis During Elective Hand Surgery

Purpose: Rheumatoid arthritis (RA) is a destructive inflammatory disease that commonly involves joints of the hand and wrist. Different recommendations exist for continuing or discontinuing immunosuppressant medications during the perioperative time period. The purpose of our study was to determine if continuing steroids, non-biologic DMARDs, and/or biologic DMARDs were associated with an increased risk of postoperative complications. Methods: We performed a single-centered, retrospective review of a consecutive cohort of RA patients who had elective hand surgery by a single surgeon. Patients were included if they had a documented diagnosis of seropositive RA by a rheumatologist, and had elective hand surgery and/or disease-related surgical procedure involving the upper extremity from January 2008 to August 2018. We stratified patients into different groups for comparison by classes of immunosuppressant medications for managing RA. These classes included corticosteroids, non-biological DMARDs, biologic DMARDs, and/or no medications. Groups were then compared for the incidence of postoperative complications. Results: Eighty-eight consecutive patients had elective hand and/or upper extremity surgeries for RA. Mean patient age at the time of surgery (±SD) was 55±13 years (range: 24 to 74 years). Of these 88 patients, eight (9%) overall complications occurred. Complications were wound healing failures, (n=5, 6%), tendon rupture, (n=1, 1%), hematoma, (n=1, 1%), and surgical site infection, (n=1, 1%). Perioperative medications included steroids (n=31), non-biologic DMARDs (n=68), and biologic DMARDs (n=5). There were no significant findings between patients on perioperative corticosteroids, non-biologic DMARDs, and/or biologic DMARDs and the incidence of complications. Mean follow-up was 69±65 weeks (range: 8 to 296 weeks). Conclusions: Patients with RA who continued corticosteroids, non-biologic DMARDs, and/or biologic DMARDS within one dosing interval of their usual dose were not associated with a higher risk for postoperative complications compared to patients discontinuing these medications perioperatively, following elective hand surgery

Rgs1 and Gnai2 Regulate the Entrance of B Lymphocytes into Lymph Nodes and B Cell Motility within Lymph Node Follicles

SummarySignaling by G protein-coupled receptors coupled to Gαi assists in triggering lymphocyte movement into and out of lymph nodes. Here, we show that modulating the signaling output from these receptors dramatically alters B cell trafficking. Intravital microscopy of adoptively transferred B cells from wild-type and Rgs1−/− mice revealed that Rgs1−/− B cells stick better to lymph node high endothelial venules, home better to lymph nodes, and move more rapidly within lymph node follicles than do wild-type B cells. In contrast, B cells from Gnai2−/− mice enter lymph nodes poorly and move more slowly than do wild-type B cells. The Gnai2−/− mice often lack multiple peripheral lymph nodes, and their B cells respond poorly to chemokines, indicating that Gαi1 and Gαi3 poorly compensate for the loss of Gαi2. These results demonstrate opposing roles for Rgs1 and Gnai2 in B cell trafficking into and within lymph nodes

A Defined and Flexible Pocket Explains Aryl Substrate Promiscuity of the Cahuitamycin Starter Unit–Activating Enzyme CahJ

Cahuitamycins are biofilm inhibitors assembled by a convergent nonribosomal peptide synthetase pathway. Previous genetic analysis indicated that a discrete enzyme, CahJ, serves as a gatekeeper for cahuitamycin structural diversification. Here, the CahJ protein was probed structurally and functionally to guide the formation of new analogues by mutasynthetic studies. This analysis enabled the in vivo production of a new cahuitamycin congener through targeted precursor incorporation.Breaking the barrier: Biofilm formation is employed by pathogenic microbes to defend against antibiotic action. This study probes both structurally and functionally CahJ, a key biosynthetic adenylation enzyme involved in generation of the cahuitamycin biofilm inhibitors, and lays a foundation for the development of effective new analogues.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145379/1/cbic201800233_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145379/2/cbic201800233.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145379/3/cbic201800233-sup-0001-misc_information.pd

Relations of Sex Hormone Levels to Leukocyte Telomere Length in Black, Hispanic, and Asian/Pacific Islander Postmenopausal Women

Background Sex hormones may play important roles in sex-specific biological aging. We specifically examined the associations between circulating concentrations of sex hormones and leukocyte telomere length (TL). Methods We conducted a cross-sectional study of 1124 black, 444 Hispanic, and 289 Asian/Pacific Islander women in the Women's Health Initiative Observational Cohort. Concentrations of estradiol and testosterone were measured using electrochemiluminescence immunoassays. TL was measured using quantitative PCR. Results Women included in the study were 50 to 79 years of age. Levels of estradiol were not significantly associated with TL in this sample of women. The associations between total and free testosterone and TL differed by race/ethnicity (P for interaction = 0.03 for total testosterone and 0.05 for free testosterone). Total and free testosterone concentrations were not associated with TL in black and Hispanic women, whereas in Asian/Pacific Islanders, their concentrations were inversely associated with TL (P-trend = 0.003 for both). These associations appeared robust in multiple subgroup analysis and multivariable models adjusted for potential confounding factors. In Asian/Pacific Islanders, doubling of serum free testosterone concentration was associated with 202 bp shorter TL (95% CI, 51 to 353 bp), and doubling of total testosterone concentration was associated with 203 bp shorter TL (95% CI, 50 to 355 bp). Conclusions Serum concentration of estradiol was not associated with leukocyte TL in this large sample of postmenopausal women. Total and free testosterone levels were inversely associated with TL in Asian/Pacific Islander women but not in black and Hispanic women, although future studies to replicate our observations are warranted particularly to address potential ethnicity-specific relations. The significant findings of the study This study elucidates the potential roles of sex hormones in biological aging, and identified that total and free testosterone levels were inversely associated with telomere length in Asian/Pacific Islander women but not in black and Hispanic women. The study adds The findings of this study suggest that Asian/Pacific Islander women may be susceptible to the potential detrimental effects of high testosterone level on biologic aging